Special Report: Operation Warp Speed: A View From the Inside

Starting in May 2020, teams from the US Department of Health and Human Services (HHS) and the US Department of Defense (DoD) acted as enablers, using the resources of the US government to accelerate development as well as creation and mobilization of the capacity to manufacture at scale. Between November and December 2020, two vaccines and two antibody treatments received Emergency Use Authorization (EUA) from the US Food and Drug Administration (FDA). Within hours after notification from the FDA, the distribution and administration of the vaccines began. By the end of Q1 2021, a third vaccine had received EUA, and over 200 million doses had already been delivered for administration, a timeline never before achieved in history.

Nothing unites humans like a common enemy, the saying goes. When the pandemic surged into global awareness at the beginning of 2020, it was not unexpected, yet the world was utterly unprepared for it.

Other viral threats had emerged in the past, and somehow faded away. Governments and non-governmental organizations had reacted, made vows to never again be caught unprepared, and then failed to follow up with resources and plans to ensure it would not happen again.

Countries around the world reacted differently to the appearance of COVID-19. From outright denial and minimization to full deployment of the containment measures used over past centuries, lockdowns were rolled out in many places with dramatic consequences for the economy and the welfare of large swaths of the global population.

Much is being written on the implications of these measures, and some of the other financial measures implemented at the time. We had to resort to these instruments because we were reacting late; we had no proactive plan in place. But as we reacted, two things happened that made a significant difference in the course of this pandemic as compared to those that preceded it: the scientific community came together to fight this threat through science and innovation, and governments around the world mobilized to support it.

Pandemic Beginning

At the end of 2019, I had just retired from my position as Executive Vice President of Operations for a large global pharmaceutical manufacturer, with plans for easing into advisory or board roles and enjoying more time sailing and biking. However, the evolution of the pandemic made my retirement plans less viable.

My first contact with the US government project to fight the pandemic occurred one morning in April 2020, while I was biking empty roads in New Jersey, which was a rare situation I had not experienced since the great financial crisis of 2008.

I received two calls, the first from Bob Kadlec, Assistant Director at HHS for Preparedness and Response, and the second from Alex Azar, Secretary of HHS. They described how the US government had determined that the best way to fight the pandemic was to mobilize the public resources of the government and the scientific innovation and the entrepreneurial spirit of the industry in order to pull out all stops and accelerate the development of safe and effective vaccines and any other treatment we could develop.

They compared this effort to the Manhattan Project, which aimed to end World War II, and they asked about my availability to participate, advise, and coordinate all aspects of the project related to the manufacturing. This proposal was a dream come true: not only had I been given the opportunity to do something for the industry and my country, which have both given me so much, but I also had a real shot at escaping the boredom of lockdown and retirement. Being in the fortunate position of having control of my time, I gave my full commitment and that’s how my experience with Operation Warp Speed started.

Operation Warp Speed

Over the following few weeks, the structure of this project was better defined and an overall leader was appointed. Moncef Slaoui, a former GSK R&D executive with significant vaccine development experience and a successful industry track record, was named Chief Scientific Advisor and overall program lead. The lead of all US government resources was General Gustave Perna, a four-star general who had been leading US Army Logistics, an enormous organization, and who had deep supply chain knowledge.

Slaoui and Perna built an incredible partnership throughout the time they worked together leading the operation, and shaped the culture and the team spirit that ultimately made everything possible. This was a culture of fact-based and data-driven decisions, empowerment with accountability, and personal commitment, starting from the leadership. Perna used to say that “as long as something is not illegal, immoral or unethical, we will find a way to make it happen.” And he certainly did.

I credit this culture of teamwork, transparency, and accountability, together with a governance process aligned with best practices, as a key driver of the operation’s success. Debates and disagreements were allowed, but at the end each decision was made based on data and owned by the team. Key decisions were escalated to a board chaired by the Secretary of HHS and the Secretary of Defense with participation from the White House, the National Institutes for Health (NIH), the FDA, the Centers for Disease Control and Prevention (CDC), the Assistant Secretary for Preparedness and Response (ASPR), and Operation Warp Speed leadership. This board met weekly to be updated on progress, endorse recommendations for critical decisions, and provide support with resources as needed.

