Policy platform for achieving equitable access to COVID vaccines
Warning that the threats, both nationally and internationally, to equitable access to COVID vaccines are significant, David G Legge and Sun Kim set out a policy platform designed to address these threats.
THE drivers of inequity, in terms of access to COVID vaccines, operate between countries and within countries.
Internationally, the promise of equitable rollout of effective COVID vaccines has been diminished by the prospective hoarding associated with massive advance purchase agreements (APAs), largely by high-income countries. The COVAX facility, which had promised more equitable access, has been undercut in terms of both funding and vaccine supplies by these APAs. However, in any case, COVAX does not include upper-middle-income countries (UMICs) and only addresses the priority fraction of the population (likely to be well below the notional 20%).
At the national level, equitable access will depend, first, on the institutional systems for vaccine supply and the delivery of vaccination (in particular, the role of out-of-pocket payment) and, second, on the explicit allocation priorities of the government.
The threats to equitable access are significant. In this article, we set out a policy platform designed to address these threats. Some of the initiatives we propose could (and should) be implemented now, during the COVID pandemic, while others may be more feasible in the longer term and may be more applicable to new vaccines in comparable future circumstances.
Immediate initiatives (for an impact during the current pandemic)
Scaling up manufacturing capacity in low- and middle-income countries (L&MICs), backed up by organised technology transfer arrangements including global and regional cooperation
In the immediate context, we see the scale-up of manufacturing capacity in developing countries as the most critical strategy for promoting equitable access to COVID vaccines.
The simplest way to make this happen would be through widespread (voluntary) sublicensing of the local production of approved vaccines, accompanied by broadly encompassing technology transfer and backed up more generally by organised programmes of technical cooperation, including South-South cooperation. It would be necessary to develop agreed standards for such sublicensing agreements, including full transparency and provision for monitoring process and outcomes.
In the context of 180 candidate vaccines (as of 9 September) and 35 candidate vaccines in the clinical evaluation stage (as of 3 September), vaccine developers are looking to ensure that manufacturing capacity is not a limit in terms of their market share. Agreements between vaccine companies and contract manufacturers, including in developing countries, are being negotiated. Leveraging national ‘loyalty’ to local manufacturers may also assist in gaining market advantage.
Countries which have an effective vaccination system, a large population and a steady number of COVID cases will be particularly attractive to the vaccine developers. Securing a wide range of clinical trial sites is also useful having regard to possible genetic differences of the population and the genetic variants of the virus.
The Brazilian Fundação Oswaldo Cruz (Fiocruz), under the Ministry of Health, has a deal with AstraZeneca. Instituto Butantan, under the Sao Paulo State Secretariat of Health also in Brazil, has a deal with Chinese firm Sinovac. In Indonesia, one of the public pharmaceutical companies owned by the Indonesian government, Bio Farma, made a deal with Sinovac. The Cuban Finlay Institute has a deal with the Russian developer Gamaleya. All of these deals involve clinical trials as well as manufacturing in the target countries.
How effective such deals are likely to be in terms of technology transfer depends on the details of the agreements and the pre-existing state of technological development. The details of many of these deals have not been disclosed.
If local production is to play a role in supporting equitable access, a more organised approach to promoting local production and supporting the associated technology transfer would be needed. Such an approach would need to address landscaping, facilitation and partnership development, and organised support for technology transfer.
Landscaping existing vaccine manufacturing capacity (both public and private entities) in developing countries is a critical first step. The focus of most published vaccine landscapes has been on the sponsors, the technology being deployed and the progress of the vaccine towards marketing approval. The Coalition for Epidemic Preparedness Innovations (CEPI) undertook a survey to figure out the manufacturing capacities across the globe but the focus was on the number of doses the respondents could produce. These surveys do not report on whether the candidate vaccines are being developed by public or private sector entities or how much public infrastructure or funding is being invested in the respective technologies. There are many universities, in most cases public entities, listed as developers, but little or no data about the funding of their research.
