IPI - Autumn 2025 - Volume 17 Issue 3

Volume 17 Issue 3

Peer Reviewed

Mushroom Supplements

Health Trends and Regulatory Environment

Safeguarding Potency

Innovative Containment Strategies for HPAPI Manufacturing

In the Pharmaceutical GMP Industry

If Quality Is Everyone's Responsibility, Is It No One's Responsibility?

More Than a Box

Inside the Cold Chain’s Quiet Revolution

Mental Health & Neurodegenerative Section (page 18–27) Sponsor Company:

Nasal and Pulmonary Subsection page 83

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Contents 04

Editor’s Letter

TALKING POINT 06

DIRECTOR: Mark A. Barker BUSINESS DEVELOPMENT: Anthony Stewart anthony@senglobalcoms.com MANAGING EDITOR: Alice Phillips alice@senglobalcoms.com EDITORIAL ASSISTANTS: Melissa Canver melissa@senglobalcoms.com Carla Devine carla@senglobalcoms.com RESEARCH AND CIRCULATION: Blossom Mercado blossom@senglobalcoms.com DESIGN DIRECTOR: Jana Sukenikova www.fanahshapeless.com FINANCE DEPARTMENT: Akash Sharma accounts@senglobal.com COVER IMAGE: iStockphoto © PUBLISHED BY: Senglobal Ltd., 2 Larch Court, London United Kingdom, SE1 3GB Tel: +44 (0) 203 3420130 Email: info@senglobalcoms.com www.international-pharma.com All rights reserved. No part of this publication may be reproduced, duplicated, stored in any retrieval system or transmitted in any form by any means without prior written permission of the Publishers.

The next issue of IPI will be published in Winter 2025.

ISSN No.International Pharmaceutical Industry ISSN 1755-4578.

The Future of Aseptic Manufacturing

Genex, a robotic gloveless system is transforming aseptic pharmaceutical manufacturing. Marcel Weizel of Bausch+Ströbel discusses how Genex enhances safety, flexibility, and compliance with Annex 1 by enabling fully automated, modular processes tailored to small-batch drug production, reducing contamination risk and operator intervention.

REGULATORY & MARKETPLACE 08 Mushroom Supplements: Health Trends and Regulatory Environment Damien Bové of ADACT Medical outlines challenges in the UK mushroom supplement market, where growing demand clashes with limited clinical evidence, regulatory hurdles, and complex compliance under food laws.

14

Navigating Compliance and Regulatory Readiness with Medical Information

Navigating post-market compliance is increasingly more complex Rajul Jain at ProPharma highlights the role of Medical Information teams in maintaining regulatory compliance, supporting AI initiatives, managing global risks, and ensuring ethical communication across pharmaceutical operations.

MENTAL HEALTH & NEURODEGENERATIVE 18

Intranasal Insulin for Alzheimer’s: Advancing Brain-Targeted Delivery

Aptar Pharma’s Julie Suman and Reenal Gandhi explore how intranasal insulin shows promise for Alzheimer’s treatment by delivering insulin directly to the brain, bypassing the blood-brain barrier, improving cognition safely, with advancing delivery technologies supporting future clinical success.

22

Mapping the Proteome to Understand the Complexity of Neurodegenerative Diseases

Mass spectrometry-based proteomics enables detailed mapping of the proteome in neurodegenerative diseases, revealing disrupted proteostasis, protein aggregation, immune mechanisms, and biomarkers. These insights from Bruker Daltonics’ Daniel Hornburg, Torsten Müller and Stefan Foser support early diagnosis, therapeutic discovery, and a deeper understanding of disease progression at molecular and spatial levels.

25

Advancements in Neuromodulation: A New Era for Respiratory Health

Neuromodulation offers a promising new approach for treating respiratory conditions like dyspnoea. Dr. Bipin Patel of ElectronRX analyses techniques such as DBS, VNS, TGNS, and SCS show early clinical benefits. Continued research aims to optimise stimulation methods, understand mechanisms, and validate long-term efficacy through larger trials.

Advancing Clinical Development Through Autoinjectors: Enabling Patient-Centric Drug Delivery

The opinions and views expressed by the authors in this journal are not necessarily those of the Editor or the Publisher. Please note that although care is taken in the preparation of this publication, the Editor and the Publisher are not responsible for opinions, views, and inaccuracies in the articles. Great care is taken concerning artwork supplied, but the Publisher cannot be held responsible for any loss or damage incurred. This publication is protected by copyright.

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2024 Senglobal Ltd./Volume 17 Issue 3 – Autumn – 2025

DRUG DISCOVERY, DEVELOPMENT & DELIEVERY

This article from Bill Welch at PCI Pharma Services explores how autoinjectors are transforming clinical trials by enhancing patient compliance, standardising drug delivery, and supporting real-world usability. It outlines key considerations around design, compatibility, regulation, and scalability for successfully integrating these devices into development programme.

30

Back to Basics: What Will Drug Safety Look Like in 5–10 Years?

Lucinda Smith at ArisGlobal calls for re-aligning pharmacovigilance with patient outcomes by modernising safety processes, using AI to reduce manual tasks, and empowering safety teams to support innovation. www.international-pharma.com

INTERNATIONAL PHARMACEUTICAL INDUSTRY 1

Contents 32

AI-Augmented Innovation in Drug Discovery

Andrew Anderson of ACD/Labs explains how AI enhances drug discovery by accelerating DMTA cycle transitions, improving predictions, reducing errors, and automating synthesis and analysis for faster candidate identification.

36

Nanomedicines: How Innovations in Drug Delivery Technology Can Unlock the Potential of Nanoparticles

Nanomedicines improve drug targeting and safety but face challenges from complex structures and analytical bottlenecks. Ardena’s Maria Marioli and Arno Vermote explore advanced techniques like AF4-MALS-DLS enable better characterisation, ensuring quality, regulatory compliance, and clinical success.

40

Empowering Drug Delivery at Scale: How Ypsomed’s Platform Approach Advances Self-Injection Globally

Ypsomed enables scalable global self-injection by combining decades of device expertise with modular platforms tailored to modern biologics. Philipp Richard explains how this means accelerating drug development, improving patient adherence, and supporting decentralised, personalised healthcare delivery.

CLINICAL & MEDICAL RESEARCH 50

AI Teammates Impact on Clinical Research

Ram Yalamanchili and Gaurav Bhatnagar from Tilda Research show how AI teammates are revolutionising clinical trials by improving data accuracy, reducing admin workload, and speeding execution for competitive drug development.

MANUFACTURING 52

Safeguarding Potency: Innovative Containment Strategies for HPAPI Manufacturing

Advanced containment strategies in HPAPI manufacturing ensure safety, compliance, and innovation, supportingcompanies worldwide. James Millar from Almac Pharma Services examines enabling high-potency drug production.

56

Building Contamination Control Strategies for ATMP Manufacturing

Patrick Nieuwenhuizen from PharmaLex explains how ATMP manufacturing requires a risk-based contamination control strategy aligned with EudraLex and ICH guidelines, focusing on managing risks from personnel, materials, and environments.

61

In the Pharmaceutical GMP Industry: If Quality Is Everyone's Responsibility, Is It No One's Responsibility?

Markus Lung at Vita Green Pharmaceuticals examines how unclear accountability weakens GMP quality systems and shares strategies for empowering QA teams, engaging employees, and reinforcing management’s responsibility in quality culture.

68 How Automation Helps to Accelerate Product Development Sumeet Dalvi from Emerson showcases how automation and data-driven tools like process simulation are transforming product development, enabling faster tech transfer, higher flexibility, and improved quality in life sciences manufacturing.

PACKAGING 76

The Importance of PRE-Coloured, Biocompatible and Pre-Tested ABS for Medical Device Approval

SUBSECTION: NASAL AND PULMONARY (PART C) 86

Complexity of Selling Orally Inhaled and Nasal Drug Product CDMO Services

Carolyn Berg and Dontae Solomon at Catalent explore the complexity of selling CDMO services for inhaled drugs, requiring deep expertise in drug development, device design, supply chains, and testing.

92

INHALED mRNA: The Race Has Begun

MERXIN analyses how inhaled mRNA therapies are advancing for respiratory and genetic diseases, with 29 candidates in development. Targeted lung delivery, soft mist inhalers, and strategic device partnerships are driving this emerging precision biologics market.

96

Safely Navigating the Transition to Low-GWP Medical Propellants

Sheryl Johnson of Orbia discusses how Orbia’s Fluor & Energy Materials leads the transition to low-GWP propellants with HFA-152a, balancing sustainability, safety, and continuity of care in inhaler manufacturing through innovation, collaboration, and education.

100 Scaling Capabilities in Nasal Drug Delivery Nasal drug delivery is advancing beyond local treatments to systemic, noseto-brain, and biologic applications. Joe DePalo analyses how Bespak supports this evolution with flexible manufacturing, specialised devices, and expertise in complex nasal combination products.

104 Unveiling the Path of Nebuliser Platforms for Combination Product Development Hernan Cuevas Brun of HCmed Innovations discusses how customisable mesh nebuliser platforms enable efficient drug delivery for complex formulations including biologics. They support early-stage pairing, technical customisation, and scalable development, streamlining regulatory approval and accelerating combination product success.

108 The Role of Nasal Cast Testing in Drug Development This article explains nasal cast testing’s role in improving nasal drug delivery by ensuring accurate deposition and regulatory compliance. Joanne Mather and Alyssa Rubino of Proveris Laboratories highlights that when combined with automated actuation, nasal cast testing enhances reproducibility, supports product development, and helps optimise formulations and devices for effective nasal therapies.

APPLICATION NOTE 44 Fragment Screening of Massively-Parallel Ligand Arrays Using the Carterra® Ultra® SPR Platform Carterra Ultra® revolutionises Fragment-Based Lead Discovery with unmatched speed, sensitivity, and scale. Its 192-region ligand array enables parallel analysis of 100+ targets, accelerating hit identification and medicinal chemistry workflows while minimising time, reagent use, and chip consumption in SPR screening.

66

Hygienic Stäubli Robots in Pharmaceutical Packaging – Proven Packaging Expertise

Pre-coloured biocompatible ABS plastics, pre-tested for safety with integrated pigments, offer consistent quality and simplified regulatory compliance. Luca Chiochia at ELIX Polymers analyses how they reduce risks compared to postcoloured ABS, making them ideal for medical device approval.

Uhlmann’s UPS 5 blister machine, equipped with hygienic Stäubli SCARA robots, enables high-speed, GMP-compliant packaging of complex parenteral medication sets. Sonja Koban explains Its modular design, precision robotics, and automation ensure pharmaceutical standards, flexibility, and throughput of up to 200 blisters per minute.

LOGISTICS & SUPPLY CHAIN MANAGEMENT

70

80

More Than a Box: Inside the Cold Chain’s Quiet Revolution

David Webber with Cold Chain Technologies explores how cold chain logistics are shifting from packaging to digital intelligence, sustainability, and service innovation to meet modern pharmaceutical and regulatory demands.

2 INTERNATIONAL PHARMACEUTICAL INDUSTRY

SCHOTT – The Next Generation of Infuse – Redefining Efficiency, Stability, Speed, and Security

SCHOTT presents its next-generation TOPPAC Infuse syringe, enhancing drug delivery through RFID traceability, first-opening indicators, and blisterfree packaging to improve stability, reduce waste, and streamline clinical workflows.

Autumn 2025 Volume 17 Issue 3

Rethink acne treatments with Benzalkonium Chloride Address the shortcomings of conventional therapies.

Here is a safe and proven antimicrobial that helps overcome antibiotic resistance and biofilm formation.

• Effective against Cutibacterium acnes and Staphylococcus epidermis.

• Compatible across delivery forms, from liquids to semi-solids and solids.

• Enhances product stability and maximizes shelf life.

Don’t let outdated perceptions limit your innovation. Explore how Benzalkonium Chloride can enhance your acne care formulations.

Let’s connect at CPhI WorldWide 2025!

Let’s connect at CPhI

novonordiskpharmatech.com/BKC

enabling better www.international-pharma.com

INTERNATIONAL PHARMACEUTICAL INDUSTRY 3

Editor's Letter As we welcome the Autumn of 2025, we continue to see rapid advancements shaping the pharmaceutical industry.

This edition of IPI reflects how innovation in drug delivery, neuroscience, and inhalation research is creating new possibilities for treatment, access, and longterm health outcomes.

I want to specifically highlight our Mental Health & Neurodegenerative Disease subsection that features some standout articles based on neurological research, reflecting its growing importance across all areas of pharmaceutical research and policy. We explore how new approaches and technologies are supporting both preventative care and targeted interventions, with the goal of achieving more inclusive and holistic health outcomes.

A personal favourite of mine comes from Julie Suman and Reenal Gandhi of Aptar Pharma, who examine the potential of intranasal insulin in treating Alzheimer’s disease. Their feature highlights how this method allows for direct delivery of insulin to the brain, bypassing the blood-brain barrier and offering a promising approach to improving cognition. With technological progress accelerating in nasal drug delivery systems, this strategy could pave the way for meaningful clinical outcomes in neurodegenerative care.

Sheryl Johnson of Orbia explores how the transition to low global warming potential medical propellants is being made possible through technical innovation, regulatory collaboration and industry education. Her article outlines how Orbia’s HFA-152a offers a significant reduction in environmental impact while maintaining the safety, efficacy and continuity of care expected from pressurised metered dose inhalers. Importantly, she addresses industry concerns around flammability, demonstrating how with the right controls, training and infrastructure, this next-generation propellant can be introduced without disruption to patients or providers. As regulations evolve and Net Zero targets become more urgent, low-GWP propellants offer a practical and scalable solution that supports both public health and environmental responsibility.

Another favourite of mine comes from our Drug Discovery, Development & Delivery section.

An article from Ardena’s Maria Marioli and Arno Vermote explains how nanomedicine is redefining the future of therapeutic innovation,

offering targeted, effective and often life-saving solutions through engineered nanoparticles.

This article explores how the promise of nanomedicines, such as those used in mRNA vaccines, relies not only on breakthroughs in formulation but also on overcoming the analytical challenges that come with their complexity. It highlights how advanced techniques like asymmetric flow field-flow fractionation and multi-modal characterisation are essential to unlocking the full clinical potential of these therapies, ensuring safety, efficacy and regulatory confidence from early development through to commercialisation.

IPI Autumn 2025 brings together expert perspectives and forward-looking research that point to a future driven by smart delivery systems, neuroscience, and a deeper understanding of human health. We hope you find this issue both engaging and enlightening as we continue to track the evolving landscape of pharmaceutical innovation.

Alice Phillips, Editorial Manager

We are also proud to include a third instalment of our Nasal & Pulmonary subsection that includes many thoughtprovoking contributions on expanding nasal and pulmonary therapeutics, including novel approaches to brain-targeted treatment, respiratory health management, and the transition to next-generation inhalation technologies.

Editorial Advisory Board Bakhyt Sarymsakova, Head of Department of International Cooperation, National Research, Center of MCH, Astana, Kazakhstan

Rick Turner, Senior Scientific Director, Quintiles Cardiac Safety Services & Affiliate Clinical Associate Professor, University of Florida College of Pharmacy

Steve Heath, Head of EMEA – Medidata Solutions, Inc Patrice Hugo, Chief Scientific Officer, Clearstone Central Laboratories

Catherine Lund, Vice Chairman, OnQ Consulting

Jagdish Unni, Vice President – Beroe Risk and Industry Delivery Lead – Healthcare, Beroe Inc.

Heinrich Klech, Professor of Medicine, CEO and Executive Vice President, Vienna School of Clinical Research

Deborah A. Komlos, Principal STEM Content Analyst, Clarivate Diana L. Anderson, Ph.D president and CEO of D. Anderson & Company Franz Buchholzer, Director Regulatory Operations worldwide, PharmaNet development Group Francis Crawley. Executive Director of the Good Clinical Practice Alliance – Europe (GCPA) and a World Health Organisation (WHO) Expert in ethics 4 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Jeffrey W. Sherman, Chief Medical Officer and Senior Vice President, IDM Pharma Jim James DeSantihas, Chief Executive Officer, PharmaVigilant Mark Goldberg, Chief Operating Officer, PAREXEL International Corporation Maha Al-Farhan, Chair of the GCC Chapter of the ACRP

Robert Reekie, Snr. Executive Vice President Operations, Europe, Asia-Pacific at PharmaNet Development Group Sanjiv Kanwar, Managing Director, Polaris BioPharma Consulting Stefan Astrom, Founder and CEO of Astrom Research International HB

Autumn 2025 Volume 17 Issue 3

www.international-pharma.com

INTERNATIONAL PHARMACEUTICAL INDUSTRY 5

Talking Point

The Future of Aseptic Manufacturing An interview with Marcel Weizel, Business Development Manager at Bausch+Ströbel Why is this development so important for today’s pharmaceutical industry?

With GENEX, a new generation of robotic systems is transforming pharmaceutical production. The implementation of fully automated processes is establishing new standards in product and operator safety, operational flexibility and cost efficiency. In this interview, Marcel Weizel, an industry expert explains how these innovations will reshape cleanroom manufacturing and why Annex 1 plays a decisive role.

Robot-assisted cleanroom production has been central to pharmaceutical manufacturing for some time. How does the new GENEX system go beyond traditional automation?

Marcel Weizel: GENEX represents a fundamental shift. While robots have long been used for handling packaging materials, GENEX extends their role to critical tasks such as automated product path installation, bio- and surface-monitoring and even troubleshooting.

These functions, which previously required manual glove interventions, are now performed fully automatically. This not only increases safety and quality but also reduces cost per unit, making advanced therapies more accessible to patients.

Marcel Weizel: The industry is moving toward smaller and more flexible batch sizes. Largescale systems have historically facilitated widespread availability of drugs such as insulin. Today's challenge lies in the ongoing development of specialised therapies, including orphan drugs and cell and gene therapies, which are manufactured in smaller quantities. GENEX is designed specifically for this environment. Its modular design allows manufacturers to adapt process chains to individual requirements while ensuring rapid and compliant setup changes.

You mentioned bio- and surface-monitoring as well as troubleshooting. What makes these capabilities unique?

Marcel Weizel: Automated bio- and surfacemonitoring is a major leap. By utilising preprogrammed robotic movements, we ensure a level of reproducibility that surpasses manual interventions, while upholding the highest standards of sterility assurance. This is consistent with the regulatory requirements outlined in Annex 1, specifically chapter 2.1 i) and 9.22, which state that technologies such as robotic systems should be used to reduce contamination risks. Additionally, aseptic

operations should be monitored through a combination of methods without negatively affecting grade A airflow. Troubleshooting is equally important. GENEX is capable of autonomously identifying and resolving problems, such as a stopper jam. These capabilities reduce the likelihood of product loss and introduce significant improvements to aseptic manufacturing processes.

How does GENEX support long-term flexibility for manufacturers?

Marcel Weizel: Scalability is a key element.

A line can be expanded or replicated to create parallel production setups. This also enables what we call “matrix production,” where modules can be flexibly rearranged to match specific process needs. In case of a malfunction, production can simply be redirected, reducing the risk of batch loss. Looking ahead, we expect robotic systems to play a larger role not only inside the isolator but also outside, for loading, supplying spare parts, and transporting finished batches.

How do you work with pharmaceutical companies in developing these solutions?

Marcel Weizel: We see ourselves as solution providers rather than just equipment

Detailed illustrations showing the biomonitoring process sequence 6 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Autumn 2025 Volume 17 Issue 3

Regulatory & Talking Marketplace Point

Until now, cleanroom robots have been used primarily for handling, supplying, and transporting packaging materials. More complex tasks – such as biomonitoring the production environment – were once thought impossible, but with GENEX, they are now a reality.

suppliers. That means working closely with customers to implement technologies that deliver measurable benefits. It also means supporting them over the entire life cycle of the system, from initial planning to operation and service. A comprehensive service portfolio is considered a fundamental component of the GENEX solution rather than an additional feature.

Regulations such as Annex 1 are shaping these technologies. What is your perspective?

Marcel Weizel: Annex 1 recognises the benefits of robotic systems in enhancing product protection against potential sources of endotoxins or pyrogens, particulate matter and microbial contamination,

including those introduced by operators.

Utilising a Robotic Gloveless Isolator such as Genex safeguards operators from exposure to highly potent substances, enhances process reliability and product quality and ultimately reduces the risk of contamination.

This trend is reinforced by regulations; for example, Section 8.9 of Annex 1 recommends the implementation of robotics to eliminate direct human critical interventions within grade A environments. As equipment suppliers, we are committed to advancing aseptic processing toward fully gloveless operation spaces, drawing inspiration from best practices in semiconductor manufacturing, where robotic waferhandling has been standard since the 2000s.

General Overview GENEX offers exceptional flexibility, adapting to the specific needs and conditions of pharmaceutical manufacturers. The line is built on a modular system, allowing individual process chains to be configured based on specific needs.

We will gladly provide you with further information on request.

Marcel Weizel Marcel Weizel is Business Development Manager at Bausch+Ströbel, a manufacturer of pharmaceutical filling and packaging systems, where he is, among other things, an expert in the use of robot technology. He will be speaking about precisely this topic at CPHI in Frankfurt.

The title of his presentation is: “Unlocking the Future of Aseptic Filling with GENEX – Robotic. Gloveless. Annex 1 Compliant.”

A look ahead: Matrix production made possible with GENEX. www.international-pharma.com

INTERNATIONAL PHARMACEUTICAL INDUSTRY 7

Regulatory & Marketplace

Mushroom Supplements: Health Trends and Regulatory Environment The mushroom supplement market in the UK has seen remarkable growth in recent years moving from niche to mainstream.

Fuelled by increased consumer interest in the use of natural health and wellness products, functional foods and plantbased trends, the UK mushroom market generated a revenue of USD 1,271.5 million in 2023 and is expected to double by 2030 reaching USD 2,513.0 with projections suggesting continued expansion.1 Mushroom supplements are botanical dietary products derived from various species of medicinal and functional mushrooms and available in whole, extract, powder, or capsule form. Common species used include reishi (Ganoderma lucidum), lion’s mane (Hericium erinaceus), chaga (Inonotus obliquus), and cordyceps (Cordyceps sinensis). These supplements may be sold as single-ingredient products or combined with other botanicals, vitamins, or minerals. Mushroom supplements are prized for their purported health benefits, which range from boosting immunity and enhancing cognitive function to supporting energy levels and reducing stress.

Use of medicinal mushrooms is not new. In Traditional Chinese Medicine (TCM) and other ancient healing systems, mushrooms have been used for centuries for their immuneboosting, anti-inflammatory, and adaptogenic properties. But what distinguishes the current mushroom supplement trend is the intersection of ancient wisdom and scientific study with the isolation of bioactive compounds responsible for many of the reported health benefits, such as betaglucans, terpenoids, and polysaccharides, and exploring the effects of these compounds in clinical studies.2 The following review looks at key mushrooms in the current supplement market with a summary of their suggested health benefits as well as an overview of the current regulation of mushrooms in the UK, including regulatory classification, labelling, safety and enforcement mechanisms.

Health Benefits of Popular Mushrooms Pre-clinical research and some small human 8 INTERNATIONAL PHARMACEUTICAL INDUSTRY

studies indicate various mushrooms have beneficial health properties. However, large, rigorous clinical trials are needed to substantiate many of the claims made by supplement manufacturers. The strongest evidence for the seven most popular mushrooms in the UK market is as follows.

viral, and anti-inflammatory activity.9 Research is ongoing into the mechanisms of action in the immune system10 as well as into their antimicrobial and antioxidant effects.11 Compounds such as triterpenes and polysaccharides in reishi are believed to be responsible for these effects.

Shiitake (Lentinula edodes) Research suggest that Shiitake mushrooms can provide a number of health benefits which in some countries are so highly valued that shiitake mushrooms are known as the ‘elixir of life.’3 Shiitake mushrooms have been found to potentially help support heart health. A laboratory study discovered that consuming Shiitake mushrooms helped lower cholesterol levels and led to less plaque on the artery walls.4 Shiitake could be a useful mushroom in supporting the immune system. A four-week study done on 52 men and women found that daily Shiitake consumption of either 5g or 10g caused their immune markers to improve and inflammation levels to drop.5

Lion’s Mane (Hericium erinaceus) Lion’s Mane mushrooms may improve cognitive function, according to laboratory research which showed that this type of mushroom could improve recognition memory.12 Very preliminary evidence suggests a possibility that Lion’s Mane mushrooms may reduce cognitive decline too through promotion of nerve growth factor (NGF) production13 which is essential for brain health and could support memory, focus and neuroprotection. Lion’s Mane may also boost immune health and be useful for anxiety and depression.

Maitake (Grifola frondosa) Maitake have been used traditionally in Chinese and Japanese medicines for hundreds of years and is now finding uses in Western countries.

Rich in vitamin D, Maitake mushrooms are being taken to support bone health and immune health. Maitake also contain antioxidants, beta-glucans, vitamin B and C, copper, potassium, fibre and amino acids.

During recent decades, Maitake ingredients, particularly beta-glucans, have been shown to have various bioactivities, including lowering blood sugar.6 A 2015 laboratory study7 showed that maitake mushroom can have a positive effect in type 2 diabetes. During the study, maitake mushroom consumption had a positive effect on glucose levels. This points to the need to evaluate maitake mushroom’s potential to help treat type 2 diabetes in humans.

Reishi (Ganoderma lucidum) Reishi (known as the Queen of Mushrooms) mushrooms are known for supporting immune health, modulating stress and improving sleep quality. Secondary outcomes from a 2016 Cochrane review were that Reishi mushrooms could improve immune function.8 Other established activities include antioxidant, anti-bacterial, anti-fungal, anti-

Turkey Tail (Trametes versicolor) Turkey tail mushrooms are being researched for immune boosting and prebiotic properties. They contain ingredients such as polysaccaropeptide (PSP) and polysaccharide-K (PSK) that boost various types of white cells that reduce inflammation, fight infection and boost immunity.14 Turkey tail contains prebiotics which help nourish healthy gut bacteria.15 Research has found that treatment with turkey tail may have a similarly positive effect on the gut microbiome as treatment with prebiotic supplements.16 A laboratory study found that turkey tail extract modified gut bacteria composition by increasing populations of beneficial bacteria like Bifidobacterium and Lactobacillus while reducing potentially harmful bacteria, such as Clostridium and Staphylococcus.17 Cordyceps (Cordyceps sinensis) Cordyceps may help boost exercise performance and reduce fatigue by increasing the production of adenosine triphosphate (ATP), a molecule required for the production of energy.18 A 6-week placebo-controlled study in healthy older adults using a stationary bike found that in participants taking 3 grams per day of a synthetic strain of Cordyceps VO2 max (a measure of fitness) increased by 7% while participants given the placebo pill showed no change.19 In a 12-week study also in healthy Autumn 2025 Volume 17 Issue 3

Regulatory & Marketplace older adults, Cordyceps given at a dose of 1g daily improved measures of exercise performance.20 Emerging evidence suggests benefits of Cordyceps on heart health but this evidence needs to be confirmed in clinical studies in humans. Cordyceps may keep blood sugar levels within a healthy range by mimicking the action of insulin. In several laboratory studies Cordyceps has been shown to decrease blood sugar levels.21,22 Chaga (Inonotus obliquus) Chaga is best known for its antioxidant content and its ability to fight inflammation which is important for overall internal health, helping in the maintenance of the health or body systems, cells and organs. It contains compounds such as polysaccharides, betulinic acid and melanin. Research has found that Chaga impacts immune response through the production of cytokines which are specific proteins that regulate the immune system in immune cells. Chaga also regulates antibody production.23 Research also suggests that Chaga can prevent harmful cytokines being produced, these can otherwise trigger inflammation.24 Chaga may also offer support for blood sugar. In a laboratory study,25 treatment with Chaga showed a mild blood sugar-lowering effect. In another study Chaga supplements led to a 31% decrease in blood sugar levels over three weeks.26 Mushroom Supplement Formats Mushroom supplements are available in a variety of formats: capsules, powders, tinctures, teas, coffees, sparkling drinks, protein bars and chocolate. Combination products containing mushrooms with vitamins, adaptogens and other botanicals for targeted benefits such as energy, immunity, relaxation are increasing in availability.

This wide variety caters to a varied demographic with differences in preferences and lifestyles, including: • • •

Young people attracted by social media and the desire for wellness Older adults looking for cognitive and immune support as part of healthy ageing Athletes, sports people and gym attenders interested in enhanced energy, endurance and recovery.

Many consumers of all demographics have preferences for healthy living through natural plant-based preparations.

Availability Mushroom supplements are widely available www.international-pharma.com

across the UK in major pharmacy chains and independent pharmacies; high street health and supplement shops; supermarkets with supplement and wellness sections; on-line retailers (e.g. Amazon); and direct to consumer brand websites.

UK Regulatory Framework Following Brexit, the UK has established its own regulatory pathway for supplements, distinct from the EU, though much of the framework remains harmonised.

Mushroom supplements are considered to be botanicals with preparations made from whole or parts of the mushroom plant and processed by for example pressing, squeezing, extraction, distillation, concentration, drying or fermentation.27 As botanicals, mushrooms can fall into any of the regulatory categories depending on their composition, intended use and health claims.

These are food supplements, novel foods and herbal medicinal products including those registered under the Traditional Herbal Registration (THR) scheme.

Food Supplements The majority of mushroom supplements in the UK are classified as food supplements.

Food supplements are defined as concentrated sources of nutrients (e.g. vitamins and minerals) or other, often botanical substances, with nutritional or physiological effects. Ingredients may be present alone or in combination, marketed in dose forms, namely forms such as capsules, tablets, pastilles, pills and other similar forms such as sachets of powders, ampoules of liquids, drop dispensing bottles and other forms of liquids and powders. They are designed to be taken in measured small unit quantities.28 Only permitted vitamins and minerals can be added to food supplements as listed in the relevant annexes to the regulations.

Mushroom supplements marketed as food supplements are mainly regulated under: •

General Food Law Regulation (EC) No 178/2002 (as retained in UK law).29 Supplements must not contain substances that are unsafe or not authorised for use in food. The Food Standards Agency (FSA) is responsible for food safety and novel foods regulation in England, Wales and Northern Ireland and Food Standards Scotland is the responsible body in Scotland. Manufacturers must notify the competent authority of any new product placed on the market.

•

Food labelling law. Key labelling requirements include the name of the food supplement; name and quantity of mushroom species used; recommended daily dose; list of ingredients, allergens and additives; warnings not to exceed the stated daily dose; statements that supplements should not replace a varied diet and healthy lifestyle; name and address of the manufacturer, packer or seller; best before or use by date.30

•

The Food Supplements (England) Regulations31 and equivalent regulations in Wales, Scotland and Northern Ireland.

•

Department of Health and Social Care (DHSC), which oversees food supplement legislation and policy

•

Nutrition and Health Claims These must be registered in the UK under the Great Britain (GB) Nutrition and Health Claims (NHC) Register.32 At the time of writing, there are no authorised claims for mushrooms themselves so only claims authorised in the NHC register in relation to the substances within the mushrooms themselves should be made. Some Article 13.1 health claims are on hold, including reishi mushrooms for immune support and blood cholesterol but these are not authorised.33 Having evidence to support that the conditions of use for any claims are met, is essential.

•

Trading Standards which enforce labelling and consumer protection regulations at the local authority level.

The Advertising Standards Authority (ASA) The ASA is the self-regulatory organisation of the advertising industry in the UK. The ASA is a non-statutory organisation and so cannot interpret or enforce legislation. However, its code of advertising practice broadly reflects legislation in many instances. The ASA has made several rulings on different mushroom products, including products claiming they treat anxiety.34 Novel Foods Some mushroom derived ingredients not traditionally consumed in the UK or the European Union (EU) before 15 May 1997 may be considered novel foods and require authorisation as novel foods. For example, Turkey Tail (Trametes versicolor) and certain species of Cordyceps such as Cordyceps militaris, are novel foods in the EU and not authorised for sale. Similarly, a UK Advertising Standards Authority (ASA) ruling said that the INTERNATIONAL PHARMACEUTICAL INDUSTRY 9

Regulatory & Marketplace FSA were likely to consider these mushroom species as unauthorised novel foods that do not have the relevant authorisation for marketing – meaning they and products containing them, should not be sold in the UK.35 Manufacturers should check they have the necessary pre-market authorisation to market any mushroom which may be a novel food.

Novel foods are regulated in the UK under the Novel Foods (England) Regulations 2018.36 Requirements for novel food authorisation include submission of a detailed safety dossier, including toxicological data; evidence of production methods and quality controls; details of the history of use and anticipated intake; approval and addition to the UK’s list of authorised novel foods before marketing and sale.

Medicinal Products If a mushroom supplement is presented for the treatment or prevention of disease, it may be classified as a medicine. Such medicinal claims can be made only by medicinal products which must be licensed by the Medicines and Healthcare products Regulatory Agency (MHRA).

Traditional Herbal Medicines A Traditional Herbal Medicine is considered to be a medicinal herbal product consisting of active ingredients of herbal origin. An application for Traditional Herbal Registration (THR) may be made to the MHRA.37 Such products are only authorised if there is evidence that the herbal medicinal product has been traditionally used to treat the stated condition for a minimum of 30 years.

A THR means the medicine complies with

10 INTERNATIONAL PHARMACEUTICAL INDUSTRY

quality standards relating to safety and manufacturing, and it provides information about how and when to use it. The product carries a THR marking on its packaging. THR is not considered a useful route for mushroom regulation.

Enforcement and Penalties Enforcement action may be taken by Trading Standards, the FSA, or the MHRA, depending on the nature of the issue:

Safety and Quality Assurance Food (supplement) business operators are responsible for ensuring that mushroom supplements are safe for consumption. This involves:

•

• • •

•

Following good manufacturing practices (GMP) Conducting hazard analysis and critical control point (HACCP) assessments Performing microbiological testing for contaminants (e.g., heavy metals, pesticides, mycotoxins, pathogenic bacteria) Ensuring traceability and accurate documentation at every stage of production.

Importation and Online Sales Mushroom supplements imported into the UK must comply with all relevant UK legislation, regardless of their country of origin Imported supplements must be notified to the FSA if they constitute a new product. Products bought online from overseas vendors may bypass UK regulations, but importers and distributors are still liable for non-compliance. Online marketplaces are increasingly scrutinised by authorities to protect consumers from unsafe or mislabelled products. Consumers should be wary of unverified health claims or supplements not labelled in accordance with UK law.

•

•

Product recalls and market withdrawals for unsafe or non-compliant products.

Fines or prosecution for serious breaches, such as misrepresentation or sale of unauthorised novel foods or medicines.

Closure of non-compliant businesses or online listings.

Consumer complaints can trigger investigations, and there are established channels for whistleblowing or reporting unsafe products.

Challenges for Industry •

Education and misinformation: With the proliferation of unsubstantiated claims, consumer education is vital for sales of mushroom supplements if they are to maintain credibility. The UK’s digitally knowledgeable population often seeks online resources before making supplement choices making science-backed marketing essential.

•

Product quality: Variability in potency, purity and sourcing can affect efficacy and consumer trust. Content analysis with appropriate third-party testing and clear, transparent labelling is essential to ensure efficacy and quality.

•

Adulteration: Mushroom supplement adulteration is a significant issue where products are mislabelled or contain

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INTERNATIONAL PHARMACEUTICAL INDUSTRY 11

Regulatory & Marketplace undisclosed ingredients, potentially compromising quality and efficacy.

Common forms of adulteration include using mycelium grown on grain instead of the desired fruiting body, incorrect species identification, and the addition of cheaper fillers.38 This can lead to consumers not receiving the intended health benefits and can damage the reputation of the mushroom supplement industry.

•

•

•

Lack of standardisation: Dosage can vary widely between brands, and the concentration is not aways indicated.

Whole mushroom powder supplements may offer wide benefits while extracts often concentrate specific bioactives with specific health benefits.

Sustainability and supply chains: Consumers are increasingly concerned about how and where their supplements are produced and sourced. Transparent supply chains, organic ingredients, regenerative agriculture to improve soil health through mushroom production and ethical labour force are important to many consumers.

Changes in compliance: Brands must remain vigilant to changes in compliance and labelling requirements.

Mushrooms in Medical Treatment Development Mushrooms are increasingly being explored for their potential in medicinal development, particularly due to the bioactive compounds they contain, such as psilocybin and other alkaloids. Psilocybin, found in certain mushrooms, is already approved in Australia for treatment-resistant depression and is under investigation for other mental health conditions in various countries.39 Over 130 medicinal effects of mushrooms have been reported, including anti-diabetic, antioxidant, antimicrobial, anticancer, prebiotic, immunomodulating, anti-inflammatory and cardiovascular benefits. Several mushrooms have been tested in phase I, II, or III clinical trials for various diseases, including cancers and neurodegenerative disorders, as well as to affect immunity.40,41 Overall, few phase III trials have been performed, and in many cases, these trials included a relatively small number of patients. Therefore, despite the promising published clinical data, especially on immune modulation, more work is required to clarify the therapeutic value of mushrooms.

12 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Conclusion The mushroom supplement market in the UK is growing rapidly with growth expected to continue. Medicinal mushrooms have a long history of use in Eastern Medicine and modern scientific enquiry is revealing several health benefits, although more robust clinical trials are needed to verify emerging findings.

The regulatory landscape is challenging.

Most mushroom supplements are classified as food supplements and subject to food law, which means they must be labelled according to UK food labelling law, contain no unsafe ingredients, with no adulteration and assured purity with no contaminants. As food supplements mushrooms can only make health claims and these must be registered with the Great Britian NHC register. Brands must remain vigilant to changes in compliance and labelling requirements. Mushrooms are increasingly being explored for their potential in drug development in various conditions, particularly due to the bioactive compounds they contain, such as psilocybin and other alkaloids.

10.

11.

12.

13.

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UK Mushroom Market Size and Outlook 20232030. https://www.grandviewresearch.com/ horizon/outlook/mushroom-market/uk Łysakowska P, Sobota A, Wirkijowska A. Medicinal Mushrooms: Their Bioactive Components, Nutritional Value and Application in Functional Food Production-A Review.

Molecules. 2023 Jul 14;28(14):5393.

Bisen PS, Baghel RK, Sanodiya BS, Thakur GS, Prasad GB. Lentinus edodes: a macrofungus with pharmacological activities. Curr Med Chem. 2010;17(22):2419-30.

Yang H, Hwang I, Kim S, Hong EJ, Jeung EB. Lentinus edodes promotes fat removal in hypercholesterolemic mice. Exp Ther Med. 2013 Dec;6(6):1409-1413. do: 10.3892/etm.2013.1333.

Dai X, Stanilka JM, Rowe CA, Esteves EA, Nieves C Jr, Spaiser SJ, Christman MC, Langkamp-Henken B, Percival SS. Consuming Lentinula edodes (Shiitake) Mushrooms Daily Improves Human Immunity: A Randomized Dietary Intervention in Healthy Young Adults. J Am Coll Nutr.

2015;34(6):478-87.

He X, Wang X, Fang J, Chang Y, Ning N, Guo H, Huang L, Huang X, Zhao Z. Polysaccharides in Grifola frondosa mushroom and their health promoting properties: A review. Int J Biol Macromol. 2017 Aug;101:910-921.

Chen YH, Lee CH, Hsu TH, Lo HC. SubmergedCulture Mycelia and Broth of the Maitake Medicinal Mushroom Grifola frondosa (Higher Basidiomycetes) Alleviate Type 2 DiabetesInduced Alterations in Immunocytic Function.

Int J Med Mushrooms. 2015;17(6):541-56.

Jin X, Ruiz Beguerie J, Sze DM, Chan GC. Ganoderma lucidum (Reishi mushroom) for cancer treatment. Cochrane Database Syst Rev. 2016 Apr 5;4(4):CD007731.

Cör Andrejč D, Knez Ž, Knez Marevci M.

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Antioxidant, antibacterial, antitumor, antifungal, antiviral, anti-inflammatory, and nevro-protective activity of Ganoderma lucidum: An overview. Front Pharmacol. 2022 Jul 22;13:934982 Swallah MS, Bondzie-Quaye P, Wu Y, Acheampong A, Sossah FL, Elsherbiny SM, Huang Q. Therapeutic potential and nutritional significance of Ganoderma lucidum - a comprehensive review from 2010 to 2022. Food Funct. 2023 Feb 21;14(4):1812-1838 Ahmad MF, A Alsayegh A, Ahmad FA, Akhtar MS, Alavudeen SS, Bantun F, Wahab S, Ahmed A, Ali M, Elbendary EY, Raposo A, Kambal N, H Abdelrahman M. Ganoderma lucidum: Insight into antimicrobial and antioxidant properties with development of secondary metabolites.

Heliyon. 2024 Feb 4;10(3):e25607 Brandalise F, Cesaroni V, Gregori A, Repetti M, Romano C, Orrù G, Botta L, Girometta C, Guglielminetti ML, Savino E, Rossi P. Dietary Supplementation of Hericium erinaceus Increases Mossy Fiber-CA3 Hippocampal Neurotransmission and Recognition Memory in Wild-Type Mice. Evid Based Complement Alternat Med. 2017;2017:3864340.

Zhang J, An S, Hu W, Teng M, Wang X, Qu Y, Liu Y, Yuan Y, Wang D. The Neuroprotective Properties of Hericium erinaceus in Glutamate-Damaged Differentiated PC12 Cells and an Alzheimer's Disease Mouse Model. Int J Mol Sci. 2016 Nov 1;17(11):1810.

Saleh MH, Rashedi I, Keating A. Immunomodulatory Properties of Coriolus versicolor: The Role of Polysaccharopeptide.

Front Immunol. 2017 Sep 6;8:1087.

Pallav K, Dowd SE, Villafuerte J, Yang X, Kabbani T, Hansen J, Dennis M, Leffler DA, Newburg DS, Kelly CP. Effects of polysaccharopeptide from Trametes versicolor and amoxicillin on the gut microbiome of healthy volunteers: a randomized clinical trial. Gut Microbes. 2014 Jul 1;5(4):458-67.

Martínez-Mármol R, Chai Y, Conroy JN, Khan Z, Hong SM, Kim SB, Gormal RS, Lee DH, Lee JK, Coulson EJ, Lee MK, Kim SY, Meunier FA. Hericerin derivatives activates a panneurotrophic pathway in central hippocampal neurons converging to ERK1/2 signaling enhancing spatial memory. J Neurochem. 2023 Jun;165(6):791-808.

Yu ZT, Liu B, Mukherjee P, Newburg DS. Trametes versicolor extract modifies human fecal microbiota composition in vitro. Plant Foods Hum Nutr. 2013 Jun;68(2):107-12.

Xu YF. Effect of Polysaccharide from Cordyceps militaris (Ascomycetes) on Physical Fatigue Induced by Forced Swimming. Int J Med Mushrooms. 2016;18(12):1083-1092.

Yi, X., Xi-zhen, H. & Jia-shi, Z. Randomized double-blind placebo-controlled clinical trial and assessment of fermentation product of Cordyceps sinensis (Cs-4) in enhancing aerobic capacity and respiratory function of the healthy elderly volunteers. Chin. J. Integr. Med. 10, 187– 192 (2004).

Chen S, Li Z, Krochmal R, Abrazado M, Kim W, Cooper CB. Effect of Cs-4 (Cordyceps sinensis) on exercise performance in healthy older subjects: a double-blind, placebo-controlled trial. J Altern Complement Med. 2010 Autumn 2025 Volume 17 Issue 3

Regulatory & Marketplace

21.

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May;16(5):585-90.

Lo HC, Tu ST, Lin KC, Lin SC. The antihyperglycemic activity of the fruiting body of Cordyceps in diabetic rats induced by nicotinamide and streptozotocin. Life Sci. 2004 Apr 23;74(23):2897-908 Yu SH, Chen SY, Li WS, Dubey NK, Chen WH, Chou JJ, Leu SJ, Deng WP. Hypoglycemic Activity through a Novel Combination of Fruiting Body and Mycelia of Cordyceps militaris in High-Fat Diet-Induced Type 2 Diabetes Mellitus Mice. J Diabetes Res. 2015;2015:723190.

