EPM May/Jun 2024

THE LATEST INSIGHTS FROM ASTRAZENECA

EMBRACING INNOVATION TO MEET FUTURE PACKAGING NEEDS

MAMMALIAN BIOPROCESS INTENSIFICATION

AS A TURNKEY SYSTEM

May/Jun 2024

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May/Jun 2024 | Volume 24 Issue 3

REGULARS

5. EDITOR’S DESK

Covid vaccine withdrawal, Wegovy, and French investment.

6. A SMALL DOSE

Covering the latest developments in pharma.

14. COVER STORY

Dr. Marten Klukkert, Vice President Customer Development Centre, Fette looks at continuous direct compression as a turnkey system.

FEATURES

8. OPINION

Venkata Shravan Indurthi, Chief Scientific Officer at Aldevron discusses improving CAR-T with smaller, safer plasmid backbones.

10. OPINION

Sarah Moores, Sarah Renshaw, and Claire Bennett at AstraZeneca look at how the Company is accelerating the electronic product information industry transition in Europe.

12. CELL & GENE THERAPY

Nick Morley, Principal Scientist, Element Materials Technology considers E&L study design for CGTs.

18. Q&A

We caught up with Eric Kaneps of Renaissance Lakewood to detail their journey so far.

21. PACKAGING

Geert Vleugels, General Manager NL, Tjoapack touches on the need to embrace innovation to meet the future packaging needs of a growing biologics PFS market.

24. BIOPROCESSING

Peter Timmerman, Head of Peptide Science at Biosynth explores the challenges of therapeutic peptide development.

27. BIOPROCESSING

Jean Aucamp, Associate Director, Biologics R&D, at Lonza explores mammalian bioprocess intensification for MABs production.

30. MANUFACTURING

Nandu Deorkar, Senior VP, R&D, Avantor analyses the formulation balancing act.

32. CONTAINMENT & CLEANROOMS

Andy Whittard, Managing Director, Cherwell on embracing sustainability in cleanroom operations.

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European Pharmaceutical Manufacturer is published by Rapid Life Sciences Ltd. European Pharmaceutical Manufacturer is distributed in electronic and print formats to a combined readership of 14,000 pharmaceutical manufacturing professionals.

Volume 24 Issue 2 Mar/Apr 2024

While every attempt has been made to ensure that the information contained within European Pharmaceutical Manufacturer is accurate, the publisher accepts no liability for information published in error, or for views expressed. All rights for European Pharmaceutical Manufacturer are reserved and reproduction in part or whole without written permission is strictly prohibited.

s seems to be the way in this industry of ours, the leading stories in pharma tend to come from the very biggest companies, which, I suppose, is natural given the interest in them and the investment they both give and receive. With that in mind, arguably the leading story since our last EPM issue is that British-Swedish behemoth AstraZeneca have withdrawn more than three billion doses of their Covid-19 vaccine made in collaboration with the University of Oxford. This follows recent reporting in the Telegraph following a UK lawsuit in which the Company admitted that their vaccine could, in exceptional circumstances, potentially cause Thrombosis

with Thrombocytopenia Syndrome (TTS) leading people to have blood clots and a low blood platelet count. However, AstraZeneca have sited this vaccine withdrawal as stemming from a lack of global demand, which naturally makes sense given the enormous number of people vaccinated since November 2020.

In a statement the company said: “We are incredibly proud of the role Vaxzevria played in ending the global pandemic. According to independent estimates, over 6.5 million lives were saved in the first year of use alone and over three billion doses were supplied globally. Our efforts have been recognised

EDITOR’S DESK

led to a decline in demand for Vaxzevria, which is no longer being manufactured or supplied. AstraZeneca has therefore taken the decision to initiate withdrawal of the marketing authorisations for Vaxzevria within Europe.”

No - 2052-4811

by governments around the world and are widely regarded as being a critical component of ending the global pandemic. As multiple, variant Covid-19 vaccines have since been developed, there is a surplus of available updated vaccines. This has

Following this slowing trend, AstraZeneca have side-stepped away from covid vaccinations opting to focus more on obesity drugs and respiratory syncytial virus vaccines. In a beautiful twist of editorial fate, we move onto GLP-1 weight loss drugs once again as Novo Nordisk have recent published new long-term data at the European Congress on Obesity in Venice, Italy highlighting that Wegovy treatment maintained an average of 10% weight loss after four years. Often ciriticised for its cost, Novo Nordisk will be hoping that these results will aid in their battle to convince both governments and insurers to cover the costs of the drug. Wegovy has been launched in ten countries at the time of writing, with prices varying from $200 - $2000 a month. Lastly, the month of May has seen Pfizer and AstraZeneca pledge a combined €1 billion investment into the French medical sector following the start of the Choose France summit at Versailles Palace. More specifically, Pfizer said it would invest €500 million in France to build up its research and development presence in the country while AstraZeneca announced an investment of $388 million for its site at Dunkirk. Sanofi have also committed to a large-scale French investment plan of more than €1 billion to create new bioproduction capacity at its sites in Vitry-sur-Seine (Val de Marne), Le Trait (SeineMaritime) and Lyon Gerland (Rhône). Exciting times!

JAI MCINTOSH

A small dose

Merck is investing more than €300 million in a new research centre at its global headquarters in Darmstadt, Germany. In the Advanced Research Centre, the Life Science business sector will research solutions for manufacturing antibodies, mRNA applications and additional products required for biotechnological production, among other things. As of the start of 2027, it will provide space for around 550 employees. Merck laid the cornerstone for the building together with German Federal Chancellor Olaf Scholz. The new building is part of an investment program in the Darmstadt site: Merck will invest around €1.5 billion in total by 2025.

Federal Chancellor Olaf Scholz: “Investments such as those made by Merck here at

Merck Invests €300

Million

in New German Research Centre

its headquarters in Darmstadt make tremendous economic, medical and scientific sense. They are a tribute to Germany as a leading pharmaceutical, industrial and research location and reflect the strength of the life sciences. All of this proves that we are on the right track with the changes that we have made with a view to offering the pharmaceutical and biotech industry better

conditions. The German Government will continue to tread this path with all due resolve.”

“With this strategic investment, we are strengthening the leading position of Merck in key technologies for the development and manufacture of novel medicines,” added Belén Garijo, Chair of the Executive Board and CEO of Merck. “As a leading provider of life science technologies, we

continue to invest in research and development ‘Made in Germany’. In doing so, we are enabling scientific progress for the benefit of millions of patients and customers around the world.”

The Advanced Research Centre brings together research on key technologies of the Life Science business sector of Merck. These include raw materials and processes for researching and manufacturing antibodies, recombinant proteins and viral vectors. The company also researches cell culture media and pharmaceutical formulation and purification aids as well as digital reference materials. In addition, the scientists are developing analytical chromatography further. This is a method for separating, identifying and quantifying chemical substances in a sample. Research along the mRNA value chain will also be based in the new centre.

With around 18,000 square meters, the Advanced Research Centre enables collaboration across departments in an open, modern work environment. Merck is planning almost carbon-neutral research operations. Energy supply is based on photovoltaics, geothermal energy and air-source heat pumps. The specially designed facades and the green roofs also help to save energy and improve the microclimate.

The Darmstadt site is one of the most important Merck centres for research and development in life science technologies. In the next ten years, approximately one fifth of the Life Science business sector’s sales with new products are estimated to come from here. Since 2020, Merck has announced investments of more than €2 billion in the business sector globally. The objective is to expand Life Science’s capacities and capabilities to meet the globally increasing demand for medicines.

JANSSEN TO ADOPT JOHNSON & JOHNSON BRAND

IN UK

Johnson & Johnson

have announced it is updating its brand and uniting both its two business segments under the Johnson & Johnson brand name in the UK.

The announcement marks the next era for Johnson & Johnson in the UK, which is leveraging its expertise in innovative medicine and medical technology to prevent and treat complex diseases and introduce solutions that are smarter, less invasive and more personalised.

Moving forward, the Company’s two segments will be more connected to the Johnson & Johnson brand.

Janssen, the Company’s pharmaceutical segment, will be known as Johnson & Johnson Innovative Medicine, and the medical technology segment will continue to be known as Johnson & Johnson MedTech. The changes are part of a

global roll out of the new Johnson & Johnson brand, announced in September 2023.

Roz Bekker, Managing Director of Johnson & Johnson Innovative Medicine UK & Ireland said:

“Though our name for our pharmaceutical segment may have changed, our ambition hasn’t. Over the past 100 years, our first responsibility has always been to the patients, doctors and nurses that we serve. Our support for the health system reaches back to before the inception of the NHS, and we recognise that only through enduring partnerships can we continue to make a positive difference to the lives of patients and their loved ones. As we look ahead to the future, we will continue to build on our legacy of care and innovation, delivering transformational medicines that improve patient outcomes and make a lasting impact on the healthcare sector in the UK.”

The transition is happening at a time when Johnson & Johnson is celebrating its storied heritage and achievements over 100 years of operations in the UK.

AbbVie breaks ground on a new central research building, “LUnA” (LUdwighafens neue Arbeitswelt) and is investing approximately €150 million in its second largest R&D location worldwide. A state-ofthe-art research and laboratory building is being built on the main campus and will be home to more than 300 researchers and scientists. The facility will be built with modern and sustainable infrastructure features, creating flexible working conditions that enable greater scientific exchange between different areas of research and implement automation and digital

AbbVie Invest €150 million Investment in New German Development Facility

research capabilities.

With this investment, AbbVie reinforces that the Rhineland-Palatinate site, with its more than 2,000 employees, will continue to be a critical component of AbbVie’s global network.

“For AbbVie Germany, the new construction of our ‘LUnA’ research building is much more than a €150 million investment in cuttingedge infrastructure. It is a promise for the future of AbbVie science and innovation. We are creating attractive working conditions for

our top scientists and attracting new talent so that we can conduct cutting-edge research at our site in the long term,” explains Martin Gastens, vice president, biologics drug product development and managing director R&D, AbbVie Germany.

“The German state of Rhineland-Palatinate is on track to become one of the leading hubs for biotechnology and life sciences. We support research, promote its translation, and continue

We empower innovators in the pharmaceutical industry to bring their products to market.

