Why SA isn’t making its own vaccines

SA is one of only a handful of African countries — the others are Egypt, Ethiopia, Morocco, Senegal and Tunisia — with at least some capability to make vaccines. And yet our country is producing next to none.

SA, for instance, has world-class local vaccine production facilities in the form of the Cape Town-based company Biovac, which was created in 2003 in partnership with the government as a way to "establish local vaccine manufacturing capability".

And though Biovac is putting a process in place to produce Sanofi Pasteur’s six-in-one jab Hexaxim, as well as Pfizer’s Prevnar 13, it has not yet produced any other vaccine from start to finish in two decades of existence. (Hexaxim protects children against diseases such as hepatitis B, polio, tetanus and whooping cough and Prevnar 13 prevents middle ear infection in children and certain types of pneumonia.)

In fact, no SA company has manufactured a shot from scratch since 2001 — and the pandemic has exposed this huge failure and its corresponding consequences.

With a dire global shortage of Covid jabs, countries with local vaccine manufacturers have consistently been able to procure vaccines faster than those nations that have no such facilities.

SA, on the other hand, has struggled to get hold of enough Covid shots fast enough.

And while the Durban-headquartered drug manufacturer Aspen Pharmacare is producing the Johnson & Johnson (J&J) Covid jab from its Gqeberha plant, it’s not from start to finish, but rather involves a process called "fill and finish", where an imported vaccine is put into vials and packaged for distribution.

So what has made producing vaccines so difficult for SA, and why do we lag far behind other middle-income vaccine-producing (and -exporting) countries such as India, Brazil, Russia, China, Mexico and Argentina?

India’s Serum Institute, for example, has become the world’s largest vaccine manufacturer, providing more than 170 countries with jabs, and Brazil produces most of its own vaccines and has exported shots to more than 60 nations. And India, Brazil, Russia and China either have produced or are in the process of producing Covid vaccines for both local distribution and export.

The answer to why SA doesn’t have the ability to make the most powerful tool to combat Covid is, predictably, multilayered. Here’s the low-down.

Then and now: SA used to make vaccines, but then stopped

SA began to produce bacterial vaccines from start to finish in 1935. At the time, the SA Institute for Medical Research produced antivenoms and typhoid jabs as well as shots for diphtheria, tetanus and pertussis (whooping cough), which today is given to children as a single jab known as DTP3.

In the 1950s, the National Institute for Virology (now the National Institute for Communicable Diseases, or NICD) started to produce viral vaccines for polio and yellow fever, and continued to do so until 1995.

And from 1965 to 2001, the State Vaccine Institute in Cape Town produced vaccines for smallpox and rabies.

Through the dark years of apartheid-related sanctions, when SA was a pariah state, the regime’s "need for self-sufficiency, and fear of sanctions impacting vaccine imports, kept local vaccine production and distribution going through much of the 1990s", says Biovac CEO Morena Makhoana.

But the last vaccine produced in the country (BCG, for tuberculosis) was in 2001, by the State Vaccine Institute, at the same site in Pinelands on which Biovac was later founded.

So why did SA stop producing vaccines?

Local production was stopped for a variety of reasons, says Barry Schoub, chair of the ministerial advisory committee on Covid vaccines.

Schoub, who is also a professor emeritus of virology at Wits University and was the founding director of the NICD, says two of the reasons are that the technology used to create newer types of vaccines had overtaken the earlier, simpler processes, and that vaccine import costs were low.

SA’s polio vaccine production decades ago was highly successful, for example, because it was a "straightforward, simple process", Schoub says. That process, he says, involved producing "inactivated" viral vaccines (such as the IPV polio vaccine which SA largely uses), which are made from a virus that has been killed by a chemical but still provokes an immune response.

Later-generation vaccines were a quantum leap in complexity. Examples are:

• Viral vectors — where an inactivated virus is used as a carrier to prime the immune system to respond to another virus. J&J and AstraZeneca’s Covid jabs work like this.
• Recombinant nanoparticle vaccines — where spike proteins are attached to the surface of a very small particle, called a nanoparticle, which is combined with a substance which creates longer-lasting immunity. Novavax’s Covid vaccine works like this.
• mRNA technology — mRNA vaccines use pieces of man-made genetic material called mRNA to instruct the body to produce proteins that can fight a particular virus. Pfizer and Moderna’s Covid vaccines use this technology.

"We essentially missed the boat in terms of adapting to new technology," says Makhoana.

Biovac was conceived towards the end of apartheid, when investing in biotechnology was not a government priority. "The vaccine game is difficult, it’s expensive, and if you don’t do the upkeep, the facilities go south," he says.

Medical regulations had also become more stringent by then, Schoub says, and the imported vaccines available at the time were cheap, so it wasn’t worthwhile for SA to invest in expensive and sophisticated technology. "It just became more cost-effective to import those vaccines," he says.