A lot of work was happening behind the scenes, of course, to gain the political endorsement and the funding for the operation, and a special credit goes to Azar and his Deputy Chief of Staff Paul Mango for successfully bringing it forward and shielding the operation from external noise.

The name Operation Warp Speed (OWS) was selected, and on a sunny morning on 15 May 2020, we were in the Rose Garden at the White House for the official announcement. The mission of the operation was clear: deliver at least one safe and effective vaccine, manufactured at scale, and distributed to 64 jurisdictions before year-end 2020.

Not many people believed at that time that this could be possible, and to be perfectly honest, we did not have a clear path defined at that point. But we had fully committed to making it happen.

We were assigned some offices on the seventh floor of the HHS building in Washington, DC, and started to immediately work on the strategy, structure, and key “business processes” in industry terms or “battle rhythm” in army jargon. Most of the HHS building was empty because people were working remotely, but the OWS team was there in person every day, traveling to clinical and manufacturing sites as needed.

The mission was translated into a plan over the following few weeks, and the critical milestones identified, while the work to compress the timeline started. We needed an EUA for a vaccine in less than 12 months from the identification of the viral genetic sequence. This level of compressed timing had never been attempted in the history of vaccine development and it was obvious that we could not handle this in the usual way.

The Development

The global effort to develop a vaccine for COVID-19 started on 10 January 2020, when a Chinese virology team posted the genetic sequence of the virus on a global public health site. Several pharmaceutical companies immediately started designing a vaccine, using many of the available platform technologies, either proven or innovative. A few days later, two companies who had been developing a pioneering new technology, mRNA, had designed their first vaccine candidate: Moderna in the US and BioNTech in Germany.

This first step had to be followed by an enormous amount of work to confirm the safety and effectiveness of each vaccine, culminating in a successful phase 3 human clinical trial on over 30,000 patients. At the same time, companies had less than 11 months to build a supply chain able to deliver between 50 and 100 million doses per month of each successful vaccine, while all the infrastructure to administer that level of inoculations was simultaneously being prepared.

It was evident that no company could have possibly accomplished all of that, regardless of how brilliant their scientists or manufacturing executives. We were in the middle of a pandemic, and supply chains everywhere were heavily disrupted. Pharmaceutical companies were already challenged in trying to maintain existing supply of necessary life-saving drugs amidst shortages in materials and the impact of fear and lockdowns on their employees and operations. Hospitals were beginning to see the impact of the surge in COVID-19-related hospitalizations: how would clinical trials be managed in that environment?

What made the accelerated delivery time possible for the vaccines was the decision by OWS to focus on being an enabler of industry innovation and execution without trying to control all aspects of the execution itself.

In effect, the US government was underwriting the development and manufacturing risk for a number of vaccines and antibody treatments. Companies could start executing activities in parallel, because they no longer had to minimize those risks.

By agreeing in advance to purchase a very large number of doses of vaccine, before having evidence of safety and effectiveness, the US government removed the biggest financial risk for the industry, effectively pulling out all the stops that would typically slow down development and manufacturing. The same approach was taken with monoclonal antibody therapies.

This was extremely impactful, especially when combined with targeted support actions to remove key constraints and accelerate clinical development and supply chain setup and manufacturing.

The first key decision to make was how many vaccines to support, and which ones. There was no shortage of opinions, of course, mostly coalescing around two viewpoints: the first for maximizing the number of programs supported, in order to maximize the probability of success. The second was to focus on a limited number of platform technologies—and a limited number of programs by technology—in order to not lose focus and disperse the energy and attention of the operation. Ultimately, the second viewpoint prevailed, together with the recommendation to select three platform technologies (mRNA, viral vector, and protein sub-unit) and two programs per platform (Pfizer-BioNTech and Moderna, J&J and AstraZeneca, Sanofi and No-vavax).

