www.epmmagazine.com INNOVATION IN MANUFACTURING
ADVANCES IN BIOPROCESSING
DIGITAL TECHNOLOGY THROUGHOUT COVID-19
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May/June 2021
The silent
pandemic
WHY IT’S TIME TO SPEAK UP ABOUT THE THREAT OF ANTIMICROBIAL RESISTANCE.
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folio
Contents May/June 2021 | Volume 21 Issue 3
REGULARS 5: EDITOR’S DESK
Reece Armstrong questions the global vaccine rollout during the pandemic.
6: A SMALL DOSE
A brief round-up of some of the latest developments in the industry.
10: OPINION
How digital innovation has emerged throughout Covid-19.
13: IN THE NEWS
A short selection of stories from the world of science.
14: COVER STORY
The antibiotic landscape and why we need to speak up about antimicrobial resistance (AMR).
26: TALKING POINTS
Stories to consider and what to look out for in EPM in the coming weeks.
FEATURES 8: PERSPECTIVE ON PHARMA
The benefits of working with global partners throughout the industry, no matter your location.
16: INNOVATION IN MANUFACTURING
How automation is helping bring new drugs to market faster.
18: BIOPROCESSING
The future and current benefits of bioprocessing technologies.
22: PACKAGING
Interviews and features on the latest packaging trends.
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folio
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ADVERTISING robert anderton tel: +44 (0)1244 952359 robert.anderton@rapidnews.com vp sales & sales talent Julie Balmforth julie.balmforth@rapidnews.com
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AS VACCINES ARE ROLLED OUT PRIMARILY ACROSS WEALTHIER COUNTRIES AND POORER NATIONS ARE LEFT UNPROTECTED, THE BALANCE HAS SHIFTED.
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arlier this month during a Covid-19 media briefing, the World Health Organisation’s directorgeneral Dr Tedros Adhanom Ghebreyesus reflected on the state of the vaccine rollout during the pandemic. In a somewhat reproachful statement, Dr Tedros reflected on how his warnings against
the emergence of vaccine nationalism had come true. Since September last year, the director-general had been warning us against the threat of vaccine nationalism – where rich countries would horde Covid-19 vaccine supplies, made possible through pre-purchase agreements with major pharmaceutical corporations. The WHO’s warnings, which some had called alarmist, he said, are now being played out on the world stage - with only 0.3% of current vaccine supply going to low-income countries. You can read more about this story in the news section of this issue, but I thought
EDITOR’S DESK it pertinent to highlight it in this editor’s letter, due to the overwhelming sense in this country that things are finally starting to get better. The emergence of Covid-19 brought with it many headlines and statements that made everyone around the world feel that they could be at threat from this dangerous and looming virus. One particular phrase that stuck out to me during this
time was “we’re all in this together.” Which, in essence, we were. But now, as vaccines are rolled out primarily across wealthier countries and poorer nations are left unprotected, the balance has shifted. Take this statistic for example. The UK has procured enough doses of Covid-19 vaccines to vaccinate 409% of its citizens. The EU 333%. The US – 199%. Canada – 493%. Compare this to Pakistan which has procured a little under 11 million Covid-19 vaccine doses, or just enough to vaccinate 2.5% of its population. India, where we’re seeing a massive increase in Covid-19 rates and deaths, has procured enough Covid-19 vaccines to cover 13.4% of its population. You can argue that this is how capitalism works. That pharmaceutical companies are at liberty to make deals with those who can offer the funding required to cover the enormous costs of R&D. We’re seeing a similar argument play out with the temporary waiver of intellectual property (IP) rights in regard to Covid-19 vaccine know-how. But, in a major health crisis, when vaccine supply is so divided, it becomes clear that whatever strategy we’ve had for tackling the pandemic has not been a unilateral one. The Covax scheme, the admirable, philanthropic effort to supply vaccines to poorer nations, has faced its own supply problems. And whilst nations such as the US and France have committed to helping the scheme, it’s obvious that we need a better approach to how we tackle vaccine inequality as a global entity, rather than a collection of nations. The next pandemic could depend on it.
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A small dose
Quay Pharma wins LONZA INVESTS IN SMALL Queen’s Award MOLECULE MANUFACTURING
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ontract development and manufacturing organisation (CDMO) Quay Pharmaceuticals has won a Queen’s Award for Enterprise in the category of International Trade. The company was recognised for the strength of its export sales, which since 2010 have always made up over 55% of its business. In the last three years, Quay Pharma has manged to double its sales, becoming particularly active in the US where it has opened a sales office and development and manufacturing facility. “We are thrilled at this honour, which is a tribute to the expertise and hard work of the entire Quay team,” said Quay CEO Maireadh Pedersen. “As a business, we are known and respected for forging our own path, with the extensive knowledge and skills of our employees helping to provide unparalleled service and value to the fast-changing priorities
of our customers as they move new innovative therapies into [the] clinic. “These abilities have been all the more critical in enabling us to maintain our growth despite the challenges brought about by Brexit and the current Covid-19 pandemic.” Quay Pharma has put part of its success down to its work in live biotherapeutics, which focus on the use of microbes to illicit a pharmaceutical response, specifically targeted at the immune system. As a CDMO, Quay was one of the first to support this new field of therapies. “We have ambitious plans to continue to develop our global business. The Queen’s Award provides the ideal foundation for the next phase of our growth, but above all it is our people who will drive our success and I would like to thank everyone for their contributions, which have led to this honour,” added Pedersen.
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ontract development and manufacturing organisation (CDMO) Lonza has announced the construction of a new small molecule manufacturing complex at its Visp site in Switzerland.
The first buildout of the complex will include a dedicated manufacturing line for antibody-drug conjugate payload molecules, which is expected to start running in Q3 2023. The facility is also expected to support around 200 jobs.
The facility will feature six levels of manufacturing space and will offer several opportunities for the future expansion of small molecules technologies.
Maurits Janssen, Strategic Business Development Small Molecules, Lonza said: “Supply is critical for our global partner in the oncology field. With
this investment, we are enabling the treatment of many cancer patients. Oncology continues to be the leading indication in biopharma and a key driver for highly potent ingredients such as antibody-drug conjugates. In addition, small molecule oncology therapies require specific technologies. These challenges were specifically taken into account when designing this manufacturing complex.”
Catalent to support manufacture of AavantiBio’s gene therapies pipeline
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ene therapy company AavantiBio has partnered with drug delivery company Catalent for support on the development and manufacture of its gene therapies. This will include AavantiBio’s Friedreich’s Ataxia (FA) programme, a genetic disease that causes difficulty walking, impaired speech, and worsens over time. Catalent will provide process development and CGMP manufacturing of AavantiBio’s adenoassociated viral (AAV) vector-based therapeutic candidate
for use in clinical trials in the US and Europe. Catalent will further support process optimisation
and look to reduce material timelines at its process and clinical development centre in Baltimore, Maryland.
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Gordon Bates, president and head of Small Molecules, Lonza, added: “Our customers developing highly potent and increasingly complex medicines trust us to handle these toxic substances throughout their clinical
and commercial lifecycle. The investment to realise this new manufacturing complex for small molecules creates a substantial footprint for accelerating future growth capacity across the range of our small molecule service offering.”
