EPM May 2022 by EPM Magazine

www.pharmaceuticalmanufacturer.media AN OPTIMAL BIOPROCESSING APPROACH

ADOPTING SUSTAINABLE PRACTICES IN BIOPHARMA

POST-PANDEMIC LESSONS

May 2022

KEEPING ON THE GREEN TRACK: THE CHALLENGES OF SUSTAINABILITY

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Contents May 2022 | Volume 22 Issue 3

REGULARS 5. EDITOR’S DESK

A welcome return to pharma trade shows.

6. SMALL DOSE

A brief round-up of some of the latest developments in the industry.

14. COVER STORY

Merck updates EPM on the steps taken to achieve its sustainability goals.

16. OPINION

CRB explains how lessons from Covid-19 can help guard against emerging pandemic threats.

26. TALKING POINTS

Stories to consider and what to look out for in EPM over the coming weeks.

FEATURES 8. COMPLIANCE

Covectra asks: what next for DSCSA?

18. SUSTAINABILITY

Cytiva comments on life science’s approach to sustainability.

24. BIOPROCESSING

Avantor explains the optimal approach for downstream bioprocessing production.

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THE ROAD TO NORMALITY

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It’s great to see the return of trade shows, with a signiﬁcant return to in-person events over the last two months across Europe and the United States

his is a rarity, but it’s great to do something a little different and introduce you to this edition of European Pharmaceutical Manufacturer, at a time when things are beginning to feel that little bit more normal. Speaking of normal, it’s great to see the return of trade shows, with a significant

return to in-person events over the last two months across Europe and the United States, notwithstanding the current geopolitical situation and Covid requirements. I am looking forward to seeing as many of you as possible at Pharmapack in Paris, while I also wish those reading this issue at

EDITOR’S DESK Pharmintech and Interphex a warm welcome back to the trade shows floors and hope we can get reacquainted in the not-too-distant future. Judging from the conversations I have had it feels that the clamour for having face-to-face interaction has really returned in earnest with its significant benefits and is

much preferred to sitting at different ends of a computer screen. Despite the progress that has been made following the emergence from lockdowns in the western world, there is that degree of uncertainty that remains. There will undoubtedly be new variants that emerge and despite the overwhelming majority being fully vaccinated, and the vast majority of those individuals also having received a booster shot, there is a feeling of “what if?” There is still that trepidation as to what the future holds for some companies as they look to six months or a year down the line. What if there is the need for more restrictions, for example? One positive to take from the last couple of years is that vaccine manufacturing is now significantly better prepared to address any supply chain issues, should the need for another ramp up be required in the not-too-distant future. Away from the Covid aspect there are a couple of things I will keep an eye on. If I were to be so bold to predict the future (and I do not have a crystal ball), I would say smaller M&A deals are likely to be a trend, compared to the mega-deal M&A’s of the past, with C&G therapies, vaccines, biologic production now taking more attention which will be music to the ears of start-ups, biotechs and university spinouts who will be the major benefactors. If this proves to be the case it would mean new names on the scene, and more entries to the market – making this a very exciting time for the industry.

A small dose

Biomarker research boost for spinout Empower Therapeutics

esearch shows that a brainwave biomarker licensed by digital therapeutic spinout Empower Therapeutics can reliably and accurately identify patients with high sensitivity to pain. The study, which was carried out in Birmingham, U.K. by an international collaboration of researchers, showed that the biomarker can predict which patients have a pain score of 7/10 or higher following chest surgery (thoracotomy).

Before surgery, the team measured the patients’ alpha waves. Over 72 hours following surgery, participants were asked to score their pain on a scale from 1-10. The researchers were able to demonstrate a clear link between the patient’s alpha waves and their responses to pain. They found that people whose alpha waves oscillated below 9 Hz were much more vulnerable to severe pain post-surgery. The brainwave biomarker is being leveraged by University

of Birmingham spinout Empower Therapeutics to both identify pain sensitive individuals and change their perception of pain. Building upon the reported diagnostic capabilities, Empower Therapeutics aims to create digital therapies that measure and modify the biomarker to reduce pain sensitivity and relieve chronic pain. Formed in 2021, Empower Therapeutics is led by CEO Steven Rothenberg, M.D., a serial entrepreneur and

COVESTRO AND PHARMAJET REMOVE STING WITH COLLABORATION

olymer company Covestro has announced its collaboration with PharmaJet, a biotech company in needle-free injection technology. PharmaJet’s Needle-free Injection Systems (NFIS) provide a more effective way of administering drugs and biologics, and are preferred by patients, caregivers, and healthcare workers. NFIS are used as the method of delivery in 20+ Covid vaccine development programs and the world’s first plasmid-based DNA vaccine which recently received Emergency Use Authorisation for Covid in India. The PharmaJet systems require a polycarbonate material to meet the specifications of the syringe and vial

adapter while standing up to gamma radiation and ethylene oxide sterilisation. Chris Cappello, president and CEO, at PharmaJet, said: “We needed a polycarbonate resin that was suitable for our biotech applications and came from a vendor we could rely on. Covestro has provided great support to PharmaJet in the fight against Covid-19, allowing the

collaboration to achieve better immunological results than needle and syringe delivery.” Mark Nichols, healthcare key account manager, Covestro, added: “Covestro is honoured to provide a reliable supply of Makrolon polycarbonate that meets the demand of needle-free injection, ultimately leading to a better patient experience, and reduced waste.”

physician, and CSO Andrew Furman, Ph.D, a pain neuroscientist who contributed to the foundational biomarker research at the University of Maryland, Baltimore and co-authored the present study. The study was led by Dr Ali Mazaheri from the University

Discovery joins Industrial Bi Discovery Park, based at Sandwich in Kent, has become the first Life Science and Innovation Campus to join the Industrial Biotechnology Innovation Centre (IBioIC), further cementing its ambition to become a centre of excellence. The move is part of Discovery Park’s wider commitment to engage with the UK’s industrial biotechnology community, supporting innovation and commercialisation of new industrial biotechnology (IB) processes and products. With the global drive towards sustainable living, IB offers a green and alternative to fossil fuels, whether it’s for energy, medicines, or sustainable food sources, and is at the heart of all net zero ambitions. Joining IBioIC allows Discovery Park the opportunity

to link with a broad but interrelated network of industry, universities, and governments to bring biotechnology processes and products to the global market. Discovery Park’s drive towards IB builds upon the site’s reputation for drug discovery and manufacture, having been home to Pfizer since the 1950s. Work is currently underway to refurbish 50,000ft2 of laboratories and collaborative workspace, creating an ‘incubator’ for start-up biotech and life science businesses. Jane Kennedy, chief business oﬃcer at Discovery Park, said: “The Industrial Biotechnology Innovation Centre has undoubtedly done a fantastic job of catalysing the growth of the sector in Scotland. It is clear to me that joining the IBioIC offers

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I am excited about the possibiities and potential of this cutting-edge research of Birmingham’s Centre for Human Brain Health with contributions from co-author Dr David Seminowicz from Western University (Canada), both of whom serve as scientific advisors to the company. Dr Blakely O’Connor, a Harvard-trained bioengineer and COO of Empower Therapuetics, said: “I am excited

about the possibilities and potential of this cutting-edge research to translate into tools and therapies that enable people to alleviate pain with fewer drugs and invasive interventions. It is encouraging to see our therapeutic target validated as a meaningful measure of pain sensitivity for patients in a clinical setting.”

