Coalition for Epidemic Preparedness Innovations (CEPI)

The 8-9 March “Global C19 Vaccine Supply Chain and Manufacturing Summit” — Efforts to Ramp-Up Production

On Monday and Tuesday of this week, the Chatham House hosted an event that was”sponsored by COVAX (the COVID-19 vaccine initiative led by the World Health Organization, the Coalition for Epidemic Preparedness Innovations and Gavi, the Vaccine Alliance), together with the Developing Countries Vaccine Manufacturers Network (DCVMN), the Biotechnology Innovation Organization (BIO), and the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA).” WTO, DG calls on COVID-19 vaccine manufacturers to increase production in developing countries, March 9, 2021, https://www.wto.org/english/news_e/news21_e/dgno_09mar21_e.htm. Because the event was conducted under Chatham House rules, the information available is from the participants’ releases.

The participants had a document and apendix to provide some factual background to help the discussion. “Towards Vaccinating the World: Landscape of Current COVID-19 Supply Chain and Manufacturing Capacity, Potential Challenges. Initial Responses, and Possible “Solution Space” — a Discussion Document” is the 28 page background document. It is accompanied by a 12 page Appendix. The introduction provides a useful overview of efforts to address the COVID-19 pandemic and the areas for discussion at the meeting. The introduction is copied below and is followed by both the background document and appendix being embedded.

Introduction

“I feel like I didn’t just get a vaccine, I got a shot of hope. It’s hope that this is the beginning of the end of this terrible pandemic.” – Dr Hagan, Frontline Worker1

“With over 2.6 million deaths as of 3rd March 2021,2 and economic cost estimated at 5-14 trillion USD per year3 due to COVID-19, mitigating the pandemic is a paramount global priority and vaccines are a critical part of the solution.

“Since the start of the COVID-19 pandemic, the world has seen unprecedented progress in vaccine development, manufacturing ramp-up, and deployment. Within a record time of less than a year, 11 vaccines are already in clinical use in the countries where they obtained approval (often with emergency/limited authorisation), more than 80 additional candidates are in clinical trials, and hundreds of candidates are in the pre-clinical phase. At the same time, vaccine manufacturers and suppliers of vaccine components are scaling up for COVID-19 vaccine production from zero to billions of doses, with an announced cumulative supply target of up to 14 billion doses by the end of 2021. This represents three to four times the pre-COVID-19 annual global demand for all vaccines of 3.5-5.5 billion.4 The impact of these efforts is starting to be seen, with over 270 million people globally vaccinated as of 3rd March 2021.5

“The increase in capacity is remarkable because of the complexity of vaccine manufacturing processes that require specific know-how and equipment. It usually takes more than five years to build manufacturing capacity and 18-30 months to transfer production to other sites or manufacturers.6 The use of new technologies such as mRNA in response to COVID-19 poses additional challenges because no large-scale manufacturing capacity nor specific raw materials existed at the outset of the pandemic. COVID-19 vaccine manufacturers ramped up their own manufacturing in parallel to clinical development (“scale-up”) in response to this challenge. They also formed more than 150 partnerships7 with contract development and manufacturing organisations (CDMOs) and other multinational biopharmaceutical companies to transfer their technology and increase their overall production (“scale-out”). Notwithstanding these efforts, the strain on manufacturing capacities and capabilities is very high, in light of the immediacy and scale of the demand, which may be exacerbated further if a broader coverage of the population is needed and if boosters are needed due to waning efficacy and need to protect from new variants.

“However, it has become apparent that many COVID-19 vaccine input supplies of raw and packaging materials, consumables and equipment are in short supply which may result in several COVID-19 vaccine manufactures not being able to meet their current vaccine manufacturing commitments. Such shortages will also impact the ability to manufacture other lifesaving vaccines and biologics. Mechanisms to ensure input supplies for current and increased manufacturing capacity intent need to be put in place with short, medium and long-term solutions.

“Supply of COVID-19 vaccines will more than double the annual volume of vaccines procured via UNICEF. These additional COVID-19 vaccine needs from manufacturers of routine vaccines and other essential supplies is of concern to UNICEF. There is a need for expanded manufacturing capacity while building on existing mechanisms to sustain and scale current investments that the Vaccine Alliance has achieved thus far.

