December 9, 2020 PAP-Q4-20-NI-006
Jeff Stein, Ph.D., CEO Cidara
A: The COVID-19 pandemic itself will have lasting impacts on the industry and the public, but one of the greatest lessons learned is the importance of prevention and protection when it comes to infectious diseases. Infectious diseases are a leading cause of death worldwide, and, as we have seen with the recent pandemic, they present an ongoing global unmet medical need. Safe and effective prevention methods must be explored that mitigate the spread of infectious diseases and protect the entire global population from contracting these types of illnesses. Preventative methods to control the spread of infectious diseases for the entire population, including the aging and immunocompromised, are also cost-effective public health tactics that help save many lives each year.
At Cidara, we have learned the importance of leveraging our capabilities and being nimble enough to adapt in times of crisis. Having a platform technology allows us to create a broad range of therapeutics for various viral diseases. We have decades of experience in the infectious disease space, so pivoting our efforts toward the coronavirus represented a natural extension of our capabilities. We have initiated programs to identify and develop a potential protective agent against SARS-CoV-2 (the virus causing COVID-19) and its complications. Our fundamental programs in development include a novel, long-lasting antifungal candidate called rezafungin and our Cloudbreak® antiviral platform, yielding a new class of drug candidates called antiviral conjugates (AVCs). Our philosophy has always centered on the development of long-acting drugs, a necessary concept for protection from serious infections.
Sean Kirk, EVP, Manufacturing & Technical Operations, Emergent BioSolutions
A: The greatest lesson is the fact that our national preparedness areas of focus, while important, historically represent risks that we have not yet realized. Preparedness for risks such as anthrax and smallpox are important because the threat remains high, but we never expected that the first significant pandemic since the flu pandemic was going to be an extreme version of the common cold.
The lesson learned is one of pandemic preparation and responsiveness, both domestically and internationally. Our preparedness must be much broader in scope, with more innovative ways of preparing, to ensure accelerated responses. One of the unique aspects of the COVID-19 pandemic is the urgency with which we have had to respond. No one envisioned that we would have to develop and manufacture a vaccine from the ground up in such a short period of time.
Over the next 5–10 years, I expect the focus on domestic preparedness to intensify. There will be novel ways to enable and incentivize the onshoring of our manufacturing capability as well as a heightened focus on risk mitigation across the global supply chain owing to our dependency on foreign suppliers. There will be fundamental changes to how we interact on a personal level. Hand shaking may go away, and the traditional way of working will be challenged, as our society has demonstrated in many different settings our ability to work remotely. Fundamentally our society will change in terms of interpersonal relationships and physical interaction, as well as workplace norms.
A: Flexibility. As a global organization, it is vital to be flexible to respond as necessary to whatever circumstances the ever-changing situation presents. Our business continuity plans, which were well established and well-rehearsed, were enacted at the very beginning of the outbreak. Given the nature of the pandemic and the pace at which it spread, we immediately established an emergency response team to effectively and efficiently assess, amend, and cascade actions right across the business.
Our ability to be agile, implement changes, pivot as necessary, and, most importantly, communicate often, enabled Almac to ensure the integrity of our supply and the safety of our employees throughout, meaning that our service levels were not impacted in any way.
It is also evident that flexibility in terms of conducting clinical trials will be required if clinical development is to continue during the pandemic. An annual global survey conducted by Almac Group, designed to keep abreast of key trends in the industry, revealed that a majority of organizations (64%) are starting to rely on technologies from outsourced service providers allowing them to conduct trials in a decentralized manner. Almac has launched a number of innovative solutions that offer clients the flexibility required without compromising on quality of service. Our Simplify™ platform was introduced during the pandemic and is an advanced IRT solution enabling faster clinical trials start-up and empowering trial sponsors and CROs to conduct patient randomization and site and drug supply management in half the time of traditional solutions. In addition, our new innovative direct-to-patient (DtP) solution offers our clients the option to ship clinical trial material direct to patients’ homes, offering more flexibility, and aiming to improve patient compliance.
Additionally, respondents expect to reduce their attendance at trade shows and workshops by approximately two-thirds for the remainder of 2020 and are most likely to rely on virtual 1:1 meetings, followed by educational webinars, in place of face-to-face events during the COVID-19 pandemic. Almac has responded to this shift by digitizing our conventional on-site audits and meetings to ensure continued quality and regulatory compliance for our operations.
