Regulatory Reliance Behind The Success Of African COVID-19 Vaccine Approvals
Executive Summary
Regulatory reliance and work-sharing are becoming increasingly popular as a way of avoiding duplication and speeding up drug and vaccine assessments, but while there are many benefits, regulators should also be aware of some potential pitfalls, delegates at the TOPRA annual symposium heard this week.
The fact that some 250 COVID-19 vaccine approvals have been awarded so far in Africa is a shining example of how medicines agencies, particularly in lower-income countries, can use regulatory reliance and work-sharing to reduce the burden of product assessment and approval processes.
That is the view of Murray Lumpkin, lead for global regulatory systems initiatives at the Bill & Melinda Gates Foundation (BMGF), who gave his assessment of the use of regulatory reliance procedures, whereby one agency relies on work carried out by another agency or engages in work-sharing.
Lumpkin was speaking at the TOPRA (The Organization for Professionals in Regulatory Affairs) Annual Symposium 2021, which is taking place virtually from 22-24 September.
Reliance covers practices such as the exchange of scientific assessment reports or inspection results, and joint assessment activities like work-sharing to inform agencies’ own regulatory decisions. It does not equal “outsourcing of decision-making,” he stressed.
As examples, he cited agreements between the European Medicines Agency and the US Food and Drug Administration, the ACCESS consortium (involving regulators from Australia, Canada, Singapore, Switzerland and the UK) and the various regional regulatory collaboration initiatives in Africa.
Reliance offers medicines agencies two benefits, he told delegates at the TOPRA symposium on 22 September. It can free their time and allow them to focus resources on a particular activity that cannot be done by another agency, and it can help to strengthen their capabilities where they lack in-house scientific or procedural expertise.
A big step forward was taken in April this year when the World Health Organization published its Good Reliance Practices document, a draft version of which was released last year. (Also see "Lean On Me: WHO Offers Practical Advice On Regulatory Reliance" - Pink Sheet, 10 Jun, 2020.) Reliance, Lumpkin said, is “not outsourcing your decision-making, it is simply getting additional information from sources that you trust that allows you to make a decision and allows you to inform that decision without having to go through redundant activities which are not adding value.”
COVID-19 Vaccines In Africa
Lumpkin, who spent 24 years at the US FDA, including as senior advisor to the commissioner and representative for global issues, highlighted the authorization of COVID-19 vaccines in Africa as “a tremendous success” and a prime example of the benefits of regulatory reliance.
“I hasten to say that we all know there is a huge problem when it comes to access in Africa and many other parts of the world. There is a huge problem with equity of access, but the point I want you to take away from this is that the problem is not registration,” he told the virtual symposium, which was hosted by the Czech regulator SÚKL.
“People tend to equate registration with access, and when they don't see access, they throw the national regulatory authority under the bus” – Murray Lumpkin, Bill and Melinda Gates Foundation
He said that people sometimes "tend to equate registration with access, and when they don't see access, they think it's registration, and they throw the national regulatory authority under the bus. This is not a case where the facts would allow one to do that,” Lumpkin stressed.
Looking at how the coronavirus vaccines were approved in Africa, he said a mechanism was created jointly between AFRO (the WHO’s Regional Office for Africa and AVAREF (the African Vaccine Regulatory Forum), and between the African Union and the Africa Centers for Disease Control.
The organizations needed to know how they could use an existing platform to allow rapid authorization of COVID-19 vaccines at national level once they had received an emergency use listing (EUL) from the WHO.
They decided that as soon as a vaccine had received an EUL, the AVAREF secretariat would organize a “technical session,” Lumpkin said. Using Zoom, all the African regulators were invited to sessions, and “the great majority” took part, as did the WHO’s prequalification (PQ) team and all the experts they had brought in for the EUL assessment. The decision to make a positive recommendation on approval was taken at the technical session.
The WHO took the opportunity to explain its assessment process, describe what the assessors found, “and why they came to the risk benefit decision that they did.” The African regulators could “ask any questions that they had about that procedure.”
In addition, rather than requiring companies to submit dossiers to each country involved, “the companies gave permission for the country simply to download the dossier that they had given to the WHO PQ program.” All the countries were able to do this from the SharePoint that they use in their communication with the WHO, Lumpkin noted. “So they all got the same dossier, and they were able to have this joint technical session.”