“The summit will evaluate all potential bottlenecks of supply chain for input supplies, from manufacturing, through procurement, export, delivery and use of the materials for COVID-19 vaccine manufacture. It is of paramount importance to anticipate, understand, and establish an open dialogue with all stakeholders to find and implement additional short-term and sustainable solutions to the inevitable supply chain challenges.

“For this reason, Chatham House – with co-sponsorship from COVAX (CEPI, Gavi, WHO, UNICEF), IFPMA, BIO, and DCVMN – has convened the COVID-19 Vaccine Manufacturing and Supply Chain Summit with key public, private, and other vaccine stakeholders on 8th and 9th March 2021, to explore the emerging input supply challenges in depth and to start to work towards strategies to avoid or mitigate them. The main goals of the Summit are:

“▪ Help to identify and define the most critical bottlenecks across the supply network for a diverse array of COVID-19 vaccines with an emphasis on input supply

“▪ Provide a platform to explore a range of solutions to address bottlenecks.

“▪ Lead to a series of recommendations, and ideally commitments, on the priority areas for monitoring and/or action.

“Today, the only element that can be predicted about the future is its high degree of uncertainty. The objective of this document is to provide a structured fact base to serve as background for participants, not to attempt to predict any aspect of the future course of this pandemic. This fact base builds on perspectives and information developed and provided by Summit conveners and participants. Given the rapid pace of events in this space, it should be considered as a ‘best effort’ guide towards a high-level analysis and assessment of the state of play today but it is unlikely to be complete and may have omissions. Any estimates should be validated before being used for decision-making. The discussion document should be viewed as a discussion guide for participants and is structured into the following sections:

“1. Introduction to Vaccine Manufacturing and Supply Chain

“2. COVID-19 Vaccine Supply and Demand Overview

“3. Input Supply Challenges

“4. Manufacturing Capacity and Interdependencies beyond COVID-19 Vaccine

“5. Overview of Potential Solutions for Discussion

“6. Moving to Action

In parallel to the Chatham House Summit, many discussions are ongoing on how further to increase available manufacturing capacity of vaccine drug substance/drug product and accelerate technology transfer.

The purpose of this Summit, and this discussion document, is not aimed to identify or assign responsibility. COVID-19 is an exceptional crisis with unforeseen and shifting challenges. The aim is to bring stakeholders together to understand and align on how to move forward together leveraging their combined capabilities to optimise access to vaccines against COVID-19 for good of the world.

“1 New York Times, ‘A Shot of Hope’: What the Vaccine Is Like for Frontline Doctors and Nurses. 2020. https://www.nytimes.com/2020/12/14/us/coronavirus-vaccine-doctors-nurses.html

“2 WHO; Economist

“3 Airfinity; IMF

“4 WHO Global Vaccine Market Report 2019, 2020. http://who.int/immunization/programmes_systems/procurement/mi4a/platform/module2/2019_ Global_Vaccine_Market_Report.pdf?ua=1#:~:text=Global%20market%20volumes%20increased%20approximately,large-scale%20campaigns%20in%20India.

“5 WHO, WHO Coronavirus Disease (COVID-19) Dashboard. https://covid19.who.int/; Bloomberg, COVID-19 Vaccine tracker. https://www.bloomberg.com/graphics/covid-vaccine-tracker-global-distribution/

“6 McKinsey & Company, Why tech transfer may be critical to beating COVID-19. 2020. https://www.mckinsey.com/industries/pharmaceuticals-and-medical-products/our-insights/why-tech-transfer-may-be-critical-to-beating-covid-19

“7 Airfinity”

Summit_Landscape_Discussion_Document

Summit_Landscape_Discussion_Document_Appendix

The background paper is useful by pulling together information on demand, likely production, a review of the challenges in supply chains, and the fact that globally only 3% of likely 2021 vaccines had been manufactured by March 3, 2021, meaning there are huge production increases coming in the remaining ten months driven by more vaccines being approved for use by countries and the WTO. Several exhibits from the report are copied below (Exhibit 2, page 7; Exhibit 5, page 12; Exhibit 6, page 14; Exhibit 7, page 16) and show the distribution of manufacturers with approved vaccines or vaccines in third stage trials, projected supply under three scenarios, input supply bottleneck issues, and a “summary of major supply challenges and drivers”.