Scientific and Regulatory Compliance Pharmaceutical Regulation

expanding the footprint. As the Government of the Federal State of Rhineland-Palatinate, we are proud of this additional investment made by AbbVie, and the trust which yet another large pharmaceutical company has placed in our state. We are working tirelessly on creating the best possible framework conditions for business and research and are collaborating closely in a network with all those involved through the biotechnology advisory board and the biotechnology academy. The research building is expected to be completed in 2027, a major milestone.

ISO 17025 and GMP quality standards

Contact us today to arrange a meeting with our scientific and regulatory experts broughton-group.com/pharma/testing

IMPROVING CAR-T WITH SMALLER, SAFER PLASMID BACKBONES

Today, there are six approved CAR-Ts to treat cancer, and more than 800 ongoing clinical trials of the technology in the United States alone. The global market for CAR-T treatments is expected to grow from $2.3 billion in 2022 to $10.3 billion in 2030.

That growth could be even greater – but only if CAR-T manufacturers can overcome key challenges inherent in these complex treatments. Currently, making CAR-T treatments is a labourious process that involves removing T cells from patients and engineering them into cancer-killing cells using plasmid DNA backbones that are large, unwieldy and prone to causing adverse effects. The good news is that recent innovations in plasmid DNA promise to improve the efficiency of CAR-T development and manufacturing, as well as the safety of the end products.

BOOSTING GENE EXPRESSION WHILE REDUCING TOXICITY

First-generation CAR-T treatments rely on old plasmid technology that was traditionally used in vaccine development. These plasmids contain instructions to transform T cells into cancer killers, which are transported via bacterial backbones that are greater than 2,000 base pairs in length.

The larger the size of the CAR-T plasmid backbone, the greater the risk of transfection toxicity and gene silencing. The more transgenes that are silenced, the lower the output of cells that are properly equipped to kill the cancer.

Furthermore, traditional plasmids employ antibiotic markers for selection, which can cause adverse reactions to

CAR-T treatments in some patients and raise the risk of antibiotic resistance over time. This is a major cause of concern for regulators, including the FDA, which highlighted it in new guidelines for the development of CAR-T therapies. The guidance, released in January of this year, recommends that CAR-T vectors exclude “unnecessary transgenes” such as antibiotic resistance genes.

Emerging plasmid DNA advances are designed to address the shortcomings of traditional CAR-T constructs. There are now plasmids on the market that are 500 base pairs in length – a two-fold reduction in size that offers several benefits over older technology. For example, a 2022 study showed that in two types of rat cells, that reduction in the size of the plasma DNA backbone improved gene expression levels more than ten-fold.

Another important advance in plasmid DNA backbones is the elimination of the bacterial-encoded antibiotic resistance marker gene. Plasmid DNA innovators are developing alternative methods that don’t require antibiotics in selection. For example, some reduced-size plasmid constructs are selected and produced in sucrose, eliminating the need for the antibiotic resistance marker gene to be encoded into the bacterial backbone.

POWERING INNOVATIONS IN T CELL EDITING

Plasmid DNA innovations are helping improve manufacturing yields in cell therapies for cancer. In 2022, a research team at Genentech put a small antibiotic-free DNA plasmid to the test, comparing it to two traditional plasmid platforms for an experimental CRISPR/Cas9 gene-edited T cell targeting a type of squamous cell carcinoma. The smaller plasmid outperformed standard plasmids, yielding up to three times the number of edited cells and resulting in lower toxicity. The researchers reported that using the next-generation backbone reduced the amount of plasmid DNA needed to edit the T cells.

RNA is also emerging as a potential tool for improving CAR-T treatments. Researchers at Stanford recently demonstrated that they could use an RNA-targeting CRISPR technique to change the metabolism of T cells, making them better cancer killers. Because manufacturing RNA requires plasmid DNA, it is easy to see how improving plasmid DNA backbones by making them smaller and safer will benefit the researchers working to advance RNA editing for cancer cell therapies.

The potential for CAR-T innovations to save lives is already clear: Five years after the pivotal trial that led to the approval of the first CAR-T, Kymriah, 55% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) who received the cell therapy were still alive. Continual improvements in CAR-T technology – and the plasmid DNA forms its backbone – will no doubt expand the population of cancer patients who can benefit from cell therapy.

Venkata Shravan Indurthi, Chief Scientific Officer at Aldevron

Accelerating the Electronic Product Information Industry Transition in Europe

Each year, medicines produce an estimated 100 billion paper leaflets, contributing significantly to carbon dioxide emissions and waste. This staggering fact is something we can’t ignore, particularly in an age where sustainability is at the top of the agenda – not just in the healthcare sector, but across all industries.

At AstraZeneca we aim to drive positive change beyond the impact of our medicines by embedding sustainability into everything we do – from the lab to the patient. As a society, we are confronted by some of the biggest sustainability challenges of our time, however one way we can take scalable action is through digital innovation.

In 2021 we initiated the integration of electronic product information (ePI) across our medicines, providing an opportunity for sustainable, patient-focused innovation. We have set ourselves an ambitious target to transition to ePI across our entire pipeline and in all markets by 2030.

A DUAL APPROACH TO DIGITISATION: PROTECTING PATIENTS AND THE PLANET

We’re working to introduce ePI across all our medicines by default.

How will we achieve this?

One key step forward will be for patients to hold the key to understanding their treatment in the palm of their hand –

Sarah Moores, AstraZeneca Sustainability Program Director; Sarah Renshaw, AstraZeneca Global Projects and Change Director; and Claire Bennett, AstraZeneca Senior Project Manager Sourcing and Supply

combining technology with human-centric care, providing faster access to rigorously validated product information and meeting patients where they are: online and on-the-go.

In a world where digital literacy is rapidly becoming as fundamental as reading and writing, facilitating easy access to ePI can help ensure that patients, regardless of their background or abilities, can access critical, up to date healthcare information in a format that is convenient and understandable. We are actively working with pharmacies, patients, and healthcare practitioners to provide flexibility for patients to access product information through alternative ways if needed, responding to specific access requirements of certain patient populations and healthcare systems.

Collectively, we must ensure that the healthcare experience is one in which clarity and comprehension are within easy reach.

While digital innovation can change the game for patient accessibility, it also has a major impact on sustainable healthcare practices. By adopting a digital-first approach, we are contributing to a healthcare ecosystem that is responsive to the needs of the planet and its finite resources.

In recent years, the drive for sustainable manufacturing processes has become a focus for European policy initiatives, including in healthcare. For instance, the European Commission’s ‘Pharmaceutical Strategy for Europe’ highlights the critical role of innovation and sustainability within the EU pharmaceutical sector. Similarly, the ‘Greener NHS Programme’

underscores the commitment to eco-conscious practices in healthcare delivery across the UK. Notably, in October 2020, the NHS set a global precedent by being the first health service to pledge to achieve net zero.

At AstraZeneca, we also have ambitious decarbonisation targets: we are aiming to reduce our Scope 1 & 2 emissions by 98% by 2026, halve our entire emissions footprint by 2030, on the path to becoming sciencebased net zero by 2045.

Adopting digital practices, in place of more traditional methods, is an important part of reaching these goals. Each digital leaflet represents a tangible reduction in waste and emissions versus using the traditional paper leaflets. By replacing paper leaflets and implementing ePI as standard practice, AstraZeneca alone could contribute to saving the equivalent of 500,000 trees, 50,000 tonnes of carbon dioxide, and 1.6 billion litres of water annually.

THE PATH TO EPI IMPLEMENTATION

Of course, the transition to digital practices requires collaboration towards a shared goal. At our Macclesfield site in the UK, a comprehensive framework is in place to assess pack readiness and ensure a seamless transition to digital formats. This involves preparing over 4,000 Stock Keeping Units (SKUs) for a not-too-distant future where digital information for medicines is the norm.

Our approach to implementing ePI has been a deliberate exercise in starting small and scaling. In an ideal scenario, adopting new sustainable manufacturing processes would be swift and straightforward. Yet,

the journey toward integrating digital platforms and sustainable manufacturing throughout production pipelines is complex, with regulatory approvals and engaging with countries critical to enabling a smooth transition.

AstraZeneca is working to accelerate the implementation of ePI together with other pharmaceutical companies, industry associations, patients and healthcare organisations by engaging in policy change, ensuring system readiness amongst healthcare systems and healthcare providers, and through updates to supply chain structures.

Despite existing challenges, the pursuit of digital innovation strategies is crucial for achieving a greener, more efficient manufacturing and healthcare delivery paradigm. It necessitates a concerted effort from all stakeholders across the value chain and the adoption of a holistic approach, that considers every aspect of the transformation, from technology to the needs of patients and healthcare professionals who access ePI.

The ambition of streamlining the delivery of medicine information through ePI, is to enhance the efficiency of healthcare delivery, reduce the risk of medication errors and support the rapid introduction of new medicines to the market.

CASE STUDY

Our Macclesfield site is one of the largest pharmaceutical manufacturing sites in the UK and a significant manufacturing site within the AstraZeneca network. From this site we manufacture, pack and distribute medicines to 117 global markets. Our Macclesfield site is at the forefront of digitisation and our ePI programme has taken learnings from a carton reduction project at Macclesfield which is being used as a pilot study for the next phase of our ePI programme. The project, part of the UK Operations Pack & Asset Standardisation programme, has highlighted some of the challenges in reducing carton sizes at a pack site, as well as the benefits that may be possible once the leaflet has been removed. The project has also set out data analysis for optimal carton sizes which will form a key part of the ePI strategy. Sharing data and digital tools across these complementary

manufacturing programmes will help accelerate carton reduction opportunities and ensure the full benefits of ePI are delivered sooner.

SETTING THE STANDARD

Our vision for ePI reflects a belief which sits at the heart of our industry: that the potential of digital health solutions will be transformative and will herald a new era of sustainable manufacturing and patient care. By championing digital initiatives, we’re addressing the challenges of environmental impact and patient accessibility, setting a new standard that not only resonates across our industry, but also sets a precedent that can trickle into other industries, fostering widereaching societal benefits.

