SESSION ONE: Drug Substance Development & Manufacturing Processes

Dr Agwale indicated that he would be sharing his experience from the last 15 years of producing vaccine candidates for the unique diseases that affect the African continent. According to recent announcements, Africa currently has facilities that can produce 4.5 billion doses of vaccines per annum (referring to the finished product); the question is how we feed these facilities (with active drug substance, which is currently mostly being imported).

The goal is to have Africa produce 60% of its own vaccines by 2040 (African CDC target); which translates to 1.5 billion doses per annum. Therefore, there are major plans to put facilities on the ground. In terms of distribution, in South Africa alone there are four major initiatives: Aspen aims to produce 500 million doses per annum, NAT SA will be producing one billion doses per annum, Afrigen’s target is 250 million doses per annum and Biovac aims to produce 100 million doses per annum. Morocco aims to produce 500 million doses, Egypt is targeting 300 million doses and Senegal is aiming for 250 million doses per annum. This demonstrates that Africa has the capacity to fill-finish 4.5 billion doses per annum. The key question is where the drug substance will come from; the business case needs to be considered.

Dr Agwale went on to stress the importance of choosing which vaccine platform the continent will use. He shared how the arrival of COVID-19 catalysed the building of vaccine manufacturing facilities in Nigeria; his team is currently in the process of developing a second-generation vaccine for COVID-19. He added that to build a vaccine production facility, a process is required; without the process, the development of a vaccine cannot be designed.

For this industry to thrive and be sustainable, one should not only look at the availability of vaccines but the business case and then build infrastructure based on the products that will help to sustain the industry; he however noted that a pandemic situation may require a different approach. The production of the product/ vaccine must sustain the facility; there must be a market/demand for the vaccine, and the venture must be viable and relevant.

Dr Agwale then went on the share his experience in developing an HBV vaccine which will provide more protection/coverage for people living in Africa (more impactful), at a reduced cost (cheaper). He concluded by reiterating that there should be justification for going into a venture; we need to carefully look at what exists and what the gaps are, and then try to produce vaccines that will fill those gaps. Dr Agwale also shared that a critical consideration when building a business case is consulting financial experts who can do the modelling to see whether the venture is profitable. Investors will want to see that the business case is viable.

Prof Terblanche indicated that she would share Afrigen’s experience in creating an mRNA vaccine and what it took to make this process successful; a case study that provides both learnings and is aligned to a strategy of drug substance manufacturing. The African continent currently produces one per cent of the vaccines it uses/needs and uses 25% of the vaccines produced globally. Pre-2020 there was very little capacity on the continent for drug substance production and insufficient capacity for fill-finish. Prof Terblanche reiterated Dr Agwale’s question – the African continent is currently over-capacitated in terms of fill-finish; how do we feed this?

Prof Terblanche shared that Afrigen developed an end-to-end vaccine manufacturing facility without a business plan; they proceeded based on the knowledge that there would be a need and opportunity for the production of their vaccines. With the arrival of COVID-19 and the Covax Initiative, there soon came the realization that for the sake of pandemic preparedness and global survival, low and middle-income countries need to be able to produce their own vaccines. These countries did not get a sufficient supply of the COVID-19 vaccine when it became available and were not able to meet the needs of their populations. The mRNA was the most versatile platform to help these countries produce their own vaccines. Prof Terblanche added that leveraging public-private partnerships is a key success factor in having an end-to-end value chain established.

In the absence of technology transfer, Afrigen and WITS University (as part of the mRNA Hub) worked together using the resources available in the public domain (the sequence of the Moderna vaccine published by Stanford University) to develop a vaccine candidate. They now have a lab-scale proof of concept vaccine candidate, which they are preparing to take through clinical development. She added that when using platforms like mRNA, intellectual property considerations are of immense importance; this is less so in the case of fill-finish. Prof Terblanche argued that the continent needs to look at the reformation of its patent laws if it wants to build a vertically integrated drug substance industry.

Another important factor in building drug substance capacity creation and manufacturing, is access to technology; particularly technology transfer. Over the last 18 months, there were 37 tech transfer deals in the COVID-19 space globally, 19 of which were in Africa; however, most of these focused on fill-finish tech transfers. The continent must make the conscious decision to create an enabling environment that will allow it to be able to do tech transfer, license and use a combination of methods for its own development for drug substance manufacturing.

A crucial component in this process is research and development (R&D) and directed research orientation. The R&D capabilities that sit within South Africa’s universities have significantly enabled the fast-tracking of the mRNA hubs production of a vaccine candidate. Through R&D the continent needs to focus on improving its ability to produce relevant vaccines, as well as creating second-generation vaccines; considering thermostability, payload and affordability of the vaccines.

Prof Terblanche shared that there will be five companies who will receive tech transfers from Afrigen for mRNA vaccine production. They will establish a platform to establish the proof of concept for new vaccines. This will form an R&D pipeline of development for vaccines of importance for the burden of disease in Africa with multiple partners to ensure that these end-to-end facilities have sustainability beyond COVID. She stressed the importance of having a bankable model; facilities that can produce multiple products, have versatility and can be operated at low cost.

Mr Gaabouri began his presentation by clarifying that he is part of Merck Life Sciences, and there is no relation to the company Merck Sharpe & Dohme which is a separate pharmaceutical company.

Mr Gaabouri shared that vaccines in the biologic space are quite unique compared to older biotherapeutics (which have a well-known manufacturing template). The technology and process that will be used have to be considered when developing a strategy for local manufacturing and capacity building, as this will determine the type of equipment used. Another consideration is biosafety for the operators, especially when producing viral vaccines that are inactivated.

Mr Gaabouri went on to share some terminology: USP (upstream processing), DSP (downstream processing), and formulation and final fill; these are the main process steps for sequencing drug substances when it comes to value chain fallbacks in manufacturing. He then proceeded to share the difference between the mRNA vaccine and the inactive process template, noting that the process one selects will determine the number of steps in your vaccine production.

He also shared some of the equipment used for upstream and downstream processes. In Africa, most pharma players tend to choose classical pharma production methods (injectable and non-injectable products) where the number of the process steps are significantly reduced compared to the biological space. There are several considerations that need to be made when determining the equipment that will be needed and the design of the plant and processes.

Mr Gaabouri shared some insights on the shifts in technology in the vaccine space, particularly the biologic space; there is a shift to single-use technologies (plastic and silicone) to try and reduce the footprint and costs of the manufacturing process. Another shift relates to time and the ability to produce a vaccine in a very short time – big manufacturers like Moderna and Pfizer now claim to be able to produce and bring to market a vaccine in 2-3 years. He concluded by saying that although Africa is well equipped to run classic pharma facilities, we have to ask whether we have qualified people to run large drug substance manufacturing (and the related devices). Therefore tech transfer and collaboration initiatives are imperative for success.