On the therapeutics side, the Regeneron and Eli Lilly antibody cocktails were initially selected, but screening for additional candidates to support (also in different therapeutic segments, such as small molecule antiviral) continued throughout the program. This ultimately led to identifying and supporting another antibody from AstraZeneca, as well as the Merck-Ridgeback and Pfizer antivirals.

The level of support required by these companies was different, of course, due to their varying size and resource availability. But the hurdles they were facing were comparable.

We set up a multifunctional team to work in close contact with each company as a single point of contact and channel for all communications. This allowed for timely and transparent communication, and included all key functional experts (clinical, development, regulatory, quality, and manufacturing).

The acceleration of the clinical program required the activation of a very large number of clinical centers, strategically selected to provide the necessary mix of patient age groups, ethnicity, and risk profiles to ensure that the safety and effectiveness profile could be appropriately assessed. Leveraging the NIH network was instrumental for that purpose. Ongoing monitoring of the enrollment allowed for course corrections when in some cases numerical enrollment for patient subgroups were behind schedule.

Manufacturing

From a manufacturing perspective, the hurdles were enormous. The board had requested that all vaccines be manufactured in the US, including both the antigen and the fill-finish process, and that to the greatest extent possible, we use components and raw materials also manufactured in the US. While this was certainly a reasonable strategy to minimize risk in a pandemic setting, it had to face the reality that there was no readily available capacity at that scale for producing vaccines and antibodies in the US. After all, we did not know which vaccine or antibody would prove successful in the clinical trials, and so we wanted to set up enough capacity for each one to independently supply the entire US population. If more than one program was going to be successful, the world could have certainly used the excess doses.

We surveyed the industry contract development and manufacturing companies CDMOs and manufacturers to identify all available capacity that could be immediately available to us, or modified and retrofitted within the time frame we had available. It was amazing to see how many companies, large and small, responded to our requests and came forward with creative proposals on how they could support the operation. It was an outstanding demonstration of mobilization against a common enemy and commercial rivalries were set aside.

The operation worked with the US Department of Justice (DOJ) to enable the exchange of capacity information between manufacturers, with the purpose of assessing potential manufacturing collaborations for COVID-19 treatments. The DOJ issued an opinion on 23 July 2020, stating that such exchanges of information for the purpose of increasing supply of COVID-19 therapies would not harm but help consumers, opening the door for collaborations between Genentech and Regeneron, Amgen and Eli Lilly, and Merck and J&J.

However, there wasn’t enough existing capacity for viral vector and protein subunit vaccine production in the US. We had to build it, and time wasn’t on our side.

The Biomedical Advanced Research and Development Authority (BARDA) within the Office of the Assistant Secretary for Preparedness and Response in HHS had developed partnerships with two companies, and started construction of general-purpose capacity to manufacture biodefense countermeasures over the past several years. That capacity had never been finalized or started up, and had never received regulatory approval. The facilities existed, but we lacked most of the equipment and there was no organization to operate them.

We focused on the effort to retrofit, accelerate construction, and qualify those facilities while hiring and training the necessary personnel. These two facilities were assigned to viral vector and protein sub-unit programs, and additional facilities were onboarded to supplement capacity. In all, five plants in the US supported those four programs, with two of the five plants shared by two programs each. It was not an ideal situation, but it could work.

Initial assessments of these facilities pointed to the lack of experience in their staff as the major risk to execution, and not surprisingly, that was in deed the biggest challenge the program initially encountered from a manufacturing standpoint. To successfully manufacture any product, you need the process, the equipment, the materials, and a trained organization. The one thing we struggled with the most to accelerate was the selection, hiring, and training across the board in all of the facilities involved.

Both Moderna and Pfizer had already started building their own capacity for vaccine production, and luckily, the manufacturing capacity for these vaccines can be built faster than classical bioreactor capacity, so construction and qualification could be completed within the timeframe we had available.

The general supply chain disruptions we all experienced during the pandemic did not spare the pharmaceutical supply chains. The industry was facing shortages of everything, which made keeping the regular drug supply very challenging. On top of that, we required equipment, capacity, and components to manufacture several billion doses of vaccines.