Our multifaceted approach is laying the groundwork for a more sustainable, accessible, and e cient future that benefits patients, health systems, and the planet.

E&L STUDY DESIGN

CONSIDERATIONS FOR CGTS

Cell and gene therapies (CGT) (or advanced therapy medicinal products – ATMPs as they are known in the EU) are a rapidly evolving area of medicine. Over the past 5 years there were reported to be over 3000 CGT trials in various stages of clinical development, with candidates covering more than 100 diseases. CGT involves the transfer of genetic material, via a vector (virus), into human cells which are then re-introduced to the patient. For example, CAR T cell therapy - a new gene is introduced into that patient’s immune cells (T-cell), which then targets the cancer cells.

Treatment involves either patient’s (autologous) or donor (allogenic) cells. These can be either stem or immunomodulatory cells. CGTs aim to treat diseases where treatments are either non-existent or ineffective. The concept behind CGT is to target the exact cause of the disease in order that the patient should no longer have recurring symptoms—ideally after a single treatment.

As the number of CGTs enter pre-approval registration, there has been a corresponding increase in extractable and leachable scrutiny. Extractables and leachables (E&L) testing is an important step in ensuring the safety of CGT products.

The aim of E&L studies is to detect, identify and quantify organic and inorganic chemical substances that migrate, or that could potentially migrate, from components used to

manufacture, store, and administer CGT products, and identify those compounds which could potentially lead to an adverse effect either to patients or impact product efficacy.

Whilst there are several similarities with the manufacturing process for monoclonal antibodies, there are some key differences with how CGTs are produced which can affect the E&L testing strategy.

KEY DIFFERENCES INCLUDE;

Batch sizes – CGTs are usually manufactured in much smaller batches than monoclonal antibody products, the difference in the surface

area of manufacturing process componentry to product contact volume can impact the threshold at or above which the method needs to be capable of detecting extractables or leachables so that they can be reported for toxicological evaluation.

Product formulation – Whilst a number of the solvent systems used to manufacture monoclonal antibodies and CGTs are similar, and the surrogate solvents defined in USP<665> and the BioPhorum extractable protocol can be considered representative for the majority of process conditions Dimethyl sulfoxide (DMSO) is widely used during the manufacture of CGTs therefore, additional extraction with DMSO should be a consideration.

Availability of product – CGTs are typically manufactured in very low quantities and can be very expensive. This can mean that the number of products available for leachable studies is very limited. Therefore, carefully designed simulation studies could be used to help understand the risk to humans. Advice from the regulatory authority would be required prior to using these studies in place of leachable studies.

Over the past 5 years there were reported to be over 3000 CGT trials in various stages of clinical development.

ONE VISION ONE FUTURE ONE SUPPLIER

In today’s ever-changing world, complexity has become an opportunity. An opportunity to create new dimensions, advanced connections and effective solutions together with a single supplier who can provide everything you need to shape the future of pharma.

Continuous production processes have made enormous progress in the pharmaceutical industry. Just a few years ago, pharmaceutical manufacturers still had numerous reservations about expensive conversions, costly revalidation, and highly complex systems. But it is now becoming apparent that continuous manufacturing can also be compact, easy and efficient. The example of a continuous direct compression line from Fette Compacting shows how this can be achieved.

In pharmaceutical and nutrition production, continuous manufacturing is increasingly gaining acceptance as an alternative to the batch-tobatch process. Continuous manufacturing systems enable faster adaptation to changing production requirements. Above all, the system design is now space-saving and operation is easy to learn. Thanks to integrated, fully controllable processes, continuous processes are generally even more reliable and efficient than many batch-to-batch processes. This is why health authorities such as the Food and Drug Administration (FDA) are also supporting the changeover and regard the process as a quality-driven instrument for modernising drug and food production.

AS A TURNKEY SYSTEM

Dr. Marten Klukkert, Vice President Customer Development Centre, Fette

Separation of the process and technical areas facilitates cleaning and conversion of the dosing-mixing unit.

A NEW CONCEPT FOR TABLET PRODUCTION

Fette Compacting has overhauled continuous direct compression and opted for a quality-by-design approach in the process. The advantages of direct compression lie in its wide range of applications, which can be combined with space and resource-saving system planning as well as embedded process analysis technology (ePAT). A newly developed continuous processing system (FE CPS) feeds the powder into the tablet press without additional granulation. Unlike granulation-based production,

this means that several steps are eliminated, which in turn reduces the space required and makes the process leaner.

Together with a tablet press and an operating terminal, the FE CPS forms a complete continuous direct compression line. By testing a wide range of material and process-related scenarios, the system can process a broad spectrum of ingredients in a variable throughput range of five to 200 kilograms per hour. Using six LIW (Loss-in-Weight) feeders, it is capable of dosing and mixing different powdered starting materials and transferring them to the downstream tableting process. The entire system can be integrated on a single level in existing production areas. The process is divided into five stages:

1. Material Feed

Smooth, continuous tablet production starts with the material feed. If powders with special properties are used – such as density, flow characteristics, cohesion or adhesion – the refilling process is susceptible to sticking, bridging and other powder phenomena. A special design therefore ensures reliable operation in the FE CPS: an automatic refill system (ARS) with special screws was specially developed for the material feed openings of individual ingredients or premixes. This system feeds even demanding raw materials evenly into the dosing process.

2. Dosing

The second step uses up to six gravimetric (Loss-in-Weight, LIW) powder feeders. The concentration of the respective material for each dosing unit is stored in the cross-system product recipe. The control system automatically calculates the feed rate in combination with

the required system throughput.

The LIW feeders use twin screws to feed the material into the next process step at the required feed rate and with minimum feed variability.

3. Mixing

The mixer used differs significantly from conventional horizontal mixers: it comprises two consecutive but decoupled mixing zones, eliminating the dead zone in the intermediate area. Each mixing zone has two inlet openings with a combination of downpipes and transfer hoppers. This allows mixing processes with high and low shear energy to be

combined in a single mixer and optimum results can be achieved for the respective recipe requirements. Which outlet of the dosing unit is connected to which inlet of the mixer depends on the specific hopper combination. Various hopper configurations ensure great flexibility, determining the individual mixing time for each ingredient. This guarantees the best possible process settings for a wide range of formulations.

4. Quality Control via ePAT

Embedded process analytical technology (ePAT) can be used in four different positions. A near-infrared sensor (NIRS) checks the homogeneity of the blended powder (BU, blend uniformity) using chemometric prediction models of the active ingredient concentration. The sensor for BU measurement can be installed at three different positions: at the outlet of the mixer, at the filling tube of the tablet press, or in the Fill-OMatic. This allows the system to be permanently monitored and quality deviations to be responded to directly. At a fourth possible ePAT position, a TU (tablet uniformity) sensor uses NIRS to measure 100 percent of the tablets produced shortly before they are ejected from the die table and is capable of directly rejecting OOS (out of specification) material.

Continuously recording and optimising the mixing process is particularly relevant in product development. NIRS detects most active ingredients in the

Fe e Compacting has overhauled continuous direct compression and opted for a quality-by-design approach in the process.

spectral range of 750 to 2,200 nanometers by penetrating the beams deeply but without causing damage. The robust system is compliant with good manufacturing practices in pharmaceutical production (cGMP) and can be installed and removed entirely without tools. Centralised control is ensured by the human-machine interface of the tablet press.

5. Conveying

Classic systems generally use gravity to transport the powder mixture to the inlet of the tablet press. However, this design requires production areas with high ceilings. The transport system developed by Fette Compacting, on the other hand, uses dense phase conveying to transport the product on a single level without the risk of segregation. The mixture easily reaches the inlet of the tablet press via a conveying hose up to 10 meters away. This allows companies to install the FE CPS system and the tablet press in separate rooms if required. As a result, installation in an existing production plant does not require any major modifications.

A COMPLETE TURNKEY SYSTEM

This combination of lean system design and integrated process analysis has not only proven itself in field trials with customers, but has already impressed several other companies, too. Numerous tests with different materials have confirmed the key benefits: simple set-up, high product quality, and consistent throughput. It has also transpired that batch production recipes can often be processed on a continuous system without changing the ingredients. This provides users in tablet production with a complete turnkey solution for continuous manufacturing.

BORMIOLI PHARMA: Supporting the Sustainable Transition of the Pharmaceutical Industry

Bormioli Pharma is raising the bar for sustainability within the industry. The company’s Environmental, Social, and Governance (ESG) Report illustrates a commitment to responsible growth.

Accountable Transparency, Strengthened Governance and Robust Targets

Bormioli Pharma proceeded with external assurance of their 2023 report two years ahead of legal obligations. This measure underscores the company’s dedication to transparency and accountability, setting a benchmark for other players in the industry.

To further bolster its ESG initiatives, Bormioli Pharma reinforced its ESG team and governance in 2023. By defining its ESG Policy, the company ensures that sustainability is woven into every facet of its operations.

Bormioli Pharma is taking strides to adopt the new reporting system required by the EU Directive Corporate Sustainability Reporting Directive. This forwardthinking approach will enable the company to meet and surpass evolving regulatory requirements, ensuring it remains at the cutting edge of sustainability in the pharmaceutical industry.

The company has set ambitious targets to significantly reduce its environmental impact. By 2030, it aims to cut Carbon Intensity by 30% and Water Withdrawal Intensity by 41%, compared to the 2021 baseline.

Furthermore, Bormioli Pharma is making progress towards increasing the share of sustainable materials in sold products. In 2023, the company reached 45%, a

15% increase from the previous year. This advancement brings the company closer to its target of 50% by 2025, underlining the company’s dedication to transforming the industry’s material usage.

EcoPositive, the Widest Sustainable Packaging Range in the Pharmaceutical Industry

EcoPositive encompasses three different approaches: Regenerate, Renew, and Reloop. The Regenerate approach involves recycling glass and plastic packaging from firstchoice waste collection. This includes rHDPE, Mechanical rPET and Advanced rPET bottles, which are produced through a depolymerisation process that achieves a “virgin quality” polymer. This innovative process allows for a broader supply of recycled material, exponentially increasing production capabilities.

