University of Namur, faculty of medicine, deptartment of biomedical sciences

Blaise Mwizerwa Nkubito

Most African countries host only a few hundred trials per year and therefore very few new medicines are marketed. Yet these countries suffer from numerous public health problems and lack accessible medicines for the various diseases that plague them. To address these concerns the African Union established a treaty announcing the creation of a continental health agency: the African Medicines Agency (AMA). In November 2021, the AMA project was launched. Currently, many African countries do not have the capacity to provide a proper health system because they simply do not have the legal framework to cover those activities. This context makes access to health products complicated. However, some countries, such as South Africa, stand out for their well-established legal framework and better-than-average health system. In creating a continental agency, the African Union’s (AU) wish was to bring together the strengths of all African countries to improve access to medicines. If the objectives of the agency for the regulation of medicines are clarified, nothing is less certain for clinical trials. Yet the two areas are closely linked. Therefore, it seems relevant to consider that if the regulation of one changes, it will impact that of the other. With the agency still in its infancy, a more comprehensive approach seems easier. This analysis will therefore be carried out through the prism of the actors already involved in the field of clinical research.

Good Clinical Practices ensure the ethical and scientific integrity of clinical trials. Although they are not law, each country is the head of its own health policy.

 Each country must therefore have a National Regulatory Authority (NRA) as well as qualified Ethics Committees (EC)

 to analyze the trial requests made by the sponsors.

Despite these fundamentals, the assessment of a trial request may differ between countries. The WHO created in 2018 a benchmarking tool for national health regulatory authorities. This tool ranks the regulatory systems on a maturity scale from 1 (lowest) to 4 (highest). These levels are based on many criteria and there are many disparities around the world. In fact, according to WHO, only 25% of countries reach the highest levels of maturity. Almost 75% of NRAs have a sub-optimal level of maturity and most of them are low- and middle-income countries (LMICs). This poorly developed regulatory context is unfavorable to the marketing of drugs and therefore indirectly to the conduct of clinical trials.

Indeed, the NRAs have as mission to regulate all health products: the investigational medical product (IMP) tested during clinical trials but also medicines already on the market. As pharmaceutical research is an expensive process, sponsors may decide to reach new markets. Low-capacity NRAs will take time to analyze a marketing application, which will waste the limited exploitation time that companies have on their drugs. Therefore, sponsors often avoid LMICs as new ground for their products but also as new places to conduct clinical trials because of their complex regulatory environment and small market. Not only, these countries have few clinical trials performed on their territory and therefore few new drugs emerging. But also, they have limited access to the medicines that already exist.

The regulatory context for clinical trials on the African continent is rather complex. Each member country of the AU, which includes all 54 African countries, has an NRA that handles clinical trial applications in a different way. Where one application could be sent to Europe to cover the whole territory, 54 applications should be needed to cover the whole continent.

 In addition to these administrative complexities, NRAs have generally low levels of maturity, 90% of them are at level 1.

 This context is not optimal for conducting clinical trials because the regulatory tasks take an abnormally long time. For example, it takes between four and sever years longer in sub-Saharan Africa than in a high-income country for a tested drug to reach the market, which discourages sponsors.

 The apprehensions of sponsors are also demonstrated by the disparity in terms of trials among the continent. Indeed, the majority (>70%) of studies are shared between Egypt and South Africa which have maturity level 3 NRAs.

 Still, the African continent represents only 3% of global clinical trials.

Aware of the flaws in the drug regulatory system on its territory, the AU mandated its development agency, the African Union Development Agency (AUDA), in 2001 to find solutions. It initiated the African Medicines Regulatory Harmonization in 2009 (AMRH).

 The principal goal of AMRH was to create better regulatory mechanisms among NRAs by joining their work. Firstly, focused on generic medicines, AMRH expanded its work to other fields. Then it designated the Regional Centers of Regulatory Excellence (RCORE), institutions that would oversee specific regulatory tasks. Afterwards, AMRH launched regulatory harmonization initiative between neighbouring countries belonging to the same Regional Economic Community (REC). It is through these progressive steps since 2009 that AMRH has been able to lay the foundation for what will become the AMA.

In February 2019, leaders of member states adopted a treaty establishing this new continental health agency.

