July 1, 2020 PAP-Q2-20-RT-001
A: There has been a massive global response to the COVID-19 pandemic. Many pharmaceutical companies have been making significant efforts to develop tests, treatments, and vaccines for COVID-19. They are leveraging and sharing their profound scientific knowledge. In addition to searching for potential new vaccine candidates (12–18 months before becoming available) and investigating inventories of research portfolio structures, existing technologies and treatments are also being looked at. These include compounds formerly tested on other viral pathogens, such as Ebola and HIV. Around 20 companies, such as Gilead, Pfizer, AbbVie, GSK, and Novartis, have potential medicines in various stages of development, with at least four existing drugs now in late-stage clinical trials.
At the end of this crisis, we will need to ask ourselves what can be done to better leverage the collective wisdom within the pharmaceutical industry and academia to accelerate the development of life-saving vaccines safely and in quantities needed for global use. Equally important will be the need to address the issue of maintaining a resilient supply chain during such outbreaks to manufacture and transport pharma goods quickly and safely to patients in need. Western countries, knowing that their pharma supply chain for APIs was mostly in Asia, realized that risks could become a reality with such a rare and critical event as the COVID-19 pandemic. Setting up local API supply chains will be a very hot topic to anticipate and to transform into reality with the support of public and pharma authorities.
A: The pharmaceutical and biopharmaceutical industries have responded promptly to the COVID-19 pandemic challenge by evaluating possible utilization of available drugs, speeding the clinical testing for the new application for drugs originally developed for diseases with similar clinical signs and complications, and looking into more innovative approaches. This is true for many different therapeutics, such as antivirals and monoclonal antibodies originally developed for other pathologies and other treatments.
At the same time, vaccine developers have immediately responded to the challenge, speeding the development of the most innovative vaccines and redesigning vaccines already in clinical trials for other diseases. To date, the global COVID-19 vaccine research and development pipeline comprises 115 vaccine candidates, of which 78 are active projects and the others are in uncertain development stages. Few of the most advanced projects have already moved into clinical trials, and others will enter the first stages of clinical evaluation soon. It is critical to ensure that projects proceed through clinical trials, since not all of them will prove efficacy.
It is essential to keep the speed of development ongoing and ensure the highest quality standards. However, a strong focus needs to be put on identification and expansion of the manufacturing capacity necessary for the vaccine manufacturing, once one or more vaccines is demonstrated as effective. At that point, the next challenge will be manufacturing and global supply. We still have a long way to go; however, the biopharma industry and all supporting industries have so far demonstrated great engagement.
A: The industry is doing all it can to tackle the COVID-19 pandemic. We have learned that early intervention, a crisis strategy, and proactive information disclosure are key, along with a mass mobilization to secure critical supplies and prevent panic via a comprehensive approach spanning resources, services, and information. In addition to widespread testing, there is a need for proactive measures, such as staying at home and practicing social distancing, which can help to flatten the curve to control the trajectory of this epidemic. Going forward, planning for the future is critical. Experts must come together and share best practices on pandemic preparedness. There is a need to step up collaborative problem-solving efforts in which leaders in our industry share knowledge and build scenario plans so that we can anticipate outbreaks before they happen and, if possible, eliminate infectious disease altogether.
A: The entire bio/pharma industry understands that the long-term solution for the COVID-19 pandemic is in their hands, and thus it has reallocated resources and expertise to tackle this challenge quickly and efficiently. It’s truly remarkable to see how the industry has come together in the form of collaborations and partnerships to leverage each other’s knowledge to expedite the development and approval of a new vaccine or treatment against the virus. Regulatory agencies are also rising to the challenge — the FDA has launched a public/private initiative called Coronavirus Treatment Acceleration Program (CTAP) to speed up the development of treatments for confirmed COVID-19 patients. The entire supply chain plays a role, including excipient suppliers that might have technologies (i.e., adjuvants) that can make a vaccine more effective by intensifying the immune response to the vaccine’s antigen. Every company in the supply chain should cooperate efficiently to solve this unprecedented health crisis.
The pandemic has also exposed the fragility and interdependency of the global supply chain for pharmaceutical drugs. It became painfully evident almost from the beginning of the COVID-19 crisis that a pandemic like this one can significantly disrupt globally integrated pharmaceutical supply chains. As an example, approximately 20 drugs in the United States are solely sourced from China, and, equally important, several intermediates essential in the production of APIs depend on a limited number of suppliers clustered in one region of the world. Similarly, fragile situations are evident in the logistics of transporting raw materials, excipients, APIs, and finished forms across regions. The industry will have to pay close attention moving forward to solid, granular, and well established business continuity plans (BCPs) for their critical materials to ensure continuity of supply.