“We look forward to working with Catalent on the development of our differentiated pipeline of innovative gene transfer therapies, focused initially on our FA program,” said Bo Cumbo, president and chief executive officer of AavantiBio. “This partnership highlights the importance of prioritising Chemistry, Manufacturing and Controls as a foundational element of the company. We believe this approach will position AavantiBio for long-term success as we begin to advance therapies to transform the lives of patients
with FA and other rare diseases.” “Catalent is committed to partnering early with innovative companies and facilitating the development and optimisation of robust, scalable manufacturing solutions,” commented Manja Boerman, president, Catalent Cell & Gene Therapy. “Our development team at the University of Maryland BioPark is focused on providing process optimisation services to meet our customers’ needs and partnering with them to bring innovative therapies to patients faster.”
We believe this approach will position AavantBio for longterm success.
Plans for £350m biomanufacturing plant in Cumbria backed by GSK
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he development of a £350 million biomanufacturing plant in Ulverston, Cumbria, has been backed by GSK. The Lakes BioScience site has already received planning permission from South Lakeland District Council. The factory will produce monoclonal antibodies and is expected to generate 250 high-tech jobs. Lakes BioScience, which has secured £350 million in funding for its proposals, is now looking to secure a key contract which will kickstart its plans for the site. GSK has pledged to help Lakes BioScience in its efforts to secure that contract which will unlock the potential for Ulverston to become a centre of biopharma
manufacturing excellence with a purpose-built factory developing modern medicines.
expected to take place in 2025.
Phil Wilson, GSK site director said: “We welcome the ongoing constructive dialogue with the community and the opportunity, through the taskforce, to share progress on support for our teams. While we are still early in the process, with no immediate changes for our teams, we are committed to transparent and open communication throughout.”
Pat McIver, director of Lakes BioScience, said: “We very much welcome GSK’s commitment to support Lakes BioScience’s plans. GSK’s help with business development guidance and technical support and their willingness to share their expertise and networks with Lakes BioScience will boost our efforts to secure a keystone contract which will unlock the huge potential of our development.
The planned development of Lakes BioScience comes as GSK announced the closure of its own site at Ulverston, due to the company selling its Cephalosporin antibiotics business to Sandoz. The closure is
“This represents a fantastic opportunity to stop what would be a decline in UK medicine manufacturing capability and demonstrate what levelling up can deliver for the north of England, for Cumbria and for Ulverston.”
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PERSPECTIVE ON PHARMA: Beyond Borders: How Life Sciences Innovators Can Fast-track Project Delivery In the Digital Age
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roject owners in the life sciences industry are uniquely familiar with that old adage, “the only constant is change.” Facing the pressures of Covid-19 and ignited by new technologies and research advances, the industry has undergone immense transformation over the last 18 months. Cell and gene therapy innovators are particularly notable agents of change; they raised $19.9 billion in 2020, exceeding 2019’s investment by more than 200%. The European Commission recognised this momentum in its recent EU Pharmaceutical Strategy, which aims to drive further competitiveness and innovation in the industry. Change isn’t coming—it’s already here, and it’s transforming life science research in the EU. To keep up with this pace, the industry’s assumptions about capital project delivery must change. In particular, the notion that working with a regional Architecture, Engineering and Construction (AEC) partner is the most effective way to balance cost, quality, and speed when developing the facilities to support the industry’s continuous growth. Rasmus Kidmose, European Business Development Director at CRB explores the benefits of working with global partners, no matter your location.
This perception is self-limiting, particularly in the era of Pharma 4.0, when organisational silos are giving way to seamless collaboration supported by advanced digital tools. For
A “borderless” partnering approach offers practical and lasting benefits.
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those working towards a new generation of commercial-scale therapeutics, success starts by finding the right partners at the right time. It’s never been easier to build a choice team of process architects, engineers, and technologists from around the world—and it’s never been more necessary to maintain a competitive position. PRIORITISE EXPERIENCE OVER LOCATION Within the EU’s life sciences sector runs an abundant current of AEC experience and innovation. The industry must eradicate the notion
of “elsewhere” altogether— that instead of considering borders when looking for project delivery solutions, drug developers consider skills, qualifications, and experience. This isn’t an either/or scenario. It’s both/and. The best team is a hybrid team, combining the borderless specialisations needed to accelerate a project forward and the in-country expertise that will ensure a smooth launch. For example, developing a robust and quality-driven compliance strategy takes local regulatory experience. But a capital project’s success story is far bigger than its regulatory strategy—from early feasibility studies through process scaleup, these projects require a diverse and integrated team of highly skilled experts, and where they live shouldn’t matter. This is especially true in novel areas of drug development, where new challenges in capital project delivery need innovative solutions, quickly. According to a CRB report that surveyed 150 leaders from the cell and gene therapy industry, process optimisation is the biggest challenge in scaling towards commercial manufacturing. We must acknowledge and understand this challenge, and address it with the right combination of emerging solutions. Is your project a candidate for the dense efficiency of multimodal manufacturing? Are you effectively managing your risks and preparing for future scale-up with closed and automated processes? How will you design flexibility into your facility to stay competitive as new opportunities arise? These and other pressing questions will determine which manufacturers of tomorrow’s advanced therapeutics will succeed, and which will fall
behind. The right experts, with the right answers, are out there—some may be close to home and some may be on the other side of the world. RIGHT-SIZE YOUR PARTNERSHIP TO FIT THE PROBLEM Within the perception that local procurement is better lies another perilous belief: you need to be big to be borderless. Or, a smallerscale innovator is not suited to partner with a large, international AEC entity. Maybe you’ve been oversold and under-serviced in the past. Maybe you’ve worked with a global company who reduced your upfront investment by outsourcing their drawings to a third party, then charged you for fixing those drawings when they arrived full of errors. These costly experiences chisel away at your willingness to look farther afield for a suitable partner. That’s understandable, but not necessary. Smaller-scale drug developers don’t need to limit themselves to smaller-scale vendors. The right AEC partner, regardless of size, will adapt their approach to suit your project’s objectives and deliver results within the target value. A large-scale AEC partner has the advantage of a diverse, broad talent pool. They can tailor-build a lean and integrated team that’s perfectly suited to a project and its CAPEX budget. In the hands of a true partner with the skill and experience to deliver what you need, quality-driven and costeffective solutions are part of the service package. HARNESS THE FLEXIBILITY AND SPEED OF DIGITAL TOOLS A “borderless” partnering approach offers practical and lasting benefits. For one thing, working across time zones—a
9 nuisance in the pre-digital era— is now a competitive advantage, particularly for companies focused on improving speed to market. If your hybrid team extends from California to Switzerland, for example, then an eight-hour working day is extended, doubling or tripling efficiency without adding a single night shift to the team. The now-ubiquitous video conference has usurped the traditional boardroom. More sophisticated platforms have joined the global team’s digital toolkit. Artificial reality makes design-build activities like site walkthroughs or factory acceptance tests, possible from anywhere in the world. Even the well-established “workhorse” tools of AEC project delivery, like 3D building information modeling platforms, are helping to collapse the distance between global partners by providing a centralised superhighway for moving design packages through the review process. GLOBAL IS THE NEW LOCAL Limiting capital project delivery teams to local partners is like limiting your diet to the backyard garden: the quality may be excellent, but it lacks the variety needed to thrive. A robust capital project strategy requires the right resources, not only those close at hand. That’s where the hybrid team becomes invaluable: local and international experts with complementary skills and experience are jet fuel for your capital project, accelerating it from concept to commercialisation with the best solutions and technologies available. This is how the EU’s pharmaceutical industry will continue its remarkable pace of change, and how we will address the unmet needs of patients at home and all around the world.