 The milestone of 15 ratifications asked by the treaty was reached in October 2021 which set the creation of the agency in November 2021.

 In April 2021, the AU has appointed Michel Sidibé, former Executive Director of UNAIDS and former Malian Minister of Health, as its special envoy for the establishment of the AMA.

 In July 2022, the AU Council voted Rwanda as the host of its future headquarters.

The AMA aims to improve regulatory capacity for medicines, provide expertise in countries that lack of regulatory framework and improve efficiency and transparency of those processes. It also aims to strengthen governance in pharmacovigilance and oversee clinical trials. However, these missions will not impinge on the activities of local authorities.

 Indeed, the AMA is intended to be a facilitator that would allow the coordination and strengthening of the various initiatives of harmonisation. By pooling resources, the AMA aims to ensure the quality and accessibility of medicines in Africa. It will work with the NRAs and RECs to bring together the strengths of each but also to avoid duplication of work.

This analysis was mainly based on the literature available online. It was first searched in online scientific databases PubMed, Scopus, and Google Scholar using several keywords: “African medicine agency,” “regulation of clinical trials in Africa,” “clinical trials in Africa.” As the scientific literature is still sparse, it was necessary to diversify the sources of information. The first step was to search for information on the websites of the different institutions mentioned in this article. As the subject of this work is still evolving, it was necessary to keep up with recent developments in the creation of the agency. Social networks, more specifically Twitter, were a great help in this process. By following the activities of the various actors around the AMA, it has been possible to keep track of the various news. To ensure the veracity of the posts, every piece of information that was taken from them was cross-checked with other sources.

The African Union stated that the AMA main mission would be to promote harmonization of health product regulation and scientific guidelines. These harmonization measures aim to provide African populations with access to safe, effective, and affordable medicines.

However, this is a very difficult task for LMICs whose NRAs are often unable to carry out the regulatory work necessary to bring certain medicines to market.

Nevertheless, the African continent is home to more than 1.4 billion people in a territory almost three times the size of Europe

 It should be fertile ground for the pharmaceutical industry: there is a need to be fulfilled. The main obstacle to this collaboration would therefore be a question of regulation, according to the African Union, and the authors working on the issue tend to agree.

Thus, researchers established, in a survey of industry players in 2019, that the harmonization initiatives led by the AMRH in the RECs were an effective way forward.

 By breaking down regulatory barriers and creating a free trade area for health products, the AMRH has made the East African Community (EAC) a more open market for the industry. The EAC has extended its free trade economic partnerships to health products and has also proposed common measures to regulate the circulation of medicines. Countries with fewer resources, have been able to benefit from the momentum created with their neighbors. Moreover, their neighbors with better resources and regulatory systems, have been able to offer a larger market to investors.

While it is true that AMA's Treaty does not explicitly stipulate connections with industry, these appear to be essential to achieving the agency's objectives. On further analysis of the structure, objectives, and future operation of the AMA, there are similarities in its operation to the European Medicines Agency (EMA).

 To ensure that its population has access to essential medicines, the EMA offers incentives to companies: more flexible legislation for certain diseases, market exclusivity, tax benefits, etc. These incentives have been discussed with the industry to be relevant. The same could be done for the AMA.

However, the Council of Europe noted the importance of balance in such incentive decisions. This concern is even more valid on the African continent and its LMICs. On one hand, the industry has the power to respond to pressing demand, and on another hand, small countries have little negotiating leverage because they need what is on offer. To ensure that these collaborations are fair, the AMA should also mediate with the pharmaceutical companies. This could only be done if the agency ensures its independence.

The African continent suffers from a lack of production units and poor supply chains, which increases the price of raw materials. These problems, combined with failures in price regulation, leave room for alternative medicines that are often counterfeit due to the lack of a proper patent policy. This also forces the continent to import most of its medicines. In addition, there is a lack of infrastructure and qualified personnel due to low fundings in the sector. However, it would be wrong to consider Africa as a single block, as each country handles the situation differently.

While some countries have the resources to improve their health systems, others have far fewer. In the AMA treaty, the African Union leaders clearly state that the agency will be supranational but that it will not override the decisions of national agencies. It will act as a facilitator and coordinator to provide political guidance to its member states. This could solve the political dimension of the problems that is plaguing Africa. By providing a better-defined framework for regulators, the agency could facilitate the work of regulators in terms of taxation and patents.