A: The COVID-19 pandemic has unveiled the complex landscape of the pharmaceutical industry, highlighting its strengths and weaknesses.
In a race to curb the pandemic, the pharmaceutical industry has taken a collaborative approach, pivoted strategic focus, and quickly mobilized resources — partnering with other pharma companies, research centers, and government agencies to develop diagnostics, small molecules, biologics, and vaccines to detect, treat, and prevent COVID-19. The progress is amazing and speaks to the power of numbers united by a common goal — especially when the stakes are high, as COVID-19–related deaths continue to soar. This is feasible because of the established clinical operations infrastructure and resources to quickly pivot and scale-up R&D driven by innovation and commitment to providing physicians, patients, and their families hope through promising treatment options. Given the global impact of the pandemic, philanthropic support beyond the United States has helped the pharmaceutical industry make strides at an unprecedented pace in its quest to contain COVID-19 and offer relief for those affected by it.
The fight against COVID-19 has also revealed industry flaws — the fragmented and inconsistent messaging that left the public confused about the proper course of action and best treatment strategies and an initial chaotic approach to the distribution of resources, which exposed the vulnerability of the supply chain. The shortage and limited rollout of personal protective gear and necessary equipment for treatment has had devastating repercussions. As an infectious disease specialist, I can understand the difficulties posed by a pandemic of this magnitude. Going forward, my hope is that we can take some of these key lessons and continue to coordinate developmental activities across companies with a coherent message for the public to change today’s vilified view of the pharma industry.
A: It has been impressive to see how fast the industry responded to the outbreak. Once the genome of the virus was discovered, many set out to shut down the viral replication with many different approaches. It has been encouraging to see the industry combine into consortiums and partnerships to move forward with the manufacturing of the vaccines and therapies under development. This contagion has highlighted the need for partnering and the need for approaches that address the symptoms and threat to health as well as a desired vaccine. If the symptoms can be controlled well with medications to the point that the death rate of the patients can be severely reduced, then a vaccine may not be required. This should push many therapeutics to the front of the line for fast tracking while the search for an effective and safe vaccine can be completed.
The interesting thing about all of the new information is that we are finding that drug products used for other indications may be helpful in treating the symptoms. The more that we can find about our arsenal of drug products, the better chances we have of being able to affect the pain, harm, and illness brought on by a new contagion. The recent testing of hydroxychloroquine that showed that it was not effective as an antiviral was seen as a disappointment; in my mind it was great information. The drug is still useful. The tests showed that it reduced the C-reactive protein associated with the inflammation that is a part of the cause of the secondary infections that are putting peoples’ lives at stake. That is great information. It helps to make the outbreak less dangerous. What else can we use that for? What other indications should that older drug product be researched for?
Moving forward, we all need to be aware of the criticality of having spare capacity for production of pandemic critical medicines. The government and our industry planned for pandemic influenza. This one caught all by surprise because it did not fit into that neat box. The facility of the future has to be robust, allow for fast implementation, and provide a way to scale out and scale up. There are approaches and strategies at each segment of research and development, engineering and construction, and manufacturing that can be applied to allow the industry to reach product launch and commercial production faster. Gone are the days when a facility/ equipment is designed for one product. A robust approach for manufacturing requires flexibility.
Partnering is being used to garner flexibility for the current scenario. Not every company houses all of the best R&D or every stage of manufacturing — so most rely on partnering to get the best of R&D, biological or chemical manufacturing, and final product filling and packaging. In each of these situations, you want to do a thorough risk assessment of your partners to ensure that, in the end, the quality and the schedule are protected.
A: The pharma, biotech, and medical device industry has taken a real ownership role in finding solutions for this COVID-19 pandemic. We have seen tremendous strides with vaccine development. Diagnostic companies are developing point-of-care tests in record time, and many of the pharma companies are assessing their existing approved therapies to see if mechanistically any of these medications could provide a therapeutic benefit.
It has been an all-hands-on-deck mentality, and when we see the overall number of products being studied, it shows how the industry has responded in record time to address this global pandemic. Additionally, it is great to see companies providing therapeutics not only at zero cost, or as part of clinical trial, but based on an altruistic approach of saving lives during a challenging period in our history. We must continue to emphasize not only some of the larger pharma companies who have products in development, but also those numerous start-up biotech and medical technology companies who are working on novel technologies to treat patients currently as well as preparing for a future pandemic. The U.S. FDA must continue to become engaged at an earlier level and have answers for companies in an accelerated period of time. Clinical development is a function of approval and action by the U.S. FDA, so the two must work in a symbiotic manner.