There is a clear need for the World Health Organization (WHO), with support from its regional offices and from member states (and the UN’s Technology Access Partnership), to undertake a survey of manufacturing capacity in developing countries, directed towards estimating potential capacity to contribute to COVID vaccine production and the technical support required.
Likewise, if there were to be a stronger focus on technology transfer, greater transparency regarding the conditions provided for under the various manufacturing contracts arranged by vaccine developers such as AstraZeneca would be needed.
A voluntary sublicensing strategy directed at boosting local production for L&MICs would also need organised partnership development, linking vaccine sponsors who are willing to include technology transfer as part of the partnership with local manufacturing enterprises.
We see an urgent need for organised programmes of technical cooperation (global and regional) in support of manufacturing scale-up. In the Asia-Pacific region, the following countries have the capacities for research and development (R&D) and vaccine manufacture: China, Australia, Japan, South Korea, Thailand, Vietnam, Malaysia and Indonesia. Several of these countries have COVID vaccines under development. All of these countries also have scalable manufacturing capacity.
From the perspective of equitable access to the safe, effective and affordable vaccine in time, we see the need for two tracks: first, the immediate development of manufacturing and supply capacity, and second, the longer-term development of pharmaceutical innovation. Countries investing public resources in the development of manufacturing capacities now could in due course build on such infrastructure to support the scaling up of R&D capacity.
Compulsory licensing, including the exploratory deployment of Articles 31, 31bis and 73 of the TRIPS Agreement to facilitate access to key technologies; a moratorium on TRIPS compliance and on the deployment of ISDS in relation to the COVID response
There are limitations to voluntary licensing, which are exemplified by the case of Gilead’s COVID drug, remdesivir. Gilead has negotiated voluntary licences (VLs) with local manufacturers for production and supply of remdesivir to designated L&MIC markets. These VLs ensure that those markets covered by such licences have adequate supplies of low-priced generic remdesivir; they also serve to reduce the pressure for compulsory licences (CLs). However, they also restrict access to the generic version and force UMICs to purchase the originator drug at market rates.
In addition, building local manufacturing capacity by encouraging voluntary sublicensing during the COVID pandemic may not work, particularly if originators are unwilling to support meaningful technology transfer.
In such circumstances, close consideration must be given to the use of compulsory licensing. Compulsory licensing facilitates the local manufacturing of medicines, increases access through the production of low-priced generics, and also depresses the price of the originator through competition. If widely adopted, it can disseminate the production and contribute to equitable and affordable distribution, as was the experience with HIV/AIDS medicines.
In a recent paper, law professors Frederick Abbott and Jerome Reichman propose that countries deploy compulsory licensing to share intellectual property (IP) related to COVID-19 health technologies. They envisage collaborating countries issuing compulsory licences in accordance with the World Trade Organization (WTO)’s Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) and then granting rights under those licences to an international patent pool. They explain that such licensing would be compliant with both TRIPS Article 31 (on compulsory licensing) and Article 73 (national security exception). They acknowledge that the licensing facilities they propose may run into obstacles caused by the opt-out of TRIPS Article 31bis by a number of high-income countries and they propose various avenues for them to ‘opt back in’.
However, it is not clear that compulsory licensing would be a sufficient condition for local vaccine production. Vaccine production requires thousands of manufacturing steps which involve non-patented know-how (trade secrets) as well as high start-up costs.
The potential costs and the delays associated with generic vaccines may be more expensive and take longer than market purchases. Some of those costs and delays could be associated with acquiring non-patented know-how not covered by the CL. This issue of access to non-patented know-how was the reason that technology pooling has been proposed, to pool not only the IP but also other types of knowledge and data. However, it appears that few or none of the vaccine companies have joined WHO’s COVID-19 Technology Access Pool (C-TAP).
The Moderna-Arbutus dispute and the Inovio-VGXI dispute illustrate the significance of technology sharing for the development and production of vaccines. However, it remains open for Moderna to ask the US government to issue a CL for the Arbutus-owned technology that is essential for Moderna’s RNA vaccine production.
Historically, compulsory licensing has often functioned more as a threat rather than as a practical pathway to local production. In most cases, the purpose of the threat was to force the originator to decrease the price or to force it to seek marketing approval in that jurisdiction and supply the medicine in need.