Similar initiatives already exist through structures such as the RECs. It would therefore be interesting to study the effects of the RECs on the countries that make them up to identify improvements and limitations.

 In this way, the effects and usefulness of a larger scale coalition could be assessed. As the EAC was the first to implement harmonization initiatives in drug regulation, it will provide the most information.

 In theory, this system is beneficial for everyone and benefits the populations of each of the countries concerned. However, as Ndomondo-Sigonda et al. point out, in practice the EAC has some problems with its funding and more specifically with its management.

It is now necessary to determine whether AMA could have known about these flaws. By acting as a go-between, AMA could redistribute the various grants and donations to the countries that need them most. Indeed, some agencies are overwhelmed by donations and do not know what to do with them when some of their neighbors are desperately short of funds.

In practice, there is no certainty about what the agency will do as its executive bodies do not yet exist and it has not yet presented any concrete actions. However, the AMA treaty gives some indication of its ambitions stating that member states will establish the focal points for its activities.

The AMA treaty sets out in its 30th article the range of actors with which the agency will be prepared to collaborate. It turns out that it does not contain any restrictions and leaves the possibility for the agency's executives to judge the merits of the relationships it establishes. However, the article specifies that it will maintain privileged contacts with the WHO, the Africa CDC, and the RECs. The same applies to the various United Nations organizations and NGOs already working on the continent.

The AMA is modelled on the EMA, so the two agencies will undoubtedly have a close relationship, if only to set up its operations. For instance, the European Union announced in February 2022 its support of 100 million euros for the AMA's regulatory tasks.

 This support also extends to the various associations and NGOs working in the wake of the EMA.

Beyond Europe, numerous links have been created in recent years with Asia, so much so that China has become the second largest importer of medicines into Africa. India also maintains privileged relations with the continent.

 As both countries have also undergone major reforms in their health systems to improve access to medicines, they could be key allies for AMA.

The agency could also count on the collaboration of the United States, which in 2020 celebrated 20 years of official partnerships to support public health in Africa. The Bill and Melinda Gates Foundation (BMGF) can also be mentioned for the various funds it raises for Africa. It has also contributed to the 100 million allocated by the EU to AMA.

 These types of private initiatives bring a considerable financial windfall to the continent but are less explicit about their actions than public initiatives.

The agency could have a large impact on research at several levels: with its member states of course, but also with industry and other regulatory agencies around the world. Assessing this impact is still complicated as the agency is still in its infancy, but it is possible to make some assumptions based on the literature. By homogenizing its regulatory context, the African continent could become an exploitable market for the pharmaceutical industry; a territory where it would be possible to carry out clinical research but also a place where production units or laboratories could be set up more easily. This situation could have a direct impact on access to medicines, making it simpler and more indirectly bringing a significant financial windfall to the continent. More directly linked to this harmonization, the member countries of the agency could communicate more easily in terms of regulation and feed off each other's experiences. Finally, the creation of the agency puts a new international interlocutor on the map, which could facilitate relations with partners outside the continent.

All authors discussing the agency see it as a boon to the continent and support its creation. Discussions about the AMA, therefore, seem enthusiastic and the project looks promising on paper. However, the AMA is not yet operational, and it should not be forgotten that only about 20 of the 54 countries have ratified its treaty. Without these agreements, it will only be possible to speak of the agency in the conditional. It should also be remembered that the agency's main mission seems to be the regulation of medicines already in circulation. In a recent paper, Michel Sidibé stressed the importance of clinical research

 to create new products in a territory plagued by endemic diseases and with a young population whose genetic profile could help and improve global clinical research. However, clinical trials are likely to be in the final stages of the agency's considerations.

It is certain that the agency will draw inspiration from its counterparts around the world to build itself. However, the creation of AMA could be an opportunity for the world to learn from Africa. Indeed, prior to the COVID crisis, the continent faced an Ebola outbreak which gave rise to the Africa CDC. This experience accumulated over the years is not to be overlooked at a time when pandemics are likely to become increasingly common.

, University of Namur, faculty of medicine, deptartment of biomedical sciences, and 

, professor of clinical trials, University of Namur, faculty of medicine, deptatment of biomedical sciences

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