Strong growth in the US boosts revenue for Boyds

oyds, the global drug development consultancy, has reported an increase of more than 20% year-on-year in annual revenue in the wake of increased demand for its expertise across the UK, US, and Europe. Since the opening of Boyds’ US oﬃce in Pennsylvania last year the company has recorded significant growth in US revenue, which now accounts for approximately 30% of its total revenue. Boyds has a reputation for its work in cell and gene therapies and has led to a steady increase in the number of companies approaching Boyds for its expertise, particularly in the US.

Professor Alan Boyd, president and founder of Boyds, said: “As a result of a two-year strategic review of the business, Boyds has evolved significantly over the past 12 months, and we are now seeing our investments in the US, our UK and Ireland oﬃces and in our team, really pay off. We have recruited 17 people to the team in the last 12 months, bringing our total global headcount to 34, with more recruitment already underway, including in the US. “Boyds has worked on multiple new projects involving investigational products for over 28 new clients over the past 12 months, all of which are at the cutting-edge as novel technologies.”

iotechnology Innovation Centre

Discovery Park opportunities to collaborate and make connections between my tenant companies in Kent with the fastgrowing network in Scotland. We hope to bring together companies that can learn from each other how to turn great ideas into great businesses.” Mark Bustard, chief executive of IBioIC, added: “The innovation centre plays an important role in supporting the growth of the UK’s bioeconomy, connecting industry partners with worldleading research teams to

explore alternative bio-based materials and processes across a range of sectors. So far, we have supported more than 200 companies to bring new products to the global market and connecting with IB research and science hubs such as the Discovery Park will no doubt unlock further opportunities. Almost £30 million of additional industry investment has been generated as a direct result of IBioIC innovation activities to date, contributing to more than 3,000 high-value green jobs.”

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COMPLIANCE

Author: Andre Caprio – director of business development, Covectra.

he Drug Supply Chain Security Act (DSCSA) has been an active topic of discussion amongst companies in the pharmaceutical supply chain for the past eight years. Enacted by Congress in November 2013, Title II of DQSA outlines the steps to achieve interoperability, electronic tracing of products at the package level, to identify and trace prescription drugs as they are distributed in the US territory. Since its inception, key industry associations, including the Healthcare Distribution Alliance (HDA), Pharmaceutical Development Group (PDG), and GS1 have dedicated exclusive panels to debate the impacts of DSCSA and to provide valuable resources in efforts to collaborate for this industry wide objective. Although considerable progress has been achieved during the previous years, much work is still required until the pharmaceutical industry can finally “flip the switch” for DSCSA. Supply chain disruptions caused by the Covid-19 pandemic, coupled with a shift in focus towards vaccine development and distribution, have contributed to creating delays in DSCSA compliance efforts. Nonetheless, per

What next for DSCSA? interoperable with approximately 1-5% of their trading partners. Furthermore, a major distributor, member of the Big Three family (the three largest distributors in the US), indicated concerns around data quality and failures caused by EPCIS/DSCSA syntax or semantics issues when receiving files from trading partners. These issues were present amongst third-party logistics providers (9% failure rate) and manufacturers (37% failure rate). Part of the challenge around data interoperability is because several serialisation solutions providers exist, each with their own proprietary software products, with thousands of trading partners in the pharmaceutical supply chain hosting their own data. Although some progress has been achieved in connecting these systems, the process has proven to be lengthy and labour intensive. DATA QUALITY CONCERNS AT THE MANUFACTURER LEVEL Throughout 2018 and 2019, the FDA ran a series of pilot studies that aimed to assess the impacts of having stakeholders verify the authenticity of a pharmaceutical product by scanning its unique data matrix barcode and authenticating it against the manufacturer hosted serialisation database. Simply put, once a product was scanned, the manufacturer’s system would provide a positive or negative result based on the unique information embedded on the product’s data matrix. Although the enforcement of this specific DSCSA milestone was later delayed in 2020, the results of the pilot studies were peculiar, with a high percentage of authentic products (upwards of 25%) returning a negative confirmation. Many manufacturers were puzzled as to the cause of these “false negative” results. Upon further investigation on the embedded data contained in the faulty barcodes, the most common issues included the wrong placement of comma separators, use of double zeroes for lot and expiry dates, amongst other technical issues. Furthermore, it was concluded that most of the data errors were because of

the FDA’s recent guidance during its public meeting in October of 2021, further enforcement discretions are highly unlikely to be granted. Therefore, the target date for full compliance and interoperability has been set for November 27th, 2023. INTEROPERABILITY REMAINS THE BIGGEST HURDLE As DSCSA legislation states, trading partners in the pharmaceutical supply chain must have systems in place which enable the capture, storage (up to six years), and transmission of data in EPCIS format amongst stakeholders. EPCIS is a GS1 standard that enables trading partners to share information about the physical movement and status of products as they travel throughout the supply chain – from business to business and ultimately to consumers. During the annual Traceability Seminar in November 2021, the HDA disclosed results of its recent supplier survey around data interoperability progress, which were far from encouraging considering the legislation was two years away from the ultimate deadline at that time. In this study, 54% of respondents were manufacturers and 46% were distributors. Amongst all participants, only 37% indicated they were actively

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10 brand owners using CMO’s and contract packagers which were utilising serialisation solutions yielding poor results. The same scenario was raised by another distributor during the HDA’s annual Traceability Seminar in 2021. Here, the distributor indicated that at that time, less than 50% of manufacturers had the means to correct errors on their EPCIS files and data matrix barcodes. Additionally, low supplier onboarding activity and steady decrease in the engagement between manufacturers and distributors for data interoperability was a cause of grave concern. ONGOING CHALLENGES IN THE DISPENSER COMMUNITY As mentioned, the Covid-19 pandemic forced the supply chain to temporarily shift its efforts from compliance towards vaccination. Dispensers were placed at the forefront of this battle and were naturally induced to focus on this matter as highest priority. This change in focus was clearly visible as only 9% of the participants during the HDA’s 2021 Traceability Seminar were organisations from the dispenser community. As well as diminished engagement around DSCSA compliance, budget constraints are an important factor which dispensers must consider, especially amongst independent pharmacies. It is anticipated that once dispensers are obligated to acquire their own serialisation

