SouthNews: South Centre promotes discussion on local production for vaccines and therapeutics in developing countries

The South Centre organized a panel workshop on “Pharmaceutical Sovereignty” as part of the Summit on Intellectual Property (IP) and Access to Medicines: The Pandemic Edition, organized by International Treatment Preparedness Coalition (ITPC) in Istanbul, Turkey, from 19 to 21 July 2022.

The workshop focused on the renewed interest in and developments regarding the local and regional production of health technologies in developing countries. The hoarding of essential COVID-19 tests, treatments and vaccines by developed countries and the interdependence and weaknesses of global supply chains have highlighted the importance of pharmaceutical sovereignty. Technology sharing has been outright refused by some companies while others entered secret, bilateral deals with a limited number of manufacturers. The negotiation at the World Trade Organization (WTO) to waive intellectual property rights during the COVID-19 pandemic to facilitate access and production of COVID-19 vaccines, therapeutics and diagnostics has been difficult, with a limited waiver agreed for COVID-19 vaccines as part of the Ministerial Conference in July 2022. To date few agreements have been signed under the auspices of the World Health Organization (WHO)’s COVID-19 Technology Access Pool (C-TAP) initiative that was set up in 2020 to facilitate the timely, equitable and affordable use of COVID-19 health products. At the same time, a promising new technology transfer and training mechanism is being advanced with support of the WHO to build capacity in developing countries on mRNA technology for vaccines. Firms producing COVID-19 vaccines, however, are reluctant to cooperate with the mRNA hub.

The workshop discussed past experiences at building and sustaining local production capacities in developing countries, focusing on examples from Brazil and in the African continent, and also the current experience with the mRNA hub in South Africa, as well as new opportunities for local production. Enabling factors and challenges for local production were considered. Participants also reflected on the limited outcome of the negotiations on a WTO Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) waiver for vaccines and on-going negotiations to extend it to therapeutics and diagnostics.

Dr. Petro Terblanche, Managing Director of Afrigen Biologics, presented the experience in the mRNA hub, a public/private partnership consortium to advance mRNA vaccine development and manufacturing for low- and middle-income countries (LMICs). The objectives are to establish or enhance sustainable mRNA vaccine manufacturing capacity in regions with no or limited capacity; introduce new technologies in LMICs and promote regional research and development; strengthen regional biomanufacturing know-how and workforce development; and develop regulatory capabilities and workforce to support and accelerate regional approval and distribution of mRNA vaccines.

Importantly, the mRNA technology that currently is being used to tackle COVID-19, can also be adapted to address other diseases, such as HIV, tuberculosis, malaria and leishmaniasis. With technological capacity, developing countries can address their own needs by building partnerships with others. The Afrigen-based mRNA vaccine technology transfer programme to LMICs will provide sufficient transfer of know-how to allow a competent technology transfer recipient to successfully manufacture and release mRNA vaccines at scale, to support further clinical development, to obtain regional and national market authorization(s) with WHO prequalification, and to sustainably meet local and regional vaccine demands. The mRNA hub is designed to be a multi-product platform and has already started to review a pipeline for mRNA vaccines relevant for the burden of diseases in LMICs. In June 2021 the South Africa mRNA hub was established at Afrigen. In September 2021 the WHO/PAHO announced the selection of Argentina and Brazil as spokes in Latin America. In 2022 the WHO has announced as spokes Egypt, Kenya, India, Nigeria, Senegal, South Africa, Tunisia, Bangladesh, Indonesia, Pakistan, Serbia, Vietnam and Ukraine (see Figure below), and a global biomanufacturing training hub in Republic of Korea. Introductory training on mRNA technology has been initiated at the Afrigen mRNA technology transfer hub.

Source: Presentation by Dr. Terblanche at the South Centre workshop

Dr. Terblanche spoke of the progress achieved in the Afrigen mRNA hub. Afrigen and the University of the Witwatersrand have produced the first mRNA COVID-19 vaccine candidate on the African continent. The first priority is for the product to reach market authorization.

In terms of technology transfer, she noted that viral vector has been the most transferred vaccine platform for facilitating local vaccine production since the start of the COVID-19 pandemic. Technology transfers have mainly been for fill & finish in Africa, while in Asia for end-to-end production, and in the Middle East and Latin America for fill & finish and end-to-end production.

