www.epmmagazine.com LOOKING AT THE YEAR AHEAD
PREDICTIONS FOR COLD CHAIN
VIRTUAL ENGAGEMENT IN PHARMA
January/February 2022
CAN KETAMINE BE THE CURE TO ALCOHOL ADDICTION?
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Contents
January/February 2022 | Volume 22 Issue 1
REGULARS 5: EDITOR’S DESK
Why we should pay attention to the latest antimicrobial resistance research.
6: A SMALL DOSE
A brief round-up of some of the latest developments in the industry.
10: OPINION
How virtual engagement will transform pharma in 2022.
13: IN THE NEWS
A short selection of stories from the world of science.
14: COVER STORY
Why latest research into ketamine shows promise for people with alcohol addiction.
26: TALKING POINTS
Stories to consider and what to look out for in EPM over the coming weeks.
FEATURES 8: WHAT’S TRENDING
What to look out for from pharma in 2022.
16: LOGISTICS & DISTRIBUTION Predictions for cold chain this year.
20: BIOPHARMA & MANUFACTURING Data integrity and streamlining the development of biotherapeutics.
24: CONTAINMENT & CLEANROOMS How targeted therapies are facilitating a rise in containment & cleanrooms.
20
24
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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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O
nce again, the scientific communit has brought attention to the devastating impact antimicrobial resistance (AMR) is having on the world. This time, it was research in The Lancet that highlighted the global impact of AMR and the 1.27 million deaths that were attributed to it in 2019. Though the study was the largest-to-date, it wasn’t the first time such warning have been issued. For years now we’ve heard of what growing resistance to antibiotics means for the healthcare industry and how it functions. AMR threatens
the foundations of medicine in such a way that it could mean the end to healthcare treatments we’ve taken for granted for years - routine surgeries, childbirth, even cancer care. Perhaps it’s because deaths attributed to AMR were so much higher than previous estimates of 700,00, or that the Covid-19 pandemic has made us aware of the global impact that health crises can have, but this time the message seemed to make an impact. Media outlets took up the story of AMR’s current impact and there seemed
EDITOR’S DESK to, at least on social media, be widespread conversation surrounding what needs to happen. That people are speaking about AMR as a major issue is encouraging but what happens next will be critical for healthcare’s future. We know that incentives for pharmaceutical companies are needed if they’re to start actively targeting new antibiotic developments. Right now, a lot of the activity within
AMR is from early-stage startups and biotechs – companies which face an enormous risk of going bankrupt once funding dries up. The problem with AMR is that it is an elusive threat. Much like that of global warming, its impact can be difficult to s , unless you’re looking for it. The fact that for many years now warnings about AMR have been linked to potential future deaths mean that it’s been an easy to ignore problem. But with yearly deaths worse than expected industry and government can’t ignore the problem for any longer. When The Lancet’s story spread, many of the same arguments about AMR were brought up – the need for push and pull incentives, how many of the major players have left the space and how current market conditions don’t encourage companies to invest in antibiotic research. Undoubtedly, it’s discouraging that these are the same arguments that have been discussed for years. Progress has been made in some areas. Several organisations such as the AMR Action Fund and the Infection Innovation Consortium (IICON) are focused on helping companies progress their products to market, but more is needed. Covid-19 has shown us that industry, government and regulators can act quickly when needed. However, we can’t afford to wait until AM is at its worst, then it will be too late. A recent report by the AMR Industry Alliance describes the problem well. “Antimicrobial resistance won’t race across the world like Covid-19, but its effects will be devastating ”
6
A small dose
Sharp invests in new gene therapy packaging and distribution capacity
C
ontract packaging and clinical supply services provider Sharp has invested in new gene therapy facilities to help meet increased demand from sponsors and manufacturers. The company has completed the construction of new production suites at its facility in Heerenveen, The Netherlands. The expansion is intended to help facilitate the packaging, storage and distribution of gene therapies. Sharp hopes that the additional capacity will help it meet demand from sponsors and manufacturers of gene therapies for dedicated, specialist packaging capacity. Sharp has fitted the Heerenveen facility with similar capabilities to that of its Bethlehem, Pennsylvania facility, as it looks to offer support for clients in both the US and European markets. The new secondary packaging area is designed to offer the
optimal environment to address the complexities of gene therapies specificall , labelling and packaging vials and injectables at low volumes and low temperatures, for distribution in cold and ultra-cold supply chains. The Heerenveen facility includes a range of systems that are designed to facilitate the storage and packaging of gene therapies. The site also provides key operational efficiencie through its electronic batch record and a standardised quality management system. Vesna Bondzulic, site manager at Sharp Heerenveen said: “We recognise the enormous promise of gene therapies, as well as the unique complexities they can present to traditional pharma supply chains. Everyone at Sharp is excited to collaborate with our clients as we help them bring lifechanging and potentially curative therapies to the patients who need them.”
RECIPHARM SIGNS VACCINE MANUFACTURING DEAL
C
ontract development and manufacturing organisation (CDMO) Recipharm has signed a deal with a pharmaceutical company to support the manufacturing of a vaccine from its facility in Kaysersberg, France. Recipharm hasn’t disclosed which business it is working with but has stated it is
one of the top 10 global “big pharma” companies. The agreement will see Recipharm aseptically pack singleuse vaccines, used to treat a severe infectious disease that affects both young children and infants. The containers will be filled using Recipharm’s specialist blow-fill-seal (BFS) capabilities, creating products that are quick
to distribute and with an aim of simplifying administration for healthcare providers. To support the product as it scales towards commercial production, Recipharm plans to recruit over 30 members of staff between 2022 and 2026. Yves Buelens, general manager at Recipharm’s facility in Kaysersberg, said: “We are very proud
Allergy Therapeutics moves closer to trial peanut allergy vaccine
T
he Food & Drug Administration (FDA) has cleared Allergy Therapeutics’ Investigational New Drug application (IND) for its novel virus-like particle (VLP)-based peanut allergy vaccine candidate. The clearance paves the way for Allergy Therapeutics to begin its Phase I PROTECT trial which will be conducted in the United States. The trial will include multiple cohorts beginning with healthy subjects, followed by peanut allergic patients who will undergo skin prick tests, and then peanut allergic patients who will receive subcutaneous injections. Previous primary and secondary data from a trial of Allergy
Therapeutics’ vaccine candidate were positive. The ex-vivo biomarker study demonstrated a 24-fold reduction in basophil activation and histamine release – the chemical which causes many of the body’s allergic reactions. Data also showed reduced IgE binding capacity to B cells, compared to exposure to the
major allergen Ara h2. This strongly suggests a promising safety profile with reduced potency to induce allergic reactions. Manuel Llobet, CEO of Allergy Therapeutics, stated: “We have achieved a key milestone with the FDA’s clearance of our IND application and look forward to advancing our innovative peanut allergy vaccine candidate into the clinic. We are now one step closer to bringing to patients a safe and effective short course vaccine with the potential to provide long-term protection and a long-lasting protective immune response. I am excited to see the start of the PROTECT trial later this year.”