Ko SK, Jin M, Pyo MY. Inonotus obliquus extracts suppress antigen-specific IgE production through the modulation of Th1/Th2 cytokines in ovalbumin-sensitized mice. J Ethnopharmacol.

2011 Oct 11;137(3):1077-82.

Kim YR. Immunomodulatory Activity of the Water Extract from Medicinal Mushroom Inonotus obliquus. Mycobiology. 2005 Sep;33(3):158-62 Sun JE, Ao ZH, Lu ZM, Xu HY, Zhang XM, Dou WF, Xu ZH. Antihyperglycemic and antilipidperoxidative effects of dry matter of culture broth of Inonotus obliquus in submerged culture on normal and alloxandiabetes mice. J Ethnopharmacol. 2008 Jun 19;118(1):7-13 Hyun KW, Jeong SC, Lee DH, Park JS, Lee JS. Isolation and characterization of a novel platelet aggregation inhibitory peptide from the medicinal mushroom, Inonotus obliquus.

Peptides. 2006 Jun;27(6):1173-8.

27.

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Botanicals. https://www.efsa.europa.eu/en/ topics/topic/botanicals Directive 2002/46/EC of the European Parliament and of the Councilhttps://www. legislation.gov.uk/eudr/2002/46/contents Regulation (EC) No 178/2002 of the European Parliament and of the Council. https://www. legislation.gov.uk/eur/2002/178/contents Food Labelling and Packaging. https://www. gov.uk/food-labelling-and-packaging/foodlabelling-what-you-must-show Food Supplements Regulation (England) 2003 https://www.legislation.gov.uk/ uksi/2003/1387/contents Great British Nutrition and Health Claims (NHC) Register https://www.gov.uk/government/ publications/great-britain-nutrition-andhealth-claims-nhc-register.

‘On-hold’ health claims on foods. https://www. gov.uk/government/publications/on-holdhealth-claims-on-foods ASA ruling on Nowt Ventures Ltd. https://www. asa.org.uk/rulings/nowt-ventures-ltd-a241239905-nowt-ventures-ltd.html Shroom for Improvement. Navigating the Advertising Rules for Functional Mushrooms. https://www.asa.org.uk/news/shroom-forimprovement-navigating-the-advertisingrules-for-functional-mushrooms.html The Novel Foods (England) Regulations (2018). https://www.legislation.gov.uk/uksi/2018/154 Apply for a Traditional Herbal Registration. https://www.gov.uk/guidance/apply-for-a-

38.

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traditional-herbal-registration-thr Sourcing quality functional mushroom ingredients (part II https://nutraceutical businessreview.com/sourcing-qualityfunctional-mushroom-ingredients-part-ii Australia Legalizes Psychedelics for Use in Depression, PTSD Therapy. https:// psychiatryonline.org/doi/10.1176/appi. pn.2023.09.9.20 Panda SK, Luyten W. Medicinal mushrooms: Clinical perspective and challenges. Drug Discov Today. 2022 Feb;27(2):636-651 Abitbol A, Mallard B, Tiralongo E, Tiralongo J. Mushroom Natural Products in Neurodegenerative Disease Drug Discovery. Cells.

2022 Dec 6;11(23):3938.

Damien Bové Damien Bové, Chief Regulatory Officer and Scientific Advisor at ADACT Medical, an authority in analysis, testing, compliance and regulation and research across a range of health-related fields, including mushrooms.

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INTERNATIONAL PHARMACEUTICAL INDUSTRY 13

Regulatory & Marketplace

Navigating Compliance and Regulatory Readiness with Medical Information Post-market regulations have grown significantly more complex over time. As populations have become broader and more diverse, the risk of off-label use or misuse has increased, and navigating local regulatory nuances, cultural differences, and varying healthcare practices has become more difficult.

Global expansion, particularly for midsized pharmaceutical companies, can be challenging due to limited resources and a lack of in-house expertise needed to navigate regulatory and operational requirements across diverse markets.

No single team can be expected to navigate every regional law, culture, and evolving technology alone. This is where a trusted Medical Information (MI) partner becomes invaluable. This article outlines the critical operational areas where pharmaceutical companies must maintain compliance and highlights how the MI team can serve as compliant hubs for scientific exchange with the public.

Regulatory Frameworks around the Globe Pharmaceutical companies are expected to operate across borders while staying aligned with each region’s expectations for data protection, marketing practices, digital transparency, and safety communication.

Here’s a summary of some of the most critical compliance challenges currently impacting the industry, along with ways MI can provide valuable support.

EU Falsified Medicines Directive (FMD) and the U.S. Drug Supply Chain Security Act (DSCSA) Many countries have implemented strict drug tracking regulations, but the most notable developments occurred in the early 2010s, when both the EU and the U.S. established regulatory frameworks to combat counterfeit drugs in circulation. These frameworks introduced requirements such as unique identifiers (serialisation) and more rigorous record-keeping. Together, they help prevent harmful drugs from entering the supply chain and enable quicker responses to remove them, ultimately protecting public health.2,3 14 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Improving Clarity with MI Support Pharmaceutical companies must ensure their packaging, distribution, and reporting systems comply with these regulations.

Serialisation expertise within MI supports faster reporting of supply chain issues and enables clearer communication during recalls or when addressing product authenticity concerns.

Personal Information Protection Law (PIPL) of the People's Republic of China China, the country of a 1.4 billion population, enacted the PIPL and Data Security Law (DSL) in 2021, which is widely regarded as one of the strictest data security and privacy laws in the world.4 PIPL requires data to be collected with consent, stored within China, and restricts cross-border data transfers.

These rules apply to both domestic and foreign organisations that process personal information of individuals in China.

adverse events, MI plays a critical role in ensuring compliance. MI specialists receive GDPR training to ensure all customer interactions are handled appropriately and all systems used for communication and documentation are fully GDPR compliant.

Health Insurance Portability and Accountability Act (HIPAA) HIPAA is a U.S. federal law that defines which types of health information are protected and outlines how protected health information (PHI) may be used and disclosed by healthcare providers and related entities. It also grants patients specific rights over their health data, including access and control over how it is shared. Non-compliance with HIPAA can result in civil penalties and lawsuits, as well as criminal penalties, including imprisonment, for wilful violations.6

Local Presence Matters for MI Pharmaceutical companies need to comply with personal data processing regulations when handling product inquiries, complaints, and adverse event reports. To ensure compliance in China, it is essential to partner with a MI provider that has a locally established entity, secure documentation platforms, and expertise in local data governance.

Upholding HIPAA Compliance Through MI Expertise In the U.S., many MI specialists are healthcare professionals with strong HIPAA expertise.

They ensure that all processes involving product inquiries and adverse event reporting comply with legal requirements, including proper handling of protected health information (PHI). Their guidance helps pharmaceutical companies maintain HIPAA compliance, along with other regulatory requirements, across all MI activities.

EU General Data Protection Regulation (GDPR) GDPR is one of the strictest privacy laws in the world,6 enacted by the EU in 2018, imposing obligations on organisations anywhere in the world collecting data related to people in the EU. The data protection principles guide organisations on how to handle personal data responsibly and transparently. GDPR also outlines the rights of individuals, such as consent, access, and request for their data.

Non-compliance can result in a high fine, up to 20 million euros or 4% of global revenue, whichever is higher.5 Beyond financial impact, reputational damage can lead to further business loss.

EU Artificial Intelligence Act (AIA) EU AIA is the first comprehensive legal framework to regulate artificial intelligence in the EU. Enacted in 2024, its enforcement will roll out in phases by 2027 to ensure safe, transparent, and fair use of artificial intelligence (AI) based systems.7 The act classifies AI according to its risks, prohibiting systems that may cause harm to individuals or society. AIA places the majority of obligations, such as risk assessment, audit trails, and transparency, on developers and deployers.

Penalties for non-compliance are higher than the General Data Protection Regulation (GDPR), up to 35 million euros or 7% of annual turnover, whichever is greater.

Embedded Compliance in Front-End Communications with MI As the primary point of contact for customers seeking product information or reporting

Aligning AI with Compliance through MI As AI tools like chatbots and virtual assistants become more prevalent, MI plays a critical role in supporting compliant Autumn 2025 Volume 17 Issue 3

Regulatory & Marketplace

implementation. MI can help ensure these tools are designed to be unbiased and transparent, while also defining appropriate practices for data capture, storage, and oversight. MI’s involvement is essential in aligning AI-enabled solutions with regulatory expectations and safeguarding patient trust.

U.S. Artificial Intelligence (AI) Regulation Development While the U.S. does not yet have federal AI legislation, states and institutions are stepping in. An Executive Order titled ‘Safe, Secure, and Trustworthy Development and Use of Artificial Intelligence’, issued in October 2024, was revoked in January 2025, signalling a shift toward decentralised regulation.

National Institute of Standards and Technology (NIST): Artificial Risk Management Framework (AI RMF) NIST worked with public and private sectors to develop AI RMF, first released in 2023 and last updated in July 2024. It is designed for organisations to voluntarily use to incorporate trustworthiness considerations into the development and use of AI systems.8 Food and Drug Administration (FDA): Software as Medical Device (SaMD) Artificial Intelligence (AI) and Machine Learning (ML) are inclusive of SaMD riskbased pathways for approval. In January 2025, the FDA released a draft guidance titled Artificial Intelligence-Enabled Device Software Functions: Lifecycle Management and Marketing Submission Recommendations.

The guidance outlines how to manage ongoing modifications to AI algorithms, with www.international-pharma.com

a focus on transparency, data quality, and performance monitoring expectations.

Federal Trade Commission (FTC): Operation AI Comply In September 2024, the FTC launched a broad crackdown on the deceptive use of AI, taking enforcement action against five companies involved in misleading practices such as false claims about AI-powered legal services, the generation of fake consumer reviews, and AI-driven business scams.9 This marked a significant step in the agency’s commitment to protect consumers and maintain market integrity as AI technologies become more widespread. In addition to these actions, the FTC is actively investigating other instances of AI misuse reported by consumers, pursuing them on a case-by-case basis.

Supporting Ethical and Compliant AI Through MI The integration of AI into medical communication presents immense opportunities to enhance efficiency, personalisation, and access to information.

However, in the absence of comprehensive federal legislation and amid a patchwork of evolving agency-level regulations, the risks are equally substantial. This is where highly experienced MI professionals bring the regulatory and operational expertise needed to responsibly evaluate AI tools before implementation.

Beyond vetting, the MI team is instrumental in developing detailed usecases, defining appropriate boundaries for AI deployment, and identifying potential

risk points. Most importantly, they serve as the essential layer of human oversight, ensuring that AI-driven communication remains accurate and ethical.

The Value of Medical Information as a Strategic Regulatory Partner Maintaining regulatory readiness is a crucial operational requirement in today's rapidly evolving, technology-driven pharmaceutical industry. With targeted medicine and the use of smart devices reshaping the treatment model,1 pharmaceutical companies are facing challenges to keep up with increasingly complex and fragmented regulations, from healthcare authorities to data security and privacy. The pressure to innovate and customise has never been greater, yet even the slightest oversight can have negative consequences for companies.

Post-Market Expansion and Compliance with Medical Information After product launch, the right regulatory partner and highly experienced communication hub, MI, can support companies navigate the complexities of applicable laws and industry standards; not only in healthcare, but also in areas such as data security and emerging technologies.

Benefits of the Right Partner •

Regulatory Foresight – Effective compliance requires anticipating regulatory shifts before they become urgent matters. A proactive partner continuously scans the global landscape, identifies emerging trends, and prepares INTERNATIONAL PHARMACEUTICAL INDUSTRY 15

Regulatory & Marketplace

your team to adapt early, reducing risk and ensuring uninterrupted operations.

•

•

•

Global Presence and Local Expertise – Staying ahead of evolving global regulations requires a deep understanding of how these changes translate at the local level. The right partner brings cross-regional expertise to help interpret, adapt, and implement regulatory requirements.

Implementation and Operation Support – Implementing compliant workflows or systems within MI requires both regulatory knowledge and practical expertise. The right partner not only understands the requirements but also brings the frameworks, technology, and operational insight to optimise and scale processes that meet global standards, ensuring compliance is embedded in daily operations.

Innovation with Compliance – Innovation can be challenging within strict regulatory frameworks. The right partner drives compliant innovation by collaborating with cross-functional experts, while MI professionals ensure that compliance requirements are clearly defined and integrated. True innovation is sustained through ongoing research, thoughtful design, continuous adoption of new solutions, and rigorous oversight.

16 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Achieving Compliance Through Strategic Alignment with Medical Information Post-market pharmaceutical compliance continues to evolve, with increasingly divergent global and local requirements. Yet, this complexity can be proactively managed by leveraging MI as a strategic compliance partner.

MI plays a critical role in ensuring regulatory readiness by: • • • • •

Adapting content to meet local regulatory nuances without losing global consistency Ensuring consistent, compliant, and medically accurate communication Supporting audit preparedness through regulatory-compliant, traceable processes Monitoring inquiry trends for early signal detection and safety insights Guiding the responsible implementation of advanced technologies and AI in medical communications

By embedding MI into compliance strategies, companies can shift from reactive approaches to proactive readiness. With the right systems and experts in place, compliance becomes a continuous state instead of a crisis response.

REFERENCES 1.

2.

https://www.grandviewresearch.com/industryanalysis/us-pharmaceuticals-market-report, https://health.ec.europa.eu/medicinal-

3.

4.

5.

6.

7.

8.

9.

products/falsified-medicines_en, https://www.fda.gov/drugs/drug-supply-chainintegrity/drug-supply-chain-security-act-dscsa Creemers, R. China’s emerging data protection framework, Journal of Cybersecurity, Volume 8, Issue 1, 1-12 (2022) https://gdpr.eu/what-is-gdpr/ https://www.hipaajournal.com/what-happensif-you-violate-hipaa/, https://artificialintelligenceact.eu/, https://www.nist.gov/itl/ai-risk-managementframework https://www.ftc.gov/news-events/news/pressreleases/2024/09/ftc-announces-crackdowndeceptive-ai-claims-schemes

Rajul Jain Rajul Jain, President of Medical Information (MI) at ProPharma, has over 20 years of global experience in MI, Pharmacovigilance, Technology, and Programme Management. With an MBA, engineering background, PMP, and certifications including AI in Healthcare (Harvard) and ACMA, Rajul brings a wealth of knowledge in her role, leading global contact centers, and is passionate about operational excellence, innovation, and delivering long-term client value in healthcare and pharma.

Email: rajul.jain@propharmagroup.com

Autumn 2025 Volume 17 Issue 3

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INTERNATIONAL PHARMACEUTICAL INDUSTRY 17

Mental Health & Neurodegenerative Disease

Intranasal Insulin for Alzheimer’s: Advancing Brain-Targeted Delivery Alzheimer’s disease (AD) represents a growing public health concern.

While earlier estimates placed global prevalence of dementia at around 50 million people, more recent evidence suggests some form of AD may affect as many as 416 million people worldwide.1 With increasing life expectancy and an ageing global population, this number is expected to rise even further in the coming decades, leading to increased demand on healthcare infrastructure and families.1,2 Growing Need for Multidisciplinary Treatment Despite decades of research and global efforts to find a cure, treatment options for AD remain limited.3,4 The amyloid cascade hypothesis – which implicates the accumulation of proteins in and around brain cells as the primary cause of AD – has long dominated therapeutic research.5 This has led to the development of anti-amyloid antibodies, which have received regulatory approval in the United States for their ability to reduce plaque burden and slow disease progression.6 However, many trials have yielded mixed results, showing only limited impact on improving cognitive symptoms.3,4,6 In addition, some individuals diagnosed with AD do not present significant plaque deposits, while others show pathological features without measurable cognitive impairment.4 As a result, the clinical value of amyloid clearance is increasingly being questioned.

A growing body of evidence now suggests that AD is a multifactorial syndrome rather than a single condition, involving a range of mechanisms including insulin resistance, hormonal changes, vascular dysfunction, and inflammation.4,5

a phenomenon sometimes controversially referred to as “type 3 diabetes”4,7 Despite accounting for only 2% of the total body weight, the brain consumes approximately 20% of glucose-derived energy.8 This high demand reflects glucose’s central role in neuronal signaling.4,8 Insulin signalling, in addition to facilitating glucose uptake into neurons, is also shown to directly affect neuronal upkeep, vascular regulation, synaptic signalling, and neuromodulation – all of which are relevant to cognitive functioning.4,9 Intranasal insulin (INI) presents a novel and promising method for addressing this dysfunction by delivering insulin directly to the brain via the nasal cavity.7,9 This noninvasive, targeted approach has shown encouraging results in early clinical studies, with evidence suggesting it may improve memory and cognitive function, preserve brain volume, and improve AD biomarker profiles.4,10,11 Mechanism of Nose-to-Brain Transport The effectiveness of INI depends largely on the unique anatomical and physiological features of the nasal cavity. Drugs delivered intranasally can access the brain through the olfactory and trigeminal nerve pathways.

These routes allow for extracellular transport to the subarachnoid space and broader distribution throughout the central nervous system (CNS).7,12 This method of delivery is particularly valuable because it bypasses the bloodbrain barrier (BBB), a highly selective barrier that prevents most drugs from entering the brain from the bloodstream.13 Traditional approaches to bypass the BBB often involve invasive techniques or chemical modification of therapeutic agents, both of which pose additional risks and limitations.13,14 In contrast, intranasal delivery offers a direct and non-invasive route to the brain.7 There are also significant safety benefits.

INI avoids first-pass metabolism in the liver and minimises systemic exposure, reducing the risks of adverse events such as hypoglycaemia.3,7 This localised approach helps to maintain insulin activity in people with AD where it is needed most, without significantly altering peripheral glucose levels.

Studies Demonstrate Feasibility and Safety of INI To support the development of INI for human use, a preclinical study was conducted

In light of these limitations, there is an increasing interest in alternative therapeutic strategies that target different aspects of AD pathology. One such approach focuses on the role of insulin in the brain.4,7 Intranasal Insulin as a Promising Alternative Research has shown that insulin signalling is disrupted in the brains of individuals with AD, 18 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Autumn 2025 Volume 17 Issue 3

Mental Health & Neurodegenerative Regulatory & Marketplace Disease olfactory region where absorption into the brain can occur.16,17 As a result, much of the medication may be absorbed into systemic circulation, diminishing its effectiveness for CNS applications.17 To achieve consistent and targeted brain delivery, specialised intranasal systems are needed. These systems must be designed to navigate the complex anatomy of the nasal cavity and deliver medication with precision.

This optimisation of nasal drug delivery for CNS applications is essential to fully realise the potential of INI in clinical settings.16

using adult vervet monkeys to assess the biodistribution of insulin delivered via an intranasal device.12 Researchers administered radiolabelled insulin using Aptar Pharma’s Cartridge Pump System (CPS) and tracked its distribution using real-time PET imaging.

This study demonstrated that INI via the CPS reached multiple key brain regions, including the amygdala, putamen, hypothalamus, and choroid plexus. Uptake in these regions was visible for up to 60 minutes postadministration, confirming successful and sustained delivery to the brain. No adverse safety signals were reported; vitals and blood glucose levels remained stable, and no signs of hypoglycaemia were observed.

Additionally, whole-body radiation dosimetry showed low exposure across all organs, indicating a favourable safety profile.

These pre-clinical findings were supported by a similar PET imaging study in human participants.15 This study included a mixed cohort of cognitively normal adults (n=7) and participants with mild cognitive impairment

www.international-pharma.com

(MCI), both with (n=6) and without (n=3) evidence of amyloid-ß accumulation.

Results showed measurable brain uptake of radiolabelled insulin in regions associated with cognition and Alzheimer’s pathology, including the hippocampus, amygdala, superior and middle temporal pole, and anterior cingulate cortex. Uptake varied based on cognitive status, sex, and vascular factors. As in the non-human primate study, no severe adverse safety signals were reported. Vital signs levels remained stable, with no signs of hypoglycaemia observed.

Optimising Delivery Systems for CNSTargeted Intranasal Therapy The promise of effective INI depends not only on the drug itself but also on how it is delivered.7 Some nasal spray delivery devices, such as those used in allergic rhinitis, are not designed for CNS targeting. These systems tend to deposit medication in the nasal vestibule (the front part of the nasal cavity) rather than the upper nasal cavity near the

Although the CPS has demonstrated effective brain delivery via the olfactory and trigeminal nerves in non-human primate studies, unpublished in vitro nasal cavity model data suggest that its ability to deposit certain formulations in the upper nasal cavity may be limited. In the Wake Forest study, an add-on device was used to assist with positioning the spray within the nasal cavity, as the CPS itself was not specifically optimised for olfactory targeting due to targeted spray technology still being in its early stages.

Since then, advances in the field have led to the development and clinical validation of an olfactory-targeting nasal pump by Aptar Pharma. Nasal cast studies have shown optimised administration parameters such as spray geometry, plume angle, and particle size distribution which allow for improved deposition of the product to the olfactory region.16,18 In vitro testing with a low-viscosity placebo formulation showed that Aptar Pharma’s specialised nasal pump reaches up to 50% olfactory deposition under varied spray angles,18 whereas the CPS achieves 4–27% in the olfactory at certain orientations as seen in unpublished data. Additional studies are needed to determine whether increased olfactory deposition could enhance insulin uptake and how it might affect the delivery of other formulations.

INTERNATIONAL PHARMACEUTICAL INDUSTRY 19

Mental Health & Neurodegenerative Disease

13.

14.

15.

16.

Future Directions for CNS Drug Delivery As research progresses from preclinical to clinical phases, additional human studies will be essential to determine its therapeutic potential. These trials will need to assess safety, optimal dosing, and ultimately, clinical efficacy in slowing or improving cognitive decline. PET imaging and physiologically relevant modelling will also be instrumental in validating nose-to-brain delivery and guiding clinical development.

Beyond Alzheimer’s the potential applications for intranasal brain delivery extend to other neurodegenerative and CNS disorders, including Parkinson’s disease, epilepsy, migraine, and psychiatric conditions.13 As a non-invasive, patientfriendly method, intranasal delivery for these therapeutic areas could enhance adherence and reduce overall treatment burden.7 Establishing a reliable and reproducible delivery method is not only critical for achieving consistent therapeutic effects, but also influences formulation strategies, patient experience, and regulatory pathways.

The goal is to have a platform of products that meet different targeted zones to satisfy the requirements of different molecules and formulations. Tailored intranasal systems that ensure targeted CNS delivery may help derisk clinical programs and accelerate development timelines across multiple CNS indications.

Conclusion Intranasal insulin offers a promising new direction for treating Alzheimer’s disease and other CNS disorders. With growing evidence supporting its safety, feasibility, and brain-targeted efficacy, INI may fill critical gaps left by current therapies.

The ability to bypass the blood-brain barrier, deliver treatments non-invasively, and potentially improve cognitive outcomes positions INI as a compelling therapeutic 20 INTERNATIONAL PHARMACEUTICAL INDUSTRY

strategy. As human trials progress and delivery technologies continue to advance, the pharmaceutical industry has a unique opportunity to lead the way in this evolving field of brain-targeted treatment.

REFERENCES 1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

Gustavsson A, Norton N, Fast T, et al. Global estimates on the number of persons across the Alzheimer’s disease continuum. Alzheimer’s & Dementia 2023;19:658–70.

Javaid SF, Giebel C, Khan MA, Hashim MJ. Epidemiology of Alzheimer’s disease and other dementias: rising global burden and forecasted trends. F1000 Research 2021 10:425 2021;10:425.

Passeri E, Elkhoury K, Morsink M, et al.

Alzheimer’s Disease: Treatment Strategies and Their Limitations. International Journal of Molecular Sciences 2022, Vol 23, Page 13954 2022;23:13954.

Yoon JH, Hwang JH, Son SU, et al. How Can Insulin Resistance Cause Alzheimer’s Disease? Int J Mol Sci 2023;24:3506.

Goetzl EJ. Current Developments in Alzheimer’s Disease. Am J Med 2025;138:15–20.

Perneczky R, Jessen F, Grimmer T, et al. Antiamyloid antibody therapies in Alzheimer’s disease. Brain 2023;146:842–9.

Wong CYJ, Baldelli A, Hoyos CM, et al. Insulin Delivery to the Brain via the Nasal Route: Unraveling the Potential for Alzheimer’s Disease Therapy. Drug Deliv Transl Res 2024;14:1776.

Mergenthaler P, Lindauer U, Dienel GA, Meisel A. Sugar for the brain: the role of glucose in physiological and pathological brain function.

Trends Neurosci 2013;36:587.

Kellar D, Craft S. Brain insulin resistance in Alzheimer’s disease and related disorders: mechanisms and therapeutic approaches.

Lancet Neurol 2020;19:758–66.

Craft S, Claxton A, Baker LD, et al. Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer’s Disease Biomarkers: A Pilot Clinical Trial. Journal of Alzheimer’s Disease 2017;57:1325–34.

Kellar D, Register T, Lockhart SN, et al. Intranasal insulin modulates cerebrospinal fluid markers of neuroinflammation in mild cognitive impairment and Alzheimer’s disease: a randomized trial. Sci Rep 2022;12.

Sai KKS, Erichsen JM, Gollapelli KK, et al. First Biodistribution Study of [68Ga]Ga-NOTA-Insulin Following Intranasal Administration in Adult

17.

18.

Vervet Monkeys. Journal of Alzheimer’s Disease 2024;101:309–20.

Lochhead JJ, Thorne RG. Intranasal delivery of biologics to the central nervous system. Adv Drug Deliv Rev 2012;64:614–28.

Gabathuler R. Approaches to transport therapeutic drugs across the blood–brain barrier to treat brain diseases. Neurobiol Dis 2010;37:48–57.

Sai KKS, Erichsen JM, Gollapelli KK, et al. First-inhuman positron emission tomography study of intranasal insulin in aging and MCI. Alzheimers Dement (N Y) 2025;11.

Djupesland PG, Messina JC, Mahmoud RA. The Nasal Approach to Delivering Treatment for Brain Diseases: An Anatomic, Physiologic, and Delivery Technology Overview. Ther Deliv 2014;5:709–33.

Trevino JT, Quispe RC, Khan F, Novak V. NonInvasive Strategies for Nose-to-Brain Drug Delivery. J Clin trials 2020;10:439.

Farias G, Hauchard N, Pringault M, et al.

Optimization of a Multidose Nasal Actuator Targeting Olfactory Region Deposition, Tuscon, Arizona: Respiratory Drug Delivery; 2024.

Julie Suman Julie Suman, PhD, is the Vice-President of Scientific Affairs for Aptar Pharma.

Dr Suman holds a BSc in Pharmacy and a PhD in Pharmaceutical Sciences.

She is co-editor for Respiratory Drug Delivery Proceedings, and an Affiliate Assistant Professor in the Department of Pharmaceutics at Virginia Commonwealth University (VA, US). She also co-founded Next Breath, an analytical services company. Dr. Suman has published in several peer-reviewed journals and presented at numerous international meetings.

Reenal Gandhi Reenal Gandhi is Global Business Development Director at Aptar Pharma’s Prescription division, focused on assessing new technologies. With over 15 years in drug delivery and pharma, she is passionate about developing combination products that balance formulation, device technology, and commercial potential.

Prior to joining Aptar in 2020, she held roles in licensing and acquisitions at global pharma and device companies.

Autumn 2025 Volume 17 Issue 3

Decades of proven Unidose delivery

Trust the first single-dose nasal spray system used in U.S. FDA- and EMA-approved Unidose products; the only system with decades of successful delivery on the market.

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The Unidose system (UDS) by Aptar Pharma is a market-proven platform, chosen by the world’s leading pharmaceutical companies.

What began as a breakthrough in single-dose delivery has become a global nasal delivery platform. Engineered for safety, quality, and performance, Aptar Pharma’s Unidose system can support you in achieving 99.999% reliability with every dose.

Aptar Pharma’s nasal delivery platform accommodates a wide range of needs – from liquid or powder formulations to unidose or bidose delivery, for adult or pediatric use, whether in routine or emergency situations – making it adaptable for most indications.

Backed by decades of manufacturing expertise and a robust quality management system, Aptar Pharma helps derisk development at every stage, effectively supporting market approval and patient adoption.

When performance matters, experience leads.

Explore the Unidose platform at aptar.com/pharmaceutical.

From formulation to patient. www.international-pharma.com

INTERNATIONAL PHARMACEUTICAL INDUSTRY 21

Mental Health & Neurodegenerative Disease

Mapping the Proteome to Understand the Complexity of Neurodegenerative Diseases Neurological conditions have emerged as the leading global cause of illness and disability, impacting more than 3 billion people.1 Among these, neurodegenerative diseases stand out for their relentless progression, lack of curative treatments, and their rising prevalence within aging populations. In particular, Alzheimer’s disease is known for its slow onset and progressive deterioration, and the lack of a cure underscores the critical need to deepen our understanding of the molecular cues that lead to neurodegeneration, with the goal of identifying effective preventative and therapeutic measures.

Neurodegenerative diseases like Alzheimer's, Parkinson’s, amyotrophic lateral sclerosis (ALS) and Huntington’s are all characterised by disrupted proteome homeostasis and selective neuronal loss.

These conditions have become a significant burden for an ageing society, with onethird of people in industrialised nations expected to develop a neurodegenerative disease during their lifetime.1 Their extended disease courses, progressive deterioration and necessity for long-term care underscore the urgency of understanding the molecular mechanisms driving neurodegeneration.

Mass spectrometry (MS)-based proteomics serves as a powerful window into neurodegeneration, enabling researchers to comprehensively analyse changes in protein abundance, modifications, interactions, and degradation pathways. A key advance of this approach is the study of proteoforms, the structurally and functionally diverse protein variants derived from the same gene as a result of genetic variation, alternative splicing and post-translational modifications (PTMs).

Investigating proteoforms sheds new light on protein function and dysfunction within neurodegenerative disease contexts and is crucial for resolving complex disease mechanisms.

MS enables highly sensitive, highthroughput identification and quantification of disease-relevant proteome alterations from model systems to human tissues. This 22 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Figure 1: A schematic highlighting key proteomics-driven strategies to dissect the molecular underpinnings of neurodegenerative diseases.

deep level of molecular resolution allows researchers to trace neurodegenerative processes from early pathology to advanced disease stages. By capturing a holistic view of the proteome and its diverse proteoforms, MSbased proteomics not only aids in uncovering critical disease biology but also accelerates the discovery of potential therapeutic targets and biomarkers, highlighting biological pathways implicated in disease initiation and progression (see Figure 1).2 Integrating these advanced techniques into neurodegenerative research will be pivotal for advancing therapeutic development in the field.

Proteostasis, Protein Interactions and Aggregation in Neurodegeneration It is essential to examine protein homeostasis, to understand the molecular mechanisms underpinning neurodegenerative diseases.

Protein homeostasis, or proteostasis, is the regulation and maintenance of the cellular functional protein environment (proteome), ensuring that proteins are correctly folded, modified, and translocated, as well as appropriately degraded when damaged or no longer needed. Characteristic of neurodegenerative disease, disruption of proteostasis leads to the accumulation of misfolded proteins or protein aggregates that impair cellular function and trigger neuronal death. Huntington's disease for example, is characterised by the formulation of extended protein aggregates that cause widespread neuronal toxicity and severe clinical phenotypes. ALS is similarly associated with hundreds of genetic risk factors which converge on pathways that destabilise proteome integrity. A particularly aggressive form of ALS is associated with the genetic Autumn 2025 Volume 17 Issue 3

Mental Health & Neurodegenerative Regulatory & Marketplace Disease risk factor C9orf72, which has been reported to drive pathology through multiple routes including production of a di-peptide repeat that forms resilient aggregates, sequestering hundreds of different proteins and driving widespread proteostasis collapse.3

to detect thousands of proteins and tens of thousands of peptides from only a few picogram (less than a single HeLa cell) opens the opportunity to work with highly limited amounts of material e.g., from axonal cell regions.

Protein aggregation is a hallmark of many neurodegenerative diseases. MSbased proteomics enables detailed analysis of the composition and structure of these aggregates, helping to understand their formation and impact on cellular function.

Unlike epitope-dependent approaches, MS can detect a vast range of peptides, including PTM-bearing ones, even after harsh denaturation of highly insoluble deposits.

Studies have revealed hundreds of proteins sequestered in such aggregates, providing insight into their formation, cellular impact, and neurotoxicity.4,5 Beyond compositional analysis, chemoproteomics strategies aimed at degrading aggregation-prone proteins may offer novel therapeutic avenues.

Deep visual proteomics (DVP) approaches combine MS with imaging techniques to study the spatial distribution of proteins within tissues and support understanding the regional specificity of protein changes in the brain by resolving distinct brain regions and cell types for their role in disease pathology. Laser capture microdissection (LCM) technologies along with unbiased, high sensitivity MS highlight new opportunities to study diseases at a sub tissue resolution.10 These technologies hold potential to resolve spatial and temporal disease phenotypes and progression in neurodegeneration from human tissues or organoids. Many neurodegenerative disorders affect specific areas of the brain, with prion-like spreading towards neighbouring regions and intricate neuroinflammatory processes being proposed as key drivers of disease progression.11 Resolving spatial and temporal progress in model systems or post-mortem human tissue may reveal better insights into the pathological cascade.

MS-based proteomics also enables the mapping of protein-protein interaction networks in neurodegenerative diseases, revealing how both stable physiological complexes and aberrant pathological protein aggregates maintain and disrupt cellular processes, respectively. High throughput proteomics has made largescale interactions studies feasible, achieving sufficient sensitivity to detect even trace protein interactions in clinical isolates.6 While changes in interaction networks driven by PTMs or disease-associated mutations cannot be elucidated through genetic or targeted affinity approaches, MS-based methods have proven particularly powerful in these contexts, such as in the study of hyperphosphorylated Tau, offering critical insights into diseaseassociated interactome remodelling.7 Similar approaches hold great promise for uncovering pathological interaction networks in other neurodegenerative diseases.

Advanced Proteomic Technologies and Spatial-Temporal Analysis Recent advancements in MS sensitivity enable proteome analysis at sub single-cell level, enabling comprehensive proteomics insights down to single bacteria and subcellular proteomes.8,9 This sensitivity is useful for studying heterogeneous cell populations in the brain and understanding cell-specific contributions to neurodegenerative diseases, in particular from organoids or working with limited material. While isolating single neurons can be challenging given their complex and fragile morphology, the ability www.international-pharma.com

Immune-Related Pathogenic Mechanisms Immunopeptidomics, the study of peptides presented by major histocompatibility complex (MHC) molecules, has significant links to neurodegeneration through various mechanisms like immunogenicity. MS-based proteomics can directly survey cell surface decoration of immunopeptides and monitor MHC shed into circulation. Tailored acquisitions enable highly effective coverage of singly and multiply charged immunopeptides, and de novo sequencing and PTM search strategies significantly enhance the capabilities of MS-based immunopeptidomics to study immune homeostasis.12 The proteasome which degrades intracellular proteins plays a key role in in both decoration of MHC as well as in dealing with aberrantly folded proteins, hence providing an intriguing yet underexplored connection between immunopeptidomics and neurodegeneration.

Additionally, because neuroinflammation plays a key role in neurodegeneration, peptides derived from aggregated or misfolded proteins could elicit adaptive immune responses and contribute to the problem. Protein-aggregates themselves may also be linked to inflammation mediated by brain-resident cells including microglia

and astrocytes, leading to neuronal damage and brain atrophy. By studying the peptides presented by MHC, immunopeptidomics can provide valuable insights into the immunogenicity and inflammatory processes involved in neurodegenerative diseases, helping to identify potential therapeutic targets and improve understanding of disease mechanisms.

Biomarker Identification for Early Detection Identifying biomarkers is crucial in early diagnosis and monitoring disease progression. MS-based proteomics can discover and validate biomarkers in body fluids like cerebrospinal fluid (CSF) and blood, facilitating early detection and supporting personalised treatment strategies. Many neurodegenerative diseases develop for years at the molecular level before the onset of any symptoms; therefore, it could be assumed that early risk trajectories are key for interventions. With the introduction of trapped ion mobility spectrometry combined with a time-of-flight mass spectrometer (timsTOF), In conjunction with deep workflows using particle technologies, MS is ideally suited to deliver high-quality population scale access and discovery of novel circulating biomarkers.13,14 Therapeutic Possibilities Chemoproteomics and targeted protein degraders offer promising avenues for understanding and treating neurodegenerative diseases.15 Benefiting from robust, quantitative, and deep insights into a cell’s protein repertoire across various model systems, MS has enabled unbiased chemoproteomics at scale. Chemoproteomics involves the use of chemical probes to study small molecule-protein interactions and functions within the cellular environment, providing insights into the molecular mechanisms underlying neurodegeneration. In addition, those modifications could change the physicochemical properties of proteins sufficiently to potentially affect their aggregation/ disaggregation propensity, which may offer a novel therapeutic avenue. Targeted protein degraders, such as proteolysis-targeting chimeras (PROTACs) and molecular glues, leverage the ubiquitin-proteasome system to selectively degrade disease-associated proteins.

This approach is particularly valuable in neurodegenerative diseases, where protein aggregates and misfolded proteins play a central role in pathology. By facilitating the removal of these harmful proteins, targeted protein degraders could mitigate neuronal damage and improve cellular function. The INTERNATIONAL PHARMACEUTICAL INDUSTRY 23

Mental Health & Neurodegenerative Disease integration of these technologies holds great potential for advancing basic research in neurodegeneration and developing innovative therapeutic strategies.

In Summary Neurodegenerative diseases pose a key challenge to an ageing society, with disrupted proteome homeostasis at the core of their pathology. MS-based proteomics offers the potential to unravel the intricacies of these disorders, from identifying and quantifying proteins to characterising PTMs, analysing protein aggregates and mapping proteinprotein interaction networks. By leveraging these capabilities, researchers can gain critical insights into the molecular mechanisms driving neurodegeneration to provide a clearer picture of disease progression from early events to advanced pathology. As these technologies become further integrated into research, they will hold greater promise for identifying novel biomarkers, illuminating therapeutic targets and paving the way toward innovative diagnostic and treatment strategies.

REFERENCES 1.

2.

3.

4.

https://www.who.int/news/item/14-03-2024over-1-in-3-people-affected-by-neurologicalconditions--the-leading-cause-of-illness-anddisability-worldwide.

Schumacher-Schuh A, Bieger A, Borelli WV, Portley MK, Awad PS, Bandres-Ciga S. Advances in proteomic and metabolomic profiling of neurodegenerative diseases.

Kharat S, Mali S, Korade G, Gaykar R. Navigating neurodegenerative disorders: a comprehensive review of current and emerging therapies for neurodegenerative disorders.

Teixeira M, Sheta R, Musiol D, Loehr J, Lambert

5.

6.

7.

8.

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12.

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14.

15.

JP, Oueslati A, et al. Combining light-induced aggregation and biotin proximity labeling implicates endolysosomal proteins in early α-synuclein oligomerization.

Woerner AC, Frottin F, Hornburg D, Feng LR, Meissner F, Patra M, et al. Cytoplasmic protein aggregates interfere with nucleocytoplasmic transport of protein and RNA. Science.

Michaelis AC, Brunner A-D, Zwiebel M, Meier F, Strauss MT, Bludau I, Mann M. The social and structural architecture of the yeast protein interactome.

Tracy TE, Madero-Pérez J, Swaney DL, et al. Tau interactome maps synaptic and mitochondrial processes associated with neurodegeneration.

Xian F, Brenek M, Krisp C, et al. Ultra-sensitivity metaproteomics redefines the gut “dark metaproteome,” uncovering host-microbiome interactions and drug targets in intestinal inflammatory diseases.

Krisp C, Bekker‑Jensen D, Hørning OB, et al.

Exceeding 1000 cells per day – scalable single cell analysis using the Evosep Whisper Zoom method on the timsTOF Ultra 2.

Mund A, Coscia F, Kriston A, et al. Deep Visual Proteomics defines single-cell identity and heterogeneity.

Zhang W, Xiao D, Mao Q, et al. Role of neuroinflammation in neurodegeneration development. Signal Transduct Target Ther.

Gomez-Zepeda D, Arnold-Schild D, Beyrle J, et al. Thunder-DDA-PASEF enables high-coverage immunopeptidomics and is boosted by MS2Rescore with MS2PIP timsTOF fragmentation prediction model.

Szyrwiel L, Gille C, Mülleder M, Demichev V, Ralser M. Speedy-PASEF: analytical flow rate chromatography and trapped ion mobility for deep high-throughput proteomics.

Viode A, van Zalm P, Smolen KK, et al. A simple, time- and cost-effective, high-throughput depletion strategy for deep plasma proteomics.

Gregory JA, Hickey CM, Chavez J, Cacace AM. New therapies on the horizon: Targeted protein degradation in neuroscience.

Daniel Hornburg Daniel earned his Ph.D. with Matthias Mann at the Max Planck Institute, studying proteome changes in neurodegenerative diseases. He continued research on computational immunoproteomics with Mann and Meissner, then developed multi-omics strategies for metabolic disorders with Mike Snyder’s team.

Previously VP Proteomics at Seer, Daniel is now VP Biomarkers and Precision Medicine at Bruker. He has served on advisory boards and received the Human Proteome Organization Science and Technology Award.

Torsten Müller Torsten started in proteomics at IBMB Bonn then gained expertise in method development and advanced MS at Boston Children's Hospital and ETH Zürich. From 2016 to 2020, Torsten completed his PhD with Prof. Jeroen Krijgsveld at Heidelberg and DKFZ, improving and automating the SP3 sample preparation method now widely used in proteomics. As a postdoc, he advanced clinical proteomics with the autoSP3 pipeline before joining Bruker Daltonics in 2022.

Stefan Foser Stefan combines academic excellence with nearly two decades of professional experience in the pharmaceutical and diagnostics sectors. Holding a Ph.D. in Microbiology, in addition to degrees from the Universities of Basel, Switzerland and Mannheim, nearly twenty publications and patents, Stefan was awarded an Executive MBA from the University of St Gallen. Stefan honed his expertise through roles at Roche, Siemens Healthineers and now as VP Global Pharma at Bruker Daltonics

24 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Autumn 2025 Volume 17 Issue 3

Mental Health & Neurodegenerative Regulatory & Marketplace Disease

Advancements in Neuromodulation: A New Era for Respiratory Health Neuromodulation is an approach that involves the use of devices to normalise or modulate nerve activity through the targeted delivery of electrical stimuli.

Electrical stimuli can be delivered either invasively through surgical implantation of the device under the skin or non-invasively through the external application of a device to the skin.

Applications for neuromodulation are increasing and include the use of deep brain stimulation (DBS) for Parkinson's disease and essential tremor, vagus nerve stimulation (VNS) for refractory epilepsy and depression, and transcutaneous electrical nerve stimulation (TENS) for menstrual cramps. These devices are already utilised widely, with an estimated 244,000 DBS devices implanted and 125,000 patients receiving VNS therapy worldwide alone.1,2 With a broad therapeutic scope and numerous ongoing active clinical trials involving neuromodulation devices, the neuromodulation market is poised for significant growth in the coming decade.

According to a recent report by Markets and Markets, the global neuromodulation device industry was valued at $5.6 billion in 2022 and is expected to reach $11 billion by 2028.3 Another emerging therapeutic application for neuromodulation, which will contribute to this growth, is the treatment of respiratory conditions. Neuromodulation techniques, which can target neural pathways involved in respiratory function, can be used as an adjunct to more conventional treatments and are already being used to improve respiratory symptoms.