The Renew approach focuses on bioplastic packaging derived from renewable sources. One example is the bottles manufactured in Bio PET 2.0; a bio-based plastic crafted from wood collected in responsibly managed certified forests. This approach emphasises material efficiency and renewability throughout the product’s life cycle, highlighting Bormioli Pharma’s commitment to resource conservation.

The Reloop approach creates glass and advanced polymer products made from infinitely reusable materials – such as Carbon Capture PET bottles - promoting a circular economy model. EcoPositive constitutes 50% of Bormioli Pharma’s portfolio and this achievement underlines the company’s success in integrating sustainability into its core business operations.

Moreover, Bormioli Pharma has recently announced a collaboration with Loop Industries, Inc. to develop an innovative pharmaceutical packaging bottle manufactured with 100% recycled virgin quality Loop PET resin, derived from lowest quality PET and polyester fiber waste. Bormioli Pharma tested Loop PET resin in its packaging, commissioning independent third parties’ additional analysis to verify extractables levels with different solutions, also taking into consideration the worst-case scenario. The results of these tests set a new benchmark for recycled plastic products within the pharmaceutical industry, as the bottles produced with Loop PET resin do not release any substance deemed of toxicological relevance.

Data-driven Approach and Scientific Analysis: The Key to Combine Safety with Sustainability

Bormioli Pharma’s commitment to sustainability extends beyond product offerings. The company also provides specialised, data-based consultancy services. Bormioli Pharma has presented compelling data proving that sustainable plastic packaging can meet the strictest requirements of the industry in terms of quality and safety. The company’s recent analyses have shown a significant 28% reduction in migrating compounds in bottles produced in rHDPE compared to conventional solutions in virgin HDPE. Even more importantly, Advanced rPET bottles recorded the complete absence of migrating compounds deemed of toxicological relevance. This groundbreaking research, conducted by the specialised laboratory Lab Analysis and reported by Tecnopolo Mario Veronesi Institute, part of the Democenter-Sipe Foundation, represents a shift for the sustainable packaging adoption in the pharma industry. It provides irrefutable evidence about the safety of recycled PET, achieving excellent results even better than virgin PET ones.

Conclusion

Bormioli Pharma is not only a leader in pharmaceutical packaging but also a trailblazer in sustainable practices. The company’s ESG efforts and EcoPositive portfolio are setting new standards for the industry, generating value for people, the environment, and society.

Jai: How would you describe Renaissance’s mission and values?

Eric Kanpes: As a patient focused organisation, we aspire to bring important life-changing drugs to patients and to fulfil unmet clinical needs across the globe. We pride ourselves on producing safe, innovative, reliable, lifesaving medicines for the benefit of patients on behalf of our customers.

At Renaissance Lakewood, we have four core commitments that inform our values:

1. Patients are at the centre of everything we do

2. Employees are treated with integrity, and respect 3. We are committed to superior ethical performance 4. We aspire to be upstanding corporate, cultural, and healthcare citizens

Our values are all about teamwork, showing up for each other, being accountable, and always trying to be our best. By upholding these commitments and having our values guide every decision we make, we support our clients in delivering their pioneering new products to market with regulatory approval so they can make an impact on patients’ lives.

RENAISSANCE LAKEWOOD

finish dosage forms. This allowed Renaissance Lakewood to further sharpen our expertise on nasal development and delivery. We tapped into the prescription nasal spray market during its early stages when it was an emerging delivery system recognising that drug-device combination nasal sprays offered something truly unique.

In an interview with Jai McIntosh, Editor for EPM, Eric Kaneps, VP, Sales and Marketing at Renaissance Lakewood explores how innovation has been at the heart of the success of the company and the market. He also provides his unique insights into some of the challenges nasal spray developers are currently facing.

Jai: Can you provide a brief overview of Renaissance’s journey and key milestones?

Eric Kaneps: Renaissance Lakewood, LLC is a US-based CDMO specialising in nasal sprays. I originally joined the company in 2001, when ‘Renaissance Lakewood’ was called ‘DPT Lakewood’, owned by the large dermatologic group, DPT Laboratories. In 2012, DPT was acquired by Renaissance Acquisition Holdings, LLC, a portfolio company held by RoundTable Healthcare Partners, a private equity company focused on healthcare investments. In mid-2016, the dermatologic division was divested to Mylan, Inc. and DPT Lakewood, LLC was renamed and repositioned as ‘Renaissance Lakewood, LLC’, reflecting our rebirth as a new standalone company.

Throughout all these changes, one aspect remained consistent: For over 25 years, we have effectively supported the development and manufacture of our client’s nasal sprays and sterile products.

In the early 2000’s, Renaissance Lakewood was mainly focused in the over-the-counter (OTC) medicine manufacturing space while supporting some unique pharmaceutical preparations. We later divested our OTC business and pivoted to prescription pharmaceuticals, and more specifically, nasal and aseptic fill/

Beginning in 2020, we further narrowed our focus on two offerings: aseptic development and manufacturing for preservative-free multi-dose nasal and injectable therapeutics, as well as non-sterile manufacturing for microdose and preserved multi-dose nasal & oral sprays. Although we were previously involved in several different treatment areas across the sector such as sterile topical ointments and ophthalmic drops, our expertise was spread too broadly. By narrowing our offering, we were able to focus our business model and provide best-in-class service in nasal and injectable development and manufacturing.

Jai: What do you think is the reason for the growth in nasal sprays in the United States?

Eric Kaneps: The European market has embraced nasal drug delivery for years. One can find multiple nasal sprays widely available in European pharmacies, while until recently, one could find just a few in US pharmacies, typically in the allergy space. With over-thecounter naloxone nasal spray being widely available, US consumers are normalising to the non-allergy nasal applications and are embracing this delivery

format, leading to the growth of this sector.

The driver behind this change rests in the fact that delivery via injection or rectal delivery is generally unpleasant, requires training and is commonly associated with fear and discomfort. Nasal sprays can provide needle-like uptake while offering an improved patient experience with ease of use.

The US pharma industry is waking up to the need for more patient-centric, innovative options as well as more sophisticated delivery methods to provide patients with these benefits.

Jai: Do you feel the pressure to innovate to ensure the company remains in line with sustainability goals?

Eric Kaneps: Sustainability is a hot topic in Europe, and we embrace the opportunity to support our clients in their green initiatives. As one example, we have developed a more efficient and compact packaging range. With our reduced packaging footprint, we can get these devices into a smaller blister and carton, taking up less shipping space, as well as reducing material consumption and waste.

The key to a successful partnership that embraces sustainability relies on partnership with the client, where both parties take steps to ensure practices strive towards eco-friendly goals.

Jai: What challenges have Renaissance encountered in pharmaceutical manufacturing, and how have these been overcome?

Eric Kaneps: The growth of the business has been rapid. As a result, a predominant hurdle has been keeping up with demand to ensure we meet the needs of customers and patients. Embracing innovation in our strategies and methods has been key to overcoming this issue.

Additionally, complexity in packaging is a challenge many developers and manufacturers face, especially since not every market wants everything written in English. Effectively packing for different countries requires a thorough understanding of the regulatory requirements and quality expectations for each, as well as the need to adopt different strategies for small countries and large countries. We’re currently refining our approach to address these matters to keep up with the expanding demand that comes from being a global player. Despite these ”growing pains”, providing global support has added tremendous value to us and our partners.

Jai: Could you share a specific instance where Renaissance’s technological advancements have positively influenced the manufacturing process?

Eric Kaneps: Renaissance Lakewood provides a fullservice offering, so we can support our clients from concept all the way to approval. For a CDMO to effectively support a project, they must work closely together with the client. This ensures the free flow of information from the early stages of development to provide a greater understanding of the characteristics of the API and help elucidate a clear pathway

to commercialisation. With this in mind, we always aim to be involved from day one.

As a specialist in nasal spray development and manufacturing, we get to work on some very exciting, innovative projects that have the potential to radically change how some illnesses are treated. We are driven by the knowledge that the products we develop, and manufacture really do make a difference and know that many of the programs we have supported are truly changing the quality of people’s lives.

Jai: How does Renaissance ensure that it stays at the forefront of innovation in manufacturing?

Eric Kaneps: When it comes to nasal development and manufacturing, we have always been at the forefront of innovation. Since day one, developing partnerships with leading device manufacturers has led to innovation at Renaissance Lakewood and has been key to our success. By working together, we can help realise the commercial potential of our clients’ novel formulations. With an established micro-dose platform and other unique devices entering the market, we can make a real difference in the lives of patients, offering them broader treatment options and the potential for greater therapeutic benefits.

Over time, the market has become noticeably more competitive, further emphasising the need to remain at the forefront of innovation. However, it is important to remember that adopting innovation can be both high risk and high reward. Many of the products we manufacture are lifesaving, and as such, a defective product can have significant implications for patients and the marketer. Three years ago, we made the bold decision to purchase a pioneering manufacturing asset that was like nothing else available in the market from a throughput and quality perspective.

In a fast-evolving delivery system like nasal sprays, you must never get complacent. Contract manufacturing companies must always be striving for improvement. I've been in this business long enough and have seen other companies fall into the trap of stagnation. Without reinvesting or planning, companies in this space will quickly be outmanoeuvred. Innovation is at the heart of Renaissance Lakewood, so I am confident in its continued strong position leading the field.

e US pharma industry is waking up to the need for more patient-centric, innovative options as well as more sophisticated delivery methods to provide patients with these bene ts.

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Embracing Innovation

Geert Vleugels, General Manager NL, Tjoapack

TO MEET THE FUTURE PACKAGING NEEDS OF A GROWING BIOLOGICS PFS MARKET

The pre-filled syringe (PFS) market is growing rapidly, driven by the rising need for innovative biologics and a desire for selfadministration treatment options offering greater convenience. This increased demand for PFS is fuelling innovation in mainstream packaging design to support advancements aiding both useability and patient safety.

However, supporting the PFS packaging needs of the expanding biologics market comes with many challenges. These include carefully selecting the right packaging solutions for each project and potentially committing considerable capital expenditure to upgrade manufacturing lines. As a result, adopting new PFS packaging and harnessing new technologies could be a

daunting task, particularly for smaller biologics developers.