7
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We are very proud to be supporting a big pharma partner. to be supporting a big pharma partner in the delivery of a vital vaccine to the market. This deal is indicative of Recipharm’s successful and ongoing product portfolio diversification. e’ve invested heavily into new capabilities that have built on our BFS expertise and as a result, strengthened our biotech offering. e
are now in a position to welcome new biopharma projects to the Kaysersberg site.” Recipharm is investing almost €14 million into its vaccine manufacturing offering at the sit . Previously the site was dedicated to the exclusive production of sterile liquids for therapeutic areas, including eye care and ear drops.
Become a TOPRA member TOPRA is the professional membership organisation for individuals working in healthcare regulatory affairs across all sectors – from medicines and combination products to medical devices and IVDs. We work with our members internationally to enable and promote excellence across the healthcare regulatory profession.
Key member privileges • Monthly Regulatory Rapporteur journal (print and digital) in addition to newsletters • A variety of free member webinars throughout the year • New TOPRA Engage community app • Access to free and discounted resources and information online • Professional development tools (e.g. CPD recorder tool, quizzes and more) • Stand out from the crowd by obtaining significant designations (MTOPRA, FTOPRA) and professional registrations (e.g. Chartered Scientist – CSci, Registered Scientist - RSci) And more…
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8
WHAT'S
TRENDING
In What we can expect from the pharmaceutical and life sciences industries in 2022.
AspenTech’s five top tips for pharmaceuticals in 2022
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By: Kelly Doering, senior director, Industry Marketing, Pharma, AspenTech
s we move into 2022, the future for pharmaceuticals is focused on how companies leverage automation and the latest digital technologies to drive process improvements. Several key areas are top of mind for decision-makers across the industry. Here we focus on five of the most important Continued drive for faster time to market - The speed at which pharmaceuticals companies developed and brought new Covid vaccines to market in 2021 was widely celebrated. Throughout 2022, manufacturers will focus on developing a more efficient production cycl to support speeding up the industry’s time to market for all medicines. The objective will be to ensure quality, automate time-consuming processes, reduce risks, remove unplanned downtime and prevent bottlenecks. To support this vision, pharmaceutical
companies are increasingly turning to a digital workflow powered by industrial AI across planning, scheduling, production and asset management. Quality control is alive and well – Automation and analytics are driving more innovation in delivering quality across pharmaceuticals. For example, using Quality by Design (QbD) principles and process analytics, manufacturers can monitor critical quality and performance to ensure final product quality within a compliant environment. Advanced Process Analytical Technology (PAT) is key to this. PAT is the implementation of at-line and in-line advanced measurement systems to provide full visibility of critical process parameters and their effects on the critical quality attributes. PAT is a powerful enabler for QbD, which helps ensure product quality through judicious process design, monitoring and control. Such
are the benefits that w ’d expect to hear much more about both PAT and QbD during 2022. Manufacturers will focus more on transforming continuous processes – With much discussion about the benefits of moving from batch to continuous manufacturing for improved quality, throughput and yield, it is important manufacturers put the right technologies in place to optimise the latter approach. Process performance monitoring becomes a network of online models supervising desired operational indicators and key performance metrics. The models will provide automated insights and propose adjustments for continuous processes. At the same time, batch control solutions are emerging that can predict batch results and anticipate deviations from target and automate corrective action, enabling more consistent efficient operation The time is now for more focus on traceability - Electronic batch record (EBR) systems will drive benefits across pharmaceuticals during 2022. They contain the logic and rules that enforce the
manufacturing workflo . They improve data integrity, minimise error, enable efficient batc review by exception, reduce paper and manual entries and capture contextualised data to power industrial AI and advanced analytics. Audit trails, electronic signatures and documentation needed for compliance are part of the feature set. The use of real-world data will have a greater impact on decision-making in pharma – Pharma companies have been seeing the benefits of aggregating and analysing real-world data from a variety of sources, including gaining insights that will help them improve the development and commercialisation of safe and efficacious drug to the marketplace. Bringing data together with real-world evidence that informs the next therapeutic, the next set of criteria for a clinical study population or to better apply learnings from post-market surveillance data requires powerful digital and analytics tools to enable this. We expect these tools to be even more widely used in the industry in 2022.
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FLEXIBLE MANUFACTURING TO BE KEY
J
ohn Carey, head of sales at ACG Engineering thinks that driving consumer trends across the pharmaceutical supply chain means that manufacturers will need to be fl xible in their infrastructure to achieve success. Fast moving consumer trends will need to be met with long-term infrastructure updates, something Carey says is “no easy feat”. “Flexibility will be a key driver for these companies in 2022. To incorporate more fl xibility, manufacturers will likely look to improved automation, data analytics, machine learning and the IIoT. Smart factories can use real-time data analytics and machine learning to reduce costs, improve quality, and reduce capacity constraints. Developments in predictive analytics have made it possible for manufacturers to draw on vast pools of data, including information on resource consumption, machine performance, and storage conditions on factory floor to troubleshoot problems, optimise processes, and boost productivity,” Carey said.
A greater focus on antimicrobial resistance
T
he fight against superbug is expected to become a large focus for the industry, according to non-profit grou , The Pistoia Alliance. Whilst the Covid-19 pandemic has – understandably – taken some of the focus o antimicrobial resistance (AMR), the industry risks losing valuable time if actions aren’t taken to combat this growing threat. The Pistoia Alliance expects a greater focus to be placed on AMR this year, with public- private partnership, funding from philanthropic
9 organisations, governments and international bodies, helping to incentivise research. Linda Kasim, Empowering the Patient theme lead, Pistoia Alliance said: “The public sector must quickly increase investment into AMR research, or the cost to national economies and public health could be devastating.” Kasim’s warning is especially relevant given deaths from AMR are higher than previously thought. A study in The Lancet has placed global deaths caused by AMR at 1.27 million, making it a leading cause of death worldwide – surpassing those caused by HIV and malaria. Previous estimates placed deaths caused by AMR at 700,000 per year.
The problem is no longer vaccines but vaccination.
LESSONS FROM COVID-19
U
ndoubtedly, Covid-19 will remain a priority for governments and health systems all over the world. As we head into the third year of living with this virus, lessons must surely be learnt if future pandemics are to be averted,
or dealt with more effectivel . The International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) recognises this. Reflecting on pandemi preparedness to the World Health Organisation (WHO), IFPMA said that “the problem is no longer vaccines but vaccination as a result of vaccine hesitancy, absorption capacity, and country readiness.” “While we are proud to be part of the largest and most
rapid global vaccine rollout in history, we know that society needs to do more and go further, urgently addressing the bottlenecks in vaccine administration while reflectin on how to achieve more equitable allocation faster in the future. Manufacturers, governments, academia, NGOs and other global health institutions have a collective responsibility to ensure that no one is left behind in this pandemic and the next outbreak,” IFPMA warned.
10
Opinion
Because virtual engagement allows patients to engage anytime and anywhere through a connected device, trials may naturally become more diverse.