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Opinion
For many, the urgent need for treatments and vaccines to combat Covid-19 revealed the pitfalls of legacy drug discovery methods.
DIGITAL INNOVATION IN UK MEDICINE - COVID-19 AND BEYOND Author: NEIL THOMPSON - chief scientific officer at Healx
How digital innovation has emerged throughout the Covid-19 pandemic and beyond.
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he battle against Covid-19 has dominated the world’s attention over the last year, impacting economics, societies, individuals and industries across the globe. In response to the pandemic, the UK in particular has seen a surge in digital innovations exploring the use of artificial intelligence (AI) and machine learning (ML) technology across the healthcare spectrum. As we reflect on the last year, I see a number of key learnings that can enable us to maximise the value that can be derived from these innovations in the broader healthcare sector. DATA AND ENTHUSIASM ARE CRITICAL FOR INNOVATION The first is that there are a vast number of innovative ideas out there - some of which may not have been realised without the urgency of a pandemic. This creativity goes well beyond some of the generally accepted uses of AI and ML in imaging, diagnosis and modelling. Indeed, from tackling misinformation to assessing people’s risk of transmission, such advancements have helped monitor the spread of the virus, keep people connected, and supercharge
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OPINION
research and development for treatments. This has been possible due to both a high quantity of data being available to make these innovations viable, and an enthusiasm from the community to actually evaluate and incorporate their use. In the UK, for example, hospitals at the Bolton NHS Foundation Trust began using the chest X-ray AI tool from Qure. ai to quickly detect signs of the virus as well as automatically monitor its progression. This, in turn, helped staff make critical decisions such as when a patient should be moved to the ICU or be intubated. Furthermore, researchers from King’s College London worked with an international consortium called icovid to develop a cloud-based AI software that could rapidly quantify the degree of lung involvement in Covid-19 patients. With this information, doctors could then triage admitted patients, potentially alleviating the burdens on intensive care units. This combination of data and enthusiasm is critical to unlock the power, and potential, of AI tools in the future as more innovative use cases evolve. ALWAYS BUILD WITH THE END-USER IN MIND The second learning is that not all of these ideas have delivered the intended benefit - and there are some interesting lessons we can take away from that. Some of the better informed assessments have highlighted approaches that can, and should, be taken in the future to ensure we get the most from these innovations. One key thing is to ensure that the technologies are developed hand in hand with the likely end-users or consumers in order to avoid a mismatch in expectations. A second is that we should expect all innovations within the healthcare space to undergo a period of testing and evaluation before wider adoption, as with many other areas of patient care such as drug discovery and development. The closer an idea is to impacting patient experience, the more heavily regulated that evaluation is likely to be. The recently published modifications of guidance on clinical trial protocols (SPIRIT-AI) and on trial reporting (CONSORT-AI) have set out specific considerations for trials involving AI approaches which have been very helpful in setting the standard of reporting such research. APPLYING AI TO DRUG DISCOVERY COULD UNLOCK HUGE PATIENT BENEFIT The third is that, when it comes to drug discovery, AI and ML could play a critical role in revolutionising the process and opening up access to life-saving treatments to many new patient populations. For many, the urgent need for treatments and vaccines to combat Covid-19 revealed the pitfalls of legacy drug discovery methods. Indeed, to bring a new drug to
market takes roughly 10-14 years, costs between $2-3 billion, and has a 95% failure rate. But with the use of AI technology, both time and risk can be reduced. In August 2020, for example, DeepMind utilised their AlphaFold algorithm to predict a variety of protein structures associated with Covid-19 which provided a critical insight into the structure of proteins crucial for virus entry and replication. With this knowledge, scientists had greater clarity on viral pathways and even potential antivirals. Others, like BenevolentAI and Insilico Medicine used machine learning to quickly identify possible treatments for the virus. These successful examples of AI impacting drug discovery have, in their own way, heeded the lessons outlined previously: starting from an informed understanding of the unmet need and working with the end users to shape the output. But this is something we, at Healx, have believed for a long time. We use our AI platform, Healnet, to identify and progress novel treatments for the 95% of rare diseases currently without an approved treatment, working in close collaboration with patient groups, their physicians and their carers to understand the precise nature of the unmet need. Healnet integrates data from multiple sources (everything from disease and clinical trial data to scientific literature and patient group information) to form a detailed knowledge graph of rare disease information. This graph is then analysed by AI and natural language processing (NLP) models, to uncover previously unknown relationships between existing drugs and rare diseases. Our team of drug discovery experts then interrogate those predictions and progress the most promising candidates to clinical trials generating the necessary data to support the regulatory process required before we initiate patient trials. By bringing together innovative technology and drug discovery experts we believe we can maximise the chances of the immense potential of AI in drug discovery. WHAT’S NEXT? In response to Covid-19, AI-powered technology has been utilised on multiple fronts - from monitoring the spread of the virus to developing vaccines, reducing the burden on staff and predicting infection. Indeed, it has been inspiring to see how far we have come in terms of digital innovation in just a few months. Beyond the pandemic, I hope to continue seeing AI being used in innovative and useful ways across the sector, but always guided by the end user and always subject to the rigorous testing we expect to ensure patient benefit.
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IN THE NEWS
Only 0.3% of vaccine supply going to low-income countries
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nly 0.3% of current vaccine supply for Covid-19 is going to low-income countries, according to the World Health Organisation (WHO) director-general Dr Tedros Adhanom Ghebreyesus. In an opening statement on 14 May, the WHO directorgeneral criticised the vaccine strategies of rich countries, where we are now seeing lower risk groups being vaccinated against Covid-19. Countries such as the UK, US and those in the EU have purchased the majority of vaccine supply for Covid-19, and could vaccinate their entire populations more than once, if necessary. Comparatively, only around 3% of the population in India have been fully vaccinated against Covid-19. So far it’s estimated that the country has enough Covid-19 vaccines to vaccinate around 8% of its population. “I understand why some countries want to vaccinate their children and adolescents, but right now I urge them to reconsider and to instead donate vaccines to Covax. “Because in low and lower-middle income countries, vaccine supply has not been enough to even immunize health and care workers, and
hospitals are being inundated with people that need lifesaving care urgently,” Dr Tedros said. Of particular concern is in India, where cases of Covid-19 rose drastically between April-May, bringing the total number of deaths to over 270,000 in the country. The WHO directorgeneral also pointed
out the spikes we’re seeing in countries including Nepal, Sri Lanka, Vietnam, Cambodia and Thailand. “Some countries in the Americas still have high numbers of cases and as a region, the Americas accounted for 40% of all Covid-19 deaths last week. There are also spikes in some countries in
Africa,” he added. Dr Tedros is urging countries to donate to the Covax scheme, which was set up to help equitably distribute Covid-19 vaccines and therapies around the world – especially to lowand-middle income countries. Recently, the scheme has saw contributions from countries
Did you know?