Neuromodulation for Respiratory Health Respiratory conditions are estimated to affect 16.8 million people and are responsible for 136,000 deaths each year in the UK alone.4 Breathlessness, commonly referred to as dyspnoea, is a common feature of many respiratory conditions, including chronic obstructive pulmonary disorder (COPD) and pulmonary hypertension. Dyspnoea can be highly disabling and have a significant impact on a sufferer's ability to perform daily activities and their quality of life. Management www.international-pharma.com

of dyspnoea typically involves a combination of pharmacological drugs, pulmonary rehabilitation, and oxygen therapy. However, these treatments often lack efficacy, with one study finding that 53% of COPD patients still experience severe and persistent dyspnoea despite optimum inhaled medication and pulmonary rehabilitation.5

with an overall mean ± standard deviation of 49±28 mm for the on state and 65±26 mm for the off state based on a visual analogue scale.8 There is also some evidence that DBS can positively impact pulmonary function, with a recent study finding that DBS of subcortical brain areas improved peak expiratory flow rate by up to 14%.9

The mechanisms that give rise to dyspnoea are not well understood, but likely involve the integration of biochemical, mechanical and neural signals, which creates a mismatch between afferent inputs and efferent pulmonary responses.6 Those neural pathways that have been implicated in dyspnoea include afferent neurons from the lungs and chest wall, the vagal nerve, and central areas of the brain, like the brainstem, cerebral cortex, and limbic system.6 The involvement of neural signals in the pathophysiology of dyspnoea presents an avenue for the use of neuromodulation as a potential treatment.

TGNS is a non-invasive approach involving stimulation of the trigeminal nerve, commonly used to treat refractory chronic facial pain syndromes. The trigeminal nerve plays a role in sensing airflow, protecting the airway, and the perception of breathlessness. Evidence for the use of TGNS comes from experiments involving the use of inhaled L-menthol or blowing cool air onto the face/nose, both of which can selectively stimulate the trigeminal nerve and have been shown to help relieve breathlessness.10 Evidence using devices in this area is sparse; however, several feasibility trials are underway exploring the use of TENS for COPD-related dyspnoea (Table 1).

TGNS stimulation may alleviate dyspnoea by modulating neural signals involved in the inspiratory neural drive and the perception of breathlessness.10

Emerging Respiratory Neuromodulation Approaches Several neuromodulation approaches are being investigated for their potential to reduce dyspnoea, including DBS, trigeminal nerve stimulation (TGNS), spinal cord stimulation (SCS) and VNS. There are currently no devices marketed specifically for the treatment of dyspnoea; however, this remains an area of active research with numerous ongoing clinical studies, examples of which are shown in Table 1.

DBS is an invasive approach that involves the surgical insertion of electrodes into the brain to stimulate specific areas, such as the motor thalamus, which is involved in the processing of sensory information, including that related to breathing. It is thought DBS may modulate signals relating to dyspnoea, such as the perception of “air hunger”, described as the sensation of needing more air. One study involving 16 patients receiving DBS for the treatment of tremor reported relief of air hunger in 13 patients and a selfreported mean reduction in air hunger during stimulation of 14.4%.7 Another study involving patients with bilateral electrodes for relief of essential tremor found that 10 out of 11 patients rated less air hunger with DBS on,

SCS is an approach that usually involves the surgical implantation of electrodes and the delivery of small electrical currents to the spinal cord and is commonly used for the treatment of chronic neuropathic pain syndromes. The spinal cord carries motor commands between the brain and respiratory muscles, including the diaphragm and intercostal muscles and transmits sensory information back to the brain. SCS has been primarily applied to the treatment of dyspnoea resulting from spinal cord injuries.

One study involving 11 subjects with cervical spinal cord injury found that five days of transcutaneous SCS in combination with inspiratory muscle training led to a significant improvement in dyspnoea, thoracic muscle strength and forced vital capacity.11 A similar study involving 10 tetraplegics receiving daily SCS found that it improved muscle strength to restore cough and inspiratory function.12 It has been suggested that SCS acts to relieve dyspnoea by modulating neural pathways involved in respiratory control and by reducing the sensation of breathlessness.

INTERNATIONAL PHARMACEUTICAL INDUSTRY 25

Mental Health & Neurodegenerative Disease

Trial sponsor

Target indication

Estimated enrolment

Device name

Device type

Trial phase

Registration

Clinica Gema Leon

COVID-19

104

N/A

Non-invasive stimulation

N/A

NCT06544395

Universidad Rey Juan Carlos

Long COVID

44

N/A

Non-invasive stimulation

N/A

NCT06456502

Hospital San Carlos, Madrid

Post COVID-19 syndrome

40

N/A

Transcranial direct current stimulation

N/A

NCT05753202

University of New Mexico

Long COVID

60

N/A

Intermittent theta burst stimulation

II

NCT06940609

Université de Sherbrooke

COPD with severe dyspnoea

8

GammaCore

Transcutaneous VNS and trigeminal TENS

N/A

NCT06985628

University of Oklahoma

Pulmonary Hypertension

50

Parasymtm

Tragus stimulation

I/II

NCT06802380

Table 1. Ongoing clinical studies involving the use of various neuromodulation strategies for respiratory conditions. (COPD, chronic obstructive pulmonary disorder; TENS, transcutaneous electrical nerve stimulation; VNS, vagus nerve stimulation)

VNS involves the delivery of electrical stimulation to the vagal nerve and can be achieved using both invasive and noninvasive methods. The vagal nerve forms a vital component of the parasympathetic nervous system and plays an essential role in regulating numerous processes, including respiration. The feasibility of using VNS to treat dyspnoea was evaluated in 25 subjects who presented in the emergency department for the treatment of moderate to severe acute asthma.13 VNS treatment did not result in any serious adverse events and was associated with improvements in forced expiratory volume in one second (FEV1) and perceived dyspnoea.13 Another clinical trial is currently underway evaluating the potential of VNS in patients with severe COPD and significant exertional dyspnoea (Table 1).14 It is understood that VNS affects respiratory function by modulating sensory afferents related to dyspnoea and parasympathetic signals.

to reach definitive conclusions about its efficacy. Other barriers include the need for invasive implantation procedures for some devices, such as those used for DBS, which are associated with risks such as bleeding, infection and the formation of blood clots.

This procedure may pose even greater risks in patients with comorbidities or severely compromised respiratory function. Moreover, many available neuromodulation devices were not developed specifically to be used for respiratory conditions, and consequently, stimulation parameter duration may not be optimal for relieving dyspnoea.

Future work in this area will undoubtedly involve the use of advanced neuroimaging

techniques to better unravel the mechanisms underlying dyspnoea and the mechanism of action of neuromodulation in different disease states. Research will also focus on refining existing neuromodulation approaches through the more precise targeting of associated neural pathways and the optimisation of stimulation parameters.

Other developments will include the use of novel stimulation approaches such as the closed-loop systems, combining physiological monitoring and stimulation devices to deliver personalised and adaptive neuromodulation based on real-time feedback on the patient's respiratory status. Additionally, there is a need for larger-scale studies using a wider range of patient populations to better

Challenges and Future Directions The use of neuromodulation for the treatment of dyspnoea faces numerous barriers, which may limit its utility. The neural pathways underlying dyspnoea are not completely understood currently, and by extension, understanding of the mechanisms by which neuromodulation exerts its effects in dyspnoea is also limited. The pathways involved may also differ between patients, and the responses to stimulation may vary depending on the underlying disease pathology. Further, clinical evidence to support the use of neuromodulation in the relief of dyspnoea is quite limited, with many studies being early-stage or involving a small number of participants, making it difficult 26 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Autumn 2025 Volume 17 Issue 3

Mental Health & Neurodegenerative Regulatory & Marketplace Disease

evaluate their efficacy, as well as long-term studies, to determine if these benefits are sustained over time.

Combine Neuromodulation Strategies and Conquer Undoubtedly, neuromodulation represents a promising approach for the management of dyspnoea associated with respiratory conditions. Early clinical studies suggest that a range of neuromodulation strategies, including DBS, TGNS, SCS and VNS, can help to alleviate dyspnoea and improve respiratory function in selected patient populations.

However, current evidence of the efficacy of these approaches remains limited, with most trials involving small patient populations and short-term observations. Further research is needed to better understand the mechanisms underlying neuromodulation in respiratory pathways, optimise stimulation parameters, and establish efficacy through additional clinical studies. Future developments may also include the integration of stimulation and cardiopulmonary monitoring devices which may further enhance the benefits of these approaches in improving respiratory health.

2.

3.

4.

5.

6.

7.

8.

9.

10.

REFERENCES 1.

Sandoval-Pistorius, S.S., Hacker, M.L., Waters, A.C., et al. Advances in Deep Brain Stimulation: From Mechanisms to Applications. J. Neurosci.

43(45):7575–7586 (2023).

www.international-pharma.com

11.

Lim, Y.G., Ker, J.R.X., Tan, Y.L., et al. Adverse Events and Complications Associated With Vagal Nerve Stimulation: An Analysis of the Manufacturer And User Facility Device Experience Database.

Neuromodulation. 27(4):781–788 (2024). https://www.marketsandmarkets.com/MarketReports/neurostimulation-devices-market-921. html https://sheffield.ac.uk/news/patients-andhealthcare-professionals-call-urgent-actionlift-burden-respiratory-disease-societal Carette, H., Zysman, M., Morelot-Panzini, C., et al., Prevalence and management of chronic breathlessness in COPD in a tertiary care center.

BMC Pulm. Med. 19(1):95 (2019).

Massé, S., St-Pierre, J., Delisle, T., et al.

Neuromodulation of dyspnea — A literature review. Respir. Med. 243:108129 (2025).

Chapman, T.P., Divanbeighi Zand, A.P., Debrah, E., et al. Deep brain stimulation of the motor thalamus relieves experimentally induced air hunger. Eur. Respir. J. 64(6):2401156 (2024).

Golding, C., Debrah, E., Green, A., et al. P235 Thalamic deep brain stimulation: a putative target for dyspnoea relief? Thorax. 73. A229.1– A229 (2018).

Hyam, J.A., Brittain, J-S., Paterson, D.J., et al.

Controlling the Lungs Via the Brain: A Novel Neurosurgical Method to Improve Lung Function in Humans. Neurosurg. 70(2):469–478 (2012).

Aucoin, R., Lewthwaite, H., Ekström, M., et al.

Impact of trigeminal nerve and/or olfactory nerve stimulation on activity of human brain regions involved in the perception of breathlessness. Respir. Physiol. Neurobiol.

311:104036 (2023).

Kumru, H., García-Alén, L., Ros-Alsina, A., et al. Transcutaneous Spinal Cord Stimulation Improves Respiratory Muscle Strength and

12.

13.

14.

Function in Subjects with Cervical Spinal Cord Injury: Original Research. Biomedicines.

11(8):2121 (2023).

DiMarco, A.F., Geertman, R.T., Tabbaa. K., et al.

Restoration of cough via spinal cord stimulation improves pulmonary function in tetraplegics. J. Spinal Cord Med. 43(5):579–585 (2020).

Miner, J.R., Lewis, L.M., Mosnaim, G.S., et al.

Feasibility of Percutaneous Vagus Nerve Stimulation for the Treatment of Acute Asthma Exacerbations. Acad. Emerg. Med. 19(4):421–429 (2012).

St-Pierre, J., Mailhot-Larouche, S., Garand, G., et al. Non-invasive neuromodulation for alleviating dyspnoea: protocol for a feasibility sham-controlled randomised trial. BMJ Open.

15(7):e103891 (2025).

Dr. Bipin Patel Bipin Patel Ph.D. is the CEO and Founder of electronRx, a deep-tech startup developing novel chronic disease and hospital patient management solutions.

He is a key digital health thought-leader with over 20 years’ experience in medical engineering, drug development and commercialisation and holds a PhD in Medical Engineering from UCL, UK. Email: enquiries@electronRx.com

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Drug Discovery, Development & Delivery

Advancing Clinical Development Through Autoinjectors: Enabling Patient-Centric Drug Delivery The biopharmaceutical industry is continually seeking innovative solutions that can improve drug delivery, strengthen patient compliance, and optimise therapeutic outcomes. Among the most significant advancements in this regard are autoinjectors, which have emerged as pivotal technologies in the evolving landscape of injectable therapies.

Their earlier adoption into clinical trials highlights their potential to transform drug delivery systems, yet their successful integration is not without challenges. To realise the full promise of these devices, sponsors must adopt a strategic approach that addresses issues of design, drug compatibility, regulatory requirements, patient usability, and long-term scalability.

From Vials to Patient-Centric Devices Traditionally, clinical trials particularly in early-phase studies relied on vials as the primary container for intravenous administration. These formats offered flexibility in fill volumes and dosages, aligning with the early objectives of establishing proof of concept, demonstrating safety, and determining tolerated doses. However, the industry’s increasing emphasis on patient-centricity has reshaped these conventions. With more therapies aimed at chronic conditions and rare diseases, selfadministration has become an expectation rather than an exception.

Prefilled syringes, needle safety devices, and autoinjectors have therefore become integral to product portfolios. For patients, they promise ease of use, reduced injection anxiety, and greater independence. For sponsors, they deliver advantages in compliance, trial retention, and data quality. The market for autoinjectors is also being propelled by device innovation, as manufacturers improve ergonomics, expand compatibility with highviscosity biologics, and explore connectivity features that can capture adherence data.

Importantly, introducing autoinjectors during the clinical trial phase rather than waiting until commercialisation provides sponsors with valuable insights into real-world use scenarios while also accelerating the path to market readiness.

28 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Why Autoinjectors Strengthen Clinical Trials One of the most important advantages of autoinjectors in clinical development is their impact on patient compliance and retention. Trials that require frequent injections often struggle with dropout rates, especially if participation demands regular clinic visits. Autoinjectors empower patients to administer doses at home with minimal supervision, reducing dependence on healthcare providers and easing logistical burdens. This convenience translates directly into stronger adherence to study protocols, particularly in long-term trials.

Equally significant is the standardisation of drug delivery. Unlike manual syringe administration, which can vary by technique and user skill, autoinjectors deliver precise, reproducible doses every time.

This consistency ensures the reliability of pharmacokinetic and pharmacodynamic data, which is vital when determining therapeutic profiles. The improved patient experience of minimised pain, intuitive operation, and reduced anxiety further supports retention, while optional connectivity features provide an added layer of data integrity by confirming adherence.

In essence, autoinjectors bring the trial environment closer to the real-world conditions in which patients will eventually use the therapy. This not only enhances the robustness of clinical data but also supports smoother regulatory submissions and market preparation.

Designing for Safety, Usability and Sustainability Despite their clear advantages, incorporating autoinjectors into clinical trials requires careful planning. At the heart of this lies device design and usability. Clinical trial participants represent a diverse population, with varying levels of dexterity and familiarity with medical devices. Ensuring ease of use is therefore essential. Ergonomic designs that can be operated comfortably by patients with limited mobility, intuitive operation with as few steps as possible, and built-in reassurance features such as audible clicks or visual indicators all contribute to safe and consistent usage.

Safety mechanisms are equally critical.

Needle shielding, retraction systems, and lock mechanisms reduce the risk of accidental activation or needle-stick injury, safeguarding both patients and caregivers. Beyond function, sustainability considerations are becoming more prominent. As companies seek to align with environmental targets, incorporating eco-friendly materials and packaging into autoinjector design can generate long-term benefits without compromising patient safety or product integrity.

Matching Devices with Complex Drug Products The performance of an autoinjector is determined not only by its mechanical design but by its compatibility with the physicochemical properties of the drug product. Many modern biologics are formulated at high concentrations to enable subcutaneous delivery, which results in increased viscosity. These formulations require autoinjectors capable of delivering sufficient spring or drive force to overcome resistance through the needle while maintaining reliable injection profiles. Device robustness must be demonstrated under worst-case conditions, including temperature excursions that may further affect viscosity.

Equally critical is the evaluation of primary container and drug–device interactions.

Stability testing should assess the potential for leachables and extractables from device components, lubricant migration, or silicone interactions that may impact protein stability.

Alignment of device materials with the formulation is therefore central to preserving shelf life and therapeutic activity.

Device selection is also influenced by volume and dosing requirements. Larger dose volumes may exceed the capacity of certain autoinjectors, while faster injection speeds though technically feasible, can negatively impact patient comfort and adherence. For biologics in particular, precise dosing is critical, as even minor variations can affect therapeutic efficacy and safety.

Finally, aligning the shelf life of both drug and device is an important consideration; discrepancies between the two can introduce usability challenges and inefficiencies across the supply chain.

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Drug Discovery, Regulatory Development & Marketplace & Delivery Putting Patients at the Centre of Development For autoinjectors to succeed in clinical trials, sponsors must adopt a patient-centric mindset. This begins with recognising demographic diversity: older patients, children, and those with limited dexterity may all face unique challenges in device use. Cultural attitudes toward self-injection also vary across geographies, influencing both acceptance and compliance.

Addressing psychological barriers is equally important. Many participants have a natural fear of needles, which can deter engagement.

Features such as hidden needles, automatic insertion or automatic retraction can alleviate these anxieties. Training and education play a decisive role: comprehensive materials, including hands-on demonstrations, training devices, and instructional videos, ensure that patients are confident and capable of using the device. Collecting structured feedback during the trial not only supports patient satisfaction but also informs iterative improvements for future device generations and market launch.

Meeting Regulatory Demands for Combination Products Introducing autoinjectors into clinical trials adds a layer of regulatory complexity. In most jurisdictions, these products are classified as combination products, requiring integrated submissions for both the drug and device components. The classification of the device itself based on its principal mode of action determines the depth and scope of regulatory evaluation.

Human factors studies are a core expectation from regulators. These studies demonstrate that the autoinjector can be used safely and effectively by the intended population under real-world conditions.

Conducting such evaluations early in development can smooth the approval process and reduce delays. Material safety must also be assured, with biocompatibility testing confirming that device components will not interact negatively with the drug formulation.

Manufacturing Strategies: Scaling for Success The successful integration of autoinjectors into clinical trials is not only a scientific and regulatory challenge but can also be a manufacturing one. Ensuring a robust, scalable, and cost-effective supply chain is essential. Sponsors must establish reliable sourcing partnerships, often through www.international-pharma.com

contract development and manufacturing organisations (CDMOs), while putting in place contingency plans to mitigate potential disruptions.

Cost-effectiveness is a recurring concern.

Custom-designed autoinjectors can provide differentiation, intellectual property protection, and alignment with specific drug characteristics, but they often require significant upfront investment and face more complex regulatory pathways. Conversely, leveraging established platform devices offers lower upfront costs, smoother regulatory paths, and robust reliability, but with less opportunity for differentiation. A well-considered strategy that balances customisation against standardisation is therefore essential.

Global and Cultural Variability in Device Adoption Autoinjector adoption is not uniform worldwide. Regional preferences and healthcare infrastructure play an important role in determining acceptance. In parts of Eastern Europe, for instance, traditional vials and syringes remain preferred, while Western Europe and North America increasingly favour prefilled syringes and autoinjectors.

In markets with limited healthcare access, the robustness of the device may matter more than advanced features. As such, it has become more common to take advantage of the flexibility of the PFS to launch with region-specific use of the PFS with accessories, with NSD or assembled into an autoinjector, depending on those regional preferences. Sponsors conducting multinational trials must be sensitive to these differences, ensuring that device design, labelling, and language meet local expectations.

Balancing Cost Pressures with Long-Term Value The inclusion of autoinjectors in clinical trials carries financial implications that extend beyond device manufacturing. Training and patient support programs add to upfront costs, while long-term investments in tooling and validation require careful planning.

Yet the long-term value proposition is compelling. Improved adherence, fewer missed doses, and reduced reliance on healthcare professionals can yield significant cost savings over the lifecycle of a product.

Evaluating these trade-offs early allows sponsors to build business cases that justify the initial expenditure.

Preparing for Commercial Transition Ultimately, the integration of autoinjectors in

clinical trials must prepare the way for postmarket approval usage. Trial data should be leveraged to refine device design, validate usability, and build comprehensive regulatory dossiers. Preparing patient education and training materials ahead of commercial launch further supports adoption. The smoother the transition from trial to market, the greater the competitive advantage for sponsors.

Conclusion: Autoinjectors as a Defining Technology for Biopharma Autoinjectors represent a transformative shift in drug delivery, offering clear benefits in patient compliance, dose standardisation, and user experience. Their incorporation into clinical trials enables sponsors not only to generate high-quality, real-world data but also to accelerate readiness for commercialisation. The path, however, is complex: regulatory hurdles, manufacturing strategies, patient variability, and cost pressures all require thoughtful navigation.

By addressing these challenges proactively, clinical trial sponsors can fully harness the potential of autoinjectors. In doing so, they not only enhance the likelihood of trial success but also contribute to a future where patient-centric drug delivery systems are the norm. As biopharmaceutical innovation continues to advance, autoinjectors are poised to play a defining role in shaping the next generation of therapies and improving the overall patient experience.

Bill Welch Bill Welch is Executive Director of Market Development for PCI Pharma Services advanced drug delivery business segment, with a focus on injectable drug-device combination products. Bill has over 30 years contract development and manufacturing experience, with over 20 years in drug delivery devices and combination products. Prior to joining PCI, Bill served as Chief Technology Officer at Phillips-Medisize, leading a 900 person global innovation, development and new product introduction service segment. Bill holds a B.S in Industrial Engineering from the University of Minnesota, Duluth.

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Drug Discovery, Development & Delivery

Back to Basics: What Will Drug Safety Look Like in 5–10 Years?

It’s understandable that regulators’ extensive demands and internal budget pressures have rendered pharmacovigilance primarily a compliance and risk management activity. But strategies now need to be revised - so that the drive to better serve patients is reinstated as the primary mission, says Lucinda Smith, Chief Safety Product Officer at ArisGlobal.

Between 2020 and 2022, as the COVID-19 pandemic peaked, the role of drug safety attracted unprecedented mainstream attention. As new vaccines entered the market and a range of treatments were applied, entire generations gained new appreciation of side-effects at scale, and of the fundamental assumption that the products they take are “safe”.

The ability to quickly and efficiently capture accurate data, spot trends, draw robust conclusions about emerging safety issues, and act on them promptly was tangible and expected by the public. Yet the pharma industry largely missed this opportunity to more permanently reframe pharmacovigilance (PV) and its place in the drug development cycle.

From Caution to Controlled Extension of Opportunity That the core remit of drug safety is to ensure optimal outcomes for patients has been overshadowed by the rising expectations of regulators over the last couple of decades.

This has contributed to the function assuming “cost centre” status, and therefore a target for significant streamlining – the goal being to enable the absorption of increasing workloads (most notably around adverse event-AE-case processing) without adding costs.

To adjacent functions, meanwhile, Safety has been seen predominantly as a “naysayer”; an inhibitor to new drug delivery – a function that is always seeking additional assurances; always conservative.

In the process, something important has been lost. That is the extended value represented by Safety, by virtue of its insights, and through its expertise.

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As products and therapies become more targeted and personalised, and expensive to develop, one of the challenges is to ensure that they are made available to as many applicable patients as possible. Early involvement from Safety enables prompter identification and management of safety issues. It can also help ‘kill’ products sooner.

All of this reduces the risk to patients and to the company and maximises the reach and beneficial outcomes of the approved product.

What’s Changed?

As long as the time and skills of Safety teams are caught up with the day-to-day burden of manually processing AEs, authoring aggregate reports and analysing false signals, their scope for more strategic deployment remains limited. The demands of regulators are so much more complex, and so divergent now, that there is rarely any capacity left after routine activities. It is why processes must be modernised, harnessing the available technology.

Artificial intelligence (AI), in particular Generative AI (GenAI) technology, can now readily streamline activities such as capturing AE information straight into a database.

That’s as long as teams trust the output sufficiently; if human experts are required to check everything, any productivity and cost-efficiency gains will be undermined. In more technologically advanced regulated industries like the financial services sector, advanced automation has been confidently

applied to repeatable processes. This is largely thanks to appropriate governance and oversight, and adapted quality assurance measures, to verify any AI-supported output.

The opportunity now is for pharma PV teams to adapt their own governance and quality processes, maximising the resource liberation that AI technology offers them.

At the same time, Safety teams are understanding afresh the need to assert their voice. This is as a supporter not only of patient outcomes, but also of the business’s strategic interests including a drug’s market success. The more that they can convey this potential, so that other internal groups see Safety as an ally (the way to get their products to market), the more influence they stand to gain. Where AEs can be anticipated in advance, there is greater scope for the company to manage risk effectively. This could result in more products succeeding, or conversely less financial exposure through waste (if a product can be “killed” earlier).

A national study in Italy published late last year, into the need for PV’s reinvention, highlighted the need for greater strategic alignment between the Safety function with business objectives and stakeholder focus – including those around patient centricity and biotech innovation . The optimal transition is likely to be two-way: whereby Safety teams embrace opportunities to better manage their time and use their voice in more influential ways; while adjacent internal functions become more open and receptive Autumn 2025 Volume 17 Issue 3

Drug Discovery, Regulatory Development & Marketplace & Delivery to the rounder value that Safety could bring to product advancement.

Closing The Loop: How to Move Forwards With intensifying pressure to shorten drug development cycles, it is imperative that companies place new emphasis on managing the Safety data that is collected at each stage. This is not about capturing more of it for its own sake but rather appreciating and seeking the optimal combination of data to support appropriate analysis – and to enable a rounded understanding of the safety profile.

Arriving at this point requires earlier collaboration, and a development of trust between the groups, so that everyone is pulling in the same direction. And, given that products are often going to market with far less clinical data now than in the past – especially in areas of unmet medical need – careful planning and close collaboration with local markets is essential. This is to ensure that on-market data is collected and assessed quickly and effectively.

A further driver of positive change could arise from pharma companies’ expansion

into medical device development, presenting the opportunity for a greenfield Safety/PV scenario. Where established processes and ways of working in PV have become complex over time, the design of new approaches for medical devices can be built from the ground up in a more connected, streamlined, and digital-first way. Any emerging learnings and best practices could then set the tone for the changes in current PV practices.

REFERENCES 1.

Whatever the current state of play, Safety leaders should be looking to make some changes now, even if these are small iterative improvements to processes – for example applying GenAI to enable automatic AE data extraction in Individual Case Safety Report (ICSR) work.

Demonstrating incremental improvements in productivity, efficiency, and quality, and learning from them, will start to drive progress, even if this is modest initially. The more that advanced technologies can take on the heavy lifting, the easier it will be for the Safety function to take up a more proactive role.

Ideally this will be both as a voice for patients, and as a strategic enabler of biopharma innovation.

Smith, L., Glaser, M., Kempf, D. et al. Might We Come Together on a Paradigm Shift to Manage ICSRs with a Decentralized Data Model? Drug Saf 48, 843–853 (2025). https://doi.org/10.1007/s40264-02501539-4 The evolution of the Pharmacovigilance department in the pharmaceutical industry: results of an Italian national survey – research by the PV working group, Ernesto Montagna, of the Italian Society of Pharmaceutical Medicine (SIMeF ETS), National Library of Medicine (National Center for Biotechnology Information), November 2024: https://pmc.ncbi.nlm.nih.gov/articles/PMC11536373/

Lucinda Smith Lucinda Smith is ArisGlobal’s new Chief Safety Product Officer, after more than two decades working in frontline scientific and strategic Pharmacovigilance and Drug Safety roles at a major pharma brand.

Web: www.arisglobal.com Linkedin: lucinda-smith-68ab8b38/

HIGH PURITY. HIGH DEMANDS. High purity equipment for clean steam

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Control valves

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Special equipment

geral@valsteam.pt www.valsteam.com +351 236 959 060 www.international-pharma.com

PRODUCTS MANUFACTURED IN PORTUGAL Zona Ind. da Guia, Pav. 14 - Brejo 3105-467, Guia PBL PORTUGAL

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Drug Discovery, Development & Delivery

AI-Augmented Innovation in Drug Discovery

Innovators in pharma/biopharma seek to implement systems that support the discovery, development, and commercial launch of new products. Of particular interest are systems to support the implementation of continuous and mutually reinforcing digital-physical feedback loops. Here, digital tools and methods enhance physical processes, and feedback from these improved physical processes informs progressive digital advancements.

In traditional, non-digitalised drug discovery Design, Make, Test, and Analyse (DMTA) cycles, each transition between stages often demands substantial human effort to transpose and translate information, bridging disparate systems and domain-specific knowledge. Inefficient management of these transitions can result in productivity loss, as practitioners must frequently consult subject matter experts to translate critical, contextdependent information from design platforms to execution and analysis systems. This reliance on manual processes also increases the risk of transposition or transcription errors, where inaccurate transfer of numerical or textual data into digital interfaces may lead to failed experiments, flawed interpretations, or misguided decisions.

Introducing modern AI-powered tools into the DMTA workflow not only streamlines these transitions but also enhances the analysis phase: advanced algorithms can rapidly process experimental data; uncover patterns that might escape human notice; and generate actionable insights. To ensure that learnings are preserved and accessible for future cycles, results from such AI-enabled analyses should be systematically documented within integrated digital repositories, allowing teams to memorialise findings, trace decisions, and enable continual refinement of the DMTA cycle. By minimising manual intervention and harnessing AI’s analytical capabilities, organisations foster a virtuous, resilient DMTA loop that seamlessly connects digital and physical domains.

Each transition within the non-digitalised DMTA cycle (from design to make, from make 32 INTERNATIONAL PHARMACEUTICAL INDUSTRY

to test, etc.) often requires significant human transposition and translation of information from systems to bridge the gap between different stages and domains of expertise. Put simply, avoiding these risks across the various DMTA transitions and from digital-to-physical steps allows for a virtuous DMTA cycle.

Innovative DMTA Cycles in Drug Discovery: AI for Prediction & Orchestration There are a variety of specific DMTA cyclesrequired for successful candidate nomination in drug discovery organisations.1 The following summarises the dual-purpose of DMTA cycles during lead optimisation in drug discovery.

specific chemical structures and sequences which should exhibit suitable physicochemical and pharmacological properties for corresponding patient populations. The resultant recommendations are tested via execution of confirmatory assays using physical composition of matter whose identity matches the AI-recommended structures.

After gathering enough SAR data on a lead series, medicinal chemists focus on optimising potency, selectivity, and druggability.

Modern drug discovery organisations have endeavoured to implement a range of welltrained generative AI systems which produce reliably accurate sets of target compounds.4,5,6

Figure 1. Machine-enabled virtuous design cycle in drug discovery. The drug design step involves the use of a structureactivity relationship (SAR) Map (2) and a variational autoencoder to generate a set of target compounds. The synthesis design step involves the use of chemical reaction large language models (LLMs),3 retrosynthesis prediction tools, and material inventory web services to generate a set of reactions. Finally, the use of specialised planning applications supports the generation of a synthesis map with machine readable operations to support the transition to digitally supported and automated execution (make, in DMTA).

AI-Enabled Drug Design – The Design Step The design phase of the DMTA Cycle in drug discovery addresses two key questions: What to Make?

Virtuous approaches involve the use of generative AI tools to produce a structureactivity relationship (SAR) map. As described in Figure 1, AI components can serve to recommend

How to Make it?

To confirm the success of sequential rounds of these generative AI outputs, medicinal chemists must design efficient synthetic routes for each of the target compounds.

As described in the figure below, chemists will perform appropriate DMTA steps to ultimately produce test articles supporting confirmatory assay execution.

Autumn 2025 Volume 17 Issue 3

Drug Discovery, Regulatory Development & Marketplace & Delivery AI-Enabled Synthesis Execution in Drug Discovery – The Make Step

Figure 2. Machine-enabled virtuous “make” cycle in drug discovery. Leveraging the synthesis map and machine-readable instructions included in the execution plan, building blocks and other reaction materials are ordered and delivered in a reaction-friendly source plate format. The preparations map and corresponding operations are sent to synthesis, purification, and assay samples for execution. The digital representation of all assay samples (including applicable sample identifiers and related metadata) enables automated transition to the testing step.

Based on the similarity within each set of recommended structures, chemists seek to minimise the number of discrete planning and execution operations to produce test articles for the entire set. Consequently, chemists will identify common starting materials which can be used for execution of divergent-thenparallel synthesis operations. This results in a smaller total number of reactions required to produce confirmatory test articles for all AI-recommended target compounds.

from material dispensing, through reaction initiation, to final workup and sample preparation (Figure 2). In modern synthesis labs, the format of machine instructions must conform to the format requirements of each instrument supporting each unit operation.

The output results in a set of test articles, labelled with appropriate machine-and-

human-legible material identifiers. These identifiers serve to associate test article information stored in appropriate software applications including output material identity, material metadata, container or vessel IDs. Similarly to design, the testing of output materials (i.e., purified target compounds) serves a dual purpose:

AI-Enabled Testing in Drug Discovery—The Test Step

Achieving an ideal number of minimum operations for parallel test article production involves the use of well-trained retrosynthesis tools.7 Furthermore, medicinal chemists use the recommendations from these retrosynthesis tools to map to experiment execution systems, including to applications which generate machine-friendly master procedure lists.8 These instructions include machine-encoded material dispenses, reaction operations, and sample preparation operations. These machine-executed operations enable far more efficient preparation and execution of Make tasks required for the preparation of test articles (when compared to manual operations).

Upon completed design, medicinal chemists can execute each unit operation, www.international-pharma.com

Figure 3. Machine-enabled virtuous “Test” cycle in drug discovery. For both product QC and bioassay, physical samples are labelled with human and machine-readable sample identifiers. Product registration generates a corporate identifier for each product structure. All assay results are related to these corporate identifiers (via the relationship between sample identifiers and corresponding assay results).

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Drug Discovery, Development & Delivery 1.

Subjecting materials to a wide range of project-applicable bioassays to confirm the performance of the target compounds as possible (future) drugs.

2.

Identity and quantitative compositional testing to assure accurate SAR. 9

As such, the modern DMTA cycle accounts for all applicable tests required to inform the overall lead optimisation effort. Samples of output materials from reaction execution steps are prepared, then labelled with system-derived sample identifiers, including: •

•

• •

Reaction quality control samples – sample type (pre-process, in-process, and post-process), sample preparation information.

Product registration samples – including chemical identity, purity, salt stoichiometry, and any applicable physical form information that is required for assessing bioassay results for SAR map.

Test article samples – including sample concentration, assay role (e.g., control, standard, blank, replicate number, etc.), Predicted properties – intended to complement the measured bioassay and quality control (QC) results, enhancing the utility of the overall SAR Model:

Figure 4. Customary physicochemical, absorption, distribution, metabolism, and excretion (ADME), and toxicological descriptors generated upon product registration.

The first analysis activities support the processing and interpretation of product QC and bioassay data. The variety of tools that support this primary analysis step has been described elsewhere.10,11,12 Modern drug discovery organisations intend to leverage the output of these analyses, by: 1.

2.

3.

Aggregating processed data into a data warehouse, Implementing a rigorously enforced controlled vocabulary for all bioassay and product QC Results, as well as associated metadata structured as JavaScript object notation (JSON) objects, Relating the test results by applicable

sample, corporate identifier, and insilico properties (generated for product registration).

Scientists can then update applicable SAR maps (Figure 1) based on the bioassay test results.

Value Realisation of AI & Digitalised DMTA Implementing the modern DMTA cycle can improve productivity in drug discovery by supporting the generation of new target compounds and enabling an efficient, iterative process. The use of structured data, controlled vocabularies, and advanced analysis digital tools streamlines the drug discovery workflow and may accelerate the identification of potential therapeutics.

AI-Enabled Analysis in Drug Discovery – The Analyse Step

Figure 5. Upon completion of assay data analysis, results as JavaScript object notation (JSON) objects are used to re-train Generative AI Models, allowing for a virtuous next round of DMTA to start.

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Autumn 2025 Volume 17 Issue 3

Drug Discovery, Regulatory Development & Marketplace & Delivery Furthermore, the use of AI-driven tools now plays a transformative role in the swift construction and refinement of predictive models based on structure-activity relationships (SAR). By leveraging expansive datasets that capture both molecular structures and their corresponding biological activities, these tools employ machine learning algorithms capable of discerning complex, non-linear relationships within the data. Generative AI further augments this process by proposing novel chemical scaffolds tailored to desired activity profiles, while continuous feedback from experimental results enables iterative model retraining, ensuring accuracy and relevance. This rapid, automated integration of SAR insights not only accelerates hypothesis generation and compound prioritisation but also enhances the reliability of chemical structure predictions – empowering scientists to select and optimise candidates with unprecedented precision and speed.

This approach allows project teams to optimise lead series more rapidly and identify molecules that satisfy clinical candidacy requirements.

Conclusion Ultimately, the integration of AI into drug discovery projects markedly elevates both project success rates and operational efficiency. Now, organisations can more accurately identify promising drug candidates earlier and faster – effectively prioritising compounds that exhibit optimal safety and efficacy profiles. This targeted approach minimises downstream failures and leads to a significant reduction in the attrition rates that historically plague clinical development pipelines – a critical key performance indicator for the industry. With AI continuously refining predictive models through rapid analysis of diverse datasets and real-time incorporation of experimental feedback, resources are allocated more judiciously, timelines are shortened, and costly late-stage setbacks are avoided. As a result, drug discovery teams are empowered to advance higher-quality candidates into clinical trials with greater confidence, thereby increasing the likelihood of regulatory approval and market success.

2.

REFERENCES

9.

1.

DMTA Cycles include disease pathology research, biological target and pathway analysis, molecular modality selection, in-vitro assay development, in-vivo study design, and test article scale-up research. Certainly, all require effective DMTA cycles to matriculate through to clinical studies.

www.international-pharma.com

3.

4.

5.

6.

7.

8.

10.

Frey, K. (2020). Structure activity relationship (SAR) maps. Curr. Pharm. Teach. Learn., 12(3), 339-346. https://doi.org/10.1016/j.cptl.2019.12.014 Vangala, S.R., et al. (2024). Suitability of large language models for extraction of high-quality chemical reaction dataset from patent literature.

J. Cheminform., 16, 131. https://doi.org/10.1186/ s13321-024-00928-8 S. Reddy N, et al. (2024, June 30). Leveraging Latent Evolutionary Optimization for Targeted Molecule Generation. 2024 IEEE Congress on Evolutionary Computation (CEC), Yokohama, Japan. https:// ieeexplore.ieee.org/document/10611790 Ochiai, T., et al. (2023). Variational autoencoderbased chemical latent space for large molecular structures with 3D complexity. Commun Chem, 6, 249. https://www.nature.com/articles/s42004023-01054-6 M. C. Ramos, et al. (2025). A Review of Large Language Models and Autonomous Agents in Chemistry. Chem. Sci., 16, 2514-2572. https://doi. org/10.1039/D4SC03921A Discovery at Your Fingertips | SYNTHIA™ Retrosynthesis Software. (2025, April 16). Synthia Online. https://www.synthiaonline.com/ Software to support HT experimentation workflows. Katalyst D2D, version 2024, Advanced Chemistry Development, Inc. (ACD/Labs), Toronto, ON, Canada. www.acdlabs.com/katalystd2d It should be noted that organisations will also subject output materials to such analyses in defence of composition of matter claims in IP Applications. Basics of claim drafting for utility patent applications. (Retrieved 2025, Apr. 22).

USPTO. https://www.uspto.gov/sites/default/files/ documents/ventionCon2021WhatsinaPatentClaim WorkshopFinalstakeholders.pdf Mercer, K. (2023, Oct. 24). Enabling End-User HTE

11.

12.

at GSK [Online presentation]. ACD/Labs Driving Efficiency with Spectrus Symposium. https:// www.acdlabs.com/resource/enabling-end-userhte-at-gsk/ Standardization of Analytical Data: Best Practices.

(2025, Jan. 6). ACD/Labs. https://www.acdlabs. com/resource/standardization-of-analyticaldata-best-practices/ FAIR Annotation of Bioassay Metadata. (Retrieved 2025, Apr. 22). Pistoia Alliance. https://fairtoolkit. pistoiaalliance.org/use-cases/fair-annotationof-bioassay-metadata/

Andrew Anderson Andrew Anderson, Vice President, Innovation and Informatics Strategy, ACD/Labs currently leads product and technology management efforts as VP of Innovation and Informatics Strategy at ACD/Labs. He previously worked in Technology Scouting at PepsiCo, and has served in a variety of Sales Management, Business Development, and Strategic Partnership roles in the Scientific Software industry. Andrew earned a BSc in Chemistry and MBA from San Diego State University and started his professional career as an Analytical Chemist and Regulatory CMC Specialist at Pfizer.

INTERNATIONAL PHARMACEUTICAL INDUSTRY 35

Drug Discovery, Development & Delivery

Nanomedicines: How Innovations in Drug Delivery Technology Can Unlock the Potential of Nanoparticles In the past few decades, nanomedicine has emerged as one of the most promising opportunities in healthcare. By engineering materials at the nanoscale, scientists have unlocked a new universe of possibilities for diagnostics, imaging and, most notably, drug delivery. The recent rapid development and success of mRNA-based COVID-19 vaccines, which rely on lipid nanoparticles (LNPs) to deliver their payload, have proven that nanomedicines are a powerful reality capable of transforming global health.

These tiny, engineered particles can protect sensitive drugs, enhance their solubility and deliver them precisely to a targeted site in the body, dramatically improving treatment efficacy while reducing side effects.

However, the very characteristic that makes nanomedicines so revolutionary – their intricate, customisable complexity – also presents the biggest hurdle to their widespread adoption. Unlike traditional small-molecule drugs, nanoparticles are not single compounds. They are complex assemblies with multiple components, and their performance is governed by a range of interdependent characteristics, from their size and shape to their surface chemistry and stability. This complexity makes developing and manufacturing them challenging, especially when it comes to ensuring they are consistently safe and effective.

To truly unlock the full potential of this technology, we must overcome the analytical bottleneck that currently affects the industry.

The standard tools and methods that have served pharmaceutical development for decades are often insufficient for the unique demands of nanomedicines. New and more sophisticated approaches are needed to provide a comprehensive, multifaceted view of these complex particles from the earliest stages of development.

The Complex Nature of Nanomedicines The power of nanomedicine lies in its intricate, multi-component design. Nanomedicines are sophisticated vehicles that encapsulate and protect their payload. These nanoparticles 36 INTERNATIONAL PHARMACEUTICAL INDUSTRY

are composed of biocompatible materials such as lipids, polymers or metal oxides, which form the structural framework. The therapeutic payload (a small molecule, a protein, or a nucleic acid) is then integrated within this matrix. Some nanomedicines are further enhanced with targeting moieties on their surface, designed to bind specifically to certain receptors, ensuring a more precise delivery. This layered complexity enables nanomedicines to protect sensitive APIs from degradation and directing them to a specific site of action.

However, this sophistication comes with a significant analytical challenge. A nanomedicine’s quality is determined by a delicate interplay of various critical quality attributes (CQAs). These include, among others: •

Particle Size and Morphology The size and shape of a nanoparticle dictate its journey through the body – how it circulates, where it accumulates and how it is cleared. A broad size distribution, or polydispersity, can lead to unpredictable behaviour and inconsistent delivery.

•

Surface Properties The surface charge and coating (like PEG) determine how the nanoparticle interacts with its biological environment.

A properly engineered surface helps the particle evade the immune system and prevent rapid clearance.

•

Drug Release Kinetics The rate and mechanism by which the payload is released must be precisely controlled. The drug must be retained long enough to reach its target but released effectively once it arrives.

The Current Analytical Bottleneck The complex nature of nanomedicines creates a formidable analytical challenge for developers. A critical first step in the development process is to identify and characterise the CQAs: the physical, chemical, and biological properties that directly impact the product’s safety and efficacy. However, in the early stages of development, the exact properties that will prove to be critical

are often poorly understood. This lack of a clear target makes it challenging to design appropriate analytical methods, which can lead to a reactive rather than proactive development strategy. Researchers often rely on a limited set of standard analytical techniques, which may not be sufficient to capture the full picture of a nanomedicine’s behaviour.

One of the most widely used methods for nanoparticle characterisation is dynamic light scattering (DLS), primarily because of its speed and ease of use. However, DLS has several significant limitations that make it ill-suited for the complex demands of nanomedicines. For example, DLS has relatively low resolution, meaning it struggles to differentiate between particles that are similar in size. A sample containing a mixture of monomers and dimers may appear as a single peak, leading to a false sense of homogeneity. Also, DLS is inherently biased towards larger particles, which scatter light more intensely. In a polydisperse sample, a small population of larger aggregates can “overshadow” the signal from the majority of smaller, appropriately sized particles, rendering them effectively invisible. While techniques like nanoparticle tracking analysis (NTA) offer higher resolution, they often have a narrower size range and only analyse a small fraction of the sample. Similarly, transmission electron microscopy (TEM) provides valuable visual information on morphology and shape, but its accuracy for size measurement is often compromised by the need for extensive sample preparation, which can alter the nanoparticle’s structure.