A: The industry response to the current global pandemic has demonstrated our ability to come together and pool knowledge/ resources in a time of need. Every company that has a relevant technology, from antivirals and vaccine platforms to DNA synthesis and antibodies, has put their best bet forward to try and defend the human population against this threat. It has been inspiring to witness.
However, as well-intentioned and committed as the industry response has been thus far, I believe it is time to begin asking both ourselves and our policy makers why such a response was necessary. For example, we currently have the technology to build a vast centralized network of known antivirals for rapid screening against emerging threats. Why is it not in place? We have the technology to build rapid-response systems for vaccinations. To that end, I can at least speak for ourselves: at Strand Therapeutics, we are working to build platform technologies to streamline and preempt the threat of emerging pandemics.
As an industry, we need to work together to motivate our policy makers to build in incentivization structures for rapid global response networks to emerging threats. Having a vaccine ready to begin phase I testing by March 2020 was quite a feat, though the infrastructure to sequence, design, and deploy these measures needs to shrink timelines drastically to prevent spreads like we are currently witnessing. Preliminary de-risking and platform testing must be deployed in advance of threats, rather than while in the throes of an international shutdown.
It is on us to design and motivate systems to mitigate future outbreaks. It is on the most influential in our industry to motivate massive coalitions against these threats, and not simply position individual companies to profit the most from contributions. This will be not only a huge step towards securing public health, but a massive leap towards restoring the public confidence in the biotech industry as an industry of goodwill that is working toward patient benefit.
A: I think that the pharmaceutical industry has responded well since COVID-19 became a pandemic. We have a vaccine going into trial and several potential drugs (both old and new) being proposed for clinical trials. I think governments, including our own, did not do so well. The U.S. response was delayed by several weeks, and we are now paying the price and playing catch-up.
A: The pharmaceutical industry responded to the COVID-19 pandemic in a responsible manner and is fully supportive of efforts of various governmental agencies in responding quickly to the challenges this pandemic represents. Several pharmaceutical companies have announced financial support to COVID-19 relief efforts, donated personal protective equipment, and donated drugs like hydroxychloroquine sulfate and chloroquine phosphate to a strategic national stockpile as possible treatments for COVID-19 patients. The pharmaceutical industry is carefully monitoring its supply chain to prevent and mitigate any potential shortages of important life-saving medicines. Thanks to the industry efforts, there is no shortage of essential drugs today. This shows the resilience of the pharmaceutical industry to quickly react and adjust its operational mode and maintain the supply chain of medicines to the public. The Pharma and Biopharma Outsourcing Association (PBOA), a trade group that represents CMOs and other service providers in the bio/pharmaceutical sector, reported that its member companies remain committed to serving patients by manufacturing effective, quality products for their customers during this global health crisis, and reports no material disruptions to their operations. Based on the FDA’s Coronavirus Treatment Acceleration Program (CTAP) update on March 31, 2020, there are 10 therapeutic agents in active trials and another 15 therapeutic agents in planning stages. This can be summarized as a remarkable effort by the pharmaceutical industry together with the FDA’s regulatory guidance to identify the effective drugs/treatments in the shortest possible time. Similarly, the developmental efforts for potential vaccine for COVID-19 are progressing at a brisk pace in various companies and laboratories.
A: The pharma industry has responded extremely well to the COVID-19 pandemic. Considering the unprecedented scope of the pandemic, all aspects of pharmaceutical supply chain contingency planning have come into play, and to date only a single drug was reported in shortage due to COVID-19 in the United States. Safety stocks across the pharmaceutical manufacturing network and warehouses have kicked in, and supply to pharmacies has been uninterrupted. This will not be indefinite and, should the lockdown extend many more months, one can expect a cascade of shortages. Nonetheless, the system has proven resilient and able to cope with a crisis.
The pandemic has laid bare the limits of the current pharmaceutical manufacturing model and its heavy reliance on China for starting materials and to a lesser extent for APIs and drug products. This reliance has become both a strategic and an operational challenge: strategic, as both the United States and the EU now consider China a strategic competitor, at the same geopolitical level as Russia; and operational, as solidarity between countries has more or less broken down and export restrictions from China and India have raised the stakes for the rest of the world.