COMPLIANCE

solution, expenditures could amount to over $20,000 yearly. Assuming there are over 67,000 dispensers nationwide, the average cost of this requirement would be over $1 billion annually for this sector of the pharmaceutical industry. With cost as a primary determinant, the industry is likely to see the continuing trend in which distributors act as the data repository for their respective dispenser clients. During the first phase of DSCSA compliance, which required trading partners to exchange lot level data in the form of EDI Advanced Shipping Notifications (ASNs), this was an easier task to achieve. However, when dealing with serialised data and the ability for a dispenser to reconcile received products against EPCIS files, additional challenges are likely to arise. The burden will be placed on the distributor to host the serialisation data and facilitate how their dispenser customers can access and utilise this data as part of a daily workflow. CHALLENGES AND OPPORTUNITIES BEYOND 2023 Once DSCSA is in full effect, the pharmaceutical industry will be well equipped with a wealth of data pertaining to pharmaceutical products flowing through the supply chain. This complex data network will provide many added benefits extending beyond the obvious compliance requirements. Improvements in internal processes will occur organically, including enhancements around product verification and visibility within the supply chain - and eventually down to the patient level. Natural enhancements are likely to occur in the drug recall process, including more accurate chargeback and rebate processes. Also, pharmaceutical suppliers will benefit from a granular view of inventory movement through the supply chain, thus having access to data to better direct sales and manufacturing operations.

The outlined benefits are not immune to potential challenges imposed by the pharmaceutical industry and its governing federal regulators. As an example, the FDA’s Enhanced Drug Distribution Security at the Package Level draft, a concept introduced by the FDA in June of 2021. This guidance provided insights pertaining to aspirations of implementing a semi-centralised data repository, managed by the FDA, in which all trading partners would have to report to - an effort not well received by key stakeholders in the pharmaceutical industry and is highly improbable to take place soon. Further improvements in DSCSA compliance are only likely to happen if it adheres to the legislation’s original draft.

Once DSCSA is in full eﬀect, the pharmaceutical industry will be well equipped with a wealth of data

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PERSPECTIVE ON PHARMA

How pharmaceutical manufacturers can beneﬁt from moving to cloud today

or pharmaceutical manufacturers, progressing digitalisation and moving to the cloud has been notoriously slow, and misperceptions of what moving to the cloud entails have been a significant factor in this lack of adoption. Manufacturers with established legacy systems are often unduly concerned about the security aspects of moving to cloud. They have also been hesitant to invest in new infrastructure, even though the long-term savings offered by cloud platforms outweigh its short-term costs. Despite this lag, the move from on-premise, local software installation, to cloud has become more commonplace. Many manufacturers have taken an intermediate hybrid cloud approach, which refers to a mixed computing, storage, and services environment made up of on-premises infrastructure, private cloud services and a public cloud. The trends of digital transformation and the International Society for Pharmaceutical Engineering (ISPE) Pharma 4.0 initiative have laid the foundations for the move to hybrid cloud. The ongoing need to drive speedKELLY DOERING - senior director, Industry Marketing, Pharma, AspenTech

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to-market and to be ready for demand spikes has been put into focus by Covid-19. In line with this, pharmaceutical manufacturers are adopting hybrid cloud infrastructure to enhance operational eﬃciencies, reduce IT burden, drive costs down and improve data accessibility and analysis. This migration is gathering pace. Thanks to the Internet

of Things (IoT), the breadth of connected equipment and systems available to pharmaceutical companies has been growing. Along with the goal of delivering medicines to market faster and minimising supply chain disruptions, another reason for embracing cloud solutions is the growing amount of data that accompanies a drug manufacturing project. The

There is a real need for pharmaceutical companies to aggregate data from multiple sources.

complexity of modalities being developed for therapeutics has resulted in more variables to measure, meaning larger data files and greater data volume. There is a real need for pharmaceutical companies to aggregate data from multiple sources, including manufacturing, lab systems and enterprise resource planning (ERP) solutions. By aggregating those data, businesses have greater opportunity to mine it, creating an integrated overview of how the whole business is performing. Cloud solutions can augment validated onpremise solutions and data can be extracted to feed machine learning. Cloud can also support the implementation of advanced digital solutions in remote locations with limited IT support. Many pharmaceutical companies are starting to think through applications and use cases around cloud, but questions remain. What sort of data from manufacturing, labs or financial systems should be in the cloud, for instance and what should reside at plant level? What kind of cloud-based applications should they use? What is the data strategy pharmaceutical companies should follow, in the pursuit of greater accessibility to data for sharing, analysis and reducing the IT burden? The biggest question, however, is how can companies take advantage of the cloud now? Simply, the first step is identifying the pain points; building strategy, aligning with the company’s business initiatives, and securing buy-in. The second is to determine key performance indicators (KPIs), plan and implement pilots, then assess and scale. New cloud-based approaches using AI and predictive capabilities are already delivering gains in the eﬃciency and time-to-market of batch releases, for example, resolving

13 the bottlenecks around reviewing of data. Electronic record-keeping and the reduction of human error mean organisations benefit from fewer lost and increased data integrity. STEP-BY-STEP Process predictions is one area pharmaceutical companies often focus on, especially if quality or reliability may be at risk. Implementing predictive technologies is often the first step pharmaceutical companies take on their move to cloud because it is lower risk. The results raised by predictive technologies around likely equipment failures further down the line are early flags that, if acted upon, will prevent problems occurring later, and minimise unplanned downtime. With relevant data collected and integrated seamlessly, the workflow can be made more efficient with data in one place, and checks and controls can be handled electronically by automated systems, both on-premise and ultimately in the cloud where there is even greater accessibility to data. REAPING THE REWARDS Most pharmaceutical companies can benefit from cost savings. The cost of building and scaling an on-premise IT set-up can be exorbitant. By moving to the cloud, pharmaceutical companies can offload much of this. Having data available in the cloud drives efficiencies. In the development process, firms can start to circumvent the process of having to churn through reports and spreadsheets. Starting out on the journey to the cloud is becoming an imperative for pharmaceutical companies. They don’t have to do everything in one go but by getting underway they can use data to drive business advantage and competitive edge.

COVER STORY

EPM sits down with Merck’s Jeffrey Whitford to ﬁnd out about where the company is up to in terms of its sustainability initiatives.

he last time we spoke to Merck KGaA the company was in the early stages of launching its Design for Sustainability initiative (DfS) – a project intended to revamp the way research & development (R&D) was conducted throughout the business, all with the aim of developing more environmentally friendly products. Then, when speaking to Whitford, head of sustainability and social business innovation, Merck he told us of some of the spot successes the company had had with designing more sustainable products. Now he tells us of a fundamental change in the business. DfS is now being “driven into our processes and becoming a part of the everyday work that the scientists are doing, [it’s] not just optional now but really required,” Whitford says. What this means for Merck is that sustainability is being systematically embedded throughout the company’s R&D teams, which each product undergoing a type of evaluation into its sustainability credentials. This doesn’t mean every product will be environmentally friendly, but Whitford insists that the number of “products coming out of our R&D pipeline are definitely going to be greener alternatives.” Of course, the trouble is that for a company involved in developing so many products used within life sciences - biologics, chemicals, instrumentation, equipment – the structural requirements needed to make

KEEPING ON THE GREEN TRACK: THE CHALLENGES OF SUSTAINABILITY

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DfS happen are huge. One of the things Merck is doing now for DfS is making it operational so that the scientists involved in developing all these products feel supported and have the tools available to do the science with a sustainable approach. “One of the things we hear from our scientists is it’s hard enough to do the science, so the sustainability layered on top, we don’t have that capability. That’s where we from the sustainability department side of things think about how do we support them so we can build that capacity, develop more trainings, get them more experience, which means then we build more systematic approaches to sustainability,” Whitford says. Merck has been somewhat of an early adopter in terms of how it presents its sustainability goals to the public. We’re speaking to Whitford shortly after the COP26 conference finished in 2021 – a conference which saw many life sciences firms sign up to green initiatives – and sustainability has firmly established itself in the lexicon of businesses all across the world.