The latter-day geopolitics swirling around Covid vaccine production, allocation and distribution — and the related inequities — were also not an issue 20 years ago, Schoub says.

"In those days vaccines were not a strategic commodity. It was a straightforward thing. Things only became complicated more recently."

Why can’t we produce jabs from scratch then?

"The part we are not yet doing is what is called API — the active pharmaceutical ingredient — the real raw material," says Makhoana.

These ingredients are the active substances in any diagnostic test, treatment or vaccine that make it work. They are made using specialised biotechnology — like cell cultures extracted from plants or animals, or chemically synthesised, for example — under stringent safety standards and laboratory controls. "No one in the country has that capability at the moment," Makhoana says. "Biovac has the know-how but on a small scale for particular vaccines — but nobody has it on an industrial scale."

This includes Aspen — which until now has largely stuck to "formulation" (compounding ingredients and filling vials or syringes), inspecting, packaging and labelling vaccines.

"When you’re looking to manufacture vaccines, which are biologic products, that’s very different to making a tablet or a capsule," says Stavros Nicolaou, Aspen’s senior executive for strategy.

Getting to an industrial stage isn’t just a matter of building a bigger factory or buying more machinery either, he says.

"These are live organisms you’re introducing into the body, so they have very different, stricter sterility and quality requirements to oral-solid products," Nicolaou says.

The constraints, he explains, are in technology, machinery and skills.

"When you start manufacturing a vaccine, you’re taking the antigen, or the API, compounding that under sterile conditions, and you then have to fill [vials or ampoules or prefilled syringes]. Filling technology and the robotics around that are really expensive technologies," he says.

Aspen’s new sterile facility in Gqeberha, for instance, cost R3.4bn – exceeding the amount that the entire SA pharmaceutical industry invested in the past decade, Nicolaou says.

And SA has a skills gap too. "You might have pharmacy schools in all the health faculties, but if you don’t have the exposure to these advanced technologies, you’re not going to keep people with these skills in the country."

Where are we now?

In the late 1990s, SA’s new democratic government decided to revive vaccine production, built along public-private partnership (PPP) principles.

The result was the establishment of Biovac in 2003, in which the government had a 47.5% stake, with private health-care companies owning the rest.

Biovac had a mandate to produce routine childhood vaccines to support the country’s expanded programme of immunisation.

The formal PPP ended in June 2020, which means Biovac now needs to tender for government contracts alongside other providers.

Fast-forwarding to 2021, Biovac has developed the capacity to do everything from vaccine formulation (blending primary ingredients) to fill and finish and inspection.

But, over the past two decades, the company hasn’t expanded enough to create vaccines from scratch (other than Hexaxim and Prevnar13), or to meet the scale of SA’s needs for even the fill and finish of imported vaccines.

There is hope that this may change, though. The drug company ImmunityBio has selected Biovac as a manufacturing partner for its Covid vaccine candidate, hAd5 T-cell, should its clinical trials now under way in the US and Khayelitsha prove successful.

Makhoana says Biovac, at a push, could manufacture a maximum of 30-million doses of vaccines per year using multidose vials ("manufacturing" here refers to any form of vaccine production — fill and finish, formulation or producing jabs from scratch).

But this number hinges on the type of technology used to produce some vaccines, and the willingness of foreign manufacturers to do "technology transfer" as part of licensing their product for local production.

"When we talk of technology transfer, we are talking about transferring the know-how from the original manufacturers into this facility," says Simphiwe Ntombela, Aspen’s production manager for the new Gqeberha sterile facility.

The plant will fill and finish up to 400-million doses of the J&J Covid jab, of which 31-million doses will be allocated to SA and the rest to other countries. But even with Biovac and Aspen ramping up their technology and capacity, SA will still not be self-sufficient for all vaccines, including routine childhood immunisations, flu jabs, Covid shots or the next pandemic’s vaccines.

One of the reasons for this is the lack of financial incentives for investment in vaccine production, which are undermined by the government’s tender system.

The government accounts for 75% of the country’s demand for vaccines and pharmaceuticals, Nicolaou says, but it operates largely on a two-year tender cycle for suppliers to manufacture those products. This makes it difficult for businesses to plan and project revenues that would justify capital investment.

"The current procurement mechanism is counterproductive to attracting investors or safeguarding existing investments," Nicolaou says.

For example, a company might invest hugely to scale up its production to meet one particular contract, but two years later, "you could lose the entirety of it if the contract changes and you have two years of nothing — then later you might have to upscale again", he says.

"Manufacturing is largely about economies of scale, and if most of [the demand] is sitting in the public sector, the public health and the economic/industrial imperatives need to meet each other."

*This story was produced by the Bhekisisa Centre for Health Journalism. Subscribe to Bhekisisa’s newsletter here