Navigating the sea change of pharmaceutical outsourcing: part I

After what has oft-been described as an unprecedented period of turbulence in almost every aspect of our everyday lives, Dr Kevin Robinson sat down with experts from a number of pharmaceutical contract development and manufacturing organisations (CDMOs) to discuss how the events of the past year have affected the activity and outlook of the industry’s outsourcing sector

Opening the discussion, I ask the panel how, in their experience, pharmaceutical outsourcing needs changed during 2020.

John Ross, President, Mayne Pharma US and Metrics Contract Services, reminds me that “2020 and the COVID-19 pandemic had a major impact on the contract service industry, changing the way it’s both decided and delivered.”

He says: “One of the most important factors when considering a potential outsourcing partner is whether they have the proper equipment, facilities and infrastructure to handle a highly potent active pharmaceutical ingredient (HPAPI) based on its known potency and potential health and safety hazards."

"The customer’s need for this information hasn’t changed; but, as a CDMO, the way we meet those needs has changed. We now support customers virtually in a more comprehensive way with due diligence, audits, testing and investigations all taking place online. Almost universally, weekly project telephone calls have become video meetings.”

John Ross

COVID-19 has brought consequences for other areas too. “Supply chain security, business continuity and our understanding of different tiers of inputs have all come into sharper focus for customers as they aim to ensure a successful partnership,” adds John.

“It seems that, owing to COVID-19, 2020 was a year of shoring up the supply chain,” comments Lonnie Barish, VP of Business Development for Bora Pharmaceuticals: “The worldwide pandemic exposed vulnerabilities in supply chain reliability in many ways."

"Concerns were raised about the availability of raw materials, equipment, component availability, personnel and even transportation. Their first priority was to shore up existing drug supplies for existing manufacturers.”

He adds: “It seemed that drugs in development were pushed to the background as the world adjusted … so outsourcing remained with existing suppliers. Companies also looked to consolidate their partnerships. Slowly, as the world reacted to a new reality, outsourcing activities resumed with suppliers who felt companies could offer much needed technical expertise and supply chain reliability.”

“Biopharma’s demand for outsourcing partners to help them deliver critical medicines to patients within shorter timeframes continues to grow,” suggests Stefan Beyer, President and Managing Director, Vibalogics.

“Outsourcing process development and manufacturing is becoming an integral part of many successful drug strategies, including fast-track vaccine development to fight the COVID-19 pandemic. Our recent collaboration to provide clinical trial material for Janssen’s investigational COVID-19 vaccine candidate is a case in point.”

“Although the pandemic accelerated many COVID-19 vaccine trials, other early phase (non-COVID) clinical programmes experienced delays because of a lack of clinical capacity in hospitals. Although late-stage clinical supply may be less influenced, biopharma will remain challenged to find the resources they need to conduct trials."

"What vaccine and antiviral drug developers are discovering now is that the earlier they bring their programmes to their clinical supply manufacturing partners, the better chances there are for the successful development of their product. They’re also finding out that it’s one of the better ways to manage a project’s financial risks and accelerate market timelines.”

Demand and drivers

Based on that input, I enquire about the requirements behind these changes and wonder which services in particular are becoming more important.

“We continue to see a rising demand for high potency and agile manufacturing services to support the sustained development of orphan drugs for niche patient groups and personalised medicines,” says John.

“Domestic outsourcing is also prevalent at this time. This is largely driven by the need for supply chain security which, while always a factor in a successful partnership, is an ongoing concern and potential barrier to drug delivery.”

Lonnie Barish

“COVID-19 is making the public aware of the need for safe, effective vaccines. Vaccine manufacturing is likely to be driving development for the next several years,” advises Stefan.

“Beyond nucleic acid-based vaccines, the need for viral vector vaccines may become even more significant … with demand rising for assistance with both drug substance formulation and the specialised capacity required to manufacture these drug products.”

“It is becoming abundantly clear,” he adds, “that there is a sustained and growing need for biologics manufacturing services of all kinds. It takes tremendous technical capabilities and operational excellence to manufacture large-molecule biopharmaceuticals economically, which is why the industry is increasingly engaging competent external partners to develop and manufacture many of these highly sophisticated products."

"COVID-19 placed a spotlight on vaccine development in 2020. Although the pandemic may have pushed programmes working on prominent indications such Zika, Noro, Dengue and HIV temporarily to the background, rarely has the vaccine development industry been more active or diverse.”

Fortune Business Insights forecasts that the global influenza vaccines market will reach $7.34 billion by 2026 at an annual compound growth rate of 7.7%.1 Increasing cases and the spread of influenza worldwide will be the major driving force behind this growth.

“Regarding our own area of specialisation,” continues Stefan, “Kuick Research projects the global oncolytic virus (OV) immunotherapy market to reach $750 million by 2026 with 500% absolute growth for the period. According to Kuick’s recent study, with more than 50 therapies in trial, the US is dominating development.”