Adding to these technical hurdles is the evolving regulatory landscape. Because nanomedicines are a relatively new class of pharmaceuticals, which encompasses a very broad range of chemistries and morphologies, there are currently limited comprehensive global standards or guidelines to steer manufacturers through the analytical process, especially in early stages of development.

Each nanomedicine is a unique entity, requiring its own set of tailored specifications and analytical methods. This absence of a standardised framework means that developers must often forge their own path, leading to uncertainty and potential delays.

Autumn 2025 Volume 17 Issue 3

Drug Discovery, Regulatory Development & Marketplace & Delivery The lack of comprehensive standardised reference materials for techniques like DLS also poses a significant challenge, as it becomes difficult to ensure the accuracy and reproducibility of results across different labs and batches. As regulatory bodies, such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), and pharmacopoeias establish new and updated guidelines, developers face the risk that methods they have already invested significant time and resources in may become outdated, requiring costly and time-consuming revalidation. This analytical bottleneck, characterised by limited tools and evolving standards, slows down the development cycle, increases costs, and ultimately hinders the translation of promising nanoparticle-based therapies into clinical practice.

Embracing Advanced Analytical Innovation Overcoming the challenges of nanomedicine development requires a strategic shift, moving away from a reactive, phase-by-phase approach to a proactive one that embraces advanced analytical technologies from the earliest stages. By investing in state-of-theart infrastructure and specialised personnel, drug developers can gain a deeper, more robust understanding of their products.

This is about getting the right data that can accurately capture the complexity of these novel therapeutics, saving time and resources in the long run. The key lies in adopting sophisticated, multi-modal techniques that can measure multiple CQAs simultaneously.

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One of the best examples of this shift is the use of asymmetric flow field-flow fractionation (AF4) coupled with multiple online detectors. Unlike traditional methods that analyse a bulk sample, AF4 first separates nanoparticles based on their size with high resolution. This is achieved by applying a gentle cross-flow force perpendicular to a laminar flow stream within a channel, which separates particles without disrupting them.

This gentle, high-resolution separation offers a significant advantage over conventional techniques, such as size-exclusion chromatography, which can shear or alter delicate nanoparticles.

The real power of AF4 emerges when it is coupled with a suite of detectors, offering a multi-dimensional view of the nanoparticles: •

AF4-DLS This pairing overcomes the limitations of standalone DLS by first separating the particles, then analysing each fraction to provide a high-resolution, accurate particle size distribution.

•

AF4-MALS Coupled with multi-angle light scattering (MALS), AF4 measures the molar mass distribution and the radius of gyration (Rg), providing deeper insight into the particle’s structure.

•

AF4-MALS-DLS By combining all three, researchers can calculate a crucial “shape factor”

(Rg/Rh) to gain indirect insight into the nanoparticle’s morphology and detect the presence of different shapes or morphologies (e.g., core-shell structure vs compact sphere) The Impact of Innovation The adoption of advanced analytical techniques is a catalyst for accelerating the entire drug development lifecycle of nanomedicines. By moving sophisticated characterisation tools, such as AF4-MALSDLS, to the forefront of the development process, companies can significantly mitigate risk and reduce the potential for costly delays. A deeper understanding of a nanomedicine’s CQAs at the bench allows researchers to identify potential issues, such as aggregation or payload instability, before they become major problems. This front-loaded approach to quality control means that product specifications are more robust, and manufacturing processes can be optimised with greater confidence, leading to more predictable outcomes and a more streamlined path to the clinic.

Additionally, this enhanced level of characterisation directly translates into improved safety and efficacy for patients.

A nanomedicine’s performance is intimately linked to its physical and chemical properties.

A formulation with a tightly controlled size distribution and stable morphology is more likely to exhibit consistent behaviour in the body, ensuring the drug reaches its target effectively and at the correct dose.

INTERNATIONAL PHARMACEUTICAL INDUSTRY 37

Drug Discovery, Development & Delivery Conversely, a poorly characterised product with significant batch-to-batch variation poses a higher risk of adverse effects or inconsistent therapeutic benefit. Advanced analytics provide the granular detail needed to ensure this consistency, offering a level of quality assurance that is simply not possible with conventional methods.

Finally, the data generated by these innovative technologies is crucial for a successful regulatory strategy. Regulatory agencies are keenly focused on a product’s CQAs and expect developers to have a deep understanding of how they relate to performance. The comprehensive, multi-modal data provided by techniques like AF4-MALS-DLS offers a compelling narrative for regulators, demonstrating a thorough and proactive approach to quality control. Instead of being reactive to new guidelines, companies can use this data to justify their specifications and manufacturing controls proactively. This helps meet regulatory expectations and facilitates a more efficient review process, enabling the advancement of groundbreaking nanomedicines from the lab to the patients who need them most.

Beyond the Bottleneck The promise of nanomedicine is immense, offering a new era of targeted, effective, and safe therapies. Yet, this potential remains partially untapped due to the profound

complexity inherent in these tiny therapeutic particles. The journey from lab to market for a nanomedicine is fraught with challenges, from deciphering the myriad of CQAs to navigating a nascent and evolving regulatory landscape. The limitations of conventional analytical methods have long served as a bottleneck, creating uncertainty and slowing the pace of innovation.

To fully realise the vision of nanomedicine, a fundamental shift in strategy is required.

We must embrace a proactive approach, integrating advanced analytical technologies early in the development cycle. Tools like AF4, coupled with detectors for MALS and DLS, offer a robust solution, providing a multidimensional view of nanoparticles that was previously unattainable. This integrated approach enables the high-resolution measurement of particle size, morphology, stability, and drug loading, providing researchers with the comprehensive data necessary to understand their product fully.

This is where working with a specialised contract development and manufacturing organisation (CDMO) becomes essential.

Partnering with a CDMO that has invested in this state-of-the-art technology enables developers to leverage expert knowledge and infrastructure from the outset, helping them navigate complexity and meet evolving regulatory demands with confidence.

This investment in analytical innovation is about scientific rigour and translating breakthrough research into tangible patient benefits. By gaining a deeper understanding of nanomedicines at the bench, we can ensure greater product consistency, enhance patient safety, and accelerate the regulatory approval process. The future of nanomedicine lies not only in designing ingenious particles but also in using intelligent tools to characterise them. This fusion of advanced drug delivery technology and sophisticated analytical methods is the blueprint for breakthroughs, paving the way for a new generation of lifesaving therapies to reach those who need them most.

Maria Marioli Maria Marioli, Senior for Principal Scientist – Group Lead, Nanomedicine Analytical Chemistry, Ardena. Maria holds a PhD in Analytical Chemistry from the University of Amsterdam, and specialises in the characterisation of large molecules and nanoparticles for pharmaceutical applications. After working for several years in large pharmaceutical companies, Maria joined Ardena and she is responsible for the analytical method development and validation of nanomedicine projects.

Arno Vermote Graduated in pharmaceutical sciences and having obtained a PhD in medicinal chemistry, Arno started his career as a medical writer for a Belgian CRO. Later, he joined Ardena as a CMC Writer, quickly advancing to Senior CMC Writer. Alongside client support, he took on a technical sales role for the CMC Regulatory team, which soon evolved into a full-time business development position. Over the years, Arno has continued to expand his commercial responsibilities, now serving as Business Development Director. In this role, Arno is responsible for driving growth across all Ardena services, including drug substance, drug product, nanomedicines, bioanalytics, and CMC regulatory.

38 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Autumn 2025 Volume 17 Issue 3

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INTERNATIONAL PHARMACEUTICAL INDUSTRY 39

Drug Discovery, Development & Delivery

Empowering Drug Delivery at Scale: How Ypsomed’s Platform Approach Advances Self-Injection Globally From Drug Complexity to Delivery Strategy As pharmaceutical innovation has accelerated over the past several decades, one reality has remained constant: the more advanced the molecule, the more sophisticated the delivery solution must be. Biologic drugs, ranging from peptides and monoclonal antibodies to novel proteinbased therapies, cannot be administered orally. They require precise, parenteral delivery, and increasingly, subcutaneous injection has become the preferred route due to its patient-friendliness and clinical flexibility.

This shift has transformed the landscape for drug delivery devices. What once were basic, functional tools, often treated as secondary packaging, are now central components of pharmaceutical product strategies. Selfinjection systems, in particular, enable decentralised care, improve adherence, and help differentiate therapies in increasingly competitive markets.

Ypsomed recognised this transformation early. With decades of experience in injection systems and a focus on patient-centric subcutaneous delivery, the company has developed platforms and capabilities that meet the evolving needs of both drug developers and end users. Today, as the requirements for combination products grow more complex, the delivery device is no longer a technical afterthought – it’s a critical success factor. Designing for success means building with flexibility, scalability, and strategic alignment from day one.

The Rise of Self-Injection: A Technological and Healthcare Shift The evolution of self-injection began with a simple yet powerful idea: if patients could reliably administer their own medication, care could move closer to where people live.

Early examples emerged in the treatment of diabetes, where insulin pens – designed 40 INTERNATIONAL PHARMACEUTICAL INDUSTRY

with familiar, intuitive formats resembling ballpoint pens – enabled patients to inject themselves safely and discreetly.

These early devices were typically reusable and relied on prefilled cartridges, designed for frequent dosing over long periods. But as more complex biologics entered the market, the requirements changed. Many of these new therapies demanded single-dose delivery, due to their preservative-free formulations and less frequent dosing regimens. This transition ushered in the widespread use of prefilled syringes and disposable autoinjectors which simplified administration and supported a broader range of therapeutic indications.

At the same time, the healthcare system itself was shifting as a result of availability of at-home treatment options. Chronic disease management relying on novel biologics increasingly relied on treatment models that extended beyond the clinic. Subcutaneous self-injection emerged as the key enabler of this decentralisation, offering flexibility for patients and cost efficiency for healthcare systems.

For pharma and biotech companies, this shift meant that the delivery system could no longer be treated as a downstream consideration. Instead, it became a central part of the therapeutic product, and a critical determinant of market readiness, user acceptance, and lifecycle success.

From Niche to Necessity: Devices Become Strategic In the early years of self-injection, devices were often seen as accessories – necessary for drug administration, but peripheral to the therapy itself. Initially, demand was driven by a small number of use cases, and most systems were designed to be reused over long service lives. For pharmaceutical companies, device development was often handled internally, with minimal specialisation, and the primary goal was to improve upon conventional vial-and-syringe handling.

As drug portfolios evolved, this view changed dramatically. The rise of biologics, the need for convenient dosing of larger volumes, and the push toward at-home treatment shifted devices from the periphery to the core of product strategy. Apart from meeting pharmacological requirements and regulatory expectations, many additional considerations such as usability, sustainability, product safety and commercial differentiation goals turned into core elements of the product strategy.

Today, self-injection devices are recognised as integral to therapy design, market access, and long-term adherence. They influence patient experience, impact outcomes, and carry substantial weight in payer and provider assessments. As such, pharma and biotech companies increasingly seek partners with the device expertise, industrial scalability, Autumn 2025 Volume 17 Issue 3

Drug Discovery, Regulatory Development & Marketplace & Delivery

Figure 1: Ypsomed’s platform strategy accelerates time-to-market, leveraging modular autoinjector components that are adaptable for diverse drugs and patient needs

and platform flexibility required to support combination product development from early-stage trials through global commercial rollout.

This shift defines the current era of selfinjection device development. And it is precisely where Ypsomed has positioned itself: as a reliable partner that helps drug developers meet these new expectations with speed, scale, and confidence.

Ypsomed’s Platform Approach: Speed, Flexibility, and Customisation In a landscape where drug development timelines are accelerating and product requirements are diversifying; pharma and biotech companies need device solutions that offer both reliability and adaptability.

Ypsomed addresses this need through a modular, platform-based approach to self-injection systems – one that balances industrial maturity with customisation flexibility.

Rather than designing bespoke devices for each project, Ypsomed builds on proven platforms – such as YpsoMate – that support a wide range of drug formulations, primary container types, and injection requirements.

These platforms have been industrialised, validated, and used successfully across multiple therapeutic areas, allowing new projects to start with a solid foundation. The result: reduced development risk, accelerated regulatory alignment, and faster time to clinic or market.

This approach also enables Ypsomed to tailor its offering to each stage of the drug www.international-pharma.com

lifecycle. For early clinical programmes, platform devices can be adapted with minimal lead time. As products move toward commercialisation, the same platform can scale up with higher volumes, added customisation.

Critically, this model supports both flexibility and compliance. It accommodates the technical demands of a broad range of biologics and the usability expectations of diverse patient populations, while adhering to evolving regulatory standards for combination products. Whether the need is for rapid prototyping or global commercial launch, Ypsomed’s platform-based development ensures that delivery systems keep pace with pharmaceutical innovation.

Global Footprint and Industrial Scale: Manufacturing Without Compromise Delivering innovative self-injection systems at scale requires more than platform flexibility.

It demands industrial infrastructure that is global, resilient, and aligned with the operational needs of pharmaceutical partners. Ypsomed has built a manufacturing network designed precisely for this purpose,

with production facilities in Switzerland, Germany, China, and soon the US, and a clear commitment to quality, redundancy, and supply chain robustness.

This geographic footprint offers multiple strategic advantages. It enables local-forlocal manufacturing models that reduce logistics complexity. It supports dual-sourcing strategies that mitigate risk and improve business continuity. It ensures that capacity can be ramped up efficiently in response to growing demand, whether for highvolume commercial launches or regionally distributed clinical supply. All sites operate under harmonised quality systems and are fully compliant with international standards for medical device and combination product manufacturing. Vertical integration and customised manufacturing solutions with a high degree of automation further ensure control over key processes such as injection moulding, printing, assembly and packaging.

For pharma and biotech companies navigating increasingly complex product pipelines and global distribution needs, Ypsomed’s manufacturing capabilities provide a foundation of industrial reliability.

Figure 2: Ypsomed’s manufacturing sites are strategically located to ensure global access and supply chain resilience INTERNATIONAL PHARMACEUTICAL INDUSTRY 41

Drug Discovery, Development & Delivery The ability to support everything from smallbatch clinical runs to multi-million-unit global supply programs, without compromising quality or timelines, is a critical enabler of successful drug delivery strategies.

Enabling Partnerships Across the Lifecycle Pharmaceutical and biotech companies require more than just a device supplier; they need a partner who understands the full scope of combination product development and can support it at every stage. Ypsomed has built its operating model around this need, offering flexible collaboration frameworks that adapt to both clinical and commercial requirements.

For early-stage programmes, Ypsomed provides ready-to-use platform solutions with short lead times, allowing developers to integrate self-injection systems quickly into clinical trials. These devices are designed to meet usability, safety, and regulatory expectations while minimising development overhead. This enables pharma teams to generate meaningful data on human factors and user handling without committing to full customisation upfront.

As programmes advance toward market readiness, Ypsomed supports the transition to commercial scale with responsive project management and support for industrialisation. Partners benefit from deep expertise in regulatory submissions, risk management, and device-specific quality systems, all critical elements for successful combination product approval.

Beyond technical execution, Ypsomed’s approach is grounded in long-term collaboration. The company works closely with partners to align on project goals, manage lifecycle changes, and address emerging market needs – whether that involves introducing new container formats, adjusting to regional requirements, or incorporating optional features like connectivity.

This partnership model reflects the reality of modern drug development: timelines shift, product strategies evolve, and scalability must be built in from the start. Ypsomed’s ability to support this dynamic process, through both flexible business engagement and robust technical delivery, has made it a trusted partner to pharma and biotech innovators worldwide.

Conclusion: The Future of Drug Delivery is Built on Platforms The pharmaceutical industry continues to 42 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Figure 3: Ypsomed’s platform approach minimises risk, accelerates time-to-market and scales globally – from clinical trials to commercial launch

advance, from increasingly complex biologics to personalised therapies and decentralised care models. Now the importance of selfinjection devices has never been greater.

These systems are no longer just delivery tools; they are foundational components of a product’s success, directly influencing patient experience and commercial performance.

As drug development accelerates and delivery expectations grow, the industry needs partners that can deliver not just devices, but certainty. Ypsomed is ready.

Ypsomed has spent decades anticipating this shift. With a modular platform strategy, a globally scaled manufacturing network, and business models tailored to both early-stage and commercial needs, the company has positioned itself not only as a device innovator, but as a strategic enabler of drug development.

Philipp Richard

For pharma and biotech partners, this means more than access to best-inclass autoinjector platforms. It means a collaboration built around speed, reliability, scalability, and long-term adaptability. From initial evaluations to global product launches, Ypsomed supports the journey with technical depth, regulatory alignment, and industrial strength.

Philipp Richard has been with Ypsomed since 2009, holding various roles in product and key account management.

With a background in electrical engineering from EPFL, he previously worked in contactless bearing technology. Since 2011, he has focused on platform-based and customised selfinjection systems, managing projects from development to market launch. He supports Ypsomed’s mission to advance next-generation drug delivery devices and digital therapy solutions.

Autumn 2025 Volume 17 Issue 3

Media and Communications

IPI

Peer Reviewed, IPI looks into the best practice in outsourcing management for the Pharmaceutical and BioPharmaceutical industry. www.international-pharma.com

JCS

Peer Reviewed, JCS provides you with the best practice guidelines for conducting global Clinical Trials. JCS is the specialist journal providing you with relevant articles which will help you to navigate emerging markets. www.journalforclinicalstudies.com

IAHJ

Peer Reviewed, IAHJ looks into the entire outsourcing management of the Veterinary Drug, Veterinary Devices & Animal Food Development Industry. www.international-animalhealth.com

IBI

Peer reviewed, IBI provides the biopharmaceutical industry with practical advice on managing bioprocessing and technology, upstream and downstream processing, manufacturing, regulations, formulation, scale-up/technology transfer, drug delivery, analytical testing and more. www.international-biopharma.com

PNP

Pharma Nature Positive, is a platform for all stakeholders in this industry to influence decision making by regulators, governments, investors and other service providers to achieve Nature Net Positive Results. This journal will enable pharma the ability to choose the right services to attain this goal. www.pharmanaturepositive.com

PHARMA POD

‘Putting science into conversation, and conversation into science.’Join some of the most esteemed and integral members of the Drug Discovery & Development world as they give insights & introspect into the latest movements, discoveries and innovations within the industry.

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INTERNATIONAL PHARMACEUTICAL INDUSTRY 43

Application Note

Fragment Screening of Massively-Parallel Ligand Arrays Using the Carterra® Ultra® SPR Platform Key Highlights •

•

•

Carterra Ultra® offers the enhanced speed and sensitivity necessary to support Fragment-Based Lead Discovery (FBLD).

Ultra's large ligand array allows for many targets, off targets, mutants, and multiple species to be measured in parallel; a 100-fold enhancement over other SPR systems.

Utilise ready-made panels of biotinylated-proteins to standardise the assay parameters so you can move directly to finding hits and drive your medicinal chemistry programmes.

Fragment-Based Lead Discovery (FBLD) has emerged as a core approach to early-stage hit finding in drug discovery programmes.1 This form of drug discovery is distinguished by the screening of libraries of very small chemical compounds (heavy atom count < 17), that bind with low affinity (double digit micromolar to millimolar KD) to therapeutic targets. Screening small compounds allows for an efficient sampling of the chemical space relevant to medicinal chemistry. The identified binders, in concert with X-ray co-crystal or cryo-electron microscopy structures, serve to provide a map of how chemical matter can interact efficiently with the targets.

The first step in FBLD is the screening of a fragment library using one or more hitfinding technologies capable of detecting the low-affinity transient interactions of

very small compounds with drug targets.

Surface Plasmon Resonance (SPR) has found widespread use in industry and academia for initiating and supporting FBLD programmes from hit finding through lead optimisation. SPR offers a broad dynamic range (mM to pM), sensitivity (100 kDa proteins), applicability to a wide range of target classes including membrane proteins, cost effectiveness, flexibility (direct binding and competition formats), and throughput.2,3 The throughput of various commercial SPR platforms has improved with successive generations of instruments through a combination of reduced sample injection cycle times and increased ligand capacity allowing the testing of a single compound against multiple proteins simultaneously. This capability is frequently used to increase the target throughput of an SPR lab in supporting screening and hit-to-lead campaigns, provide information about mutants and off targets, and compile data on target ligandability.

To further capitalise on the benefits of larger ligand capacity in an SPR platform we developed and launched Carterra Ultra®, a high-throughput SPR (HT-SPR) instrument with >10-times the ligand capacity of any other commercial SPR platform. Ultra divides a single sensor chip surface into 192 regions of interest (ROIs) using two successive ligand deposition steps via Carterra’s multi-channel manifold comprised of 96 independent fluidic paths (Figure 1). In typical operation, 96 of these ROIs are used to couple ligands of interest in one round of deposition, and the other 96 as in-line references during the second deposition, that provide for the highest quality reference subtraction. It is possible to extend the ligand capacity up

to 191 ligands, maintaining a single spot for referencing. After the ligand deposition step, Ultra removes the multi-channel manifold from the chip and covers the ROIs with a single-channel flow cell (SFC) where analytes are directed across the entire array allowing collection of binding data from all 192 ROIs simultaneously using an enhanced version of Carterra’s SPR-imaging array technology.

Ultra has numerous enhancements over prior platforms to provide the sensitivity and speed necessary to support FBLD. Several hardware changes and internal process updates have resulted in a dramatically reduced injection overhead time. Our previous instrument, the LSAXT, requires ~12 minutes to perform an analyte injection cycle. In Ultra this has been reduced to ~3.5 minutes providing for much faster experiment setup and execution. In two days of unattended run time Ultra can efficiently process 768 analytes from two 384-well plates. The thermal range and performance have been significantly enhanced. The new Advanced Single Flow Cell technology does not contain pneumatic valves for more robust performance and enables automated washing of the fluidics with 50% DMSO. This design also reduced the required volume of analyte solutions from 270 µL to 200 µL. Ultra’s optics have been improved and along with advances in ROI integration, ROI size, placement, and flowcell geometry, the shortterm noise has been reduced to < 0.25 RU RMS and the data collection rate has been increased to 2 Hz for each of the 192 ROIs. At that noise level, Ultra is able to detect weak binding by small analytes with molecular weights as low as 100 Da.

Figure 1: Ultra’s ligand array. Target ROIs are interspersed with reference ROIs to give the best possible referencing. If desired, some reference ROIs can also be made into target ROIs to increase throughput.

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Summer Autumn 2025 Volume 17 Issue 2 3

Application Note

Figure 2: Example of applying the Excluded Volume Correction with Ultra and Kinetics 2.0. Seven calibration solutions with higher and lower DMSO concentrations than the running buffer are plotted in red resulting in 96 points per solution. The raw response on the reference ROI is plotted versus the difference between the reference ROI and ligand ROI for each standard.

The orange circles along the X-axis represent the raw response on the reference ROI for each analyte injection. The amount of correction needed for each analyte injection is determined from the calibration curve and applied to the analyte sensorgrams.

Ultra’s control and analysis software have been updated to support the Excluded Volume Correction (EVC) (sometimes referred to as the DMSO correction or solvent correction), which is required when working with ligand surfaces coupled to high density.

This removes the signal differences between ligand and reference ROIs that arise due to the presence of high levels of coupled ligand.

(Figure 2). Ultra also employs a calibration routine that calibrates the RU scale across all ROIs. A user simply provides two solutions with a higher and lower refractive index than the running buffer and, at the end of the experiment, the instrument will automatically generate a 12-point titration curve and apply the calibration curve across the entire experiment (Figure 3).

Numerous other hardware and software changes have been incorporated including washing between cycles with 50% DMSO, software tools to support screening and hit identification, and improvements in software speed and performance. These changes allow

for an instrument capable of determining KD values from low picomolar to low millimolar in full support of FBLD from hit-to-lead, and/ or antibody programmes.

Screening a Panel of Kinases Against a Fragment Library To demonstrate Ultra’s capabilities in FBLD we performed a fragment screen using off-theshelf biotinylated human kinases provided

by Carna Biosciences. To demonstrate the ability to go beyond the standard 96 ligandarray format we selected 125 high-value therapeutic kinases targets and their relevant off-targets for parallel screening against the Maybridge 1000 fragment library. This library has been well-curated for chemical diversity and solubility and is a good representative of fragment collections that have been assembled in various industrial and academic groups. Kinases were shown to be active and sufficiently stable once captured to a sensor chip through testing to the nonhydrolysable ATP analog AMP-PNP. After a

small amount of condition optimisation the full 1000 fragment library was tested at a single concentration against all 125 kinases over three days. Control AMP-PNP injections, along with blank buffer injections for double referencing, were injected at regular intervals through the screen to monitor surface binding stability for each kinase. No surface rebuilds were necessary and the entire dataset was collected using a single chip.

Over the three days of data collection approximately 210,000 sensorgrams (ligand & reference ROIs included) were obtained.

To our knowledge, this represents the largest single fragment-screening endeavour yet reported and, notably, was executed by an individual scientist. We estimate that a similar screen utilising the next-highest throughput commercial SPR system on the market would take approximately six months of business days to complete. Thus, Ultra represents an enormous value proposition in time savings as well as reagent and chip use.

Figure 3: The raw injection data for the ladder of calibration injections automatically mixed and injected by Ultra from provided high- and low-RI solutions bracketing the RI of the running buffer. The ligand ROIs are colored red through orange and the reference ROIs are colored green, blue, and purple. After application of calibration, the response signals from all surfaces are aligned to the same scale. www.international-pharma.com

INTERNATIONAL PHARMACEUTICAL INDUSTRY 45

Application Note Methods and Materials A panel of 125 singly biotinylated kinases with verified purity and enzymatic activity was kindly provided by Carna Biosciences.

The Maybridge 1000 library was purchased from Thermo. All binding studies were performed using a Carterra Ultra HT-SPR platform set for 10 °C. For these studies, a single Carterra SAD200M sensor chip was used. This chip has a carboxymethyl dextran hydrogel pre-derivatised with sufficient streptavidin protein to achieve high capture levels necessary for FBLD activities. The chip was thawed, docked, and thermally equilibrated for 30 minutes prior to automatic application of an airnormalisation routine. After priming into capture buffer (HBS + 0.005% Tween-20, 5% glycerol, 0.5 mg/ml BSA, pH 7.4) the chip was preconditioned with four pulses of 20 mM NaOH and two pulses of 10 mM sodium acetate pH 5.5 for 60 seconds each using the SFC. This treatment minimises baseline drift due to changes in hydrogel volume by pre-swelling the dried matrix. The SFC was automatically undocked from the chip and replaced with the mutlti-channel head creating 96-individual chambers, each with an independent flow path to the 96-needle manifold. Kinases were diluted into 96-well plates and cycled over the chip surface for ~90 minutes (Figure 4). After the first 96 kinases were captured the multichannel head automatically lifted, moved over, and resettled on the chip to create the second 96-channel array. The remaining kinases were captured as in the first step. Finally, the multichannel head was automatically

Figure 4: Capture of 96 biotinylated kinases to a SAD200M chip. Capture levels varied from 1,000 to 35,000 RU. 200 μL of each protein solution was taken from source plates and cycled back-and-forth over the surface. This allows for longer captures without using larger volumes of protein samples. The regular vertical oscillations are indicative of this cycling behavior and allow for very dilute samples to be captured to high levels. This process is non-destructive since the samples are returned to the source plate and may be used for other experiments or additional captures.

undocked and the single channel side redocked. Any remaining free biotin binding sites on streptavidin were blocked with two 30 second pulses of amino-peg-biotin

(0.0025 mg/mL) over the surface. This is important as fragments can bind to the biotin site on streptavidin and be recorded as false positives.

Figure 5: Affinity determination for AMP-PNP against captured kinases. Triplicate dose-responses are overlayed. The last 5 seconds of data points from the association phases were averaged and plotted on the Y-axis against the log of the analyte concentration (X-axis) in the insets. Fits to these curves yielded the equilibrium KD values and standard errors as reported by Kinetics and shown for each panel.

46 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Summer Autumn 2025 Volume 17 Issue 2 3

Application Note The system was primed into assay buffer (HBS + 0.005% Tween-20, 5% glycerol, 1 mM DTT, and 5 mM MgCl2, 3% DMSO at pH 7.4).

Surface activity of all kinases was assessed by triplicate injections of AMP-PNP from 5–400 µM in a 2-fold dilution series to determine the affinity for every kinase to this control compound (Figure 5).

Fragments were plated in 384-well plates at 300 µM. After every 20 fragment injections an AMP-PNP control injection and a buffer blank injection for double referencing were collected. After priming the instrument in running buffer 10 startup cycles were run to equilibrate the instrument followed by fragments and controls. The injection of EVC correction solutions and calibration solutions completed the experiment. Data reduction and analysis was performed with the Carterra Kinetics 2.0 software package.

After applying the calibration, the data were zeroed, EVC and referencing were applied, and the data was double referenced by subtracting the nearest buffer blank injection. Sensorgrams were also normalised for the molecular weight of each analyte.

Screening performance was evaluated in the new Screening tab in Kinetics 2.0 to assess protein stability and apparent hit rate.

Report-point data were created by averaging the last 5 seconds of association phase for each injection and exported from Kinetics into Excel®. These were assembled in

Datawarrior (www.openmolecules.org) and merged with the SMILES strings representing each compound for a comprehensive cheminformatic analysis of all 125 screens simultaneously.

Results Over the course of three days, over 125,000 fragment/protein interactions were characterised (Figure 6). This amount of data stands in stark contrast to that typically acquired in pharmaceutical fragment screening campaigns where 1,000–10,000 fragment/ligand interactions for 1–3 targets are typically collected over a course of 1–2 weeks utilising one or more instruments simultaneously. Analysis of the hits selected for individual kinases frequently exhibit the hydrogen bond donor/acceptor ‘hinge’ motif typical of kinase binders. An example of an aminothiazole compound is highlighted binding to CHK1 kinase in figure 5, lower right corner. Since this represents the largest fragment screen ever reported, a comprehensive analysis of the complete dataset is beyond the scope of this application note, but was consistent with expected hit rates. Figure 7 shows representative reportpoint analysis from the Screening tab in Kinetics 2.0 for seven kinases. Hovering over the individual points shows the sensorgram allowing the user to quickly perform quality control on their binding data and remove any data-points that come from badly-

behaved samples such as those exhibited by promiscuous binders.4 While many kinases showed no significant loss in control binding capacity throughout the multi-day experiment, others showed some degree of decay. While the apparent affinity of the control remained unchanged, the total binding capacity decreased. This is a typical feature of SPR-based fragment screens where proteins are required to be stable for at least a day or more, which is a high bar compared to biochemical assays that usually require only a few hours of stability.

If a protein doesn’t decay more than 50% in 24 hours it is possible to model this drift, apply data corrections and normalisations for control binding and baseline drift, and recover reliable binding data for the fragments that were tested later in the run.3 Virtually all the tested kinases in this panel met that requirement and hit selection can be robustly applied across the screen.

Discussion and Takeaways The combination of increased sensitivity, speed, and the > 10x larger ligand capacity relative to other commercial biosensors makes Ultra a valuable tool in the pursuit of FBLD from screening through hit-tolead activities. The large array can support endeavours to study on- and off-target binding, compound selectivity across all the members of a signalling pathway, and

Figure 6: Compiled data for the 125,000 interaction fragment screen. Individual rows with data and chemical structure are shown at the top. The upper graph shows binding levels of fragments (red) and AMP-PNP controls (blue). The lower panel shows all data coloured by individual kinase. Each colour represents a single 1,000 compound screen on a single kinase over three days. Prior to graphing each kinase/day, data had adjustments applied for control and baseline drift including a vertical adjustment so negatives evenly scatter around zero RU.3 www.international-pharma.com

INTERNATIONAL PHARMACEUTICAL INDUSTRY 47

Application Note

Figure 7: Example data taken from the new screening tab in Kinetics 2.0. The binding levels of analyte replicates (purple) are shown vs. injection order for easy assessment of on-chip target stability. Hovering over individual data points will trigger a pop-up showing the injection cycle that generated the point allowing for fast sensorgram quality control and falsepositive elimination. Structure view is added for clarity here and not present in the analysis software.

provide ligandability information on more than 100 proteins simultaneously for triaging target entry into discovery portfolios. The improvements in hardware and software described here will help scientists apply the best practices in small-molecule SPR at more than 10-times the scale of other instruments easily and efficiently helping ensure that every assay produces quality decision-making data. Ultra’s ability to run for several days unattended to collect up to 768 single-point fragment tests, or 96 six-point dose-response curves for accurate KD determinations, allows users to spend less time setting up experiments and more time on analysing the vast amounts of data that can be generated in parallel using the large ligand array. While Ultra represents Carterra’s first instrument intended to fully support small-molecule applications, it was also designed to carry out all the same large-molecule workflows that have typified our prior instruments, including large-scale epitope binning, but now with higher sensitivity and speed.

Acknowledgments Thanks to Carna Biosciences for providing the kinases, and Drs. Anthony M. Giannetti and Daniel Bedinger for developing this work.

REFERENCES 1.

2.

3.

4.

Kang C, Weijun X. J Med Chem. 2024, Feb;68(5):5000-5004 Giannetti AM Methods in Enzymology, V493:169-218 Giannetti AM, Gilber, HN, Huddler DP, Reiter M, Strande C, Pitts KE, Bravo BJ RSC Drug Discovery Series Fragment-Based Drug Discovery, 2015:19-48 Giannetti AM J Med Chem. 2008 Feb;51(3):574-80

48 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Josh Eckman, Carterra CEO, with newly launched Carterra® Ultra® platform for small molecule and fragment analysis Autumn 2025 Volume 17 Issue 3

Introducing Carterra Ultra™ A new frontier in fragment and small molecule drug discovery.

Fragment hit identification against 96 proteins using the Carterra Ultra platform.

Maybridge fragment library screening against a kinase panel.

Open up a whole new universe of possibilities with HT-SPR technology.

www.international-pharma.com

Contact us at questions@carterra-bio.com INTERNATIONAL PHARMACEUTICAL INDUSTRY 49

Clinical and Medical Research

AI Teammates Impact on Clinical Research

Clinical research is in a pivotal moment.

Over the past two decades, we’ve witnessed extraordinary advances in biology, genomics, and drug discovery.

Yet the infrastructure supporting clinical trial execution has not kept pace.

Despite breakthroughs at the molecular level, the operational backbone of drug development remains manually intensive, fractured by point solutions, and heavily reliant on an overstretched workforce.

Artificial intelligence offers a way forward through “AI teammates”: specialised, operationally grounded AI systems designed to work alongside coordinators, clinical operations staff, and sponsor teams to reduce site burden, automate compliance, improve data quality, and ultimately accelerate access to new therapies.

From our experience working across sponsors, CROs, and sites, we believe AI teammates are more than simply the next innovation wave. They are quickly becoming a prerequisite for the next chapter of biopharma growth.

The Bottleneck: Not Discovery, But Delivery The burden of operational complexity has become one of the most limiting factors in modern clinical research. Investigators report that their coordinators are routinely reentering the same data across multiple portals, manually tracking protocol amendments, and juggling redundant documentation requirements.1,2 These are everyday realities that prevent sites from expanding capacity. This is the real crisis. While the industry debates decentralised trial designs or the promise of synthetic control arms, the coordinators at the heart of trial execution are spending late nights reconciling PDFs, formatting logs, and chasing signatures. It’s no wonder that turnover at research sites remains stubbornly high.

AI teammates offer a lifeline. Not by replacing these staff, but by relieving them of repetitive, low-value work and giving them more time for protocol adherence, patient care, and communication. By offloading even a portion of this work to AI-enabled systems, sites report being able to take on 50 INTERNATIONAL PHARMACEUTICAL INDUSTRY

additional studies without risking burnout among staff.1,3 The AIQ Imperative A pharma company’s Artificial Intelligence Quotient (AIQ) is a way to measure its ability to adopt, integrate, and scale AI across the clinical research lifecycle.4 Just as digital maturity once separated early software leaders from laggards, AIQ now distinguishes those who can run faster, more efficient trials using AI from those who are not adopting it.

For companies that have a portfolio of rare disease studies that must be managed in parallel, the ability to move quickly and confidently is critical. That’s where AIQ can be a real competitive advantage. One such example is Opus Genetics (NASDAQ: IRD), a gene therapy company based in Raleigh, NC. AI teammates support key operational workflows, allowing it to not only gain execution speed but also better data integrity and decision-making confidence.5 In the current capital-constrained environment, this is an increasingly important strategic differentiator.

For Opus, the strategic value of AI teammates goes beyond time savings. They allow sponsors to de-risk development by enabling earlier detection of site issues, protocol deviations, and operational gaps.

That has significant implications. Investors are increasingly looking for operational leverage in addition to scientific novelty. Sponsors who can demonstrate high AIQ and superior operational efficiency, made possible by embedding AI into trial execution, will be in a stronger position to raise follow-on capital in a difficult funding environment.6 From Fragmentation to Integration One of the major reasons clinical research has failed to scale is the proliferation of disconnected platforms. The typical research site today juggles a dozen different systems (including CTMS, eSource, EDC, IRB portals, email threads, etc.) and many of these do not talk to each other.

In contrast, AI teammates are designed to seamlessly function across systems.

They monitor inboxes for IRB updates,

extract protocol changes from PDFs, update tracking logs, and even initiate downstream workflows. They are the operational scaffolding enabling sponsors and sites to work in sync without overloading alreadystretched teams. For example, at Georgia Retina, Dr. David Chin Yee notes that task automation through AI has reduced coordinator workload, improved query turnaround times, and accelerated firstpatient-in milestones.2 Importantly, adoption of AI teammates should be low-friction by design: they should plug into existing systems and SOPs, so roles, approvals, and RACI stay unchanged.

Change management becomes a matter of simple SOP addenda and thresholds so that the transition is quick, auditable, and predictable.

As Dr. Houman Hemmati, clinical development executive and founder of Optigo Biosciences stated: “Our industry has overindexed on building systems and underinvested in the glue. AI is finally giving us that connective tissue”.7 In other words, AI teammates don’t replace platforms. They make them work together.

AI’s Measurable Impact on Sites Among the most immediate and measurable gains of AI are happening at the site level.

Clinical research sites have long been burdened with redundant documentation, staff shortages, and overwhelming regulatory requirements. “Chasing paper” is one of the most time-consuming aspects of clinical trials for site staff. By offloading repetitive administrative tasks (such as reconciling deviations, entering duplicative data, or manually checking protocols), AI teammates are vastly improving both quality and efficiency.

For example, Dr. James Fox of ICON Eyecare reports that, within three months of implementation of AI, his site experienced a 47% decrease in data entry time, 31% improved query response time, and a reduction of manual queries per site of 42%. In addition, he noted that study startup processes accelerated significantly, with templates, reg binders, and delegation logs prepared in hours instead of days.8 Autumn 2025 Volume 17 Issue 3

Clinical and Medical Research Dr. Chin Yee describes this as “giving time back to our coordinators,” allowing his team to handle more trials without increasing burnout.9 AI is making regulatory compliance and documentation more automated, auditable, and accurate, which, in turn, helps sites improve quality while expanding their capacity.

AI helps by surfacing critical requirements in real time, flagging missing labs, reminding teams of patient visit windows, or catching subtle protocol deviations before they escalate. This operational intelligence layer doesn’t just improve compliance; it boosts confidence. Staff feel more supported.

Investigators trust their data. And sponsors get cleaner results, faster.

Sites are no longer passive recipients of technology but active beneficiaries. As AI becomes embedded in daily workflows, the best-performing sites won’t be the ones with the most headcount, but the ones who’ve figured out how to work smarter with it as an internal teammate.

Regulators Are Already There A common concern from industry executives about technology in general, and AI in particular, is: what will the FDA think? The answer is that they’re already using AI themselves.

The FDA’s recent deployment of ELSA (Enhanced Lifecycle Submission and Analysis) is a signal that regulatory agencies aren’t waiting for the industry to modernise.10 In a rare circumstance, FDA is leading the modernisation effort starting with applying AI to streamline review processes. This creates a subtle but important shift: if regulators are using AI to evaluate submissions, then what steps do sponsors need to take towards adoption of AI? The answer varies for each organization, but it is something that needs to be considered going forward.

We believe that sponsors with higher AIQ, those able to deliver well-structured, traceable, and real-time data, will be better positioned in future regulatory interactions.

They’ll also be better prepared for inspections, audits, and data lock processes.

Implications for CROs As FDA moves forward, and as AI teammates take on increasingly sophisticated coordination and compliance tasks, sponsors are reevaluating their needs from CROs. What they want is flexibility, speed, and visibility.

Sponsors will begin asking harder questions www.international-pharma.com

going forward, and evaluating who can actually help them move faster.

This is an opportunity for innovative CROs to stand out, and leapfrog ahead. Those who embrace AI teammates as a force multiplier, streamlining workflows, enabling real-time risk mitigation, and improving site support, can become even more strategic partners.

But those who resist may find themselves bypassed by sponsors building agile, techenabled internal ops teams.

From Adoption to Differentiation AI teammates are not a silver bullet. They require thoughtful implementation, training, and change management. But the gap between proof-of-concept and production deployment is closing. What used to be futuristic is now live across dozens of trial sites.

More importantly, the benefits are cumulative. A site that uses AI to reduce its regulatory burden is more likely to take on additional studies. A sponsor that uses AI to detect risk signals early is more likely to hit milestones. An executive team that moves up the AIQ curve is more likely to secure follow-on funding and scale its portfolio.

2026 is the year of the tipping point for AI in clinical research. As Dr. Hemmati observed, “AI is no longer an experiment.

It’s an accelerant”.7 The Path Forward For clinical research to keep pace with scientific innovation, the industry must rethink not just what it studies, but how it runs studies. That means investing in systems that scale so that headcount doesn’t burn out. It means treating AI not as yet another technology but as a strategic enabler. And it means recognizing that sponsors with higher AIQ will have a measurable advantage in speed, efficiency, and ultimately, patient impact. We believe that AI teammates are the infrastructure we’ve been waiting for.

REFERENCES 1.

2.

3.

Reducing Operational Complexity With AI. Retinal Physician. 2025 May;22(5). Retrieved July 2025, www.retinalphysician.com/issues/2025/may/aiin-clinical-trials Reducing Site Burden and Expanding Research Capacity with AI. Modern Retina. 2025. Retrieved July 2025, www.modernretina.com/view/reducingsite-burden-and-expanding-research-capacitywith-ai Reimagining Clinical Trial Operations With AI Teammates at the Site Level. Ophthalmology360.

2025. https://ophthalmology360.com/trendingtopics/reimagining-clinical-trial-operations-with-

4.

5.

6.

7.

8.

9.

10.

ai-teammates-at-the-site-level The AIQ Imperative: A New Competitive Paradigm for Biopharma. MedCity News. 2025.Retrieved July 2025, https://medcitynews.com/2025/04/ the-aiq-imperative-a-new-competitive-paradigmfor-biopharma/ “How Opus Breaks Trial Bottlenecks,” Breaking Protocol, Tilda Research [Video]. 2025.

Retrieved July 2025, https://youtu.be/O2C0m7IEU4?feature=shared Medicine Maker. The economics of clinical trials in the age of AI. July 2025. Retrieved July 2025, https:// themedicinemaker.com/issues/2025/articles/july/ the-economics-of-clinical-trials-in-the-age-of-ai/ “Why Clinical Trials Fail,” Breaking Protocol, Tilda Research [Video]. 2025. Retrieved July 2025, https:// youtu.be/v-aikU6EnKs?feature=shared Reimagining clinical trial operations with AI teammates at the site level. Ophthalmology360. 2025.

