Equitable Access Toolkit
Access to safe and effective vaccines has been–and continues to be–critical to the worldwide response to the COVID-19 pandemic. The research, development and manufacturing of vaccines took place at an unprecedented pace, but access to the resulting vaccines has not been equal across the globe. Vaccine research and development (R&D) and manufacturing processes have been supported by partnerships between vaccine developers and a variety of funders and other organizations. The agreements behind these partnerships have included funding agreements with public or philanthropic organizations, license agreements with intellectual property owners, technology transfer agreements with manufacturers, and supply agreements with governments and multilateral procurement agencies. The terms of these contracts have had an impact on who has access to vaccines and, critically, when they have it.
GHIAA has undertaken research to identify the ecosystem of contracts supporting the research, development, and manufacturing of different COVID-19 vaccines, with the aim of identifying specific contract terms that have, or could have, impact on equitable access to the vaccine. Initial findings indicate that there is generally very little transparency around actual contracts (as opposed to press releases containing general statements). However, one example for which a larger body of contracts is available (through SEC filings) is Novavax’s Nuvaxovid (NVX-CoV2373) vaccine.
As was the case for several other COVID-19 vaccines, Novavax faced well-documented challenges with its manufacturing processes and regulatory applications, not receiving its first regulatory approval until November 2021 (from Indonesia). Now, Nuvaxoid is approved for use in 40 countries, and has a WHO Emergency Use Listing and a Caribbean Regulatory System Emergency Use Recommendation. Nuvaxoid is potentially easier to produce than mRNA vaccines and does not need to be stored at extremely low temperatures, meaning that it may be easier to distribute in lower-resource settings. Novavax also hoped that the more ‘traditional’ manufacturing method used to produce Nuvaxoid will be more acceptable to those who have been hesitant to be vaccinated with mRNA vaccines.
Some of the key partnerships supporting the development and commercialization of Novavax’s vaccine include:
Funding agreements for more than $380 million from the Coalition for Epidemic Preparedness Innovations (CEPI – see below) and approximately $1.6 billion from U.S. government provided Novavax with a substantial part of the funding needed to help the vaccine progress from early stage development and clinical trials through to manufacturing scale-up and to regulatory approval.
Manufacturing arrangements with a number of partners helped expand Novavax’s own limited global vaccine manufacturing capacity. These include license and technology transfer agreements with Serum Institute of India (SII – see below; marketing the vaccine product under the brand name Covovax), Takeda (marketing the vaccine product in Japan under the brand name TAK-019) and SK BioScience.
Novavax entered into advance purchase agreements and supply agreements with national governments including the U.S., UK and European Commission, as well as with the COVAX Factility through Gavi (see below for supply of the vaccine. In its quarterly report for the period ending 30 June 2022, Novavax reported that 73 million doses had been delivered under these supply agreements to date.
This case study will examine the terms of some of these agreements, with a focus on those intended to support equitable access to the Novavax vaccine.
Funding Agreement with CEPI
On March 10, 2020, CEPI announced the signature of a $4.4 million funding agreement with Novavax to support the development of a COVID-19 vaccine candidate using Novavax’s proprietary recombinant protein nanoparticle technology platform. Two months later, CEPI announced an agreement for additional funding of up to $384 million, for pre-clinical studies, Phase 1 and 2 clinical trials, and manufacturing scale-up to enable the production of a larger volume of the vaccine.
CEPI’s mission is to “accelerate the development of vaccines and other biologic countermeasures against epidemic and pandemic threats so they can be accessible to all people in need.” To support the achievement of “accessible to all,” CEPI includes equitable access obligations in its product development funding agreements. The terms of CEPI’s funding to Novavax included requirements for Novavax to:
- Negotiate a separate agreement for supply of the vaccine to a ‘Global Allocation Body’ (subsequently established as COVAX), supply a certain proportion of the vaccine that it produces to the Global Allocation Body, and not allocate doses to a third party in a way that conflicts with this obligation;
- Price the vaccine at an affordable and sustainable price to achieve equitable access for populations in need;
- Identify one or more geographically dispersed “Trusted Manufacturers” to produce the vaccine under a separate agreement;
- Ensure the vaccine is registered for use in priority countries (as identified by CEPI); and
- Adhere to “open access” publication requirements for project data, as well as guidance on data sharing from the WHO and Wellcome Trust.
Supply and License Agreement with SII
On July 30, 2020, Novavax signed a supply and license agreement with SII that granted a license to SII to develop, manufacture, and commercialize the NVX-CoV2373 vaccine product (marketed under the brand name Covovax). The agreement was amended in September 2020 to additionally allow SII to manufacture the drug substance component of the vaccine, with the adjuvant component to be purchased from Novavax. The agreement includes technology transfer from Novavax to SII, at no cost, to ensure SII is able to manufacture the drug substance and the finished vaccine.