3 WAYS VIRTUAL ENGAGEMENT WILL TRANSFORM PHARMA IN 2022 Author: MIKE ABBADESSA - VP SME Head of Medical Affairs at Within
F
The benefits of pharma going virtual and whether the industry is prepared to do so.
or pharma companies, predicting where the sector will evolve is key to business planning. By staying ahead of the curve, companies can best position themselves to get results. While the unpredictable events of both 2020 and 2021 threw the pharma sector off track, the industry proactively adapted to the situation. In 2021, we saw decentralised trials come to the forefront, along with an acceleration of virtual care by the wider healthcare sector. Many were predicting virtual engagement to be the trend for the next fiv , 10, 15 years, but its adoption has taken just two. So, what follows this? How does virtual engagement continue to move at pace throughout the pharma industry to drive results, gain insights and equip teams for a post-covid pharma sector? THE COMEBACK OF IN-PERSON EVENTS? Gone are the days of extensive, unnecessary travel to attend pharma events in person. Not only does this waste time unnecessarily, but a 2019 study from McMaster University found that the pharma industry’s carbon emission intensity is higher than that of the automotive industry. Virtual engagement amplifies collaboration while being a better environmental choice.
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The pandemic changed the game, creating a virtual world which has altered our ways of working for good. However, as we look ahead throughout 2022, it is clear we will not see a return to the ‘old normal,’ nor is the ‘new normal’ here to stay. Instead, pharma companies will use virtual engagement to create new and improved in-person events. Across the life science space employees are prioritising flexibility above everything else. Although some professionals have stuck to their old ways and choose to travel to work, others are choosing to remain virtual. Therefore, medical affairs and other pharma teams must be flexible to these demands and ensure no one gets left behind. In our hybrid world, if you can bring the event to the participant, why would you expect them to travel? By engaging with audiences in this way, companies can increase reach and attendance and ensure a greater audience engagement. However, most importantly, organisations will be able to develop a successful process that can be repeated across teams, organisations and geographies. Key opinion leaders (KOLs) may struggle to attend advisory board meetings because of the time zones and travel involved. However when incorporating asynchronous features, KOLs can choose to take part in more opportunities for scientific exchange. This facilitates wider contributions, flexible working, and builds peerto-peer relationships. As we look ahead to 2022, virtual engagement will continue to facilitate global collaboration, more diverse perspectives, and a higher participation rate for KOLs overall. THE YEAR TO IMPROVE DIVERSITY IN TRIALS One priority that continued to emerge in 2021 was a need for drug developers to include people from different backgrounds in clinical studies. Despite a lot of focus on this in recent years, at the end of 2021, ethnic minorities in UK clinical trials were drastically under-represented. While the momentum will continue into 2022, virtual engagement in trials can become a main facilitator of more diverse studies. Because virtual engagement allows patients to engage anytime and anywhere through a connected device, trials may naturally become more diverse. Those who had previously been excluded from trial recruitment can now participate, with results that benefit a broader patient population.
This potential allows patients to participate on their terms and removes financial or travel burdens that traditional trial participation induce. In 2022, we can expect virtual engagement in trials to contribute to reduced health and socioeconomic disparities. DEEPER INSIGHTS AS A PRIORITY Companies regularly speak to stakeholders throughout the product development process, but what perspectives are they hearing? Nurses, researchers, and academics may all have valuable insights, but how can pharma companies ensure all relevant voices are being heard? This year, life sciences companies will bring strategic insights management to the forefront. Through a shift in approaches to engagement, pharma organisations will see the benefits of a holistic, insights-based approach as opposed to tackling each engagement one by one. With pharma companies increasingly aiming to achieve more in less time, strong insights management gives teams bespoke insights to equip them for success. For example, advisory boards tend to fall victim to hierarchy influence, in which loud voices dominate and monopolise in-person or webcast meetings. However, asynchronous communications allow for a safe, reflective environment that adapts to the strengths of participants. Virtual engagement reduces the chance that a few voices will dominate, and offers an easier way to follow up or ask for more information when interesting points are raised. 2022 will see virtual engagement continue to occupy centre stage within pharma companies, as organisations rely on disruption-proof means to gather deeper, more diverse insights. Not only this, but virtual engagement strengthens relationships with key stakeholders and creates an environment where everyone can participate, regardless of location or schedule. These predictions come from reflecting on another unusual and unpredictable year. However, by looking at how virtual engagement transformed the life sciences industry over the last few years, it is somewhat inevitable that a return to some in-person events, prioritising the collection of deeper insights, and a move toward more diverse perspectives will also be accelerated by virtual engagement.
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IN THE NEWS
Breast cancer takes top spot for must studied disease B reast cancer was the most studied disease area in 2021 even beating Covid-19, according to research from analytics company Phiesi. Results from Phiesi’s global analysis of all clinical trials conducted in 2021 placed breast cancer at the top of researchers’ interests. This was followed by Covid-19, non-small cell lung cancer, solid tumours, and multiple myeloma, highlighting the place oncology has within clinical research. Since 2017, 25,000 investigator sites have been solely dedicated to recruiting patients, a trend that was not impacted by Covid-19. Phiesi estimates that this means an average of 5,000-7,000 people are working on breast cancer clinical trials. The typical clinical trial for breast cancer recruits between 100 to 150 patients, with the optimal number of sites to achieve an efficient enrolmen time being around 40. The typical enrolment cycle time in this case was approximately 650 days. However, only 14% of trials analysed were optimised. Data show that fewer or more sites than 40 increased enrolment cycle time, and
therefore caused delays to the trial as a whole. “The fact that oncology takes four of the top five spots for most studied disease area underlines its status as the area still receiving the most investment – and it is good news for patients that even as the biggest public
health crisis for 100 years is ongoing it is still taking the top spot,” commented Dr Paul Chew, chief medical offic , Phesi. “Breast cancer affects 2.2 million people a year globally and is the second most common cancer in women in the United States, making up about 30% of all new female cancers
each year. Over the last decade, studies in HER 2+ and triplenegative breast cancer have contributed to significant advances in prolonging survival in these patients. Our analysis shows a lot more is being done to ensure we find better ways to prevent, detect and treat all cancers. We’ll
Did you know?
In the UK, breast cancer is the fourth most common cause of cancer deaths.
In 2020, there were 2.3 million women diagnosed with breast cancer.
It’s thought that one in eight women will get breast cancer in 2022.
continue to see high levels of investment in oncology throughout 2022, and we expect to see more emphasis among sponsors on making data-driven decisions to drive more successful trial outcomes.” In terms of geography, the data show that in the USA clinical trials for breast cancer actually decreased from 2020 to 2021. In China, they increased by almost 300 from January 2020 to July 2021, going from 736 to 1,023. By contrast in the UK, there has been a downward trend of recruiting sites over the last three years. “Our analysis shows there is a considerable room for optimisation in trial recruitment in the top investment areas. There is heavy competition for patients in cancer trials. Inadequate planning and a lack of understanding on the current trial landscape causes delays to patient recruitment and prolonged cycle times,” commented Dr Gen Li, president, Phesi. “Inclusion/exclusion issues in trial planning and protocol design, will accelerate trials and improve efficienc bringing innovative
.Human touch. .Industrial performance.