Retrieved July 2025, https://ophthalmology360.com/ trending-topics/reimagining-clinical-trialoperations-with-ai-teammates-at-the-site-level “Streamlining clinical trials,” Breaking Protocol, Tilda Research [Video]. 2025. Retrieved July 2025, https://youtu.be/V8z3GmsIPPE https://www.fda.gov/news-events/pressannouncements/fda-launches-agency-wide-aitool-optimize-performance-american-people

Ram Yalamanchili Ram Yalamanchili is the founder and CEO of Tilda Research, a developer of AI teammates for clinical research. At Tilda, he is focused on building data and operational infrastructure to better execute clinical trials. Previously, he was a founder and CTO at Lexent Bio, which was acquired by Roche, where his team built novel liquid biopsy technologies to help change the way we manage cancer.

Email: ram@tilda.bio

Gaurav Bhatnagar Gaurav Bhatnagar is Chief Growth Officer of Tilda Research. He is an accomplished clinical development executive with over 25 years of experience in leading global CROs and biopharma companies.

He is passionate about accelerating the development of new therapies through the use of data and technology.

Email: gaurav@tilda.bio

INTERNATIONAL PHARMACEUTICAL INDUSTRY 51

Manufacturing

Safeguarding Potency: Innovative Containment Strategies for HPAPI Manufacturing The pharmaceutical and biotech industries are undergoing a significant transformation, driven by the rise of precision medicine, biologics, and targeted therapies. At the heart of this evolution lies a growing reliance on high potency active pharmaceutical ingredients (HPAPIs)—compounds that deliver therapeutic effects at extremely low doses. These ingredients are increasingly central to oncology, hormone therapies and rare disease treatments, and their use is expanding rapidly across both large pharmaceutical companies and emerging biotech firms.

As demand for HPAPIs accelerates, so too does the need for advanced containment strategies. Manufacturing these potent compounds requires not only scientific expertise but also purpose-built infrastructure, rigorous safety protocols and global regulatory alignment. For contract development and manufacturing

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organisations (CDMOs), containment is more than a compliance requirement – it is a strategic capability that enables innovation, protects workers and ensures product integrity.

This article explores the drivers behind the industry’s shift toward HPAPIs, the containment challenges it presents and how CDMOs are responding with cutting-edge solutions that support pharmaceutical and biotech companies worldwide.

The Industry Shift: Why HPAPIs Are Surging The global HPAPI market is projected to reach USD $31.5 billion by 2029, with more than 25% of drugs currently on the market formulated with HPAPIs. This growth is fuelled by several converging trends: Oncology Pipeline Expansion Cancer therapies increasingly rely on highly potent compounds to target specific cells with minimal off-target effects. HPAPIs are foundational to antibody-drug conjugates (ADCs), cytotoxic agents and hormone-

based treatments. These therapies demand precise dosing and robust containment to ensure both efficacy and safety during manufacturing.

Personalised Medicine As treatments become more tailored to individual patients, the need for smallbatch, high-potency formulations grows.

HPAPIs enable precise dosing and targeted delivery, making them ideal for personalised therapies. This shift requires CDMOs to offer flexible manufacturing solutions that can accommodate variable batch sizes and complex formulations.

Biotech Innovation Start-ups and mid-sized biotechs are driving innovation in rare diseases and niche indications, often using HPAPIs in early-stage development. These companies typically lack internal manufacturing capacity and rely on CDMOs for technical expertise, containment infrastructure and regulatory support. The ability to scale quickly and safely is critical to their success.

Autumn 2025 Volume 17 Issue 3

Manufacturing

Regulatory Pressure Regulatory agencies such as the MHRA, EMA and FDA are tightening guidelines around occupational exposure limits (OELs), cross-contamination and facility design.

Compliance is no longer optional – it is a prerequisite for market access. CDMOs must demonstrate robust containment capabilities to meet these evolving standards and support global product launches.

Globalisation of Drug Development With clinical trials and product launches spanning multiple regions, pharmaceutical companies must ensure that HPAPI containment strategies meet diverse regulatory standards and cultural expectations. CDMOs with multi-site operations and harmonised quality systems are well-positioned to support global programmes.

Defining High Potency HPAPIs are typically defined by their biological activity at low doses, with OELs at or below 10 μg/m³ over an 8-hour timeweighted average.

These compounds may also exhibit: •

High receptor selectivity, which increases therapeutic precision but also toxicity risk.

•

Carcinogenic or mutagenic potential, requiring stringent handling protocols.

•

Hormonal or steroidal activity, which can disrupt biological systems even at trace levels.

www.international-pharma.com

•

Unknown toxicity profiles, particularly in novel compounds, necessitating conservative containment approaches.

To manage these risks, manufacturers use Operational Exposure Banding (OEB) systems that classify compounds from low to high potency. Compounds with a high OEB level, for example, require glovebox isolators, rapid transfer ports (RTPs) and closed transfer systems to ensure safe handling.

Containment Capability – The CDMO Response CDMOs are responding to the HPAPI challenge by embedding containment into every aspect of their operations – from facility design to operator training. This holistic approach reflects a deep understanding of both the science and the operational realities of highpotency production.

Purpose-Built Facilities Modern CDMO facilities are designed with containment in mind. Key features include: •

Isolators for dispensing, blending and milling operations, which prevent operator exposure and cross-contamination.

•

Wash-in-place (WIP) systems, which automate cleaning and reduce manual intervention.

•

HEPA-filtered HVAC systems with pressure differentials to maintain

cleanroom integrity and prevent airborne contamination.

Modular GMP suites, which allow for scalable production and rapid reconfiguration based on project needs.

These design elements ensure that containment is not an afterthought – it is a foundational xprinciple that supports both safety and flexibility.

Advanced Equipment Containment is also a function of equipment.

CDMOs are investing in: •

Split butterfly valves for contained powder transfer between vessels.

•

Tablet compression and capsule filling systems with integrated containment features.

•

Flexible packaging lines capable of handling potent products without compromising operator safety.

This equipment enables safe, efficient processing while maintaining product quality and regulatory compliance.

Agile Process Design HPAPI manufacturing often involves variability in particle size, solubility and stability. CDMOs address this through adaptable process design, using real-time analytics and flexible configurations to ensure consistency.

INTERNATIONAL PHARMACEUTICAL INDUSTRY 53

Manufacturing For example, oxygen-sensitive formulations may require nitrogen purging during bottling, while variable particle sizes may necessitate customised blending protocols.

These solutions are developed through crossfunctional collaboration and rigorous process development.

Operator Training and Culture Containment is only as strong as the people who implement it. CDMOs invest in: •

•

•

Regular training on PPE, gowning and emergency protocols to ensure safe handling.

Operator engagement in continuous improvement initiatives to identify and mitigate risks.

Cross-functional collaboration between manufacturing, quality and engineering teams to maintain containment integrity.

This culture of safety ensures that containment is a shared responsibility – not just a technical requirement.

Global Impact The rise of HPAPIs and the need for containment have profound implications for pharmaceutical companies worldwide.

Large Pharma Global pharmaceutical companies are expanding their oncology and specialty pipelines, often outsourcing HPAPI manufacturing to CDMOs. They require partners who can: •

Meet global regulatory standards across multiple jurisdictions.

•

Scale production efficiently while maintaining containment.

•

Ensure data integrity, traceability and audit readiness.

Experienced CDMOs with multi-site operations and harmonised quality systems are well-positioned to support these needs.

For Biotech Innovators Biotechs face unique challenges: limited internal capacity, tight timelines and evolving formulations. They need CDMOs that offer: •

Flexible batch sizes and rapid tech transfer capabilities.

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•

Collaborative problem-solving and transparent communication.

•

Access to containment infrastructure without long lead times.

CDMOs that can adapt quickly and provide tailored support are essential to biotech success.

•

Expanded peptide and small molecule API capacity to support a broader range of therapies.

Regulators and Investors Containment is increasingly viewed as a marker of quality and risk management.

Facilities that lack robust containment may face delays, recalls or reputational damage.

Investors and regulators are scrutinising CDMO capabilities more closely than ever, making containment a strategic differentiator.

•

Enhanced analytical infrastructure to ensure product quality and regulatory compliance.

•

Digital tools for process monitoring and control, enabling proactive risk management.

•

Talent development programmes to build the next generation of containment experts.

Strategic Drivers Behind the Shift Beyond therapeutic innovation, several macro-level drivers are accelerating the shift toward HPAPI containment: Employee Safety and Retention As awareness of occupational hazards grows, companies must demonstrate a commitment to employee safety. Robust containment systems reduce exposure risk, improve morale and support long-term employee retention.

Environmental Sustainability Containment systems reduce waste, emissions and contamination risk. Technologies such as WIP and closed-loop systems support sustainability goals while maintaining safety and compliance. CDMOs are increasingly integrating environmental considerations into facility and process design.

Digital Transformation Advanced monitoring systems, data analytics and automation are enhancing containment strategies. Predictive maintenance and realtime environmental monitoring are helping CDMOs optimise HPAPI production and reduce downtime.

Therapeutic Complexity As drug formulations become more complex – combining multiple APIs, delivery systems and excipients – containment strategies must evolve to accommodate diverse manufacturing needs. CDMOs are developing modular solutions and investing in multi-functional equipment to meet these demands.

Looking Ahead: Scaling for the Future As HPAPI demand grows, containment strategies must evolve. CDMOs are investing in:

These investments position CDMOs to support the next generation of high-potency therapies – whether in oncology, neurology or beyond.

Conclusion The pharmaceutical industry’s shift toward HPAPIs is reshaping how drugs are developed, manufactured and delivered. Containment is no longer a niche concern – it is a strategic enabler of innovation, safety and global access.

For CDMOs, containment is built into the DNA of operations. Through purposebuilt facilities, advanced equipment, agile processes and a culture of safety, they empower pharmaceutical and biotech companies to navigate the complexities of high-potency manufacturing.

As the industry continues to evolve, those who invest in containment will be best positioned to lead.

James Millar James Millar, Operations Support Manager (Manufacturing Support), Almac Pharma Services. With over 10 years' experience, James leads operational support for manufacturing with a focus on equipment qualification, cleaning validation and process optimisation.

Autumn 2025 Volume 17 Issue 3

www.international-pharma.com

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Manufacturing

Building Contamination Control Strategies for ATMP Manufacturing Advanced Therapy Medicinal Products (ATMPs) represent a novel class of complex biological products that are at the forefront of scientific innovation and hold great potential to improve health care. To ensure that appropriate measures are put in place by the manufacturers to safeguard the quality of the product, all ATMPs produced for human use from clinical Phase I onward must comply with current Good Manufacturing Practice (cGMP) regulations.1 cGMP requirements can be very complex and guidance on how to interpret the minimum expected standards specific to ATMPs are laid down in EudraLex Volume 4 – Part IV “Guidelines on Good Manufacturing Practice specific to Advanced Therapy Medicinal Products”.

As ATMPs are administered to the human body as an injectable medicine, these are required to be sterile. Hence, the manufacture of these products requires specific focus and requirements to minimise the risk of microbiological contamination. Considering the level of complexity in the often-manual manufacturing process and the complex manipulation steps involved, aseptic manufacturing is paramount.

Regulatory bodies expect that pharmaceutical companies have a risk-based contamination control strategy (CCS) in place that outlines the control of contamination of utilities, manufacturing systems and environment, raw materials, intermediate products and ultimately the pharmaceutical product itself. Key questions that often arise are: What are the key elements to be considered in order to meet the quality system requirements detailed in ICHQ10 in addition to ICHQ9, and guidance as provided in EudraLex Volume 4 Part IV for a CCS? What points need to be considered to support the implementation of such a programme within an ATMP manufacturing facility? What makes a CCS robust and how to ensure its effectiveness?

These are all valid questions and a useful regulatory reference that provides additional 56 INTERNATIONAL PHARMACEUTICAL INDUSTRY

guidance on points to consider is EudraLex Volume 4, Annex 1 “Manufacture of Sterile Medicinal Products”. Both Annex 1 and Part IV expect that a CCS is based on the principles of quality risk management (QRM) across their manufacturing facilities to manage any potential contamination risks. Fundamentally, the CCS is about establishing a tight focus on patient safety by thoroughly assessing all the different areas where contamination can happen and determining what is in place to mitigate the risk of contamination.

The development of a CCS should be carried out by a multidisciplinary team with a detailed understanding of the process, the utilities, and equipment that serve the process. Cross-functional expertise allows scientifically justified assessments to be made of potential contamination risks to the ATMP product. A risk-based CCS can be used as a pro-active tool, giving an estimation for the likelihood of a risk occurring and severity of the impact to the patient if the risk occurred. This allows the company to identify the key areas of focus in the CCS and provides rationale for implementation of control or detection measures if unacceptable risks were identified.

The CCS comprises a repository of documents that provide a high-level overview of how the company controls and prevents contamination. The CCS is a not a standalone plan but a summary of interlinked practices and measures. The sum of all these individual aspects and how well these interact determines the effectiveness of the CCS, from the selection and management of raw materials to the final packaging of the product. For example, how the material and personnel flows are designed, equipment maintenance, cleaning and disinfection practices, and how the robustness of controls is monitored through the environmental monitoring programme and in process or in finished product testing.

When controlling raw materials, the primary aim is to exclude any contamination which may subsequently be contained in the product. If raw materials are not of the desired quality, they may be sources of contamination for the (intermediate) product. The origin and composition of raw materials provide a good

indication as to whether the ingredient has the potential to be a source of contamination or can cause a proliferation of microbial growth. Besides product contamination, raw materials have the potential to contaminate equipment and the manufacturing facility.

Because of the high level of complexity, and often manual processes, the number one source of contamination is usually personnel. As such, education and training are key. The CCS must address challenges with manipulations and activities done by personnel potentially causing contamination as these must be designed for aseptic manufacturing of ATMPs. As per regulatory requirements, training and qualification should involve a practical element through completion of successful aseptic process simulations, and ongoing monitoring is an essential part of an effective CCS. Based on the type of activities and cleanroom specification the CCS should describe the rationale for the level of gowning chosen, the frequency of gown cleaning, behaviour of personnel in the controlled rooms, and the acceptability of the gown materials for the type of manufacturing process. Personnel working in the area must rigidly adhere to the gowning procedures.

Training should include an initial and periodic assessment of gowning and, until fully qualified, personnel access to the cleanroom should be restricted. A risk-based approach should be undertaken to assess frequency of retraining.

After personnel, the second highest risk of contamination is from the introduction of materials and equipment into the controlled environment from the outside. For material transfer airlocks, it is essential that decontamination practices are in use prior to entry into the controlled environment.

Items to be considered include the use of interlocking airlocks between entry points for classified areas of different grades, and restricted and controlled access to aseptic areas. Disinfection of materials should include use of a sporicidal agent where appropriate. The process of material intake should be sufficiently detailed in material transfer procedures and assessment of transfer techniques by a subject matter Autumn 2025 Volume 17 Issue 3

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Manufacturing

expert to validate compliance with the procedures.

The frequency of any cleaning and disinfection programme should be riskbased and similar to the training program and should also be regularly reviewed. In accordance with Part IV of the EudraLex ATMP GMP guidance disinfectants must be validated for their intended use, those being a broad-spectrum disinfectant rotated with periodic use of a sporicidal agent. Other items to be considered under the cleaning and disinfection programme include the frequency and method of residue removal.

Contamination control is not a single item, but an amalgamation of various elements that together determine the effectiveness of the Programme. Contamination control is a continuous process in which data trends, product information, and new regulatory requirements are to be evaluated on an ongoing basis.

The contents of this article are solely the opinion of the author and do not represent the 58 INTERNATIONAL PHARMACEUTICAL INDUSTRY

opinions of PharmaLex or its parent Cencora.

PharmaLex and Cencora strongly encourage readers to review the references provided with this article and all available information related to the topics mentioned herein and to rely on their own experience and expertise in making decisions related thereto.

REFERENCES 1.

2.

3.

Commission Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004, article 30. Accessed through: https://ec.europa.eu/health/sites/ health/files/files/eudralex/vol-1/reg_2007_1394/ reg_2007_1394_en.pdf EudraLex Volume 4, EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use, Part IV (2017) Guidelines on Good Manufacturing Practice for Advanced Therapy Medicinal Products. Accessed through: https://ec.europa.eu/health/sites/health/files/ files/eudralex/vol-4/2017_11_22_guidelines_gmp_ for_atmps.pdf ICH Harmonized Tripartite Guideline Quality Risk Management Q10: Guideline on pharmaceutical quality system (2008) Accessed through:

4.

https://www.ema.europa.eu/en/documents/ scientific-guideline/international-conferenceharmonisation-technical-requirementsregistration-pharmaceuticals-human-guidelineq10-pharmaceutical-quality-system-step-5_en.pdf ICH Harmonized Tripartite Guideline Quality Risk Management Q9: Guideline on quality risk management (2023) Accessed through: https://www.ema.europa.eu/en/documents/ scientific-guideline/international-conferenceharmonisation-technical-requirementsregistration-pharmaceuticals-human-use-ichguideline-q9-r1-quality-risk-management-step5-revision-2_en.pdf

Patrick Niewenhuizen Patrick Nieuwenhuizen is Director and Principal Consultant at PharmaLex and has more than 30 years of experience in the industry across a variety of platforms including Biologics, Sterile Fill Finish and Solid Oral Dose.

Autumn 2025 Volume 17 Issue 3

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INTERNATIONAL PHARMACEUTICAL INDUSTRY 60

Manufacturing

In the Pharmaceutical GMP Industry: If Quality Is Everyone's Responsibility, Is It No One's Responsibility?

The phrase "Quality is everyone's responsibility" is often misinterpreted in the Pharmaceutical Inspection Cooperation Scheme – Good Manufacturing Practices (PIC/S GMP) pharmaceutical industry, leading to the belief that quality oversight is solely the responsibility of the Quality Assurance (QA) department.

This article explores the critical role of QA professionals in fostering a collaborative quality culture, asserting that quality should be integral to every employee's responsibility. It emphasises management commitment in establishing effective Pharmaceutical Quality System (PQS) and encourages viewing QA as partners. By engaging teams across various functions, organisations can cultivate a unified commitment to quality and implement strategies for overcoming resistance and measuring success through quantifiable metrics.

Introduction In the regulated pharmaceutical GMP industry, the phrase "Quality is everyone's responsibility" is often misinterpreted, leading to the belief that quality is solely the QA department's responsibility. This disconnect can foster neglect of quality oversight, with employees feeling their roles don’t impact overall quality. This article addresses these misconceptions and highlights the vital role of QA professionals in fostering a culture of quality. It emphasises the need for management to promote quality actively and for all employees to recognise their contributions to product integrity and patient safety. By viewing quality as integral to every role, organisations can enhance their commitment to excellence and continuous improvement.

Edwards Deming famously stated, “Quality is everyone's responsibility.”1 While this sentiment is valid, it can easily be misinterpreted. If Deming's quote is considered in isolation, it risks falling into the familiar “everybody, somebody, nobody” trap, where individuals assume that someone else is accountable for quality. This leads to complacency and oversight. It is important to recognise that most employees www.international-pharma.com

do not come to work intending to perform poorly or resist improvement. When lapses occur, it is often due to a lack of awareness or clarity regarding their responsibilities.

To emphasise the significance of quality across the organisation, we must frame it as integral to every role and function, not just the responsibility of the QA department.

This requires concerted communication to highlight that quality impacts all aspects of the organisation, from manufacturing to marketing, and that each employee plays a vital role in ensuring product integrity and patient safety.

What Is the Basis for Concern?

Management responsibilities have been a topic with regulatory agencies for quite some time, as evidenced by the various regulations and guidance we work within.

For example: • 1.

2.

3.

•

PIC/S GMP defines: Senior management has the ultimate responsibility to ensure an effective PQS is in place, adequately resourced, and that roles, responsibilities, and authorities are defined, communicated, and implemented throughout the organisation. Senior management’s leadership and active participation in the Pharmaceutical Quality System is essential. (PIC/S GMP PE 009-17 (Part I), Chapter 1, sections 1.5) There should be periodic management review, with the involvement of senior management, of the operation of the Pharmaceutical Quality System to identify opportunities for continual improvement. (PIC/S GMP PE 009-17 (Part I), Chapter 1, sections 1.6) A Quality Manual or equivalent documentation should be established and should contain a description of the quality management system including management responsibilities. (PIC/S GMP PE 009-17 (Part I), Chapter 1, sections 1.7) EU (European Union) GMP applies ultimate responsibility for quality and the PQS to senior management and assigns specific responsibilities for product and process quality to

the heads of quality and production, along with the head of quality control (Eudralex V4, Chapters 2 and 6).

•

ICH (International Council for Harmonisation) Q10 defines senior management as having ultimate responsibility for ensuring an effective PQS is in place, emphasising that management responsibility is integral to a functioning pharmaceutical quality system.

• 1.

ISO 9001:2015 specifies: Senior management must demonstrate leadership and commitment by communicating the importance of effective quality management and conforming with requirements. (Clause 5.1.1(f)) Top management must ensure that the quality policy is communicated, understood, and applied throughout the organisation. (Clause 5.2.2(b) Top management must establish objectives and communicate them to relevant functions and levels. (Clause 6.2.1(f)

2.

3.

Bridging the Gap Given these frameworks, it is evident that QA professionals must bridge the gap between the ideal of 'everyone's responsibility' and the practical implementation of quality in daily operations.

The Importance of Management Responsibilities: The international guidelines underscore that senior management has ultimate responsibility for the effectiveness of the PQS. This leadership is critical in establishing a culture of quality that permeates the organisation. When senior management demonstrates commitment to quality by actively participating in quality initiatives, it sets a tone that encourages all employees to prioritise quality in their roles.

Engaging Teams Effectively: The first step is to shift the perception of QA from enforcers to collaborators and educators. For instance, a pharmaceutical company could hold regular crossdepartmental workshops where QA staff and INTERNATIONAL PHARMACEUTICAL INDUSTRY 61

Manufacturing operational teams collaborate on quality initiatives.

In one workshop, the QA team trained on purified water sampling techniques, emphasising proper glove sanitation with alcohol to minimise contamination risks in the water samples. This adjustment enhanced test reliability and fostered a shared sense of responsibility among QC staff, empowering them to maintain product quality.

Empowering Employees: When management communicates the importance of quality, as specified in ISO 9001:2015, it empowers employees to take ownership of their contributions. For instance, after introducing a quality dashboard displaying real-time metrics, employees on the pharmaceutical outer packaging lines took pride in their performance. This dashboard provided immediate feedback on key quality indicators, such as defect rates, adherence to specifications, and production efficiency.

The availability of real-time metrics allowed employees to monitor their performance continuously, fostering accountability and proactive problem-solving. For example, when defect rates increased, employees could swiftly identify issues and implement corrective actions, leading to a 20% reduction in errors over six months and promoting a culture of continuous improvement. Additionally, a team that regularly reviewed quality metrics identified specific areas for enhancement.

By aligning departmental objectives with the organisation’s quality goals, they built a shared commitment to quality that boosted overall productivity and morale. This collaborative environment encouraged employees to contribute suggestions based on real-time data, further enhancing engagement in maintaining high-quality standards.

(Corrective and Preventive Action) statistics, and change control provides insights into quality performance and areas needing attention.

•

Product Complaint Handling: Reviewing product complaints helps identify recurring issues and informs necessary corrective actions.

•

Audit Findings: Analysing internal and external audit results helps identify systemic issues and evaluate the effectiveness of corrective actions.

•

Risk Assessments: Evaluating potential risks allows management to prioritise areas for improvement and mitigate future issues.

•

Training and Development: Reviewing training effectiveness ensures employees are equipped to meet quality standards and regulatory requirements.

•

Action Plans and Effectiveness Checks: Tracking progress on action plans ensures accountability and followthrough on identified issues.

By emphasising management's role in fostering a culture of quality, we can bridge the gap between theory and practice, creating an environment where quality is genuinely everyone's responsibility, supported by strong leadership and collaboration.

Communication must be tailored to resonate with different teams and individuals. Here’s how we can do this effectively: •

Ongoing Leadership Involvement: Periodic management reviews, as outlined in PIC/S GMP and EU GMP, should focus on compliance and opportunities for continuous improvement. For example, a generic drug manufacturing company established a regular review process that enabled quick identification of non-compliance trends, leading to proactive measures that enhanced overall quality.

The regular review process includes several key items: •

Performance Metrics: Assessing indicators like deviation rates, CAPA

62 INTERNATIONAL PHARMACEUTICAL INDUSTRY

•

Production Team: When working with the Production team, QA can participate in process reviews and workshops, including Gemba walks to observe processes firsthand. This involvement helps QA identify potential sources of variation and implement controls to minimise risks to product quality. Additionally, QA can conduct CAPA effectiveness checks and safety assessments. Performance metrics such as yield rates, defect rates, and adherence to SOPs can be monitored to evaluate the effectiveness of quality initiatives and drive continuous improvement.2 Engineering Team: In collaboration with the engineering team, QA provides

essential input during the design and validation of equipment, ensuring it meets GMP requirements and performs effectively throughout its lifecycle. QA also oversees adherence to annual preventive maintenance checks and the validity of equipment qualifications.

Key performance indicators (KPIs) like equipment downtime, validation success rates, and compliance with design specifications can track the effectiveness of engineering solutions in supporting quality objectives.

•

Quality Control Team: QA should maintain a strong partnership with the quality control (QC) team to ensure testing protocols align with regulatory requirements and organisational standards. This includes conducting regular checks for computer system validation, data integrity, and security.

Additionally, QA should review out-ofspecification and out-of-trend results, managing investigations effectively.

Performance metrics such as test accuracy, turnaround time for results, and non-conformance rates can assess the QC team’s effectiveness in maintaining product quality.

•

Procurement Team: In collaboration with the procurement team, QA can define quality specifications for materials and services, ensuring that all purchases meet organisational standards before reaching production.

Key activities include supplier qualification and tracking performance metrics like on-time delivery and quality compliance. By providing training on quality requirements, QA empowers procurement professionals to make informed decisions. Metrics such as the percentage of compliant materials received and the rate of supplier-related quality issues can effectively measure procurement’s contribution to quality objectives.

This approach enhances collaboration and fosters a unified commitment to quality across all departments, driving continuous improvement and compliance. By regularly monitoring performance metrics, teams can identify areas for enhancement and collaboratively pursue shared quality objectives.

Rather than enforcing compliance that breeds resistance, we should emphasise how specific quality practices prevent errors, Autumn 2025 Volume 17 Issue 3

Manufacturing save time, improve profitability, and enhance patient safety. Communicating the rationale behind quality initiatives is crucial, making quality personal by showing its impact on both the final product and individual roles. This transforms the abstract notion of "everyone's responsibility" into concrete actions and attitudes.

Fostering a Quality Culture A quality culture in the pharmaceutical industry refers to the collective mindset, values, attitudes, and behaviours within an organisation that prioritise and promote a commitment to quality. Here are key elements that contribute to fostering a strong quality culture: 1.

2.

3.

4.

5.

Leadership Commitment: Top management must demonstrate leadership and commitment to quality by communicating its importance and setting clear expectations. They should allocate necessary resources and lead by example, inspiring all employees to prioritise quality and understand their roles in achieving these goals.

Employee Engagement: Engaged and empowered employees are vital for a strong quality culture. Encouraging open communication, involving employees in decision-making, and recognising quality contributions fosters accountability and a sense of ownership.

Training and Education: Comprehensive training is essential for equipping employees with the knowledge and skills needed to perform effectively. Training programs should emphasise quality principles, regulatory requirements, and GMP, ensuring employees understand the importance of quality and compliance, thereby fostering a culture of excellence within the organisation.

Clear Quality Objectives: By establishing SMART (Specific, Measurable, Achievable, Relevant, and Time-bound) quality objectives, organisations can ensure that everyone understands their contributions to quality improvement.3 Regular communication and review of these objectives help maintain focus and accountability, fostering a culture of continuous improvement.

Documentation and Standard Operating Procedures (SOPs): Clear documentation and SOPs are vital for ensuring consistency in processes and ad-

www.international-pharma.com

herence to quality standards.4 They provide a structured framework for knowledge transfer among employees, maintaining continuity in operations.

This consistency enhances efficiency and supports compliance and quality assurance across the organisation.

6.

7.

8.

9.

Risk-Based Thinking: Adopting riskbased thinking fosters a proactive approach to quality management, promoting a strong quality culture. By encouraging employees to identify and address potential risks, organisations empower them to take ownership of quality. This mindset strengthens overall quality performance and enhances resilience against challenges.

Continuous Improvement: Emphasising continuous improvement is vital for sustaining a strong quality culture.

By encouraging employees to identify enhancement areas, organisations create an environment that values learning and innovation. This focus boosts quality performance and motivates employees to actively contribute to the organisation's success.

Collaboration and Communication: Effective cross-functional collaboration and communication are essential for enhancing quality outcomes. By sharing knowledge and best practices, organisations leverage diverse perspectives, fostering a unified commitment to quality and ensuring all teams work towards common goals and continuous improvement.

Audits and Inspections: Regular internal audits and external inspections are vital for ensuring compliance with regulatory requirements. These assessments verify adherence to standards and identify improvement areas. By systematically evaluating processes, organisations can enhance their quality management systems and effectively drive continuous improvement initiatives.5

10. Customer Focus: Placing the customer at the centre of quality efforts is essential for meeting their needs and expectations. This customer-centric approach fosters a quality culture that prioritises satisfaction and loyalty. By actively seeking and responding to feedback, organisations can continuously enhance their products and services, ensuring lasting success.

Hypothetical Scenario: Building a Quality Culture A pharmaceutical company implemented a comprehensive training program on quality principles, encouraging employees to share experiences related to quality issues. One department identified a recurring problem with a supplier’s materials. By collaborating with Quality Control and Procurement, they established stricter inspections for these suppliers. This initiative significantly reduced defects and improved product reliability, with new procedures integrated into the relevant incoming material sampling and inspection SOPs. Measuring Success To gauge the effectiveness of our shift towards a more collaborative approach to quality, we need to establish clear, quantifiable metrics that can provide insights into our progress and impact. Here are some key areas to focus on: •

Reduction in Deviations and CAPAs: Tracking deviations and Corrective and Preventive Actions (CAPAs) over time can indicate the effectiveness of quality management practices. A significant reduction suggests successful implementation of proactive measures and adherence to protocols. Regularly reviewing these metrics in team meetings reinforces accountability and highlights areas for ongoing improvement.

•

Improved Process Capability: Measuring process capability indices (like Cp and Cpk) allows us to assess how well our processes meet specifications. An increase in these indices indicates greater stability and capability, leading to higher quality outputs. This can be complemented by Six Sigma methodologies to set improvement targets and track progress.6

•

Increased Employee Engagement in Quality Initiatives: Employee engagement is crucial for fostering a quality culture.

We can measure engagement through surveys, participation in quality training sessions, and involvement in quality improvement projects. High engagement levels often correlate with improved morale and a stronger commitment to quality objectives. Celebrating employee contributions to quality initiatives further enhances this engagement.

•

Positive Feedback from Other Departments: Gathering feedback from various INTERNATIONAL PHARMACEUTICAL INDUSTRY 63

Manufacturing departments about QA's collaborative approach provides valuable qualitative insights. Surveys or informal feedback sessions can assess perceptions of QA's support and involvement. Positive feedback indicates that QA is effectively partnering with other teams and contributing to a shared quality vision.

•

Performance Metrics Specific to Each Team: Each department should have specific performance metrics related to quality that can be monitored, including supplier performance in procurement, equipment downtime in engineering, and test accuracy in quality control.

Regularly reviewing these metrics drives accountability and fosters continuous improvement within each team.

•

Timeliness of Issue Resolution: Tracking the speed of issue identification and resolution provides insights into the effectiveness of our collaborative efforts. A decrease in resolution times for CAPAs and other qualityrelated issues indicates that teams are effectively working together to address problems.7

•

Training and Development Outcomes: Measuring the effectiveness of quality training programs ensures that employees have the necessary knowledge and skills. Pre- and posttraining assessments provide insights into knowledge gains, while tracking the application of training in daily operations highlights its practical impact.

64 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Real-World Example: Measuring Success A pharmaceutical company that implemented employee engagement surveys found that departments with higher engagement scores reported fewer deviations. For instance, after introducing a comprehensive quality training initiative including workshops, hands-on sessions, and interactive e-learning – one department saw a 30% decrease in errors within three months. The initiative focused on key quality principles like GMP, risk management, and documentation standards.

Employees engaged in case studies and role-playing exercises, enhancing their understanding of how their work impacts product quality. This direct engagement demonstrated a strong correlation between employee engagement, quality training, and improved quality outcomes.

Overcoming Resistance Individuals or teams may initially resist this shift due to concerns about changes to established processes or fears of increased scrutiny. To overcome this resistance, we can take several proactive steps: •

•

Demonstrate Value Through Small Wins: Highlighting small successes can build momentum for broader change.

For example, if a collaborative project results in reduced cycle times or improved quality metrics, sharing these achievements with the organisation illustrates the tangible benefits of collaboration.

Engage Stakeholders Early: Engaging stakeholders early in the process is

crucial for alleviating concerns and fostering buy-in.8 By soliciting input during the planning stages, organisations can ensure that initiatives address specific team needs. This collaborative approach enhances commitment and leads to more successful, relevant outcomes.

•

Communicate Openly and Frequently: Open and frequent communication about the goals of quality initiatives is essential for fostering engagement and collaboration. Regular updates and success stories keep everyone informed, reinforcing the benefits of teamwork. This transparency builds trust and motivates employees to actively participate in quality improvement efforts.

•

Provide Support and Resources: Offering training and necessary tools can ease the transition and empower teams to collaborate effectively. By equipping employees with the right resources, organisations facilitate smoother integration of changes, enhancing overall productivity and quality outcomes.

•

Celebrate Collaborative Efforts: Recognising and rewarding teams and individuals who embrace collaborative quality practices is essential for reinforcing desired behaviours.9 This recognition fosters a culture of quality, motivating others to adopt similar practices. By celebrating successes, organisations encourage ongoing

Autumn 2025 Volume 17 Issue 3

Manufacturing commitment to quality improvement and collaboration.

Hypothetical Scenario: Overcoming Resistance In a pharmaceutical company facing resistance to a revised quality control procedure, management involved employees in the development process and provided hands-on training sessions, which reduced resistance. Employees were encouraged to share concerns and suggestions during pilot implementations. After several months, the revised procedure improved documentation accuracy and enhanced workflow efficiency, leading to better compliance with regulatory standards. This collaborative approach fostered a sense of ownership among employees, ensuring a smoother transition to the new practices.

Final Thoughts Reflecting on the preceding discussion, consider the following question that often arises among pharmaceutical professionals: Who is ultimately responsible for quality and the pharmaceutical quality system?

The options are: • • •

Option A: All personnel in the company Option B: Quality Assurance Department Option C: Senior Management within the organisation

This question examines shared responsibility for quality within the organisation. Recognising quality as a collective effort is vital for fostering commitment at all levels. Senior management should position Quality Assurance professionals as collaborators and educators, engaging teams and demonstrating the value of quality through measurable outcomes.

Ultimately, we must cultivate a culture where quality is a core value integrated into all aspects of our operations, embraced by every employee.

Conclusion To bridge the gap between the ideal of "everyone's responsibility" and practical implementation, senior management must engage with teams, empower employees, and establish clear quality objectives. The notion that “it is no one's responsibility” is misleading; this "everybody, somebody, nobody" trap leads to assumptions about accountability. Measuring success through quantifiable metrics will help track progress and reinforce accountability. Ultimately, cultivating a shared commitment to www.international-pharma.com

quality is essential for ensuring product integrity, enhancing patient safety, and achieving excellence in the pharmaceutical industry.

REFERENCES 1.

2.

3.

4.

5.

6.

7.

8.

Institute for Healthcare Improvement. Quality Is Everyone’s Responsibility [Internet]. 2016.

Available from: https://www.ihi.org/insights/ quality-everyones-responsibility Tambare P, Meshram C, Lee C-C, Ramteke R, Imoize A. Performance measurement system and quality management in data-driven Industry 4.0: a review. Sensors. 2021;22(1):24. doi: 10.3390/s22010224.

Setting and applying SMART objectives | CQI |IRCA [Internet]. Available from: https:// www.quality.org/knowledge/applying-smartobjectives The critical role of standard Operating procedures (SOPs) in the pharmaceutical industry [Internet]. 2024. Available from: https://speach.me/blog/the-critical-roleof-standard-operating-procedures-sops-inthe-pharmaceutical-industry Hut-Mossel L, Ahaus K, Welker G, Gans R. Understanding how & why audits work in improving the quality of hospital care: A systematic realist review. PLoS ONE [Internet].

2021 Mar 31;16(3):e0248677. Available from: https://doi.org/10.1371/journal.pone.0248677 Senvar O, Toz H. Process capability and six Sigma methodology including fuzzy and lean approaches. In: Sciyo eBooks [Internet]. 2010.

Available from: https://doi.org/10.5772/10389 Nour, Reham Osama. Good Capa Practice - A Six Sigma Approach To Reduce Cost Of NonCompliance. 2018. Open Access Theses. 1431. https://docs.lib.purdue.edu/open_access_ theses/1431 Section 2: Engaging stakeholders in a care

9.

management program [Internet]. Agency for Healthcare Research and Quality. Available from: https://www.ahrq.gov/patient-safety/ settings/long-term-care/resource/hcbs/ medicaidmgmt/mm2.html Jerab DA, Mabrouk T. The role of leadership in changing organizational culture. SSRN Electronic Journal [Internet]. 2023 Jan 1; Available from: https://doi.org/10.2139/ ssrn.4574324

Markus Lung Chi-ho Markus Lung Chi-ho (MBA, BPharm., BPharm(ChinMed)), is a registered pharmacist and qualified person in Hong Kong. As the General Manager at Vita Green Pharmaceutical (HK) Limited, he oversees full portfolio management, strategic operational management, quality and regulatory compliance, and technical optimisation of pharmaceutical and nutraceutical manufacturing plants.

Markus brings nearly 30 years of experience in the traditional Chinese medicine, nutraceutical and pharmaceutical industry.

He is a Chartered Fellow of the Chartered Management Institute, a Fellow Chartered Chemist of the Royal Society of Chemistry and a Fellow of the Hong Kong College of Pharmacy Practice. His extensive expertise contributes to advancing quality standards and operational excellence in the sector.

INTERNATIONAL PHARMACEUTICAL INDUSTRY 65

Application Note

Hygienic Stäubli Robots in Pharmaceutical Packaging Proven Packaging Expertise How do you package medication sets with four components each, at a rate of 200 per minute, in compliance with pharmaceutical manufacturing requirements? Uhlmann Pac-Systeme has the answer: with a UPS 5 blister machine. Their system concept, which uses hygienic Stäubli SCARA robots for cycle time-critical handling processes, can be scaled on a modular basis. The longest UPS 5 system to date, featuring four robot stations and high-speed feeding systems, recently went into operation.

Parenteral is better: This is the guiding principle of physicians for numerous medications. It means avoiding the “detour” through the digestive tract and delivering active ingredients directly to the bloodstream or tissue, for example, with syringes, pens, and other drug delivery devices.

Uhlmann Pac-Systeme develops and manufactures the perfect secondary packaging systems for parenteral products.

The injection devices used to administer the medications are typically packaged in single-dose blister packs containing several different components. To accommodate this format, Uhlmann developed the modular UPS 5 blister machine, which can be expanded to adapt to different user requirements.

Uhlmann recently supplied the longest and most powerful UPS 5 system yet to a global pharmaceutical company that produces a medication set consisting of a disposable syringe and a two-component active ingredient. Each blister therefore contains four components: a syringe filled with ingredient 1, two needles, and a vial containing active ingredient 2. Their combination produces a single injectable dose of the active ingredient.

For this project, Uhlmann chose to use SCARA robots from Stäubli. These precise four-axis robots, mounted directly on each station’s machine frame, place the parenteral products into blisters formed by the UPS 5.

Uhlmann’s SyPro and LiPro feeders deliver the products to each station. Individually 66 INTERNATIONAL PHARMACEUTICAL INDUSTRY

configured robot grippers, also developed in-house, allow medication sets to be packaged at high speed while complying with pharmaceutical industry requirements.

Three Robots, Four Components, One Blister The project engineers at Uhlmann PacSysteme have successfully addressed this packaging challenge by utilising three Stäubli TS2-60 SCARA robots and ensuring maximum flexibility with the addition of an extra robot station that is not currently in use.

This configuration will enable the system to package even more complex pharmaceutical products in the future.

The first workstation of the UPS 5 produces the blister cavity: Using compressed air, the machine heats and forms a PET film into the desired shape at the “forming station” and then cools it again in a matter of seconds.

The UPS 5 can produce blisters with a depth of up to 40 mm, but for this system, a depth of just under 20 mm is sufficient. A total of 10 blisters are arranged in parallel and fed to the following robot stations.

First Robot Station: Inserting Filled Syringes The first robot station is used to place filled syringes into the blisters. A highly dynamic Stäubli SCARA TS2-60 is put through its paces, reliably inserting an impressive 200 syringes per minute. They are presented to the four-axis unit via a SyPro feeder specially developed by Uhlmann for sensitive glass syringes. The syringes are initially transported in a suspended vertical position and gently rotated 90 degrees shortly before pickup, allowing the robot’s vacuum gripper to pick up and place 10 syringes at a time.

Second Station: Handling 2 x 200 Needles per Minute At the second station, two different needles – color-coded in blue and orange, for example – are added. The speed is therefore twice as fast: A second, identical robot places 400 needles per minute into the blisters.

Janina Triska, Project Manager at Uhlmann Pac-Systeme, explains why each blister needs two different needles: “As with many other parenterally administered drugs, this

injectable agent requires two components to be mixed before administration. Once combined, the active ingredient is released.

In this case, one component is contained in the syringe, and the other is contained in the vial. One needle is used to draw the contents of the vial into the barrel of the syringe, while the other is used to administer the medication.”

A second SyPro feeder is used at this station, but it uses a different transport concept and feeds the needles side by side.

A closer look at the insertion process reveals that the robot, which picks up and inserts 10 needles at a time, operates through two distinct cycles. Janina Triska: “This is the only way we can achieve the required high output across the two blister rows and ensure that 200 blue and 200 orange needles are inserted.”

Station 3: The Vials are Coming At the third station, a third identical robot places vials containing the second ingredient into the blister. Here, the vials are transported upright on a servo-controlled LiPro feeder and rotated by 90 degrees at the pickup point. The TS2-60 uses its vacuum gripper to remove 10 vials at a time and place them in the corresponding blisters simultaneously.

In the next steps, the UPS 5 routes the assembled blisters through automated visual inspection, seals them, and then separates them at the punching station. Only perfect blisters proceed to the cartoning machine, which packs them into folding boxes.

The blister machine has a fourth feeding unit, which is also equipped with a robot, but it is not currently in use. Janina Triska explains why: “The customer wanted not only a very powerful system, but also a very flexible one. That’s why we designed the machine to allow for the addition of another component. However, this feature is not in use at the moment.”

Stäubli Robots: The Benchmark for Pharmaceutical Applications All four stations – and UPS 5 systems in general – are equipped with Stäubli TS260 SCARA robots for good reasons: This type of robot is especially prevalent in pharmaceutical manufacturing. In addition Summer Autumn 2025 Volume 17 Issue 2 3

Application Note to superior hygienic design, the key factors here are high precision, long service life, and impressive dynamics, which make a decisive contribution to meeting cycle time specifications.

The system is designed to be as simple and intuitive to operate as possible. The robot controller communicates with the higherlevel Schneider PLC, and Uhlmann’s Red Dot Award-winning SmartControl operator terminal (https://www.red-dot.org/project/ smartcontrol-31791/) is used as the humanmachine interface. It can be operated intuitively, much like an app, allowing the user to see a 3D model of the system in front of them and zoom in on the areas and features they want to observe or control with a single click.

A Special System Based on a Tried-and-Tested Standard The system, which of course is GMP-compliant, is nearly 15 meters long, making it the longest that Uhlmann has ever designed and built. Its less complex blister machines require only a few square meters of space.

This system is impressive not only because of its dimensions. Janina Triska

Three Stäubli robots work together in parallel on a Uhlmann blister line to ensure the blisters are loaded safely.

adds, “The machine continuously packs various components via different feeders at very high speeds. The robots and other automation components boast outstanding performance. That is impressive and the result of the enormous expertise that goes into these highly sophisticated solutions.”

