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Jan/Feb 2023 | Volume 23 Issue 1

5: EDITOR’S DESK: An uphill climb.

6: A SMALL DOSE: A brief round-up of some of the latest developments in the industry.

12: IN THE NEWS: A short selection of stories from the world of science.

14: COVER STORY: Catalent discusses the potential of ADCs in innovating oncology treatments.

10: OPINION: IDT shares the story so far of mRNA vaccines - achievements and objectives.

26: TALKING POINTS: Stories to consider and what to look out for in EPM over the coming weeks.

FEATURES

13: CONTAINMENT & CLEANROOMS: Avantor explains how using a dedicated training room can ensure the reliability of single-use systems.

17: DRUG DELIVERY & DEVICES: Owen Mumford examines the benefits that patients are set to receive as the connected drug delivery devices market grows.

20: PACKAGING: Broughton discusses the importance of packaging in manufacturing pMDIs.

22: LOGISTICS & DISTRIBUTION: Bomi Group explores the future of healthcare supply chains in a post-pandemic world.

24: BIOPHARMA & MANUFACTURING: Veeva Systems gives three digital strategies to modernise QC in biopharma.

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Volume 23 Issue 1 Jan/Feb 2023

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AN UPHILL CLIMB

It’s been a long winter –and an expensive one for a lot of us. The European energy crisis remains a pressing concern, for both the industrial sector and on a personal scale.

Disruption to access of raw materials from Covid-19 lockdowns in China, coupled with a surge in energy costs following Russia’s invasion of Ukraine, has left pharma companies sounding the alarm on the rising manufacturing costs.

Being that pharma is an energy-intensive sector, from

containment labs through to industrial manufacturing sites, cutting down costs would not prove easy without impacting product quality and capacity. Both of which are non-negotiable when it comes to pharma.

On top of this, the rising costs are widespread across Europe. Combine this with the looser regulatory requirements, many pharma companies have been indirectly swayed to move their production of active pharmaceutical ingredients (APIs) to less energy

EDITOR’S DESK

intensive countries – such as India and China.

European drug manufacturers are also warning they may stop making some of the cheap generic medicines. Generic drug pricing is reduced by 80-90% from patented drugs, and these small profit margins are not able to absorb the extent of inflation pressures - despite the fact

that generics account for about 70% of all dispensed medicines in Europe. A recent Teva report found that the breast cancer drug, tamoxifen, was halted due to the sole European API producer stating that it was no longer economically feasible to manufacture. With drug shortages headlining the news at the end of 2022, who knows what this could mean for supply chains down the line of 2023?

On the upside however, pharma is no newbie to providing innovative solutions in unprecedented circumstances. Take the pandemic, for example.

Vaccines were rolled out in a matter of weeks compared to the typical vaccine development timeframe of 5-10 years. Meanwhile, the pharma industry donated over 29 million doses of essential medicines to Ukraine and its neighbouring countries in 2022. I think it’s in examples like these where the pharma industry shines in its resiliency and efforts, to identify and commit to alternative solutions during uncertain times.

As stated by Matt Watson, European Manufacturing Sector expert at Aggreko Europe: “the pharmaceutical industry cannot stand still.”

This is true in the sense that doing nothing and continuing to act in the same way will yield a bigger cost than investing in alternatives. I believe 2023 will see a lot more news surrounding energy consumption, carbon footprint and sustainability.

Problems activate new ways of thinking. With an industry as large as pharma, even incremental changes can make a big step towards a sustainable future.

REBEKAH JORDAN

A small dose

PROCESS FOR WATER TO ABSORB OIL COULD PAVE NEW WAY FOR CBD AND DRUG DELIVERY

Water and oil don’t mix, right? It’s one of the first lessons you learn in science classes at school.

A new technique, developed by a team of UK researchers from Aston University for Max Bio+, means we will have to rethink this truism.

The Max Bio+ technology enables oil to be dissolved in water. It doesn’t just mix the two together, it makes oil soluble in water, which could be a gamechanger for the medical industry.

Max Bio+ was founded by Professor Shah, professor consultant ophthalmologist, Professor Aston University, and philanthropist Sean Ngu.

The team started by looking at eye drops as there was evidence that the anti-inflammatory, antimicrobial, anaesthetic and analgesic properties of cannabidiol (CBD) could help patients with dry eyes. The question was how to get the CBD

delivered to the eye when dropping oil in the eye clearly wasn’t a good option.

It was while creating the eye drops that the team discovered a new way of creating a soluble CBD product by making the oil completely soluble in water. Perfect for eye drops – and a wide range of other applications.

Max Bio+’s resulting CBD liquid is 25,000 times more soluble than standard CBD, and laboratory testing has indicated that Max Bio+’s technique makes CBD much easier for the body to absorb.

For now, the team is focusing mainly on working with CBD oil, but the technique works just as well with any oil-based product, opening the door for a range of new products and breakthroughs in the future. For example, the team is also looking at the delivery of insulin for diabetics.

The research has primarily been performed within the Aston University Pharmacy Department in Birmingham, UK. Thus, it has been tested to UK pharmaceutical levels, which is higher than required for CBD products.

Max Bio+ uses its proprietary technique to create a clear, tasteless, odourless product manufactured without alcohol, surfactants or heat. This clear CBD liquid can then form the basis for a variety of products from drinks to drug delivery.

The liquid can also be freeze-dried to create a powder making transport easier and further opening up the range of potential applications.

“This breakthrough in mixing oil and water is a genuine gamechanger. Just imagine how it can change the health industry by allowing the oral delivery of many drugs that currently have to be injected. Insulin is a prime example. This could spell the end of painful injections for thousands of diabetics,” said Professor Shah.

FOUR PHARMA COMPANIES TEAM UP TO REDUCE ENVIRONMENTAL BURDEN IN PHARMA PACKAGING

Astellas Pharma, Eisai, Daiichi Sankyo Company, and Takeda Pharmaceutical Company aim to promote the use of more environmentally friendly packaging for pharmaceutical products, by sharing knowledge on packaging technologies to reduce environmental burden. One example being blister packs made of biomass-based plastic instead of petroleum-derived plastic, compact packaging, recycled packaging materials, and recyclable packaging materials.

The four companies aim to ensure that society benefits from this collaboration to harmonise corporate activities with the global environment. In the future, they expect to expand this collaboration beyond the four companies by calling on other companies to reduce further environmental burden.

Astellas has set “Deepen our engagement in

Clinical trials pla orm

Ascension-Q lands

£250,000 round

Ascension-Q, the clinical research operating system, has secured £250,000 in a pre-seed round led by early-stage focused venture capital firm, Jenson Funding Partners. The funding will be used by the start-up to continue its mission of enabling as many hospitals and clinics as possible in the UK and Ireland to conduct clinical trials.

In the clinical research drug trials space, the goal is the continued development of new drugs to improve patient care and treatment options. But the work required is complex,

since research teams at the ground level often lack the support required to deliver diligent research. This leads to delays and difficulties in recruiting and retaining patients to participate in the trials. Historically, the drug design process has operated in a top-down approach, the company says, where the decisionmaking of Contract Research Organisations (CROs) primarily focuses on working with pharmaceutical companies. Rather than site-first, this approach risks shortcuts and pain points in the research process that are often ignored.

sustainability” as one of the strategic goals in its Corporate Strategic Plan 2021. The reduction of environmental burden is one of Astellas’ priority themes within sustainability.

Eisai established the “Eisai Environmental Management Vision” this fiscal year, in addition to climate change countermeasures aimed at achieving carbon neutrality by fiscal 2040, and has formed a medium- to long-term plan for environmental issues - including efficient use of water and recycling of resources.

As a healthcare company with the purpose

to “contribute to the enrichment of quality of life around the world,” Daiichi Sankyo considers global environmental conservation, which is the basis of life and livelihood, as a key management issue (Materiality) and promotes environmental management.