The next 5–10 years will bring a sea-change in how “normal” working practices are carried out across the globe. Telecommuting, virtual meetings, increased emphasis on digital methods of conducting business, and reduced business travel could become the norm well beyond 2020.
Antony Fitzpatrick, Executive Vice President Operations, Vectura
A: The greatest lesson we have learned is that cumulative ability, expertise, and knowledge offer the best path forward in developing new drugs and therapies.
We have seen the industry come together, with collaborations being forged between companies from the outbreak of the crisis, and the pharma industry has been lauded from all sides for the efforts that it has taken to mobilize quickly to try to help contain and treat the coronavirus.
Going forward, I hope that this level of openness, decisiveness, and will to collaborate on projects continues. This pandemic has seen companies re-evaluate molecules from previous programs against the new COVID-19 disease threat, and this is a model that could continue into the future. Whether a molecule has been launched or shelved during development previously, the opportunity to repurpose and reposition drugs offers the prospect of a faster route to patients than a discovery project for a new molecule, which is both expensive and lengthy. Given the time invested in the countless projects by pharmaceutical and biotech companies over the decades, the work undertaken during this pandemic to find a solution is a key reminder for medical scientists and the industry that, before embarking on new expensive discovery projects, we should look at what is in our existing medicinal arsenal.
A: The biggest lesson learned from the COVID-19 pandemic is how interdependent and global the pharmaceutical supply chain is.
Interdependencies affect every aspect of the industry, from the discovery of a new active pharmaceutical ingredient (API) to the efficient manufacturing of an established and mature generic drug. The pharma industry is only as strong as its weakest part, and each participant in this space needs to understand and comply with the most stringent quality and regulatory requirements. Pharma needs to develop robust and resilient supply chains based on the principles of transparency, open dialogue, and collaboration across chain participants — something that will help the industry improve in the long term.
A: We knew a pandemic would happen; we just didn’t know when and what the virus would be. Although we were trying to be prepared, we obviously weren’t prepared enough. Hopefully, we will not forget the COVID-19 pandemic anytime soon, and we can increase our preparedness efforts.
The COVID-19 pandemic has taught us how much collaboration can impact results. Traditionally, a vaccine would take 10 years to create, but now, because so many groups within the industry are working together, we are looking at a timeline closer to 12–18 months. In the next 5–10 years, we anticipate that this increased level of collaboration will continue as we prepare for future pandemics.
In order to foster this high level of collaboration, effective communication among vaccine developers, manufacturers, and regulatory bodies should be a priority, and we must put protocols in place to help facilitate this. When these protocols aren’t working, they should be analyzed and improved upon immediately.
It’s also important that different groups that may not traditionally work together pair up so that differing areas of expertise can be leveraged. We’ve seen that the leading vaccine candidates come from diverse groups that pull together many complementary but different areas of expertise, such as small biotechs or universities that work together with established developers. These groups can then collaborate with contract manufacturing organizations that have the production capacities and with life sciences suppliers that bring with them robust supply chains and funding.
We have also learned how much strong industry associations, such as the Coalition for Epidemic Preparedness Innovations and other non-profit and expert groups that are focusing on pandemic preparedness, can help move the field forward. In the future, we believe it is important to strengthen and properly fund these groups so they can be prepared for the future.
Ben Zeskind, Ph.D. CEO, Immuneering
A: First, the importance of our industry: both the ability of biopharmaceutical companies to directly address the challenges of COVID-19 and the fact that our sector has remained so strong in such turbulent times. In an era when so many discretionary activities have been paused, the continued development of new medicines for people with cancer, neurodegeneration, and other serious diseases — by us and others — is as essential as ever.
During these uncertain times, a new priority has been placed upon logistical agility while also focusing on the importance of geographic diversification. We have achieved this through partnership with smaller, highly specialized CROs (across several geographic locations) without compromising our ongoing commitment to data reproducibility or robustness. This approach has enabled our drug development team to remain highly productive while staying interactive and remaining safe, despite spikes in viral transmission around the world.