There was a joint press release which is embedded below. See Global C19 Vaccine Supply Chain and Manufacturing Summit Press Release, March 9, 2021, https://www.dcvmn.org/IMG/pdf/global_covid-19_vaccine_supply_chain_manufacturing_summit_press_release_1_.pdf.

global_covid-19_vaccine_supply_chain_manufacturing_summit_press_release_1_

Several paragraphs on the first page review the supply chain issues and then review areas for potential additional work. Because of their importance, they are copied below (emphasis added).

“Vaccine manufacturers and upstream suppliers are increasingly reporting shortages of raw and packaging materials, critical consumables, and equipment. Over time such shortages, if left unaddressed, will lead to shortages of vaccines and impact delivery commitments. Such shortages will also impact the ability to manufacture other lifesaving vaccines and biologics. Preventing bottlenecks in the system requires among others: addressing export restrictions, immediate easing and facilitation of access to raw materials and upstream supplies; regulatory prioritization of validation of supply, batch release and achieving greater visibility on vaccines demand forecasts to enable upstream suppliers to do better supply planning.

“All stakeholders agreed there is a need to expand capacity and in a way that promotes equitable access and leaves no one behind. Other approaches were discussed including:

“1. Free flow of goods and workforce;

“2. Continue technology transfer and manufacturing partnerships between innovators and manufacturers to scale up and scale out COVID19 vaccine capacity;

“3. Better demand forecasting and inventory management of raw materials and critical consumables;

“4. Support from the highest political level is needed;

“5. Value of regulatory harmonization and streamlining to accelerate manufacturing capacity and supply;

“6. Better production, demand and supply, forecast and visibility;

“7. Give consideration to the potential impacts of COVID-19 production on non-COVID products

The quotes from the six organizations participating fell along predictable lines — CEPI’s CEO focused on the need to address bottlenecks to ensure delivery of supplies; IFPMA’s DG reviewed the huge build up of capabilities and need to address bottlenecks while recognizing the need to continue to expand capacity; the CEO of GAVI viewed the event as “an important step in building the global consensus needed to solve the bottlenecks and supply constraints”; the WHO’s chief scientist focused on equitable distribution and in the “longer term more sustainable approach will be to enable technology transfer to manufacturing sites in LMICs that have the capacity”; the President and CEO of BIO noted that “We must invest across all of the ecosystem to ensure that there is not only manufacturing capacity but also increasing amounts of the vital production supplies needed for that capacity”; the President of the DCVMN focused on expanding production in developing countries, “Global products, local manufacturing, and leave no one behind.”

The WTO’s Director-General Ngozi Okonjo-Iweala who is a former Chair of GAVI, spoke to the participants on March 9 urging licensing and partnerships with vaccine manufacturers in developing countries and repeating her themes of recent days of focusing on ending or phasing out export restrictions. See WTO, DG calls on COVID-19 vaccine manufacturers to increase production in developing countries, March 9, 2021, https://www.wto.org/english/news_e/news21_e/dgno_09mar21_e.htm. The press release is copied below.

“Director-General Ngozi Okonjo-Iweala on 9 March called on COVID-19 vaccine manufacturers to do more to ramp up production in developing countries to combat the vaccine supply shortage that is excluding many lower-income nations from access. In remarks to an event hosted by the UK think tank Chatham House, she said cooperation on trade, and action at the WTO, would help accelerate vaccine scale-up.

The scarcity of COVID-19 vaccine supplies had led to a situation in which around 75 countries are able to move ahead with vaccination while 115 countries wait as people die, DG Okonjo-Iweala told the Global C19 Vaccine Supply Chain and Manufacturing Summit.

Not only was this morally “unconscionable,” she said, it would prolong the pandemic and cause economic harm to all countries. Instead of restricting exports and bidding up prices, she argued, “it is in all of our self-interest to cooperate in dealing with this problem of the global commons.”

The Director-General saw cause for hope in the first vaccine deliveries to developing countries by the COVAX facility, the global mechanism for procuring and equitably distributing COVID-19 vaccines. Nevertheless, production and delivery volumes remained too low.

“We have to scale up and scale out COVID-19 vaccine production, particularly in emerging markets and developing countries,” she said. Given the years required to build new manufacturing facilities from scratch, increasing production in the short-term means “making the most of existing manufacturing capacity — finding existing sites and turning them around.” Recent experience suggests that repurposing facilities and vetting them for safety and quality can happen in six or seven months, less than half as long as previously thought.