Many companies now sport longer term goals to reduce their carbon footprints and Merck is among those businesses that have ambitions stretching as far as 2040 – which by then the company wants to have achieved climate neutrality. But whilst its ambitions are worthy, pharma’s path to climate neutrality isn’t clear. “To be honest I don’t think anyone has a clear roadmap to 2040 and to zero [emissions],” Whitford suggests. Merck though, he thinks at least has a plan to build more clarity and more consistency in its approach. With DfS acting as the cornerstone of the company’s sustainability efforts, any product coming out of Merck will be assessed in terms of its environmental impact. This means that over time, Merck will get a clearer idea for how each product impacts Scope 1, 2 & 3 emissions – in other words the greenhouse gases it produces directly, its indirect emissions such as those covered by heating and electricity, and the emissions the company is indirectly responsible for throughout its value chain. Right now, DfS is being applied to the new products Merck

is developing but the plan is, over time, to apply it to the company’s legacy products. “One of the challenges with those products is that there are certain products that are basically impossible for us to make changes to because they’re already specced into governmental approvals,” Whitford explains. However, for products that aren’t burdened by regulatory barriers, Merck can go back and examine whether they can be developed through more sustainable means. There are about 53 products that currently exist in that portfolio, Whitford says, explaining that he hopes to see this number dramatically increase in the future. Coming out of COP26 Whitford feels encouraged by the increased activity he’s seen within the pharma sector. Disregarding the announcements made at that conference, Whitford says that as a supplier, Merck is now being asked more questions by the likes of major pharma companies into how they can decrease their environmental footprint. As Whitford puts it - “we’re feeling it.”

We need people to plant the flags for others to see where people are headed

It’s definitely a boon that the likes of AstraZeneca, Takeda, Johnson & Johnson, and other of the major players, have now signed up to a global initiative aimed at decarbonising pharma’s global supply chain. Whitford knows that the supply chain is the industry’s biggest hurdle when it comes to sustainability, so having the big players announce their intentions shows the sector’s commitment to change. “We need people to plant the flags for others to see where people are headed. That signals to the market that this is going to be something that people are doing. That changes peoples’ preparation, it changes the reference point because people can point back and say we put ourselves out on the line on COP26, there are people holding us accountable, the whole world is looking at us,” he says. The announcements made at COP26 then show an industry which is ready to commit to becoming more sustainable. And, much like what Merck is doing through DfS, the industry has nowhere to run if it fails to deliver on its sustainability targets. This space for accountability will be so important going forward. Merck seems prepared to show where it’s succeeding and where it isn’t, and the company’s commitment to sustainability mean that it must stay on this path going forward. Whitford knows that if the company or industry strays too far, then they’ll be called out for it.

Opinion

For all its bleakness, the Covid-19 pandemic showed what was possible when industries unite

POST-PANDEMIC LESSONS Authors: NOEL MAESTRE, PE, vice president of Life Sciences and DAVID ESTAPE, technology manager Biotechnology at CRB

Virus response rewrote the playbook for vaccine response, but even more change is necessary to deal with emerging threats. Across the world, governments and biopharma organisations are absorbing the lessons of the Covid-19 pandemic. With much of the world now in endemic protocols – managing the virus, yet wary of variants potentially in wait -- there is an enormous amount to understand about what worked, and what didn’t, in the race to deliver effective life-saving vaccines and therapies. As we move toward virus management, we marvel about everything it took to get us here. New ways of accelerating from R&D to manufacturing. New models for partnership and collaboration. A whole new mindset, which casts off our industry’s conservative nature in favour of more innovation, more speed, and more flexibility with the goal of more lives saved. As the Omicron variant emerged in late 2021, CRB released its newest Horizons: Life Sciences report, built with an exhaustive survey of more than 500 industry leaders who answered nearly 80 questions. The resulting data revealed two intersecting trends which will define the post-pandemic era for our industry. First, the science of drug manufacturing: Clinical teams are developing novel therapies capable of preventing and curing diseases that, until now, have eluded effective treatment. We watched this happen in real time as the world’s first mRNA vaccines emerged last year, but it’s a shift long in the making; consider the scale of private investment in cell and gene therapy

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research, which reached nearly $20 billion in 2020 and subsequently $23 billion in 2021. The last 24 months have only accelerated that trajectory. Second, a radical reconsideration of the way drug developers think about how our industry operates. Dissatisfied with traditional design-bid-build methods and galvanised by the speed of our industry’s pandemic response, many project leaders are turning to much faster and more agile solutions. They’re leveraging the predictive capabilities of AI and machine learning to build smarter, more secure, and future-ready manufacturing centres. And they’re redesigning the traditional GMP cleanroom to accommodate closed and automated processes—a necessary step toward improving the cost and quality of tomorrow’s medicines. With these macro shifts underway in both the science and the practical realities of drug manufacturing, what’s happening at a more micro level—the level of on-the-ground decisions that today’s companies make every day, around the world? WARP SPEED DRUG DELIVERY: What began as a rallying cry to ignite our industry’s rapid pandemic response is now a permanent feature of drug delivery—warp speed, in other words, is the new cruising speed. In fact, our survey finds that “speed-to-market” jumped from a lower-ranking business driver before the pandemic to the top priority today, overtaking cost-based considerations by a healthy margin. We reveal what this “warp speed” state of mind means for companies planning their commercial scale-up strategies. CELL AND GENE THERAPIES: We examine what cell and gene therapy developers can do to plan for long-term commercial success while so much change is underway at the lab bench. Drawing from our survey data, Peter Walters takes a close look at how technologies like single-point, process-in-a-box systems will transform the future of drug manufacturing. RNA TECHNOLOGIES: The pandemic thrust mRNA technology into the spotlight, rapidly catalysing years of research into life-saving vaccines. But as our survey data shows, that’s just one slender chapter in a complex story. More than one-quarter of respondents are pursuing or plan to pursue RNA therapies across a wide array of indications, from autoimmune diseases to oncology. As their pipelines mature, these companies face new questions about supply chain management, facility design, and scale-up. THE NEW WORLD OF 4.0: Four-fifths of our survey respondents identified their company in the top three tiers of the five-level Digital Plant Maturity Model (DPMM), and most aspire to Level 4, defined by digital facilities that leverage predictive analytics. We explored the obstacles to unlocking the full potential of AI and machine learning.