In this article, Marcelo Cruz, VP of Business Development and Marketing of Tjoapack, examines the driving forces behind PFS packaging innovations and highlights the need for partnerships with packaging experts to provide more patient-centric and safe therapies to patients.

THE RISING DEMAND FOR PFS IN THE BIOLOGICS SPACE

Over the past decade, the injection market has rapidly evolved, with demand for PFS, as opposed to traditional syringes, steadily increasing over several years. Between 2022 and 2023, the global PFS market expanded from $6.39 billion to $7.29 billion at a compound annual growth rate (CAGR) of 14.0%. By 2027, this market is anticipated to reach a value of $12.19 billion, with a CAGR of 13.7%.

Two key areas are driving the rising demand for PFS drug delivery:

1. The expanding biologics market

Since their introduction, biologics have continued to transform a wide variety of therapeutic areas, including dermatology, immunology, endocrinology, ophthalmology and oncology. With a growing demand for innovative therapies and the rising burden of chronic diseases, biologics now constitute approximately 44.7% of the drug development pipeline. This percentage is predicted to continue to grow, with the global biologics market size expected to rise from $348.03 billion in 2022 to $620.31 billion in 2032, at a CAGR of 6%.

The loss of patent exclusivity of the leading biologic drugs is also fuelling the expansion of the biosimilars markets. As of December 2022, the U.S. FDA has approved 40 biosimilars. With many blockbuster biologics set to come off patent by 2030 — including AbbVie’s antiinflammatory treatment Humira and Merck & Co.’s top-selling cancer medicine Keytruda — the biosimilars market is also

expected to rapidly expand.

Due to their sensitive nature, biologics are typically administered parenterally and not orally to avoid the harsh conditions of the gastrointestinal tract and firstpass metabolism. As a result, most biologics are still delivered via injection. Consequently, the biopharma industry is seeing greater demand for new packaging solutions for injectables.

2. A need for selfadministration options Treatment options enabling self-administration can help improve patients’ well-being by giving them the confidence to manage their health and freeing them from the inconvenience of frequent travel to the clinic.

However, self-administering injectable medicines has not always been easy for patients, with difficulties involved in manual syringe preparation and the potential risk of contamination or other errors.

The pharmaceutical industry has invested extensive research and development (R&D) efforts to create an optimal user experience and realise the potential of self-administration.

One outcome of R&D efforts in the pharmaceutical industry has been the PFS. This revolutionary device comes already charged with a single dose of the drug product, helping to prevent under or over-dosing, and ensuring both patient safety and convenience.

Drug developers have increasingly harnessed PFS in the delivery of a wide variety of biologics. Research on the global PFS drug molecules market indicates that among

drug classes, vaccines will lead the market with a projected revenue of over $23 billion by the end of 2027 while insulin will have a higher growth rate. With this rising demand, PFS have consequently become the primary alternative to multi-vial solutions for biologics, as well as small molecule drugs.

SECONDARY PACKAGING SUPPORTING THE RISING PFS NEED FOR BIOLOGICS

Packaging has always been essential in safeguarding the integrity of medicines while enhancing ease of use and supporting compliance. It is vital for biologics leveraging PFS to have the right packaging to ensure safe and correct administration for patients and to enable this delivery system to live up to its full potential.

By embracing packaging innovations, drug developers and manufacturers can overcome future challenges to continue to meet patients’ PFS needs with agility and flexibility. As we look to the future, meeting the needs of biologics relying on PFS will require further advances in technology in the secondary packaging space in several ways:

1. Protecting the stability of sensitive biologics

With rising numbers of biologics in the pipeline, developers and manufacturers must ensure their secondary PFS packaging protects against breakage of the primary packaging and prevents the potential exposure of these sensitive drugs to the environment. Many biologics, including vaccines, require temperature-controlled transit to ensure the product remains stable, safe and efficacious until it reaches the patient.

As we look to the future,

biologics producers will embrace technologies such as smart labels containing radiofrequency identification (RFID) or near-field communication (NFC) to minimise the risk of temperature anomalies. These innovative technologies can be added to product packaging to monitor the conditions and temperatures each product unit experiences in real time as it is transported through the supply chain. With processor cores that enable real-time monitoring of the temperature near the product unit, smart labels can send the data to nearby receivers to be fed to a central database.

As a result, pharma companies leveraging smart labels will be able to identify any units that have experienced a temperature excursion for safe disposal. They also provide data allowing companies and their partners to understand the root cause of an excursion to prevent it from happening again in the future.

2. Enhancing patient convenience and useability

Self-administration of biologics is an established therapeutic option for a wide variety of conditions, including rheumatologic, immunologic, neurologic, dermatologic, gastrointestinal, and endocrine diseases. As the demand for self-administration treatment options rises, secondary packaging will be integral in providing greater convenience and comfort for patients receiving biologic therapies.

The right secondary packaging will support efforts to enhance the useability of the PFS by including vital additional materials, such as replacement needles or swabs, usage instructions and

other information. For patients to prepare the PFS, inject themselves comfortably and safely, and then dispose of the device, the instructions included as part of the secondary packaging must be easy to read and understand.

Looking ahead, further developments in kit packaging — and the manufacturing equipment to support kitting — could make self-administration with PFS even easier. Packaging alternative, more ergonomic PFS grips within a kit could for example provide more options for patients to help them find the right grip to administer their treatments effectively and with minimal discomfort.

By enabling the inclusion of new components, accessories, and alternative grips, even patients with manual dexterity issues could see enhanced useability, helping them to feel more confident while giving them more independence and autonomy.

3. Protecting against criminal activity

Counterfeit drug products pose a significant threat to patient safety and undermine global supply chain integrity. In 2021, seizures of counterfeit drugs increased by 101% from the previous year, resulting in a pressing need for more robust packaging solutions to prevent drug counterfeiting.

Serialisation provides a comprehensive means of ensuring the traceability and authenticity of drug products throughout the supply chain. However, compliance with increasingly stringent serialisation regulations in the US and the EU is a challenging prospect for many companies in the pharmaceutical industry.

Biologics developers and manufacturers will increasingly rely on smart labels to support serialisation while preventing falsified medicines from entering the supply chain.

Carrying more information than traditional labels, smart labels support the latest serialisation regulatory requirements, furthering efforts to harmonise data systems across the pharmaceutical supply chain. They are also easier to scan during transport as they do not need to be near the reader.

4. Preventing tampering

Tampering is another risk to patient safety and can involve falsifying the chain of custody of medication through the changing of labels or serial numbers or opening of packaging to change the product within it for a substandard alternative. It is estimated that 13.6% of medicines in low- and middle-income countries are substandard or falsified.

Patients risk not receiving critical medications if they are tampered with. If patients become ill from consuming counterfeit medicines, the company’s reputation could also be at serious risk.

Most prescription medicines and some over-the-counter drugs supplied in the EU are already required to have an anti-tampering device on their outer packaging and a unique identifier. These can be in the form of:

• Blister packs for oral solid dose products

• Perforated caps for liquid products

• Foil stickers across secondary packaging closures With ongoing innovation

focusing on finding new solutions to eliminate tampering that might not be immediately visible while making them more efficient to install throughout filling and packaging, biologic PFS will be safer for patients in the future.

FACILITATING INNOVATION THROUGH STRATEGIC PARTNERSHIPS

Harnessing new packaging technologies for the first time can be a daunting task, with significant capital expenditure needed to purchase and install new equipment. Due to the complexity involved, more biopharma companies are looking to CPOs for support in leveraging the latest packaging innovations.

Forgoing the need to invest in equipment, biopharma companies can rely on CPOs with the infrastructure and capacity to fill and seal high volumes of PFS in a sterile environment. This also helps to ensure compliance with stringent regulatory requirements such as Annex 1 of the EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use.

Additionally, CPOs can offer biopharma manufacturers expert insight into the unique packaging needs of different products, leveraging their unique role in the supply chain. Providing value for their partners in the long term, CPOs can also ensure the flexibility and capacity needed to develop customised packaging services.

By working together from the onset of a project, CPOs and manufacturers can combine their expertise to optimise cost and time efficiencies. A collaborative approach also promotes improved packaging design sustainability and can enable a streamlined time-to-market.

THE FUTURE OF BIOLOGIC SECONDARY PACKAGING

In the rapidly growing biologic PFS market, packaging is set to play a vital role in the sector’s success for years to come. With many innovations anticipated in the PFS packaging space supporting improvements in useability, convenience of selfadministration and safety, embracing advancements is more important than ever. Helping to overcome the challenges of adopting new PFS packaging, CPOs are enabling their customers to avoid the considerable capital expenditure needed to upgrade manufacturing lines while providing expert insight and efficiency.

Close partnerships with experts who specialise in packaging will be crucial for pharmaceutical companies to thrive as we enter a new era of PFS therapeutics.

In

2021, seizures of counterfeit drugs increased by 101% om the previous year, resulting in a pressing need for more robust packaging solutions.

The peptide drug market occupies a distinct space between small molecule drugs and biological products, offering unique therapeutic properties (Figure 1). With approximately 80 peptide drugs on the global market, over 150 in clinical trials, and between 400 and 600 undergoing preclinical development, the pharmaceutical industry’s interest in peptides has surged in recent years. Valued at USD $38 billion in 2023, the global peptide therapeutics market is expected to grow at a compound annual rate of 10.8%, driven by increasing cancer and metabolic disorder incidences like osteoporosis, obesity, and diabetes.

Furthermore, peptides can be chemically synthesised in large quantities, reducing production costs and streamlining manufacturing processes compared to biologics. Peptide synthesis is also incredibly flexible, allowing for fine-tuning physicochemical properties, such as solubility and hydrophobicity, to optimise drug delivery and efficacy. This can make the manufacturing and development process more straightforward.

Head of Peptide Science at Biosynth

The Challenges of Therapeutic Peptide Development

certain amino acids, such as histidine, presents challenges in maintaining the desired peptide configuration and can impact peptide functionality.

Target identification and validation: Identifying and validating molecular targets is complex, requiring thorough validation processes to ensure reliability.

