On Sunday, President Cyril Ramaphosa confirmed at the G7 Summit in Cornwall in the UK that the US regulator, the Food and Drug Administration (FDA), found that the active substance (or main ingredient) with which two-million Johnson & Johnson (J&J) Covid vaccine doses allocated for use in South Africa was made, wasn’t safe for consumption.
As a result, South Africa has no J&J doses to administer right now, setting the country back with its vaccine roll-out goals and timeline in the midst of a third Covid wave that’s rapidly filling hospital beds.
The active substance was produced by a US factory in Baltimore, but the doses were stored at the pharmaceutical company, Aspen, in Gqeberha. Aspen has been contracted by J&J to “fill and finish”, in other words, import vaccine doses made in bulk, mix them with another ingredient (an inactive substance) and then put them in vials and label the jabs.
The setback comes on the heels of another hold-up in April when South Africa had to pause the roll-out of J&J jabs via an implementation trial called Sisonke. The country’s regulator, the South African Health Products Regulatory Authority (Sahpra), was reviewing data relating to blood clot-related side-effects associated with the jab. Although the occurrence of the blood clots is extremely rare, Sahpra wanted to ensure that the shots were safe to use and therefore temporarily stopped the study for two weeks while assessing the information.
But what exactly happened this time around? We look at why our two-million J&J doses are unsuitable for use, when we’ll get new ones and what the implications are for our vaccine roll-out.
- What happened with our J&J vaccines?
South Africa has procured 31.2-million J&J vaccines. Two-million of these doses (our first batch of 1.1-million doses and our second batch of 900 000 doses) had been manufactured by April/May and were ready for distribution. The jabs were kept at the pharmaceutical company, Aspen, in Gqeberha, as they handled the final packaging of the jabs.
The active vaccine substance, which Aspen used to mix with an inactive substance and then divide the vaccine into vials, was made at a company in Baltimore called Emergent BioSolutions. In March, the FDA inspected the company’s production facility and found the conditions to be substandard.
The regulator established that a batch of 15-million doses of J&J’s active substance had been contaminated with some of the active substance of another vaccine (AstraZeneca), which was manufactured in the same factory. The FDA therefore instructed Emergent BioSolutions to discard those doses.
As a precautionary measure, the FDA stopped all J&J production at Emergent BioSolutions and decided to also investigate four batches of active substance which were produced during the same period as the contaminated batch.
But by that time, some of the active substance doses had already been distributed to contractors such as Aspen to use to produce finished jabs. The FDA therefore told J&J to tell such companies not to release the vaccines until the regulator had concluded its investigation.
The results of that investigation, as far as they pertain to South Africa’s doses, were shared with Sahpra and Aspen over the weekend. The FDA cleared two batches, but special conditions are attached, and found “several other batches are not suitable for use”. Some batches are also still under review.
South Africa’s two-million J&J jabs were made with active substance from batches the FDA found unsuitable for use. Over the weekend, Sahpra reviewed the data provided by the FDA, and decided to “not release the vaccine produced using the drug substance batches that were not suitable”.
Aspen’s chief executive, Stephen Saad, told eNCA on Monday night that the FDA found that none of the doses used in South Africa were contaminated, but that the vaccines made with them shouldn’t be used as a precautionary measure.
- Why did we have to wait for the FDA’s data?
Emergent BioSolutions falls under the FDA’s jurisdiction, as the active substance they produce is made in the US. It is the FDA’s responsibility — just like it’s Sahpra’s responsibility for medicine produced in South Africa — to ensure that good manufacturing practices are followed by drug companies in the US.
Although South Africa’s two-million J&J doses were mixed and packaged here, the active substance used was produced in the US. So it’s the FDA’s responsibility to ensure that the product used by Aspen is of a good standard. Moreover, the doses don’t belong to Aspen, but to J&J, as Aspen is only a manufacturer contracted by J&J to complete the production process of the jabs.
Sahpra registered J&J’s vaccine in South Africa on 31 March — but with conditions. One such requirement is that it should be “manufactured under conditions of good manufacturing practice as determined by Sahpra and aligned with global best practice”.
Almost all vaccines used in South Africa are made in other countries, so Sahpra always needs documentation from the regulatory authority in the country of manufacture that confirms the quality of the jabs. In a statement, Sahpra explains that “through an arrangement called reliance”, it has “formal relationships with certain regulatory authorities that allow for the confidential exchange of information”.
This allows Sahpra to access reports produced by other regulatory agencies on inspections, testing and various other aspects of manufacturing and testing compliance. Sahpra has such a reliance arrangement with the FDA. So, our regulator relies “on lot release testing undertaken by these partnering agencies which involves reviewing manufacturing documentation and performing certain quality tests to ensure compliance with the approved and registered requirements”.
- Are the J&J jabs that the Sisonke trial used contaminated?