SMA treatment bring hope to NHS patients
A
new medicine has become available on the NHS offerin potential hope to thousands of patients with Spinal Muscular Atrophy (SMA). SMA is a genetic disease that causes the muscles to waste away. People with SMA have been without a daily medication for their condition, leaving many of them unable to walk and requiring the use of a wheelchair. However, last year saw the NHS grant access to Risdiplam, an oral medicine that improves motor function. The drug is the first non-injectabl treatment for patients which can be taken at home. Dr James Lilleker, consultant neurologist at Salford Royal, said: “The landscape has now completely changed for SMA patients with two drugs being available. The fact that Risdiplam is an oral medication is a game changer as we are unable to access the
spine of many people with SMA to administer the alternative spinal treatment. Sam Turner, who has SMA, has been in an electric wheelchair since he was two years old, after his parents noticed that at 18 months old, he wasn’t developing like other children his age. Sam is currently taking a daily dose of Risdiplam and believes he is showing small signs of improvement. He said: “I was watching a film wit my mum one night and she suddenly said, ‘Did you feel that?’. I had squeezed her hand for the first time and sh was quite emotional. I struggle to grip and clench things so this doesn’t sound much but to mum it was. “When I found out I could have the new drug it was a great feeling and mum was pretty excited. We just hope the treatment will help maintain the strength I have now or I may even get a bit stronger.”
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14
COVER STORY
European Pharmaceutical Manufacturer explores the rise of ketamine as a treatment for depression and why a recent study shines hope on the drug being used to treat alcohol use disorder.
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study published in January in the American Journal of Psychiatry has pointed to the use of ketamine as a treatment for people with alcohol use disorder (AUD). The study was labelled as the first of its kind to investigate how ketamine-assisted therapy can treat AUD and the results were positive. Of the results available, perhaps the most significant is the fact that without treatment, one in eight patients would have died. Following treatment, that number decreased to one in 80, representing a 10-fold decrease in the risk of mortality. Awakn Life Sciences, the biotechnology company behind the study, was encouraged by its results, and believe that its work could represent a radical shift in how alcohol addiction is treated.
CAN KETAMINE BE THE CURE TO ALCOHOL ADDICTION? Author: REECE ARMSTRONG – Editor, European Pharmaceutical Manufacturer
KETAMINE AS A TREATMENT To understand the use of ketamine as a treatment for AUD, you first have to look at how it’s been used to treat depression. Ketamine has a long history of being used in medical settings. It was first approved for human use as a general anaesthetic and short acting analgesic in 1970. Before then, clinical trials had shown the compound as able to relieve physical pain, but also that it had a range of psychological effects including hallucinations, paranoia, emotional withdrawal, and a feeling of patients being disconnected from their body and environment. It wasn’t until the millennium when a small-scale study tested the use of ketamine as a treatment for patients with major depression. Though that
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study only featured a handful of patients, the results paved the way for further research, and the next two decades saw more studies launched investigating the use of the drug to treat depression. In 2019, the Food and Drug Administration (FDA) approved Janssen’s Spravato nasal spray treatment for patients who have cycled through multiple anti-depressants with no success. Spravato is a modified form of etamine, and its launch represented the first new type of treatment to be approved for depression in decades. Ketamine does have its critics, however. Spravato’s clinical trials for instance were called into question for their mixed results. The spray was tested in three, four-week trials, as well as a longer-term trial assessing patients’ time-to-relapse. In two of the short-term trials Spravato did not demonstrate its targeted effica , though data from the remaining trials show that patients experienced a reduction in the severity of their depression, as well as a decreased chance of relapsing into depressive symptoms. More so, a statement by the Royal College of Psychiatrists in 2017 cautioned against ketamine as a long-lasting treatment for depression. The paper stated that whilst “short term efficacy ha been demonstrated after a single treatment, benefits are not lasting for most patients, and mood can rapidly decline after initial improvement, potentially increasing suicide risk.” However, there’s no doubting that ketamine remains an interesting option to treat depression and it’s this link which could be one part of its use in helping treat those with alcohol problems. THE AWAKN STUDY In the Awakn study, a cohort of 96 patients with severe AUD were separated into four groups, two of which included the use of ketamine whereas the other patients received a saline injection. What’s crucial about this study though is how in one group, ketamine was given to patients alongside a form of psychological therapy. Awakn gave its patients three infusions of ketamine alongside seven sessions of therapy in a four-week period. Quite a condensed timeframe then but the results show that the treatment had longerlasting effects. t six-months, patients in the therapy & ketamine group managed total abstinence for 162 of those days. Researchers are still trying to understand exactly why ketamine can produce the kind of responses seen in studies where patients have depressive symptoms. Celia Morgan, professor of Psychopharmacology at the University of Exeter and Awakn’s head of Ketamine-Assisted Therapy for Addiction told European Pharmaceutical Manufacturer how they tried to apply what they knew about ketamine’s effects on the brain to their own study. “On a neurobiological level a lot of the animal studies have shown that ketamine produces an increase in synaptic plasticity - so the ability of the brain to make new connections. We kind of timed what we know about the peak of synaptic plasticity with our psychological therapy to try and enhance learning from
the psychological therapy,” professor Morgan told EPM. Awakn designed the study in a way so it could determine whether ketamine on its own was effectiv , or if psychological therapy alongside it was just as important. As professor Morgan puts it: “It seems to be more than just the drug.” The approach of using ketamine alongside psychological therapy looks to be key to treating, in this case, patients with a form of alcohol addiction. In essence, the use of ketamine in this trial aided the impact of the therapy. Professor Morgan can’t tell us exactly why ketamine assists with therapy, but says that it could be due to the “unique subjective effect” of the drug “It gives patients a new perspective on their life, it enables them to disengage a bit with their problems and their own issues and take quite an observant perspective and we think that’s really helpful in psychological therapy,” professor Morgan said. Understanding how the drug has been used in depression trials also seems to have bolstered its use alongside therapy. The Awakn study saw a statistically significant reductio in depression in patients after three months, alongside a decrease in patients’ inability to experience pleasure.
15 “We think it might reduce depressive symptoms at a time you know a risky window where people are likely to relapse, and that might actually reduce drinking in that timeframe. Often when people are drinking with alcohol problems it’s to manage negative emotions,” professor Morgan explained. GOING FORWARD Awakn is now looking at launching a phase III trial to further determine ketamine’s efficacy in treating UD when used alongside a form of therapy. More so, the company believes this kind of treatment could be applied to other forms of behavioural addictions, including gambling, compulsive sexual behaviour and binge eating disorders. If successful, Awakn’s treatment could offer new hope to people suffering from UD. Many current treatments are designed to reduce a person’s urge to drink or induce a physical reaction such as vomiting if they have a drink. At a time when alcohol-specific deaths have increased 18.6% when compared to 2019 in the UK, there is clearly an opportunity for a different type of treatment for patients. If Awakn gets this form of treatment approved, it could mark a turning point for how industry and regulators examine the possibilities of psychedelic medicines in treating behavioural addictions such as AUD.