At Takeda, “Purpose-led Sustainability” is about creating both business and societal value through its core business. Takeda continues to reduce its operational carbon footprint and are now committed to achieving net-zero GHG emissions for scopes 1 and 2 before 2035 and for scope 3 before 2040.

Medical-grade fridge supplier, CoolMed featured in 2023 Startups Index

It’s no secret that the UK healthcare industry is under signifi cant strain. Understaffi ng and underfunding have put a fi nancial strain on the NHS, while an ageing population means that health and social care services have never been more in demand.

Launched in 2020 by Dr. Amitava Ganguli, Ash Mahmud, and Professor Richard FitzGerald, Ascension-Q sought to change that by creating a platform that helps researchers and operational staff carry out their work more efficiently, in turn improving both the user and patient experience. Its cloudbased platform can be tailored according to site needs and provides real-time metrics on study participants. It also allows for the design and management of studies with multiple cohorts and across multiple sites.

In one hospital that barely conducted research, Ascension-Q was introduced nearly 18 months ago. The hospital has since run six research programmes

and is now engaged in its seventh. The use of the platform in that time has enabled the hospital to generate nearly £2m a year.

Ascension-Q is now being used in 16 hospitals and has been utilised during 70 clinical trials, while reaching 5,000 patients on the platform. The company aims to triple the number of hospitals using the platform over the next

year, with its sights set on the European market and later the US by 2024.

Dr. Amitava Ganguli, founder and CEO at Ascension-Q, said: “We are delighted in raising investment from Jenson Funding Partners and continuing our incredible journey with their support.

AscensionQ was created to tackle the everyday challenges researchers face through automation in one platform, connecting people and not just processes. 2022 was great validation of our system, and for 2023 we are excited to push on and help the thousands of research clinics in the UK and beyond.”

CoolMed has been supporting the healthcare sector since 2017 by manufacturing and supplying medicalgrade fridges at exceptionally low prices – something the Startups Index recognised and were ‘wowed’ by.

The Startups Index also commented on CoolMed’s design strategy, through which they’ve provided real added value to big-name partners such as Lloyds Pharmacy and American pharmaceutical distributor, McKesson.

CoolMed’s commitment to sustainability and CSR was also commented on, with the judging panel stating: “CoolMed has gone two steps further than its market competitors” due to their charity partnerships with Earthly and Cool Earth.

Stephen Johnson, CoolMed CEO, stated: “We look forward to continuing to support the UK’s healthcare industry, as well as healthcare services further afi eld.”

HOW CLOUD TECHNOLOGIES SUPPORT THE EVOLUTION OF BIOPHARMA MANUFACTURING

Through cloud-based solutions, outsourcing/ partnership models can be designed to share scientific and process information by merging collective expertise from both the innovator and the CDMO.

Outsourcing biopharmaceutical manufacturing was already a growing trend before the pandemic, and now the biologics contract development and manufacturing (CDMO) market is projected to grow at 12.2% from 2021-2026. The forecast is even higher for cell and gene therapies (CGT), where the current level of outsourcing is more than 60% and the CGT CDMO market is expected to grow at 25% annually. While there are many economic factors driving this growth, one clear outcome is that cloud computing is quickly becoming a key enabling technology.

Cloud solutions support the need for more effective collaboration across an increasingly complex network of external partners and suppliers. While skills and capacity shortages, particularly for advanced therapies like CGTs, can make in-house manufacturing seem a worthwhile investment, most small biotechs don’t have the budget to afford it without support from big pharmas. The idea of outsourcing can

raise concerns around loss of control, but outsourcing doesn’t have to mean handing the project entirely over to external partners. Through cloudbased solutions, outsourcing/ partnership models can be designed to share scientific and process information by merging collective expertise from both the innovator and the CDMO.

The importance of data visibility and transparency in this context cannot be overstated. CDMOs need a scientific understanding of the product, while innovators need insight into process steps, process controls, and even raw materials. If this data can be digitised with appropriate context from the start, the entire lifecycle becomes more efficient and streamlined, leading to faster time to market. Cloud-based systems provide an attractive entry point for small biotechs as they don’t require investment in IT infrastructure yet still provide the ability to scale up, as business needs change such as recruitment of new employees. For CDMOs, the right digital architecture can ensure high availability for their clients with appropriate data access controls while moving towards real-time monitoring and predictive analytics, such as machine learning.

Cloud solutions make communication between

CDMOs and innovators more seamless. It is common for new therapeutics to be developed at one site and produced in another, or for the same product to be produced in multiple locations across the globe. For an innovator, gaining insight into process performance at different sites used to require flying technicians and experts over for physical inspections. Now, with augmented reality (AR) technologies, inspections can be conducted remotely. Cloud solutions enable sideby-side comparison across sites, providing a holistic view that supports more fluid collaboration across teams.

The good news is that enabling cloud solutions are available today. However, the lack of data standardisation

and common terminology for bioprocesses remains an obstacle. While many big pharma companies have attempted to create their own data standards to address this, there is still a lack of consensus across the industry which can lead to data discrepancies when multiple groups are involved. The silver lining is that increased data visibility and data sharing is creating urgency around this issue. Industry consortia, such as BioPhorum, are actively working to address this common challenge.

It’s time for small biotechs, big pharmas, CDMOs, and other players in the biopharma network to think differently about their data, and the value it can provide. Cloud-based solutions are here to stay.

Author: Christian Marcazzo, vice president/general manager of IDBS, discusses how cloud-based solutions can create seamless communication between innovators and CDMOs.

APPLICATIONS OF mRNA VACCINES: FROM THE 1990s TO TODAY

Although mRNA-based vaccines came to the forefront with SARS-CoV-2, they have a much more deep-rooted history. Pioneering research was conducted in the early 1990s when scientists realised that synthetic mRNA could induce the expression of a foreign protein and prompt antibody production by the immune system. Influenza was the first disease tackled by mRNA vaccines, and efficacy was shown when injections induced cytotoxic T-cell response in mice. While its preventative potential was still being explored, other studies focused on cancer, with researchers theorising that injection could prompt the body’s natural defence system to attack tumour-associated antigens.

Several clinical trials involving mRNA-based vaccines were already in the works before the COVID-19 pandemic boosted their visibility. These included phase I and II clinical trials for ovarian cancer, multiple myeloma, brain cancer, acute myeloid leukaemia, lung cancer, zika virus, parainfluenza virus, and rabies. In addition, mRNA vaccines are currently being tailored to unlock personalised cancer treatment through patient-specific targeting strategies.

As the number of cases and casualties from COVID-19 exponentially increased, pharmaceutical companies turned to mRNA while racing against time to deliver an efficient preventative treatment. Scientists demonstrated that laboratory-engineered mRNA instructed muscle cells to produce the spike protein found on the virus surface,

Opinion THE STORY

SO FAR… AND THE PATH AHEAD

ACHIEVEMENTS AND OBJECTIVES OF mRNA VACCINES

One of the many lessons learned during the COVID-19 pandemic was that our immune system was still the ultimate way to combat disease. Building on the success of the Moderna and Pfizer-BioNTech vaccines, more than 155 mRNA-based vaccines are in the clinical pipeline today, with market value expected to surpass $2 billion by 2026. The question remains: what makes mRNA-based medicine so compelling, and what are the challenges in vaccine development?

prompting the body to produce antibodies. mRNA vaccines launched less than a year after the sequencing of the SARSCoV-2 virus, helping to save lives and accelerate a return to normality.

mRNA AS AN ACTIVE VACCINE INGREDIENT

The main takeaway from all these examples is that mRNA-vaccines harbour several advantages that deem them feasible, safe, and efficient. This could come across as rather surprising, given that there was a shift in the 1990s toward the development of DNA vaccines because of the higher stability of DNA when compared to mRNA. Yet, mRNA vaccines exhibited advantages over DNA vaccines, which compensated for this deficiency and is why mRNA vaccine development is significantly more

common than DNA vaccine development. Unlike DNA vaccines, which must pass through the cytoplasm and into the nucleus to be expressed, mRNA vaccines are targeted for cytoplasmic delivery and break down shortly after triggering an immune response. This circumvents the risk of integration into the host genome. In addition, mRNA is suitable for cell-free production through a DNA template and in vitro transcription system, eliminating the need for cell cultures.