“By bringing more production online around the world, she said, vaccine manufacturers would send a signal that they are taking action, and ‘that people and governments in low- and middle-income countries can expect to get access to affordable vaccines within a reasonable timeframe.’

“DG Okonjo-Iweala observed that companies in India and elsewhere were already manufacturing COVID-19 vaccines under licence but said that more such arrangements are necessary.

“Discussions during the conference had highlighted three constraints to ramping up production, the Director-General noted: scarcity of raw materials, shortages of qualified and experienced personnel, and supply chain problems linked to export restrictions and prohibitions as well as excessive bureaucracy. The WTO’s mandate on trade facilitation, quantitative trade restrictions, and trade policy monitoring were relevant to the latter challenges in particular.

“Because vaccine production relies on sourcing components and ingredients from multiple countries, she said, trade restrictions would slow down production, and make it more expensive.

“Nevertheless, DG Okonjo-Iweala noted, WTO rules do allow for export restrictions or prohibitions to be ‘temporarily applied to prevent or relieve critical shortages’ of essential products. That said, such restrictions must be notified to all members. Restrictions should be transparent, proportionate to the problem at hand, and members should provide timelines for when they will be phased out, she said.

“She reported that WTO monitoring indicates that 59 members and 7 observers still had some pandemic-related export restrictions or licensing requirements in place at the end of February, primarily for personal protective equipment. It was welcome that these figures were lower than the 91 countries that had brought in such measures over the past year. However, ‘not all pandemic-related export restrictions have been notified,’ she said. ‘Not all of them appear to be temporary. Not all of them are proportionate.’

“’We must strengthen our monitoring and reporting function,’ DG Okonjo-Iweala said, explaining that her objective would be to encourage members to drop or reduce export restrictions, or set timelines for phaseout, to help minimize problems in the vaccine supply chain.

“With regard to trade-related bureaucracy, she invited manufacturers to tell the WTO about the problems they are encountering in real time, ‘so we can put them before our membership and find ways they can be minimized and if possible solved.’ She said a little-appreciated fact about trade policy during the pandemic is that members’ trade-facilitating measures, such as electronic customs procedures and simplified paperwork requirements, have far outnumbered trade-restricting policies, and covered a higher value of merchandise.

“On both export restrictions and trade facilitation, DG Okonjo-Iweala noted, prospects for action at the WTO would improve as businesses are seen to step up efforts on vaccine production.

“The Director-General referred to the ongoing debate at the WTO on a proposal to waive standard WTO intellectual property rules for COVID-related vaccines, therapeutics, and diagnostics.

“’Many of the proposal’s supporters are developing and least developed countries, deeply marked by the memory of unaffordable HIV/AIDS drugs,’ she told conference participants. ‘Many, many people died who should not have. More recently, they remember being left at the back of the queue for H1N1 vaccines as richer countries bought up available supplies, which in the end were not used.’ Critics of the proposed waiver, she noted, say it could threaten investment and innovation, and other members have asked for more evidence that intellectual property protections are an inhibiting factor in vaccine scale-up.

“While these ‘vitally important discussions are intensifying here in Geneva,’ she said, ‘the fact is that each additional day the vaccine shortage continues, people will pay with their lives.’ She argued that it was possible to ‘walk and chew gum at the same time,’ continuing the search for solutions in the TRIPS debate, while simultaneously taking action to increase production, ‘especially in emerging markets and developing countries where such possibilities exist.’

“She expressed hope that it would be possible for manufacturers from developed and developing countries to come together with civil society groups, organizations such as the World Health Organization, Gavi, and the Coalition for Epidemic Preparedness (which together run the COVAX facility), and business associations including the International Chamber of Commerce to find ways to increase vaccine production.

“’We must make sure that in the end we deliver so that the millions of people who are waiting for us with bated breath know that we are working on concrete solutions,’ she said.