The terms of the licenses to SII allow Novavax to retain its own exclusive territory (details have been redacted from the publicly available agreement) for sales of the vaccine while allowing SII to supply the rest of the world for the duration of the WHO-declared Public Health Emergency of International Concern (PHEIC) in relation to COVID-19. SII may also continue to supply low- and middle-income countries (LMICs) after the end of the PHEIC however Novavax can ensure continued competition in these markets through a provision that allows Novavax to remove countries from SII’s territory if it is able to negotiate better terms with a third party that SII cannot match.
The agreement supports Novavax’s fulfillment of the obligations in its funding agreement with CEPI to identify geographically dispersed “Trusted Manufacturers.” The terms negotiated by Novavax and SII also recognize the requirements under the CEPI agreement for Novavax to sell a certain volume of the vaccine to a “Global Allocation Body”; SII therefore agrees that any finished Covovax vaccine that is produced with drug substance manufactured by any third party may only be made available for purchase by the Covax Facility.
Advance Purchase Agreement with Gavi
On February 18, 2021, Gavi announced that it had signed a memorandum of understanding with Novavax for the supply of a total of 1.1 billion doses of Novavax’s vaccine candidate to the COVAX Facility to be made available through a combination of:
- An advance purchase agreement (APA) subsequently signed between Novavax and Gavi, under which Novavax committed to supplying 350 million vaccine doses, thereby fulfilling its obligations under the funding agreement with CEPI to negotiate an agreement with a “global allocation body”; and
- An agreement with SII made possible by the license agreement and technology transfer from Novavax, and facilitated by a Long Term Agreement with UNICEF under which the vaccines are priced at approximately $3/dose for LMICs.
The vaccines secured under Novavax’s APA with Gavi agreement were intended for supply to high- and upper-middle income countries, as well as the 92 lower-income countries supported by the Gavi COVAX Advance Market Commitment (sometimes referred to as the “AMC 92 countries”). To facilitate equitable access to the vaccines, the purchase prices for individual countries are tiered, with different prices for high-income, upper-middle-income and AMC 92 countries.
The APA supports timely access to the vaccines by requiring Novavax to:
- Make submissions to the WHO for Emergency Use Listing or Prequalification no later than the time of submission to a Stringent Regulatory Authority, and make reasonable efforts to obtain regulatory approvals for use in each COVAX participant country;
- Give first priority in supplying doses to COVAX buyers, in line with Novavax’s obligations in the funding agreement with CEPI; and
- Provide a ‘backstop’ supply if SII is unable to meet its volume commitments under its separate agreement with Gavi.
Notably, Novavax has faced criticism for seemingly not meeting its obligations to prioritize supplies to the COVAX Facility. Looking at this issue in more depth, however, shows the importance of the detailed terms that were negotiated and perhaps the limitations of the collective leverage of the COVAX parties (CEPI and Gavi) for those negotiations. The CEPI funding agreement provided support for certain Novavax manufacturing facilities; the COVAX Facility was able to negotiate priority access for the vaccines containing drug substance manufactured at those facilities. The Novavax manufacturing network has other facilities that did not receive CEPI funding, facilities with which COVAX is likely to have had less negotiating leverage, particularly considering the scale and scope of funding that Novavax received from the U.S. Government and other potential funding and vaccine supply opportunities for Novavax.
Novavax also did not meet its initial regulatory approval targets, resulting in delayed access to the vaccines for COVAX participants, as well as for other countries. Agreements can include provisions that mitigate against these risks to a certain extent. For example, the Gavi APA includes requirements for Novavax to make commercially reasonable efforts to meet timelines set out in a regulatory submission plan, as well as rights for Gavi to amend its purchase commitment if certain conditions are not met. However, product development funding and advance purchase agreements inherently carry a degree of risk that the agreement parties must be willing and able to accept. In the case of the Novavax vaccine, the delay in bringing the product to market has now been compounded by a general decrease in demand for any COVID-19 vaccine, raising questions about how and where the vaccine will be used.
As this analysis shows, not all agreements result in their intended outcomes, but the inclusion of equitable access terms in funding agreements can have a positive downstream impact on further agreements–and therefore increase the chances of equitable access to a final product.
Contracts have an important role in formalizing the partnerships between funders, PDPs and product developers and ensuring alignment on equitable access goals.
GHIAA has developed an infographic providing an overview of the key terms to be included in R&D funding agreements in order to support the achievement of equitable access policies.
Measuring the impact of the implementation of equitable access policies through funding agreement requires the establishment and monitoring of key metrics.
This toolkit has been built based on the data in the MAPGuide and the GHIAA team’s experience of negotiating and implementing agreements. We intend that the toolkit will evolve and expand over time based on input from MAPGuide users and availability of new agreements showing examples of alternative approaches. We welcome ongoing constructive dialogue around these materials and encourage you to contact us or fill in our feedback survey to share your thoughts, questions and suggestions.
Authors: Bridie Telford, Trisha Gupta
First publication date: November 21, 2022