Another significant impact is in how people work. As a company that uses computational technology for drug discovery, we have been fortunate that 100% of our full-time employees can do their jobs from home. We do miss in-person interaction and discussion, but since we have remained fully productive, we are able to avoid pushing our employees back to the office until the level of risk is exceedingly low.
Radek Špíšek, Ph.D. Global CEO, Sotio
A: With respect to cell therapy clinical development, we see an impact on our logistics operations. The mere fact that the number of flights has decreased by more than 70% complicates the logistics of blood-derived products with time limited viability.
We have also experienced slower recruitment into clinical trials caused by the COVID-19–related restrictions at the clinical sites. The situation caused by COVID-19 was not anticipated, and it caused a significant effort to adjust operations and keep the trials active. We will certainly plan for this kind of situation for the visible future, as there is very little visibility on the duration of the COVID-19 pandemic and related restrictive measures.
A: Over the past three decades, the pharmaceutical supply chain has grown more complex and international to meet policies focused on aggressively decreasing drug prices. Though this worked from a pricing perspective, it also impacted the global supply chain. Many drug manufacturers were pushed to outsource APIs and other manufacturing steps to China and India. Today, it is estimated that 80% of all drugs sold in the West contain some form of precursor, whether basic or advanced, from either country.
At the start of the pandemic, we saw the level of vulnerability this approach has created as trade restrictions and logistical complications arose. Now, Western societies are seeing the strategic and operational chaos this reliance could have if essential ingredients or drugs are again restricted in the future. As a result, myself and many other industry experts predict a trend towards a reverse of this approach with onshoring efforts for pharmaceutical manufacturing supported by national production incentives.
Politicians can no longer argue that complete globalization is a “necessary thing” because we now see that the core theory underlying the concept of globalization has been proven wrong. Wealth has not transformed dictatorships into democracies; rather, it has threatened democracies at their core, causing a rise in populist authoritarian regimes. And while pharma remains a global industry, business as usual will have to transform to ensure that access and quality drugs are maintained across the globe during a crisis. A new approach to sourcing and securing supply with a more realistic cost structure is needed.
A: To me, the greatest lesson learned from the COVID-19 pandemic is resilience: the CDMO industry has proven to be capable of outstanding resilience over the past months.
When governments decided to prioritize the supply chain for the health industry, there was a lot of uncertainty. Nobody knew for sure whether we could meet our engagement. But we have a very honorable mission as a CDMO: our mission is to produce APIs and, in the end, to contribute to help save people’s lives. That is the reason why, when half of humanity was on lockdown, our employees have continued to operate our plants, even though they knew there was a risk for them. And I would like to thank them again for their commitment and resilience.
We had to face several operational challenges during lockdown. First, we had to work under degraded conditions: there were many people in telework. But it didn’t prevent us from reaching our objectives, and it made us realize that we can work in a more efficient way in order to be even more competitive.
We also suffered from the fragility of the supply chain in Southeast Asia. Therefore, one of the lasting impacts I foresee over the next years is a rebalancing of our supply chain towards Western countries. And we now know that we can do this while remaining very competitive.
A: COVID-19 has drawn attention to a critical step in the drug development process that has typically been behind the scenes: safety testing. Because safety testing happens long before a drug ever touches a human patient, this is often unknown to the general public. Safety testing isn’t about finding the cure for a disease — it’s about ensuring that the treatments people receive are safe and effective. As more consumers track the accelerated development of COVID vaccines, there is an increasing awareness of and emphasis on the importance of safety testing. Though timelines may decrease, the focus on safety and quality remain the highest priority.
At the same time, from an organizational perspective, COVID-19 has shown companies that it’s imperative to focus on their people. For Charles River, the pandemic shifted our employees’ perception of us as “just an employer” to an integral part of their lives. We’ve seen many of our employees step up to face the challenges of COVID-19. We have listened to our people to provide the resources and support they needed to succeed both professionally and personally.
COVID-19 has taught us that we must be ready to shift demand based on priority — priorities that can dramatically and quickly change. We as a CRO — and as an industry — have to be agile and adjust our own priorities to be able to react to something like this in the future. Moving forward, companies will continue to make investments to ensure more flexibility in handling similar situations and supporting our employees during stressful times.