Such threats need to be credible so countries considering this strategy need to think through the practical pathways involved. At the very least, this would involve exploring the deployment of Articles 31, 31bis and 73 of the TRIPS Agreement to facilitate access to key technologies (including beyond patents) and to explore mandatory pooling as proposed by Abbott and Reichman. This might need to be linked to a campaign to encourage countries which have committed not to use Article 31bis, to revoke such commitments. (See further discussion of TRIPS below in the section on longer-term initiatives.)
Making COVAX work (within the bounds of its limited funding and uncertain access to vaccine supplies)
While we argue strongly for a focus on scaling up local production, either voluntarily or through compulsory licensing (or both), we also urge continuing attention to making COVAX work, including encouraging full funding and firm measures to preserve access to vaccine supplies.
However, the restriction of COVAX to the priority population fraction is a limitation, particularly if that fraction is reduced from the notional 20% to 15% and perhaps 10% if funding remains insufficient. Once the priority fraction is served, each country must resort to purchasing on the open market.
A focus on scaling up local production will be needed whether or not COVAX is fully funded and able to secure sufficient supplies.
Transparency by vaccine developers in relation to clinical trial data, costs, prices, patent status and market approval status
In 2019, WHO’s governing World Health Assembly approved resolution WHA72.8 titled ‘Improving the transparency of markets for medicines, vaccines, and other health products’. The resolution urged member states to promote transparency in relation to prices, clinical trial data, market data, patent status and market approval status. It also urged member states to improve national capacities, including through international cooperation, open and collaborative research for development and production of health products, especially in developing countries, as well as for product selection and cost-effective procurement, quality assurance and supply chain management.
The draft resolution had been proposed by Italy and was driven by the increasing costs of pharmaceuticals in the national health service. The increasing cost pressures are partly a response to the growing importance of ‘orphan’ medicines or medicines for ‘rare’ diseases. These are generally expensive medicines (including biopharmaceuticals, gene therapies, cell therapies) with small markets, increasingly associated with personalised medicine. The increasing number of expensive drugs for rare conditions being funded through national pharmaceutical subsidy schemes threatens the sustainability of publicly funded healthcare. Increasing transparency in relation to cost of development, cost of production, clinical data and market data would strengthen governments’ capacity to negotiate appropriate prices and reimbursement arrangements.
On 24 July during the COVID pandemic, Italy officially published the long-anticipated Pricing and Reimbursement Decree, which made it the first country to implement resolution WHA72.8.
The US had strongly opposed resolution WHA72.8 and finally dissociated itself from it. However, transparency has been an issue in the US as well, where pharmaceutical companies have greater discretion in pricing. There is considerable support in the US Congress for greater transparency. A bill introduced in June would allow Americans to monitor tax dollars used by federal agencies to research COVID-19 medical products by creating a single database. The database would include all financial and non-financial federal support provided to drug makers, along with associated clinical trial data, patent information, and the full terms of agreements made between the federal government and manufacturers.
Equitable and affordable access to effective COVID vaccines would be greatly facilitated by mandating pharma transparency (through statute or funding conditionality).
Ensuring equitable and strategic distribution of vaccines within countries
Equitable and strategic allocation of vaccines and access to vaccination opportunity will be important in containing spread and alleviating the burden of both illness and lockdown.
Published commentary on vaccine allocation has encompassed both ‘in country’ and ‘between country’ allocation.
The WHO Allocation Framework was conceived in the context of the COVAX discussions in which case the focus was on identifying the priority population fraction (up to 20%) to be assigned priority in receiving vaccine supplies from COVAX. This framework was largely designed for the allocation between countries, and only for the priority fraction. However, the underlying principles are broadly relevant to within-country allocation and to allocation beyond the putative 20% priority fraction.
The prospect of equitable ‘between country’ allocation of vaccine doses has been progressively weakened with the progress of APAs and the underfunding of COVAX as well as the prospective hoarding of anticipated vaccine supplies. (Under these circumstances, the WHO Framework is largely irrelevant.)