OLIGONUCLEOTIDES: After decades of research, the science of oligonucleotide manufacturing is on the brink of graduating from the lab bench to the bedside—and once it does, it will change many patients’ lives. That’s why nearly a quarter of our survey respondents have oligo therapies in their pipeline, or are planning to add them in the near future. What challenges will these companies face as they approach commercial manufacturing? LEAN DELIVERY: When we asked about project delivery, we noticed an interesting schism: most say that they rely on design-bid-build or design-build, and yet, in the next question, they ranked those very delivery methods as least satisfactory compared to more lean and integrated models. How can companies better match their project delivery approach with the need to move fast and maintain quality. SUSTAINABILITY: Moving from chronic treatments to one-time curative therapies is our industry’s next big innovation, but if we’re destroying our planet in the process—well, where does that leave us? That’s why it’s encouraging to see that the majority of respondents have a sustainability strategy in place. But how are different organisations using that strategy to balance the needs of the planet, the people inside their company, and their bottom line? Disruption is the only constant For all its bleakness, the Covid-19 pandemic showed what was possible when industries unite. Those of us who rolled up our sleeves for an mRNA Covid-19 vaccine may do the same for an mRNA cancer vaccine in the future, and we have the playbook to move smart, safe and fast. And February’s latest scientific breakthrough of the first CRISPR edited heart transplant spells very promising implications for the future of in-vivo gene editing. Those whose diseases would have once shortened their lives will have access to genetically engineered therapies that could eliminate their diseases altogether. This is the future of life sciences. These revolutionary ideas promise effective therapies and sustainable new business models, but they also introduce all-new challenges. We won’t overcome these challenges using the same old tools that served our industry in the past. To succeed, we need the willpower to undertake an honest examination of our industry, our companies, and our facilities, eliminating the systems that no longer work and making room for innovation and reinvention. Instead of slow and incremental change, we need bold action. Instead of outdated checks and balances, we need delivery strategies that balance risk with progressive new ideas. Instead of competition, we need collaboration. This is how we will prepare ourselves for what’s to come. It’s the only way.

SUSTAINABILITY

Adopting sustainable practices in biopharma One example from our packaging targets is to eliminate polystyrene from our packaging materials from our supply chain.

Quick questions with Ryan Walker, Cytiva’s sustainability program leader How does biopharma compare to other sectors when it comes to sustainable practices? Sustainability is a great unifier for the life sciences industry. In recent years we have seen an acceleration in the adoption of sustainable business practices. The industry is coalescing around how we should deal with plastics, waste management, carbon, and emissions. It’s going to take all of us working together – customers, manufacturers, and suppliers to tackle these issues. Are you encouraged by the life sciences industry’s progress in becoming more sustainable? Yes, I am very encouraged by the how the life sciences industry has come together to tackle this challenge. Progress in sustainability is complex and we must remember that each ‘action’ has domino effects, so something such as the recycling of plastics must be looked at from all environmental and societal angles. Cytiva has committed to ambitious targets toward 2025 – spanning carbon emissions, water, plastics, and packaging.

The life sciences industry uses a lot of single-use plastics. What have been some of the challenges when trying to recycle single-use plastics? It’s important to point out that single-use plastics are a better alternative than stainless steel manufacturing methods, which require a lot of water and chemicals to change batches. According to two life cycle assessments (LCA) commissioned by Cytiva in 2016 and 2018, single-use technologies have the environmental advantage over traditional stainless-steel manufacturing. It requires less energy and eliminates water and chemicals for cleaning during use, yet it still has its challenges. Complex composition, plus the biocontamination, make some plastics used in the manufacture of biological medicines diﬃcult to recycle. Some of the other challenges include: • Limited ability to process different types of plastic • Some products include rubber and metal, in addition to plastic. Then the question becomes who is responsible for the recycling? • Many recyclers are not capable of ‘cleansing’ a plastic product that has been biocontaminated so it can be recycled. Progress is being made but this part is strictly regulated and therefore diﬃcult to do. This is a great example of how the industry has come together to find innovative solution to recycle plastics. Representatives from Cytiva are working with industry organisations to find ways we can work with other life sciences companies to redesign products, rethink packaging, and address the end-of-life recycling options. There are shorter-term focus areas in mechanical recycling

and longer-term focus areas in advanced (chemical) recycling. The goal is to design products that take environmental factors into every phase of the design process. Could you tell us about Cytiva’s initiative with TerraCycle on recycling plastic ﬁlters? This is dedicated to reducing plastic lab waste – specifically it’s set up to recycle filtration devices and turn them into something new. Labs collect their plastic waste in a Zero Waste Box, send it back to TerraCycle, who sorts and recycles the plastic. What do you think of some of the announcements made by pharma companies at COP26? The commitment from companies to create more sustainable business practices was very exciting. Our goals will be achieved by working together- not just industry, but governments, NGOs, to address this global challenge. Our mission and vision align with good health and well-being, but we aren’t stopping there. We conducted a materiality assessment to understand where we can have the greatest impact and that has led to environmental focus areas such as climate action, clean water, and responsible consumption and production to working across the value chain in partnership for the goals. Is the need to become sustainable encouraging innovation within the biopharma manufacturing process and supply chain? The need to be more sustainable is encouraging innovation across the life sciences ecosystem. From programs such as TerraCycle to commitment to creating products that minimise the use of resources and materials. Circular design is bringing more functions together to share expertise and create more sustainable solutions.

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SUSTAINABILITY

The steps the industry has taken so far in relation to sustainability and the remaining possibilities

Author: MICHAEL EARL - director, Pharmaceutical Services at Owen Mumford

he pharmaceutical industry has an important role to play as the world strives to create a more sustainable future. The significance of big pharma’s impact is highlighted by the fact it produces 13% more carbon emissions than car manufactures do assembling vehicles. Pharma companies are now determined to reduce their carbon footprint, eliminate pollution, conserve water, and use sustainable components. This means the entire supply chain will need to improve environmental, social and governance (ESG) standards as businesses seek to work with sustainable partners to strengthen their own credentials. Additionally, the ‘Greener NHS’ programme includes a commitment to be net zero with any emissions it can influence by 2045. All healthcare suppliers looking to have a continued relationship with the NHS must adapt as quickly as possible to remain a viable choice as the NHS seeks to meet this goal. In line with this, Owen Mumford Pharmaceutical Services has committed to achieving net zero emissions by 2045 and

to achieve a 50% reduction in emissions by 2030. To get a clearer picture of the measures being taken by the pharmaceutical industry, Owen Mumford Pharmaceutical Services has reviewed the current state of play on ESG compliance among the top 25 pharmaceutical companies

reporting ESG scores. This article will look at the key areas where progress is being made and where improvement is needed to create a sustainable industry for the future. PROGRESS SO FAR This article focuses on four key areas of activity:

carbon emissions, water use, waste management and sustainability by design. Owen Mumford Pharmaceutical Services’ analysis focuses both on ESG policies that have been put in place as well as where companies have publicly set concrete targets.