CHALLENGES: mRNA STABILITY, CELLULAR UPTAKE AND STORAGE

Despite their rising profile, mRNA vaccines come with challenges that have only been partially addressed so far. In particular, the transient nature

of mRNA is a double-edged sword. While it can prevent mRNA from overstimulating the immune system, it also makes mRNA unstable and susceptible to rapid degradation by RNases before even reaching the target. Several approaches have been implemented to tackle this pitfall. Synthetic 5’ cap analogs can be integrated into mRNA to shield it from exonucleases and immune sensors while mediating binding to the eukaryotic initiation factor during translation. Sequence optimisation is another strategy to modulate the immunogenicity of the mRNA vaccine. The addition of untranslated sequences before and after the gene, codon optimisation of the gene sequence, the addition of nucleic base analogs, and

the length of a poly A tail can all affect the stability and level of expression of the mRNA. Together, these factors offer powerful options to modulate the immune response to be specific to the antigen while limiting non-specific side effects.

Another major hurdle in mRNA vaccines is successful intracellular delivery. The possibility of degradation by endonucleases and exonucleases aside, highly polar mRNA cannot pass the nonpolar cell membrane. This required researchers to invent delivery systems for maximum protection and cellular uptake. To that end, lipid nanoparticles (LNPs) have become the primary delivery vehicle due to their ease of scaleup, biocompatibility, cellular uptake via endocytosis, and pH-controlled mRNA release inside the cells. However, they require additional analytical tools to ensure that mRNA integrity is retained inside the LNP. Furthermore, the type of LNP must be taken into account, as some studies revealed that they stimulated pro-inflammatory cytokine secretion. More research is crucial to uncover the delivery mechanism and safety profiles of LNPs.

The monitoring of mRNA integrity and stability continues even post-manufacturing. Moderna and Pfizer store their vaccines between -20°C and -70°C to prevent breakdown by hydrolysis; however, the LNPs could form aggregates at these temperatures, impairing

their function. To overcome these challenges, LNP-mRNA vaccines can be stored in sucrose solutions to keep LNPs apart and stable. Furthermore, freeze-drying allows them to be stored at slightly higher temperatures in refrigerators to prevent aggregation.

FUTURE STEPS IN mRNA VACCINE OPTIMISATION

With optimisation strategies for safety, stability, and targeted delivery, the potential of mRNA vaccines can be augmented. That said, many challenges still exist. For example, can we better optimise delivery and dosages, particularly for those who may be immunocompromised? Can we formulate or stabilise mRNA vaccines to eliminate the need for cold chain storage that prevents access in areas of the world with limited biomedical infrastructure? Also, how can researchers predict posttranslational modifications of the target antigen, which are the key players evoking immunogenicity? In fact, research suggests that the spike protein, which is responsible for viral binding and entry to host cells, is heavily glycosylated. Therefore, considering various post-translational modifications during in vitro transcription can yield stronger immunogenic reactions and enhance efficacy, opening the door for a new era of next-generation vaccines designed to improve human health.

Author: ADAM CLORE, director of development & innovation at Integrated DNA Technologies.

Government support withdrawal sparks rethink on pharma’s energy strategy

Pharmaceutical manufacturers are increasingly reevaluating equipment procurement strategies following concerns expressed over winter blackouts and the planned withdrawal of government financial support.

The observation from temporary hire specialists Aggreko comes in the wake of the news that the government is poised to reduce assistance provided on business energy bills after March. This latest announcement, combined with a recent survey from trade body Make UK stating that two-thirds of manufacturers fear blackouts this winter, has led to concerns over the continued performance of the UK national grid.

With this in mind, Matt Watson, European Manufacturing Sector expert at Aggreko Europe, is highlighting the importance of alternative technologies to help maintain power baseloads at a challenging time for the industry.

“The energy crisis remains a pressing and ongoing concern across all walks of life in the UK, including in the manufacturing sector,” explained Matt. “With a recession expected and support being cut,

the need to safeguard production output and profitability is more important than ever.

“In order to mitigate the pressures associated with grid constraints, alongside energy availability and pricing, equipment specifiers at manufacturing sites are exploring strategies that were previously overlooked. With ageing grid infrastructure and global factors continuing to impact financial bottom lines,

one thing is clear – the pharmaceutical industry cannot stand still, and it is encouraging that new ways of thinking and acting are being embraced.”

According to Matt, decentralised energy solutions may mitigate challenges posed by grid power constraints and build site resilience. “A major consequence of volatile energy costs and supplies is that businesses are finding it more difficult to plan ahead,” concluded Matt. “Consequently,

manufacturers need to expand their equipment approach beyond simply purchasing generators outright. Given the large fluctuations in fuel costs and required output, such an approach may be costly in both the short- and long-term.  “Instead, we would recommend organisations look at alternative strategies, including the hire of load-ondemand, combined heat and power, and battery energy storage systems. With the business landscape continuing to look challenging for manufacturers, stakeholders must work more closely with suppliers to identify solutions that not only guard against power shortfalls, but also improve overall efficiency.”

Did you know?

82% of pharma firms have been forced to make changes to counter rising energy bills, 36% of which describe the changes as radical.

The pharma industry produces significantly more emissions than the automotive industry.

Pharma produces 48.55 tons of carbon dioxide equivalent (CO2e) for every $1 million USD generated.

BREAST CANCER WAS THE MOST STUDIED DISEASE AREA IN 2022

The analysis of 80,917 trial records, from Phesia, reveals that breast cancer retained its position as the moststudied disease area in 2022, followed by COVID-19. Three of the top five most-studied disease areas fell within oncology, with prostate cancer the third moststudied disease, solid tumours fourth, and stroke fifth.

“Oncology remains an area of high investment in clinical development, however, 2022 has seen a widespread scale back of overall activity. The reduction of recruiting trials in the top most-studied disease indications is due to several global factors including the pandemic and the war in Ukraine,” commented Dr Gen Li, president, Phesi. “With an increase in available vaccines and therapies, it is not surprising that the number of recruiting trials for COVID-19 therapies has fallen. However, the reduction in breast cancer trials is unexpected, with 113 fewer recruiting trials in 2022 compared with 2021.”

The analysis has also revealed an increase in Phase II terminations. In 2022, the attrition rate for Phase II clinical trials was 28% – 42% higher than the previous five-year average. This is the highest proportion of terminations at Phase II in recent years and is even higher than in 2020.

AND CLEANROOMS

Optimising single-use cleanroom manufacturing through associate training

Using a dedicated training room to ensure the reliability and quality of single-use (SU) systems.

Author:

The rapid growth of single-use (SU) systems in pharmaceutical and biopharmaceutical production processes has introduced efficiencies into drug manufacturing workflows; it has also introduced new challenges for SU manufacturers. Single-use manufacturers must expand to meet global demand.

However, even with redundant suppliers and facilities, manufacturers — and, by extension, their customers — face substantial risks if manufacturing errors disrupt workflows or yield SU products that do not meet safety and performance requirements.

In order to maximise throughput and meet customisation goals for SU technology customers, SU manufacturers need to reduce contamination risks while limiting changeover times. This needs to be done in environmentally controlled cleanrooms, with associates wearing the appropriate personal protection equipment (PPE) specified for that cleanroom and product assembly process.