Consequently, the customer’s specifications and objectives were completely met.

About Stäubli Stäubli is a global industrial and mechatronic solution provider with four dedicated Divisions: Electrical Connectors, Fluid Connectors, Robotics and Textile, serving customers who aim to increase their productivity in many industrial sectors. Stäubli currently operates in 28 countries, with agents in 50 countries on four continents. Its global workforce of 6,000 shares a commitment to partnering with customers in nearly every industry to provide comprehensive solutions with long-term support. Originally founded in 1892 as a small workshop in Horgen/ Zurich, Switzerland, today Stäubli is an international Group headquartered in Pfäffikon, Switzerland. www.staubli.com/global/en/home.html

About Stäubli Robotics At the first robot station, a Stäubli TS2-60, equipped with a tenfold gripper, inserts filled syringes.

Stäubli Robotics’ unique product portfolio contains 4 and 6 axis industrial robots, cobots, mobile robotics and Automated Guided Vehicles. The powerful, high precision solutions allow clients in many demanding industries to tackle the challenges of Industry 4.0 under specific manufacturing conditions. www.staubli.com/global/en/robotics/ products.html

In the second feeding unit, up to 400 needles per minute are inserted into the blister cavity. www.international-pharma.com

View of the gripper on the four-axis robot. Clearly visible: the various components with which each blister is filled.

www.linkedin.com/company/staublirobotics/

INTERNATIONAL PHARMACEUTICAL INDUSTRY 67

Manufacturing

How Automation Helps to Accelerate Product Development Sumeet Dalvi from Emerson explains how advanced automation solutions, paired with unified data strategies, are enabling life sciences organisations to expedite technology transfer and bring new treatments to market faster.

It is widely recognised within the healthcare industry that patient expectations are rapidly evolving, with an increasing demand for higher service standards and prompt access to safe and effective therapies.

This puts life sciences manufacturers under growing pressure to bring innovative new drugs, devices and treatments to market as quickly as possible, without compromising safety or efficacy. This in turn creates significant challenges throughout the entire development chain as organisations strive to achieve more efficient production processes, faster clinical trials and streamlined regulatory approvals.

Today, there are more emerging therapies in development that are patient centric than traditional blockbuster therapies.

This challenges manufacturers to become increasingly flexible and agile, ensuring they can quickly switch production between different therapies. The ability to rapidly pivot their manufacturing can give organisations a competitive edge, making them better positioned to capture emerging market opportunities.

The need to streamline changeover efficiency is driving manufacturers to introduce variable, rather than fixed, product recipe parameters as part of a more integrated control strategy. This means that vital parameters such as ingredient proportions, processing conditions and timing can be adjusted to accommodate variations in product formulations, production scales, or regulatory requirements without having to redesign the entire process. This flexible approach reduces downtime and costs by enabling manufacturers to quickly switch between different products or therapies, while maintaining high product quality.

Along with offering greater flexibility, production facilities must of course 68 INTERNATIONAL PHARMACEUTICAL INDUSTRY

continue to operate smoothly and efficiently. Operational integrity and timely product delivery requires the ability to adjust to unforeseen disruptions, with the prediction and prevention of equipment failures and process deviations that could impact production schedules and create manufacturing losses. Organisations are also striving for real-time release and sustainable operations. With the integration of in-line quality monitoring, this enables real-time process adjustments and automatic exception handling helping to eliminate or reduce timeconsuming manual checks, batch reviews and testing. Continuous real-time monitoring and analytics enables manufacturers to quickly identify any process deviations, make informed decisions and adjust operations proactively. This then enables them to maintain high product quality, reduce downtime and production costs, and ensure regulatory compliance. Greater operational insights and improved process control can also help to drive the changes necessary to reduce waste and optimise energy usage, helping companies to achieve sustainability goals.

Optimised Data Management For manufacturers looking to optimise their operations, increase speed-to-market and secure an advantage over their competitors, effective data management must be a core foundational element. To optimise data management, manufacturers need to bring together diverse data from disparate systems, ranging from process control to quality assurance. This integration prevents critical production data from becoming trapped in silos, instead ensuring that it is readily and coherently available at a single, unified point. Today’s life sciences organisations are embracing automation as a core element of data management. The goal is not just gaining access to more data but unlocking ‘data as a product’. This requires a boundless automation approach, with seamless and traceable movement of contextualised information across the entire development and manufacturing chain, from research through to commercial-scale production.

This will help to make technology transfer faster and easier and enhance operational sustainability. Ultimately, achieving these objectives helps to ensure that treatments

are delivered to patients around the world in the shortest time possible.

Process Knowledge and Workflow Management During the process development and clinical manufacturing stages, the focus is on identifying the most effective and reliable means of manufacturing a new product consistently. Whilst undertaking the many experiments during these stages, the teams involved need to know which version of the process is the current one at any point in time, the order of unit operations and the specific parameters for each experiment. With greater experience of the manufacturing process and more results from experiments, the teams will refine the process and quality parameters, update risk assessments and devise control strategies to mitigate any potential issues.

Achieving these objectives demands integration and analysis of a lot of data from multiple sources. Storing and organising this data across various systems, formats and recording tools can lead to significant delays and potential errors if performed manually.

Advanced automation tools designed to provide seamless data mobility can help to maintain data integrity and context, reduce manual work and streamline the management and transfer of information across development, clinical manufacturing and commercial scaling. Tools such as process knowledge management (PKM) systems and digital workflow management solutions help to standardise processes and improve flexibility.

PKM software facilitates the seamless management of product and process specifications throughout the drug development lifecycle, while digital workflow management solutions provide intuitive interfaces to enforce workflows and support quick, efficient task execution no matter the skill level of authors. PKM software provides a development team with centralised recipe management – a single source of truth for the product definition, specification structures, and process terminology needed throughout the product lifecycle. Data within PKM software can be accessed securely from Autumn 2025 Volume 17 Issue 3

Manufacturing change happens, helping to ensure smooth, uninterrupted production.

anywhere via a web-based interface, making it easier for users to collaborate and access essential documents and data for real-time decision-making.

Organisations also need a means of storing all their process and manufacturing data in a federated data fabric, accessible by any authorised user and application.

Many therefore plan to extend enterprise service buses and centralised data lakes to an integrated industrial and business data fabric. The fabric seamlessly connects diverse systems to collect and store large volumes of data, which is then made accessible for analysis and reporting locally and across the enterprise. Together, PKM software and an industrial data fabric reduce the amount of time spent on low-value tasks and dramatically shorten the technology transfer process.

Simulation Solutions As companies prepare to transition to commercial-scale manufacturing, selecting the right production site is crucial. Whether constructing a new manufacturing facility, identifying an existing location with the necessary capacity, or outsourcing manufacturing to contract manufacturers, robust data management remains vital. For greenfield sites, companies often perform design simulation to ensure the plant meets the required specifications. Simulation tools help to identify potential bottlenecks before construction begins and can also be used to train operators in advance of start-up, helping ensure optimal performance from day one.

Simulation tools also benefit existing facilities.

For example, by using automated model creation software, organisations can assess a site’s capacity for specific products and uncover and eliminate potential inefficiencies before they impact production.

Efficient and accurate simulation requires vast amounts of data, and to supply this, teams are increasingly connecting simulation software to their integrated data fabric solutions. By leveraging contextualised www.international-pharma.com

information in a data fabric, teams can quickly and easily build the various models necessary to take full advantage of what the simulation software can deliver. The more data and context the team has, the more accurate the results will be.

For existing or outsourced manufacturing sites, companies often perform facility fit assessments to determine the best site for manufacturing a certain product at a given scale. Advanced PKM solutions include facility fit tools that use data to identify whether a site has the necessary equipment and capacity to meet production goals.

These tools can provide highly specific recommendations and alert users when manufacturing configurations do not meet their needs.

Commercial Manufacturing at Scale When moving into large-scale production, the need for fast, flexible data access increases.

Manufacturing teams must be able to view data from a variety of sources, such as the process control system, manufacturing execution system, quality management tools and edge sensors. They also need to contextualise the data and present it to multiple personnel, enabling them to make critical decisions quickly.

To ensure batches are consistently produced according to requirements, production and quality teams rely on precise data that confirms product quality. Every manufacturing and release step must always be right first time, which requires continuous monitoring of the entire process, including the calibration and health of all the devices involved. To support this, device management systems are essential. These systems run alongside the distributed control system (DCS) to help teams calibrate assets and document the status and health of devices such as measurement instrumentation. They track device status and calibration details, and provide an automatic audit trail of device changes, for validation and auditing purposes. They also issue alerts when a

Alongside device management, teams need high-quality data on the health of balance-of-plant assets that are integral to the process, such as cooling towers, HVAC systems and pumps. Monitoring these systems ensures potential failures are identified and addressed before they impact manufacturing.

Modern plants use wireless vibration sensors and edge analytics to feed critical health data from rotating machinery into their DCS and data fabric. This helps teams stay on top of the overall health of the plant and identify issues before they deteriorate and lead to failures that can impact operations.

Moreover, having all connected data within a unified data fabric, teams can leverage more complex, AI-based analytics systems to provide the instantaneous feedback and decision support necessary to support more autonomous operation.

Conclusion As life sciences companies strive to enhance their speed to market, manufacturing flexibility, operational efficiency and sustainability, their reliance on data continues to grow. Fortunately, modern automation systems are designed with seamless data flow in mind, ensuring data reaches the right place at the right time, with full contextual accuracy to support real-time decisions.

Building a foundation of data mobility now will provide long-term advantages, helping organisations to stay flexible and agile in an increasingly complex global marketplace. Not only will this foster a competitive edge, but it will also enable the faster delivery of lifesaving therapies to patients worldwide.

Sumeet Dalvi Sumeet is Life Sciences Software Solutions Manager at Emerson.

Sumeet is responsible for delivering technical competency and driving value proposition and revenue ownership for Emerson's DeltaV Process and Knowledge Management (PKM) software platform, across Europe. Based in Baar, Switzerland, Sumeet has a degree in Computer Engineering and Master of Business Administration degree from the Xavier School of Management in Jamshedpur.

INTERNATIONAL PHARMACEUTICAL INDUSTRY 69

Application Note

The Next Generation of Infuse Redefining Efficiency, Stability, Speed, and Security Over the past decade, the pharmaceutical industry has experienced rapid growth in using new and advanced ideas. Prefilled syringes have become a popular method of drug delivery to treat an increasing number of patients suffering from chronic diseases, cancers, or autoimmune diseases due to increased safety, ease in usage, convenience, accuracy in clinical use, and the ability for self-injections.

Moreover, they gained strong acceptance for chronic conditions requiring repeated medication administration.2.3 A prefilled syringe (PFS) is filled with one or more active medicines at the required concentration and volume and correctly labelled before it enters the final clinical area, where it can be administered immediately without further preparation.

One of the recent reports, published in November 2024 by Fortune Business Insights, shows the global prefilled syringe market is expected to continue experiencing exceptional growth over the next eight years.

The global prefilled syringes market size was $7.91 billion in 2023 and is projected to grow from $8.70 billion in 2024 to $20.62 billion by 2032, exhibiting a CAGR of 11.4% during the forecast period 2024–2032. Europe dominated the prefilled syringe market with a market share of 40.33% in 2023. North America is likely to hold the second-largest market share after Europe, owing to the rise in several chronic diseases, such as diabetes and rheumatoid arthritis. These diseases are likely to enhance the demand for prolonged drug administration at an accurate dosage.4 In hospital settings, where decisions must be taken more quickly or under stress (i.e., operating theatres, during urgent interventions, emergency department, ICUs), medication error rates in preparing injectable drugs from vials and ampoules are substantially higher. These errors can result from standard human factors and resource constraints, leading to Adverse Drug Events (ADEs). Such ADEs can substantially increase hospital operating costs. Several literature reports suggest that PFS can ensure sterility and help reduce medication errors associated with mislabelling, dosing errors, 70 INTERNATIONAL PHARMACEUTICAL INDUSTRY

and related expenses. It’s also reported that usage of PFS can also benefit drug/ disposables/packaging waste reduction and medication preparation time reduction by more than 50%.

and health systems face looming questions about deploying technology to improve the patient experience without further burdening clinical staff, from telehealth to electronic health records.

WHO has identified unsafe medication practices and medication errors as leading causes of injury and avoidable harm in healthcare systems across the world, with an estimated associated cost in the range of $42 billion annually. Often, medication errors occur when weak medication systems and/or human factors take effect, such as fatigue, poor environmental conditions, or staff shortages.

These can all impact the preparation and administration of injectable drugs and result in severe harm to patients (Medication Without Harm, WHO).

Challenges Faced by Healthcare Workers It was prevalent during the COVID-19-induced pandemic, which has had a psychological, emotional, and physical impact on healthcare workers, including pharmacists and nurses.

Hospital pharmacists have been playing a crucial role during the pandemic. They had found themselves facing particularly stressful factors, such as working extra hours to ensure a sufficient supply of medication to intensive care units and to mitigate drug shortages and disruptions in the supply chain. The latter faced the suffering and death of an extraordinary number of patients and the work overload caused by the shortage of personnel. Many were asked to work in unfamiliar clinical areas, hurriedly set up to deal with the patient overload. The contagious virus forced all healthcare personnel to wear extra personal protective equipment (PPE), which undoubtedly limited movement, restricted vision, constrained communication, and reduced speed of action. It followed an increased risk of errors during the preparation and administration of drugs.5,6

Errors Related to IV Administration The highest error rates involve intravenously administered drugs (48%–81%), mainly related to the complexity of preparation, administration, and monitoring.4 These medication error allied problems appear to be mainly in clinical settings (e.g., during emergency interventions, emergency rooms, intensive care units, and operating rooms), where there are many possible human factor error steps in medicine preparation and administration, and decisions are made quickly or under stress.5 IV medication errors pose an increased risk of patient harm due to the medication's immediate bioavailability, narrow therapeutic window, and challenges involved in reversing systemic effects. These errors can negatively impact both patients and nurses.10 Challenges Faced by Healthcare Providers Ensuring safe injection practices is one of the most significant challenges for the healthcare system in developing countries.

Unsafe disposal and reuse of contaminated syringes are standard. Interventions with the active involvement of several stakeholders are essential to address the problem. Many healthcare industry challenges stem from a need to respond to external forces from regulators, competitors, or cybercriminals.

Inefficient workflows for documenting patient appointments, submitting insurance claims, and normalising unstructured data add to organisations’ expenses. Hospitals

The Role of the Prefilled Syringe in Solving Those Challenges The role of PFS, with specific reference to situations of heavy workload and high stress, such as those experienced during the COVID-19 pandemic, has recently been reviewed by a systematic review of several authors and reported by observational studies, surveys, case reports, and risk analysis.5 The use of PFS provides the following advantages:5 1.

2.

3.

4.

5.

6.

Reduced number of preparation steps and associated cognitive complexity Simpler use (no labelling needed on the point of care, as it is already correctly labelled) Reduced infection (reduced microbiological contamination) Reduced drug, disposables, and packaging wastage Reduced nursing time allocated to the preparation and administration of drugs Quicker to administer in an urgent crisis Summer Autumn 2025 Volume 17 Issue 2 3

Application Note 7.

8.

9.

Reduced the likelihood of medication errors Reduced needlestick injuries Overall cost savings (although more money is spent to purchase PFS, the use of PFS led to significant cost savings)

Like all businesses, hospitals try to reduce costs as much as possible. Labour costs and product waste are two areas where the right drug delivery product can impact their bottom line. For example, patients in medical and surgical units receive an average of 10 injections daily. PFS products have been shown to reduce preparation and administration time significantly.

Figure 1: SCHOTT TOPPAC® infuse – the next generation

The Next Generation of SCHOTT TOPPAC® infuse Syringes Redefines the Benchmark Preparing anaesthesia trays requires manual checks of each syringe's shelf life and medication. Additionally, syringes in anaesthesia trays often lead to drug waste, as not all drugs are used during a single procedure, and the syringes do not indicate if they have been used. Space in hospital environments is also limited, so product packaging should be as compact as possible.

The next generation of SCHOTT TOPPAC® infuse prefilled polymer syringes features a new cap and label design that covers the entire shoulder of the syringe, providing a first opening indication to reduce drug waste.

This design also forms the basis for a new blister-free packaging concept that can offer additional protection, such as from light or oxygen, guaranteed by the label instead of a blister. The label can be equipped with an RFID chip for seamless traceability and a digital-first opening indication, increasing the efficiency of anaesthesia tray preparation from 20 minutes to just 1 minute. Existing verification packages and connector tests can expedite the time to market for new and existing customers. The syringe features: • • • • • •

First-opening indication: Ensuring the syringe has not been compromised or used before.

Protection from contamination: Dust, moisture, microorganisms Protection against mechanical stress: Precise product fixing Gas Barrier: Protection against moisture, O2, etc.

Visibility identification: Ability to inspect and see the expiration date UV/Light protection: Shielding the product from environmental factors such as light

www.international-pharma.com

Figure 2: A. Traditional blister packaging; B. SCHOTT TOPPAC® infuse blister-free packaging.

•

User-friendly: Separation of single units via perforation or blister with tear tab

Secure and Blister-free Packaging We must question and revolutionise traditional packaging methods to minimise environmental impact and maximise efficiency. While once ubiquitous, blister packaging poses significant challenges regarding waste generation and logistical complexity.

The new blister-free packaging concept that was created together with the Alliance to Zero members, SCHOTT Pharma, Schreiner MediPharm, and Körber Pharma, was enabled by the new cap and label of the SCHOTT TOPPAC® infuse syringe. It minimises waste and reduces space by containing 20% more syringes per container, resulting in up to 58% lower CO2 footprint during transport. 3 times less storage space is required in hospitals and 500 kg less plastic and packaging waste is generated (All numbers are valid for 151.200 units of one sort for a 5 ml SCHOTT TOPPAC® syringe. Given values are valid for best-case scenarios. PCF data are not considered).

Using Labels to Add Relevant Functionalities Labels in pharma packaging are the most common way to provide the relevant information directly on the primary container of a pharmaceutical product. However, as stated, labels offer many more options to add value to pharma packaging. They can contribute significantly to patient safety or user experience, provide a strong first-opening indication, or represent the interface for track and trace solutions and the digital world. Since a label covers a significant part of the primary container's surface, they are predestined to add additional protection to the packaging system, such as UV/light protection or gas barrier.

The Label Technology for the SCHOTT TOPPAC® infuse Syringes Increasing Security and Efficiency Since the Commission Delegated Regulation (EU) 2016/161 (Source: Delegated regulation – 2016/161 – EN—EUR-Lex) supplementing the falsified medicines directive 2001/83/EC became effective in February 2019, tamper INTERNATIONAL PHARMACEUTICAL INDUSTRY 71

Application Note that the syringe has been opened and is no longer sterile.

Figure 3: Overview of label-based functions for the next generation of SCHOTT TOPPAC® infuse syringes

indication on secondary medicine packaging has become mandatory in Europe, making tampering much more difficult for criminals.

Illegal medicines inflict considerable damage on the pharmaceutical industry, but above all, they pose a massive risk to patient safety. The unauthorised use of medicines, e.g., in hospitals, or re-use of empty original medicine syringes with original labels from waste containers, pose a growing and significant threat: whenever criminals refill the container with ineffective or even harmful substitutes and put these adulterated medicines back into circulation in an uncontrolled way, patients are exposed to acute health risks. Thus, appropriate security solutions should be implemented on the primary container level to achieve comprehensive product and patient safety due to a consistently secured supply chain.

This includes tamper-evidence and anticounterfeiting technologies, together with unique serial codes.

The current standard packaging for syringes consists of a standard syringe without an integrated first-opening indication, plus a standard label packed

in blister packaging sealed with lidding foil. Thus, the blister packaging takes over the crucial irreversible first-opening functionality on the secondary packaging level. If the blister is removed from the packaging concept at all or during the last mile to the patient (for space-efficient storage), this crucial functionality is removed, and the syringe is unprotected.

PFS are one of the most frequently used means of primary packaging, in addition to vials. Most standard syringes do not allow for a convenient label-based sealing up to the cap due to the different radii of closure and syringe barrel. The next generation of SCHOTT TOPPAC® infuse features a unique design to allow for label-based sealing and reliable first-opening indication on the primary container level. The new Cap-Lock Label wraps around the entire cap and the syringe like a second skin, thus securing the integrity of the syringe until the injection is performed. Use of the label is easy and safe: The syringe can be opened in a single move, opening the syringe and label simultaneously. This purposefully destroys the label, clearly and irreversibly indicating

Special security die-cuts and print layers result in the intended partial destruction of the label upon opening and prevent reclosing it unnoticeably, even after authorised opening. An initially covert warning message or colour can be integrated as an additional feature to enhance visibility. Healthcare staff can immediately detect whether the syringe has been tampered with or opened.

This enhances supply chain security, minimises insider threats in hospitals, and contributes to the unnecessary disposal of drug products. Integrating an RFID chip can be considered to improve the functionality and security of the solution.

The new label offers an up to 25% larger label area as it uses the extra space on the top and above the transparent inspection window. Thus, there is more design flexibility to include customised branding, written information, or colour coding.

The security label can be applied to the syringe in conventional dispensing processes in pharmaceutical production, thus in a process without heat, so the SCHOTT TOPPAC® infuse syringe plus CapLock Label combination is suitable even for sensitive substances. This combined solution approach helps ensure the syringe's sterility and integrity until its use.

Increasing Drug Stability Light-Protect-Labels Many drugs are degraded by exposure to light, which can have serious consequences for the formulation and, ultimately, for the patient, e.g., altered efficiency, loss of efficiency, or an adverse biological effect. Therefore, light protection is needed for various formulations such as biologics, biosimilars, and many vitamins and minerals.

The new SCHOTT TOPPAC® infuse syringe's advantages, as a ready-to-use solution with irreversible first-opening indication, can also be fully exploited for light-sensitive formulations.

Figure 4: First-opening and re-capping indication via label, which covers both the syringe body and closure 72 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Using functional films, optionally combined with printing, label solutions can be provided with a specific UV and light protection profile based on three protection levels. To the formulation in the SCHOTT TOPPAC® infuse syringe, Cap-Lock Label LP 1 adds protection against UV light (< 370 nm), Cap-Lock Label LP 2 against UV and violet/ Summer Autumn 2025 Volume 17 Issue 2 3

Application Note

Figure 5: Cap-Lock Label LP combines multi-level UV and light protection with first-opening indication

blue light (< 480 nm), and Cap-Lock Label LP 3 against the whole spectrum of UV and visible light. Customised protection levels can also be achieved by adapting functional films and printing inks.

Lock Label GP for the SCHOTT TOPPAC® infuse syringe has the advantage that the irreversible first-opening indication of the label also allows for indication of the integrity status of the barrier function.

Any deviation from the test procedures or conditions may lead to different results. Consequently, test results cannot be transferred to individual customer applications without testing. Deviations may also occur due to different printing techniques.

The 10 ml SCHOTT TOPPAC® infuse syringe (previous generation) with a Gas-ProtectLabel (syringe barrel label) demonstrated a reduction in oxygen ingress of up to 86%.

With the SCHOTT TOPPAC® infuse syringe, a higher degree of coverage is possible. Thus, an enhanced gas barrier function can be expected with the SCHOTT TOPPAC® infuse syringe (permeation tests with Cap-Lock Label GP are still being carried out).11 The optimisation of the barrier performance of Cap-Lock Label GP is constantly being continued.

The next generation of SCHOTT TOPPAC® infuse syringes, combined with Light-Protect labels, prevents light from entering from the top of the syringe, allowing maximum light protection.

All Light-Protect-Labels have an inspection window to enable a complete, true-colour inspection. This window allows for easy examination of discolouration or particles through the transparent primary container.

Increasing Traceability with RFID RFID has fundamentally changed how

inventory is managed, and goods are tracked along the supply chain. The ability to track products throughout their lifecycle – from production to shelf placement – has led to significantly greater visibility and efficiency.

The technology allows retailers and manufacturers to track an item precisely (track & trace), minimising losses and optimising warehouse processes while reducing logistical costs and improving responsiveness in the supply chain. Global use has reached impressive numbers, with over 34 billion RFID inlays worldwide.12 Even in drug management, RFID has made immense progress, with more than 250 million tagged drugs in over 750 hospitals in the USA.13 This is where RFID plays a key role in improving drug safety, efficiency, and traceability. Thanks to real-time data transmission, RFID enables up to 90% faster stocktaking than conventional, manual processes. Inventories can be recorded automatically and without direct visibility of the item, significantly reducing the workload and minimising the susceptibility to errors when recording data. Tracking medicines along the entire supply chain – from production to transportation to administration to the patient – ensures that the right medicine is in the right place at the right time. The automatic identification of medication also minimises the risk of mix-ups or incorrect administration, which is a key factor in patient safety.

To ensure an overview and, more importantly, the integrity of medication in everyday hospital settings, RFID technology

Gas-Protect-Labels Medical polymer containers made of COC have the disadvantage of low barrier properties, as they allow gaseous substances to pass through. Numerous medications, therefore, suffer from gas permeability, which may result in severe consequences such as adverse biological effects or a reduction of shelf life.

Oxygen and the associated oxidation are a particular problem for many formulations.

To reduce permeation, Gas-Protect labels can be customised and applied flexibly to a container without changing the primary container. The adhesive is suitable for applications with a high migration risk and complies with FDA 175.105. Implementing Gas-Protect labels without any adjustments to the dispensing process is also easy. Capwww.international-pharma.com

Figure 6: Three different Cap-Lock Label LP protection levels show very low transmittance in the UV, violet/blue, and visible light spectrum.

INTERNATIONAL PHARMACEUTICAL INDUSTRY 73

Application Note

Figure 7: Digital First-opening functionality combined with Cap-Lock solution

for inventory can be expanded to include digital proof of initial opening. Thanks to its special design, it irreversibly indicates the first opening of the container and enables automated integrity tracking. It is no longer necessary to manually check whether the container has been opened. It optimises inventory management while making work easier for medical staff, as unused medication can be efficiently returned to stock. At the same time, possible diversions and the misuse of drugs can be monitored.

It is not only unique solutions that characterise Schreiner MediPharm's RFID labels. In addition, the label experts work on customised solutions to meet the special performance, implementation, and readability requirements, particularly in the pharmaceutical market. By individually adapting the RFID label to specific environments and applications, exceptionally high reading speeds and reliable detection can be achieved even under challenging conditions. The solution also greatly simplifies implementing RFID in existing systems, which means no costly machinery adjustments are necessary. As a result, an optimised RFID solution reduces operating costs and improves data accuracy and product traceability, leading to optimised operational performance and higher customer satisfaction.

74 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Conclusion In conclusion, the next generation of SCHOTT TOPPAC® infuse syringes represents a significant leap forward in addressing the challenges encountered in anesthesia tray preparation and pharmaceutical packaging.

The innovative design, characterised by a cap and label that envelops the entire shoulder of the syringe, introduces a pioneering first-opening indication. This groundbreaking feature not only diminishes drug waste but also offers enhanced protection from light or oxygen, obviating the necessity for conventional blister packaging.

Furthermore, the integration of tailored functional labels for SCHOTT TOPPAC® infuse syringes serves to bolster security, efficiency, drug stability, and traceability, effectively addressing critical regulatory requisites and minimising environmental impact.

This pioneering approach not only ensures the safety of patients and the integrity of products but also contributes to reduced waste generation, decreased CO2 emissions during transport, and enhanced operational performance. Ultimately, this innovation revolutionises traditional pharmaceutical packaging methods, setting a new standard for the industry.

Moreover, by providing the option to integrate an RFID chip for seamless traceability, the efficiency of anesthesia tray preparation can be markedly improved, reducing the time required from 20 minutes to a mere 1 minute. Additionally, this advancement facilitates the expedited launch of new products for both new and existing customers, streamlining the overall process. The syringe's comprehensive array of attributes, including safeguarding against contamination, mechanical stress, and UV/ light exposure, and its user-friendly singleunit separation, render it a cost-effective and space-efficient solution within hospital environments.

REFERENCES 1.

2.

3.

4.

Vizcarra, C., Cassutt, C., Corbitt, N., Richardson, D., Runde, D., & Stafford, K. (2014). Recommendations for improving safety practices with short peripheral catheters. Journal of Infusion Nursing, 37(2), 121-124.

Padhi, S., Bullock, I., Li, L., & Stroud, M. (2013).

Intravenous fluid therapy for adults in hospital: summary of NICE guidance. Bmj, 347.

Whitaker, M. C. A., & Whitaker, D. K. (2024). The impact of using prefilled syringes on a standard operating procedure for preparing injectable medicines in clinical areas. Anaesthesia, 79(1), 98-99. https://www.fortunebusinessinsights.com/ industry-reports/prefilled-syringes-market101946 (accessed on 18th November 2024).

Summer Autumn 2025 Volume 17 Issue 2 3

Application Note

Figure 8: Added value of RFID along existing processes

5.

Westbrook, J. I., Rob, M. I., Woods, A., & Parry, D. (2011). Errors in the administration of intravenous medications in hospital and the role of correct procedures and nursing experience. BMJ quality & safety , 20 (12), 1027-1034. A

6.

7.

Special Interest Group on the Use of Prefilled Syringes in Intensive Care Units and Operating Theatres – Report by European Association of Hospital Pharmacists December 2023.

Manzano García, G., & Ayala Calvo, J.C. (2021). The

8.

9.

10.

11.

12.

13.

14.

threat of COVID‐19 and its influence on nursing staff burnout. Journal of advanced nursing , 77 (2), 832-844.

Eijsink, J. F., Weiss, M., Taneja, A., Edwards, T., Girgis, H., Lahue, B. J., ... & Postma, M. (2024). Creating an evidence-based economic model for prefilled parenteral medication delivery in the hospital setting. European Journal of Hospital Pharmacy, 31(6), 564-570. https://www.who.int/teams/integrated-healthservices/infection-prevention-control/injectionsafety (accessed on 20th November 2024) Malik, P., Rangel, M., & VonBriesen, T. (2022). Why the utilization of ready-to-administer syringes during high-stress situations is more important than ever. Journal of Infusion Nursing, 45(1), 27-36.

Measurements performed with specific gas carrier method and SCHOTT TOPPAC® Syringes by an external institute. The data displayed were collected under specific test conditions.

Any deviation from the specific procedures or conditions may lead to different results.

Consequently, it is not possible to transfer without testing any test results in the test to individual customer applications. https://www.nanalyze.com/2023/11/impinj-stockbest-rfid-tracking/ (accesses on 06th December 2024 https://www.linkedin.com/posts/bluesight-inc_ we-recently-hit-an-exciting-milestone-reachingactivity-7239294138720862208-XQab?utm_ source=share&utm_medium=member_desktop (accessed on 06th December 2024) https://www.linkedin.com/posts/bluesightinc_hospitals-kitcheck-healthcareinnovationactivity-7209601116848676864-rJEA?utm_ source=share&utm_medium=member_desktop (accessed on 06th December 2024)

Authors: Zauner Christoph,1 Pawar Jaywant,1 Hofenauer Andreas,2 Endres Corinna,2 Lampka Nadine,2 Muenscher Sebastian,2 Kummergruber Eduard.2

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INTERNATIONAL PHARMACEUTICAL INDUSTRY 75

Packaging

The Importance of PRE-Coloured, Biocompatible and Pre-Tested ABS for Medical Device Approval Biocompatibility is a key property that needs to be complied by most medical devices to fulfil with medical regulations (e.g. EU MDR or US FDA regulatory requirements). Final medical devices must be tested according to ISO 10993 and it is the responsibility of the Medical OEM manufacturer to make sure that such tests are conducted and passed.

Biocompatibility tests are expensive and there is the risk that the required medical device may not pass one or more of them. The implementation of specific production procedures like GMPs (Good Manufacturing Practices), clean rooms etc. is critical, but positive test results cannot be assured without the correct pre-selection of all materials needed to produce each component of the device.

ABS plastics are widely used materials in external enclosures applications of medical devices. In this article we will discuss the different ABS material options available in the market to cover the biocompatibility needs of medical devices, and the risks associated with each one of them.

A first distinction is between what ABS manufacturers call as “medical ABS grade”, “food contact grade”, “healthcare grade” or “biocompatible grade”. These definitions are very different and refer to different concepts.

A medical grade includes a set of services and material properties that have been developed for medical device applications, but the term itself does not specify exactly what is really included or not. It is important to go through to the complete regulatory compliance list and to the set of services included, like for example the duration of the no-change agreement, notification periods, or the extended sample storage availability.

Such services are specific to guarantee the long-term supply and quality support to the medical device industry and are normally not available for a general ABS portfolio.

In any case, “medical ABS grade” does not automatically mean that the biocompatibility property was previously verified or even tested on the ABS as provided by the supplier.

This should be indicated by the material 76 INTERNATIONAL PHARMACEUTICAL INDUSTRY

manufacturer and even in this case it does not necessarily cover the PRE-coloured version of that biocompatible ABS, as it may refer only to the ABS in natural colour, without including the colour pigments. A food contact ABS refers to food or drug contact properties in terms of control of migration risks from the polymer to the food or drug during the device lifetime, but not to the set of services associated to the term “Medical ABS”, nor specifically to the biocompatibility properties (IUPAC definition: ability of a material to be in contact with a living system without producing an adverse effect). Healthcare ABS grade is an even broader term than medical ABS grade and it may not be specifically indicated for medical devices. It may include for example cosmetic devices (e.g. body care enclosures, caps etc..) or devices used for general exercise, measurement and basic support (e.g exercise bike or mobility chairs that are not specifically for a disability) and does not necessarily require biocompatibility verified or pre-tested in the material.

The highest-risk option for a medical device is represented by selecting an ABS material that is not specifically declared biocompatible by the material manufacturer, and that is post-coloured during the injection moulding process with a colour masterbatch not declared biocompatible.

The possibilities to pass the biocompatibility tests on a final device assembled with such material components are still existing, but very low.

The manufacturer denomination “biocompatible ABS grade” is therefore very important for medical device applications, but there are still several aspects and level of risks to be considered, also among the possible biocompatible ABS options available on the market.

A lower risk option is the choice of an ABS material that has been declared biocompatible by the ABS manufacturer based on raw material formulation, even if not on real biocompatibility tests conducted on the material. This type of solution can be combined with posterior ABS colouring with a colour masterbatch, that is also declared biocompatible by the masterbatch manufacturer, based on the formulation of

the masterbatch (pigments + carrier material) and without performing real biocompatibility tests.

Luckily, safer alternatives than the ones previously mentioned for biocompatible ABS are also available. ABS material can be indeed pretested according to ISO 10993 by initiative of the material manufacturer, and the same can happen for the colour masterbatch through the masterbatch manufacturer. The level of safety increases if biocompatibility tests are repeated periodically, even if this represents higher costs for the material and masterbatch manufacturers.

Still, there is a biocompatible ABS version that offer higher levels of safety, and this is possible when the periodically repeated ISO 10993 tests are performed on the PRE-coloured ABS compound, including ABS and colour pigments. This normally doesn’t happen in the case of POST-colouring natural ABS with a colour masterbatch during the injection moulding process. In fact, low volume annual needs and/or the many possible combinations of masterbatch-materials would not justify the high cost of the biocompatibility tests, not only in case of periodical tests repetition, but even in case of a single session of testing. On the other hand, if the colouring responsibilities are assumed by the ABS manufacturer, this higher value can be offered, increasing the level of biocompatibility safety for the interested medical device. In this case, in addition, not necessary variables that could provide further risks, like the masterbatch carrier, can be excluded. In fact, it is possible to consider the natural biocompatible ABS itself as carrier for the colour pigments, without needing any additional carrier. To understand this, we need to think about how a masterbatch is produced, creating a colour formulation made of a combination of different pigments. Such pigments are also in different concentrations, and compounded together through a material carrier, that acts as matrix for them to be homogeneously mixed.

For example, in the case of a certain target colour, several pigments are needed (e.g. even very different ones, like white or black, etc...). Each one corresponds to a different substance (typically in powder form) with a different CAS number and a different own colour appearance. The sum of all the colour Autumn 2025 Volume 17 Issue 3

PRIVATE LABEL & CONTRACT MANUFACTURING TO GROW YOUR BRAND MDR READY

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LET’S COLLABORATE TO CREATE YOUR NEXT PRODUCT

Come visit us at booth 5.0A52 at CPHI 2025 in Frankfurt

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www.aurenalabs.com • contact@aurena.se

Packaging

contributions of the different pigments and the specific proportions in the formulation will give the specific colour appearance to the color masterbatch, and posteriorly to the postcoloured ABS material. A similar concept in terms of pigments management applies in the case of PRE-coloured ABS entirely produced by the ABS manufacturer, with the difference that it uses the natural biocompatible ABS as unique carrier of the colour pigments, avoiding the need of an additional carrier material from a third part. A specific integrated colour development department and a strict cooperation with a product stewardship department for regulatory support at the ABS manufacturer are key value-added resources to produce PRE-coloured ABS. Pigments’ regulatory compliance is required to be continuously supervised. If a colour formulation contains a pigment that cannot be used anymore due to regulatory updates, or in case of regulatory concentrations reduction, the target colour should be reviewed with an alternative pigment, and if necessary, a completely new colour formulation should be developed again. These are also the reasons why the periodical repetition of biocompatibility tests on PRE-coloured ABS are so important and offer additional safety and value.

PRE-coloured biocompatible ABS, periodically pretested, offers also additional advantages vs POST-coloured biocompatible ABS with masterbatch: the problem of masterbatch dosage during the injection moulding process is eliminated. This alone represents a relevant risk of exceeding the pigments concentration in the compound 78 INTERNATIONAL PHARMACEUTICAL INDUSTRY

that may affect the biocompatibility tests results on the final device. Another possible side effect is the colour instability on the injected part during different production campaigns, or colour inconsistence of a same part produced at different moulders with the same or different masterbatches.

There are more advantages of PREcoloured vs POST-coloured biocompatible ABS: the complete formulation ABS and colour pigments can be contained in a unique safe place (e.g. Drug Master File – DMF# at the FDA), that can be easily accessed by notifying bodies and regulatory authorities, making easier the PRE-coloured ABS medical application compliance and speeding up the medical device approval process. New pigments can be included in new colour formulations and tests can be repeated acc. to ISO 10993 along with the complete PREcoloured ABS compound. Furthermore, these new colour formulations can be added to the already existing DMF through an amendment, updating all the information needed for the required verifications of the medical device approval authorities.

The biocompatibility of PRE-coloured ABS can be also assured in specific sustainable medical ABS versions that are ISCC+ certified with a mass balance approach. The first ABS manufacturer to obtain the ISCC+ certification has an important advantage in comparison to the others, because they already introduced certified sustainable feedstocks in their supply chain already several years ago.

During all these years, biocompatibility tests on PRE-coloured medical ABS grades continue to be periodically performed with success

and new sustainable versions with Certified Raw materials (CR) are being accepted at the FDA for the inclusion in the same DMF# of the biocompatible fossil version.

Luca Chiochia Luca Chiochia is a Business Development Manager at ELIX Polymers. Graduated in management engineering at the "Politecnico di Milano" University (Milan, Italy), Luca has 20 years’ industrial experience in the fields of plastics, composites, and OEMs devices. Luca joined ELIX Polymers in 2017 in the position of Business Development Manager for the healthcare strategic sector. Since 2020 he is actively involved in the development of ELIX E-LOOP sustainable solutions and circular innovations, that include a new growing sustainable ABS and blends material portfolio, with chemically recycled, bio-attributed, bio-based and mechanically recycled content. Luca wrote several technical articles on behalf of ELIX about specialties and sustainable ABS for medical applications that were published on several renowned medical and pharmaceutical magazines. He lived in different European countries and speaks fluently 6 languages (Italian, English, German, Spanish, French and Catalan).

Email: luca.chiochia@elix-polymers.com

Autumn 2025 Volume 17 Issue 3

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INTERNATIONAL PHARMACEUTICAL INDUSTRY 79

Logistics & Supply Chain Management

More Than a Box: Inside the Cold Chain’s Quiet Revolution In today’s pharmaceutical and life sciences landscape, delivering a cold chain container is no longer enough.

With the growing pressure to ensure product integrity, comply with regulations and cut carbon emissions – all while navigating global uncertainty – the definition of what makes a “leading” cold chain provider is shifting fast. Packaging performance is just the baseline. What sets modern providers apart is what happens around the container, such as the intelligence, infrastructure and insight that drive every shipment from planning to delivery.

Smart tools, real-time visibility, sustainability strategies and agile support are no longer value-adds; they are expectations.

As the cold chain becomes more complex, service innovation is emerging as the true differentiator.

The Rise of Intelligence-driven Logistics Real-time visibility and predictive logistics are no longer optional, they are imperative.

With increasingly fragile supply chains and heightened regulatory scrutiny, life sciences companies now seek data-rich platforms to inform and optimise their shipping decisions.

Modern cold chain container providers are meeting this demand by integrating digital tools into their offerings. These tools allow stakeholders to monitor route risks, track live shipment status and make informed choices about transport lanes. Predictive features such as weather impact modelling or geofencing delivery zones are helping to proactively reduce delays and excursions.

while offering environmental and cost benefits, introduce additional complexity in the form of reverse logistics, return coordination and asset tracking.

To address this, leading providers are beginning to implement comprehensive service programs that manage the full lifecycle of reusable assets. These services often include return optimisation, refurbishment workflows and centralised visibility over program performance, making large-scale reuse feasible and reliable across international supply chains.

Just as important are customer support structures that go beyond generic onboarding.

Scalable service models are increasingly tailored to the specific workflows, regulatory environments and geographic footprints of each client. Whether it’s optimising SOPs (Standard Operating Procedures), coordinating delivery handoffs, or enabling mid-shipment reroutes for high-value goods, these adaptive support programs allow logistics managers to maintain agility in an otherwise rigid system.

Long-standing Expertise as a Differentiator While digital platforms and automation

continue to grow in importance, the role of human expertise still remains vital. The most advanced cold chain container providers invest in highly specialised technical advisory teams. These are groups capable of offering neutral, context-driven guidance around packaging selection, risk management, regulatory compliance and thermal strategy – all in the best interests of the customer.

These experts help organisations design robust cold chains that can accommodate evolving product portfolios and international expansion. More importantly, when things go wrong – as they occasionally do – the ability to speak to someone who understands the full scope of the cold chain and can troubleshoot effectively becomes invaluable.

In this context, service is no longer viewed as a layer added after the fact. Instead, it is embedded within the core offering, with expert insight available throughout the solution lifecycle, from planning and procurement to operations and post-shipment analysis.

Aligning with Sustainability and Circularity Goals Sustainability is increasingly a top priority across healthcare supply chains. As a result,

The ability to track and analyse shipment performance across lanes, carriers and locations enables smarter decision-making.

It also plays a critical role in supporting operational efficiency and reducing environmental and financial waste – two goals that are now central to cold chain strategy.

Programs That Support Scalability Another area of transformation lies in the operational services designed to streamline logistics. Reusable cold chain containers, 80 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Autumn 2025 Volume 17 Issue 3

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INTERNATIONAL PHARMACEUTICAL INDUSTRY 81

Logistics & Supply Chain Management

cold chain container providers are expected to offer more than packaging efficiency and must contribute to customers’ broader environmental strategies.

Reliable, circular models, such as reusable containers paired with efficient return programs, are gaining traction. However, to be effective, these models require not just durable packaging but infrastructure to support repeated use, data to track lifecycle performance, and services to simplify adoption.

Providers who invest in logistics networks, refurbishment capabilities, asset tracking and program design are helping partners reduce carbon footprints without compromising compliance or reliability. In doing so, they help shift the sustainability conversation from aspiration to action.

From Product Provider to Strategic Partner Perhaps the most defining trend is the changing nature of the relationship between cold chain providers and their customers.

Historically viewed as product vendors, 82 INTERNATIONAL PHARMACEUTICAL INDUSTRY

providers are now becoming integrated partners in the supply chain strategy. This shift has been driven not only by the increasing complexity of pharmaceutical shipments, but also by the demand for resilience, speed and cost-efficiency in a post-pandemic world.