The US government had put agreements in place to support expansion of capacity in critical components early as part of the general pandemic response plan, and we took full advantage of that. Many times we deployed a provision in the Defense Production Act (DPA), which allows the government to request priority fulfillment of its orders to the government and its contractors. This provision was administered by the DoD personnel in OWS. Material procured under the DPA can only be used to fulfill government orders and must be used in the US.

This was a very powerful tool, and we were extremely careful in its use, monitoring not only the delivery to OWS contractors but also the impact that this prioritization was having within the broad pharmaceutical supply chain. We worked in close contact with the FDA Drug Shortage Staff within the Center for Drugs and Evaluation and Research (CDER) to find alternative sources for every situation that could have led to potential shortages, and I can honestly say we prevented many crises this way.

Fill-finish capacity was already in short supply and at a premium in the US before the pandemic, and we leveraged multiple companies to enlist enough capacity to support the OWS programs. Several companies had expansion plans in place, mostly started before the pandemic, and we helped them accelerate readiness of the new capacity.

That involved mobilizing the US Army Corps of Engineers to support construction, using the DPA to accelerate deliveries of equipment and construction efforts, dispatching US Army cargo planes for deliveries, and providing logistic support for shipments of equipment and components, at a time when cargo capacity was limited around the world. When we needed the support of foreign technicians for the qualification and startup of filling lines or other critical equipment, we worked with the Department of State to ensure the timely issuance of visas.

During Labor Day weekend 2020, a convoy of trucks carrying oversize HVAC units to one of the factories was stopped, and we were risking start-up delays of three days. We prevented that by organizing special permits with the Departments of Transportation of the four states being crossed by the convoy, along with state patrol escorts.

We monitored all the activities, providing support as needed when risks to the execution schedule were identified, coordinating with the DoD and other government agencies.

Early in the program, we made a decision to install a “person in the plant” in each critical node of our supply chain where the antigen was manufactured and the fill-finish was happening. This proved to be very valuable, not only for providing real-time insights on progress and issues, but also to improve trust and communication.

The scientific community came together to fight this threat through science and innovation, and governments around the world mobilized to support it.

These individuals were majors from the DoD and expert supply chain professionals. We briefly trained them on the uniqueness of vaccine manufacturing, and they were dispatched at a moment’s notice for a nine-month assignment. These individuals all deserve a lot of credit for their selfless service and for having helped reduce the impact of the many issues that normally occur during a startup.

Ultimately, 14 plants (many with more than one filling line) supported the fill-finish activities for the six vaccines and two antibodies, and a few more plants were involved in ancillary activities.

Distribution and Administration

Distribution of the vaccines was flawlessly organized by the DoD logistics team with OWS. The criteria to allocate and distribute the vaccine were decided by the board. Distribution had to be fair and equitable and was based on the population of each of the 64 states and jurisdictions we needed to supply. We partnered with McKesson, UPS, and FedEx to establish distribution centers and a next-day air delivery system to ensure chain of custody as well as cold-chain integrity. Each jurisdiction administration point could order vaccines for next-day delivery on the mainland US and 48- to 72-hour delivery for the other jurisdictions.

A logistics “war room” and control tower were set up on the second floor of the HHS building, and a system to collect data on inventory and immunization from all states and jurisdictions was developed in record time. This system was called Tiberius, and it allowed visibility and a single source of information for all logistics operations. As Perna used to say, it allowed us to “see ourselves.” After having personally seen implementations of IT systems in large corporations for many years, I have to say that this system greatly exceeded my expectations, both in terms of capabilities and time to deployment.

The team also had to provide each vaccine administration center with all the ancillary materials needed for a successful vaccination campaign. This included syringes—which were different for different vaccines gloves—sanitizing pads, CDC vaccine cards and other items, in quantities to match the number of doses shipped. For every vaccine supply chain, there was a matching supply chain to provide the kits customized for that specific vaccine.

From a logistics perspective, the most critical vaccine was the Pfizer product, which had to be stored in dry ice at -80ₒ C. Each shipper contained a GPS monitor that allowed tracking in real time, and a resupply process for dry ice. Nothing was left to chance.