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AIR EMISSIONS Almost 70% of pharma companies have specific targets for reducing carbon emissions and gaseous pollutants. Acid gases, dust and aerosols, pharmaceutical ‘actives’ and volatile organic compounds are typically being targeted for filtering. ENERGY Most energy policies have a threefold approach – combining use of renewable energy, self-generation and increasing energy eﬃciency in the manufacturing process. Reducing energy use in the manufacturing process can be focused on either the production line or industrial

buildings, with savings of 25% or more common in both areas. WATER Water usage focuses both on consumption as well as cleaning and reprocessing water. One international generics giant aims to achieve 100% water neutrality by 2025 meaning all wastewater will be recycled, reused, or captured from rainwater. Our review shows an impressive 50% of pharma companies have set hard targets in this category. WASTE Over a quarter of pharmaceutical companies have already set targets to reduce their waste emissions

plastic components in medical devices are being explored, and immediate progress is being made by reducing the number of disposable parts. At Owen Mumford Pharmaceutical Services, we are using our experience in auto-injectors to develop new designs for reuseable auto injectors, which will help our partners reduce plastic waste considerably. AREAS FOR ACTION Although the industry achieved an impressive ESG score of 61% in the Ecoact’s October 2021 Climate Reporting Performance report – well above the all-industries average of 53 % – the performance of individual companies varied

Pharma companies are now determined to reduce their carbon footprint by 25%. Companies are attempting to remove reliance on landfills or pursue a zerowaste approach. Additionally, commercial incentives are becoming a factor as waste becomes more expensive to dispose of, while rising commodity prices may encourage firms to recognise waste as a source of scarce resource. For medical device suppliers, reducing the footprint of their products is particularly challenging since infection control often demands that devices are single use and immediately disposed of after use. One strategy to mitigate this is to review the entire manufacturing process and product life cycle for ineﬃciencies. Meanwhile, alternatives to disposable

significantly. Our study shows a 40% difference between top performers and those behind the curve. Moreover, it appears that neither size nor location impede progress; corporate will and commitment to improve ESG scores are as important as big budgets, allowing smaller firms to progress at similar levels to large multi-nationals. CONTAMINATION The Anti-Microbial Resistance Alliance reports that emissions from the production of active pharmaceutical ingredients and their formulation into drugs are a further source of emissions – particularly in countries where discharges are not well controlled. Yet, while 84% of companies have a policy on Pharmaceuticals in the Environment (PiE) and 36%

21 have a policy on Anti-Microbial Resistance (AMR), there are very few concrete targets in these areas. PACKAGING Since this is a relatively straightforward area for setting targets, many other industries reviewed packaging as a first step in their journey, particularly in the distribution phase. Meanwhile, in the pharma industry, 76% have policies for packaging, but only 13% have set concrete targets. Progress could be made by converting to sustainable alternatives or reducing weight and increasing packing eﬃciency to reduce shipping resources. Some leading companies have set specific targets – focused on converting to recyclable/ sustainable paper where possible, to replace plastics. It is likely that this area will gain traction within the rest of the industry in the coming years. CONCLUSIONS Studies show the pharmaceutical industry is heading in the right direction in the drive for sustainability – with performance better than many other industries. Regardless, policies have to turn into targets – particularly within the areas of contamination and packaging – and targets must continue to be met if they are to remain ahead of the curve. Initiatives such as the B Corp certification achieved by Owen Mumford help companies to set achievable targets, and then set milestones to stay on track. Third party audits hold businesses accountable and make sure they don’t lose sight of their goals. Collaboration between pharma businesses and their suppliers may help to narrow ESG variance and consolidate sustainable action in the industry.

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Figure 1 – Borealis Circular Cascade Model

ACCELERATING ACTION

on environmental sustainability in Healthcare Author: Paulo Cavacas Business Development Manager, Healthcare The vital role of plastic solutions in healthcare became even more prominent during the Covid-19 pandemic with many single-use medical devices, pharma packaging, diagnostic consumables and masks being used – now not only used by medical personnel, but have become an essential of daily life. Yet the associated carbon emissions and wastefulness inherent in today’s linear economy in the healthcare sector needs to change. Healthcare’s climate footprint is equivalent to 4.4% of global net emissions, which represents 2 gigatonnes of carbon dioxide equivalent,

meaning if the health sector were a country, it would be the fifth-largest emitter on the planet.1 In the past few years, pharma and medical OEMs have increasingly embraced their role in the fight against climate change and have been developing their sustainability strategies. Pledges for carbon and plastic neutrality were made; many included Scope 3 emissions in their targets and started to consider using more sustainable raw materials for existing applications or new design developments. However, what does more sustainable or eco-friendly really mean?

A FUTURE-POSITIVE REVOLUTION FOR PLASTICS Polyolefins (polyethylene PE and polypropylene - PP) have frequently been used in healthcare as an alternative product to glass and metal, but also to other plastics due to their combination of good property profiles and value in use, as well as often offering a better sustainability profile by being lighter, easier, safer to use, chemically inert and recyclable. Borealis, a polyolefin resin manufacturer, has embarked on a sustainability journey by taking a broader view at the circular economy for plastics via its circular

cascade (Figure 1) – not only looking into the technical cycle by incorporating Design for Recycling or Reuse principles and mechanically or chemically recycling end products of these streams, but also by replacing fossil-based feedstocks with renewablebased ones that do not compete with agricultural crops for food and livestock feed. THE DESIGN FOR RECYCLING CHALLENGE IN HEALTHCARE Some healthcare applications today already follow the principles of Design for recycling and incorporate mono material solutions such

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as 100% PE infusion bottles or bottles for irrigation solutions. Interestingly, the large majority of waste produced by the healthcare sector (approximately 85%) is actually non-hazardous and similar to post-consumer waste i.e. much of it can be recycled. However, recycling hospital waste even if not hazardous or contaminated, poses a separate challenge to hospital staff in terms of collecting and sorting such waste. Consumer health is the segment where increased awareness for environmentally sustainable solutions is more pressing. Particularly in oral solid dosage products, consumers tend to regard such packaging like any other and require similar recycling solutions. Blister packaging is omnipresent in every single household and it became the priority for many pharmaceutical companies to replace commonly used PVC/ Al structures by recyclable ones. For more than 20 years, Borealis has offered a Bormed™ PP medical grade as an alternative route for blisters - Designed for Recycling while keeping the packaging integrity, drug safety and shelf life intact. CLOSING THE LOOP ON PLASTIC WASTE Borcycle™ is the Borealis portfolio of recycling technology solutions giving polyolefin-based, postconsumer waste another life. Specifically interesting for the healthcare industry is the Borcycle C line, converting plastic waste that typically goes to incineration or even worse, landfill, to virgin quality materials and thus closing the loop even for diﬃcult-torecycle plastic waste.

