Operation Warp Speed’s Notaristefani on Getting Every Last American Vaccinated

The Vaccine Challenge

This episode of The Vaccine Challenge is hosted by Priyanka Asera and features Carlo de Notaristefani, Lead Advisor Manufacturing & Supply Chain at Operation Warp Speed.

Operation Warp Speed is a public–private partnership initiated by the US government to facilitate and accelerate the development, manufacturing, and distribution of COVID-19 vaccines.

We’ve asked Carlo some really important questions around how OWS works with the FDA and CDC, what are the actual number of vaccines in the pipeline waiting to be authorized, how many Americans have already been inoculated, why the embargo on vaccine raw materials to rest of the world, the basic supply chain of vaccine development, and whether there will be permanent changes in the world of drug discovery, development and approval timelines given the speed at which these vaccines have come to market.

If you want to hear more from Carlo, he is a speaker this year at the Disease Prevention & Control Summit, a two-day virtual event taking place on July 20-21st, focusing on some of the most important topics across the COVID-19 space, including vaccines, therapeutics, diagnostics, and health equity. Priyanka will also be moderating a panel on vaccine distribution, so make sure not to miss it! Link to register for free is below.

Link to free registration: https://bit.ly/2Qzvjpy

Summary of the podcast interview:

What is Operation Warp Speed and What Are Its Objectives?

• OWS is a public-private partnership set up to accelerate the delivery of vaccine and therapeutics in order to supply to the whole US population
• Model was set up initially like The Manhattan Project. A special task-force set up within the US Government bringing different kinds of experiences and expertise to deliver a well-defined outcome
• Integrated effort between Health and Human Service Department (HHS), and the Department of Defence (DoD) that brought their logistics expertise, and some experienced pharma experts like Carlo. FDA which is the regulator is tasked with regulating and approving the vaccine and was not included as part of OWS in order to retain its full independence to judge the outcome in an objective manner

What goals were set up originally and what has been actually achieved?

• Initial goal that was set was to deliver 100mn dozes of vaccines by end of 2020, and 300mn dozes by end of Q1 2021. OWS didn’t fully accomplish that goal, but came close. Did 30mn dozes by end of 2020, and 230mn dozes by end of Q1. Distributed over 280mn dozes as of today.
• As of today, 70mn people have had both dozes, and over 130mn people have had at least one doze.

How did OWS decide which vaccines to support prior to approvals?

• In May 2020, the first significant decision to be made was which vaccines should be selected to support, accelerate and develop, out of the 60 candidates under development in the world at the time. Driver of this decision was based on “likelihood of success” and “minimization of risk”
• 3 key platforms were selected– Messenger RNA, viral vector and spiked protein. For each of these 3 platforms, 2-3 candidates were chosen based on what appeared most promising based on the preliminary data available and the stage of development.
• Finally, 7 candidates were selected. Pfizer/BioNTech, Moderna, Astra Zeneca Oxford, Janssen, Novovax, Sanofi, & Merck.

How did these vaccines get approved so quickly in record time? Since this has never happened before, can its quality be relied upon?

• “Speed” is a doubled edged sword. People get concerned that by trying to accelerate you may cut corners and impact the quality of the outcome.
• We’ve absolutely not cut corners with regards to the safety, efficacy, compliance and quality. Instead, financial risks were taken to reduce lead times. We decided to look at what can we do in parallel? So we started manufacturing the vaccines well before knowing whether the vaccines will be safe and effective. That means, if the clinical trial delivered a negative result we’d have wasted a significant amount of money from manufacturing millions of dozes without knowing whether the dozes will be effective or not.
• We built the refrigeration capacity over time. We decided to take the financial risk to build the infrastructure and capacity without knowing whether the vaccine was going to be effective
• The resources that the US government has allowed us to take that financial risk. A private company could never have done it. That’s how we managed to reduce timelines.
• Similarly we partnered with NIH and hospital chains to support clinical studies of the US government. We set up a mobile network of clinical study centers to follow where the pandemic was in the country. This was a very capital intensive way of doing it but allowed us to recruit patients exactly where the hotspots of the country were.

Which vaccines have been approved, and which are waiting to be approved?

• In the US, 3 vaccines have been approved (as of April 16th).
• First was Pfizer/BioNTech, followed shortly by Moderna. Both of these are mRNA platform. We knew this would be the fastest platform to deliver the result. Didn’t know of course if the result would have been positive or negative at the time, but knew the path to an outcome would be the quickest
• The third vaccine to receive emergency use authorization was Janssen – which is a viral vector vaccine.
• Have 3 more under development – Astra Zeneca, another viral vector. And Novovax and Sanofi which are both spiked protein – we knew the spiked protein would take longer than others. So the sequence in which they became ready was expected.
• Expecting approval of AZ vaccine in the very near future within weeks. Followed with Novovax and Sanofi.
• What’s actually surprising is that of the 7 vaccines considered, only 1 has been discontinued (Merck) – and not because of failure to deliver but because of length of development required. 6 out of the 7 have all delivered positive efficacy results so far as well as very good safety data. This is better than anybody thought possible.

Have all vaccines been produced domestically for American consumption?