High income countries have procured 5.9 billion doses of Covid-19 vaccines.
The African Union, Syria and Somalia have procured 270 million doses of Covid-19 vaccines.
The Covax scheme has procured 2.7 billion doses of Covid-19 vaccines.
including the United Arab Emirates (UAE), which is set to donate 1 million doses of Covid-19 vaccines to Covax, and Spain, which will donate at least 7.5 million vaccine doses to Latin American and Caribbean countries through Covax. “International cooperation is a really important mechanism that we as government officials have been speaking about for decades. The pandemic has shown us what can happen when we truly do cooperate with one another, but also what doesn’t happen when we don’t,” said H.E. Reem al Hashimy, UAE Minister of State for International Cooperation. Croatia too has pledged to share 50,000 doses of Covid-19 vaccines with Bosnia and Herzegovina, Montenegro, and Kosovo, and committed €500,000 (US$ 600,000) to Covax. “We shall continue to be one of the countries that supports these activities, both on the national level, but also at the European and global level, too,” said H.E. Andrej Plenković Prime Minister of Croatia.
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COVER STORY
Article and interviews by EPM editor Reece Armstrong.
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n April this year, as the Covid-19 pandemic continued to dominate headlines across global media channels, the World Health Organisation (WHO) published its latest annual review evaluating the current clinical and preclinical pipelines for antibacterial candidates. Conclusions from the report were stark, with WHO assistant director general on antimicrobial resistance (AMR), Dr Hanan Balkhy, saying that AMR is being fuelled by “the persistent failure to develop, manufacture, and distribute effective new antibiotics.”
The silent
pandemic
A month prior, The Pew Trusts in the US updated its findings on the global pipeline of antibiotics and the conclusions were similar. With 43 antibiotics in clinical development - with some inevitably failing to win approval – it’s obvious that there are too few therapies in development to tackle the growing threat of AMR. Of particular concern is how the larger pharmaceutical companies have completely taken themselves out of the picture when it comes to antibiotics. The Pew Trusts’ report says that of the 38 companies currently developing antibiotics, only two are classed as being among the top 50 pharma companies when it comes to commercial sales.
WHY IT’S TIME TO SPEAK UP ABOUT THE THREAT OF ANTIMICROBIAL RESISTANCE.
In 2016, AstraZeneca sold its antibiotics division to Pfizer in a deal worth over $500 million, so it could focus on its three main therapy areas of respiratory & autoimmunity, cardiovascular & metabolic diseases, and oncology. Since then, the likes of Novartis, Sanofi and Allergen have exited the space to focus on disease areas which offer a better return on investment (ROI).
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The space then is dominated by smaller biotech companies, and with fewer resources than the major players, the market can be a volatile one to enter. Biotech Achaogen gained regulatory approval from the FDA for its antibiotic plazomicin back in June 2018. Achaogen’s antibiotic was designed to treat complicated urinary tract infections (UTIs) caused by multidrug-resistant Enterobacteriaceae – a pathogen which is of critical priority for new antibiotics according to the WHO. However, a year later Achaogen was declaring bankruptcy and auctioning off its assets. It’s a story that has sadly been repeated by similar companies over the years and it’s a trend which points to one culprit as the catalyst. THE MARKET Anyone following the discourse on antibiotics will know that for some time, pharmaceutical companies have been put off by the lack of ROI for developing new antibiotics. For instance, the Review on Antimicrobial Resistance chaired by Lord Jim O’Neill in 2014, shows that on average, it takes pharmaceutical companies 23 years to start achieving profitability for antibiotics. Then there’s the looming threat of the patent life for antibiotics, or indeed any drug. When a new antibiotic launches onto the market, clinicians may be wary of using it lest resistance begins to develop. During this time, cheaper, generic antibiotics that still work against infections will be used instead. Indeed, the Review on Antimicrobial Resistance report states that whilst the total market for antibiotics is relatively large at $40 billion sales a year, only $4.7 billion of these sales come from patented antibiotics.
Compare this to oncology drugs for instance, which are used as first-line treatments once they reach the market and can make massive profits, then it’s understandable why pharma companies choose to invest elsewhere. NEXT STEPS With pharmaceutical developers put off from investing in new antibiotics, there is an obvious need for new solutions to incentivise the market so that new innovations can emerge. For that to happen though, there needs be more interest put into the science underpinning antibiotic research – microbiology. Lloyd Czaplewski, Chemical Biology Ventures’ director and someone who was on the advisory group for the WHO’s latest report sees the deficit of microbiologists as a major obstacle to antibiotic development. “When I got into this space 20 years, most major pharma would have a team of 100 or 200 people working in the space – it’s all gone. That size and shape of team doesn’t exist in any one organisation any longer,” he tells me over a phone interview. This has left antibiotic development work up to academics and a selection of biotechs, who don’t have a large enough portfolio to survive when a project fails. “We don’t have the hundreds of people or thousands working in that space that we probably need for training, for career development, for longevity. Because you need to make fundamental discoveries to turn into new products. We don’t have enough of that,” Czaplewski adds.
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It makes sense that there’s a deficit of microbiologist and infectious disease specialists. The Review on Antimicrobial Resistance highlights that in 2012, doctors in the US working in infectious diseases and HIV were the lowest paid compared to other medical fields. Move to 2021, and data from the National Residents Matching Program showed that 12% of infectious disease trainee positions in the US remain empty. For comparison, there were no positions left unfilled for oncology or pulmonary diseases in 2021.
to be sustainable, and ideally market-driven. What we want to do is allow the innovation to advance, and to finance the best innovation that is developing the most critically needed products. And to do that in a sustainable way over a long period of time. That’s the goal – to really bring the market back here so that the best antibiotics are getting financed and advanced, and the best drugs for the greatest needs are getting to patients. That needs to come together organically with input from all sides – the public sector as well as the private.”
Given how long it takes to find new drug discoveries and for drug development work to take place, promoting an interest in microbiology is needed if the industry is to have specialists at hand who can undertake work against AMR.
Funding is definitely key, but as the WHO’s report states, many companies will not be able to survive once their products are registered, as new antibiotics are often held in reserve, something which can limit sales and make it difficult for companies to pay back investors.
Action is needed now though, and thankfully we are seeing efforts. One of the major talking points in the WHO’s report is the AMR Action Fund. Set up by a range of pharmaceutical companies and investors, the AMR Action Fund has been designed to sustain antibiotic development funding by supporting smaller biotechs involved in the sector. When asked about the funding situation for antibiotics, Dr Henry Skinner, the CEO of the AMR Action Fund told EPM: “There’s no question that we need more capital to be funding innovation in this area from a number of fronts. It needs
But, as Czaplewski asks me during our interview, “do we have to make a profit for antibiotics?” The pharma industry would say yes, but international efforts such as the Large Hadron Collider and the International Space Station provide scientific benefits without explicitly selling a product, all in the name of science and the public good. It’s food for thought but one thing is for certain, change needs to occur if we are to tackle AMR. Time will tell whether or not our current efforts are enough.
The space then is dominated by smaller biotech companies, and with fewer resources than the major players, the market can be a volatile one to enter.