Often when people are drinking with alcohol problems it’s to manage negative emotions.
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LOGISTICS & DISTRIBUTION
Creating a new Normal Predicting what’s in store for the cold chain sector in 2022.
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t this time last year, the world was eagerly anticipating the coming months. Covid-19 vaccines delivered hope for normalcy and excitement grew over convenience-related changes to healthcare, work and more. But the pandemic had other plans. New Covid-19 variants emerged, supply chain issues deepened and much of the day-to-day still looks different than pre-pandemic. The cold chain industry experienced rapid growth in 2020 and continues to experience both growth and change for the foreseeable future. The pandemic’s influence remains, which creates opportunities to innovate and better serve pharmaceutical and healthcare customers delivering medicine in new ways. This sets the stage for a few of our predictions this year. While Covid-19’s influence persists, we also see renewed interest in sustainability and the evolving impact of Brexit’s export regulations in the United Kingdom (UK). These will also shape how the pharmaceutical and cold chain industries operate. Let’s take a look at what all of this means for 2022. Author: ADAM TETZ - director of Worldwide Marketing at Peli BioThermal
It is still too early to draw concrete conclusions about the overall impact of Brexit on trade with the EU.
OUTSOURCING THE COLD CHAIN In our predictions last year, we anticipated that more pharmaceutical companies would outsource capabilities to contract manufacturing organisations (CMOs) and contract development and manufacturing organisations (CDMOs). Pharmaceutical companies already engage these organisations in the manufacturing and development of therapies, but adding additional services allows pharmaceutical companies to focus valuable time and resources on areas where they have the most expertise. We did see a shift last year to CMOs and CDMOs adding additional services, like cold chain logistics. We expect to see outsourcing grow again this year. Offering end-to-end xpertise
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will help reduce additional supply chain complexities by standardising more of the supply chain during a time when raw materials are scarce and transportation is unpredictable, necessitating dedicated and seasoned professional resources. Additionally, we expect companies not yet ready to fully outsource their supply chains to increase their use of services that make cold chain operations easier and eliminate the challenges associated with unforeseen circumstances. These include services like offsit conditioning of coolants or onsite conditioning with coolants inventoried to their unique needs. DIRECT-TO-PATIENT AND DIRECT-FROM-PATIENT GROWTH Also on our list last year was a new focus on direct-to-patient and direct-from-patient care, including significant growt in home-based clinical trials. In December 2019, 38% of pharmaceutical and contract research organisations expected to engage in a high volume of virtual research trials, with 48% of those expecting to run a trial, with most activity conducted in participants’ homes. According to management consultancy Mckinsey, these numbers increased to 100% and 89% respectively in December 2020. Many research organisations initially piloted this new model of clinical trials with smaller Phase I and Phase II trials. In the past year, we saw organisations pilot fully homebased and hybrid clinical trials in Phase III trials. This year we expect to see trials using
home-based care grow, with continued focus on improving the experience for patients and physicians. Logistics remain a challenge, especially given the narrow timeframe for deliveries and pick up of biologics or sample materials. All timing must coordinate with homecare visits and ensure temperature-sensitive materials arrive at their fina destination still within the required temperature range. Services like phlebotomy, drug administration and sample collection that require refrigeration will require cold chain solutions. We anticipate an ongoing drive toward solutions that require little training and are easy for home healthcare professionals and patients to operate. We should also see even more assessment and evaluation of the cold chain for home-based care in 2022. BREXIT RUNS SMOOTHLY Brexit, or the UK’s exit from the European Union (EU), officially began on Janua 31, 2020. However, nothing changed until a new trade deal was reached nearly one year later. Implemented in January 2021, the new deal outlined how the UK and EU would live, work and trade together. The most significan concern: new paperwork for export businesses. As new trade rules began, export businesses did in fact experience significant issue with increased paperwork. As a result, a large number of shipments were delayed, held at customs points or cancelled altogether. The impact of Brexit was further affecte by the global shortage of shipping containers and lack
of drivers to transport goods. Over time, exporting companies, shipping agents and logistics companies began to understand the nuances of paperwork required to enable shipments to the EU to take place without issue. This was a learning process for companies that hadn’t dealt with the complexities of customs clearance for decades. To enable this, companies recruited for new sta , which further slowed down the processes required. It is still too early to draw concrete conclusions about the overall impact of Brexit on trade with the EU. The Offi of National Statistics (ONS) noted survey data suggesting businesses’ trading activities were being held back by Brexit frictions, such as extra paperwork and higher transportation costs. However, the UK economy showed improvement during the course of the year. Shipments to the EU began to return to pre-Brexit levels as companies became more confident wit the complexities of the new rules. Further growth is expected into 2022, and with the general improvement with trading conditions as Covid-19 restrictions are relaxed, we can expect a surge in UK - EU trade during the course of the year. SUSTAINABILITY INITIATIVES MOVE FORWARD Only a few short years ago, pharmaceutical manufacturers viewed supplier sustainability initiatives as a nice-to-have, but not a deciding factor in their decision to do business
17 together. That shifted in 2020 with companies focusing on how they could impact the United Nations’ Sustainability Development Goals (SDGs), as well as building plans to execute and measure their efforts What began as internal initiatives quickly turned to a focus on how vendor and supplier sustainability initiatives impact a company’s sustainability goals. Pharmaceutical companies soon required vendors like Peli BioThermal to demonstrate that temperaturecontrolled packaging and modes of transportation minimise negative effects o the environment. Additionally, vendors were also asked to provide tools that help pharmaceutical manufacturers measure their actual environmental impact so they can monitor and demonstrate reductions in carbon footprint and waste. We expect to see this trend continue in 2022. However, we also expect pharmaceutical companies to dig deeper into the supply chain. Vendors and suppliers will be asked to also look at their supply chains and begin monitoring how their own vendors and suppliers contribute to their environmental impact. Each year brings hope and anticipation of new challenges. This upcoming year is no different. Thoug Covid-19 continues to influence supply chains companies are learning to operate in an unpredictable world. Overall, we anticipate this year will bring more stability and renewed focus on pre-Covid-19 priorities.