Linda-Gail Bekker, one of the co-lead investigators of the trial, says all the jabs used in the study were manufactured at J&J’s Leiden factory in The Netherlands — so none of them were manufactured by Emergent BioSolutions in Baltimore where contamination was an issue.
On Monday night, J&J confirmed in a statement that “doses previously distributed to South Africa as part of the Sisonke study have met all product specifications and requirements for quality, safety and efficacy”.
The 479 768 healthcare workers who were vaccinated with J&J shots in the Sisonke study have therefore all been injected with safe and uncontaminated shots.
- Was only South Africa’s consignment made with contaminated ingredients?
No, many more millions of doses have been contaminated. The New York Times reports that the FDA told J&J that 60-million doses couldn’t be used “because of possible contamination”, but J&J told Bhekisisa it couldn’t confirm this number.
However, Aspen also “fills and finishes” doses for 220-million jabs that J&J are providing to the Africa Union’s African Vaccine Acquisition Trust for distribution to countries on the continent.
Aspen senior executive Stavros Nicolaou confirmed to Bhekisisa that there are “several millions of other doses” at Aspen which have also been affected by the FDA’s decision.
Several European countries will also not be using vaccines with an active substance produced by Emergent BioSolutions during the same time as the batch that the FDA found to be contaminated in March.
- When will we get new J&J jabs?
J&J will have to replace the jabs that South Africa now can’t use. On Monday night, on eNCA, Saad said the country’s two-million doses will be replaced by J&J within the next two weeks.
In a statement released on 14 June, Aspen said:
- 300 000 J&J doses will arrive in South Africa “within days”. Saad told eNCA the jabs will likely arrive within the next two days. The health department says these shots are specifically for teachers and other staff working at primary and high schools.
J&J’s medical director in South Africa, Abeda Williams, told Bhekisisa that these doses have been made with an active substance that comes from the two batches that the FDA has cleared, with special conditions. The requirement is that J&J and Emergent BioSolutions agree that “the FDA may share relevant information about the manufacture of the batches under an appropriate confidentiality agreement, with the regulatory authorities of the countries in which the vaccine may be used”.
Williams has confirmed that this data was supplied to Sahpra, and that the regulator reviewed the information and approved the jabs for use in South Africa. Sahpra confirmed this in a statement on Sunday, saying the active substance used in the jabs “meets the requirements and will subsequently be released and shipped to South Africa”.
The 300 000 doses will arrive in the country as finished vaccines, so Aspen wouldn’t need to package them. The jabs will, however, first need to be quality checked by the National Control Lab for Biological Products at the University of the Free State, according to Nicholas Crisp, the deputy director-general in the health department who is managing the distribution of Covid vaccines. The quality checking is a routine procedure that all vaccines arriving in the country undergo — it’s not a special procedure followed because the shots were produced by Emergent BioSolutions.
- Saad says Aspen will release one-million J&J doses in the week of 21 June, likely on Monday. Aspen started to “fill and finish” these jabs about a month ago, with an active substance supplied by J&J’s factory in Leiden in The Netherlands. These shots have already been quality tested, so they wouldn’t first have to go to the National Control Laboratory, and will therefore be flown to OR Tambo airport in Johannesburg as soon as they’re released and then be distributed to provinces. In its statement, Aspen said it will release more doses in July (the July doses will be for both South Africa and other African countries).
- Aspen said J&J will also be “delivering substantial quantities of compliant finished vaccines to South Africa to replace the lost stock” within the next few weeks (these jabs will be produced with an active substance made by J&J’s Leiden factory).
- Will South Africa have to pay for the replacement of the jabs which can now not be used?
Neither the South African government nor Aspen would have to cover any costs of the replacement of jabs, as it’s not their fault that the shots have to be destroyed. Saad says the cost will be covered by either J&J, Emergent BioSolutions or the companies’ respective insurers.
- Will we reach our original vaccination goals?
South Africa will almost certainly not reach its goal of having 90% of people of 60 and older vaccinated by the end of June. Crisp told eNCA that, if we continue to vaccinate at our current pace, we will only have 52% of the population group vaccinated by the end of the month.
The main reason for this is that we don’t have enough jabs to speed up our vaccination campaign. Crisp says that because we’ve only had Pfizer shots to use since the start of our mass roll-out on 17 May, we haven’t been able to scale up to more than 80 000 vaccinations per day, as we’ll run the risk of running out of jabs. According to him, we can administer double the number of doses if we had access to the J&J shots we were promised.
But with two-million J&J shots that Saad says will be delivered within the next two weeks, we’ll be in a position to catch up — eventually. The most important thing, the former co-chair of South Africa’s Covid ministerial advisory committee, Salim Abdool Karim, says, is that we get phase two of the roll-out (people older than 40 and those living in congregate settings) done by December, before a potential fourth wave hits the country. “Those are the people who are most likely to be hospitalised or die,” he says. “So they’re the most important population to reach first.”