Lead identification and optimisation: The process of lead identification, screening, and optimisation demands careful consideration of time and resource constraints, as well as the quantity of materials needed.

However, there are still difficulties encountered in peptide drug discovery and development, especially those that are tricky to make, for small-scale clinical trials moving to larger-scale commercial supply. Contract Manufacturing and Development Organisations (CDMOs) have become critical components in overcoming these challenges by offering expertise and experience that can help develop strategies to realise time and cost savings.

CHALLENGES ALONG THE PIPELINE FOR PEPTIDE MANUFACTURING

Peptide Design

One of the commonly employed approaches in peptide discovery and design is to screen combinatorial libraries, comprising a myriad of peptide variants of either chemical or biological origin. These libraries serve as repositories for screening, allowing researchers to identify peptides

with desired therapeutic properties. However, navigating the landscape of peptide sequences to uncover promising leads is akin to finding a needle in a haystack.

Screening methods, such as phage display, allow for high-throughput screening of peptide-protein interactions, facilitating the identification of promising lead candidates. However, while this approach holds theoretical promise, several practical challenges must be addressed:

Intellectual property (IP) infringement: There is a risk of inadvertently infringing upon existing patents or IP rights when exploring peptide sequences.

Chemical or physical stability: Peptides are susceptible to degradation, and issues such as incompatible side chains can compromise their stability and effectiveness.

Racemisation: Racemisation of

Using an appropriate CDMO can provide access to vast peptide libraries and high throughput screening services. These services can support a wide range of scientific applications, including peptide libraries, protein characterisation, epitope mapping, and various high-throughput screening processes. Also, CDMOs offer flexibility to accommodate specific requests, providing linear peptides and those with complex folds, disulfide bonds, posttranslational modifications such as ubiquitin.

Regulations

As promising candidates progress through clinical development, it is essential to ensure consistent and high-quality production. Peptide manufacture must be done complying with Good Manufacturing Practice (GMP) and ISO 9001 standards. Additionally, comprehensive Quality Assurance (QA), Quality Control (QC), and In-Process Controls (IPCs) protocols are essential for meeting the stringent requirements of regulatory bodies such as the European Medicines Agency

Peter Timmerman,

Figure 1: Comparison of small molecules, peptides, and biologics, and their key manufacturing characteristics

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(EMA) and Food and Drug Administration (FDA). For example, the EMA has implemented new regulations governing the introduction of a new supplier, requiring the production of two pilot scale Active Pharmaceutical Ingredient (API) batches by the new supplier, which must undergo comparison with those from the original supplier. These evolving regulatory landscapes highlight the necessity of partnering with a proficient CDMO equipped to navigate complex regulatory requirements, while ensuring the successful development and commercialisation of peptide therapeutics.

Peptide Synthesis

Peptides with intricate folding patterns or unconventional structures require specialised manufacturing processes and analytical techniques to maintain product integrity and purity. The synthesis of peptides often results in various impurities, including those with similar chemical structures, requiring complicated purification techniques. This can be particularly demanding when separating complex peptide mixtures due to their diverse physicochemical properties. Moreover, posttranslational modifications (PTMs) add another layer of complexity, requiring sensitive and robust analytical methods for detection and quantification.

The ability to produce long, complex peptides while

avoiding substantial amounts of contaminants is notably constrained with traditional peptide synthesis methods like Solid Phase Peptide Synthesis (SPPS). Chemoenzymatic peptide synthesis (CEPS) now serves as an alternative to conventional chemical peptide synthesis, due to its excellent regio- and chemo-selectivity, mild reaction conditions, and low waste generation. CEPS is ideal for production of small proteins up to 160~200 amino acids in length and can address PTMs as part of the same process.

Scaling Up

Large-scale peptide synthesis entails more than just increasing the quantity of raw materials in the process. Scaling up peptide production often requires the development of de novo protocols to ensure the maintenance of quality standards throughout the manufacturing process. In addition to potential operational and manufacturer changes, this can disrupt production timelines and increase costs.

Additionally, as the complexity of synthesised molecules increases, yields may decrease, necessitating innovative strategies to optimise reaction efficiencies and maximise product yields. These manufacturing processes use enormous amounts of solvents and produce considerable quantities of waste, especially the purification step. Managing solvent usage and waste

disposal is increasingly critical to minimise environmental impact and comply with regulatory requirements.

Support Through the Entire Drug Journey

Time lost due to inefficiencies in library screening, lead optimisation, or clinical trial delays can significantly impact project timelines and budgetary constraints. Moreover, the inherent complexities of peptide synthesis and manufacturing further exacerbate the time-sensitive nature of drug development. Each additional day spent navigating regulatory hurdles or troubleshooting manufacturing issues represents lost opportunities and increased risks.

As peptides continue to rise in prominence, outsourcing development, and manufacturing to CDMOs has become a strategic choice for many pharmaceutical companies. CDMOs offer specialised expertise, state-ofthe-art instrumentation, and a deep understanding of peptide design and synthesis, ensuring high-quality and compliant results.

For example, even support when ordering peptides can be crucial to ensure that customers fully understand the naming conventions for amino acid forms (L- and D- isomers) and so are ordering the correct peptide for their required activity.

ABOVE:

Figure 2. Biosynth can support the entire drug development journey and peptide production needs

By offering comprehensive support throughout the drug development journey, CDMOs, such as Biosynth, help to streamline processes, reduce transfer times between contractors, and ensure consistency across manufacturing processes (Figure 2). In fact, several studies have indicated that by working with a single CDMO as their development partner, biomanufacturers can significantly shorten timelines and reduce costs.

CONCLUSION

While peptides hold immense promise as therapeutic agents, their development is fraught with challenges across discovery, design, synthesis, and manufacturing. Overcoming these hurdles requires a multidisciplinary approach, combining innovative technologies with rigorous validation processes and strategic partnerships. By providing expertise in process optimisation, analytical development, and manufacturing scalability, CDMOs enable drug development companies to overcome challenges and accelerate the transition of promising leads through to the manufacture of transformative therapies for patients in need.

MAMMALIAN BIOPROCESS INTENSIFICATION for Monoclonal Antibody Production

THE NEED FOR INTENSIFIED PROCESSES

Bioprocess intensification represents a key strategy for the biopharmaceutical industry as it helps achieve more sustainable and efficient processing, while reducing the cost of goods manufactured (CoGs) and energy consumption per gram of product produced. Higher titre in the bioproduction process is the most significant driver to reduce CoGs. The primary separation and purification processes provide the best opportunities to reduce materials and water consumption.

Jean Aucamp, Associate Director, Biologics R&D, Lonza

Recently, several technologies and strategies for process intensification have become available and are increasingly deployed in manufacturing settings. There is a strong interest from therapeutics providers in implementing process intensification for both new and existing products across all manufacturing scales. At the same time, manufacturers are considering ways to improve the utilisation of existing equipment and producing more

product within the existing facility footprint.

CONSIDERATIONS FOR PROCESS AND TECHNOLOGY SELECTION

The introduction of new technology is often associated with a significant capital cost. To rationalise the investment, it is important that the new technologies are readily scalable, applicable to produce a broad range of product modalities, and compatible with

legacy products or processes.

Some of the technologies used to intensify production, primary separation and purification are described in this article, along with considerations for the successful implementation thereof.

INTENSIFICATION OF THE PRODUCTION PROCESS

One approach used to intensify production processes relies on a perfused N-1 step to generate very high cell density cell cultures used to inoculate the production bioreactor. As a

result, the growth lag phase in the main production bioreactor is significantly reduced, leading to both the cell culture reaching maximum viable cell density sooner and the product accumulating more rapidly. Typically, the intensified fedbatch is operated for a shorter period than the traditional fed-batch process. In spite of the shorter production length, a significant increase in titre and product per batch are achieved. This has been demonstrated for both mAb and bsAb modalities. An additional benefit stemming from the shortened production process is the increase in the number of batches in a facility.

To benefit from this applied process, change and higher productivity, the product quality (glycation, charge variant and product related impurities) needs to be comparable with that of a traditional fed-batch process. To achieve this, a suitable aeration strategy needs to be developed.

In addition, another key consideration is the facility’s media production and storage capabilities to meet the increased demand of the N-1 perfusion stage.

PAT AS A KEY ENABLER

Raman spectroscopy and the associated chemometric models are pivotal for measuring the concentrations of glucose and key amino acids nutrients in situ. Similarly, in situ capacitance sensors provide reliable measurement of the culture’s cell density, enabling the automation of inoculation processes.

During the N-1 stage, the perfusion and glucose feed rates are based on the cell mass and prevailing glucose concentrations in the bioreactor. Both glucose and media

component feed rates are tightly controlled based on concentration measurements using Raman spectroscopy as a process analytical tool (PAT).

Implementing regular concentration measurements in high cell density cultures ensures that rapidly consumed key nutrients are not depleted, detrimentally impacting cell viability. Similarly, it prevents the presence of excess nutrients, which may alter the cell metabolism and product quality profile. Applying the same feed control strategy in both traditional and intensified fed-batch production processes greatly improve the likelihood of a successful conversion where product quality remains comparable.

CHALLENGES FOR THE PRIMARY SEPARATION STEP

The higher cell density, increased titre, and shortened production times put pressure on primary separation and purification processes.

While depth filtration is a workhorse as the primary separation step for bioreactor volumes up to 2,000 L, it is not readily amenable for use with high cell densities or multiplexed production strategies. Single-use continuous discharge centrifugation is an alternative technology demonstrated to robustly clarify cell culture over a broad range of cell densities. A key consideration for this approach is the integration of such a system with a subsequent fine-grade depth filtration stage. Replacing an entire course depth filtration stage with centrifugation also significantly reduces in-depth filter area requirements and the associated waste disposal.

The similarity between single-use and stainless-steel centrifuges brings the potential benefit of a simplified scale-up with minimal process change for this part of the process. A key consideration upon further scale-up will be the impact of high cell densities on the interval length of the intermittent discharges for this type of stainlesssteel centrifuge.