In addition, SU manufacturers scaling up to meet surging demand must maintain a reliable supply chain while ensuring that single-use systems meet rigorous quality standards for component qualification, contaminant-free assembly operations, in-process testing and final product release (including proper packaging in aseptic delivery containers).

However, it’s important to recognise that SU manufacturing is still largely a manual assembly process conducted in cleanrooms with little automation. For this reason, it is highly susceptible to disruption by human error. Due to the critical nature of the drugs produced using SU technology, the most stringent quality controls to prevent contamination must be maintained with little room for error.

In practice, this means that even a simple mistake or an

accidentally skipped step could result in the entire assembly process needing to be restarted to ensure that the final product meets the highest quality product standards, and follows requirements established with the end-user drug manufacturer.

THE VALUE OF A DEDICATED CLEANROOM TRAINING PROGRAM

One way to help satisfy these stringent requirements is through a training program that centres on a dedicated cleanroom training facility. In this approach, the training room mimics the production line in a controlled cleanroom environment and uses rejected, returned or non-cGMP-compliant materials that would otherwise be wasted.

This kind of program can provide an immersive, applicable training experience in all major aspects of SU assembly practices and procedures in use in production sites. New associates would receive training based on a carefully developed curricula, that guides them through the SU manufacturing process from start to finish, with all the same tools used in an actual cleanroom.

The program can be conducted by trainers with strong backgrounds in quality production and the training curricula, providing immersive, hands-on training that guides the development of the highest-quality production skills and professionalism, while providing value through dedication

and continuous attentiveness to all the associate’s needs.

By ensuring all associates operate from the same knowledge base, the training room offers a major contribution to further standardising production. This not only results in a happier and more responsible workforce (helping manage retention rates), but it also contributes to a reduction in manufacturing errors. If a problem arises on the production line, well-trained associates are primed to identify it quickly, reducing the impact on production.

This kind of training resource can also have a broad impact on SU manufacturing areas such as IT, sales, engineering and product management. For example, if a customer requests samples or engineering is analysing a modification to an existing assembly, the training room can fulfil these needs without requiring engineers to enter working cleanrooms, preventing disruptions or contamination risks.

Ultimately, SU manufacturers that depend on cleanroom assembly facilities can experience significant improvement in quality control, productivity and workforce satisfaction through investments in training facilities.

Dedicated cleanroom training facilities can become a robust component of the workforce development process. They can provide a significant impact on the ability of SU manufacturers to supply their customers with products that fully meet their critical drug development and manufacturing needs.

TIMOTHY KORWAN, director, new product introductions, Avantor.

Antibody-drug conjugates (ADCs) have the correct combination of tools to target and help eliminate tumour cells. They have three components: an antibody designed to identify tumour cells within a patient; a toxic payload to cause cell death; and a linker that connects the two. Initial success for ADCs came with the approval of Pfizer’s Mylotarg in 2000 for acute myeloid leukaemia. ADCs have since diversified from treating blood cancers into the realm of solid tumours, and have achieved commercial success over the last ten years, with 12 drugs currently being U.S. FDA approved.

First-generation ADCs faced multiple challenges

The initial hope was that ADCs would be the “magic bullet” for cancer treatment. With their ability to selectively direct highly potent cytotoxic payloads to target cells, ADCs offered the prospect of more precise treatments, and a reduction in the offtarget effects seen with chemotherapies. However, the first generation of ADC candidates were prone to early release of their payloads, indicating the need for improved linker chemistries. Additionally, developers found that controlling the number and location of the payloads on the antibodies is critical to improving the pharmacological profile of ADCs and expanding the therapeutic window. New technologies that offer sitespecific conjugation, as well as innovative linkers have since been developed and are enabling the next generation of ADCs to overcome some of these initial challenges.

NEXTGENERATION ADCs,

antibody. Through method development and optimisation, this process can be robust, reproducible, and high yielding. The limited number of steps and reagents keeps the costof-goods low and makes the process readily scalable and highly reproducible.

SMARTag tandem-cleavage linkers improve ADC stability

Common approaches to making a cleavable linker include incorporating substrates for protease cleavage, disulfide reduction, or acid-mediated hydrolysis into the design. Regardless of the cleavage mechanism, most cleavable linkers share a common design element: Site-specific conjugation of ADCs

BETTER ONCOLOGY TREATMENTS THROUGH INNOVATION

There are numerous technologies available to engineer ADCs with sitespecific conjugation. One such method uses an aldehyde tag, which is a six amino acid sequence that is genetically encoded into the desired location of antibody constant regions. The sequence is a substrate for the naturally occurring human enzyme, formylglycine-generating enzyme (FGE), which converts a cysteine residue in the tag sequence to a formylglycine residue, which contains an aldehyde functionality. The aldehyde chemical reactivity is bioorthogonal to other reactive groups within the antibody, and thus serves as the handle for site-specific bioconjugation.

There are a variety of locations on the antibody that can be modified without affecting its biophysical properties or negatively impacting product titres. This affords flexibility in payload placement, which provides opportunities

for conjugate optimisation and design innovation. The enzymatic transformation of cysteine to formylglycine occurs co-translationally as the protein is being expressed in the cell, and to ensure full conversion, cell lines that overexpress the FGE enzyme can be used. The antibody is secreted into the cell culture medium with aldehydes installed and is purified using standard techniques. At this point, the antibody can be conjugated by adding the linker-payload to the modified

Author: Penelope Drake, Ph.D., head of R&D, bioconjugates, Catalent.

only one cleavage event is required for payload release. This reduces the stability of the ADC, as only one “lock” protects conjugate integrity, which increases the potential for loss of payload as the drug circulates in vivo, leading to reduced efficacy, greater toxicity and side effects.

To increase stability, a cleavable linker system has been developed to increase stability of ADCs in circulation, thereby improving the therapeutic index.

The principle behind the design was that by adding a second “lock” to the linker— namely, a second enzymatic cleavage event that would

be dependent on ADC internalisation— in vivo stability would be improved.

The first “lock” in the tandem-cleavage system is a standard valinealanine dipeptide, which is a substrate for cathepsins and other proteases. For the second “lock”, a glucuronic acid was placed very close to the dipeptide to sterically prevent access by proteases to the dipeptide substrate. In order to release the payload, the tandem-cleavage linker requires two orthogonal enzymatic activities to occur in sequence. First, glucuronidase—which is only active in low pH environments, such as lysosomes—removes the monosaccharide, liberating the dipeptide from protection. Then, a protease can cleave the dipeptide, triggering payload release. The tandem-cleavage component is a modular element, so is versatile and can be added to any cleavable linker system in order to impart stability and hydrophilicity.

Catalent SMARTag technology and stable linkers support growing ADC field

The SMARTag technology was conceived in Carolyn Bertozzi’s laboratory as part of the suite of bioorthogonal chemistry innovations that earned her the 2022 Nobel Prize in Chemistry,

and combines site-specific conjugation and tandemcleavage linker technology.

In collaboration with licensed partners, several ADCs using Catalent’s SMARTag technology are currently in the development pipeline. The most advanced of these, Triphase Accelerator’s TRPH222, has completed Phase 1 studies for non-Hodgkin lymphoma. Additional SMARTag ADCs are in preclinical development, including Exelixis’ nextgeneration 5T4-targeting ADC (XB010) for various forms of solid tumours.

Catalent’s technology overcomes the limitations associated with conventional protein chemistries that produce heterogeneous products with variable conjugate potency, toxicity, and stability. It enables sitespecific, controlled drugprotein conjugation and uses only naturally occurring protein modifications requiring minimal cell-line engineering. SMARTag technology is agnostic to payload and is compatible with cytotoxic and non-cytotoxic payloads, including nucleic acids and peptides.