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Acino expands contract manufacturing services in Ukraine
Acino Contract Manufacturing services now include the company’s EU GMP-certified plant in Ukrain , serving as a manufacturing and packaging hub with a focus on technology transfer excellence. Here, they tell us more about the project. Author: YULIYANA MANOLOVA - Director Business Development Contract Manufacturing
Q: Acino Contract Manufacturing recently expanded its services by adding the plant in Ukraine as a manufacturing and packaging location for its partners. The plant successfully passed its EU GMP certification in 2020 and offers high quality service. What advantages does the site bring with it to make it so successful? A: We are excited to start offering contract manufacturing services from our plant in Ukraine. It will allow us to provide our customers with competitive
solutions for more costsensitive products. This site complements well the Swiss and Estonian ones as each of these locations has different strengths. It is very motivating to work with our colleagues in Ukraine who are enthusiastic about this new opportunity for business expansion. We have a strong team of professionals who have broad experience, strong know-how and a proven track record of product transfers and bringing products to market. The site in Kyiv is fully equipped for handling and processing of small
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molecule oral solids. We will continue to specialise in this segment and to strengthen our position in this growing market. We are doing so by positioning ourselves as a high-quality service provider. Q: As a growing contract manufacturing organisation, what strategies do you have in place to ensure Acino continues its recent trajectory? A: As we are constantly growing, new resources have been added in all departments working on product transfers. We have used the last year to strengthen our foundations and internal processes in order to facilitate the upcoming growth. We are putting a lot of emphasis on technology transfer excellence. Our dedicated project managers, who are solely responsible for ensuring our contract manufacturing clients’ expectations are met, set the pace to enable the teams to execute all transfers in a timely and complete manner. Proactive communication and attention to detail are crucial, and in order to enable them, we are making sure there are enough available and welltrained people to work on the transfers. Another important goal is to expand our oral solids dosage (OSD) portfolio. We are looking into new technologies which would complement our existing equipment and will allow us to be the preferred OSD service provider for our existing and future customers. In 2021, we
prepared a plan to expand into higher potency products and we are looking forward to building a manufacturing suite in our Swiss facilities by the beginning of next year. Q: What challenges do you see for the contract manufacturing business in the upcoming years and how are you going to address them? A: Some of the challenges we are facing are well known for years and we have been operating in this environment for a while now. The industry is moving towards more personalised products. This increases the demand for CMOs which can handle high complexity. For example, projects with a lot of SKUs and relatively low annual SKU volumes. Our plant in Ukraine is a location where we could handle such projects at a reasonable price. We have upgraded the site in Switzerland with larger scale equipment and we transfer high volume products there. These complementing services are allowing us to build product baskets and ensure the more financially challenging products can also find a home. Since 2020, we have had to show a lot of dedication and determination to make sure we remain on the right track and bring essential medication to patients. When we look at the pharma supply chain, manufacturing is usually the least affected by short term market fluctuations. However, this does not make us immune to changes. We
are currently dealing with significant increases in material prices. Excipients, APIs, packaging materials, all of them are affected. e proactively communicate with suppliers and clients to make sure we can maintain fair and reasonable prices and ensure continuous supply. Q: How will 2022 look for Acino Contract Manufacturing? A: Our Management’s vision and guidance is paving the way to exciting years ahead of us and we are enthusiastic about 2022. This is the year in which we continue strengthening our foundations for future growth and we make important steps to position Acino as the preferred EU oral solids manufacturing partner.
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BIOPHARMA & MANUFACTURING
STREAMING SERVICE How a new method streamlines the development and quality control of biotherapeutics and offers opportunities for contract organisations to better serve the pharmaceutical industry.
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he biopharmaceutical industry requires robust, efficient an reliable analytical methods to demonstrate the safety and efficacy of product during the development and manufacturing of new drugs, in order to safeguard patients. As biotherapeutic molecules become increasingly complex, the methods for analysing them must also evolve. The multi-attribute method (MAM) has emerged as a new approach for analytical characterisation and testing during process development and in quality control (QC) of biopharmaceuticals. What is MAM? MAM is a peptide mapping approach using liquid
chromatography-mass spectrometry (LC-MS). It can be used to monitor several different product quality attributes and therefore has the potential to replace multiple conventional methods including: reverse phase high performance LC; cation exchange chromatography; reduced capillary electrophoresissodium dodecyl sulfate (CE-SDS); and enzyme-linked immunosorbent assays (ELISA). Why would contract organisations want to implement MAM? To keep up with demand for new biopharmaceuticals and ever-changing regulatory requirements, pharmaceutical
companies are increasingly outsourcing analytical testing to contract organisations to gain extra capacity and expertise. Several big pharmaceutical companies are already using or planning to implement MAM in process development and QC testing. Therefore, offering MAM workflows provides opportunities for contract organisations to better meet the needs of their customers. MAM typically uses high-resolution reverse phase chromatographyMS to provide high accuracy mass data on many different quality attributes at the same time. It provides more detailed information about quality attributes compared to conventional approaches, for example, identifying changes in proteins at the amino acid level and performing site-specific
relative quantitation. The high sensitivity of MAM may be particularly advantageous for biosimilar development as it could help to show the new products are comparable to reference originator biotherapeutics with greater confidenc . Performing a single method approach is more efficien and produces less waste than generating and analysing data from multiple different assays, thus saving time and money. In addition, MAM can be performed using lower sample concentrations and volumes that may not be feasible with some of the conventional methods. MAM can be applied at different stages in the development process from cell line development to the
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fill-finish of the product witho making any changes to the method. Using MAM for forced degradation and comparability studies helps researchers to understand the critical quality attributes and the appropriateness of the analytical method tool kit. Ahead of using MAM in QC, it is typically necessary to perform qualification an validation activities for MAM methods to ensure consistent and expected results for the method, data analysis and reporting. This continuity enables more streamlined knowledge to be transferred between teams working at different stages of th programme, which can improve collaboration and efficien , and may give contract organisations and their customers an edge over competitors who still use conventional methods. What challenges might a contract organisation face when implementing MAM? Although MAM has many advantages over conventional analytical approaches, there may be some challenges in introducing the workflows into an xisting laboratory infrastructure. The initial investment and ongoing maintenance costs for high resolution mass spectrometers may be a significant hurdle fo many organisations, especially if they already have access to instruments suitable for the conventional approaches. As with any new venture, building a team with the right expertise is key to success. Training programmes need to be developed to ensure users have the expertise to use MAM at different stages in proces development and in QC. Contract organisations may also need to allocate time and resources into adapting their MAM workflow for diverse projects, such as the various phases of clinical trials,
or to study different types o molecules. To make full use of the large volumes of data MAM produces, users will need access to the appropriate data management and analytical software. Furthermore, it will be important for contract organisations to communicate effectively with thei customers to ensure the data analysis meets their expectations and the requirements of the regulatory authorities across the globe. MS is not currently widely used in QC and, therefore, individuals working in this space may not be familiar with MAM and other MS approaches. Since MAM offers site specific informati and higher sensitivity compared to some conventional analytical methods, it could bring to light new data that may need more initial work to interpret but will ultimately provide new insights for better product development. For example, the MAM profile of molecule may show changes that conventional methods miss. The clinical significance of an differences between MA data and conventional data needs to be understood before making important decisions on the direction of the product development. Therefore, while MAM workflows are bein established, it is important to use orthogonal to conventional methods during the early stages of product development. During Investigational New Drug filing it is recommended to use MAM data to support the chemistry, manufacturing and controls data acquired using conventional approaches. The data collected in the early stages of development will allow organisations to use MAM instead of conventional methods later on in the process to achieve better timelines.