“The 8-9 March ‘Global C19 Vaccine Supply Chain and Manufacturing Summit’ was convened by Chatham House and sponsored by COVAX (the COVID-19 vaccine initiative led by the World Health Organization, the Coalition for Epidemic Preparedness Innovations and Gavi, the Vaccine Alliance), together with the Developing Countries Vaccine Manufacturers Network (DCVMN), the Biotechnology Innovation Organization (BIO), and the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA). The meeting was held under the Chatham House rule, so the above report on the Director-General’s speech does not reflect views attributed to other participants.”

Conclusion

Countries around the world are starting the process of vaccinating their populations. The COVAX vaccine roll-out, which includes efforts to get doses to low- and middle-income countries, appears to be on target for its goal of two billion shots in 2021. While vaccine doses from COVAX started at the very end of February, by March 11, COVAX was reporting 28.5 million doses had been shipped to 37 countries. See Gavi, COVAX has so far shipped over 28.5 million COVID-19 vaccines to 37 countries, March 11, 2021, https://www.gavi.org/covax-vaccine-roll-out.

All countries working with vaccine producers have encountered some delays as manufacturers are having both start-up challenges at their own facilities and supply chain issues as reviewed in the background paper used by participants at this week’s Chatham House event. There are clearly supply chain issues that pose risks to current manufacturing efforts and already scheduled ramp ups of capacity. The major pharmaceutical groups have worked hard to develop capacity and upgrade supply chains. They all appreciate that more can and will be done.

There are a host of issues on COVID vaccines that need to be addressed that fall within the WTO’s wheelhouse — control of export restraints, easing and access to raw materials and upstream supplies to name two. As DG Okonjo-Iweala noted, the WTO TRIPS Council is considering whether to recommend a waiver of TRIPS obligations for medical products for COVID-19 use during the pandemic. Indeed another meeting of the TRIPS Council was held on March 10-11. See WTO, Members discuss TRIPS waiver, LDC transition period and green tech role for small business, March 11, 2021, https://www.wto.org/english/news_e/news21_e/trip_11mar21_e.htm. However, not only is the requested waiver opposed by major developed countries and at least one developing country (and hence unlikely to obtain consensus to forward to the General Council), but also a review of the background document shows the complexity of technology transfer in the best of situations. Pharmaceutical and biotech companies are opposed to the waiver and view such action as almost certain to slow the ramp up of production. See, e.g., IFPMA, Pharma delivers COVID-19 solutions, but calls for the dilution of intellectual property rights are counterproductive, 20 December 2020, https://www.ifpma.org/resource-centre/pharma-innovation-delivers-covid-19-solutions-beyond-expectations-but-calls-for-the-dilution-of-intellectual-property-rights-are-counteproductive/; Bio, Letter to President Biden, March 5, 2021, https://www.bio.org/letters-testimony-comments/bio-sends-letter-president-biden-discussing-collaboration-ensure-patient; PhRMA, letter to President Biden, March 5, 2021, https://phrma.org/Public-Communication/Letter-to-President-Biden-from-31-PhRMA-Board-Members.

The Chatham House event was a timely and practical effort to have the major participants review challenges currently being faced and to exchange ideas on how to move forward. Efforts such as we have seen under the Biden Administration to help address bottlenecks through the use of the Defense Production Act should be undertaken by other governments to help streamline the ramp up process for both vaccines and the key inputs and other materials needed for expanded production. The seven “other approaches” identified in the joint press release are sound and ambitious but will require not only government involvement (regulatory harmonization; support at the highest level of government) but also improved data gathering and dissemination (supply and demand forecasts). The size of the planned ramp up of production (assuming vaccines that are in stage three end up being approved and supply chain issues can be handled) as shown in Exhibit 5 of the background document is truly impressive. The addition of more capacity through additional licensing or partnership arrangements will further improve the outlook for 2021 for the world.

While COVAX was set up with the ambitious objective of 2 billion doses to the 192 countries (including 92 low- and middle-income countries were vaccines will be provided without charge) COVAX is serving in 2021, most scenarios in the background paper show the likelihood of additional billions of doses available by the end of the year. This suggests that the challenge may not be production but rather securing funding for the additional doses that will be available and/or movement of additional unneeded supplies from developed countries in the latter part of 2021. The G20 and others should be able to help with the financing. It is likely that doses may be available for transfer from at least some developed countries by the fourth quarter.

So there is a lot that is happening and lots that needs to be done to see that the COVID-19 pandemic is fully addressed. Waiving TRIPS obligations is not one of them.