A: As the world leader in serving science, Thermo Fisher Scientific has been involved in virtually every aspect of the fight against COVID-19, including more than 200 projects in vaccines, antivirals, and treatments. Over this time, there are several important learnings for pharma services businesses to keep in mind:
1. Robust business continuity planning is crucial. You will need to adapt over time, meaning your business plan should be flexible and agile. Be proactive, not reactive — this plan needs to be tested and in place before a major event happens.
2. Reinforce the supply chain. It is more important than ever to work closely with supplier partners and monitor and reassess your supply chain. It is equally critical to validate alternative sources of supply and expedited transportation modes wherever possible to ensure critical inventories for both COVID-19 and vital non-COVID-19 medicines. The pandemic has underscored the need for redundant capacity to eliminate single points of failure. Businesses should continue to prioritize second sources within a single network or leverage multiple supply organizations.
3. Continue to invest. Despite the uncertainty created by the COVID-19 pandemic, continue to invest in your business. For pharma services, this means growth in capabilities, capacity, and supply to ensure that critical medicines are never delayed.
4. Innovate and leverage digital. The adoption of digital technologies is critical to ensure business continuity and connectivity with colleagues and customers in new, virtual ways. For example, VR/AR technology can provide virtual site visits and inspections for regulatory agencies and customers.
A: All of us benefit from the tremendous expertise, infrastructure, and investments that exist in the United States to deliver lifesaving medicines. We have come to appreciate this more as a result of this pandemic.
In addition, the COVID-19 response has highlighted leading indicators of a new era in the pharmaceutical industry, one in which we will develop therapies that leverage nature’s information-encoding schema (the genetic code) to turn genes and their resultant proteins on or off, as appropriate, to address most diseases at their root cause. The traditional method of testing libraries of chemicals against targets in the hopes of stumbling onto something that works is inefficient and slow, as we cannot predict target engagement or off-target effects reliably. We see this industry transformation evident in the vaccine trials for SARS-CoV-2. The platform technologies that embrace a genetic approach to design were among the first to generate viable candidates, some of which are now leading the race.
In my mind, the ultimate goal is to develop transformative, scalable platforms that could provide us with an entirely new arsenal of tools at our disposal for current areas of unmet need in monogenic disease, cancer, and common disease, as well as in infectious disease. Beyond the next 5–10 years, we believe that there will be increased reliance on scalable, high-Impact platforms that employ a digital approach to design and development. At NeuBase, we have such a platform that has the potential to create a limitless pipeline through this exact strategy.
A: The COVID-19 pandemic has clearly demonstrated the need for decentralized, low-cost, rapid point-of-care testing. Before the pandemic, the diagnostics industry was producing around 2 billion lateral flow tests per year for testing everything from HIV and malaria to pregnancy and allergies. Right now, for COVID-19 testing in the United States alone, we’re talking about testing 300–400 million people, 2–4 days per week. That equates to 600 million to 1.6 billion tests per week — over 10 times more than what the market was making to test for every disease combined. The scientific community is in agreement that COVID-19 is not the last pandemic we will experience in our lifetimes, and it is clear that the capacity we’re building to meet testing demand will be vital not only to continue battling COVID-19 even after a vaccine is developed, but also for future outbreaks and pandemics of viruses known and unknown.
BioDot, which makes automated, ultra-low-volume, non-contact dispensing platforms that are used to produce COVID-19 tests, began expanding its manufacturing capacity in the earliest days of the pandemic, anticipating that diagnostic companies would need to start sending in orders for the equipment that would be needed to ramp up test production as quickly as possible. To ensure that it could meet demand, BioDot strengthened its supply chain, began production at a new facility, and hired additional personnel, reducing prior lead times for most orders.
A: The COVID-19 pandemic has been a great proving ground for our ever-evolving technology. Before the COVID-19 pandemic, we were able to deliver pharmaceuticals with less than 0.1% temperature excursions, but the real test came when lockdown happened — and a recent audit of shipments made since global lockdowns found that we have retained that level of proficiency. This has shown us that furthering the integration of new technology into pharmaceutical logistics is vital if we are to efficiently deliver products around the world with near-zero spoilage rates.
The proliferation of biologic pharmaceuticals, which form the base of a number of COVID-19 vaccines, means the maintenance of stable conditions in transit will become even more vital if we are to deliver these lifesaving treatments around the world in viable condition, especially as these specific types of treatments are more vulnerable to changes in external conditions where limited temperature stability and their side effects are known, and therefore will require better hardware and software to keep them within usable parameters during transit.