With recent approvals, ADCs are seeing a resurgence in popularity as potential treatments for cancer, as well as other diseases. The limitations associated with conventional protein chemistries that produce heterogeneous products with variable conjugate potency, toxicity, and stability are no longer inhibitory, and sitespecific, stable ADCs are filling development pipelines and show promise to deliver the therapies of the future.

Whilst the need for refrigeration or ultralow temperature storage for vaccines is not new, demand increased considerably during the pandemic, meaning the cold chain industry had to rapidly scale up production. The recent surge in the industry requiring reliable, ultra-low temperature medical cold chain solutions, is down to factors such as the rise in adoption of mRNA technology and the growing prominence of Cell & Gene Therapy (CGT). With this rise, we have seen increased support from the government for research activities and clinical trials focusing on immunisation, in turn increasing demand for vaccine transport carriers further.

Within the pharma industry, we are seeing the increased need for vaccine transportation boxes which are sustainable and can be used worldwide, particularly in ‘off-the-grid’ and remote locations. As with every industry, there is an increasing demand for brands to act sustainably and this is certainly true for the pharmaceutical industry.

At Secop, we draw on our experience and talented pool of people in order to create battery and solar-powered active cooling systems into our development to ensure we can offer the sustainable option so many are looking for. We

have developed the innovative ultra-low temperature (ULT) cooling box, which is optimised for the last mile of distribution. The box has a compressor which can be used to precisely control temperature and, unlike passive systems, ensures that no valuable vaccine is rendered unusable and wasted. In addition, there is no dependence on dry ice which in turn produces tons of CO2. Not only offering environmental benefits, this creates advantages especially for distribution in remote areas where the availability of CO2 cannot be guaranteed.

Additionally, we recently partnered with B Medical to develop a new generation of medical transport boxes to safely store and transport vaccines, biospecimen and

other temperature-sensitive specimens at ultra-low temperatures.

One trend we are also seeing in the pharma industry is an increase in partnerships to combine skill sets and technologies to support successful development of vaccine transportation products. For example, we partnered with Global Health Labs to develop a new Solar Direct Drive controller, which is tailored to the WHO Performance, Quality and Safety specifications. The controller meets demands for solar direct drive as well as range, unstable power grids and weak installations and enables vaccine refrigerator manufacturers to meet the latest voltage stabilisation requirements.

However, similar to other

industries, both global and local disruptions have had a knock-on impact for the pharma industry, including disruption to the supply chain and shortages of drivers affecting the movement of goods around the world. Coupled with significant increases in fuel and freight costs, times are particularly challenging for the pharma sector.

The demand for effective and efficient last mile delivery of new generation vaccines is challenging the medical cold chain for reliable and robust solutions, to guarantee storage and distribution in safe conditions - with minimum waste of precious vials - and maximum control of transport conditions, including areas with poor grid connections or severe ambient conditions.

Dr. Jan Ehlers, chief executive officer at Secop GmbH, shares the trends and challenges in the cold chain industry and the rising demand for vaccine transport solutions.

THE FUTURE OF PATIENT EXPERIENCE:

The expansion of the connected drug delivery market is set to create an improved treatment experience for patients in the coming years; some of these benefits to patients are self-evident, but others in the early stages are not yet mainstream. Simplifying the process of using these devices, along with human factors-based product design, will help to make connected drug delivery a more inclusive experience, and a more attractive treatment option for patients.

DIGITAL GUIDANCE AND FEEDBACK

With patient treatment taking place outside of healthcare settings more frequently, drug delivery devices must be as intuitive as possible to encourage self-administration. With digitalisation, devices can support the patient during the injection process through confirmation of drug delivery – such as confirmation of drug delivery and injection reminders. The ability of connected devices to provide guidance and feedback at each stage of drug delivery is particularly valuable, as drug formulations evolve to allow longer periods of time between injections – meaning some patients may require more guidance, but also reassurance that they are completing the injection correctly and successfully. Additionally, training devices can give

specific guidance, so patients will know at what point they may require additional support from a healthcare professional (HCP).

STREAMLINED DATA COLLECTION WITH

5G

Currently, smartphone apps play a significant role in the connected device system, providing an interface for patients and HCPs to track and manage therapies. However, downloading apps can be a burden for patients who are not habitual smartphone users or have impairments restricting their use. The emergence of 5G will remove these issues, with connected devices able to send data directly to the cloud without the need for secondary applications.

APPLICATION OF DATA IN HEALTHCARE SYSTEMS

Wearable devices - such as smartwatches - can collect

physiological and lifestyle data on a patient, creating a unique profile for them. Integrating this information with data collected from connected drug delivery devices could build a more holistic view of the patient, their condition and related treatment. However, we are some way off from this being mainstream. Data from connected devices is currently captured and siloed rather than being combined with other sources, such as electronic health records. This is due to the complexity and processing power needed for successful data integration across multiple platforms - yet this is beginning to change. Once this data use becomes more commonplace, HCPs will be able to access real-time data and suggest personalised treatment plans, improving adherence and therefore, generating better healthcare outcomes.

A PICK & MIX OF DEVICE CONFIGURATIONS

There are now different options and configurations for medical device manufacturers to consider when designing connected drug delivery devices, between single use and reusable auto-injectors as well as integrated or addon connectivity. Evolving technology and regulations as well as increased focus on environmental impacts mean that the optimum device design is constantly changing depending on the patient group, market and therapy area. Flexibility, as well as expanding the potential patient population, may facilitate commercialisation in different geographic markets where regulations may not be the same. These considerations are driving device research and development, giving pharma companies growing choice, as well as the patients.

ENCOURAGING CONSISTENT DEVICE USE

Better collection and application of patient data will streamline treatment for patients and allow for patient groups to receive more personalised care based on their individual needs. Additionally, the growing number of device configurations will allow pharma companies to choose appropriate features for the needs of different patient groups.

Read the article in full at: pharmaceuticalmanufacturer.media

Michael Earl, director, pharmaceutical services at Owen Mumford, examines the benefits that patients are set to receive in the coming years, as the market for connected drug delivery devices continues to expand.

how connected drug delivery will promote inclusivity and adherence

Kerstin Pohl, sr. global manager, gene therapies, at SCIEX, and Thomas Kofoed, co-founder of Alphalyse, discussed the harmful effects of HCPs and strategies to mitigate them.

LC-MS TO REINVENT IMPURITY ANALYSIS IN

GENE-BASED DRUGS

Genomic medicine and gene-based vaccines show promise for treating cancer and rare diseases, correcting for gene deficiencies and accelerating vaccine production. However, purification of these products can be quite intricate, and incomplete purification can lead to complications. Most recently, one of the FDAapproved adenoviral COVID-19 vaccines was associated with vaccine-induced thrombosis with thrombocytopenia syndrome (VITT) with 1:125,000 frequency, inducing blood clotting in vital organs. Although the factors leading to VITT are still being studied, investigation of the vaccine components revealed adenoviral proteins that may have stimulated antibody production for attacking platelet factor 4 (PF4), triggering coagulation.

This raised concerns about process-related impurities in gene-based vaccines and safety implications. During viral vector development, proteins expressed by the packaging cells (host cells) can co-purify with the delivery vehicle (the viral vectors). These host cell proteins (HCPs) are impurities that can alter the mechanism of action in many ways.

Kerstin Pohl (KP): How exactly do HCPs affect vaccine quality and safety? How does this impact the vaccine production timeline?

Thomas Kofoed (TK): Certain HCPs, such as lipases and proteases, could impair stability and integrity by degrading the vaccine vector, stabilisers or adjuvants. Others can activate an immune response and trigger adverse effects, such as excessive inflammatory cytokine release or thrombosis.

Once the harmful effects from HCPs show up in later stages of the product life cycle and clinical settings, optimising the product becomes an insurmountable challenge. Therefore, pharmaceutical companies must analyse and eliminate these impurities as early as possible.

