Gathering of Regulators from Southern Africa Tackles Vaccines and Microbicides

By Abigail Bing

On 18-20 November 2002, regulators and Institutional Review Board (IRB) members from 14 southern African countries met with officials from the World Health Organization (WHO), researchers, and others working on HIV vaccine and microbicide development to discuss regulatory issues in the region. * The workshop, held in Gaborone, Botswana, built on two previous WHO regulatory meetings in Geneva and Villars-sur-Ollon, Switzerland. It was the first gathering in the series to take place in Africa, and the first to focus on specific regional challenges.

The meeting was the latest response to the pressing need for greater regulatory capacity in Africa. Historically, vaccines and other health products have been primarily tested and approved in developed countries. Resource-poor countries often lack many of the decision-making groups needed to review clinical research—including ethics committees, IRBs, and data safety and monitoring boards. They also frequently lack capacity to license and approve products. Instead, introduction of new drugs and vaccines is guided by global health organizations like WHO and UNICEF and, indirectly, by regulatory decisions made in the US and Europe.

But the urgent need for strategies to quell the raging epidemic is changing this paradigm. As more clinical trials take place in resource-poor settings, countries must be able to ensure that research done within their borders is safe and ethical. Also, without independent capacity to regulate new medical products, African nations could experience significant delays in their ability to deploy HIV vaccines and microbicides once effective products are available.

These are new expectations for many African regulators. “We have had virtually no experience with testing of vaccines,” said Esnart Mwape, a regulator with Zambia’s Pharmacy and Poisons Board.

According to meeting co-organizer Tim Farley (WHO Department of Reproductive Health), a key question is how to ensure speed without compromising safety. In some cases, there has been relatively little scrutiny of clinical trials conducted in the developing world—for example, where privately-funded investigators may not have to submit protocols to IRBs at their home institutions. “People could come in and do trials without any sort of regulatory oversight,” said Margaret Magagula (Ministry of Health and Social Welfare, Swaziland). “Government officials may be consulted and lend support for trials, but medical experts aren’t [always] involved.”

The meeting also revealed a need among regulators for more discussion and information about vaccine trials. Their questions ranged from basic safety concerns—such as whether trial participants could become infected through HIV vaccines and whether the use of viral vectors could produce dangerous new viruses—to issues such as liability for adverse events during trials or after licensure. Another hotly-debated point was whether or not to approve trials of HIV vaccine candidates that do not match a clade prevalent in the region.

Without clear correlates of protection or reliable animal models, regulators have limited data on which to base trial approval decisions. For vaccines that don’t prevent HIV infection but work by blocking progression to AIDS, they must therefore decide on appropriate surrogate markers of efficacy (such as viral load) and on the duration of post-trial surveillance. “How do we decide when information is sufficient?” asked Dr. Ishmael Joseph of Botswana’s Ministry of Health, adding that it is especially difficult to answer such questions if medical professionals from the host country were not involved in developing the trial protocol. Decisions can be even more difficult in microbicide trials, where data is drawn largely from volunteers’ reports on their use of the product.

The regulators also expressed concerns about treatment of trial participants, including standard of medical care, prevention education and informed consent. Several African representatives pointed out that US-style in-formed consent forms, which often contain exhaustive catalogues of potential side effects and adverse events, are too long and complex for local needs.

To feel confident approving trials, many meeting participants said they would need to see safety data from trials in the country where the product was developed. “For safety I’d like to have information from the country of origin; however, for efficacy it makes sense to have [trials] done in the country where [the product] will be used,” said Prof. Norman Nyazema of the University of Zimbabwe. But a requirement for testing in the country of origin could pose problems for vaccines where demand (and therefore incentive to test the product) in industrialized countries is low.

Looking ahead, participants discussed the need to prevent “brain drain” of qualified professionals away from the continent, and for regional harmonization and collaboration on common guidelines. Rubell Brewer (Sechelles Ministry of Health) called on participants to lobby their ministers to prioritize and fund regulatory structures. In addition to continuing WHO training, other suggestions included asking the Southern African Development Community Harmonization on Drug Regulation Initiative for assistance and lobbying research universities to devote resources to IRB review. The need for improved mechanisms to ensure appropriate post-marketing surveillance of product safety and efficacy was also highlighted.

“WHO can do work in this, but everyone should see their own role in this process,” Ivana Knezevic (WHO Department of Vaccines and Biologicals) told the gathering. “Without your support, we won’t go anywhere.”

Abigail Bing is a Policy Associate at IAVI.

*Scientific Guidance for Regulation of Research and Development of Microbicides and HIV Vaccines: Southern African Regional Workshop, co-sponsored by UNDP/UNFPA /WHO/World Bank Special Programme of Research Development and Research Training in Human Reproduction, Department of Reproductive Health and Research