OVs preferentially infect, replicate in and kill cancer cells, leading to the presentation of both viral and tumour antigens and the induction of innate and adaptive immune responses.

In addition to selectively targeting and invading cancer cells, OVs can be tailored to deliver therapeutic payloads such as immunomodulating cytokines. Shown to trigger a lasting immune response, the actual mechanisms of action for any given OV depend on the type of virus, how the virus is engineered and the tumour itself.

"Viral vector vaccines use the same manufacturing platform as OVs and this may present the industry with a gap in capacity to meet OV development trends,” says Stefan.

“We’re addressing the possible shortfall in capacity with our new facility in Boxborough, Massachusetts. If the deficit in capacity is not addressed, it may delay important cancer-fighting therapies from reaching patients.”

“With more than 150 OVs headed for clinical trial globally, few CDMOs are capable of supporting biopharma companies advancing OV therapies toward late-stage clinical trials."

"Vibalogics has been at the forefront of many breakthroughs associated with advanced OV development and we plan to continue to invest robustly in this technology and its capabilities, namely with our late-phase and commercial facility in the US that is set to be operational in the second half of 2021.”

Lonnie Barish contributes: “The most obvious activity spike was for drugs to treat the primary COVID-19 infection, as well as those to address the secondary complications from the virus (antibiotics, respiratory drugs, etc.). With time, industry shifted back to progressing drugs that were in development, primarily oral solid dose forms, which remain the most prevalent and patient preferred dosage form for a multitude of reasons.”

“There is still a growing trend to promote the development of even more complex — but still functional — drug forms. Further, with the 505(b)(2) regulatory path and many existing drugs reaching the end of their patent life, we are seeing newer and potentially better ways to deliver these ‘older’ medications."

"This includes the combination of APIs for related disease states and deploying them in bilayer/trilayer tablets and more sophisticated combination products. With patient groups responding well to oral medications that allow easy administration, require fewer doses to be effective and reduce or eliminate unpleasant side-effects, oral solid dose (OSD) delivery remains the most popular route for administering drugs!”

The show goes on

Despite all the changes, however, some things remain constant. I propose that the selection criteria for selecting an appropriate outsourcing partner are just as rigorous as they were before the pandemic.

“There has been a great deal of research into how pharmaceutical companies select their CDMO partners,” says Lonnie Barish: “The consistent message seems to circle around several key themes."

"First, there are several givens that must be meet before a CDMO makes it into the selection round. These include a having the appropriate equipment, a strong regulatory history, scientific integrity and, of course, solid financial backing.”

Stefan Beyer

“After meeting these requirements, the key section criteria shift to organisation and people attributes. Trust is paramount. Are the people at this CDMO the kind that I can trust with my drug to meet our corporate goals (make a quality product, at a fair price, and deliver it on-time)? Good communication is also key. Will I enjoy working with these individuals or will it be a struggle? A sponsor needs to have absolute faith in their partner to deliver.”

“Next, adds Lonnie Barish, “is adaptability/flexibility: the ability to rapidly pivot and tailor a process to the client’s needs. Although drug development is a science, there is plenty of ‘art’ involved."

"Equipment needs to be tweaked, processes improved, costs contained, components changed, etc. Underpinned by experience, a good CDMO partner should understand your challenges before (from experience) and react and respond quickly.”

“Lastly, and this is the most difficult to assess upfront, is whether the CDMO will treat the relationship as a partnership or, with time, devolve into an adversarial role. Will they look for ways to help me cut costs or watch costs, help me meet surges in demand or dial back as demand might wane?”

Adding to the list, John advises that, “besides the required technical capabilities and appropriate costs, it is important that pharmaceutical companies choose a partner that is reliable, customer-oriented and delivers on time with the customer’s objectives front of mind."

"This creates a collaborative and trustworthy partnership that’s centred on continuous improvement, which is an important factor for long-term success.”

And, bringing the first part of the discussion to a close, Stefan mentions specialist expertise, including deep analytical product understanding and manufacturing capacity.

“CDMOs are focusing their operations to stand out and attract particular types of clients. Many, such as Vibalogics, are offering capabilities and facilities to support leading development trends. Many of our clients have come to us specifically because of our focus on OVs and viral vector vaccines.”

“As Lonnie Barish stated, flexibility and adaptability are particularly valuable attributes, especially in process development and early phase clinical supply. Experience helps CDMOs be more agile and more adept at dealing with issues that all developers confront during development and commercialisation."

"Being responsive to client needs and being able to meet timelines are both key when selecting an outsourcing partner. This is one of the reasons why Vibalogics is adding another 500 L single-use bioreactor manufacturing line in Cuxhaven to offer clients more options to get their products manufactured.”

“Finally, clinical and commercial understanding are vital. With outsourcing partnerships growing closer and more strategic, there is an emphasis on engaging partners that are capable of sustaining long-term relationships throughout the commercial life of the product."

"During the development stages, it is important to consider the future commercialisation of the drug product. The ability to support both clinical and commercial manufacture is often a priority when selecting a partner,” he concludes.”

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