RENEWABLE-BASED CIRCULAR POLYOLEFINS Recycling post-consumer plastic waste is not enough to truly transform the polyolefin industry and its environmental impact. Already at the beginning of 2020 Borealis achieved a milestone on the journey to replacing fossil fuel-based feedstocks in a large-scale commercial production by launching the Bornewables™ solutions: Circular polyolefins produced with renewable feedstock derived entirely from waste and residue streams. The Bornewables offer the same material performance and regulatory compliance as virgin polyolefins, but with a reduced carbon footprint and decoupled from fossil-based feedstock. PROVEN REDUCTION OF GREENHOUSE GAS EMISSIONS Making decisions based on life cycle assessment (LCA) is crucial to have a fact-based analysis and a clear path forward to implementing more environmentally sustainable materials. The cradle-to-gate LCA conducted on the Bornewables has shown that renewablebased polyolefins contribute towards the mitigation of climate change by providing significantly lower greenhouse gas emissions (at least 120% reduction) compared to polyolefins made from fossil-based feedstock. This means, that when replacing one tonne of conventional PP with Bornewables, 2.1 tonnes of CO2-eq are saved. This is comparable to the greenhouse gas emissions of three return flights from London to Beijing2. Download the Bornewables brochure

WHY IS MASS BALANCE KEY TO BRINGING CIRCULARITY FORWARD? ENABLING VISIBLE PROGRESS NOW The change to using recycled and renewable feedstock is not as simple as flipping a switch. It is a journey. Chain of custody models can help move forward by increasing the proportions of sustainable feedstocks that are used. Specifically, Borealis believes that the mass balance model offers the greatest set of benefits and the best path to visible progress for circular plastics, while building stakeholder trust in the right chain of custody model. It helps the whole value chain to track, trace and verify the sustainability of the renewable feedstocks and end-products throughout the chain to make it more visible and tangible. Thus, the Bornewables and Borcycle C solutions are offered on an ISCC Plus certified mass balance model. THE IMPORTANCE OF MEDICAL GRADES When considering incorporating more sustainable solutions in a medical device, diagnostic consumable or a pharmaceutical packaging, healthcare producers need the assurance that the materials they qualify for use today, can also be used for years to follow. This means, for

REFERENCES

instance, reliability of supply, receiving a formulation lockdown commitment, proper change management and extended notification period, appropriate pharmacopeia testing results and US FDA DMF registration from the raw material supplier. All of this and more is at the core of the Borealis service package offered with the Bormed medical polyolefin grades. The introduction of the Bornewables and Borcycle C solutions in existing Bormed products does not affect product performance nor does it represent formulation change, as the hydrocarbons produced by renewable or chemically recycled streams are indistinguishable from the ones derived from crude oil feedstock. INDUSTRY COOPERATION FOR A MORE SUSTAINABLE FUTURE At Borealis we believe in the circular revolution: A revolution that’s world-critical and urgent. Because today we take, we make, we dispose and this is linear, wasteful and unsustainable. The whole healthcare industry needs to work together to find ways to reduce, reuse and recycle and to decouple from fossilbased production to lead the transformation of the plastic value chain from linear to circular to Beijing.

1. Healthcare Without Harm. Sustainable healthcare waste management in the EU Circular Economy model; 2020 2. 1404 kg CO2/journey. Source: https://www.icao.int/environmental-protection/Carbonoffset/Pages/default.aspx

BIOPROCESSING

The correct optimisation of chromatography technology for downstream bioprocessing production

An optimal approach

Author: DR NANDU DEORKAR - vice president of research and development at Avantor

ptimisation is critical for the continual improvement of manufacturing, automation, and business processes. Biologics manufacturers are investigating ways to improve process eﬃciencies in downstream production. The growing demand for biologics across multiple therapeutic applications and categories raises concerns about the cost and availability of these types of treatments.

improvement in downstream recovery can increase the ultimate process yield for the target biologic drug product. Complexity of downstream production: Upstream productivity may be simpler to optimise due to a more straightforward process. Once the target molecule and raw materials are loaded into the bioreactor, the process runs to completion with the appropriate testing and quality control.

KEY CHALLENGES Downstream production currently encompasses about 60% of the total cost of biologic drug production. There are several challenges to remove bottlenecks and improve yields in downstream for more costeffective production results. Increased upstream yields: There have been investments in the technologies and processes used in upstream processing to improve yields. Efforts to optimise raw material characterisation, add single-use systems, perfusion systems and more precisely controlled bioreactors lead to detectable increases in upstream yields. However, improvements in downstream throughput have not kept a similar pace, leading to potential bottlenecks in the end-to-end process. Loss from upstream to downstream: One of the fundamental structural challenges in biologic production is the approximate 30 to 40% loss as harvest material goes through downstream purification. Any

In contrast, downstream production involves multiple steps, where the biological material is moved from harvest, centrifugation and/or filtration to multiple chromatography steps before reaching final fill and finish. Each step requires a unique set of resins and buffers among other materials; storage and production systems at multiple steps; and parallel analytical and quality control sampling activities. Finding efficiencies across downstream processing steps requires additional complex analysis and optimisation. Improvements may be reached after investigating key aspects of current purification steps and technologies, including: • Expanding the use of high-performance affinity, mixed-mode, and multimode chromatography resins, including resins with targeted ligands that increase selectivity to process targeted molecules more efficiently. • Exploring methods to make chromatographic buffers more effective by using novel

additives, as well as prepackaged single-use buffer materials to streamline buffer exchange steps. OPTIMISING PROCESS CHROMATOGRAPHY TECHNOLOGY The goal of downstream optimisation is to improve recovery and therefore normalise the cost per gram of protein produced; thereby enabling the production of more drug product in less time, with the same amount of resin and buffer material. One way to do this is by optimising use of the newest generation of affinity, mixed-mode, and multimode resins. Undesired glycosylated molecules and aggregates can have limited differential binding to traditional affinity and ion exchangers and can co-elute, therefore presenting major challenges. Aggregates can impact dynamic binding capacity (DBC), where a false increase in signal from aggregates can lead to artificially low DBC data, in turn affecting yield. Thus, the combination of increased upstream yields and more complex molecules needs novel approaches to chromatography resins. In response, chemistry suppliers have focused their efforts on process chromatography selectivity and efficiency. The traditional solution to this type of challenge is to use multiple downstream ion exchanges. While this lowers

the yield of the targeted drug, the cost per gram can become prohibitive. More advanced methods of achieving effective selectivity are based on new ligand chemistries engineered to achieve precise selective interaction with the targeted protein. This increases selectivity while reducing the required number of steps, helping control process complexity and cost. Targeted affinity chromatographic media are based on ligands tailored to interact with specific proteins, offering high selectivity for a target drug molecule. This can be time-consuming if implemented for every new molecule; therefore, mixed-mode and multimode approaches should be considered. To overcome this obstacle and increase efficient throughput, new protein A resins with high DBC have been developed and have increased the protein amount that can undergo the purification process, compared to traditional resins. Figure 1: Impact of DBC on theoretical number of cycles per batch – comparing advanced vs traditional affinity resins This results in decreased cycles, leading to savings in both cost and time. These new protein A resins can also purify IgG or FcFusion proteins at both high and