Here our focus is on within-country allocation. While the WHO allocation principles provide general guidance, this is fundamentally an issue for governments. WHO highlights healthcare workers and first responders and then vaccine trial participants. In the second rank, WHO would prioritise the old and those with pre-existing co-morbidities.
We would also urge close attention to:
• low-income families living in crowded circumstances with minimal opportunities for social distancing; this group may include homeless people, some migrants and refugees;
• precarious workers at risk of unemployment and destitution, who may see no alternative to continuing to attend work even when symptomatic;
• frontline workers who are at higher risk of infection during their work but are not considered as formal ‘healthcare workers’; this group may include informal care workers and delivery workers.
Clearly other axes of disadvantage cut across these three groups, including race/ethnicity and gender.
These groups do not appear in the 20% priority population fractions discussed by WHO or Gavi, the Vaccine Alliance, but control of the virus within these groups could make a significant contribution to human rights and to containing the pandemic.
However, without proactive government intervention, existing economic and institutional inequalities may shape vaccination access along very different lines, including where capacity to pay influences access or where powerful interest groups are able to jump the queue.
National and subnational governments must also be held accountable for implementing equitable guidelines for accessing vaccination. This calls for close attention by civil society, hopefully supported by WHO national and regional offices.
Longer-term initiatives (starting now for outcomes in the medium to longer term)
Most of the initiatives proposed above for immediate action (scaling up manufacturing, compulsory licensing, transparency) also call for longer-term policy formation and institutional development. However, there are important policy issues arising from the COVID experience which point towards reforms which may take longer to implement and may be more relevant to the next pandemic than to this one.
Establishing and strengthening public sector innovation and manufacturing in developing countries
We argue that establishing and strengthening public sector pharmaceutical innovation and manufacturing should be a policy priority for developing countries, on either a national or a regional basis. The need for local manufacturing is self-evident in the current context of prospective vaccine hoarding. Building local (or regional) innovation capacity is necessary to ensure countries have the technical expertise to support local manufacturing under compulsory licensing and to facilitate ongoing technology transfer.
As discussed above, many vaccine developers are striking sublicensing deals with vaccine manufacturers in different countries and regions as part of scaling up their manufacturing capability. We presume that distributed manufacturing under voluntary licensing will be associated with technical support from the licence holder. Such deals may serve as bridges for technology transfer.
However, voluntary licences have limitations and such technical support will not be forthcoming for manufacturing under compulsory licences. Accordingly, countries need to invest now in ensuring that they have the technical capacity to launch such manufacturing.
Local (or regional) research and innovation capacity is critical in terms of mediating and facilitating technology transfer, either through individual training and experience or through organisational development.
The reasons for insisting on public sector capacity in both innovation and production arise from: a long history of price gouging; the long-term failure of the private sector to invest in R&D for vaccines; the refusal of private sector originators to participate in C-TAP or in WHO’s Solidarity Vaccine Trial; and the ongoing lack of transparency of private sector originators. The successful experiences of public sector production under compulsory licences, especially in the case of HIV/AIDS medicines in Brazil, Thailand and Indonesia, and the current involvement by these public producers in COVID vaccine development (see below) demonstrate their capacity. We can also note the successful South-South cooperation between the Cuban Finlay Institute under BioCubaFarma and the Brazilian BioManguinhos under Fiocruz, as well as between the Finlay Institute and the Vietnamese Vabiotech.
The idea of public sector innovation and production is not only for the L&MICs. In times past, most high-income countries (HICs) had public pharmaceutical producers, especially for vaccines. Some of them remain, but others have been privatised. In many HICs, there are ongoing campaigns by civil society groups and politicians to (re)nationalise the pharmaceutical industry, including vaccine production. This was the case even before COVID but such calls have increasingly gained relevance and support under the pandemic. Restoring public sector innovation and production capacity in the HICs would also strengthen the capacity for North-South public-public cooperation.