I would advocate focusing on removing any incentives — and perhaps even creating economic barriers — to importing essential drugs. This could include import duties or establishing incentives that support local manufacturing. Regulations could also be established via the military industrial complex to mandate use of locally made products. A combination of approaches can be very targeted and simple to implement with focus. By creating a stable economic environment, countries will have what they need to establish sustainable manufacturing for essential APIs and drug products in the United States, Europe, Japan, and other countries who wish to establish independent supply chains.
We should create transparency via drug product labels and a publicly accessible database displaying the country of origin for both the API and the drug. This way, patients can be given relevant information for them to be selective about where their drugs are manufactured.
A: The pharma industry has rallied in the face of this pandemic. It’s been encouraging to see the innovative thinking, fast reaction, and collaboration among companies on potential therapeutics to address SARS-CoV-2, the novel coronavirus that causes COVID-19. We’ve focused, as usual, on helping patients first and letting the economics follow that. It’s been unfortunate to see the impact on ongoing programs for other diseases, with R&D largely shut down in the laboratory and clinic. Going forward, we should find safe ways to work as closely to full speed as possible on all projects, even in the face of contagion. We greatly contribute to the broader societal health outcome of an additional two years of life expectancy gained every decade. When multiplied across the billions in population that we serve, every day of shutdown in our industry translates to hundreds of thousands of quality years of life sacrificed when the availability of new therapies to patients is delayed.
A: The pharma industry has come with full force in collaboration with scientific experts, academia, and governments to help diagnose, treat, and prevent infection from the virus. The decades-long investments made by the pharma industry in new technology, research, and treatments have prepared the industry to act in these unprecedented times.
We’ve learned that unprecedented collaboration between government, health authorities, hospitals, and the private sector is crucial to a rapid response to any new virus outbreak. Rapid global response to early warning signs on new viruses and social distancing measures by governments have tremendous influence on the overall impact and duration of a new virus outbreak. Moving forward, the pharma industry will have to review its supply chain and implement contingency plans to better respond to medicine shortages. Additionally, the industry will strengthen its virtual engagement with patients and health providers around the globe.
A: From my Irish perspective, the pharma industry has responded in a very humanitarian manner to the challenges we are all now facing due to the COVID-19 pandemic. It has responded with urgency, quite alien in what is considered a conservative and cautious industry. In fact, all pre-existing business barriers have been blown away in a united effort to fight this global pandemic. The industry is working tirelessly as a fully committed and united team to develop a vaccine, evaluate existing therapeutics, and share resources and information with its historical industry competitors and peers. Alliances have been formed; former rivals are now allies, with everyone working together for the greater good. An example of this is the Covid Alliance that was set up in the Republic of Ireland at the outset of the pandemic on Irish shores. The Covid Alliance comprises all the major pharma manufacturing and engineering firms in the Republic of Ireland, with the sole aim of supporting the Irish Health Service Executive (HSE) in their management of the COVID-19 pandemic in Ireland.
A: We currently find ourselves in a global public health pandemic that none of us have experienced before. From a corporate perspective, Cambrex has adapted and has rallied to protect our employees, customers, suppliers, and communities. From a wider perspective, we are proud to be part of an industry that is demonstrating how fast it can move in times of extreme need through the number of programs that have been initiated in a short space of time to attempt to find treatments that could save the lives of critically ill patients who have contracted the COVID-19 virus today and to develop a vaccine for the virus tomorrow.
There will be much time in the future to reflect on the lessons learned from this pandemic, but it will be right to look at supply chains, which have become more global over the last decade and more. We have always been very selective when choosing our worldwide partners and suppliers, and to date, this strategy has proven to be extremely valuable and effective in managing our supply chains in such difficult times. The closure of borders and delays by governmental activities were unforeseen.
Going forward, supply chains have to remain global as our industry provides products and services that are needed by patients across the world. Post–COVID-19, there will likely be international agreements as to how to manage the production and distribution of critical products should we face a similar situation in the future, in an effort to minimize disruption to the industry’s supply chain and ultimately ensure that patients have access to them.
Communication and the methods used to communicate are likely to change forever based on this situation. Without the ability to meet face-to-face with our customers to discuss projects, we — like everybody else — have been forced to use more telephone or video calls. In reality, this has been easy for us to do, and business has continued largely unaffected. However, we recognize that this is a result of the close relationships that we have built with our customers over past years, which were founded on close interaction, joint meetings, and a track record of successful collaboration. We hope that this will continue to be possible in the post–COVID-19 times.
A: From a corporate point of view, I think it is obvious that the biggest lesson is that you cannot be overprepared for a situation such as this. As a CDMO working in inhalation pharmaceutical and device development, the products and therapies that we help design and develop with our partners play key roles in supporting patients with respiratory diseases, so the consequences of this virus and the needs of a response are very well known to us.