Higher cell densities and product titres are inevitably associated with elevated concentrations of host cell proteins and nucleic acids. Suitable charged fine-grade depth filters have been demonstrated to provide a significant reduction in nucleic acid concentrations. A moderate reduction in host cell protein concentrations may also be achieved, but the challenges are more reliably addressed in the affinity capture step.

CHALLENGES FOR THE CAPTURE STEP

Increased titre can adversely affect the duration of this process step. The capture step’s productivity, therefore, must increase suitably to match that of the bioreactor. While diverse technical solutions are available, several criteria must be simultaneously met:

1) increased use of available binding capacity to reduce chromatography media used, especially in a clinical manufacturing setting,

2) increased number of cycles to make better use of the resin lifetime,

3) reduction in buffer consumption on a product per mass basis,

4) increase in product concentration in the eluate to limit intermediate volumes, and

5) wide selection of affinity ligands to broaden product coverage.

An approach combining a high binding capacity Protein A resin, reduced column bed height and multi-column chromatography meets all the criteria. Placing columns in series during the load stage allows for greater resin utilisation, directly impacting the resin volume required. Short bed height columns operate at higher linear flow rates, reducing cycle time, allowing for more cycles to be completed. By modifying the elution buffer conditions and utilising resins with milder elution pH, lower eluate volumes and higher product concentrations are achieved without impacting product aggregate formation. A continuous load strategy provides more flexibility to tailor for either a short process time or low resin volume requirement.

FUTURE OUTLOOK

With the global biopharma industry maturing from focusing on blockbuster drugs towards more specialised and diverse biologics, there is a need for flexible and robust manufacturing strategies that provide supply for a varied range of market needs, while improving drug accessibility for patients with unmet medical needs. Process intensification fits into this changing landscape by providing processes that are more robust, economic and sustainable. The next step on the horizon will be advancing digitalisation aspects and using data-driven simulations to optimise processes.

THE FORMULATION BALANCING ACT:

Overcoming Composition and Manufacturing Challenges

Nandu Deorkar, Ph.D., MBA, Senior Vice President, Research & Development — Biopharma Production, Avantor

Monoclonal antibodies (mAbs) are a class of therapeutic proteins used in the treatment of cancers, autoimmune diseases, and other chronic diseases. Though these drugs have been on the market for 20+ years, with over 100 approvals, efforts are continuing to enhance efficacy, safety, cost-efficiency, and patient access.

Though many mAbs are developed with low protein concentrations and administered through an IV, there has been a shift to intramuscular or subcutaneous (SC) injections, mainly so that a patient can self-administer the drug at home. This patientfriendly approach has grown from the desire to reduce hospital stays and/or treatment costs while increasing patient compliance.

Biopharmaceuticals intended for SC injection create two distinct challenge areas when it comes to formulation development. One, they must be developed at a high concentration to ensure dose delivery volume does not exceed 1 – 2 ml, as larger doses are not well tolerated by the patient. Additionally, manufacturing challenges, including the risk of crosscontamination in fluid handling and losing valuable products while sampling must be overcome to ensure patients have access to critical therapies.

PHARMACEUTICAL CHALLENGES

High concentration mAbs are formulated at acidic pH with a

variety of stabilising agents including buffers, tonicity adjusting agents, antimicrobial preservatives, and stabilisers. Viscosity-reducing agents like arginine, histidine and polysorbate are also commonly used.

The wrong formulation of these various chemicals can lead to pain and pressure at the injection site. The root cause of this response differs, but may include buffer type, pH, temperature, viscosity, tonicity, individual experience, speed of injection, needle size, anatomical region, and dose volume.

commonly used derivatives of arginine, histidine, lysine and serine. Their ability to reduce viscosity of high concentration protein formulations and prevent degradation across a wide range of concentrations may offer manufacturers greater flexibility for production and storage conditions.

Loss of stability in mAbs formulations is a common issue to contend with. However, high concentration formulations increase the solution viscosity, which can lead to difficulties in manufacturing and possible product loss. High concentrations also create undesirable protein-protein attractive interactions that leads to high aggregation and low stability.

Finding new approaches to formulation development, or the process of creating a final product that maintains stability and potency throughout its lifecycle, is thought to be the key to solving the challenges of injection administration, time, and pain at the site.

EXCIPIENT SELECTION

Typical approaches to solve viscosity challenges have centered around formulation development using a combination of amino acids and salts. Researchers have studied the effect of various amino acids and their acetyl and propionyl derivatives on the viscosity, protein-protein interactions, physical and chemical stability of mAbs. Two amino acid derivatives, bis acetyl lysine and propionyl serine, showed superior performance in comparison to

Commercial formulation development activity is typically undertaken after initiation of phase I development. During the discovery and preclinical development phase there is little information of molecule behaviors. In some instances, the default formulation with phosphate buffer may impact the stability of the molecule providing false negative results due to molecule degradation or aggregation. This uncertainty is addressed by using functional excipientbased platform formulation in the development phase. We have evaluated platform formulation by designing several mAb products using functional bis acetyl-lysine. Figure 1 (above) demonstrates the potential of such platform formulation in improving stability by minimising deamidation of each molecule that can eliminate issues during discovery and development phase.

Finally, surfactants may also play a part in pain levels at the injection site. For example, Polysorbate 80 has been shown to cause hypersensitive reactions in patients; illustrating the need to properly control surfactants, as well as excipients, when

formulating high concentration mAbs.

BUFFER SELECTION

Buffer selection and strength has been shown to impact subcutaneous injection-site pain. For example, formulations containing citrate cause more pain upon injection as compared to histidine and saline. Another study indicated that the epoetin alfa formulation using a sodium phosphate buffer was associated with less injection-site discomfort and a shorter duration of pain than the formulation containing a citrate buffer.

One theory is related to the pH at the injection site, which does not dramatically change unless strong ions are used in the formulation as buffering agents. Given that citrate is a strong ion, unlike histidine and saline, the pH change in the SC tissue might be more pronounced upon administration, potentially leading to a more painful injection.

Buffer concentrations, too, affect a patient’s discomfort and local tolerance, including redness and swelling. A study comparing phosphate buffer concentrations of 5 to 50 mM concluded that for subcutaneous injections at non-physiological pH, the buffer strength should be kept as low as possible to avoid pain upon injection.

MANUFACTURING CHALLENGES

Reliable sterile filtration is critical to maximise product recovery and maintain sterility in the final filling process, as is a sampling procedure that is closed and accurate.

The challenge is that this process is not one-size-fitsall; customised and flexible solutions are necessary that

Figure 1: IgG1 formulated at 10mg/ml in 10mM Phosphate, pH 8.0 (designated as bu er in the figure above) with and without the amino acid derivatives bis-acetyl lysine or propionyl serine at both 4°C and 40°C following 8 weeks of storage

fit the molecule, volume, and facility environment. Manufacturers must also ensure adherence to regulatory and quality standards, and ensure product availability with a global, reliable supply chain.

The growing use of modular single-use technologies (SUT) offers many advantages for efficient and secure fluid handling and sampling that are site- and process-specific. SUT adds flexibility, reduces capital requirements, and improves ease-of-use in biopharma manufacturing operations. Solid or hydrated buffers and salts that come ready-to-dispense in single-use bags and buffer preparation using single-use systems and in-line dilution can both help eliminate or reduce weight and dispense operations. Single-use raw material delivery systems also help reduce the risk of contamination and minimise the need for frequent cleaning steps.

Further, single-use sampling solutions have evolved to offer precise volume accuracy while maintaining sterility with closed, aseptic conditions. This provides agility and efficiency to specific manufacturing

conditions while avoiding contamination risks during sampling.

However, one of the greatest advantages of SUT is also one of its greatest vulnerabilities: the flexibility of choice and selection. The wide range of component choices available — from filters and connectors to tubing and bags — can lead to supply chain vulnerability. Designing for the application, using agnostic components wherever possible, allows for substitutes and second sourcing when needed.

In addition, drug manufacturers with multiple locations across the globe need to assure compliance with regulatory, manufacturing and quality requirements of these systems. Using SUT introduces new logistics challenges that, if not properly understood, can

leave biopharma manufacturers vulnerable to supply chain complexities.

As the increase in titers and the trend toward continuous biomanufacturing grows, demand in buffer volumes and prep times will increase. To address this gap, strategies for improving mAb manufacturing productivity by optimising powder and liquid buffer and media prep process flow are worth considering. When combined with innovative new technologies such as in-line dilution, single-use powder and liquid formulations can help reduce facility footprint, labour hours and the overall cost of goods.

CONCLUSION

There are numerous reliable studies and reviews that detail the performance of excipients and other stabilisers for high concentration mAbs. They are all used in unique combination and concentration levels to reduce protein aggregation, increase stability, mitigate viscosity, and provide a stable commercial product.

Selecting a partner who has the in-depth expertise to support formulation end to end is paramount to drive patient access to lifesaving drugs. This includes the selection of the right ‘ingredients’ for the formulation, implementation of globally aligned quality standards and providing a transparent and secure supply chain.

is patient- iendly approach has grown om the desire to reduce hospital stays.

EMBRACING SUSTAINABILITY IN CLEANROOM OPERATIONS

Andy Whittard, Managing Director, Cherwel

In pharmaceutical manufacturing, the challenge of maintaining clean and controlled environments is paramount. This necessity, however, comes with a significant environmental toll. As the world grapples with the escalating climate crisis, the need for our industry to diminish its environmental impact is more urgent than ever.

From heavy use of single-use consumables to the continuous operation of cleanroom systems, pharmaceutical manufacturing is characterised by its reliance on energy-intensive processes and materials. While these resourceand energy-intensive practices ensure the highest standards of cleanliness and control in cleanroom environments, they also contribute to the industry’s huge carbon footprint.

As the pharmaceutical industry strives towards net zero operations, it is crucial for manufacturers to reassess and improve the sustainability of their operations. Although the challenge may seem daunting for cleanroom operators, there are several strategies that sterile manufacturers can adopt to slash carbon emissions whilst maintaining the utmost standards of sterility and compliance.

EVALUATING ENERGY CONSUMPTION

Cleanroom operations consume vast amounts of energy. The energy demand from production-scale machinery,

particulate air (HEPA) filters can reduce energy consumption by approximately 40%.

