Sustainable vaccine manufacturing in low- and middle-Income countries.

The sustainable manufacturing of vaccines in developing countries is critical to increasing equitable access to vaccines and pandemic preparedness globally. Sustainable manufacturing requires that organizations engaged in the development, production and supply of vaccines have viable business models and incentives to manufacture vaccine products. The expanding manufacturing capabilities and capacities of developing countries vaccine manufacturers (DCVMs) are increasingly positioning these organizations to meet the national and regional public health needs in developing countries; however, key industry challenges such as regulatory barriers, low prices and demand uncertainty for vaccine products, and limited R&D funding threaten the long-term viability of vaccine manufacturers. This study assesses the technical capabilities, manufacturing capacities, and aspirational plans of DCVMs, exemplifying the business models and strategies undertaken to sustainably manufacture vaccines in developing countries. The public health importance of a healthy vaccine industry which enables manufacturers is discussed throughout. Vaccine manufacturers reported diverse product portfolios and R&D pipelines and utilized an array of vaccine technology platforms. Large manufacturing capacities were reported, a critical factor in manufacturers achieving economies of scale and supplying large volumes of vaccine doses to the world's most populous regions. Partnerships and collaboration within the industry and with international organizations along the vaccine value-chain were cited with high frequency. Manufacturers also reported aspirational plans to enter new markets, acquire new technologies and invest in the development of novel and improved vaccines. As DCVMs aim to have an increasing impact on the global vaccine ecosystem, a coordinated multi-stakeholder approach is required alleviate critical industry barriers to ensure that all efforts produce vaccines are sustainable and enable developing countries to realize the public health benefit of vaccines.

Developing-country vaccine manufacturers' technical capabilities can make a difference in global immunization.

Members of the Developing Countries Vaccine Manufacturers' Network (DCVMN) have been actively engaged in the development of COVID-19 vaccine candidates. According to the WHO COVID-19 vaccine landscape updated on 29 December 2020, 18 member manufacturers had vaccines in preclinical or clinical trials, including three members with candidates in Phase III trials. Once successful candidates have been identified there will be a need for large scale vaccine manufacturing and supply, in which DCVMN member manufacturers can play a key role. In an internal survey in 2019, DCVMN members reported the capability to supply over 3.5 billion vaccine doses annually, and the provision of over 50 distinct vaccines to 170 countries. To describe the capabilities of DCVMN member manufacturers more precisely, a 121-question survey was circulated to 41 Network members. The survey assessed the manufacturers' capabilities in utilizing various technology platforms, cell cultures and filling technologies, in addition to their capacities for manufacturing drug products. The survey also evaluated manufacturers' preparedness to dedicate existing capacities to COVID-19 vaccine production. Results revealed that sampled manufacturers have strong capabilities for manufacturing vaccines based on recombinant technologies, particularly with mammalian cells, and microbial and yeast expression systems. Capabilities in utilizing cell cultures were distributed across multiple cell types, however manufacturing capacities with Vero and CHO cells were prominent. Formulating and filling findings illustrated further large-scale capabilities of Network members. Sampled manufacturers reported that over 50% of their capacity for vaccine manufacturing could be dedicated to COVID-19 vaccine production.

COVID-19 vaccine capacity: Challenges and mitigation - The DCVMN perspective.

Vaccine manufacturers from developing countries have a proven track record of developing, producing, and supplying high-quality vaccines globally. However, due to the complexity of vaccine manufacturing, numerous stakeholder organizations support manufacturers across a variety of functions. To optimize the support from stakeholders it is instrumental to first understand which manufacturing processes these manufacturers require support for and what support functions are most beneficial. To this end, the Developing Countries Vaccine Manufacturers Network designed a comprehensive survey to assess the specific needs of the Network's member organizations. We found that almost all sampled manufacturers are interested in obtaining funding or technology transfers for COVID-19 vaccines. Furthermore, results indicated that manufacturers have a strong appetite for modern technology platforms, particularly RNA technologies. Scale-up, phase III clinical trials, and formulation were also key processes for which manufacturers require support.

Vaccines for a healthy future: 21st DCVMN Annual General Meeting 2020 report.

The Developing Countries Vaccine Manufacturers' Network held its 21st Annual General Meeting virtually in November 2020 given the COVID-19 pandemic. Vaccine manufacturing experts, leaders from local and global public health organizations and multilateral organizations, through diverse presentations, questions and answers, focused on the pandemic and the response of vaccine manufacturers where many are engaged in research and development and production agreements. The pandemic is expanding rapidly which makes the global availability and equitable access to safe and effective COVID-19 vaccines critical. Strategies put in place include the establishment of the Access to COVID-19 Tools Accelerator (ACT-A) within which the COVAX facility aims to distribute 2 billion COVID-19 vaccine doses by the end of 2021, with procurement mechanisms already being established. At the same time, regulatory authorities have emergency use authorizations aimed at the rapid approval of safe and effective vaccines, with a push for harmonization in regulatory approaches being advocated. The Meeting was also apprised of other innovations being developed for vaccines including multi-array patches for easier vaccine application, increased heat stability for mitigating cold chain and storage challenges, the barcoding of primary packaging for enhancing vaccine traceability, and gathering data for decision-making. Over time, these innovations will facilitate the widespread availability and equitable access of vaccines including those addressing epidemics and pandemics. In addition, a number of manufacturers described technologies they have for accelerating vaccine manufacturing and supply globally. Overall, there was agreement that manufacturers from developing countries play a critical role in the global research, development and supply of vaccines for a healthy future, with increasing collaboration and partnering between them a growing strength.

Emerging manufacturers engagements in the COVID -19 vaccine research, development and supply.

The World Health Organization declared the COVID-19 disease as a pandemic requiring a rapid response. Through online search, direct communication with network members and an internal survey, engagements of developing countries' vaccine manufacturers' network members in the research and development of COVID-19 vaccines and their capacities in the manufacturing, fill-finish and distribution of vaccines were assessed. Currently, 19 network members engaged in research and development of COVID-19 vaccines, using six principal technology platforms. In addition, an internal survey showed that the number of vaccines supplied collectively by 37 members, in 2018-19, was about 3.5 billion doses annually. Almost a third of network members having vaccines prequalified by the World Health Organization comply with international regulations and mechanisms to distribute vaccines across borders. The use of existing manufacturing, fill-finish and distribution capabilities can support an efficient roll-out of vaccines against COVID-19, while maintaining supply security of existing vaccines for on-going immunization programmes.

Advancing innovation for vaccine manufacturers from developing countries: Prioritization, barriers, opportunities.

Development of novel vaccines and improving existing vaccines is critical to addressing areas of unmet or under-addressed health needs globally and to improving existing vaccination coverage and equity. However, vaccine innovation is costly and highly complex. To understand how vaccine manufacturers from developing countries approach innovation, a survey was conducted among company members of the Developing Countries Vaccine Manufacturers Network, in collaboration with the Clinton Health Access Initiative. The survey confirmed that vaccine manufacturers from developing countries are committed to vaccine innovation: 95% of respondents have interest in pursuing vaccine innovation, with strategies targeted towards supplying to low- and middle-income countries. Key barriers to innovation were also surveyed, with respondents highlighting challenges regarding access to in-licensing or joint venture partnerships, financing, and regulatory barriers. Opportunities for innovation are also discussed.