Success today is measured not just by how well a cold chain container performs under test conditions, but by how well the full ecosystem around it functions under realworld pressures. Providers are now expected to collaborate with customers, share insights and co-develop smart solutions to navigate regulatory hurdles, capacity constraints or urgent delivery windows.

This partnership mindset enables greater alignment between operational objectives and service offerings, leading to better outcomes in product quality, patient safety and ultimately business continuity.

As the role of cold chain containers continues to expand, the industry is witnessing a critical redefinition of value. As dependable physical packaging becomes a

given, true value now lies in the surrounding services, tools and expertise.

Digital intelligence, expert guidance, reusable infrastructure and personalised, smart service programs are fast becoming the benchmarks by which leading providers are measured.

In this new era, the most successful cold chain container providers will be ones who can deliver more than just a box, and those that can provide foresight, flexibility and lasting trust across every link of the temperature-controlled supply chain.

David Webber David Webber, Senior Global Marketing Manager, Reusable Solutions & Services at Cold Chain Technologies.

Autumn 2025 Volume 17 Issue 3

Subsection:

Nasal and Pulmonary (Part C)

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INTERNATIONAL PHARMACEUTICAL INDUSTRY 83

Edinburgh International Conference Centre and Virtual

10/11/12 December 2025 th

The Premier International Conference Covering All Aspects Of Respiratory Drug Delivery • 3 days of expert lectures • 1000+ attendees expected • Large Industry exhibition • 100+ scientific posters

• Free registration for students • Networking opportunities • Awards and grants for young researchers

www.ddl-conference.com

info@ddl-conference.com

84 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Autumn 2025 Volume 17 Issue 3

Regulatory Nasal && Marketplace Pulmonary

Drug Delivery to the Lungs 2025

DDL2025 will be delivered live at the Edinburgh International Conference Centre (EICC) and virtually for those unable to travel to Scotland, on Wednesday 10th, Thursday 11th and Friday 12th December 2025.

Celebrating its 36th year, the Drug Delivery to the Lungs Conference will again look to showcase the latest research in the area of inhaled drug delivery. Alongside the talks, exhibition and posters, there will be the usual convivial hospitality and networking opportunities for which the conference is renowned, with complimentary Drinks Receptions on both Wednesday and Thursday Evenings for all delegates.

DDL2025 provides a balance of coverage across key areas of aerosol science and the development of inhaled medicines, e.g. CMC, clinical, device development, to appeal to both academia and industry, with a single conference stream meaning no difficult decisions as to which presentation to attend.

The DDL Annual Lecture – the prestigious annual lecture has been awarded to Gerhard Scheuch from GS BIO-INHALATION GmbH, who will be delivering a talk on "Transmission of Viruses by Breathing – What have I (an aerosol researcher) learned from the Corona Pandemic."

The conference programme will include talks from invited speakers as well as those who have submitted papers to be considered for podium presentations. The session themes for the conference are: Advances in Preclinical Drug Development • Innovation in early drug discovery through to the clinic • AI and in silico models • Organ on a chip • Advanced in vitro and ex vivo models • Preclinical models of lung disease Making Innovation Happen • Overcoming barriers to innovation • Connecting business with research and education www.international-pharma.com

•

Turning ideas into commercially viable products

To the airways & beyond!

• Innovative nasal and pulmonary formulations • New delivery methods and devices • Delivery of biologics • Nose to brain • Novel approaches to targeting diseases Supporting Young Researchers: The New Researcher Network – The New Researcher Network (NRN) are a sub-group of the DDL Conference focused on engaging and supporting young researchers starting out in their careers. The NRN Committee will host two networking events at the DDL Conference to provide an opportunity for young researchers to help facilitate discussions surrounding research ideas/ challenges, exchanges, joint projects and personal and professional development.

Students will continue to enjoy complimentary registration (https://ddlconference.com/ddl2025/), providing the next generation of aerosol and drug delivery researchers an extra-ordinary opportunity to engage with world-renowned scientists from across the aerosol and respiratory delivery field, to promote their own work, and to gain experience participating in a premier conference in their research field.

DDL are proud to recognise and encourage new talent through our awards and activities: •

The Pat Burnell Young Investigator Award. Named in honour of one of the founders of the Aerosol Society, shortlisted applicants for this prestigious award will have the opportunity to deliver a live presentation at DDL2025, with the winner being announced during the conference. https://ddl-conference. com/awards-and-grants/pat-burnellaward/

•

The DDL Emerging Scientist Award.

The winner of this award will have demonstrated significant scientific accomplishment or innovation during the early stages of their career in

inhalation science (within 15 years from achieving their PhD). The winner will be announced and give a keynote presentation describing their research achievements at the conference. https://ddl-conference.com/awardsand-grants/ddl-emerging-scientistaward/ •

The DDL Career Development Grant.

This flexible grant is intended to support new and emerging scientists by funding projects which contribute to a scientist’s career development. The grant can support individuals from public, private and university organisations. https://ddl-conference.com/awardsand-grants/ddl-career-developmentgrant/

As a “not for profit” organisation, we would like to extend our thanks to our valued conference sponsors, without whom we would not be able to bring you the great value, high quality DDL conference experience.

Registration costs will continue to be held at a level that enables attendance across the breadth of industry, with attendance from academia actively encouraged, to facilitate cross fertilisation of knowledge across the sector.

For more information about the conference and to register to attend, please visit www. ddl-conference.com

INTERNATIONAL PHARMACEUTICAL INDUSTRY 85

Nasal & Pulmonary

Complexity of Selling Orally Inhaled and Nasal Drug Product CDMO Services Selling Contract Development and Manufacturing Organisation (CDMO) services is a complex task that demands a versatile skill set, encompassing drug development expertise, technical and analytical knowledge in drug product manufacturing, equipment familiarity, and overall selling skills. Drug-device combination products bring an additional layer of complexity due to the variety of devices, intricate supply chains, and additional manufacturing processes for filling and assembly. This complexity is heightened in inhalation (nasal/ pulmonary) product development, where device variability and rigorous analytical testing are significant challenges. This article explores the intricacies of selling these services and highlights the essential attributes of an exceptional business development professional.

Figure 1: Key Components in the Development of Drug-Device Combination

The CDMO industry, as we know today, largely started in the late 1990s driven by multiple factors, amongst these the selling of excess manufacturing facilities by global pharmaceutical companies as older products went off patent.1 The greatest growth driver, however, was the explosion of early-stage bio/pharma companies, thanks to the maturity of biotechnology and the availability of external funding.1 Due to the cost of establishing owned manufacturing facilities, these emerging biopharma companies (EBPs) fuelled the CDMO industry by outsourcing all or part of their product development and/or manufacturing requirements.

Essential to the booming CDMO industry is the sales and business development (BD) function, which plays a pivotal role in driving revenue growth. Selling CDMO services is inherently complex and demands a unique blend of technical expertise and deep knowledge of the drug development process. Unlike traditional sales roles, BD professionals must understand intricate scientific concepts, regulatory requirements, and the nuances of pharmaceutical formulation and manufacturing. They must also be able to communicate effectively with cross-functional stakeholders and translate technical capabilities into strategic value.

86 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Adding to this is the need to tailor solutions amplified by the need to tailor solutions to each client’s development stage, therapeutic area, and commercialisation goals, making the sales process highly consultative and relationship driven.

This complexity is significantly amplified when working with drug–device combination products. Unlike traditional pharmaceutical products such as oral solids, drug-device combination products are subject to more rigorous and multifaceted regulatory scrutiny, encompassing both drug and device requirements. As a result, navigating the development and approval process

demands a deep understanding of crossdisciplinary standards. As shown in Figure 1, BD professionals must also be well-versed in drug delivery devices, the criteria for device testing and selection, and the scientific, technical, and regulatory requirements specific to drug–device combination products.

As of July 1, 2025, there were a total of 22,641 drugs (molecules) in development from pre-clinical through Phase III – thousands of these are drug-device combination products.2 Of these, 457 were for orally inhaled and nasal drug products (OINDPs), all of which are drug/ device combination products.

Figure 2: Types of Nasal Devices Autumn 2025 Volume 17 Issue 3

Regulatory Nasal && Marketplace Pulmonary 1. Device Platform Technologies and Selection OINDPs rely on a device to consistently generate an aerosol for the drug to be delivered to the patient. They are administered using a variety of device platforms, ranging from single dose to multi-dose systems designed for pulmonary or nasal delivery. Nasal administration devices support both liquid and dry powder formulations, and are available in unit-dose, bi-dose, and multi-dose formats to accommodate varying therapeutic and dosing requirements, as shown in Figure 2. Pulmonary drug delivery systems accommodate both liquid and dry powder formulations. Liquid formulations are typically administered via metered dose inhalers (MDIs), nebulisers or soft mist inhalers (SMIs) (Figure 3), while dry powder inhalation (DPI) products are delivered using a range of single-dose (sDPI) and multidose (mDPI) devices (Figure 4).

Figures 2–4 are generated by (Open AI, 2025) to depict common OINDP devices and are intended for illustrative purposes only.

The devices in Figures 2–4 represent a very limited subset of those that are commercialised or are currently under development. The choice of device depends on numerous factors, including drug formulation, the device’s ability to deliver the intended dose, the drug’s indication (emergency or chronic use), and various patient-related considerations such as patient age and ability to use the device correctly.3 These factors can influence the lung or nasal deliverable dose, the distribution of the dose in the intended organ and, ultimately, determine the success of the treatment.3 For business development professionals, a thorough understanding of the full range of drug delivery devices, both approved and in development, is essential. This knowledge supports the selection of a device that aligns with the drug developer’s specific needs.

Figure 3: Liquid Aerosol Delivery Devices

sDPI device

mDPI device

mDPI device

Figure 4: Common Dry Powder Inhalation Devices

2. Container Closure Systems The FDA’s definition of a container closure system is the sum of packaging components that together contain and protect the dosage form – these include both primary and secondary packaging.4 Container closure systems (CCSs) are critical for maintaining the safety, efficacy, and quality of medical devices and pharmaceutical products throughout their lifecycle. The CCSs act as a barrier against contamination and degradation, ensuring product sterility and stability, and are essential for regulatory compliance.

Primary packaging is considered any component that “is or may be in direct contact with the dosage form” whereas secondary packaging can provide additional protection to the product from humidity and other factors.5,6 CCSs for OINDP products are extremely diverse and can range from blister packaging of capsules used in sDPI devices,

metal or glass canisters used in SMIs, vials or nebules used for nebulisation, and the wide variety of containers, closures, and pumps used in nasal sprays. Table 1 summarises the FDA’s guidance for industry regarding CSSs for DPIs, nasal sprays, inhalation solutions and suspensions, and oral tablets or capsules.

Given the potential for dosage form interactions in OINDPs, the FDA maintains heightened regulatory scrutiny and enforces more stringent requirements.

For BD professionals, this translates into increased complexity due to the wide array of OINDP devices and CCSs available, some of which may be interchangeable. As such, BD professionals must not only have a deep understanding of the various CCSs types but also possess specialised knowledge of the manufacturing equipment specific to each device configuration.

Route of Administration

Degree of Concern*

Likelihood of Packaging Component-Dosage Form Interaction

Primary Packaging (Examples)

Protective Packaging (Secondary Packaging)

Inhalation powders

High

Medium

Foil pouch, blister device

Overwrap, carton, foil

Inhalation aerosols sterile powders and solutions

High

High

Container, closure, pump, and any protective packaging, if applicable

Foil overwrap

Nasal aerosols and sprays

High

High

Container, closure, pump, and any protective packaging, if applicable.

Foil overwrap, blister

Oral tablets and oral capsules

Low

Low

Plastic (usually HDPE) bottle with a screw-on or snap-off closure, pouch or blister package

Carton

*Refers to the level of FDA of concern given to the nature of the packaging components that may come in contact with the dosage form or the patient.

Table 1: FDA Guidance for CCSs for DPIs, Nasal Aerosol and Sprays and Inhalation Aerosols Sterile Powders and Solutions4,5,6 www.international-pharma.com

INTERNATIONAL PHARMACEUTICAL INDUSTRY 87

Nasal & Pulmonary

3. Characterisation Studies of OINDP Drug-Device Products Product characterisation for OINDP is a crucial aspect of development, ensuring the product's quality, performance, and ability to deliver the drug effectively to the lungs or nasal cavity. This involves a range of studies to understand how the drug formulation and device interact and how the product performs under various usage conditions.

Important components of these studies include drug product characterisation testing, stability testing and release testing.

Dry Powder Inhalation

Nasals

In-Use Period

✓

N/A

Temperature Cycling

✓

✓

Priming and Repriming

✓

✓

Effect of Patient Use

✓

N/A

Effect of Orientation of the Device on Delivered Dose

✓

✓

Drug Deposition on Mouthpiece and / or Accessories

✓

N/A

Cleaning Instructions

✓

✓

Profiling of Actuation Near Device Exhaustion / Tail off

✓

✓

Effect of Flow Rate on Performance

✓

✓

Table 2 summarises the tests specific to OINDPs, which are designed to demonstrate the product’s robustness and performance, and to support labelling instructions related to proper use (e.g., storage, cleaning, shaking.)5,6 These tests are not applicable to oral solid dosage forms, as they are unique to drugdevice combination systems.

Robustness

✓

✓

Effect of Resting Time

N/A

✓

In Vitro Dose Proportionality

N/A

✓

Effect of Storage on the Particle Size Distribution

N/A

✓

Plume Geometry

N/A

✓

Preservative Effectiveness and Sterility Maintenance

N/A

✓

Tables 3 and 4 provide a comparison of stability and release testing requirements needed for oral solid dosage forms and OINDPs.

Photostability

N/A

✓

Stability of Primary (Unprotected) Package

N/A

✓

88 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Test

Table 2: Drug Product Characterisation Studies5,6 Autumn 2025 Volume 17 Issue 3

Regulatory Nasal && Marketplace Pulmonary Test

Oral Solid

DPI

Nasal (Liquid)

Nasal (Powder)

ID

✓

✓

✓

✓

Appearance

✓

✓

✓

✓

Assay/RS

✓

✓

✓

✓

Dissolution

✓

N/A

✓

✓

Content Uniformity

✓

✓

✓

✓

Microbial Limits

✓

✓

✓

✓

XRPD

✓

✓

N/A

N/A

APSD

N/A

✓

N/A

N/A

FPM (HIAC)

N/A

✓

✓

✓

Delivered Dose

N/A

✓

✓

✓

Impurities and Degradation Products

N/A

✓

✓

✓

Water/Moisture Content

N/A

✓

✓

✓

pH

N/A

N/A

✓

✓

Preservatives and Stabilising Excipients Assay

N/A

N/A

✓

✓

Leachables

N/A

N/A

✓

✓

Osmolality

N/A

N/A

✓

✓

Particulate Matter

N/A

N/A

✓

✓

Net Content

N/A

N/A

✓

✓

Weight Loss

N/A

N/A

✓

✓

Actuation Force

N/A

N/A

✓

✓

Fill Weight

N/A

N/A

✓

✓

Spray Content Uniformity

N/A

N/A

✓

✓

Plume Geometry

N/A

N/A

✓

✓

Pump Delivery

N/A

N/A

✓

✓

Droplet Size Distribution

N/A

N/A

✓

✓

Spray Pattern

N/A

N/A

✓

✓

Viscosity

N/A

N/A

✓

✓

Total

7

10

22

22

5. Conclusion The role of BD professionals is vital in the highly competitive and innovative CDMO market. Those focused on OINDP development and manufacturing face even more demanding tasks due to the unique and complex challenges these drug-device products entail.

Beyond their core responsibilities, BD professionals must possess a deep understanding of the drug delivery device landscape, including device design, functionality, and therapeutic compatibility.

Moreover, they need to be familiar with the evaluation and selection processes for these devices, along with the intricate scientific, technical, and regulatory frameworks that govern drug-device combination products.

A highly skilled BD professional, especially in the inhalation field, is a valuable asset

Table 3: Comparison of Stability Testing Requirements (Oral Solids vs. OINDPs)5,6,7

OINDP products require comprehensive testing to ensure the safety and efficacy of both the drug and its delivery device, as well as their interaction. This is illustrated in Tables 2–4, which highlight the significantly more extensive testing requirements for OINDPs compared to oral solid dosage forms.

Not only are these tests more numerous, but they also tend to be more complex and costly.

As a result, BD professionals must also be well-versed in all relevant testing protocols to effectively guide drug developers through each stage of the development process.

4. Human Factor Studies Human Factor (HF) studies are required by the FDA to demonstrate that the device in a www.international-pharma.com

combination product can be used safely and effectively.8 The term describes the usability of devices and how it “determines the efficacy, efficiency, and the ease of learning and satisfaction of the user”.8 Not all CDMOs offer HF study services.

For those that do, the BD professional will guide the client through the process, leveraging their expertise to align HF study offerings with the client’s needs. For CDMOs that do not provide HF studies in-house, the BD professional will facilitate the process by coordinating the manufacturing, compliance, and logistics of the drug-device product for HF testing at a third-party provider.

INTERNATIONAL PHARMACEUTICAL INDUSTRY 89

Nasal & Pulmonary

Test

Oral Solid

DPI

Nasal (Liquid)

Nasal (Powder)

ID

✓

✓

✓

✓

Appearance

✓

✓

✓

✓

Assay/RS

✓

✓

✓

✓

Dissolution

✓

N/A

N/A

N/A

Content Uniformity

✓

✓

N/A

N/A

Microbial Limits

✓

✓

✓

✓

Valve Delivery (Shot Weight)

N/A

✓

N/A

N/A

Net Content (Fill) Weight

N/A

✓

N/A

N/A

Hardness

✓

N/A

N/A

N/A

Friability

✓

N/A

N/A

N/A

XRPD

✓

N/A

N/A

N/A

APSD

N/A

✓

N/A

N/A

FPM (HIAC)

N/A

✓

✓

✓

Osmolality

N/A

N/A

✓

✓

Delivered Dose

N/A

✓

✓

✓

pH

N/A

N/A

✓

✓

ID

N/A

✓

✓

✓

Spray Content U

N/A

N/A

✓

✓

Plume Geometry

N/A

N/A

✓

✓

Pump Delivery

N/A

N/A

✓

✓

Droplet Size Distribution

N/A

N/A

✓

✓

Spray Pattern

N/A

N/A

✓

✓

Viscosity

N/A

N/A

✓

✓

Pump Delivery

N/A

N/A

✓

✓

Droplet Size Distribution

N/A

N/A

✓

✓

Spray Pattern

N/A

N/A

✓

✓

Viscosity

N/A

N/A

✓

✓

Total

9

11

15

15

Table 4: Comparison of Release Testing Requirements (Oral Solids vs. OINDPs)

5,6,7

to any CDMO operating in this space. They play a pivotal role in cultivating successful, collaborative partnerships – effectively balancing the priorities of both the CDMO and the client to ensure mutual success.

3.

4.

REFERENCES 1.

2.

Miller, J. Contract Manufacturing Through the Years. Pharmaceutical Technology, 41(7).

Accessed at: https://www.pharmtech.com/view/ contract-manufacturing-through-years Pharmaprojects. (2025). "Drug Name" profile.

Accessed July 1, 2025. Available from: https:// clinicalintelligence.citeline.com/drugs/ results?qId=9334262c-a652-43bc-99bf0106fd0bfbf5

90 INTERNATIONAL PHARMACEUTICAL INDUSTRY

5.

6.

Formulation, Device, and Clinical Factors Influencing the Targeted Delivery of COVID-19 Vaccines to the Lungs. AAPS PharmSciTech 2022 Nov 23;24(1):2. doi: 10.1208/s12249-02202455-x U.S. Food and Drug Administration. (1999).

Container Closure Systems for Packaging Human Drugs and Biologics: Guidance for Industry.

Accessed at: https://www.fda.gov/media/70788/ download U.S. Food and Drug Administration. (2018).

Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Products-Quality Considerations: Guidance for Industry. Accessed at: https://www. fda.gov/media/70851/download U.S. Food and Drug Administration. (2002). Nasal Spray and Inhalation Solution, Suspension, and Spray Drug Products – Chemistry, Manufacturing,

7.

8.

and Controls Documentation: Guidance for Industry. Accessed at: https://www.fda.gov/ media/70857/download World Health Organization. (2018). TRS 1010 – Annex 10 Stability testing of active pharmaceutical ingredients and finished pharmaceutical products. Accessed at: https:// www.who.int/publications/m/item/trs1010annex10 U.S. Food and Drug Administration. (2002).

Applying Human Factors and Usability Engineering to Medical Devices: Guidance for Industry. Accessed at: https://www.fda.gov/ media/80481/download

Carolyn Berg Carolyn Berg, Vice President, Business Development, Inhalation, has more than 25 years of experience in pharmaceutical sales, marketing, and business development. Since 2021, she is the Vice President of Business Development for Catalent’s inhaled drug delivery solutions where she is responsible for all commercial, strategic, and sales efforts to develop and grow the Inhalation business globally. Throughout her career, Carolyn has produced a solid record of meeting sales and business targets through individual and team efforts.

She brings an optimistic, high-energy approach to fostering strong relationships and positive teamwork.

Dontae Solomon Dontae Solomon, Sr. Account Director, Business Development, Inhalation. With over 25 years of experience in scientific and business development, Dontae Solomon has a proven track record of driving sales and revenue growth, building strategic partnerships, and expanding market presence across the pharmaceutical industry. Known for a results-oriented approach, teamwork, and strong leadership, Dontae has successfully contributed to high-functioning teams, and spearheaded initiatives that have delivered measurable value to organisations. Dontae brings deep expertise in sales strategy and client relationship management, making him a trusted advisor and growth catalyst in a robust and competitive CRO/CDMO space.

Autumn 2025 Volume 17 Issue 3

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Nasal & Pulmonary

INHALED mRNA: The Race Has Begun With targeted delivery and potential for improved patient adherence, inhaled mRNA therapies are emerging as the new frontier in respiratory and genetic medicine. A growing pipeline of candidates are laying the groundwork for a new class of precision biologics.

In short: • • • •

•

•

There are 29 inhaled mRNA drugs currently in development.

44% of all mRNA candidates target infectious diseases.

There are no candidates beyond Phase II as of April 2025.

Cystic fibrosis and primary ciliary dyskinesia are the leading respiratory indications being considered for inhaled mRNA therapies.

Nebulisers are used in the preclinical phase, while soft mist inhalers offer greater precision, portability and scale up continuity from Phase I trhough to commercialisation.

Strategic partnerships between drug developers and inhalation device innovators are essential to move the field forward.

INHALED mRNA: A New Market for Drug Delivery Messenger RNA (mRNA) vaccines have become a significant trend in the drug development world. These mighty molecules contain the ‘instructions’ needed for cells to make specific proteins that match with a pathogen’s antigens. The immune system responds by dispatching antibodies and T-cells, an attack which can then be repeated if the patient is infected with the real virus.

This approach was tried and tested on a large scale during the COVID-19 pandemic, where novel Lipid Nanoparticle (LNP) technology helped vaccine developers overcome some of the challenges of transporting mRNA into cells smoothly. Thanks to this important advancement and the many benefits that mRNA offers, from powerful immune responses to rapid development timelines and flexible 92 INTERNATIONAL PHARMACEUTICAL INDUSTRY

manufacturing, investment in the field has since surged.

There are now 386 different mRNA vaccines in development or pre-registration for various infectious diseases ranging from influenza to HIV/AIDs. Researchers are seeing a future for mRNA that extends beyond viral infections.

Looking at the pipeline for all mRNA-based drugs in April 2025, 44% are indicated for infectious diseases, followed by 29% for oncology. Other therapy areas with mRNA activity include metabolic disorders (5%), respiratory (3%), and immunology (3%).

In this article, we explore the unique intersection of this drug development trend with another important trend in the industry, inhaled drug delivery.

The Benefits of Inhaled mRNA As the development of mRNA-based drugs accelerates, inhaled delivery is emerging as the next frontier in the field. This is a particularly exciting trend in the respiratory therapy area, where inhaled mRNA therapeutics will deliver genetic instructions for fighting diseases like Cystic Fibrosis (CF) directly to the lung cells.

When it comes to vaccines, an inhalable formulation is believed to improve patient compliance amongst individuals with needle phobia. Inhaled vaccines can stimulate strong mucosal immune responses in the respiratory tract, where most vaccines enter the body.

By inducing an immune response at the site

of entry rather than the systemic response triggered by injected vaccines, inhalable formulations could help to reduce viral transmission more effectively than traditional ones.

There are currently 29 inhaled mRNAbased drugs under active development, with several being pursued in multiple indications. It is clearly early days in this field, with most candidates in the discovery stage and, as of April 2025, no companies having taken this technology further than Phase II (Figure 1).

Five clinical trials have been completed in this space while seven are currently ongoing, five of which are recruiting. The industry commenced an equal number of trials in 2023 and 2024, more than double that which started in 2022 (Figure 2).

Inhaled mRNA Pipeline Insights The main therapeutic indications for inhaled mRNA (Figure 3) include CF and Primary Ciliary Dyskinesia (PCD) (Figure 4). CF is a rare inherited genetic condition which impairs the clearance of mucus in the airways, causing damage to the lungs, digestive system, and other organs. Beginning in childhood, it is a life-long and life-limiting condition with no cure. PCD is a similar rare genetic disease in that it also causes mucus build-up in the lungs, though the root cause of this effect is different.

Both diseases are associated with recurrent respiratory infections and an increased risk of premature death.

Inhaled mRNA-based by development stage – April 2025 18 16 14 12 10 8 6 4 2 0

Phase II

Phase I

IND/CTA Filed

Preclinical

Discovery

Figure 1 Autumn 2025 Volume 17 Issue 3

Regulatory Nasal && Marketplace Pulmonary mRNA as a credible alternative to steroidbased or systemic biologics.

New clinical trials for inhaled mRNA-based drug by start year 6

In the US, a biotech is developing a nextgeneration biodegradable polymer platform for mRNA delivery, an alternative to the LNPs commonly used in the field. The goal?

Increased stability and tolerability in the respiratory tract.1 The proprietary formulation is currently being used in several intranasal vaccine programmes, including COVID-19 boosters aimed at neutralising the virus in the upper airway before it can spread deeper. Respiratory Syncytial Virus (RSV) and influenza candidates are also in early-stage development.

5

4

3

2

1

0

2022

2023

2024

Preclinical

Figure 2

CF drugs are at the most advanced stage of the pipelines, Phase II. One therapy is a nebulised mRNA, designed to boost CFTR protein expression in the lung’s secretory cells is currently in Phase II and has a 50% probability to progressing to Phase III. That’s nearly double the bench market success rate for this stage, which stands at just 26%.

Initial results are expected by June 2025, with full trial completion by year-end.

efficient absorption in the respiratory tract.

Recently, they completed its first-in-human trial in asthma, and recruitment is ongoing for a separate Phase I study in COPD. These two diseases represent large global markets with substantial unmet need and they offer developers the chance to position inhaled

This is not just a vaccine play, this can be applied in oncology. According to public data, there are at least three discovery-stage assets for non-small cell lung cancer, leveraging inhalation to drive immune response at the tumour site. A bold step in the evolution of mRNA beyond infectious disease.

In Asia, a dry powder formulation is being delivered through a proprietary inhaler

Inhaled mRNA-based drugs by therapy area

In early 2023, a biotech launched an inhaled mRNA programme shortly after receiving fasttrack designation. This followed an earlier licensing deal with a leading mRNA developer.

The candidate is a liquid aerosol aimed at correcting CFTR dysfunction.

A third molecule is being developed as an inhaled CFTR regulator and expects to complete a Phase I/II trial by the end of 2025. All three programmes share the same challenge: getting therapeutic particles through the thick mucus barrier in the lungs to reach epithelial cells – a key bottleneck in CF. Beyond CF, a fourth asset is targeting PCD with an inhaled mRNA therapy now in Phase I. It’s not alone. In Europe, a biotech has three early stage inhaled assets for PCD and is positioning itself as a major player in respiratory gene delivery.

Who’s Racing to Own the Inhaled mRNA Market?

In Europe, five different inhaled mRNA candidates aimed at respiratory diseases are in early stages. The lead programme is in Phase I and is targeting both asthma and Chronic Obstructive Pulmonary Disease (COPD). The therapy is delivered via the nasal route using a proprietary nanoparticle system designed to stabilise mRNA and enable www.international-pharma.com

Respiratory Infectious Disease Oncology Cardiovascular Immunology

Figure 3

Inhaled mRNA-based drugs by top 10 indications Metastatic Lung Cancer Pulmonary Arterial Hypertension (PAH) Asthma Respiratory Syncytial Virus (RSV) Infections Unspecified Respiratory Disorders Non-Small Lung Cancer Unspecified Influenza Virus Infections Coronavirus Disease 2019 (COVID-19) Primary Ciliary Dyskinesia (PCD) Cystic Fibrosis (CF)

0

1

2

3

4

5

6

7

Figure 4 INTERNATIONAL PHARMACEUTICAL INDUSTRY 93

Nasal & Pulmonary device. The lead programme is in a Phase I trial for advanced lung cancer and lung metastasis of solid tumours. The therapy is designed to train the immune system to recognise tumour antigens, enabling targeted destruction of cancer cells in the lung.

Bypassing traditional injections by using a powder inhalation method, the formulation aims to achieve localised immune activation without systemic side effects. The trial is expected to run through to early 2027. If successful, this could mark one of the first clinical validations of dry-powder mRNA delivery in oncology – a major milestone for the field.

Future Outlook for Inhaled mRNA While inhalable mRNA formulations are still emerging, they offer exciting therapeutic potential and are driving innovative developments in drug delivery. mRNA is inherently unstable, which makes maintaining its integrity during aerosolisation a key focus.

Delivery requires the use of nebulisers and leads to Intellectual Property (IP) filings.

Additionally, LNPs used to deliver mRNA may undergo changes such as aggregation or size increase, during aerosol delivery.

Encouragingly, recent studies have shown that these effects can be mitigated through smart formulation strategies, such as incorporating polymers into the LNP structure. Zwitterionic polymers have shown promise in supporting efficient and stable aerosol performance.2 For inhaled mRNA formulations to advance further in the clinic and eventually reach the real-world patients that need them, collaboration will be required between the drug development community and inhaled platform experts such as Merxin Ltd. Merxin Ltd’s Soft Mist Inhaler (SMI), MRX004, is the solution. By generating a slow-moving plume, MRX004 protects delicate molecules as they reach the deep lung.

Current inhaled mRNA delivery often relies on nebulisers for early clinical trials, which are bulky and non-portable devices that limit patient convenience. Compact, scalable alternatives like MRX004 will unlock new possibilities for inhalable mRNA, especially in rare and chronic respiratory diseases. Clinical trials can start with MRX004 and bypass the time-wasting stages of nebulisers. As the inhaled mRNA field grows, the integration of cutting-edge delivery platforms with pharmaceutical innovation will be critical to realising its full potential.

MRX004 MRX004 is a multidose Soft Mist Inhaler (SMI) 94 INTERNATIONAL PHARMACEUTICAL INDUSTRY

MRX002+

MRX003

MRX004

MRX006

designed for aqueous and ethanol-based formulations. MRX004 uses mechanical energy (no propellant or battery) to generate a fine, slow-moving aerosol for deep lung deposition.

MRX004 is environmentally friendly and wellsuited for novel molecule delivery, lifecycle management, or reformulation from nebulised products.

Get in touch: info@merxin.com, explore our work with biologics and accelerate your path to market. www.mrx004.com REFERENCES 1.

2.

https://xanadubio.com/#technology https://www.acs.org/pressroom/presspacs/ 2024/november/an-advance-toward-inhalablemrna-medications-vaccines.html

About Merxin Ltd Merxin Ltd specialises in the design and supply of inhaler devices, including multidose and capsule-based Dry Powder Inhalers (DPIs) and Soft Mist Inhalers (SMIs). From concept to commercial supply, we are your partner in inhalation drug delivery. To explore how MRX004 can accelerate your mRNA Programme, contact us at www.merxin.com/contact.

We Make Inhalers.

We Make It Better.

We Will Launch You.

MM-2409-V01

Autumn 2025 Volume 17 Issue 3

MAKE IT BETTER

www.international-pharma.com

We M a k e I n h a l e r s .

Merxin Ltd specialises in designing and supplying inhaler devices, including dry powder and soft mist inhalers, for evaluation through to commercial supply. Our expertise spans therapeutic catergories, from biologics and small molecules to generic and novel therapies.

W e W i l l L a u n c h Yo u .

O u r D N A i s i n t h e p h a r m a i n d u s t r y . We a re c o m m i t t e d t o delivering quality, reliability, and efficacy. Our reputation is built on excellence.

Make It Better.

We a re c e r t i f i e d a s m e e t i n g t h e re q u i re m e n t s o f I S O 13485:2016 for the Design, Development, and Supply of inhalers. Our goal is to improve your molecule’s efficacy and improve patient outcomes worldwide.

INTERNATIONAL PHARMACEUTICAL INDUSTRY 95

MERXIN.COM

Nasal & Pulmonary

Safely Navigating the Transition to Low-GWP Medical Propellants The pressure to reduce greenhouse gas emissions has transformed nearly every industry, and respiratory pharmaceuticals is no exception.

Pressurised metered dose inhalers (pMDIs) have long relied on hydrofluoroalkane (HFA) propellants like HFA-134a to deliver the active medicine directly to the patient’s lungs. They are valued for their safety, reliability, and proven track record in supporting asthma and COPD patients.

However, medical aerosols like HFA-134a and HFA-227ea contribute to the healthcare sector’s carbon footprint. For example, in the UK, propellants used in inhalers account for around 3% of the NHS’s total emissions.

With environmental targets becoming more of a focus globally, and propellantfree options like dry powder inhalers (DPIs) unsuitable for approximately 30% of patients, the development of lower global warming potential (GWP) propellant alternatives is essential for the future of respiratory care.

At Orbia Fluor & Energy Materials, we have successfully developed a viable propellant alternative in HFA-152a. With a GWP of 124 (100-year timescale relative to CO2), it offers a dramatic reduction in climate impact by at least 90%, depending on the replaced propellant.

We are currently ready to support product submissions for inhalers containing HFA152a formulations across the UK, EU, and US, with first product approvals and subsequent product launches expected to begin in 2026.

This milestone will give GPs and procurement teams the ability to offer more sustainable inhaler options without disrupting continuity of care.

For formulary managers, regulators, and manufacturers working toward Net Zero targets, low GWP MDIs present a practical, clinically robust solution.

Unlike DPIs, they don’t require retraining of large groups of patients in how to effectively 96 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Flammability testing equipment at Orbia’s lab in the UK

use the product, or rethinking emergency protocols in respiratory conditions. Instead, they simply replace the higher GWP propellantcontaining MDIs with an equivalent lowerimpact alternative, once available. The goal is to ensure healthcare professionals have the choice to make environmentally responsible decisions without compromising patient care.

Managing the Flammability Risks However, creating low-GWP alternatives isn't without complications. HFA-152a is more flammable than its high-GWP predecessors, a characteristic that has raised questions in the industry.

Transitioning to a new propellant often begins with a change in perception, and the term ‘flammable’ can sound alarming, particularly in a medical context. The reality, however, is far more nuanced. HFA-152a is classified as flammable in air at standard conditions in concentrations between 3.7 and 18.0 w/w%, meaning it can be ignitable in a manufacturing setting, but is not inherently unsafe to handle, particularly in a medical aerosol.

At Orbia Fluor & Energy Materials, our development strategy for HFA-152a has been underpinned by two core principles: the application of proven scientific controls and the execution of detailed materialcompatibility studies to ensure both safety and efficacy. Beyond safety, we of course had to evaluate how this compound would behave in the human body, and what impact it might have on the atmosphere.

From the outset, we recognised the flammability properties of HFA-152a. However, this characteristic is far from unprecedented in the pharmaceutical industry, which routinely handles flammable excipients such as ethanol in inhaler formulations, which can push formulations of non-flammable propellants into the flammable range from levels above 1% w/w. Consequently, while flammability represents a hazard during manufacture, it is a well-characterised and manageable risk when appropriate mitigation measures are applied and has no impact on safety in use.

During the testing phase, we found that laboratory handling of HFA-152a required targeted adjustments – particularly, the use of ATEX-rated equipment and gas detection for operations such as propellant filling and during specific formulation or transfer steps.

This demonstrated that at manufacturing scale, the safe handling of HFA-152a is manageable with a suite of established controls including; ATEX-rated filling equipment; properly classified and zoned areas around filling lines and bulk storage tanks; controlled ventilation systems; continuous leak-detection technology; and comprehensive operator training supported by updated standard operating procedures.

The technology and infrastructure required for these measures already exist and have been proven over decades of application in other aerosol-based manufacturing environments.

Autumn 2025 Volume 17 Issue 3

Regulatory Nasal && Marketplace Pulmonary In practice, once hazards are fully understood and engineered controls are implemented, our experience has shown that HFA-152a can be managed with the same level of safety assurance as other flammable excipients and propellants in use today.

Building the Foundation for Low-GWP Propellants Since entering the HFA propellant space in the mid-1990s, following the phase-out of CFCs, Orbia Fluor & Energy Materials has consistently invested in production facilities. At that time, we worked alongside partners to build capacity for supplying the global market with the new generation of HFA propellants. This directly addresses the aims outlined in the Montreal Protocol, which initially highlighted the need to reduce CFC production and consumption by 50% by 1998.

Over the years, we recognised early on that another transition was inevitable.

Being a key supplier of fluorinated gases to other industries, we had already seen regulations introduced and implemented in the refrigerants sector, with a phasedown underway, underpinned by the Kigali amendment to the Montreal Protocol, calling for a phase-down of HFAs by more than 80% by 2050. Once we understood that a regulatory-driven phase-down would shape the industry and that innovation would be key to supporting it, we knew we had to develop the next generation of medical propellants.

About 15 years ago, we began evaluating our toolbox of potential molecules. Using our expertise of what makes a successful medical propellant along with an elimination process, we identified the 152a molecule as the best candidate when considering all needed outcomes.

Since then, we have invested tens of millions of pounds to prove the absolute safety of this molecule for medical applications, completing a rigorous 10-year toxicology programme to demonstrate its safety to pharmaceutical companies and regulators worldwide. To date we have proven that HFA152a has low acute and chronic toxicity, no genotoxic, carcinogenic or developmental effects. It exhibits no respiratory, sensitisation, cardiopulmonary or respiratory effects and juvenile studies support its use in patients from 2 years old.

The overall toxicity of HFA-152a has been proven to be cleaner than any other HFA propellant already in use. A testament to the physical properties that led to its selection as a next generation medical propellant.

Ensuring Confidence in the Sector Whilst adapting the technical procedures we use to manufacture this product is imperative to a healthy transition, we also need to consider other implications that could affect the transition to a new sustainable propellant.

Transitioning an industry to a flammable propellant such as HFA-152a requires more than technical adaptations; it demands a cultural shift within organisations. This transition is not solely about redesigning manufacturing equipment or updating supply chains, it also involves reshaping perceptions and building confidence around the safe use of flammable materials.

In addition, we began investing in production, because a good candidate is only useful if it is produced in sufficient quantities. In the early 2020s, we built a smallscale facility to supply the volumes needed for product development, clinical trials, and regulatory approval.

Success depends on actively managing expectations, addressing concerns openly, and embedding comprehensive education on flammability into everyday practice. By reframing flammability as a well-understood, controllable factor rather than an unfamiliar threat, organisations can foster the mindset needed to ensure a smooth and secure transition.

By investing in production, we gave the industry the foundation it needed to move forward in the early stages of transition. And just last year, we announced plans to build a larger facility that will produce enough propellant for a global switch of current customers to Zephex® 152a.

Building this confidence involves increasing awareness among operators, engineers, and maintenance teams, and drawing on the extensive experience of consumer aerosol manufacturers who have worked safely with flammable propellants for decades.

Construction is underway, and the larger scale plant is expected to be operational in the second half of next year at our Rocksavage site in Runcorn, United Kingdom.

The response so far from our customers and the industry on this has been positive, and so we look forward to leading the global transition from the UK.

To address this, we are investing in both technical systems and workforce capability – developing standard operating procedures specifically for flammable propellants, delivering training programs that educate flammability as a manageable and routine issue, and ensuring transparent communication of laboratory and production data. These measures are designed so that safety protocols are understood, trusted, and applied with confidence.

My own role as Pharma Application Development Manager bridges laboratory research and external communication, translating experimental findings into practical, operational guidance for customers.

This dual focus on both technical preparation and workforce procedures ensures that concerns over flammability do not become barriers when it comes to the wider industry being confident in its transition to our next generation propellant.

Collaborative workshop hosted by Orbia at DDL 2024, with Bespak and DH Industries on the topic of flammability www.international-pharma.com

The Impact of Collaboration The integration of HFA-152a into the INTERNATIONAL PHARMACEUTICAL INDUSTRY 97

Nasal & Pulmonary pharmaceutical supply chain will be inherently multidisciplinary, and will require close cooperation between manufacturers, suppliers, and engineering specialists.

Because of this, Orbia Fluor & Energy Materials has partnered with Bespak and DH Industries to produce a comprehensive safety handling guidefor HFA-152a, incorporating best practices for bulk storage, in-factory management, and pMDI line operations.

This document is an excellent example of essential industry collaboration, ensuring that the guidance covers everything from bulk storage and safe handling protocols, to incorporating low-GWP propellants into pMDI manufacturing environments.

What’s more, this collaboration extends beyond written guidance and into active industry engagement. Together, our teams attend at key sector conferences – including the Drug Delivery to the Lungs (DDL), Respiratory Drug Delivery (RDD) and International Society for Aerosols in Medicine (ISAM) Congress – sharing operational experience, technical findings, and safety data in real time. For example, at ISAM this year, Orbia detailed the timeline of Zephex 152a from its inception, covering its formulation behaviour, toxicological safety and current regulatory and commercial status.

Our experts also participate in regulatory and scientific forums such as IPAC-RS and FDAhosted events, as well as delivering targeted presentations at DDL, Respiratory Drug Delivery (RDD), and other global platforms.

Podium shot of Dr Isaac Mohar, toxicologist and immunologist, delivering a paper on the safety of Zephex® 152a at RDD Europe 2025

In this transition, collaboration is just as much about ensuring that patients can continue to rely on their inhalers as it does about achieving technical readiness. By working side by side with our partners to share knowledge, address safety concerns, and smooth the path to implementation, we’re helping to make sure that no patient experiences a break in treatment. At the same time, we’re creating the foundations for the safe, confident adoption of low-GWP propellants across the industry.

Maintaining 134a Supply During the Transition While the industry prepares to adopt HFA-152a, it is vital to ensure that patients continue to have uninterrupted access to existing inhaler therapies that rely on HFA-134a.

A sudden shortage of 134a could also jeopardise patient care, particularly for those who cannot use DPIs or other alternatives.

Recognising this, Orbia Fluor & Energy Materials has committed to maintaining a reliable supply of HFA-134a throughout the transition period for as long as the market requires it.

This dual approach – introducing HFA152a while securing ongoing 134a availability – provides healthcare providers with the flexibility to make the shift at a pace that ensures patient safety and continuity of care.

Orbia’s poster presented at RDD Europe 2025 on the flammability potential of Zephex 152a 98 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Our production facilities have been optimised to manage both propellants molecules simultaneously, and our supply chain teams work closely with pharmaceutical partners to anticipate demand fluctuations, prevent shortages, and maintain confidence in medical propellant and subsequent inhaler availability.

By guaranteeing a consistent 134a supply, we are helping the sector navigate the transition smoothly, giving clinicians and patients time to adjust to low-GWP alternatives without disruption to treatment.

This commitment underscores our patientfirst philosophy that environmental innovation should not come at the expense of care.

REFERENCES 1.