HVAC systems typically account for 50-75% of the electricity used in sterile manufacturing facilities, with high airflow rates required under ISO regulations demanding an enormous amount of energy. As such, any cleanroom facility seeking to reduce their energy usage should regularly assess the performance of their HVAC system. Updating to newer, more efficient models can reduce the energy required for heating, cooling, and air filtration.

For cleanroom facilities that only operate in daytime hours, reducing the HVAC system overnight can bring significant energy savings. A vaccine manufacturer who adopted a

regime of reduced air flow after closing hours, achieved a 20% reduction in energy usage.

Cleanroom operators seeking to reduce or shut down their HVAC system during quiet periods should first evaluate the impact on particulate contamination and recovery of the environment upon restarting. Harnessing Biofluorescent Particle Counters (BFPCs) such as the BioAerosol Monitoring System (BAMS), is a swift and convenient way to achieve this. These ISO-certified systems employ laser-induced fluorescence to identify and enumerate airborne particles in real time.

A pharmaceutical manufacturer recently used a BFPC to monitor a Grade C cleanroom to study the impact of HVAC shutdown and discovered that the HVAC system could self-purify the

heating, ventilation, and air conditioning systems (HVACs), lighting and much more besides, contributes to the pharmaceutical industry being responsible for 55% more greenhouse gas emissions than the automotive industry.

Tackling this vast energy consumption will be critical in the race for net zero, but what steps can sterile manufacturers take to reduce energy while ensuring operations remain safe and compliant?

Many pharmaceutical manufacturers are turning to smart energy management systems to curtail their energy usage. Building management and environmental monitoring systems leverage software, sensors and IoT (Internet of Things) technology to monitor and control cleanroom equipment, lighting and other electronic devices based on occupancy and operational schedules. By ensuring that energy is used only when and where it is needed, smart building management systems can bring a marked reduction in energy usage.

Another step that cleanroom operators can take is to update equipment and appliances to more energy efficient alternatives. While this may seem obvious, there are a respectable number of ways in which cleanrooms can make a substantial energy saving. For instance, adopting new generation high-efficiency

Figure 1

cleanroom in 20 minutes following a 2-hour shutdown. Gaining these real-time insights into the microbial landscape of a cleanroom can be invaluable when evaluating energy-saving interventions.

RETHINKING RESOURCE USE: CONSUMABLES AND WASTE

Energy usage is just one factor when considering the environmental impact of pharmaceutical manufacturing operations. To reach the industry target of net zero within the next 30 years, corporations must also take steps to reduce waste. Waste produced from sterile manufacturing can take many forms – from single-use plastics and multilayer sterile packaging to the chemical waste which brings ecological implications.

Eliminating single-use sterile consumables altogether is an unrealistic prospect at present. GMP-classified cleanrooms, quite rightly, adhere to strict regulations surrounding the sterility of consumables that uphold the safety of pharmaceutical products. What can be done to reduce the considerable plastic waste produced by pharmaceutical operations?

Suppliers of consumables could make an impact on waste by adopting more flexible product supply strategies, such as offering a variety of pack sizes tailored to customer needs. For instance, providing smaller pack sizes of five poured media plates instead of the traditional 10 (Figure 1) may slightly increase packaging material use, but significantly cuts the environmental costs from manufacturing, transporting, and disposing of unused consumables from larger packs. By aligning the supply

of consumables closely with actual usage, pharmaceutical companies could significantly reduce waste and costs.

THE GLASS VS PLASTIC DEBATE

The material composition of consumables can have a significant impact upon their carbon footprint. Choosing the most environmentally friendly consumables is a nuanced task. The use of plastic versus glass consumables is a current hot topic – and the emerging consensus might surprise you.

A consumable’s overall carbon footprint is influenced by many factors, including the material used, manufacturing processes, weight, transportation, recycling, reusability, and end-of-life disposal. Glass, while widely regarded as a sustainable material due to its recyclability, is also ‘carbon expensive’ to manufacture, distribute, and recycle. In contrast, plastic, often criticised for its environmental impact, presents a lower carbon footprint when considering the entire lifecycle from production to recycling.

Environmental researchers at the University of Southampton recently found that glass bottles have a greater environmental impact as containers for prepackaged drinks compared to plastic bottles. Other recent studies have reached similar conclusions. Considering the emerging evidence, the impact of glass consumables upon sustainability could be reduced by adopting recycled, or more readily recyclable, plastic instead.

Lab consumables made from recycled plastics have started to become a reality – global supplier Eppendorf recently launched their BioBased

consumables range, featuring pipette tips and tubes made from at least 90% renewable feedstock. Made from used cooking oil and other sustainable sources, this offers labs a tangible opportunity to reduce the environmental impact of plastic consumables.

Commitment from suppliers to offer options is key, even though developing new sustainable plastic products can be surprisingly time intensive for simple items. Another example involves prepared media which has been supplied in easily autoclaved glass bottles as industry standard for decades. Developing a plastic equivalent required many subtle variations

in process to produce a consistent high-quality product; yet autoclavable plastic bottles are now widely available (Figure 2).

TAKING STEPS TOWARDS A GREENER FUTURE

As the pharmaceutical industry intensifies its journey towards net zero emissions, it’s imperative to reassess and innovate every aspect of production, especially within energy-intensive cleanroom operations. Environmentally friendly alternatives are quickly emerging to help save energy and curtail waste – and their adoption and further development brings optimism that net zero can be achieved.

Lab consumables made om recycled plastics have started to become a reality.

Figure 2

ELRIG UK AND SRG ANNOUNCE PARTNERSHIP

The European Laboratory Research & Innovation Group (ELRIG) UK, a not-for-profit, volunteer-led organisation for the drug discovery community, has entered into a partnership with SRG, leaders in life science recruitment, to support the advancement of science professionals in their careers.

The partnership offers the ELRIG community access to career opportunities and provides organisations of all sizes with SRG’s specialist talent solutions to help grow the life science sector. Early career professionals (ECPs) in industry and academia can attend forums and networking events where they can meet, and learn the skills needed to help them advance their careers in drug discovery.

Sanj Kumar, CEO, ELRIG UK,

ChargePoint Technology has invested in a new manufacturing facility dedicated to its single-use products in Speke, Liverpool, to address an increased demand in the market for disposable technologies and equipment. The new site will boast a new high-tech cleanroom alongside a temperature and humidity-controlled storage facility for single-use solutions.

The new single-use centre of excellence is adjacent to ChargePoint’s current headquarters and will become fully operational in June 2024. It will significantly increase ChargePoint’s overall cleanroom capacity at this location.

The investment supports a trio of product launches to meet growing demand in the market for solutions that maintain optimum containment and sterile integrity for closed powder

Talking points

said: “ELRIG and SRG have a shared ambition to advance the careers of early-stage professionals in drug discovery.

ELRIG will provide opportunities for ECPs to connect, whilst SRG can help them to expand their skillset and progress in their careers. Building such networks is an imperative as they navigate the myriad of collaboration and career options ahead of them. We are delighted to be working with the team at SRG, who bring 30 years of industry experience supporting scientific endeavours to this exciting collaboration.”

ELRIG brings together academic and biopharma industry experts and thought leaders to exchange ideas and information through the provision of free-toattend scientific meetings

and conferences. Its primary objective is to provide leadingedge knowledge to the life sciences community on an open-access basis. As part of the ELRIG events programme, there are a range of activities designed specifically for ECPs. SRG, powered by Impellam Group, are experts in finding the specialist skills needed to support biotech and pharmaceutical research. They help life science companies — from start-ups to big pharma — to find, attract and nurture emerging talent, and aim to ensure outstanding career prospects for candidates. Together ELRIG and SRG will provide support to life science professionals that will allow them to gain a deeper understanding of the industry,

ChargePoint to Invest in New UK Manufacturing Facility

transfer, for both small and medium-scale production. These include:

ChargeBag XL: New 3D powder transfer bags have been developed to increase the range of sizes available to ChargePoint customers for batch transfers more than 150L in volume in API, OSD and aseptic production. Using the proprietary HiPure ULP7 film, the 3D powder takes the current range of 2D bags beyond 40L capacity for the same effective and efficient powder handling at enhanced scales.

ChargeBag QF (Quick-Fill): The ChargeBag QF (QuickFill) bag is designed to speed up the dispensing and transfer of biopharmaceutical and chemical powders in high throughput production environments such as buffer and cell culture media preparation. To reduce the risk of spillage and waste it features a large ‘full diameter’ top-opening for fast filling and easy fine tuning of target weight and a separate process connection port meaning the bag does not need to be rotated. In addition, its top-opening features and flexible skirt to protect the main bag chamber and filling stand from external contamination during this process to reduce clean up time.

ChargePoint SUP: The larger sized DN150 Single Use Passive adds to the existing DN100 offering and connects to ChargePoint(R) Split Butterfly Valve (SBVs) with a 150mm aperture and supports the transfer of powders up to and beyond 150L in volume. The system

select the right career path, and develop the tools needed to progress, while helping the drug discovery industry to flourish.

Andrew Turner, Managing Director, SRG, said: “As technological innovations accelerate, new fields emerge, and competition intensifies, the demand for professionals within STEM industries continues to outpace the available talent pool. Our partnership with ELRIG, an organisation that shares our passion for innovation, will focus on talent enablement, and supporting the advancement of science professionals at each stage of their career. ELRIG’s commitment to enabling early talent aligns wonderfully with the work that we perform across the life sciences sector to create opportunities for future generations. Together, we are creating world-class communities that empower individuals and businesses to shape tomorrow’s world.”

can help contain a broad spectrum of products such as HPAPI’s and those with aseptic processing as part of a hybrid single-use / multi-use system ensuring manufacturers get both cost efficiency, flexibility and performance.

Chris Eccles, CEO of ChargePoint Technology, commented: “The new facility will become a centre of excellence at ChargePoint HQ as we introduce a dedicated product development and test cell. Alongside the opening, we’re about to launch three new products that mark a significant milestone in ChargePoint’s growth strategy as we look to expand our operations and evolve our solutions to meet our customers’ ever-changing needs. This is just the beginning of a busy year for ChargePoint”.

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