KP: Manufacturers have commonly used ELISAs to analyse HCPs. What are the advantages and disadvantages of this approach?

TK: One of the critical quality attributes in pharmaceutical production is the HCP concentration or amount in the final product, typically established as 100 ng per mg of therapeutic (100 ppm). Manufacturers mainly use enzyme-linked immunosorbent assays (ELISAs) to estimate overall HCP content. ELISAs have proven valuable since they can rapidly detect impurities at levels as low as parts per million. However, it is challenging to develop a set of antibodies to recognise extensive HCP profiles, especially small HCPs with relatively weak immunogenicity to raise antibodies for ELISAs.

There is then the problem of HCP composition, which ELISAs cannot provide since they only reveal the overall HCP quantity. The insight gained from ELISA does not suffice to distinguish and quantify individual HCPs, so an orthogonal approach is required.

KP: Liquid chromatography-mass spectrometry (LC-MS) is often called an orthogonal approach. Can you elaborate on that? What makes LC-MS feasible for HCP analysis?

TK: LC-MS can be a useful complement to ELISA because of its ability to identify and quantify individual HCPs from a mixture. We have gained extensive experience on this topic over the past seven years, owing to our partnership with SCIEX and the use of high-resolution mass spectrometry (HRMS). While ELISAs are blind towards changes in composition, HRMS can reveal changes and identify individual HCPs, allowing for informed decision-making. You can detect thousands of proteins, and then identify and quantify them, in a single LC-MS injection. HRMS allows for the quantification of HCPs present in trace amounts as well.

This initial analysis can then be used to identify problematic HCPs, which can be monitored in a targeted manner with high throughput using triple quadrupole LC-MS through multiple reaction monitoring (MRM) at later stages of development or even quality control (QC).

KP: Is LC-MS for HCP analysis used only at later stages of development, or is it flexible enough to be implemented for process optimisation?

TK: One of the advantages of LC-MS is its flexibility. It can be used to analyse both the final product and in-process samples at various stages during downstream processing. In fact, we have several clients using the provided LC-MS results to optimise their downstream purification processes, remove challenging HCPs more efficiently and thus improve yield. Furthermore, LC-MS can be used for analysing the final product - we recently showed that LC-MS for HCP analysis can be used under GMP as a release assay. This is the world’s first case of using LC-MS in that context, and it significantly shortened the development time of our client’s virus-like particlebased vaccine booster.

KP: We sometimes hear about concerns related to the bias of the methods used for HCP analysis. Is there bias in LCMS-based HCP analysis, and if so, how do you overcome it?

TK: While both ELISA and LC-MS can be affected by their own biases for different reasons, LC-MS is a less biased technique overall. However, when using data-dependent acquisition (DDA), the LC-MS results will be skewed towards more abundant proteins. This can be explained by the stochastic acquisition process of DDA, during which the most abundant ‘n’ analytes are fragmented at any given time point. Less abundant analytes might not be chosen for fragmentation or maybe only in an unreproducible manner. This can be overcome by using data-independent acquisition (DIA), which enables unbiased and reproducible analysis.

SWATH DIA, for instance, ensures that the entire detectable HCP spectrum is analysed, without prior knowledge of the analytes. This approach minimises the risk of overemphasising high-abundance proteins and missing the ones in trace amounts. It also reduces the variability seen with DDA methods as it relies on a stochastic acquisition process. Thus, this unbiased HCP detection method eliminates variation between replicates and drives reproducibility.

KP: How do you see advancements in LC-MS technology contributing to HCP analysis in the future?

TK: Commercial ELISA kits cannot account for the variations in process-related impurities, especially when it comes to novel gene-based

therapies and vaccines, which are often based on many different cell lines and production methods. Developing ELISAs tailored to specific manufacturing processes would involve lengthy antibody production, which is very time-intensive. In contrast, LC-MS workflows can be adopted within days and meet the rising demand for efficient analysis of genebased products.

The HCP content of a biotherapeutic or vaccine is subject to change depending on process variations and process developments, such as changes in culture conditions and scale-up. Therefore, HCP analysis must begin from the early drug development phase. This will inform process developers about the possible trigger points and their downstream effects. This knowledge can be used to optimise the production workflow to minimise contamination at later stages, which would otherwise be time-consuming and costly to resolve.

The technological advancements in HCP identification and quantification pave the way for better interpretation and elimination of impurities. Drug innovators must implement benchmarks to reveal the impact of individual HCPs and determine the potentially harmful ones. Once there is sufficient information about the impact of various HCPs, research must also focus on eliminating these impurities with high efficiency and ideally high specificity. This can reshape the HCP analysis framework and the entire biopharmaceutical manufacturing process, and LC-MS plays a crucial role here.

AIDING RESPIRATORY DRUG DELIVERY: PMDI VALVE CONSIDERATIONS

Packaging selection is an important consideration for many drug products, particularly pressurised metered dose inhalers (pMDIs). In particular, pMDI valve design can be an important factor, as these components are crucial to the correct drug delivery.

pMDIs are a common treatment option for the 5.4 million people with asthma and the further 1.2 million who have COPD in the UK. The devices utilise pressurised canisters of propellant, with the drug in solution or suspension, to deliver small, metered doses into a patient’s lungs. This delivery can occur either directly, or via add-on devices like spacers and valved holding chambers (VHCs).

BEST PRACTICE FOR PMDI DESIGN

Metering valves are key components in pMDIs; responsible for ensuring a consistent amount of formulation (and ideally drug) is delivered. In Stephen Stein et al.’s paper, they were described as “the heart of the system,” with “greater complexity than any other hardware subsystem”. For the product to perform optimally, the valve must be matched to the product, accounting for factors such as formulation viscosity and

desired particle size distribution.

Valve design variations can vary according to the exact formulation and dose required. Take an active pharmaceutical ingredient (API) suspended in the propellant, for example. Such a formulation would require a gathering ring as part of the metering valve to disperse the suspension and ensure uniform filling of the suspended API into the valve. However, the need for a gathering ring is completely negated if the drug substance is a solution.

Most pharmaceutical businesses will not manufacture their own valves. Instead, they will often partner with a reliable third-party manufacturer, and select from their available options. At the design stage, this will include making decisions on a suitable material and marrying up the metering chamber size (which is directly correlated to the dosage size) with the formulation. Based on the available valve configurations, the pharmaceutical manufacturer may need to adjust their formulation chemistry to suit the valve design. They will also need to conduct their extractables and leachables studies to ensure the selected material has no impact on patient safety.

WHAT ARE THE RISKS?

As well as being a crucial component for consistent drug delivery, concerns about pMDI valves can lead to a mass product recall. In 2017, GlaxoSmithKline voluntarily recalled some 590,000 inhalers from the US market due to concerns that a packaging defect had occurred. The defect could cause propellant to leak via the valve and/or closure of the canister whilst the drug product was stored on pharmacy shelves.

Similarly, large recalls of mini spacers — often used by children and the elderly, in conjunction with pMDIs to coordinate inhalation — have occurred when manufacturing defects have caused incomplete fill via the entry orifice. This meant that patients might

have received insufficient API amid a potential asthma attack.

Historically, such defects were a real issue, however, as the plastics industry has become more aligned with good manufacturing practice (GMP), such recalls have become rarer.

pMDI valves are crucial, helping millions of respiratory disease patients receive the correct dosage of API. To ensure safe and effective pMDI design, pharmaceutical manufacturers can partner with a science and regulatory consultancy that can advise on their design choices, perform extractables and leachables studies, and support with regulatory approval.

Andrew Lee, senior consultant at lab services and consultancy specialist, Broughton.