2.

https://www.england.nhs.uk/greenernhs/whatsalready-happening/improving-health-outcomesfor-respiratory-patients-while-reducingcarbon-emissions/#:~:text=The%20issue,a%20 consideration%20in%20treatment%20choice https://www.kouraglobal.com/

Sheryl Johnson Sheryl Johnson, Pharma Application Development Manager at Orbia Fluor & Energy Materials, is a highly respected authority in the pharmaceutical aerosol industry with almost two decades worth of experience in medical chemical development and research. She is on the board at the International Pharmaceutical Aerosol Consortium on Regulation & Science (IPAC RS), frequently contributed to the publishing of papers, and speaks at events such as the International Aerosol Society Congress. Now, with nearly 15 years experience at Orbia Fluor & Energy Materials, she serves as Pharma Application Development Manager, overseeing the safe production of research and clinical products containing zephex 152a.

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Nasal & Pulmonary

Scaling Capabilities in Nasal Drug Delivery

Nasal drug delivery has traditionally been used for local, inflammatory conditions within the sinus cavity, such as rhinitis and nasal congestion. In recent years however, it has evolved into a versatile route for systemic drug uptake via the nasal epithelium, intranasal vaccination and even emerging nose-to-brain delivery. This evolution has made nasal administration a promising route for both new chemical entities (NCEs) and reformulated therapies with patentexpired formulations.1 As applications grow, so does complexity.

Every nasal product is unique, defined by where it needs to act, how quickly it needs to work and how it needs to be delivered.

Developers must navigate formulation and device challenges, from mucosal clearance to bioavailability, whilst meeting stringent manufacturing and regulatory demands.

These factors are driving more innovators to

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partner with specialist contract development and manufacturing organisations (CDMOs) with the expertise, technology and facilities to help scale their bespoke nasal drugdevice combination products to the clinic and beyond.

naloxone nasal sprays for opioid overdose, dihydroergotamine (DHE) for acute migraine and epinephrine for anaphylaxis. Ongoing research is also exploring direct nose-to-brain delivery through the olfactory epithelium, bypassing the blood-brain barrier.

Next-Generation Nasal Applications As a route of drug administration, the nasal cavity offers several advantages over oral, intravenous and even pulmonary delivery.

Its highly vascularised epithelium allows for rapid drug uptake. Additionally, bypassing first-pass metabolism can enhance the bioavailability of certain therapies. Intranasal delivery can also generate strong immune responses, making intranasal vaccination particularly attractive. Beyond this, nasal administration can offer improved patient experience and compliance through noninvasive, needle-free delivery.

One of the most promising frontiers for nasal delivery is biologics, such as peptides, monoclonal antibodies (mAbs) and stem cells. Unlike small molecules, however, biologics are larger and more susceptible to stability issues due to factors like pH, osmolality and enzyme activity in the nasal mucosa. Delivering these molecules therefore requires precise formulation development and targeted device technologies which do not destabilise the biomolecules.

These benefits have led to the successful emergence of nasal systemic therapies that reach the bloodstream, such as

Challenges in Formulation and Device Development Nasal products are drug-device combination products, meaning the drug and delivery system must be developed in parallel to ensure optimal performance. Targeting the

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Nasal & Pulmonary challenges. The unique Resyca nozzle, which creates precise droplet size with low shear forces and delivers them with a lower spray velocity, has been demonstrated to protect fragile molecules.3 Furthermore, precision targeting allows enhanced delivery to specific regions and slower, longer-duration sprays improve coverage of the nasal epithelium.4 These features open opportunities to deliver fragile molecules, higher drug loads and improved access to hard-to-reach regions of the nasal cavity, like the olfactory region.

For therapies where consistent dosing and molecular stability are critical, this soft plume technology shows promise.

Manufacturing Complex Products Manufacturing challenges are equally significant when looking to take a product to clinical and commercial scales. Standard multi-dose lines can accommodate many products, but next-generation nasal therapies often require bespoke solutions to support patient safety, product efficacy and regulatory approval. To solve these challenges, developers are increasingly partnering with CDMOs that have expertise and experience in nasal drug delivery. correct site of action, whether local, systemic or nose-to-brain, dictates requirements for other factors, such as droplet size, spray pattern and plume velocity.

Formulations themselves vary in complexity, from aqueous solutions and suspensions to powders, each with specific storage, stability, dosing, and delivery considerations. Biologics, in particular, demand delicate handling, and traditional formulation components, such as preservatives, can be detrimental. While the nasal route offers a gentle delivery environment that can handle these larger, more sensitive molecules, it does not come without challenges. For example, the nasal cavity is designed to protect against pathogens and debris, and so leaves only a short residence time before a drug is cleared.

This makes mucosal clearance a critical factor for advanced therapies. One solution to this challenge is targeted deposition using delivery devices that aim for the olfactory region of the upper nasal cavity, where mucosal clearance is slower and epithelial permeability is higher.

Soft mist nasal devices, such as those developed by Resyca®, a joint venture between Bespak® and Medspray®, are designed to address many of these 102 INTERNATIONAL PHARMACEUTICAL INDUSTRY

Early engagement with a CDMO can help smooth the journey to commercialisation and reduce costly delays. In nasal drug delivery, where formulation and device development are tightly linked, early collaboration helps ensure that technical, regulatory and manufacturing considerations are understood. Choosing a CDMO that has been manufacturing nasal drug-device combination products for many years means gaining insight into optimal devices and access to a ready network of specialist partners.

Bespak, a specialist inhalation CDMO, offers decades of expertise in multi dose aqueous nasal sprays and has expanded into nasal powder systems for systemic applications, soft mist technology for the delivery of fragile molecules, and has a novel unit dose delivery device in development.2 At its Holmes Chapel site, Bespak provides customised manufacturing for complex nasal products, with flexible clinical suites, bespoke equipment validation and seamless scale-up to commercial supply. This expertise is especially valuable for late-stage clinical candidates with unique dosage forms, non-standard devices or challenging delivery needs, helping to shorten timelines and reduce risk.

These site capabilities have been proven through recent customer experiences.

Bespak recently partnered with a late-stage biopharmaceutical company to support the scale-up and commercial manufacture of an innovative intranasal migraine treatment.

Another recent project demonstrated the site’s capability to scale complex nasal therapies from early clinical supply to full commercial readiness. With these bespoke services, Bespak offers a flexible, future-ready partnership for even the most demanding and unique projects.

Capabilities for Bespoke Nasal Drug Delivery Nasal drug delivery is not one-size-fits-all and, as the field continues to evolve, the need for manufacturing flexibility will only increase. The pipeline for nasal therapies is expanding, driving demand for CDMOs capable of bridging the gap from clinical development to commercial supply.

Bespak, with its proprietary device technologies, adaptable facilities, custom equipment capability and proven scaling experience, is positioned as a trusted partner for developers seeking to bring innovative nasal therapies to patients.

REFERENCES 1.

2.

3.

4.

Kaneps, E. (2025). Nasal drug delivery: Overcoming the challenges of formulation development. Drug Development & Delivery.

Bespak, Nasal drug delivery device manufacturing & development.

Zhang, M. X., et al. (2023). Improved olfactory deposition of theophylline using a nanotech soft mist nozzle chip. Pharmaceutics, 16(1), 2.

Verhoeven, F., et al. (2024). Pre-filled syringe soft mist nasal spray for improved intranasal drug delivery [Poster]. Resyca.

Joe DePalo Joseph DePalo is a Director of Business Development at Bespak, with 13 years of experience delivering pharmaceutical drug products to the U.S. market. Over the past four years, he has leveraged his foundation in biomechanical engineering, medical device development, and pharmaceutical expertise to support the unique challenges of combination drug products for inhalation and nasal delivery. He earned his Bachelor of Science in Biomechanical Engineering from Marquette University.

Autumn 2025 Volume 17 Issue 3

THE SPECIALISTS IN INHALED AND NASAL DRUG DELIVERY

Your innovation partner for novel unit dose devices, liquid & powder formulations, soft mist technology and multidose nasal sprays.

Scan the QR code to find out more.

bespak.com www.international-pharma.com

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Unveiling the Path of Nebuliser Platforms for Combination Product Development With the objective to providing more efficient and user-friendly solutions for inhalation therapy, companies developing mesh nebulisers have adopted customisable platforms to fulfil an important unmet need in the market. As new therapies are developed, an increasing number of new biologic formulations in liquid form require the use of nebulisers.1 This fact has gradually reignited the interest in these delivery systems. Among the nebuliser types, mesh nebulisers utilise a mesh plate to aerosolise liquid medication, offering an effective and portable solution for localised drug delivery, while reducing systemic adverse effects.

Formulations and nebulisers require an appropriate degree of tailoring to achieve higher delivery efficiency and adherence.

Therefore, identifying the right formulationnebuliser fit during early feasibility studies or at the pre-clinical stage greatly benefits the overall development; however, formulationnebuliser combination implementations can be initiated at different stages of the development process. Nowadays, customisable mesh nebuliser platform developers can assist pharmaceutical companies in navigating several aspects of this journey through integrated services and solutions.

Formulation Implications When working on a new drug-nebuliser combination product, understanding the formulation physiochemical properties as well as the delivery system characteristics are fundamental to succeed.

Candidate formulations for an active pharmaceutical ingredient (API) may present different physicochemical properties such as viscosity, surface tension, osmolality, pH, and others.2 These differences are commonly related to the excipients and solvents in the formulations as well as the API concentration.

When it comes to inhaled formulations, the combination of these elements is crucial as they could affect how the formulation is aerosolised.

On one hand, excipients can help to stabilise the API in the formulation or in the case of biologics even protect the API from stress forces.3,4 However, their concentration can impact the viscosity and/or surface tension among other properties, making it challenging for mesh nebulisers to aerosolise the formulation.5 This can be observed with high viscosity or low surface tension formulations. The same can be said about the concentration of the API, with typically higher concentrations resulting in more difficulties for aerosolisation.

Other than the mesh plate and driving mechanism, which are directed linked to the performance, the device design and the indicators play a key role when it comes to usability factors. Aspects that are essential from a human factor perspective and to an extend also relevant to patient adherence.

Customisable mesh nebuliser platforms have the capability to tailor most if not all the features of common mesh nebulisers and incorporates new ones that add extra value.

When it comes to the delivery of biologics, which are known to be more costly APIs, the implementation of some of more innovative features is fundamental. A clear example is the implementation of breath-actuation, because it can significantly increase drug delivery efficiency and reduce fugitive aerosol emission.8 Some of the most important customisable features are (Figure 1).

Due to the situations mentioned above, the selection of a suitable candidate formulation during early development is critical for the appropriate matching with the delivery system. When identifying nebulisers as the desired delivery platform, focusing on delivery performance for the selected formulation can derisk the combination product development as well as potentially shorten timelines. Moreover, for biologics, stability and activity post-nebulisation is critical to lead to therapeutic effect, making mesh nebulisers a desirable option to deliver these large molecules as heat and shear forces are minimal when compared to other types of nebulisers.6 Customisable Mesh Nebuliser Platforms Mesh nebulisers generate aerosol by the means of a mesh plate. These mesh plates can be made of several materials such as nickel, nickel-palladium alloy, stainless steel,

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and others.7 Each plate has thousands of pores through which the liquid medication passes turning it into droplets throughout the aerosolisation process. In active mesh nebulisers, a controller works as the driving mechanism that sends a signal to the mesh module, which oscillates of the mesh component.

Figure 1. Customisable features of a mesh nebuliser platform Autumn 2025 Volume 17 Issue 3

Regulatory Nasal && Marketplace Pulmonary •

•

•

•

•

Mesh Plate / Mesh Module: other than utilising different materials for the mesh plates, an ideal pore size can be identified to better fit the delivery requirements of a formulation. For some difficult-todeliver formulations, the geometry of the plate can also be adjusted along with the plate thickness and pitch (distance between two pores). When it comes to the modules, some platforms claim to offer distinct mesh modules for different types of formulations.

Driving Power: platforms can be flexible to adjust the driving power that oscillates the mesh plate with the aim to increase delivery output or to deliver highly viscous formulations. This type of modification may require a combination of hardware and software components within the controller of the nebuliser to be applicable in the tailored device.

Mechanical Parts: to accommodate the needs of some specific population groups based on their age, or indication, and treatment requirements, platforms can adapt their mechanical components to match ergonomics or functional parts.

Some examples are the modifications on the medication container fill space, aerosol chambers volume, button size, etc.

Indicators: a combination of visual, auditive, and tactile feedback can commonly be incorporated to customisable nebuliser platforms. Some platforms already contain and can further accommodate additional LED indicators, add vibration for defined functions, or even include a speaker/buzzer to guide patients during treatment. Because of their nature, these modifications inquire both hardware and software modifications.

Additional Functions: functions such as breath-actuation, activation, and connectivity can be adjusted, enabled, or disabled, depending on the requirements.

Some platforms can further adjust the trigger span during the inhalation stage or incorporate guiding systems to ensure an ideal lung deposition.

Finding the Right Fit: Formulation-Nebuliser Combination For formulation-nebuliser combination development, the earlier the product begins to be developed as a combination, the better chances to derisk some of the steps. However, a balance between cost and derisking is usually www.international-pharma.com

follow by sponsoring companies. It is for this reason that in some developments, and more particularly during a proof-of-concept phase, pharmaceutical companies would opt to use off-the-shelf nebulisers in early stages.

There is still a certain degree of unawareness that the development of a drug-specific nebuliser with a nebuliser platform does not require the development of a completely new device. Some of the main nebuliser platforms already count with fully developed or approved standard devices in highly regulated markets. This status guaranties their immediate use in early clinical studies, providing robust devices that can be customised at later stages to fulfil additional requirements. Moreover, some nebuliser platform developers also offer special kits that contain a range of configurations that are readily available for testing, thus facilitating the selection of candidate formulations with suitable device configurations. The configurations in the development kits may include different pore size ranges, aerosol chambers, or driving powers.

For the actual initiation of the development process of a formulation-nebuliser combination a feasibility study needs to be conducted. This step is fundamental to understand how the two parts of the combination product interact. A common feasibility study may include aerosol characterisation and delivery performance, which can be summarised as follows.

•

•

Droplets Size Distribution (DSD): the test relies on the use of a laser diffraction particle size analyser for a quick assessment that provides key values such as volume median diameter (VMD), fine particle fraction (FPF), and geometric standard deviation (GSD). No API quantification is conducted.

Aerodynamic Particle Size Distribution (APSD): by using a cascade impactor, the mass median aerodynamic diameter (MMAD) is computed on the basis of the amount of API that is collected at

different stages of the system, with each stage being defined by a specific size cutoff. This process is commonly suggested for higher accuracy when working with suspensions. However, the process is lengthier and requires assay methods for API quantification.

•

Delivery Performance: commonly conducted by using a breath simulator, several performance parameters are computed with this study, including emitted dose, delivered dose, output rate, treatment time, and residual mass.

Although gravimetric methods can be applied, quantification assays need to be in place to obtain delivered dose performance which is suggested to both continuous output and breath-actuated mesh nebulisers.

•

Other Tests: particularly for biologics, post-nebulisation studies to assess the integrity of the molecules after aerosolisation is indispensable. Due to the potential impact of stress forces (e.g. shear forces) stability and activity assays are required to understand if the aerosolisation process may have led to aggregation, denaturation, etc.

The list above can serve as a general rule for understanding overall combination performance; nonetheless, to ensure that this information is meaningful, developing methods with the correct setups for combination product testing is essential.

Consequently, working with companies offering customisable platforms as well as experienced contract research organisations (CROs) is a necessity to ensure the generation of meaningful data.

At the end of this stage, a selected match, or it some cases a narrow down among the possible options, is expected to identify a suitable candidate formulation and customisable platform (Figure 2). From here on, mesh platform developers can map the customisation development based on performance requirements for the drug-specific nebuliser.

Figure 2. Right fit for formulation-nebuliser combination product INTERNATIONAL PHARMACEUTICAL INDUSTRY 105

Nasal & Pulmonary Customisable Nebuliser Platform Implementation Identifying an initial match for a combination product is the first major step moving towards the product customisation. From a device perspective, the standard nebuliser of a platform is sufficient for preclinical studies, including toxicology assessment or even to enter clinical studies, such as a Phase 1 prior to customisation. Subsequently, customisation of combination products can start at different stages. Some of the most common scenarios for the implementation of customised drug-nebuliser combination products is listed as follows: •

•

•

Pre-clinical Stage: the most ideal case as previously described maps a development in which the formulation and nebuliser are paired at an early preclinical stage, accelerating the development and shortening the overall full path. These combinations may require prompt commitment and upfront payments when it comes to bounding to a platform in the beginning, but in the long run could significantly reduce further expenses thanks to the mature stage of the combination product.

Clinical Stage: it is common change devices between Phase 1 and Phase 2 clinical trials.

These changes may be due to the several factors, but the reluctance of working with a platform in the early beginning thus opting for more conventional nebulisers and unexpected supply availability of certain products are the leading reasons. On either case, a bridging study is fundamental to compare aerosol characterisation, while justifying the means for the switch. All customisations can be implemented at this stage. From Phase 2 and onwards justifying a device switch may be more complex, requiring bioequivalence and in some cases repeating pivotal studies.

The final pathway may vary and can be highly dependent on the territory where the product will be launched.

Marketed Stage: for marketed products, switching to new devices is also possible.

However, the process may require extensive safety data, bioequivalence, and in most cases conducting additional clinical trials with the new customised nebuliser.

At each one of the stages, companies offering customisable nebuliser platforms provide the needed support for the development of the device, which extends from technical documents for filing clinical trial approvals or regulatory filings to device supply and training when required. These integrated services go beyond the development process, reaching to the commercial stage for which scaling up is a key factor during development as well as post market surveillance support (Figure 3).

Business Perspective and Other Implications When it comes to the business-related matters, the development process can be segmented in different stages, especially for the early-stage development in order to derisk. For initial feasibility studies, the supply of devices under a material transfer agreement or a feasibility study proposal to trigger the performance assessment is sufficient to begin the collaboration. At this stage, the purpose is to evaluate a potential long-term collaboration, and therefore, the commitment to an agreement may be premature.

As soon as positive results are recorded in a feasibility study, the tailoring of a customise platform can commence.

This opens the path to negotiating a development or licensing agreement that may significantly vary according to the scope of the project. The definitions of field (related to the API and indication), territory, and exclusivity combined to the level of customisation of a mesh platform are some of the contributors that shape the device and development milestones, royalties, and other development activities.

They often comprise late pre-clinical tests, clinical studies, and part of what would be the commercial supply; nonetheless, it is usual to have commercial agreements being

executed at later stages to cover activities related to commercial supply terms and distribution. For projects that are initiated in between clinical stages, the milestones may also be adjusted to adapt to the stage of the project.

There are cases in which the commercial strategy is not fully defined during the earlier stages. For these situations, there are also other alternatives that would focus on more specific tasks such as clinical trials.

Clinical supply or even research agreements are options that allow for a shorter-term collaboration as the development and/or commercial strategy is outlined. Commonly, milestones would concentrate on tasks that could be completed within shorter periods and with lower costs for the sponsoring side.

Due to the difference among development projects, there is no one-size-fits-all strategy from the business nor the development perspective. Nonetheless, this allows for room to hold discussions and negotiation between the formulation and nebuliser platform parties to come to an agreement that fits the expectations of both parties.

Empowering Drug-Nebuliser Combination Products The success of a drug-nebuliser combination product development is subject to multiple factors, starting with the right pairing of the formulation and nebuliser. Formulation combined with mesh nebuliser platforms can further optimise delivery performance allowing to derisk the development process and potentially shorten timelines.

New drug entities, including small molecules and biologics, can significantly benefit from customisable solutions as the development and/or implementation could take place at different stages of the combination product development.

Pharmaceutical companies can then feel reassured of having a partner that can assist with the device part from either technical or regulatory perspective. Nowadays, paving the track for a more efficient development has

Figure 3. Fully integrated pathway for drug-nebuliser combination product 106 INTERNATIONAL PHARMACEUTICAL INDUSTRY

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Regulatory Nasal && Marketplace Pulmonary become an option thanks to the integrated services of mesh nebuliser platform developers, who can support throughout the entire development process to market access.

REFERENCES 1.

2.

3.

4.

Shaibie NA, Mohammad Faizal NDF, Buang F, et al. Inhaled biologics for respiratory diseases: clinical potential and emerging technologies.

Drug Deliv Transl Res. Published online July 14, 2025. doi:10.1007/s13346-025-01909-6 Carvalho TC, McConville JT. The function and performance of aqueous aerosol devices for inhalation therapy. J Pharm Pharmacol.

2016;68(5):556-578.

Yousry C, Goyal M, Gupta V. Excipients for Novel Inhaled Dosage Forms: An Overview.

AAPS PharmSciTech 25, 36 (2024).

Cipolla D, Gruenloh CJ, Kadrichu N, et al.

Inhalable and Nasal Biologics: Analytical,

Formulation, Development, and Regulatory Considerations. J Aerosol Med Pulm Drug Deliv.

5.

6.

7.

8.

Published online April 8, 2025. doi:10.1089/ jamp.2024.0058 Zhang Y, Davis DA, AboulFotouh K, et al. Novel formulations and drug delivery systems to administer biological solids. Adv Drug Deliv Rev. 2021;172:183-210.

Brun EHC, Hong ZY, Hsu YM, et al. Stability and Activity of Interferon Beta to Treat Idiopathic Pulmonary Fibrosis with Different Nebulizer Technologies. J Aerosol Med Pulm Drug Deliv.

2023;36(2):55-64.

Pritchard JN, Hatley RH, Denyer J, et al. Mesh nebulizers have become the first choice for new nebulized pharmaceutical drug developments.

Ther Deliv. 2018;9(2):121-136.

Brun EHC, Wang CT, Chen YT, et al. Assessment of Fugitive Aerosol Emission During Actuation of a Breath-actuated Mesh Nebuliser. Drug Delivery to the Lungs, Volume 33, 2022

Hernan Cuevas Brun Hernan Cuevas Brun is Director of Business Development and Senior Aerosol Scientist of HCmed Innovations. He has over 10 years of experience in the drug delivery field, holding a BS in Biomedical Engineering from National Tsing Hua University and a master’s in business administration. He is responsible for expanding and coordinating the establishment of new partnerships with global pharmaceutical and biotech companies, assessing and mapping strategic development of drug-nebuliser combination products from feasibility stages to commercialisation. Moreover, Mr. Cuevas supports with the customisation of HCmed’s delivery platforms, covering aspects related to the performance and usability of tailored devices for pharmaceutical partners.

www.international-pharma.com

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The Role of Nasal Cast Testing in Drug Development

Nasal drug delivery has emerged as a major focus in pharmaceutical development because it combines convenience, rapid absorption, high bioavailability, and the potential for both local and systemic effects. Recent approvals and pipeline candidates for conditions including Alzheimer’s disease, depression, migraines, diabetes, seizures, and opioid overdoses illustrate the expanding therapeutic scope of nasal delivery.

The nasal cavity is especially attractive because it provides a direct pathway to systemic circulation and, in some cases, to the central nervous system. This has opened opportunities for innovative nose-to-brain therapies. Similarly, nasal vaccines target the nasal-associated lymphoid tissue (NALT), stimulating mucosal immunity as a needlefree alternative to injections.1,2,3 A key challenge in nasal drug delivery is ensuring accurate and consistent deposition within targeted regions of the nasal cavity.

This is complicated by natural anatomical variability and the many factors that influence spray performance, including device design and formulation properties.4 Nasal cast testing has emerged as a valuable

Figure 1: Nasal anatomy and spray deposition

tool, providing developers with a rapid, cost effective, and reproducible method to evaluate deposition and guide optimisation early in development.5,6 This paper explores the importance of nasal cast testing, its regulatory relevance, and the specific benefits it offers in accelerating the development of effective nasal products.

The Problem: Understanding Nasal Deposition Drug efficacy for nasal delivery depends on where the spray deposits within the nasal cavity.

For example: •

Nose-to-brain delivery requires targeting the olfactory region and upper turbinates.

• •

Nasal vaccines benefit from deposition at the NALT region to trigger immune response.

Systemic delivery relies on maximising deposition in the middle and lower turbinates for absorption.7

Traditional methods such as gamma scintigraphy and CT imaging have been used to study deposition.8 These approaches provide detailed maps of distribution but are resource-intensive, costly, and impractical for iterative development. Early formulation and device screening requires a faster, safer, and more reproducible alternative.

The Solution: Nasal Cast Testing Nasal cast testing fills this gap by using anatomically accurate replicas of the human nasal cavity to simulate drug delivery.

• • •

Rapidly evaluate multiple device types (unit-dose vs. multidose, liquid vs. powder).

Optimise formulation parameters such as viscosity, droplet size, mucoadhesion, and Spray Pattern.

Systematically vary device settings such as spray angle, insertion depth, and actuation force.

These studies are reproducible and controlled, allowing developers to generate consistent data free from the inter-subject variability that complicates human trials. This enables rational decision-making earlier in development, reducing reliance on costly in vivo methods and accelerating go/no-go decisions.9,10,11 Regulatory Perspective Although nasal cast testing is not a formal regulatory requirement, its relevance in regulatory science is steadily growing, 108 INTERNATIONAL PHARMACEUTICAL INDUSTRY

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Regulatory Nasal && Marketplace Pulmonary especially in the evaluation of locally acting nasal drug products. The FDA’s 2003 Guidance for Industry on Bioavailability and Bioequivalence Studies for Nasal Aerosols and Nasal Sprays for Local Action outlines three foundational pillars for demonstrating bioequivalence: formulation sameness, device equivalence, and reproducibility of delivery.12 The guidance places strong emphasis on in vitro testing methods such as Spray Pattern analysis, Plume Geometry, Droplet Size Distribution, and Aerodynamic Particle Size Distribution (APSD). However, the FDA also underscores the importance of a mechanistic understanding of drug deposition and the reproducibility of actuation – areas where traditional in vitro tests may fall short.

This is precisely where nasal cast testing becomes invaluable. By using anatomically accurate models of the human nasal cavity, nasal cast testing provides direct insight into how and where the drug is deposited after actuation. It offers both quantitative and visual data that align with the FDA’s call for deeper mechanistic understanding.

For innovators, this can reduce downstream risk, especially for nose-to-brain or vaccine applications, where demonstrating targeted delivery is critical. For generics, regulatory agencies expect bioequivalence to the reference listed drug (RLD). While APSD and in vitro actuation studies remain central, region-specific deposition maps from casts can provide valuable supportive evidence, strengthening equivalence arguments in borderline cases.

The European Medicines Agency (EMA) continues to emphasise the importance of pharmaceutical quality, device performance, and in vitro reproducibility for inhalation and nasal products.13 The latest regulatory and scientific guidelines published in 2024 reaffirm that: • • •

Figure 2: The Proveris Vereo® NSx Automated Actuator – an automated solution for actuating a variety of nasal sprays and syringes during in vitro testing.

Variability introduced by manual actuation, such as inconsistent force, angle, or timing, can significantly distort the assessment of a product’s true performance. This inconsistency poses challenges not only for reproducibility but also for meeting the stringent expectations of agencies like the FDA and EMA which prioritise precision and reliability in both device and formulation characterisation.

In essence, the pairing of automated actuation with nasal cast testing not only enhances scientific rigor but also aligns seamlessly with the FDA’s and EMA’s evolving expectations for data integrity, robustness, and reproducibility. It’s a forward-looking approach that reflects the industry’s commitment to precision and quality in nasal drug development.

Automated actuation platforms, such as the Proveris Vereo® NSx, offer a compelling solution to this challenge. These systems eliminate human variability by delivering consistent, programmable actuation parameters (stroke length, velocity, acceleration, and hold time), ensuring that each spray event is uniform and repeatable. When integrated with nasal cast testing, the result is a powerful, regulator-aligned methodology that generates anatomically relevant deposition data with high fidelity. This combination supports the mechanistic understanding of drug delivery and strengthens the overall data package submitted for regulatory review.

Benefits of Nasal Cast Testing Nasal cast testing delivers multiple advantages that address critical development challenges: 1.

Cost-Effectiveness – Enables rapid, affordable screening of multiple formulation and device combinations before advancing to expensive in vivo or imaging-based deposition studies.

2.

Reproducibility – Provides a controlled test environment, eliminating intersubject variability and allowing systematic evaluation of key parameters.

Device performance is critical to ensuring consistent drug delivery.

In vitro testing plays a central role in demonstrating therapeutic equivalence, especially for locally acting products.

These principles are aligned with the FDA’s approach, particularly in the context of bioequivalence and combination product evaluation.

Regulatory agencies across the globe are placing growing emphasis on actuation control in the evaluation of nasal drug products. www.international-pharma.com

Figure 3: Proveris Nasal Cast – an anatomically accurate model of the human nasal cavity INTERNATIONAL PHARMACEUTICAL INDUSTRY 109

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Figure 4: Deposition Concentration by Region with Various Angle and Flow Rate Conditions

3.

4.

5.

Targeted Insights – Generates regionspecific deposition data, essential for therapies that depend on precise targeting (olfactory region for CNS drugs, NALT for vaccines, turbinates for systemic absorption).

Formulation and Device Optimisation – Facilitates side-by-side comparison of devices and formulations, enabling rational selection and refinement of both components of the combination product.

Regulatory Alignment – While not mandatory, cast studies complement regulatory requirements for device performance characterisation and bioequivalence demonstration, providing supportive evidence for submissions to FDA and EMA.

Case Study: Evaluating Deposition Using the Proveris Nasal Cast The Proveris Nasal Cast was developed as one of the first in vitro tools to evaluate nasal spray deposition under physio-logically relevant conditions. Early models employed a 110 INTERNATIONAL PHARMACEUTICAL INDUSTRY

water-indicating gel to provide photographic, qualitative visualisation of spray distribution.

While useful for initial insights, these casts offered limited data.

The Proveris cast can be disassembled into six anatomically defined regions of the nasal cavity, enabling extraction and quantification of active pharmaceutical ingredient (API) deposited in each region. This advancement provides truly quantitative deposition profiles, aligning with the FDA’s CMC guidance on characterisation and supporting more predictive assessments of product efficacy.

Automated actuation of devices into the nasal cast ensures highly consistent dosing, minimising operator variability and establishing reproducibility that is critical for regulatory acceptance. In addition to deposition mapping, Proveris Laboratories complements cast studies with metered shot weight determination – confirming delivered dose accuracy – and actuation force measurement, which provides insight into device usability and patient compliance.

In a recent case study, Proveris Laboratories evaluated deposition patterns of an over-the-

counter, multi-dose nasal spray under varied testing conditions. The experimental setup used: •

0° (device upright), 45°, and 60° insertion angles

•

0 vs. 15 L/min airflow to simulate nasal breathing (no-flow vs. flow conditions)

•

90% methanol extraction solvent

•

18 replicate actuations

Shot weight results confirmed robust dose delivery, indicating the methodology was sound and repeatable.

Deposition Outcomes •

No-flow condition: Deposition was highly sensitive to spray angle. At 0° (device upright), more drug deposited in the nasal vestibule. At 45° and 60°, vestibular deposition decreased, while deposition in the inferior turbinate increased. Across all angles without flow, very little API reached the middle turbinate.

Autumn 2025 Volume 17 Issue 3

Regulatory Nasal && Marketplace Pulmonary •

Flow condition (15 L/min): Deposition became less dependent on spray angle. Regardless of device orientation, the airflow carried particles deeper, reducing variability and promoting more consistent deposition patterns.

Regulatory and Clinical Implications: These findings underscore several key points directly relevant to FDA and EMA expectations for CMC submissions: 1.

Clear dosing instructions – Angle, insertion depth, and patient posture must be specified and justified, as they directly affect reproducibility of deposition.

2.

Inclusion of airflow simulation – Since deposition is strongly influenced by breathing flow, in vitro studies should incorporate airflow to better mimic patient use.

3.

4.

development timelines, support regulatory submissions, and ensure that nasal products are delivered effectively and consistently to their intended target sites, ultimately advancing patient care and expanding therapeutic possibilities.

REFERENCES 1.

2.

3.

4.

Validation of actuation methodology – Low RSD values demonstrate robustness and reproducibility, supporting method validation under ICH Q2 principles.

5.

Patient and device relevance – For rescue sprays like Narcan, patients may not be upright, highlighting the importance of deposition consistency under varied angles and flows. For vaccines or CNS drugs, ensuring delivery to turbinates or olfactory region is essential to therapeutic success.

6.

In summary, the case study demonstrates how modern nasal cast testing, paired with automated actuation, generates robust, regulator-relevant data. It validates dosing instructions, strengthens product characterisation, and provides developers with confidence that their products can deliver consistent, targeted therapy across real world use conditions.

Conclusion Nasal cast testing has become a cornerstone of nasal drug product development, bridging the gap between in vitro device characterisation and costly in vivo imaging studies. By enabling precise, reproducible, and cost-effective evaluation of deposition, nasal casts help developers optimise both formulations and devices to achieve reliable therapeutic outcomes.

Advanced models, such as the Proveris Human-Realistic Nasal Cast, when paired with automated actuation technologies like the Proveris Vereo NSx, accelerate www.international-pharma.com

12.

7.

8.

9.

10.

11.

Nose-to-brain drug delivery: from bench to bedside | Translational Neurodegeneration | Full Text First‐in‐human positron emission tomography study of intranasal insulin in aging and MCI - Sai - 2025 - Alzheimer's & Dementia: Translational Research & Clinical Interventions – Wiley Online Library Nguyen, L. T.-T., & Duong, V.-A. (2025). Noseto-Brain Drug Delivery. Encyclopedia, 5(3), 91. https://doi.org/10.3390/encyclopedia5030091 Gao M, Shen X, Mao S. Factors influencing drug deposition in the nasal cavity upon delivery via nasal sprays. J Pharm Investig.

2020;50:251–259. https://link.springer.com/ article/10.1007/s40005-020-00482-z Pathak YV, Yadav HKS, eds. Nasal Drug Delivery: Formulations, Developments, Challenges, and Solutions. Cham: Springer; 2023. Accessed September 9, 2025. https:// link.springer.com/book/10.1007/978-3-03123112-4 Xi J, Yuan JE, Zhang Y, Nevorski D, Wang Z, Zhou Y. Visualization and Quantification of Nasal and Olfactory Deposition in a Sectional Adult Nasal Airway Cast. Pharm Res. 2016;33(6):1527– 1541. Accessed September 9, 2025. https:// link.springer.com/article/10.1007/s11095-0161896-2 Yadav HKS, Lim-Dy A, Pathak YV. An Overview of the Anatomy and Physiology of Nasal Passage from Drug Delivery Point of View. In: Pathak YV, Yadav HKS, eds. Nasal Drug Delivery: Formulations, Developments, Challenges, and Solutions. Springer; 2023:1–13. Accessed September 9, 2025. https://link.springer.com/ chapter/10.1007/978-3-031-23112-4_1 Newman SP, Illum L. Radionuclide imaging studies in the assessment of nasal drug delivery in humans. Am J Drug Deliv.

2004;2(2):101–112. Accessed September 9, 2025. https://link.springer.com/article/10.2165/ 00137696-200402020-00003 Gondhale-Karpe P, Bhope S, Puri M, Manwatkar S, Mahajan B. Analytical Tools for the Characterization of Nasal Spray Drug Products. In: Kulkarni S, et al., eds.

Biosystems, Biomedical & Drug Delivery Systems. Springer; 2024. Accessed September 9, 2025. https://link.springer.com/content/ pdf/10.1007/978-981-97-2596-0_4 Kimbell, J.S., et al. (2007). Deposition of inhaled particles in the human nasal airway: Effects of airway geometry and particle size. Aerosol Science and Technology, 41(5), 408–423. https://doi.org/10.1080/02786820701282677 Per G Djupesland, John C Messina & Ramy A Mahmoud (2020) Role of Nasal Casts for In Vitro Evaluation of Nasal Drug Delivery and Quantitative Evaluation of Various Nasal Casts, Therapeutic Delivery, 11:8, 485-495, DOI:

13.

10.4155/tde-2020-0054 U.S. Food and Drug Administration.

Bioavailability and Bioequivalence Studies for Nasal Aerosols and Nasal Sprays for Local Action: Guidance for Industry. April 2003.

Accessed September 9, 2025. https://www. fda.gov/regulatory-information/search-fdaguidance-documents/bioavailability-andbioequivalence-studies-nasal-aerosols-andnasal-sprays-local-action European Medicines Agency. Guideline on the Pharmaceutical Quality of Inhalation and Nasal Medicinal Products (Revision 1).

EMA/CHMP/QWP/49313/2005 Rev. 1.

Accessed September 9, 2025. https://www. ema.europa.eu/en/documents/scientificguideline/guideline-pharmaceutical-qualityinhalation-nasal-medicinal-productsrevision-1_en.pdf

Joanne Mather Joanne Mather is a scientific marketing leader with many years of experience in the analytical science space. As senior director of Marketing at Proveris Scientific, she focuses on translating complex scientific and regulatory challenges into practical solutions that help companies in the OINDP space accelerate development and ensure product quality. With a strong background in analytical science and a customercentric approach, she is dedicated to supporting the industry in bringing effective and reliable aerosolised drug products to market.

Alyssa Rubino Alyssa Rubino drives product marketing at Proveris Laboratories, where she helps communicate the value of tools and services that support development of orally inhaled and nasal drug products (OINDPs). With a background in life sciences and regulatory strategy, she brings a unique perspective that connects scientific innovation with customer needs. Alyssa works closely with both internal teams and industry partners to share how Proveris can help improve product performance, streamline development, and support regulatory success.

INTERNATIONAL PHARMACEUTICAL INDUSTRY 111

28-30 October 2025 Messe Frankfurt

The heart of pharma, all in one place Where the global pharma community gathers to shape the future.

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Autumn 2025 Volume 17 Issue 3

Regulatory Nasal && Marketplace Pulmonary

CPHI Frankfurt 2025: Where the Global Pharma Supply Chain Converges Join us at CPHI Frankfurt 2025 CPHI Frankfurt 2025 returns to Messe Frankfurt from October 28–30, celebrating its 36th year as a global convergence point for pharmaceutical manufacturing and supply chain stakeholders. With over 2,000 exhibitors and six content theatres, the event remains a key hub for business development, innovation and strategic collaboration.

There’s a reason why CPHI Frankfurt claims to be at the heart of pharma, and according to event director, Tara Dougal, “It’s the place where the pharmaceutical supply chain gets together every year to collaborate, build relationships, and get business done.”

“CPHI Frankfurt is where the entire pharmaceutical ecosystem, from raw materials to packaging and final delivery, connects to shape future capabilities and drive industry progress.” says Tara Dougal, Event Director.”

Last year’s event in Milan welcomed around 60,000 visitors, the highest attendance in CPHI Europe’s history. CPHI Frankfurt 2025 is expected to surpass that, with more than 62,000 pharma professionals anticipated to attend over the three days.

New Ones for 2025 In addition to the established zones, this year’s event introduces four new feature zones, designed to drive sector-specific engagement and innovation and reflect emerging industry trends and market growth areas. The new feature zones aim to deepen engagement around emerging challenges and solutions across key pharmaceutical workflows, reflecting rising demand for targeted innovation.

This year, the zones will cover an array of hot industry topics: • AI & Tech Attendees can explore the latest AI & technology solutions reshaping the future of pharma, from drug discovery and clinical trials to manufacturing, operations, and commercial analysis.

• Cleanroom Critical to quality, this zone invites visitors to explore solutions for contamination www.international-pharma.com

•

•

control, environmental monitoring, and controlled manufacturing environments.

Coldchain & Logistics An opportunity to connect with suppliers focused on temperature-controlled logistics, packaging, monitoring, and transport solutions.

Sustainability Suppliers With sustainability at the core of CPHI, this zone highlights companies offering environmentally responsible solutions for pharma.

[Established zones at CPHI Frankfurt: APIs /Bioproduction/Contract services/CRO/ Exipients/Fine chemicals/Finished dose/ Integrated pharma/Machinery & equipment/ Natural extracts/Packaging & drug delivery.]

Still More to Explore Leadership Summit New for 2025, this year CPHI Frankfurt is inviting an exclusive gathering of pharmaceutical industry visionaries, C-suite executives, and decision-makers to the Leadership Summit.

A premium event, it is a unique platform for collaborative problem-solving, strategic insights, and transformative discussion that will help shape the future of healthcare delivery.

The Leadership Summit brings together a stellar lineup to highlight some of the key issues currently shaping the pharmaceutical landscape, setting the tone for the entire event. On the first morning of the conference, Leaders from major pharmaceutical companies will discuss topics such as globalisation of manufacturing, supply chain resilience, regulatory strategy, and evolving market dynamics.

An exclusive event open to Leaders, Leaders Platinum, and Networking Accelerator pass holders, there’s still time to be part of this exclusive gathering and secure a pass to hear leading voices in pharma tackle the industry’s most important challenges.

technical advancements from across the pharmaceutical supply chain – including formulation, processing, packaging, and commercialisation. Leading voices in the sector will share their expertise and knowledge on the following topics across all three days of the event: • Packaging & Device Innovation • The Future of Pharma & Ingredients • Next-Gen Bio • Manufacturing 5.0 • Sustainable Futures • Clinical Innovation Networking Opportunities From informal happy hour gatherings to the CPHI Celebration Awards recognising leadership and innovation across 14 categories, CPHI Frankfurt offers multiple touchpoints to connect with peers, partners, and prospects.

The annual CPHI Celebration Awards & Networking Party takes place on the first night, live at Messe Frankfurt. This year, it recognises innovation and leadership across 14 categories, including Women in Pharma and Future Leader of the Year. An event not to be missed!

Top Tips With so much more to discover at CPHI Frankfurt, Download the official CPHI event app to build your agenda, pre-book meetings, and access real-time floor navigation. The platform remains active post-event to support follow-up communications and ongoing lead generation. It remains active post-show to support follow-up activities.

A final top piece of advice from event director, Tara Dougal: “Whether you're a first-time attendee or a returning exhibitor, planning is key. Our digital platform helps attendees get the most value by pre-booking meetings, building agendas, and navigating efficiently on site.”

Content Agenda This year, there are six content theatres running sessions featuring content track features presentations from organisations from across the pharmaceutical supply chain.

Sessions will spotlight applied insights and INTERNATIONAL PHARMACEUTICAL INDUSTRY 113

Advertisers Index

Page 21 Aptar Page 77

Aurena Laboratories

Page 59 & 60

Bausch + Ströbel Maschinenfabrik Ilshofen GmbH + Co. KG

Page 101

Bespak Limited

Page 55

Biopharma Process Systems Ltd.

Page 49

Carterra Inc

IBC

Cold Chain Technologies

Page 110 CPHI Page 57 Cypheme Page 84

DDL 2025

Page 17

Gerresheimer AG

Page 99

HCmed Innovations Co. Ltd.

Page 81

Krautz Temax

Page 93

Merxin Ltd

Page 11 Nipro Page 3

Novo Nordisk A/S

Page 99 Orbia Page 39

PCI Pharma Services

BC

Proveris Scientific Corporation

Page 43

Senglobal Ltd.

Page 5

Stoelzle Glass Group

Page 91

UPC Cambridge Ltd

Page 13 & 31

Valsteam ADCA

Page 79

The Wool Packaging Company Limited (Woolcool)

IFC Ypsomed AG

I hope this journal guides you progressively, through the maze of activities and changes taking place in the pharmaceutical industry

IPI is also now active on social media.

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Autumn 2025 Volume 17 Issue 3

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INTERNATIONAL PHARMACEUTICAL INDUSTRY 115

YOUR PARTNER…

FROM DEVELOPMENT TO APPROVAL

Scientific expertise and testing strategies for innovator and generic OINDPs

cGMP

• Hand Actuation Parameter Design Studies

• In Vitro Testing

• Root Cause Analysis

• IVBE Studies

• OOS/OOT Investigations

• Device and Formulation Screening

• Development Stability Testing & Storage

• Method Development

• Method Validation & Transfer

• Spray Characterization Studies

• Device Reliability Studies

• Product Consultation when Design, Supply Chain or Manufacturing Changes Occur

• Regional Deposition Studies (Human Realistic)

• Device Robustness

T L I-VI N A I L II OMP hedule

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RY

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tered S

egis DEA R

116 INTERNATIONAL PHARMACEUTICAL INDUSTRY

LEARN MORE: www.proveris.com contactus@proveris.com Autumn 2025 Volume 17 Issue 3 +1 508 460-8822