How to accelerate the supply of vaccines to all populations worldwide? Part II: Initial industry lessons learned and detailed technical reflections leveraging the COVID-19 situation.

Vaccine discovery and vaccination against preventable diseases are one of most important achievements of the human race. While medical, scientific & technological advancements have kept in pace and found their way into treatment options for a vast majority of diseases, vaccines as a prevention tool in the public health realm are found languishing in the gap between such innovations and their easy availability/accessibility to vulnerable populations. This paradox has been best highlighted during the unprecedented crisis of the COVID-19 pandemic. As part of a two series publication on the vaccine industry's view on how to accelerate the availability of vaccines worldwide, this paper offers a deep dive into detailed proposals to enable this objective. These first-of-its-kind technical proposals gleaned from challenges and learnings from the COVID-19 pandemic are applicable to vaccines that are already on the market for routine pathogens as well as for production of new(er) vaccines for emerging pathogens with a public health threat potential. The technical proposals offer feasible and sustainable solutions in pivotal areas such as process validation, comparability, stability, post-approval changes, release testing, packaging, genetically modified organisms and variants, which are linked to manufacturing and quality control of vaccines. Ultimately these proposals aim to ease high regulatory complexity and heterogeneity surrounding the manufacturing & distribution of vaccines, by advocating the use of (1) Science and Risk based approaches, (2) global regulatory harmonization, (3) use of reliance, work-sharing, and recognition processes and (4) digitalization. Capitalizing & collaborating on such new-world advancements into the science of vaccines will eventually benefit the world by turning vaccines into vaccination, ensuring the health of everyone.

How to accelerate the supply of vaccines to all populations worldwide? Part I: Initial industry lessons learned and practical overarching proposals leveraging the COVID-19 situation.

The COVID-19 pandemic has shown itself to be an unprecedented challenge for vaccines which are widely recognized as the most important tool to exit this pandemic. We have witnessed vaccine scientists, developers, manufacturers, and stakeholders deliver several vaccines in just about a year. This is an unprecedented achievement in an environment that was not ready to manage such a global public health crisis. Indeed, the pandemic has highlighted some hurdles that need to be addressed in the system in order to streamline the regulatory processes and be in a situation where life-saving pharmaceutical solutions such as vaccines can be delivered quickly and equitably to people across the globe. More precisely, trade-offs had to be made between the need for regulatory flexibility in the requirements for manufacturing and controls to enable rapid availability of large volumes of vaccines vs the increased stringency and the lack of harmonization in the regulatory environment for vaccines globally. It is also characterized by a high heterogeneity in terms of review and approval processes, limiting equitable and timely access. We review and highlight the challenges relating to several topics, including process validation, comparability, stability, post-approval-changes, release testing, packaging, genetically modified organisms and variants. We see four areas for accelerating access to vaccines which provide solutions for the regulatory concerns, (1) science- and risk-based approaches, (2) global regulatory harmonization, (3) use of reliance, work-sharing, and recognition processes and (4) digitalization. These solutions are not new and have been previously highlighted. In recent months, we have seen some progress at the health authority level, but still much needs to be done. It is now time to reflect on the first lessons learnt from a devastating pandemic to ultimately ensure quick and wide access to medicines and vaccines for the citizens and patients.

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.

The role of manufacturers in the implementation of global traceability standards in the supply chain to combat vaccine counterfeiting and enhance safety monitoring.

The counterfeiting of vaccines is an increasing problem globally with the safety of persons vaccinated, the trust in vaccines generally and the associated reputation of vaccine manufacturers and regulatory agencies at risk. This risk is especially critical with the on-going development of COVID-19 vaccines. The ability to track and trace vaccines through the vaccine supply chain down to persons vaccinated has to be enhanced. In this context of traceability, the global immunization community has recently set the barcoding of the primary packaging of vaccines, specifically vaccine vials and pre-filled syringes, as a top priority. Emerging vaccine manufacturers are already engaged in investigating ways to incorporate barcoding in their labelling and packaging using GS1 international standards. A specific pilot taking place in Indonesia by the national vaccine manufacturer, Bio Farma, shows the innovation of barcoding on primary packaging already underway with a relatively modest level of investment and success at this stage. This article highlights the efforts of industry and governments on the value of traceability and introduction to 2D barcodes. Access to financial resources and support from the international immunization community would accelerate such innovations leading to enhanced security of the vaccine supply chain.