Once the initial hurdles of setting up MAM workflows are overcom , contract organisations will be in a good position to offer mor streamlined and higher sensitivity analytical testing to their customers. What is the future of MAM? Over the next 4-5 years, it is expected that MAM will start to replace conventional analytical approaches in biopharmaceutical process development and become more widely used in QC. The adoption will be mainly driven from the growth projected in bi-specifics, fusion protein and other complex biomolecules. MAM may also be adopted for in-line testing of molecules during upstream and downstream operations to highlight potential issues in real-time and allow adjustments to be made during the manufacturing process, rather than having to wait until the batch harvest to determine successful product quality and yield.
Author: DR AMIT KATIYAR - director, Pharma Services Group within Thermo Fisher Scientific
While there are short-term challenges in implementing MAM, these are likely to be outweighed by the long-term benefits for contract organisation and their customers. As an LC-MS approach, MAM has the potential to replace several conventional methods for monitoring product quality attributes during the development of new biopharmaceuticals, including some LC methods, cation exchange chromatography, CE-SDS and ELISA. It has the potential to accelerate biopharmaceutical development and manufacturing and is set to become a critical tool for analytical testing.
Performing a single method approach is more efficient.
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BIOPHARMA & MANUFACTURING
T Author: CALVIN KIM - Senior Director and Head of IT Quality Systems & Validation at Samsung Biologics
hroughout every project, contract development and manufacturing organisations (CDMOs) will generate an abundance of data while relying on an array of computerised systems. These systems can assist CDMOs in their data management, security enhancement, human error reduction, and efficient xecution of processes. While advances in technology have enhanced and accelerated digitisation of processes, they have also highlighted the many complexities involved in safeguarding data integrity (DI) and maintaining regulatory compliance. Without fully understanding the intended use of the computerised systems utilised and the required mitigation of the associated risks, robust DI controls cannot be established.
If DI cannot be assured, the data cannot be reliable and could result in safety risks, recalls, delays, and denied drug approvals. The importance of DI and the potential risks involved in its absence have necessitated the introduction of guidance and regulations by regulatory bodies globally. WHAT DOES IT MEAN TO BE COMPLIANT WITH THE FDA AND EMA REGULATIONS? Following the initial introduction of DI regulations in the early 1960s by the FDA, there have been consistent updates corresponding to advancements in computerised systems and digitalised solutions over time. FDA’s 21 CFR (Code of Federal Regulations) Part 11 (published in 1997) and EMA’s EudraLex Vol.4 Annex 11 (2011)
Critical
THINKING
The fundamentals of data integrity and why a lack of critical strategic thinking could be affecting the success of implementing the technology properl . MAINTAINING DI WHILE GENERATING AN ABUNDANCE OF DATA Heavily automated equipment and computerised systems used in development and manufacturing processes have led to the generation and management of an abundance of data over a single project. Ensuring DI throughout the project–data lifecycle is essential, meaning data should be complete, consistent, and accurate when they are collected, maintained, backedup, transferred, and analysed throughout its retention time period. With DI, the data generated can be used to make informed decisions to minimise the risk to product quality and patient safety.
provide the key regulatory requirements surrounding electronic records and electronic signatures (ERES), including DI controls and computerised system validation (CSV). FDA, MHRA, and other regulatory guidelines also state that all data created in GxP operations should adhere to the ALCOA principles: ‘Attributable, Legible, Contemporaneous, Original, and Accurate’. Further DI assurance is achieved through following the additional ALCOA+ principles: ‘Complete, Consistent, Enduring, and Available’. Being compliant with the FDA and EMA DI regulations requires CDMOs to establish a
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strong understanding of ERES/ CSV regulatory requirements, especially the implementation of ALCOA+ principles in various digitised solutions. This starts with benchmarking the industry for the robust user requirements; in particular, those that lead to the implementation of the system features/functions that meet the latest industry standard on regulatory requirements such as security, audit trail, and DI controls. However, in the past few years, compliance with FDA regulations has been a particular challenge for many CDMOs. Despite the increased efforts by the regulator authorities to publish various DI related regulatory guidelines, DI related inspection findings persist Between 2014 and 2018, 79% of global drug warning letters issued by the FDA cited that there were DI
solutions to be able to offe the benefits outlined, CDMO need to approach DI with a clear understanding and a strategy that: • Defines and optimises th processes of the digitised solutions being introduced. • Establishes the fundamental requirements of the process. • Identifies the requirements limitations, gaps, challenges, and potentials of the solution to be used. CDMOs that skip this interrogation and instead adopt a “technology-first” approach t quickly fix a problem can easil become dependent on a vendor and form an overreliance on an ineffective digitised solution In many cases, this becomes a working relationship that can be difficult to escape fro Some CDMOs (as well as the solution providers) utilising a
In the past few years, compliance with FDA regulations has been a particular challenge for many CDMOs. violations. This highlights the need for CDMOs to fully comprehend that regulatory compliance is not just about awareness of the regulations, but to continuously implement robust DI controls to meet or exceed the current industry standards. A LACK OF STRATEGY AND CRITICAL THINKING Technologies that record, manage, and store data with robust DI controls can minimise human error and improve conformance with the ALCOA+ principles when implemented correctly. Consequently, digitised solutions are often equated to enhanced or improved processes. However, for these digitised
digitised solution may also not be aware of, or know how to be compliant with, the necessary regulatory requirements surrounding DI controls. This can lead to further complexities. When designing these solutions, it is important that regulatory requirements, such as audit trail, e-signature, security, and technical DI controls are adequately benchmarked for their latest industry standards and implemented with a streamlined CSV process. ASKING THE RIGHT QUESTIONS The best approach to building robust DI controls is to implement a top-down approach. Those in management roles need to establish
23 a robust governance programme incorporating appropriate organisational, procedural, and technical controls. Throughout, they need to remember what it means to be compliant with the regulatory requirements, as well as asking key questions: • What is the critical data that needs to be protected and maintained? • Not all data is of equal importance: DI controls on data that have a direct impact on patient safety and product quality are critical and should be a priority. • How can the validated computerised system enhance product quality or reduce risk to product quality? Establishing an efficient ri -based computerised system validation (CSV) and change management processes can improve product quality. This requires: • Defining the intended us , requirements, and specification of the computerised system. • Subjecting the computerised system to design enhancements based on a robust risk management process. • Improving the technical design and reducing potential human errors thereby mitigating risk to patients and product quality. • Carrying out validation activities based on the user requirements, with full traceability throughout. • Streamlining testing to verify the system design and risk mitigation measures. ENSURING DI: A KEY LESSON CDMOs that employ digitised solutions without fully understanding the gaps in their DI controls are at risk of making decisions based on unreliable data and could face repercussions during regulatory inspections and client audits as a result. More importantly, robust DI controls are needed throughout product manufacturing and the lifecycle of the associated data to ensure patient safety and product quality.
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CONTAINMENT & CLEANROOMS
Why targeted therapies are fuelling a growing demand for containment and cleanrooms.