The intellectual property landscape on mRNA technology is rapidly evolving. Partners operating in the mRNA technology transfer programme need freedom to operate. Patents can be an obstacle. New patent applications filed in developing countries that seem relevant to the mRNA technology transfer hub programme have recently been identified; some are in the “international phase” through the Patent Cooperation Treaty and therefore it is not clear in which developing countries they will be filed. In some patent applications the claims are very broad and should be narrowed when they enter the national stage. However, in some developing countries, such as South Africa that currently does not undertake substantive patent examination, the patents will likely be granted. For the time being patents on the underlying mRNA vaccine technology have not been filed or granted in most low- and middle-income countries, including in key countries that are participating in the mRNA Technology Transfer Hub Programme. However, there are patents/applications on COVID-19 vaccines that have been filed in some LMICs. Where granted, the key issue will be what those patents will cover (i.e. breadth of claims) in each country and whether the patent holder(s) intends to enforce such patents.

Some of the important factors for the success of the mRNA technology transfer programme are:

To build sustained political will and actions in support of technology transfer and the establishment of sustainable ecosystems for vaccine manufacturing in LMICs;
To ensure the full financing of the mRNA Tech Transfer Hub Programme and the development of the needed technologies and capabilities;
To ensure that relevant LMIC governments and regional bodies contribute to any investments that may be needed to develop the hub/spokes and build resilience;
To secure the commitment of governments, regional bodies and relevant international organizations to the procurement of vaccines emanating from the Programme to encourage private sector investment and ensure sustainability;
To address demand barriers including vaccine hesitancy;
To address freedom to operate in relation to intellectual property rights.

Mr. Patrick Tippoo, Head of Science and Innovation, Biovac, and Executive Director of the Africa Vaccine Manufacturers Initiative (AVMI), provided a historical overview of efforts on vaccine production in Africa, noting that there is established but limited vaccine manufacturing capacity in the continent. There is also limited research and development capacity and dependence on technology transfers. There is a need to break the cycle of dependency. Availability of financing, skilled workforce, secured procurement and partnerships between the public and private sector and multilateral agencies are essential for success and for sustaining vaccine production capacities. It is also important to strengthen the regional vaccine regulatory capacity. Mr. Tippoo further provided information on partnerships that have supported the expansion of Biovac’s existing vaccine manufacturing plant capacity.

Dr. Gabriela Costa Chavez, independent consultant, provided a review of the experience of public pharmaceutical manufacturers in Brazil. There are around 18 public laboratories in Brazil with potential to produce about 16.6 billion pharmaceutical units/year. From the 1990s to date, a number of policies influenced or supported local production, including in the mid 1990s the obligation to provide HIV treatment through the Public Health System (SUS), investments by the Ministry of Health in public manufacturers (expansion of production capacity), the supply of medicines for primary health care by public manufacturers and, in 1999, the introduction of a law on generics to promote a national generic industry based on the importation of Active Pharmaceutical Ingredients (APIs). Dr. Costa explained how public production has helped address situations of insufficient supply or discontinuation of production and has built capacity to produce serum for venomous animals and the development of formulations for neglected tropical diseases. For example, Farmanguinhos/Fiocruz and Drugs for Neglected Diseases initiative (DNDi) development of a fixed-dose combination of artesunate+mefloquine (ASMQ FDC) for malaria, and Lafepe and DNDi development of a pediatric dosage form (12.5mg) of benznidazol. Local producers have tried to overcome patent barriers by filing pre-grant oppositions (third party observations); for example, Farmanguinhos/Fiocruz filed pre-grant oppositions in 2005 against patent applications for Lopinavir/ritonavir, in 2006 for Tenofovir and in 2017 on the patent application for Sofosbuvir.

Brazil local manufacturers have also engaged in COVID-19 vaccine production. One route has been through agreements for local production, as in the case of the Oxford/Astrazeneca-Fiocruz collaboration. In June 2021 a technology transfer agreement was signed between Fiocruz and Oxford-Astrazeneca whereby Fiocruz received cell and virus banks for the national production of the active ingredient. In January 2022 the national regulatory authority, ANVISA, approved the registration of the vaccine, allowing for Brazil to have a 100% nationally produced vaccine. Currently Brazil is creating a Health Biotechnology Industrial Complex, with the expectation that the production capacity can reach 120 million vials of vaccines and biopharmaceuticals/year and may exceed 600 million doses/year. In 2021, the Institute of Technology in Immunobiologicals of the Oswaldo Cruz Foundation (Bio-Manguinhos/Fiocruz) was selected by the WHO regional office as one of two partner centers for the mRNA hub in Latin America to produce COVID-19 vaccines. In May 2022, Fiocruz entered into a partnership with Merck Sharp & Dome (MSD) to produce Molnupiravir in Brazil. Fiocruz will be responsible for the storage, administration, labeling, packaging, testing, release, import and supply of this drug for the Unified Health System of Brazil.

Dr. Costa noted that Brazil continues to be highly dependent on the importation of APIs and medicines, bringing continuous challenges to respond to health needs. Moreover, technology transfer poses challenges in terms of the technological capacity of local producers. Despite those challenges, Brazil has shown that having some production capacity in place, specially from public manufacturers, has allowed the government to respond to some of the health problems in the country. However, Brazil’s experience shows the negative effects of the implementation of the TRIPS Agreement in the pharmaceutical market as it has led to high prices of certain medicines.