Moving forward, COVID-19 will undoubtedly have lasting impacts on the industry. Over the next 5–10 years we will see greater importance placed on minimizing spoilage rates in transit. The industry still accepts that as much as 12% of pharmaceutical payloads will be not immediately released due to temperature excursions, which lead to hundreds of millions of additional inventory, express shipping costs, and quality assurance costs. The pandemic has shown that we need to be aiming to bring that rate down to as close to zero as possible.
A: The coronavirus crisis definitely taught the world many lessons, and within BASF I would like to highlight the learnings around collaboration, automation, and digitalization. During the crisis, we felt that it was more important than ever to stay close and communicate often with our employees, customers, and the entire value chain. We remained in close contact with our customers, suppliers, and logistics service providers in order to find practical solutions, regardless of the situation, and to maintain the supply of critical ingredients to our customers as fast as possible, even with increasing challenges and uncertainties within the global supply chain. Automation was already efficiently integrated into our manufacturing processes, which was strategic during the crisis, and because of this preparation the BASF Pharma Solutions production sites operated without major disruption and continued supplying pharmaceutical companies around the globe. Finally, the COVID-19 pandemic offered an opportunity to accelerate the use of digitalization: first and foremost, a quick pivot to virtual meetings and digital collaboration spaces, but then an increasing reliance of our customers on our Virtual Pharma Assistants, ZoomLab™, RegXcellence®, and MyProductWorld, providing technical, regulatory, and quality services to our customers instantly and online. Each of these initiatives will continue to impact our business in a positive way for years to come.
Dr. Stein has been President, CEO, and Director of Cidara since January 2014. Previously, he was the CEO of Trius Therapeutics, Inc., from 2007 until its acquisition by Cubist Pharmaceuticals, Inc., in September 2013. Dr. Stein currently serves as a Director of Paratek Pharmaceuticals (NASDAQ: PRTK) and Ideaya Biosciences (NASDAQ: IDYA). Dr. Stein conducted his postdoctoral research as an Alexander Hollaender Distinguished Postdoctoral Fellow at the California Institute of Technology and his graduate work as a NASA Graduate Student Researcher Fellow at the University of California, San Diego.
Many of the change agents I have seen in 2019 are derived from changes in regulatory law, commercial downscaling, and impact from patent expiry strategies. The largest external regulatory change came from the issuance of the long-awaited EMEA Annex I, clarifying which technologies are required and acceptable, when and why.
The change in operational focus, from clinical scale-up to commercial scale-down, is enabling use of smaller, modular, flexible fillers with self-contained isolators. In parallel with the approval of biosimilars and biobetters, there is strong industry focus on individualized micro-batches, for CAR-T solutions and gene therapy products. The use of process automation and robotics have increased in all fill-finish unit operations. Widespread implementation of ready-to-use/ready-to-sterilize components and single-use (SUT) in upstream and downstream (SUS) through final fill designs have changed how facilities are planned, reducing plant size and changing warehouse space to accommodate densely packaged plastics goods.
Filling modalities have also been changing; bags that can be mated to lock-luer fittings with pre-sterilized needles and blow-fill-seal/form-fill-seal are re-emerging as processes that offer potential unit cost reduction. Traditional vial and syringe container designs are also changing as suppliers improve standardize offerings while having options including clear plastics.
The most exciting technological or scientific advancement that has influenced our business strategy in 2019 is our novel epigenetic regulator program. Unlike gene therapies, which target and modify DNA directly by inserting specific genes into patient’s cells, epigenetic regulators control or modify gene expression through processes that do not alter the sequence of DNA directly. Our lead asset DUR-928 is a small endogenous molecule that plays an important role in regulating cellular functions such as lipid homeostasis, inflammation and cell survival, crucial pathways involved in many acute and chronic diseases. DUR-928 has shown positive results in a phase IIa trial for the treatment of alcoholic hepatitis, a devastating acute condition with high mortality rates and limited therapeutic options. We are also advancing programs in other indications that could benefit from DUR-928, such as non-alcoholic steatohepatitis (NASH) or psoriasis. We believe that epigenetic regulation is a powerful and untapped treatment approach for many challenging diseases.