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INNOVATION IN MANUFACTURING
How automation is being used throughout the pharma industry and how it is helping bring new drugs to market faster. especially at the lab bench, where the need for versatile, easy to use automation to replace laborious manual pipetting has never been greater. A key driver is to reduce error rates whilst freeing up highly skilled analysts for higher level tasks.
Quick questions with Nigel Skinner, Marketing Director at Andrew Alliance. Many people think of automated systems as being linked largely to packaging and inspection processes but what about their use in the lab? Automation continues to find increased adoption within the drug discovery groups of not just large pharmaceutical companies but also smaller companies, including start-ups. An initial obvious fit was in high throughput screening (HTS) labs, to identify hits from compound libraries that may become leads for medicinal chemistry optimisation. Covid-19 has seen significant growth in the adoption of automation to accelerate vaccine development,
How else is automation being utilised throughout the lab? Today it is being used for far more than high throughput screening (HTS). It is also being used for compound management, assay development, biochemical and cell-based screening, cell culturing, antibody/protein production and purification, and ADME-Tox assay systems, as well as applications such as next generation sequencing. Thanks to the increasing integration of artificial intelligence (AI), tasks can now be performed at rates and precision beyond human capability. Can automation be used to improve the efficacy of a therapy? (Through screening for better targeted molecules etc. Yes. Automation can be used to speed up the process of screening drug-target binding in order to screen for desired therapeutic characteristics, by enabling much larger libraries to be screened in parallel using so-called ‘lights out’ automation where screening is done 24-7. Is there a deficit of skilled lab employees who know how to work automated systems or can training be provided? Yes, automation systems tend to require staff specialised in Python or C++ programming in order to adapt or develop new protocols. These are a limited resource even in the largest pharma companies, and pretty much non-existent in smaller companies. Biologists and
chemists are typically not trained in this area. Does automation offer researchers more time to focus on other areas of work? This is one of the most important benefits of automation in the drug discovery lab. Once laborious workflows, involving considerable manual intervention, are rapidly becoming seamless. Moreover, reduced error rates and the increasing drive to the paperless lab, is further reducing lower value activity whilst boosting productivity. Biologists can focus on accelerating their
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understanding of the biological pathways of disease. Why is automation so critical for the pharmaceutical manufacturing market today? There are several reasons for this. The importance of throughput, productivity, remote operation, install and set-up of automation, as well as versatility, has been amplified by Covid-19. Also, the drive to the paperless lab is supported by more automated processes. What are some of the common challenges of the automation journey specific to pharma? Labs have a lack of skilled technicians and analysts so increased productivity is essential. We’re seeing
increasingly complex workflows through things like CRISPR and NGS Library Preps. There is also a prevalence of RSI (repetitive strain injury) caused by excessive pipetting e.g. in serial dilutions and concentration normalisations for library preps, screens, PCR.
What specific types of technologies are helping companies? AI is taking automation well beyond the limits of human capability by eliminating the need for human decision making at critical workflow chokepoints. Fully remotely programmable pipettes using cloud-native protocols
Once laborious workflows, involving considerable manual intervention, are rapidly becoming seamless.
17 facilitates ring trials, enhanced intra- and inter-lab repeatability, and proficiency testing as well as getting new less experienced staff up to speed far more quickly. What guidance can you offer pharmaceutical manufacturers looking to invest in automation? Today’s automation is neither as complex nor as costly as it used to be. It does not require a background in automation or programming and automation solutions can be purchased for as little as $10k, depending on requirements. What do you think are some of the trends or upcoming technologies that have an impact on customers looking into automation? Two rapidly evolving areas are lab 4.0/connected Lab and AI. Lab 4.0 promises a fully connected, smart lab, with digital interaction between all elements. Smart materials with sensors and actuators (e.g. for emergency cooling) make it possible to digitally monitor and control reaction vessels continuously, thereby ensuring improved safety where potentially dangerous processes are involved. Lab furniture with functional surfaces and integrated instruments and devices (including robotic systems) make standard procedures easier, while modular furniture can readily be reconfigured to create new process sequences. In this way, production can be constantly adapted to changing market needs. Furthermore, the decision rules for applying tacit human expert knowledge are readily codified by automation experts but are frequently unavailable to end users in the laboratory. AI changes that!
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BIOPROCESSING
The digital age of bioprocessing and how manufacturers are benefitting from advancements in the sector.
STREAMLINING
BIOPHARMA MANUFACTURING
D Author: KEVIN SEAVER - general manager, Bioprocess Automation and Digital, Bioprocess Program at Cytiva
iscovering and making a new drug can take up to 10 years before regulatory approval. We have an opportunity to use tools in the digital world to shrink this timeline dramatically, but our industry is slow to take advantage. This is partly due to cybersecurity concerns as well as clinical and regulatory changes, but we can mitigate risk by turning custom bioprocessing projects into products. Without this advancement, the industry will fail in its responsibility to improve human health. Companies can mitigate some of this risk by engaging early with drug manufacturers and using laboratory and testing facilities to lay the groundwork for the complicated processes involved. Lessons learned from the labs and testing facilities can be transferred and scaled up for a full-scale manufacturing plant. The standard operating procedures (SOP) for bioprocessing plants currently require custom designed
The future of bioprocessing lies in equipment that harnesses digitised records for realtime analytics and predictive analysis and maintenance.
software and firmware that run bioprocessing equipment. In a highly regulated and audited industry, the financial and time investments needed to write and validate code for these projects can be immense. Even using some standard code base, the scope of a project can change rapidly as the development process advances. Turning custom bioprocess projects into standardised products allows customers to choose from a catalogue of hardware which can be integrated with other functions in the manufacturing process. Having bioprocess equipment that is more of a product than a project that has already completed the development cycle, and that fits the functional and user specifications, allows manufacturers to pre-test the equipment in a variety of environments and provide clear documentation and validation ahead of an expensive project. Instead of having to plan a new manufacturing system from the ground up, changes from developers can be accommodated relatively easily as only the updated parameters would need to be validated rather than the entire system. Extensive pretesting increases the overall quality of the system because of the comprehensive equipment testing required, which helps deliver nearly off-the-shelf bioprocess manufacturing
capabilities. Another benefit of bioprocessing equipment products is a reduction in time to set up a bioprocess plant. It no longer takes years to design, test, update, and re-test equipment as all of the testing and regulatory hurdles have been passed before the project begins. With the use of bioprocessing equipment products, records can easily be digitised and integrated. In this digital age, paper remains a constant in drug manufacturing, and the development of a single product can produce hundreds or thousands of paper documents. The transition to digital not only reduces some of this material production but makes records easier to audit and track. This helps speed up the validation of systems and can reduce time to product release down to months or even days. Additionally, digitising records allows manufacturers to apply a deeper analysis or simulation than they would normally get from paper documents. Bringing drug development into the digital age also allows for the use of digital twins – a virtual representation of a real-world plant or piece of equipment – a testing simulation which has been used in other industries over the last decade. Digital twins allow technicians to test various parameters to reduce costs, proactively anticipate issues, and optimise performance. The goal
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is to develop a “golden batch,” a benchmark for the most productive batch possible. With drug batches costing upwards of $1 million, there is little room for mistakes, and the digital twin model helps drive maximal improvements in yield. These innovations mark a new phase of digitisation for bioprocessing plants. Most plants in the industry are – according to the Digital Plant Maturity Model (DPMM) – at level one or level two, meaning that they mostly run on paper records. Getting to a level three plant offers an increasingly automated system with more connectivity that requires standardised equipment that a standard bioprocessing equipment plant offers. This approach provides a high-quality plant that saves drug developers money because of its quick set up time. A major challenge in digitising and automating these highly regulated drug manufacturing facilities is connecting them to the internet. Cybersecurity remains a primary concern because cyber-attacks can shut down an entire facility and cost millions to address. Cyber-espionage and the security of proprietary information and processes is another concern. Taking a standardised approach is one way to address this with builtin security and extensive testing to validate a piece of equipment. The future of bioprocessing lies in equipment that harnesses digitised records for real-time analytics and predictive analysis and maintenance. Standardised bioprocessing equipment allows for a rigorously tested plant to be put together in less time with higher quality outputs. As the industry continues to undergo a digital transformation, this platform offers integrated predictive capabilities and big data analytics that can help streamline the drug development process.