THINK BIGGER:

ADVANCING CARTRIDGE-BASED SUBCUTANEOUS DRUG DELIVERY

In the past decade, notable advancements in formulation science facilitating better delivery of subcutaneous injections have resulted in several defining moments within the space of parenteral drug delivery. For example, a second-generation GLP-1 receptor agonist suspension drug was approved in 2017 in a cartridge-based autoinjector to offer its patients a more convenient injection experience.1 And in 2020, the industry saw the regulatory approval of a 2.0 mL autoinjector format of a breakthrough biologic therapy for atopic disorders,2 a first in the self-injection space.

The constant evolution of drug formulations across various disease areas has opened a wider avenue for subcutaneous drug delivery, and fortified the merits of drug delivery devices like autoinjectors. One reason behind the growth of autoinjectors is their ease of use. Autoinjectors are conventionally developed around the prefilled syringe; which with their staked needles can be designed into two- or three-step selfinjection devices that do not expose the user to the needle. In comparison, cartridge-based injectors traditionally required the user to manually attach the needle to the device before injection, resulting in an extra step for the user and also, posing a risk of contamination and needle stick injuries.

Another reason lies in the expanded scope of container choices built for self-injection technologies. Syringe-based systems, which have traditionally been limited to 1.0 mL, have seen successful expansion into 2.0 mL dosing volumes. Meanwhile, cartridges can go up to 3.0 mL, and at the same time, we see that largervolume cartridges holding 5.0 mL are well-adapted for complex formulations. This expanded scope of container choices built upon self-injection technologies enables pharmaceutical companies to further explore cartridge-based autoinjectors for the next generation of drug formulations under development.

An innovative mechanism called Needle Isolation Technology (NIT) has been developed to address the challenges associated with cartridge-based injection systems. Based on a pre-installed needle hidden inside the device, the technology eliminates the need for users to manually attach the needle. With NIT, users simply untwist the cap to introduce the needle prior to injection, opening up the fluid path and allowing the injector to automatically prime.

Because NIT makes it possible for the cartridge to behave like a traditional pre-filled syringe with a staked needle, it means that the device can be built into an integrated autoinjector with complete needle covering and shielding - before and after injection. Such a cartridge-based technology also allows for increased delivered dose volume and accommodation of lyophilised or

suspension formulations. More recently, treatments in the oncology area have also been exploring the subcutaneous route through enzyme-assisted drug formulations, further opening the possibility for cartridgebased autoinjector combination product development.3 Finally, the technology supports complete control of cannula gauge and length to enable target injection time and depth.

As we enter a post-pandemic healthcare landscape, advancements in parenteral drug delivery will not waiver. With an evolving industry understanding of autoinjector devices, their usability, and the continued rise of novel drug formulations – cartridgebased subcutaneous drug delivery will continue to redefine the field of patient self-injection.

References

1. Drugs.com. (n.d.). Bydureon BCise FDA Approval History. (https://www.drugs.com/history/ bydureon-bcise.html, accessed January 2023).

2. Drugs.com. (n.d.). Dupixent FDA Approval History. November 2021. (https://www.drugs.com/ history/dupixent.html, accessed April 2022).

3. biopharmadealmakers.nature. com. June 2018. Enhanced hyaluronidase-based drug delivery. (https://media.nature. com/original/magazine-assets/ d43747-020-01054-8/d43747020-01054-8.pdf, accessed April 2022).

SHL Medical discusses the evolution of drug formulations and how it’s supporting cartridge-based subcutaneous drug delivery in redefining the field of patient self-injection.

RESILIENT AND RELIABLE CREATING THE HEALTHCARE SUPPLY CHAINS OF THE FUTURE

The future of postpandemic healthcare has challenged us to rethink our supply chains from end to end.

Shortened clinical trial cycles, new technologies, next-generation medical innovations, risk management, and digitisation have, and will, set new standards and

Author: MARCO RUINI, president, Bomi Group, a UPS Healthcare company

redefi ned norms for the industry.

More than half of all new drugs today are biologically derived. This makes them fragile, requiring very specifi c storage and transport temperatures. The clock is ticking on every sample, so logistics companies face the challenge of being on time

and retaining uncompromised quality 100 percent of the time.

Cold chain networks are now a must at every stage of shipment (and even development), and are now fundamental to medical innovation and patient-centric care.

THE NEED FOR SPEED

Thanks to the rapid development of COVID-19 vaccines, we have seen governments moving quickly to pass policies to accelerate clinical trials and new drug development reviews. To maintain a competitive advantage, how can pharma companies get their

treatments from clinical trials to the patient as safely and quickly as possible?

As trial stages and review times shorten, healthcare companies must have dependable, and adaptable, supply chain processes ready to go. A patient who needs a cancer drug or vaccine just hitting the market can’t wait for weeks while a logistics partner designs a new supply chain. Logistics partners must rapidly adapt and fl ex existing supply chains.

MAINTAINING VISIBILITY

The best healthcare logistics partners have evolved their physical supply chain

networks into global quality end-to-end digital ones. Their agile and smart platforms off er granular visibility as well as digital data insights that produce control, a consistent experience, and reliable speed.

They’re ready with cold chains and temperature monitoring, and they have GPS location and track-and-trace solutions in place that allow for the rerouting or recovery of highly priced shipments.

It’s not only the fragility of these next-generation products that is driving this change, but also a burgeoning shift to value-based care.

Health providers, both public and private, are looking at hospitals less as a physical space and more as a hub that connects the patient from their local pharmacy or their home. This presents an entirely new distribution mechanism for pharmaceutical companies and other healthcare services.

Underpinned by technology, ‘last mile’ deliveries will be increasingly important with kits, samples, treatments, and patient samples coordinated to monitor inventory levels, and connect the dots to align the placement of orders and deliveries.

WORKING WITH COMMUNITY PARTNERS

Importantly, this added control also reaps benefi ts for companies whose customers, investors, and relevant public authorities are keeping a close eye on their Environmental, Social, and Governance (ESG) goals, focusing on managing complexity, consumption of fuels, and compliance.

It also improves the company’s abilities to engage with new public-private

partnership programs which have been spurred by the success of COVID-19 vaccine delivery and an increased focus on the delivery of equitable healthcare. Blending long-term public perspectives and fi nancial resources with private industry’s infrastructure has, and will, continue to reap benefi ts and deliver healthcare treatments where they need to be, at the right time and the right temperature.

BUILDING RESILIENT AND RELIABLE CONNECTIONS

Resilient and adaptable supply chains are now more important than ever. They need to be able to adapt to a broad range of risks, from economic and social, to geopolitical, all of which can change at a moment’s notice. Creating and relying upon multimodal supply chain networks that can pivot on a global scale to meet these needs will be essential.

To avoid these risks, companies are also actively seeking alternative sources closer to home for their drugs and devices. Nearshoring and diversifi cation of supply chains aren’t simply theoretical. They’re happening now. Operations that are closer to home can reduce expenses and complexity. It provides enhanced control over products and the moderation of the fi nancial impact of restrictions on shipping and deliveries. Simply being in the same time zone as production and shipping simplifi es business and improves collaboration.

Healthcare companies are also seeing growing competitive issues in India and China’s substantial generic drug industries. Companies are asking whether they want to operate side-byside with competitors in nations with diff ering standards of intellectual property protection.

LOOKING AHEAD

A combination of shortened clinical trial cycles, new technologies, next-generation medical innovations, reappraisals of risk tolerance, partnerships, equitable care, and home-based healthcare has set new standards and redefi ned norms for the industry. A shift in healthcare philosophy underlies these advancements. To achieve and prosper under these new norms, healthcare fi rms want the same things – control and consistency, and reliable speed, quality, precision, and visibility/tracking.

A patient who needs a cancer drug or vaccine just hi ing the market can’t wait for weeks while a logistics partner designs a new supply chain. Logistics partners must rapidly adapt and ex existing supply chains.

