1. Background and Context

This roundtable was the second in the series of roundtable discussions hosted by the Nelson Mandela School of Public Governance at the University of Cape Town (UCT), to make policy recommendations for the development of regional value chains in the healthcare and pharmaceutical sector across Africa through leveraging opportunities presented by the implementation of the African Continental Free Trade Agreement (AfCFTA).

Global vaccine purchase data indicates potential supply security challenges in two key areas: 1) very few suppliers of individual vaccines or vaccine components and 2) countries limiting their available choices by relying predominantly on supply from certain manufacturers or manufacturer groups.1

The monopoly of the small number of manufacturers in just a few countries producing health tools needs to be broken. Protectionist approaches to manufacturing and trade will only aid the spread of the COVID-19 virus. Instead, we must act globally to ensure that tools such as vaccines can be produced worldwide if we are to end the acute stage of this pandemic. As WHO Director-General Dr Tedros Adhanom Ghebreyesus puts it: “No other event like the COVID-19 pandemic has shown that reliance on a few companies to supply global public goods is limiting, and dangerous.”2

The first roundtable discussion focused on the formulation aspects of the vaccine manufacturing process, which most of the vaccine manufacturing initiatives and partnerships in Africa have focused on to date. This focus is very much needed and a necessary step towards developing local African vaccine manufacturing capacity – however, this does not alleviate the external dependency since the ‘drug substance’ (DS) or active ingredient for the vaccines still needs to be imported. Access to the DS remains a challenge due to intellectual property arrangements as well as limited capacity to manufacture it in Africa. Recently, however, an announcement made by Moderna regarding the first mRNA manufacturing facility to be established in Kenya looks to change the manufacturing landscape. It is unclear at this stage as to what the practical arrangements will be and what the benefits to the market will be in terms of local capacity building. The facility will focus on manufacturing vaccine drug substances, with potential plans to expand its capacity to also include the filling of vaccine vials “as early as 2023, subject to demand.”3

It also announced a new initiative “that will offer researchers use of Moderna’s mRNA technology to explore new vaccines against emerging or neglected infectious diseases.” This will allow researchers globally access to the company’s “preclinical manufacturing capabilities and research and development expertise.”4

The manufacturing of vaccines is a complex process that is very different to that of small molecules used in medicines. The drug substance/API production stage is commonly described as a two-phase process. Upstream processing includes cell isolation and cultivation (in some cases a process of direct DNA synthesis is adopted at this stage), followed by the cell banking and culture expansion steps using bioreactors. The second phase (downstream) includes the cell harvesting and purification steps, which entails the cell disruption, purification and polishing steps.5

Vaccines are often produced using raw materials that are obtained from biological production processes (e.g., yeast extract, natural or

1 WHO. (Dec, 2019). Global Vaccine Market Report 2 Dr Alakija, A. (2022, March 10). Opinion: It’s time to smash the bottlenecks to global health care. https://www.devex.com/ news/opinion-it-s-time-to-smash-the-bottlenecks-to-global-health-care-102795#:~:text=https%3A//www.devex,Find%20 a%20service 3 Green, A. (2022, March 10). The looming COVID-19 treatment equity gap. https://www.devex.com/news/the-loomingcovid-19-treatment-equity-gap-102816#.YjB2FcGI7Ks.twitter 4 Green, A. (2022, March 10). The looming COVID-19 treatment equity gap. https://www.devex.com/news/the-loomingcovid-19-treatment-equity-gap-102816#.YjB2FcGI7Ks.twitter 5 Sarkis et al., 2021; Alzahrani & Harris, 2020; Puetz & Wurm, 2019

recombinant enzymes). These materials add inherent biological variability to the manufacturing or analytical processes. Due to their specialized nature, these raw materials may be limited in supply, and subject to shortages or process changes as suppliers change methods to increase productivity or their bottom line.6

Plotkin, et al. 7 argue that equipment and skilled labour that are not available in low-resource countries will need to be imported, and maintained or replaced, for years if not decades. Countries seeking to augment or localize vaccine supply will need to invest heavily in facilities, equipment, skilled labour and ongoing quality management with a long time horizon – requiring ‘‘patient capital” and development of in-house technical skills. Countries or companies must also carefully weigh the systemic risks and inherent difficulties in high-quality vaccine manufacturing and be prepared that returns may only accrue in the long-term, if at all.

The first roundtable discussion revealed that there are at least 150-200 production inputs that are required in the vaccine production process. Many of these production inputs are common across different vaccine platforms and therefore opportunities for localisation would need to be investigated. The Futures report also identified various opportunities across the vaccine value chain, both in terms of production and service inputs, that could be potentially localized.

Some would argue that African countries should not even pursue developing DS manufacturing capabilities at all due to the level of complexity and the late stage that the continent would be entering these industries.

In this roundtable discussion, key questions were asked to understand the actual processes involved in DS manufacturing from entrepreneurs and experts who are involved in this area as well as experts involved in developing manufacturing equipment for DS manufacturing.

6 Adapted from Plotkin, S. et al. (2017). The complexity and cost of vaccine manufacturing – an overview. Vaccine. 7 Adapted from Plotkin, S. et al. (2017). The complexity and cost of vaccine manufacturing – an overview. Vaccine.