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BIOPROCESSING
The benefits precision dispensing technology can offer biopharma manufacturers thanks to its versatility and customisability.
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hanks to the everincreasing demand for its services, the biopharmaceutical industry has found itself at the centre of global attention and is growing every day. The far-reaching effects of the Covid-19 pandemic have left biopharma manufacturers under increasing pressure to bring quality lifesaving drugs to market faster. It is this pressure that is driving demand for rapid innovation and the simplification of complex workflows – all while maintaining safety and reducing costs. This is no easy task, especially when handling complex raw materials. As a result, single-use bioprocessing technologies have risen to the fore as a means for biopharma manufacturers to adopt new setups. These single-use systems have become an important tool for the industry – helping to streamline complex workflows, while offering the flexibility needed for on-demand and fluctuating capacity requirements; enabling manufacturers to keep pace with the ever-changing landscape.
bioreactors and product-holding sterile bags, to connection devices and sampling receptacles. Despite the recent growing interest in this type of technology, “single-use” is not a new phenomenon. First emerging in the early 1980s, biopharmaceutical manufactures utilised it in their production processes as the industry started to produce drugs in larger quantities. However, it is the advances
in single-use systems that have resulted in its increasing popularity today. Single-use technology is dominating the biopharma market, and is thought to currently be used in over 85% of preclinical and clinical manufacturing processes. With no signs of slowing down, the market is predicted to grow at an annual growth rate of 17.5% between 2020 and
Single-use bioprocessing technologies have risen to the fore as a means for biopharma manufacturers to adopt new setups.
2025, according to research from Market Data Forecast. Even with the success of single-use though, stainless steel workflows are unlikely to disappear, and so manufacturers must seek innovative ways to ensure their setup is as efficient and versatile as possible. That’s where precision dispensing technologies hold promise. These precise, flexible, disposable solutions do not require a complete overhaul of a facility and can achieve a wide range of efficiencies as part of different manufacturing setups and processes. Especially suited to applications like raw material handling, they can also minimise the amount that a product must be manipulated within a workflow to safeguard its integrity.
WHAT ARE SINGLE-USE SYSTEMS? Single-use technologies come in all shapes and forms from tubing, capsule filters, ion exchange membrane chromatography devices,
Author: UDO LOSEHAND - head of Global Technical Developers at Roquette
THE RISE OF PRECISION DISPENSING T
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6 WAYS PRECISION DISPENSING TECHNOLOGY CAN BENEFIT YOU Easily integrated into new or existing workflows, precision dispensing solutions bring fresh opportunities for manufacturers that are still reliant on stainless steel, single-use, or hybrid systems and can have a real impact on process efficiencies and your bottom line. Reduced handling time Products can be introduced at all steps of manufacturing, from the earliest stages at which ingredients are weighed and measured to their storage and transfer between different parts of a facility. Drug products must be handled, stored and manufactured using validated processes and equipment to protect the integrity of the final product, and assure the health and satisfaction of the end
ECHNOLOGY
consumer. This can be extremely time and labor-intensive, requiring additional procedures to be put in place, and increasing the margin for risk or contamination. With precision dispensing technologies, raw materials are pre-weighed and packaged according to manufacturing requirements, eliminating the process of having to manually weigh out different quantities of product from large drums – reducing handling time and thus increasing efficiency for manufacturers.
range of fill types and weights, while outlet port sizes can be changed to suit equipment design. Such attributes allow for a fully customised solution, and offer complete assurance of a controlled delivery, allowing processors to seamlessly discharge the right amount of raw material into the bioreactor for a given formulation.
Lower contamination risk By reducing the need to handle or manipulate raw materials, precision dispensing technology removes any inadvertent errors that can occur when manually weighing materials. Not only this, but manufacturers can also benefit from the minimised risk of external product contamination from handlers, equipment, and the surrounding environment – a crucial requirement to guarantee the safety of the final drug formulation. This is achieved via a clean connection and dust-free transfer of the product from the containment packaging to the bioreactor. In addition, precision dispense packaging that complies with extractables and leachables regulation for single-use technologies, can also minimise the introduction of contaminants via the packaging itself.
Increased productivity To avoid contaminating extremely valuable batches of product, manufacturers must implement extensive cleaning and sterilisation-inplace (CIP, SIP) workflows. This can be challenging as CIP and SIP workflows require time, monetary investment, energy and space, and force manufacturing downtime. Equipment must be completely shut down while it is cleaned, sterilised and validated – all of which can result in up to two weeks of downtime between batches, creating a significant bottleneck in pharmaceutical production. Precision dispensing technologies help to overcome these issues by reducing the time spent handling materials, sampling, dispensing and processing, as well as reducing the significant downtime that comes with cleaning and validating product containers. This means manufacturers are able to process more batches per year, resulting in increased productivity.
Customisability Precision dispensing technology offers numerous benefits to manufacturers through its closed architecture and customisability. Single-use packaging, for instance, can be tailored to suit specific fill and weight requirements, so products can be matched to the desired chemistries and processes. Containers are typically available for a wide
Ease of integration Thanks to its range of customisable “plug and play” options available to suit numerous applications, precision dispensing technology can be quickly and easily integrated into existing manufacturing processes. This offers new opportunities for manufacturers reliant on either stainless steel or single-use equipment and ensures the flexibility needed
21 to keep up with industry as well as guarantee they remain cGMP and FDA compliant. Technologies such as this also reduce the amount of training required to operate the systems, reducing the amount of work hours in streamlining workflows, whilst also offering the same benefits regardless of setup specifics and further enhancing process efficiencies. Greater compliance and control Manufacturers should look for single-use packaging solutions that are produced in line with the highest standards of production (ICH Q7 GMP) to further reduce contamination and ensure greater compliance. Meanwhile, precision dispensing technology from a vertically integrated supplier with a single point of audit can offer additional advantages in terms of assurance too, by delivering high levels of transparency and compliance, as well as the added benefit of having extensive knowledge of the raw material science and its provenance. LOOKING AHEAD As the industry moves away from the ‘blockbuster’ mindset, we expect the popularity of single-use systems to continue to rise. The growing focus on personalised medicines and smaller populations increases the complexity of pharmaceutical manufacturing and requires the swift repurposing of existing assets – making it critical to optimise efficiency wherever possible. Throughout the Covid-19 pandemic, the world looked to the biopharma and pharmaceutical industry for a swift response and the progress made this year in terms of vaccine formulation has forever changed the way the industry will continue to develop.