Following the session, each national regulatory authority (NRA) took its own authorization decision on the vaccine. Some of them were able to issue a full approval, some gave an emergency approval, and some issued only an import permit, Lumpkin said. “It all depended on their local legislation, but it was all based on the information and the assessments that were shared at this technical session.”
248 Vaccine Authorizations In Africa
The former FDA official said that as of 20 September, “there have been 248 authorizations in Africa of EUL vaccines, and often these have occurred within a day or two or at most a week of the technical session.”
He displayed a chart showing that at least one WHO-listed COVID-19 vaccine has been approved in all of the 54 African countries. The highest number of approvals were: 43 for the AstraZeneca/Serum Institute of India vaccine, 37 for AstraZeneca/SK Bioscience, 36 for Sinopharm, 34 for the Janssen vaccine, 29 for Pfizer/BioNTech, 21 for Sinovac and 19 for Moderna.
“I think this has been a very successful example of reliance being used during a public health emergency for the purpose of making sure their registrations get done as quickly and as robustly as possible,” Lumpkin declared.
He stressed that it was not just less well-resourced agencies that were being encouraged to use regulatory reliance procedures. “We know the two most well-resourced agencies on the globe, the US FDA and the European Medicines Agency, have even found that they need to employ this in certain situations.”
Challenges
Lumpkin did note, though, that there were some challenges in using reliance, whether in emergencies or business-as-usual situations. “We see this in a lot of the settings in which we are engaged with national regulatory authorities.”
One of the biggest problems is that there are multiple versions of the same product in global commerce, he said. “By this, I mean not that there are generic versions and there are innovative versions, but there are multiple versions of the same company's product. Often this is because of business considerations or manufacturing considerations,” Lumpkin observed.
“Oftentimes, people are able to have access to documents, but they are so redacted that they really are not helpful” – Murray Lumpkin, BMGF
If a regulator receives an application for “a version of a product that is manufactured at a site that your reference agency did not inspect, or is not shipping to your reference agency, it makes it very difficult to rely on that reference agency’s assessment,” he pointed out. This is because “in essence, they haven’t looked at the manufacturing, they haven't done an inspection at the plant where your version of the product is coming from.”
Another issue is making sure the documents a regulator receives from another agency are “helpful,” Lumpkin said. “Oftentimes, people are able to have access to documents, but they are so redacted that they really are not helpful.”
In this respect, he asked whether current confidentiality laws and expectations were “still fit for purpose in this 21st century globalized world. And this is something that both regulators and industry are going to have to come to grips with if indeed we truly want regulation through reliance to fulfil what I think we all believe in.”
Reservations Over Job Security
Lumpkin also noted that some assessors within agencies might have reservations about reliance procedures because they are concerned about what it might mean for their jobs. They might ask, “if we’re just going to rely on this, then what’s my purpose, what’s my job here?”
Part of the message here is that “first of all, it takes specific skills and training to be able to regulate through reliance,” Lumpkin said. “You're not just an automaton, you're not just a robot, you're having to look at the information, you're having to assess the information, and you're having to look at it within the context of your own legal system and your own health care system.”
A “tremendous amount of expertise” is required to operate reliance processes, Lumpkin continued, noting that the aim is to “get away from redundant work” and use agency resources in a value-added way.
Work-Sharing & Measuring Success
One problem in the work-sharing area, such as the conduct of joint assessments, the BMGF official noted, is using that joint assessment for a national regulatory decision.
Often people are focusing on the joint assessment and meeting the timeline for the assessment, “but then getting to the national authorization based on that joint assessment is often still a challenge. And as we all know, until you have the national authorization, the joint assessment doesn't have a whole lot of meaning.”
Finally, Lumpkin addressed the thorny question of how to measure the success or otherwise of reliance pathways. “Are they having a beneficial impact on public health? Are they having a beneficial impact on the economic health of countries, on agency efficiency, on agency resource utilization?” And how does one agency know it can rely on another?
He suggested that some agreed metrics were needed to determine what kind of an impact these approaches were having. One answer was the WHO’s Global Benchmarking Tool, which assesses the “maturity levels” of national regulatory bodies.
“I do think it will give people a way of saying this is an agency that has been assessed at a certain maturity level, and for that reason we know that we can rely on them.”