• Yes. This was quite debated in a heated way initially. Pharma supply chains are global. Trying to develop a regional supply chain is a challenge in itself, but try doing that in the middle of a pandemic is an even bigger challenge. Several of us questioned the need for that.
• But, having local manufacturing allows you to support and control the progress a lot better. It’s a trade-off – so we finally decided to manufacture locally. This decision has allowed us to follow the manufacturing set up and identify the issues in advance and work in a more proactive way and deliver on the target we set for ourselves.

The world’s biggest vaccine-maker, Serum Institute of India, has complained about the embargo placed by the US on vaccine raw materials. What’s your take on that?

• The pandemic knows no borders. The big concern is if every country tries to block their borders and prevent export of vaccines or components globally, ultimately we will all be losers because I cannot see a scenario where one country is safe and the rest of the world still has the pandemic. These are problems that we need to address globally.
• Having said that, I can certainly understand the challenge of the governments that are tasked with protecting their citizens first, and this is a matter of prioritization. I am always of the opinion that collaboration is better. Supply chains are global and no one country can resolve this problem alone. I’m sure that reason will prevail, and while there are certainly tensions going on, ultimately the governments will have to collaborate. And I’ve seen signs that this is actually happening besides the formal public positions that governments have to take.
• Ultimate decision lies with the White House under advise from the CDC which is part of HHS.

How do you plan and execute for the “double-doze requirement” and therefore the accuracy in production and distribution of it?

• In the beginning we were in a supply constraint. So we set up an S&OP style process creating a forecast of availability managing the interval between the dozes.
• Pfizer-BioNTech vaccine has a 3 week interval, Moderna has 4 weeks, and Janssen is a single doze vaccine.
• Through an IT system set up by the DoD called Tiberius, we planned the distribution based on the availability – keeping track of every location in the US where the vaccine was shipped, by setting aside the second dozes of the same vaccine for that location. The CDC guideline was that we would go for an analogous second doze –so that meant we could not mix and match the different vaccine to the same individual.
• Right now we have 35000 “shipping points” where we ship. For each shipping point we know exactly how many dozes are received, how many dozes are administered, how many second dozes are pending and when are they due, so we can plan the shipment of the second dozes.

What were some cold chain challenges considering the temperature requirements of the vaccine(s)?

• The supply chain involves a significant amount of refrigerated storage space or freezer storage space.
• Pfizer established a “freezer farm” with almost 1000 freezers at -80 degree Celsius to store material, work in process, and finished goods- pending testing. The set-up of this chain required several months of preparation and work. This is another example of public-private partnership. If not for this partnership, we’d still be building the plant as we speak, instead of injecting vaccines in people’s arms
• We purchased a very large amount of refrigerated space and freezers as early as June, based on the assumption that we’d get to 300mn dozes for each vaccine. We had a mission to deliver 300mn dozes of each one of the 6/7 vaccines we supported, because we didn’t know which one was going to be successful in the end.

What are/were OWS’s three biggest challenges?

• Shortage of supply materials: All materials and components were short because everyone in the world was trying to get a vaccine that works. Within the US, of course the US government had priority to get whatever we needed. Outside the US though, we didn’t have any power. But we had to scour the world to get materials and components.
• People: While we had some infrastructure, we had to build a lot more. But, you need people to run the plant. There were many people with experience in manufacturing vaccines available. But we’re talking about manufacturing couple of billion dozes within a 3-6 month period. That requires a huge amount of quality people
• Science: We decided we wouldn’t cut any corners. And so sometimes, you cannot compress. So how do you build the plan to optimize overall without compromising on the science and data needed to ensure safety and efficacy. That was the challenge

CDC has asked to put the Janssen vaccine on hold due to blood clots - how do you stop the vaccine from use where it’s already at health centers or in-transit?

• It was a huge coordination effort. We sent messages to each of the 35000 administration point that received the vaccines and got confirmation of receipt of messages. The entire administration was paused. All storage was done in agreement with necessary storage conditions. We wanted to make sure we were ready to receive them as soon as we got the green light in a safe way for everyone involved.

• This all happened in 24 hours – all thanks to Tiberius and the DoD’s resources that have done an incredible job with setting up the logistics network

What permanent or lasting changes do you think will persist in drug

• The industry has learned a lot with regards to what is possible when you put up a collaborative set up.
• The regulators have learned a lot – the FDA has been able to redesign their review process and deliver a decision sometimes within 2 weeks of submission – that’s unheard of.
• We’ve all learnt new ways of working and that’s changed the industry forever. Eg. We’ve all learned to work remotely now because there was no other option. A year or two years ago, I’d never have thought this to be possible.

About Carlo de Notaristefani

Dr. Carlo de Notaristefani became President and Chief Executive Officer of Teva’s Global Operations in August 2012.

Prior to joining Teva, Carlo was a member of the Senior Management Team at Bristol-Myers Squibb since 2004, as President Technical Operations and Global Support Functions, with responsibility for the operations of the global Supply Chain, Quality and Compliance, Procurement and Information Technology for the corporation.

During his tenure at BMS, Dr. de Notaristefani led one of the most successful productivity transformation of the supply chain in the Pharma industry.

Before joining BMS, Dr. de Notaristefani held several senior positions of increasing responsibility in the Global Operations and Supply Chain management areas with Aventis, Hoechst Marion Roussell and Marion Merrell Dow, based in Italy, Spain, France and the US.

Dr. de Notaristefani holds a degree of Doctor of Chemical Engineering from the University of Naples, Naples, Italy, is a registered PE, and APICS CIRM certified.