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step—ultimately impacting cost per gram. For example, typical chromatography processes may first use a separate cation exchange step, then an ion exchange step. The yield is approximately 80% pure after the first step, reaching upwards of 95% purity after the second step. With a multimode resin, it is possible to reach 95% purity in one step. A multimode resin in the column is more eﬃcient, processing 70 grams in one batch versus running 100 grams through separate cation and ion exchange steps. This is due to the overall higher throughput and the lower cost of materials, since this approach reduces the buffer consumption, types of filtration systems used, and ancillary costs associated with each chromatographic step. Each step typically takes up to two hours, cutting production time and labour in half. Another method for optimising process chromatography is using the continuous chromatography method, in which the large column is split into several smaller columns that operate in series over an increased number of cycles. While product

Fig 3 Fig 1

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low molecular weight, increasing purity and decreasing pressure on subsequent purification steps. Figure 2: Advanced aﬃnity resins with improved Fc-specificity lead to higher quality of Fc-fusion protein Mixed-mode chromatography media are based on ligands that offer two or more interaction possibilities with the targeted drug molecule. The mixed-mode approach has proven to be effective and more productive in applications, such as intermediate and polishing steps, for purifying proteins based on differential salt-induced hydrophobicity. An advantage of the mixedmode approach is that the same media can be used for different purification steps, and can be modulated by solution conditions, such as using multiple buffers or multiple elution steps. Newer mixed-mode resins have ligand chemistry that enable the use of multiple sequential interactions during the normal chromatographic process. Figure 3: Mixed-mode ligand structure - mixed-mode media offer more interaction possibilities with the targeted drug molecule.

Multimode resins offer greater potential for eﬃciencies and improved yields. Rather than requiring multiple chromatographic purification steps, the simultaneous interaction can separate closely related proteins in a single step. This concurrent purification can occur without requiring additional intermediate steps, such as buffer exchange, titration, or dilution. Figure 4: Multimode ligand structure - multimode resins can simultaneously interact with different sites or regions of the protein molecule. Using a multimode or mixed-mode ligand with multiple interactions can boost chromatography yields while merging two process steps—as well as the ancillary time and costs associated with each HO

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NEW APPROACHES TO BUFFERS Optimising the resin chemistry presents significant opportunities to improve downstream production. Improving the ways buffers are formulated and delivered to the end user can also positively impact productivity. Additives in buffers can optimise performance of chromatography columns by increasing binding capacity, stability, and separation thereby increasing recovery and purity of the protein of interest. Established methods of buffer generation are for large volumes and need extensive infrastructure and space in large scale facilities. Novel approaches such as using single-use technology, or a hybrid approach of both outsourcing and in-house preparation enable small- and medium-scale facilities to implement different buffer preparation processes. Premade buffers or buffer concentrates enable cost-, time, and resource-saving.

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is loaded onto some columns, others are simultaneously going through the wash, elution, and regeneration phases. The combination of resin optimisation and merging two chromatography steps can potentially confer for a three-fold improvement over traditional processes.

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Fig 4

Finding efficiencies across downstream processing steps requires additional complex analysis and optimisation

NEW POTENTIAL The goal for downstream optimisation is clear: managing and reducing the cost per gram of valuable biologic drugs. The more expensive elements of current downstream process steps, such as chromatography media, can be made more eﬃcient by investigating how newer materials and methods offer ways to condense and streamline process steps.

Pistoia Alliance calls for restructuring around patient centricity

embers of the Pistoia Alliance have called for the life science and healthcare industries urgently to restructure around patient centricity. More than 150 attendees meeting at the Pistoia Alliance’s annual European conference in London agreed that the sector is undergoing a significant shift. In the wake of the global pandemic and driven by continual advances in technology, the voice of the empowered patient is on the rise. The Pistoia Alliance is now calling for greater collaboration between links in the biopharmaceutical value chain to support and advance this shift and ensure that patient centricity is embedded right from early discovery to healthcare delivery. In a keynote address, Cristina Ortega Duran, chief digital health oﬃcer R&D for AstraZeneca, said: “We are living through the largest transformation in human history. “Technology is growing exponentially and that’s diﬃcult to comprehend. Change doesn’t happen at the pace of technology development. Industries take a longer time to change than technology because changing behaviour is much harder. But the pandemic has changed behaviours. Billions of people changed the way they interact with healthcare in a matter of months. “In this new era of targeted precision medicine, we all play a role in creating the patientcentric future that patients deserve.”

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Talking points

OUTSIDE EPM

€125 BILLION LOST EACH YEAR ACROSS EUROPE DUE TO NONADHERENCE TO MEDICATION

he International Longevity Centre-UK (ILC) has launched a report which calls for better support to help people to stick to their “doctor’s orders” by taking their prescribed medication regiments. According to the report, nearly half of all adults and approximately 8% of children (aged 5-17) worldwide have a chronic condition. Yet, adherence to medication for these conditions is as low as 50% in high income countries and even lower in lower income countries. ILC, the UK think tank on the impact of longevity on society, argues that encouraging adherence has the potential improve health outcomes and longevity, and the cost-effectiveness of medications. The research finds that 10% of hospitalisations in older people are attributed to non-adherence and that the typical non-adherent hospital patient requires three extra medical visits a year for an increased cost of $2000 per annum. The estimated overall cost of non-adherence, defined as taking less than 80% of a prescribed dose of medication, is between $100290 billion in the USA, €125 billion across Europe and AU$7 billion in Australia. To increase levels of adherence, the “Doctor’s orders” report calls for urgent prioritisation of adherence as an effective disease management tool, funding annual medicine reviews between patients and their providers to identify gaps in care

and medication access. Alongside this, ILC argue there should be investment in healthcare technology for universal electronic health records, so providers and patients alike can access their full medical record at any time as a tool to help with medication adherence. Arunima Himawan, research fellow at ILC, said: “Frankly, it’s a scandal that almost half of medications we prescribe aren’t being taken properly. There is a massive, missed opportunity for governments and healthcare systems to intervene. It’s essentially money down the drain. “We’re getting better at preventing, managing, and treating conditions. But it doesn’t end there. A prescription or a lifestyle change is just the starting point. With more and more of us living longer with multiple conditions, it really shouldn’t just be up to us as individuals. Trying to navigate 10 different-coloured pills each day isn’t an easy task. “Governments must drive solving the adherence problem. Measuring adherence at a national level is a key first step, as is investing in person-centred interventions for people at risk of and already living with chronic conditions.”

Catch all of the build-up to the Med-Tech Innovation Expo with all of the latest news dedicated to the show on: www.med-technews. com/Medtech-expoand-events/med-techinnovation-expo-news.

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EPM May 2022

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