When the COVID-19 crisis started to unfold, we immediately executed our crisis management procedures, which include a variety of potential crises such as this one. Many of our team members also have experience from previous virus outbreaks, such as SARS and MERS.
The plan rapidly established key priorities for the business, which we reinforced frequently and clearly to our employees. We have learned that daily communications are essential to maintain the physical and mental well-being of employees who have demonstrated unbelievable levels of resilience and creativity to keep patients supplied, and that the risk management process and strong relationships with suppliers that we have allow us to maintain our position and manage daily issues.
A: The COVID-19 pandemic is a truly universal event. It has affected raw materials, workforces, compound development strategy, and logistics, with no country or site left untouched by the crisis. As a result, the industry’s ability to provide materials and drugs to hospitals and clinics has been challenged, and the pharmaceutical industry (and the entire world) has had to react in real time, often testing the effectiveness of solutions while implementing them. We will need to wait until the pandemic is resolved to take a full appraisal of how we responded and what else we might do in a similar future scenario.
That said, the pandemic has already brought to light some lessons for our industry. The first has to do with supply chains. As most companies have a globally distributed supply chain, the coronavirus outbreak has at times led to strained, disconnected, and disrupted supply. Supply chain weaknesses have been exposed, especially around the supply of personal protective equipment (PPE). We have also seen some countries restrict exports of medical equipment and ingredients.
The lesson for pharma and biotech leaders is to double down on building agile but resilient supply chains. Ideally, supply will not be dependent on any one region so it can withstand temporary shocks without being interrupted. We may see more companies move toward localization of resources, supply, and manufacturing as a result of the current crisis. Experienced CDMOs can use their databases of cross-sourcing options to help customers diversify supply sources both reactively and proactively.
Another lesson is the importance of collaboration, both among pharma companies themselves and with regulatory bodies to get permission to produce additional materials and products. The ability to adapt one’s manufacturing equipment, technology, and workforce is particularly important during a crisis. Indeed, we face a decreased demand for clinical trial materials for some types of diseases, but we also see a significant increase in demand for compounds starting new clinical trials to treat COVID-19. The flexibility that we are witnessing is impressive; the secure connection with customers is driving new developments based on existing technology. The takeaway for CDMOs is to maintain and reinforce this agility to serve our customers. Learning from the current COVID-19 outbreak, our goal for a future crisis will be to reinforce dynamic risk management to minimize the impact on the business, our customers, and ultimately on patients.
A: If there is one thing industry is learning from this crisis, it is that we need a more diversified system of manufacturing supplies and completing research. In order to reduce the vulnerabilities that have been exposed in the system, supply chains should consist of suppliers within multiple geographic areas, with less complicated transportation and distribution routes. Additionally, by beginning to outsource research programs, the industry reduces their necessity for constant on-site support, and places that requirement on the CRO industry, which is equipped and capable to carry out those activities anyway, with expertise across drug development.
What does that mean for day-to-day business? When looking for suppliers, organizations need to understand the full production and transportation chain. By carefully choosing suppliers, they can ensure that all supplies come from different geographic regions that could serve as each other’s backup. Companies need to look into the production chain of suppliers to find out if it includes multiple transportation steps to get to the final product. Production from raw materials to the end product at a single location is the optimum — a single source at lowest price might no longer be the best strategy.
In a pandemic situation like COVID-19, human travel is the biggest risk. Going forward, the industry needs to strategically think about how they can reduce the amount of travel for their people. Working with suppliers who are (relatively) local is a key part of that. Additionally, using existing technologies to connect with people and implementing new, virtual forums for collaboration will help to reduce the need for travel while allowing sponsors to maintain control and consistent interaction.
Running a modern research lab with many suppliers, constantly changing technology, and high demand for highly qualified staff is complicated. Creating that complete infrastructure and having it be able to continue functioning under extreme circumstances, like a pandemic, makes it even more difficult. Moving forward, increased reliance on outsourcing will allow the biopharma industry to better continue research under the extreme circumstances we’ve experienced with COVID-19.
Thierry Durand, Ph.D., joined the Minafin Group as managing director of Minakem in 2019. Prior to that, Durand worked at Naturex as VP Pharma BU. Between 2005 and 2016, he worked at Novasep where he held several R&D and strategic project management roles. Before that, Durand worked for Merial, Rhône-Poulenc and Synthelabo. He holds a PhD in Organic Chemistry – New Antibiotics, LPGD from Université Catholique de Louvain.
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.