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argeted therapies in the fields of oncolog , cardiovascular disease and diabetes are proving to be one of the most exciting areas of modern medicine. Doctors are now able to prescribe drugs that can treat very specific areas of the bod , such as cancer causing lymph nodes, to prevent fatal disease. This precision medicine has become a key focus for drug development in recent times – and research continues to look at how these new therapies can target molecules, such as proteins and genes, as well as our cells. Aided by modern chemistry techniques, advanced technologies and more stringent manufacturing processes, this growth in molecular targeted drugs has led to an increase in super-potent compounds being produced in drug discovery labs as well as CDMO and CMO facilities across the world. Due to the impact of using highly potent active pharmaceutical ingredients (HPAPIs) in these medicines, we are seeing an urgent demand for drug manufacturers to upgrade their production lines and processes. As these HPAPIs increase the risk of airborne exposure of cytotoxic substances in manufacturing environments, standard PPE is no longer considered adequate – and occupational exposure band (OEB) levels have been raised.
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Where detailed information on these novel compounds is limited, technicians are also forced to assume the highest occupational exposure level (OEL) – because they just don’t know how the compound will affect the wor er with repeat exposure.
QUALITY CONTROLS To protect pharmaceutical technicians and meet good manufacturing practice (GMP) compliance standards, companies are often required to install engineering controls that will ensure safety before work can begin.
This has sparked a growing need for new labs that are fitted with higher standard containment and cleanroom technology. This is most noticeable in Europe – especially since the pandemic began. With many existing labs tied up by managing huge
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numbers of PCR tests, newly built and converted facilities have been required to handle other contractual work. This demand in new European labs has also been driven by a desire to bring drug manufacturing closer to home. Concerns around quality controls in other regions and doubts around the reliability of the global supply chain, has increased the amount of nearshoring and in-house production and development. The deployment of containment technology in these new labs is helping manufacturers to take steps to improve drug production techniques. This is not just preventing issues such as cross
contamination or worker exposure to hazardous substances; it is allowing manufacturers to improve their drug yields and processing quality. For example, where oxygen has been shown to degrade a product during manufacturing, containment technology allows manufacturers to control the environment, replacing the oxygen with nitrogen to provide an anaerobic chamber. Where a grade A cleanroom is expensive to create, manufacturers are increasingly likely to deploy grade A isolators to create a sterile environment that can meet the required standards. HPAPI READY In a contract manufacturing scenario, where the drug being manufactured on the production line changes regularly, working with high potent compounds will mean upgrading facilities. Increased toxicity may require companies to move workbench manufacturing processes to contained environments. To be ‘HPAPI-ready’, manufacturers will often retrofit multiple parts of their existing manufacturing process – such as weighing, mixing and milling. This may sound like a complicated and disruptive process but, in reality, 98% of all existing process equipment can now be retrofitted with xible containment technology – and this work can be completed within a few days. For many contract manufacturers, this fl xible containment technology – which contains disposable elements – is also often seen as a preferable option to the traditional rigid isolator. The ability for disposal, rather than cleaning, means that manufacturers do not face the same cross contamination challenges when drug production changes.
In the pharmaceutical industry, where cleaning may mean going right down to the submicron level to remove product, cleaning costs can run into the thousands of euros a day. The accompanying validation process, which involves detailed swab testing and analysis, also adds to the period of downtime this creates. With a fl xible approach, however, manufacturers can simply throw away those disposable elements, such as single use glove bags, and store the frames and control systems until they are needed again.
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Author: MARK ARNOLD - MD of ONFAB, part of Envair Technology
GROWTH TO CONTINUE This is certainly an exciting time for our industry, with containment and cleanroom technology playing a crucial role in the development of new life-saving drugs. As the research into targeted therapies increases, the volume of drugs being produced to treat various cancers, cardiovascular conditions and diabetes is only going to grow. The likelihood is that these will need to be produced through that mix of new labs, with cleanrooms using rigid isolators, and existing manufacturing environments, where production lines are being converted, using fl xible containment technology. We need to prepare ourselves for this trend, and ensure the best solutions are available to meet that demand.
This growth in molecular targeted drugs has led to an increase in super-potent compounds being produced in drug discovery labs as well as CDMO and CMO facilities across the world.
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Pharma dominates university spinouts
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he life sciences sector has been responsible for 8 out of 10 of the most successful UK spinout companies from the last decade, according to a new report published by GovGrant. GovGrant’s University Spinouts Report 2021 analysed 958 spinouts that had launched between 1998 & 2018. It shows that pharma and biotech companies within the top 10 have a combined value of £3.63 billion, making those sectors the most attractive for investment. Indeed, 11 spinout pharmaceutical and biotech companies are featured in the report’s top 20 companies founded since 2000. In the last 20 years, the pharma and biotech sectors accounted for over half (£6.1 billion) of all capital raised by university spinouts in the UK Of those pharma and biotech spinouts, 119 drug discovery spinouts account for £3.6 billion of capital raised, whereas 114 biotechnology spinouts account for £2.2 billion of investment. Adam Simmonds, investment research analyst at GovGrant, says it’s no surprise that UK pharma and biotech companies are so successful. “This report highlights the huge value to the economy of UK universities, as well as their incredible depth of creativity and talent. The UK is particularly renowned for innovation in these areas. You only need to look at the recent development of Covid-19 vaccines in the UK to see how accomplished we are in pharmaceutical innovation,” he said.
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Talking points
OUTSIDE EPM
AMR DEATHS HIGHER THAN EXPECTED
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study published in The Lancet has shown antimicrobial resistance (AMR) to be a leading cause of death worldwide. The study is the largest to-date assessing the global impact that bacterial AMR has on patients and countries’ health systems. It found that in 2019, the deaths of 4.95 million people were associated with drug resistant bacterial infections. Of these, 1.27 million deaths were directly caused by AMR. This figure almost equals the combined deaths caused by HIV and malaria, and in terms of deaths caused by infections, AMR sits only behind Covid-19 and tuberculosis. These figures are much higher than previous estimates which put deaths caused by AMR at 700,000 a year. The study highlights how the clinical pipeline for antibiotics is too small to combat the problem and calls on political leaders to make AMR a higher priority going forward. More so, the study calls on research efforts
to be accelerated to address knowledge and innovation gaps, and to help inform policy and practices. The researchers identified that low-resource countries were impacted the most by AMR, with western sub-Saharan Africa found to have the highest death toll. The researchers from the study are now calling on access to effective antibiotics to be made a global priority. AMR should be seen as a worldwide problem, the study states, and should be tackled with a One Health approach. Steps needed to combat AMR include better surveillance, improved diagnostics, less oversubscribing of antibiotics, and a better antimicrobial and vaccine pipeline. Whilst these calls have been made in the past innovation in the area still remains slow. Vaccines are available for only one of the six leading pathogens described in the study.
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aisy Leung, associate at EIP and Rosie McDowell, associate at EIP, explore the legal implications that entrepreneurs need to consider when bringing a femtech product to market. Make sure to read the full article on www.med-technews.com
BE SURE TO LISTEN TO Biointeractions on The MedTalk Podcast discuss its infection prevention technology and how its efforts are being adopted by the UK government.
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