Beyond providing resources and support for development and manufacturing, the government ensured an unprecedented level of access and flexibility from regulators. The Center for Biologics Evaluation and Research, the FDA division responsible for vaccine review, allowed companies to execute rolling submissions and the review to proceed in parallel with the submission. This flexibility, however, did not extend to any requirement for the quality and safety of the vaccines: At no point in time did I see any compromise on those critical aspects.

In addition to the clinical package with the phase 3 data including the safety follow-up, the submission package needed to include data from the validation lots. And, assuming success, we also wanted to be in a position to have inventory available and start the immunization campaign as soon as the FDA completed their review and issued the EUA.

That put manufacturing squarely on the critical path: During fall 2020, we were completing equipment qualifications, going into engineering runs, followed back-to-back by validation, and then stockpiling. The schedule did not allow for much inventory buildup in preparation for approval, and it was a startup, after all, with all the risks interconnected. In every plant, people were working extended shifts and weekends in order to meet deadlines, with tremendous personal commitment despite the risks.

By the end of 2020, we had about 30 million doses already shipped or ready to ship, with many more at different stages in the manufacturing process, and we had clear visibility to an acceleration in supply to support an acceleration in vaccine administration, which was already close to about 1 million doses per day with a target to get to 3 million doses per day very quickly. Manufacturing activities continued uninterrupted throughout the holidays. Many people at the sites told me they had not taken a day off in many months, and they did not plan to take any until there was assurance of ample availability of doses. That is real commitment!

Of course, as in every startup, not everything was smooth sailing. We were always running hand to mouth with materials, and any issue with the quality of a component would have had an immediate impact on the manufacturing schedule. The Army logistics team was tracking all shipments in real time, and at times we had to invite some CEOs to phone conferences with Perna when we saw a risk to a delivery date. Some equipment failed, and we had to rush replacements, and so did some of the materials. But when you look at the sheer size of the manufacturing operation, these were really small issues that had no material impact on our ability to deliver.

Conclusion

Was everything really successful, and what did we learn from it? These are the questions I am most often asked and I have pondered quite a bit.

If you look strictly at the mission OWS took on, it was certainly successfully accomplished, with two safe and effective vaccines approved before the end of the year, and a third one by the end of Q1 2021. Of the six vaccines, five have obtained approval in the US or Europe, and they have been administered in several countries. The sixth has recently announced positive clinical results, and it will soon be submitted for approval. That is a remarkable achievement for our industry and for science, and it is already making a difference in the world.

How should we rate our manufacturing performance? I keep asking myself what we could have done differently to ensure even better outcomes in volumes and timing. I’ve concluded that beyond having manufacturing capacity available and ready to use when the pandemic started, I cannot think of anything else that could have made a difference in this situation.

I also wish we had taken a more forceful approach to the one site that failed to deliver, which caused delays to two programs. But even then, this would not have changed the situation for the first two months of supply.

What have I learned from this experience? The short answer is: a lot! First, I have been reminded once more that leadership truly matters. Thanks to the impactful leadership of Slaoui, Perna, and many others in the companies and organizations we worked with, along with those at HHS and DoD, thousands of people selflessly dedicated themselves to fighting the pandemic, setting aside personal priorities, and focusing 100% on this mission.

I have also learned firsthand that the industry alone, and the government alone, could not have achieved what we did. You need both, with the best that each can bring to the table, to make it happen.

And finally, I have learned how critical it is to prepare for the next pandemic. Because there will be another one. We don’t know when and where it will emerge, but it will. That, we can all count on.

Special Report: Pandemic Progress: Industry’s Journey From 2020 to Today

In 2020, the world was grappling with how to slow the spread of the SARS-CoV-2 virus and appropriately treat people who had the COVID-19 infection without approved therapies or vaccines. In two years, there are multiple vaccines and treatments along with great knowledge about the virus—and about how the industry mobilized, partnered, and achieved tremendous strides in addressing the global pandemic.