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PACKAGING
EPM speaks to GARETH BAKEWELL, joint managing director at Reelvision about the evolution of packaging technologies in pharma and what this means for the safety of medicines.
LEADING THE PACK Packaging in life sciences is constantly evolving with new safety features (anti-tampering, tracking technologies etc). Despite this, do you think these technologies are being implemented in enough of a widespread manner throughout the industry? Without question there are many pharma companies that have a good strategy when it comes to protecting their products from targeted counterfeiters. These businesses have adopted a number of both physical and digital techniques. At Reelvision we have a constant flow of new designs and often received artwork that contains various counterfeiting features ranging from micro dots that appear randomly to micro text with hidden copy errors and pattern gloss varnishes with intentional imperfections. However there are many missed opportunities for brand owners to implement counterfeit features into their products and this could be due to a misconception that their inclusion will affect the cost of the packaging, which is not always the case. But with any advancement, the uptake of technology can be gradual and this is not always a bad thing as a slow uptake can often make the advancement more robust leading to long term positivity.
Reelvision’s lead time is particularly fast in this industry. How do you achieve this? To achieve this service and quality performance, we developed an inline print and die-cutting machine which controls colour through the utilisation of an engraved anilox roller with metered doctor blade that consistently delivered colour without variation. This secure singlepass manufacturing process eliminates the risk of admixture and is combined with a streamlined BSI approved MIS system to enable fast accurate order administration. This generates clear unambiguous instructions for production processing and dispatch of product with simultaneous invoicing.
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I think dialogue is the key to improving the implementation of counterfeit techniques and this needs to be done prior to MHRA artwork approval. You’ve been in the industry a while now and have worked with a range of clients. How has packaging evolved over your time to account for things such as counterfeiting or tampering? I have seen an improvement, driven by ISO, an independent non-governmental international organisation, where through the implementation of ISO9001/2015 PS9000/2016 accreditation, printing companies such as Reelvision have to demonstrate a robust secure disposal process of all manufacturing waste. Thus preventing the counterfeiter from gaining access to confidential documentation. More so, can the cost of implementing these technologies put companies off using them? Many counterfeiting measures are cost free if implemented at the point of artwork generation. However the printed packaging industry needs to be careful not to confuse brand owners with jargon & terminology, after all this is an industry that quotes such buzz words as grips, chokes and bleeds to stochastic and samba screens! Therefore it’s vital that a good dialogue chain is established between brand owners and converters where a plan can be formulated to implement
the right solutions for a multi layered approach to a sound counterfeit strategy. So, we know about tracking features and things like holographs and invisible printing for protecting packages but what other technologies are available that manufacturers may not know about? Most organisations will be aware of counterfeiting techniques such as bifluorescent and colourshift inks, debossed emblems, QR codes, RFID tags and smart labels. But even the most sophisticated anti-counterfeit approach is worthless if you can’t identify a genuine product from a fake or that the genuine pack has not been tampered with. I feel brand identity protection through the control of material specifications and colour consistency is a critical layer of the cake. Packaging converters need to be challenged to reduce the gap between light and dark colour standards and tasked with matching agreed pantone references. It should not be acceptable for colour to drift during production runs or repeat orders as this variation raises a question with the end consumer… is it a fake or has the colour faded because it’s passed its sell by date?
With such a plethora of technologies available, is there a way (either through policy or regulation) for them to be better integrated throughout pharma? I think dialogue is the key to improving the implementation of counterfeit techniques and this needs to be done prior to MHRA artwork approval. From my experience the food retail sector has this nailed down. I recall as a trainee salesman back in the 90’s, I’d spend hours driving up and down the M1 visiting Baker Street, Blackfriers, Cheshunt, Leeds with a few deviations down the M4 to Bracknell. All these visits would enable me to participate in a group discussion with brand managers, designers, food technicians, food manufacturers and fellow printers. This created the opportunity to view artwork concepts, discuss material grades, check the correct machine drawings have been submitted, voice any concerns and agree a critical path to ensure launches are always achieved on time. Subsequently final artworks were created and approved by all parties. These days all this is achieved via a time saving digital workflow but the principle is still the same with opportunities to voice your opinion prior to artwork being formalised.
23 Has the implementation of the Falsified Medicines Directive (FMD) in the EU improved the overall safety of medicines in the supply chain? Introducing measures to ensure all medicines are safe to use can only be a good thing and by adding extra features such as 2D matrix codes with tamper evident features only enhances the security of all drugs. Do you think the UK’s departure from the EU will harm the safety of medicines being imported into the UK? In short no. Both the EU and the UK have mirrored each other on the safe flow of medicines back and forth. The fact that the UK is now outside of that shared policy, we will still see the UK following the same rules and regulations. Outside of FMD, is there anything regulators can do to ensure that companies are adopting technologies that prevent counterfeiters? Understanding the impact of counterfeit goods is an incentive to drive companies to protect their brands as surveys would suggest that approximately two thirds of consumers who have unintentionally purchased a counterfeit product have in turn lost their trust in a brand. Within the pharmaceutical world the ‘trust’ element is essential as consumers need to know that the product they’re using is a safe and effective treatment.
About the company Reelvision was founded in 2007 as a company specialising in the manufacture of small to medium order volumes of printed folding cartons. From the start, Reelvision offered a standard 10-day lead time for clients wanting to buy small batches from an accredited source that came with all the required quality checks. In the past 12 months, Reelvision has been involved with supplying folding cartons for numerous Covid-19 clinical trials and has worked with the NHS as a key supplier for the Oxford/AstraZeneca and Pfizer vaccines to be delivered around hospitals and vaccination centres.
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PACKAGING
ADVANCES IN SAFETY How the pharma industry has continued to advance its efforts to improve the safety of child-resistant packaging.
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nintentional poisoning continues to be a widespread medical emergency across the globe, with medication being one of the most common causes, putting children at the highest risk of potentially fatal accidents. In the European Union (EU), poisoning is the fifth leading cause of unintentional death among children and adolescents. Research from the European Child Safety Alliance estimates that 3,000 children under the age of 14 die from acute poisoning every year. More recently, this has sparked increased efforts into improving parental education in ‘child-proofing’ homes, as well as patients and stakeholders calling on pharmaceutical companies to recognise the importance of child-resistant closures (CRCs) in medical packaging. The reduction in the rates of child poisoning since 2010 in the United States (US) is indicative
of a global decrease (Figure 1), but accidents can and do still occur, and regulations are continually evolving to optimise the safety of childresistant packaging for drugs. As the industry is improving its packaging standards and unintentional child poisoning therefore decreases, it continues to be a prominent factor in the development of pharmaceutical packaging. Effective CRCs for medical packaging must protect young children from gaining access to harmful substances, without hindering the ability of older patients to access their medication. GLOBAL GUIDANCE AND REGULATIONS There are varied mechanisms for incorporating CRCs on medical packaging, which are broadly categorised into: • re-closable bottles, which include push and turn caps or squeeze and turn caps.