Regional and plurilateral agreements on biopharmaceutical technology transfer and capacity building
There is clearly a need for organised technical assistance programmes in relation to pharma and biopharma (for both R&D and manufacturing). These could be based on bilateral, regional or plurilateral agreements, including South-South or South-North cooperation. This kind of technology transfer could involve scholarships and fellowships and various forms of institutional partnering.
There are already centres of excellence in pharmaceutical (and biopharmaceutical) research and development in the Global South.
In Brazil, the public laboratories Fiocruz and Instituto Butantan are developing their own vaccines for COVID. The Indonesian public laboratory Bio Farma is developing its own candidate vaccine as well. In Thailand, the Government Pharmaceutical Organization (GPO), under the Ministry of Health, is supporting a range of COVID vaccine development initiatives, working with Mahidol University, Chulalongkorn University and the National Center for Genetic Engineering and Biotechnology (BIOTEC). Chula Vaccine Research Center (Chula VRC) under Chulalongkorn University is itself working on three vaccine initiatives. It is working with the University of Pennsylvania on an LNP-mRNA vaccine which is expected to enter clinical evaluation in September. This would make Thailand one of the first L&MICs to undertake clinical evaluation of a COVID vaccine.
In Vietnam, the Vaccine and Biological Production No. 1 Company (Vabiotech), under the Ministry of Health, is developing a recombinant S protein in IC-BEVS vaccine using a protein subunit platform in partnership with Bristol University. This is the first time a vector-based vaccine is under development in Vietnam. This vaccine is expected to enter clinical evaluation in October at the earliest. The company is optimising production procedures for large-scale production of the vaccine and could produce up to 100 million doses a year.
In late August, Cuba’s BioCubaFarm launched a phase 1 clinical trial of one of four vaccines which are under development in that country. Cuba also has been contracted to assist in the trialling and production of the Russian Gamaleya vaccine.
Enterprises such as these could participate in South-South capacity building.
Open licensing as a condition of public funding of research
There has been increasing pressure on universities in many countries to commercialise the products of their research, including through patents or facilitating start-ups. This makes sense in terms of the financial health of universities but actually contributes to significant barriers to affordable access to medicines and vaccines.
The public funding of research should be conditional on an agreed policy of open licensing of intellectual property developed under public funding. This has been a core demand of Universities Allied for Essential Medicines (UAEM) for many years. UAEM has sought to mobilise students to build pressure on university administrations. There is resistance from the universities in relation to this proposition. Further mobilisation and alliance building with university staff, professional staff associations and university students will be needed.
Conditionality tied to public funding of the private sector through grants, subsidies and various tax and regulatory concessions
Civil society organisations have repeatedly highlighted the role of public funding in yielding private patents on COVID technologies. Public Citizen estimates that taxpayers contributed $70.5 million to government agency work that helped lead to the discovery of remdesivir, the experimental COVID-19 therapy patented and developed by Gilead.
The COVAX strategy includes no conditions governing technology transfer or the open pooling of intellectual property and know-how; in fact, it serves to undercut the modest C-TAP proposal. Even before COVID, several civil society groups were advocating for conditionalities tied to public subsidies (national and international) to R&D and production (including through COVAX).
Such conditionalities should address issues of transparency (clinical trials, R&D costs, production costs, prices), fair pricing, sufficient production volumes, and open licensing and participation in technology pooling in times of declared public health emergencies of international concern (PHEICs).
Mandatory participation in ‘Solidarity trials’
In future pandemics, there must be provision for mandatory participation in inclusive comparative trials such as WHO’s Solidarity trials. Participation in such trials should be a condition of public funding and perhaps also linked to WHO prequalification and national/regional marketing approval.
It would be worth exploring provisions within the International Health Regulations giving the WHO Director-General the authority to require participation in comparative clinical trials in the event of pandemics declared to be PHEICs.
Using the TRIPS Agreement (and making it easier to use)
The provisions for compulsory licensing and government use in the TRIPS Agreement are important resources in the campaign for equitable and affordable access. Compulsory licensing may serve simply as a threat to encourage pharmaceutical companies to curb prices or to seek marketing approval. However, this provision is only available if countries’ domestic legislation provides appropriate authority and procedures for the deployment of compulsory licensing as needed. Too many developing countries have been persuaded or forced to adopt IP legislation which does not facilitate the full deployment of the flexibilities which are provided for in the TRIPS Agreement.