Dr. Costa offered some lessons from partnerships for the local production of COVID-19 vaccines noting that beyond the installed production capacity the following need to be considered:

Ability to carry out technological prospecting;
Legal framework that enables the contracting of technology in the development phase;
Ability to conduct clinical studies;
Regulatory pathway for the approval/authorization of these technologies.

Dr. German Velasquez, Senior Advisor, Health and Policy, South Centre, provided a reflection on the context for and outcome of the negotiations in WTO to waive intellectual property related to vaccines, therapeutics and diagnostics for COVID-19.

Access to medicines is today a juggling game where the ball of the "South" is on the ground. A game where only markets, the pharmaceutical industry and the rules of the WTO count. Between 2021 and 2022, 20 months passed in which non-governmental organizations from all over the world mobilized to say: "Lives before profits... the TRIPS exception now!”. Many members of the WTO were deaf, and the 12^th Ministerial Conference demonstrated its inability to listen. The developed countries' negotiating strategy was to create a labyrinth that delayed the debate in order to weaken the possible outcome over time. Nothing new. In 1998 at the WTO ministerial conference, Nelson Mandela said: "We must be frank in our assessment of the results of the Uruguay Round. Developing countries were not able to ensure that the rules reflected their realities." The imbalance between the urgent needs of the South and the trade interests of the North is evident. Twenty months of "negotiations" were like a dialogue of the deaf that finally emptied the proposal from India and South Africa supported by 100 developing countries of its content. In the end it was not an exemption to intellectual property during the time of the pandemic, but a decision that adds little room for maneuver. It would apply only to exports of vaccines but not to diagnostics and treatments.

Some have said that the TRIPS Decision was a compromise cooked up in the so-called "green room" of the WTO without wide participation of the WTO membership. According to the glossary posted on the WTO website, the ‘green room’ is: "The informal name of the director-general's conference room. It is used to refer to meetings of 20-40 delegations, usually at the level of heads of delegations. (...) can be called by the minister chairing the conference as well as the director-general". The delegates of the United States of America, the European Union, Canada and Japan, sit there in a permanent manner while the rest of the WTO members selectively participate in the negotiations when called for. Some say that the expression "green room" comes from a practice in English theatre at the turn of the last century where there was a quiet room where the main actor of the play could rest and concentrate and think while the rest of the troupe waited in the noisy corridors of the theatre's back room. Afterwards it was all who performed the play, which does not seem to be the case with the contemporary version of the WTO's "green room".

The multilateral negotiating process on the TRIPS waiver request has been too slow and unbalanced to respond to the urgent needs of the largest part of the world population. WTO Members can and should consider other options to respond to the current (and future) pandemic(s). They can and should, in particular:

use compulsory licensing, including for government non-commercial use, without being subject to limitations regarding products, duration of the authorization and re-exportation/ importation as established in the TRIPS Decision;
invoke the national security exception contained in article 73 (b) of the TRIPS Agreement;
interpret article 30 of the TRIPS Agreement to allow for the manufacture and export of such products;
allow for the parallel importation of products manufactured under a compulsory license.

Dr. Viviana Munoz Tellez, Programme Coordinator, Health, Intellectual Property and Biodiversity, South Centre, identified enabling factors and challenges for developing local capacities to achieve pharmaceutical sovereignty.

There has been a historical trend in developing countries towards de-industrialization and import dependency in the pharmaceutical sector. This has meant a loss of productive capacities and reduced scope for technological learning, accompanied by reduced intervention by governments/regulators in pharmaceutical markets. Multinational enterprises have taken a lead role, with profit-maximizing and market capitalization objectives driving their overall research and development investments & pricing strategies. Moreover, global supply chains remain opaque and unstable. Options for low-priced medicines and other health technologies are reduced with the changing market interests of major global generic suppliers.

The COVID-19 pandemic offered an opportunity to foster local production capacities with a renewed recognition of the value of learning by doing and of greater self-reliance to respond to local unmet health priorities and empowerment to have stable supply and increased procurement options.

Some of the challenges for building local production capacity are to gain access to technology, raw materials and know-how, adequately define the public and private sector roles and create synergies between them, develop economies of scale (for example through regional production and procurement) and access to financing. There is also a need to build a supportive international institutional, financial and regulatory environment.

The panel presentations were followed by questions and answers, and an open group discussion on regional and national experiences.

Author: Viviana Munoz Tellez is Coordinator of the Health, Intellectual Property and Biodiversity Programme of the South Centre.

SOUTHNEWS

South Centre promotes discussion on local production for vaccines and therapeutics in developing countries