Figure 1: Estimated number of emergency room (ER) visits in the United States for accidental medicine poisoning under the age of 6 years. (Source: Safekids Worldwide)
• non-re-closable blister packs which include a peel and push method. Now, in many countries, pharmaceutical and healthcare companies are required by law to produce packaging that is child resistant. The US has been leading the way in child-resistant packaging for years, where protocols were originally established in 1966. In 1970, the Poison Prevention Packaging Act (PPPA) was passed and placed under the jurisdiction of the Food and Drug Administration (FDA). In addition, the International Organisation for Standardisation (ISO) has published an internationally recognised agreed standard test procedure for re-closable child-resistant packaging and in Europe, several regulations have been introduced to complement this ISO standard. For packaging to be classed as child-resistant, it must meet one of the following standards: • ISO 8317:2015 – the International standard • EN 14375:2018 – the European standard • US 16 CFR § 1700.20 – US regulation To qualify as CRC packaging, pharmaceutical companies must now have certification of child resistance for their full packaging solution – including the container and closure – and must recertify
if either component is changed. One barrier that drug manufacturers face is the time and cost associated with certification. By partnering with a packaging manufacturer that can provide innovative packaging, as well as the required certification, this process can be streamlined, and companies can ensure child safety for their drugs. As awareness of unintentional child poisoning increases globally, large pharmaceutical companies are driving recognition and innovation in child-resistant packaging, with more advanced designs every year. One example is GlaxoSmithKline (GSK) which, as one of the world’s largest pharma companies, has made significant contributions to increasing awareness of the importance of child-resistant packaging and has integrated this approach into its drug manufacturing pipeline. However, there are important considerations when advancing packaging designs, such as the cost and sustainability. For example, failure to comply with exact requirements of child-resistant packaging could result in company fines or payouts in the event of child injury, while brand damage is also at risk in the event of unintentional poisoning. In terms of sustainability, increasing
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environmental awareness across the global pharmaceutical industry has drawn attention to the need for more sustainable packaging solutions. Aligning child-resistant packaging with additional components that make these solutions sustainable are increasingly important for both customers and company initiatives alike. Moreover, innovative user-friendly childresistant packaging solutions are driving the move to a more patient-centered treatment approach. SENIOR-FRIENDLY PACKAGING When developing child-resistant packaging for pharmaceuticals, one of the greatest challenges is designing a closure that both prevents children from gaining access to harmful substances, without limiting the ability of senior patients to take their medication. Increasing population age
combined with the growing trend for home care is directing the focus of child-resistant packaging simultaneously onto the accessibility needs of older patients. There has been criticism over the lack of acknowledgement in current protocols for disabled and vulnerable patients, who, if their needs are not met, may leave the closure off their medication and, in turn, increase the risk of child access. This, therefore, provides an opportunity for pharmaceutical packaging manufacturers and pharmaceutical companies to lead the industry in designing truly child-resistant seniorfriendly (CRSF) packaging for medicines. Strong relationships between drug manufacturers and packaging suppliers, as well as with healthcare providers and patients, will help facilitate this approach, for example by overcoming the currently perceived trade-off between child resistance and seniorfriendly packaging. THE FUTURE WITH SAFE, COMPLIANT CHILD-RESISTANT PACKAGING Following the introduction of child-resistant packaging requirements, the incidence of poisoning in children has decreased steadily throughout the last 10 years. As well as enhanced regulation, this decrease is thought to be attributed to increasing
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awareness campaigns and educational efforts, through initiatives such as the Centers for Disease Control and Prevention (CDC) PROTECT Initiative and Up and Away Campaign, and Safe Kids Worldwide’s medicine safety programme. However, unintentional poisonings and fatalities still occur across the globe. The risk to children depends heavily on their environment, and with more adults receiving prescriptions for medication such as sleeping aids, strong painkillers, and antidepressants, childhood exposure to harmful medication increases. As certain drugs have become more problematic for child safety, such as the increased prescription of opioids, the need for safe, compliant childresistant packaging has received increased attention. There is always room to improve the safety of pharmaceutical packaging that also maintains medication compliance with patients, particularly seniors. Innovation is continuing to take place to ensure child-resistant packaging is truly senior-friendly. As we look towards the future, it is vital that drug manufacturers and pharmaceutical packaging manufacturers collaborate to supply the safest packaging solutions and meet the regulatory requirements to prevent unintentional deaths across the world.
Following the introduction of childresistant packaging requirements, the incidence of poisoning in children has decreased steadily throughout the last 10 years.
Authors: NAJET MEBARKI - senior product marketing manager at SGD Pharma. DR ROLF ABELMAN - managing direction at IVM Childsafe.
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Talking points
OUTSIDE EPM
WHO COMMENDS US FOR SUPPORTING TEMPORARY WAIVER OF COVID-19 IP RIGHTS Malaria vaccine first to reach WHO efficacy level in clinical trial
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malaria vaccine undergoing testing has become the first to have reached efficacy levels of 75%, a target set out by the World Health Organisation (WHO). Researchers from the Jenner Institute - based in the University of Oxford - reported findings from a Phase IIb trial of the malaria vaccine candidate (R21/Matrix-M), showing that the candidate had a 77% efficacy rating. The vaccine is being developed between the University of Oxford and biotechnology company Novavax. The team is the first to reach the WHO’s Malaria Vaccine Technology Roadmap goal of a vaccine with at least 75% efficacy. The Phase IIb study consisted of 450 participants aged between five and 17 months. Participants were split into three groups, with the first two groups receiving the vaccine candidate and the third receiving a rabies vaccine as the control group. In the higher-dose adjuvant group, the efficacy results were 77%, with 71% being reported in the lower dose adjuvant group over 12 months of follow up. Now, the researchers are recruiting for a phase III trial which will involve almost 5,000 children across four African countries.
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he World Health Organisation has commended the US government for supporting the waiver for intellectual property (IP) protections for Covid-19 vaccines. On 5 May, the US government announced that the waiving of IP property protections on vaccines was needed to help end the Covid-19 pandemic. The action was announced by US Trade Representative Katherine Tai who said that “the extraordinary circumstances of the Covid-19 pandemic call for extraordinary measures.” “The Administration believes strongly in intellectual property protections, but in service of ending this pandemic, supports the waiver of those protections for Covid-19 vaccines,” Tai continued.
Speaking about the action, WHO directorgeneral Dr Tedros Adhanom Ghebreyesus said: “I commend the United States on its historic decision for vaccine equity and prioritising the well-being of all people everywhere at a critical time. Now let’s all move together swiftly, in solidarity, building on the ingenuity and commitment of scientists who produced life-saving Covid-19 vaccines.” UK prime minister Boris Johnson is now facing the same pressure from a letter signed by over 400 academics, MPs, healthcare workers and others. The letter, organised by social justice organisation, Global Justice Now, calls on Johnson to stand on the “right side of history” and ensure that vaccines can be made available to everyone.
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riana Papin-Zoghbi, CEO and co-founder of AOA spoke to Med-Tech Innovation News to discuss its offering, which includes an early-stage ovarian cancer biopsy test. Make sure to read the full article on www.med-technews.com
BE SURE TO LISTEN TO On this episode of The MedTalk Podcast, Joe Barnes, Brussels correspondent from the Daily Express discusses the latest developments in the ongoing dispute between AstraZeneca and the European Commission over Covid-19 vaccines.
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