Further, Article 73 of TRIPS provides for security exceptions. ‘Nothing in this Agreement shall be construed: …(b) to prevent a Member from taking any action which it considers necessary for the protection of its essential security interests … taken in time of war or other emergency in international relations.’ It appears self-evident that a pandemic threatens the essential security interests of countries. (For a discussion of the application of this provision to compulsory licensing, see: Frederick Abbott, ‘The TRIPS Agreement Article 73 Security Exceptions and the COVID-19 Pandemic’, South Centre Research Paper 116, August 2020.)
Article 31 of TRIPS provides for compulsory licensing for domestic manufacturing but not all countries have domestic manufacturing capacity. It was for this reason that, following the 2001 WTO Doha Declaration on the TRIPS Agreement and Public Health, the Agreement was amended (through Article 31bis) to provide for compulsory licensing for export, involving a compulsory licence for both the exporter and the importer. Unfortunately, due to the way this provision was conceived, it has proved to be extremely difficult to implement. The renegotiation of TRIPS to facilitate compulsory licensing for export is urgently needed although it is not clear when an opportunity to achieve this will arise. A further impediment to the wider use of Article 31bis is the fact that a range of high-income countries committed to not using it following its adoption. Writing on the Medicines Law & Policy website, Christopher Garrison has argued that revoking these opt-outs would greatly increase the scale on which compulsory licensing for export can be used and thus further reduce prices.
It is important to continue to advocate for countries to ensure that their national law provides for the full deployment of the existing flexibilities of TRIPS and for necessary revisions of the Agreement, including around the use of Article 31bis. This kind of advocacy is part of building a global constituency to ensure the necessary reforms are achieved.
It would also be worth exploring the possibility of including provisions in the TRIPS Agreement which enable the WHO Director-General to require technology pooling in the event of pandemics which are declared to be PHEICs.
In the first instance, campaigning around the need for a moratorium on TRIPS obligations in the pandemic context (as suggested by the South Centre) would help to build such a constituency.
In a similar vein, the international humanitarian organisation Medecins Sans Frontieres (MSF) is campaigning around ‘No patents or profiteering in a pandemic’. ‘MSF is calling for no patents or profiteering on any tests, treatments, or vaccines used for COVID-19.’
‘Pharmaceutical and diagnostic companies must commit to not seek nor enforce patents. If they won’t do the right thing, then governments can take action,’ urges MSF.
Continuing advocacy around delinking and R&D treaty proposal
The full delinking of phar-maceutical R&D and the negotiation of an R&D treaty (see box) do not appear likely in the short term. However, the logic for delinking can only become more obvious as support for implementing universal health coverage (UHC) grows. Financial protection for consumers is a key principle of UHC and it is widely recognised that single-payer funding is the most strategic and efficient way of achieving financial protection. In this context, the savings associated with delinking and public funding of R&D will be increasingly evident to national finance officials.
It will be important to keep this conversation alive.
David Legge, MD, scholar emeritus at La Trobe University (Melbourne, Australia), has practised, researched and taught in public health, health policy and global health for many years. He has been active in the People’s Health Movement (PHM), including its WHO Watch project, since its creation in 2000. Sun Kim, MS, PhD, Director of the Health Policy Research Center at the People’s Health Institute (Seoul, South Korea), has researched vulnerability and healthcare, and access to medicines and pharmaceutical production, from a political economy of health perspective. She has served as South East Asia and Pacific region coordinator of PHM since 2019.
The above is extracted from ‘Equitable access to Covid vaccines: cooperation around research and production capacity is critical’, a working paper prepared for the 75th Anniversary Nagasaki Nuclear-Pandemic Nexus. The full paper including references is available on the PHM website at https://phmovement.org/wp-content/uploads2020/10/Legge-Kim_EquitableAccess2CovidVaccine_ 2020-1001-1.pdf
*Third World Resurgence No. 345/346, 2020, pp 41-47