South Africa: Will the red tape hold back the strengthening of mixed and assorted vaccines in South Africa?
The South African Health Products Regulatory Authority (SAHPRA) this week gave the green light for a third dose of Pfizer’s COVID-19 vaccine to people who had received their second dose of the same vaccine six months or more previously. No go-ahead has yet been given for a booster dose for people who have received the Johnson & Johnson (J&J) vaccine – although healthcare workers who participated in the Sisonke study are being offered such boosters in as part of a follow-up study.
The SAHPRA has yet to give the green light to any form of mix-and-match, or heterologous reinforcement. Such a heterologous booster may, for example, allow people who have been injected with the J&J vaccine to be offered a Pfizer booster – an option according to the South African Medical Association should be offered to healthcare workers.
The United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have both approved certain heterologous booster combinations. The EMA / ECDC recommendations on heterologous stimulation are worth reading to get a feel for the available evidence.
What is SAHPRA waiting for?
It is not uncommon for drugs or vaccines to be approved by the FDA or EMA several months before they are approved by the SAHPRA. One of the reasons for this is that companies usually first apply for registration in the United States and Europe before doing so in South Africa. To some extent, the deadlines are out of the hands of SAHPRA.
In Wednesday’s media statement, the regulator said: “SAHPRA recognizes the strong interest in the effectiveness and safety of heterologous recall schemes (so-called ‘mix-and-match’ approaches), and invites submission of data in this regard. “
We asked the CEO of SAHPRA, Dr Boitumelo Semete-Makokotlela, who can submit such supporting data. She replied that “although a third party may share them, for the regulator to change the status of the authorization, we will need a formal submission from the manufacturer.”
Our understanding, therefore, is that it is up to Pfizer, and Pfizer alone, to submit data to SAHPRA in support of modifying the indication to enable J&J to be stimulated with Pfizer.
This poses a potential problem. What if Pfizer, for whatever reason, decides not to submit the relevant data to support heterologous boosting? We understand that there would be no way around such an impasse in the current legal framework. The law could, of course, be amended to allow third parties to submit data in cases where it is in the public interest to allow it – but amending the law in the time frame relevant to this case would require little levels of coordination. probable. Incidentally, security information from third parties, such as adverse event reports, is taken into account by SAHPRA.
Rely on other regulators
In recent years, SAHPRA has increasingly used dependency pathways. In short, this means that the SAHPRA can build on work already done by other regulators, such as the EMA. When asked if such trust channels could be used in the event of a heterologous recall, Semete-Makokotlela replied, “Yes, SAHPRA will enforce trust once we receive a request for it. She specifies that no such request has yet been submitted.
Semete-Makokotlela’s reference to the requirement of an application suggests that just having the EMA conduct an assessment and publish it on their website will not be enough. It will still be Pfizer’s responsibility to submit this EMA assessment to SAHPRA.
One ray of light is that EMA / ECDC will be publishing, in the “near future”, “a detailed review of the literature“ in support of its advice. ”The data to“ build upon ”should therefore be there. – it will be enough for Pfizer to submit it to SAHPRA.
But do we really have to wait for SAHPRA?
In South Africa, drugs can be used off-label. This means that a doctor can prescribe a drug for a use other than that for which the SAHPRA registered it. This raises the question of whether heterologous stimulation can be performed off-label. In fact, in this case it would not even be totally off-label since it would be for the prevention of the same condition for which it is authorized, although it is for use in a combination other than that for which it was. authorized.
This could lead to complications, as off-label use typically requires medical prescriptions – which is not possible for mass vaccinations – and off-label use applies to registered products, rather than to products available under Section 21 licenses. Even so, based on conversations with a few regulatory experts, it is not clear to us that the off-label use or flexible interpretation of existing licenses under section 21 are dead ends.
What is the point of view of the Ministry of Health?
We asked the national health ministry if it had had proactive discussions with SAHPRA regarding the heterologous recall, or if it was taking a wait-and-see approach.
Dr Nicholas Crisp, deputy director of the department responsible for the deployment of the COVID-19 vaccine, responded by pointing out that the President and CEO of SAHPRA all participate in the meetings of the Ministerial Advisory Committee on Vaccines. “We are all well aware of the evidence and the debates. [The] The national health ministry is not telling the regulator what to do. This would undermine the independence of the regulator, ”he said.
“The national health ministry always acts within the framework of the law and respects the regulator (SAHPRA), so it will wait for the regulator’s approval. They have specialists on their teams. We also have very experienced people on ministerial advisory committees, so we rely on their advice. They follow the evidence and advise. It will be exceptional for the minister to cancel these structures, ”said Crisp.
So what happens next?
The next most likely step is for Pfizer to submit data to SAHPRA that supports the heterologous use of their vaccine. Since such apps have been successful in the FDA and EMA before, there’s a good chance they will be successful here.
The Ministerial Vaccine Advisory Committee will then advise the Department of Health on the heterologous booster – after which the Department of Health will decide whether or not to give people the option of receiving heterologous boosters as part of the immunization program. mass of South Africa.
None of this will happen overnight. In fact, we would be surprised if heterologous boosters became widely available in South Africa during the current wave of COVID-19.
On the other hand, at the Department of Health’s weekly press conference this morning (Friday), Crisp indicated that counterpart boosters will be available from January – people who have received two doses of Pfizer will be offered. a Pfizer booster six months after their second dose. People who have been injected with J&J will likely be offered J&J boosters (also from January), although SAHPRA approval has yet to be given.
Either way, it’s probably not a good idea to wait for your favorite booster. As with the Covid-19 vaccines from the start, the best booster is simply the first you can get.