THREE DIGITAL STRATEGIES TO MODERNISE QUALITY CONTROL IN BIOPHARMA LAB OPERATIONS

Author: Jason Boyd, senior director, Vault LIMS, Veeva Systems

With the proliferation of quality control (QC) digital projects to improve lab efficiency, more QC leaders are adopting standalone applications focused narrowly on a specific need. This can lead to individual biopharma labs using different tools to execute processes, making connectivity and unification difficult. Without a holistic quality data and workflow view, these disjointed solutions, coupled with increasingly complex lab workflows, cannot deliver the expected outcomes or planned ROI.

The opportunity to transform the QC lab is driving LIMS market growth. Although positive change in QC labs operations is happening, more work remains to address growing system silos and complexity while improving quality and agility.

Quality leaders looking to drive change in QC can implement three strategies that will help them advance toward an agile, digital, and connected lab. The approach can streamline sample management, test execution, and lab investigation processes for faster batch

release and reduced inventory expenses.

START WITH THE PROBLEM

While every biopharma organisation is unique, lab managers are expected to find improved ways to streamline their lab throughput. Rather than starting with “this specific tool will solve our challenge,” approach your organisation’s key technology strategists (think CIO or head of IT) to bring together identified business opportunities with the organisation’s technology pursuits.

Often, QC includes a mix of manual processes that rely on a mix of paper, spreadsheets, homegrown solutions and vendor-provided point solutions. Looking at the complete quality ecosystem, and evaluating improvement options that modernise multiple business processes, can make a significant positive impact on the organisation. For example, if analysts use various systems to upload and download files across several departments, a single document repository for all document collaboration can increase right-first-time completion; while relieving some of the pain they experience daily logging in and out and choosing the right system for each document type.

Since QC labs need more than one application to bring together their operations, mapping out end-to-end business processes can help leaders determine what systems or activities need to be streamlined. This process helps assess what to keep, what to expand, and what to decommission. Key considerations include whether the applications currently being used are sustainable, driving cost savings, and aligning with the organisation’s roadmap.

CONNECT PEOPLE ACROSS BIOPHARMA LABS AND TEAMS

Driving successful transformation across quality requires an investment to establish a comprehensive quality platform. Assemble a team representing the complete quality business process to define an achievable timeline, detail the priority of capabilities, and establish a strategy for organisational change management.

Consider consulting firms and vendor services as an extension of this team, to ensure all the capabilities and expertise needed to address any bumps encountered along the journey. Combining internal leaders, industry experts, and partners can provide the right mix of people to ensure a successful transformation.

PRIORITISE TECHNOLOGY THAT FACILITATES COLLABORATION

Once you have the right people on board, decide whether building or buying technology makes the most sense. Developing a matrix for technology selection that encompasses current and future needs and new and existing products, services, and support can drive the conversation forward. The goal should be to enable more connection and collaboration across quality and manufacturing. When evaluating technology, consider:

• Master data management: determine the level of harmonisation or rationalisation for master data within the project and select systems; to be publishers and consumers of data definitions. This should also provide the flexibility and agility to support your long-term data interface strategy without requiring an exhaustive upfront investment

• Anytime, anywhere access to information: arm teams with real-time data and visibility into documents for improved collaboration and better productivity across lab operations, with a goal of bringing all necessary data to each decision point

• Applications built on the same platform: information sharing is seamless in this environment, increasing visibility and efficiency across teams

• User experience: an intuitive UI, robust training, and ongoing services drive faster process improvements and ROI

• Automation: industrystandard workflows automate quality processes and remove tedious, repetitive work, freeing up lab managers and allowing them to focus on high-value deliverables

• Connectivity: open APIs allow for easy integration with other lab systems, like enterprise resource planning (ERP) or lab equipment, streamlining processes, improving efficiency, and speeding batch release times

• Vendor alignment: identify a partner that fits in with your organisation’s goals, is committed to innovation and continually invests in building out their core competencies, and has a solid track record.

Modern systems on a single technology platform can

make it easier to unify the quality ecosystem, from quality assurance (QA) to training to change control and QC. Completing this transformation streamlines end-to-end processes for more efficient execution.

ENDING THE “WHAT’S WHERE” QUESTION

Having a connected solution for all quality data and documents will end the “we don’t know what’s where?” conundrum. Because creating and using a spreadsheet is often viewed as the easiest solution to an existing challenge, organisations need to establish a comprehensive business process supported by an intuitive platform. This will stop the swivel chair approach where personnel pivot from one screen to another, often logging in to different systems simultaneously.

By bringing an opportunity into the broader quality ecosystem, establishing a team of key stakeholders, and conducting a thorough technology evaluation, lab leaders can drive speed and agility across the manufacturing lab. This can optimise lab management and accelerate batch release, improving operations and delivering more value from QC.

Looking at the complete quality ecosystem, and evaluating improvement options that modernise multiple business processes, can make a signi cant impact on the organisation.

Nearly half (48%) of senior decision-makers working for drug development companies or manufacturers said data silos derailed the efficiency of cross-functional collaboration in their organisation. This was a key finding of research commissioned by Aspen Technology, which surveyed 400 global professionals with expertise in drug development or manufacturing to find out where drug manufacturing is headed in the next 3-5 years.

According to the research, larger pharma businesses in particular are more likely to see data silos hinder internal collaboration efforts. More than half (53%) of businesses with total annual revenues of more than US$1 billion said these silos derailed the efficiency of cross-functional collaboration in their organisation versus 44% for companies with annual revenue between US$50 million and US$249 million and 47% for companies with revenues between US$250 and US$999 million range, who said the same.

Raman Bhatnagar, vice president and general manager at Aspen Technology, said: “Information silos are often created by lack of connectivity between data sources across departments, which can hinder efficiencies across the product lifecycle.”

He added: “One way of breaking down the barriers is by deploying products that utilise a common data ecosystem enabling real-time data access.”

Talking points

INDUSTRY-FIRST CANCER SCREENING TECHNOLOGY SECURES BMC FUNDING

Medicines Discovery

Catapult (MDC) and SMi have secured a Biomedical Catalyst (BMC) grant to validate a new approach to detect cancer biomarkers. It will transform their use for routine cancer screening and enable monitoring of treatment efficacy in real-time.

Liquid biopsies are where a simple blood sample is analysed for tiny quantities of cancer-related material (cancer biomarkers). They are increasingly used for early cancer detection, improved treatment guidance (as a companion diagnostic), and to check for recurrence. However, many factors in current approaches hinder their routine use. These include the complexity of test procedures, the expertise and time needed to run tests, and the high costs. New solutions are needed to speed up the adoption of the technique to diagnose this devastating disease.

Under the BMCfunded project, MDC will use SMi’s super-resolution optical platform to demonstrate a new approach that inspects liquid biopsies at single molecule resolution. This will allow

researchers to detect and quantify each cancer indicator. As SMi’s optical platform can be adapted for an almost unlimited range of molecule types, it can be widely used across research and diagnosis applications. This was shown most recently in another successful MDC and SMi project to detect viral genomes, viral proteins, and the associated antibodies the patient produces in response to viral infection.

A crucial part of the current BMC-funded cancer project is screening paired samples using SMi’s optical platform and droplet digital PCR (ddPCR) testing. These technologies are available in MDC’s laboratories at Alderley Park in Cheshire.

SMi’s technology will overcome current technical challenges by rapidly and simultaneously detecting different cancer-associated biomarkers, from a single patient blood sample, in less than one second. This capability will be useful at a time when the number of cancer biomarker panels is growing, but the market still relies upon complex biochemical assays and costly, time-consuming next-generation sequencing (NGS) techniques.

Check out the latest news and insights from the Med-Tech Innovation magazine at: www.med-technews.com.

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The latest episode of The MedTalk Podcast featuring Zillah Anderson from Faculty AI, providing her thoughts on what AI can do for healthcare this year.

Data silos threaten e ciency levels for nearly half of pharma businesses

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