Knowledge Brief Health, Nutrition and Population Global Practice Regulatory Systems Strengthening for Medicines in Africa: Shining a Spotlight on the World Bank Group’s Decade-Long Contributions A. Mercado, A. Seiter, K. Boateng and L. Philippe Kagan August 2022 KEY MESSAGES: Introduction • The African Medicines Regulatory Harmonization Ten years ago, the World Bank Group (WBG) committed its (AMRH) initiative, a multistakeholder partnership, support to helping African countries strengthen their focuses on improving fragmented regulatory medicines regulations, governance, and accountability in the systems in the region to ensure faster access to pharmaceutical sector of their health care systems. safe, efficacious, and good quality medicines and Strengthening the medicines regulatory environment is a well- vaccines. established prerequisite for increasing access to safe, • With support from the Bill and Melinda Gates efficacious, and good quality medicines, and for the successful Foundation, the World Bank Group set up a trust development of a functioning pharmaceutical industry. While fund in 2011 to support AMRH work. affordability remains the cornerstone of access (WHO 2020), • Since then, significant improvements have been other factors play a role in hindering access to quality made across the region, including notable medicines. In Africa, these barriers can be attributed, in part, decreases in timelines for the registration of to “weak or non-coherent regulatory standards and medicines, more harmonized registration requirements among countries; lengthy medicine registration systems, and an enhanced focus on quality processes that lead to delays in approval decisions; technical management and transparency in the drug capacity and capability; overall resource constraints; and registration process. failure to leverage regulatory review activities already performed by better-resourced regulatory authorities and the • The COVID-19 pandemic has shown that World Health Organization (WHO)” (Ndomondo-Sigonda et al. harmonized and well-established regulatory 2018). systems are critical to ensure access to safe, efficacious, and good quality medicines and At the WBG, ensuring that such barriers are removed so that vaccines. every person can lead a healthy, productive life is central to • The establishment of the African Medicines our shared goals of ending poverty and boosting our shared Agency, the next chapter in the AMRH initiative, prosperity. In 2011, to help make life-saving health products provides the opportunity to continue more accessible in poor countries, the WBG with generous institutionalizing this important medicine regulatory funding from the Bill and Melinda Gates Foundation (BMGF), system’s strengthening work, while increasing set up a trust fund to support the African Medicines Regulatory Harmonization (AMRH) initiative (Figure 1). country ownership and ensuring sustainability. Page 1 HNPGP Knowledge Brief • Figure 1: Key Milestones of the AMRH Initiative Source: Adapted from presentation on “The AMRH Program: Overview of World Bank Support, Achievements and Planned Activities” by L. Philippe Kagan et.al., November 18, 2021. Notes: EAC MRH = East African Community Medicines Regulatory Harmonization; WA MRH = West Africa Medicines Regulatory Harmonization; SADC MRH = Southern African Development Community Medicines Regulatory Harmonization; IGAD MRH = Intergovernmental Authority on Development Medicines Regulatory Harmonization; CEMAC MRH = Economic and Monetary Community of Central Africa Medicines Regulatory Harmonization; BETF = Bank-executed trust fund; AMA = African Medicines Agency. Two years before WBG’s involvement, the AMRH initiative In this paper, we discuss the remarkable achievements of the was launched by a consortium of partners 1 to expedite market AMRH Trust Fund managed by the WBG over its decade-long authorization to facilitate alignment of national legislative frameworks with the African Union (AU) Model Law on Medical existence. We showcase the range of technical support and Products Regulations. The AU Model Law guides member strong partnerships undertaken by the WBG, in collaboration states and regional economic communities (RECs) in with its program partners, the World Health Organization harmonizing regulatory systems and in providing an enabling (WHO) and the African Union Development Agency (AUDA- environment for the development and scale-up NEPAD), to support the AMRH initiative. We discuss some of health technologies. As laid out in the treaty adopted on lessons learned from project implementation and conclude by February 11, 2019, by the AU Commission, the AMRH highlighting some opportunities for future donor engagement initiative serves as the foundation for the establishment of the in the area of medicines regulatory systems–strengthening in African Medicines Agency (AMA). Moving from 55 countries Africa. acting independently to six RECs with centralized regulatory functions through AMA, brings many benefits, especially for Background countries with limited regulatory resources to carry out oversight activities. Africa has only 16 percent of the world’s population and yet bears a disproportionately higher share of diseases: A decade later, a dynamic movement toward more communicable, maternal, nutritional, and newborn diseases harmonized registration systems, improved overall efficiency continue to dominate and present significant challenges for in medicine registration, and an enhanced focus on quality the health care systems in the region (World Bank 2013). management and transparency in the drug registration Adding to this grim reality, the lack of regular access to process has been established in Africa, thanks to the AMRH essential medicines is particularly concentrated in Africa initiative. Additionally, this important work has increased (WHO 2004). Without the availability of quality-assured, collaboration, information, and work-sharing among RECs, affordable drugs and vaccines in sufficient quantities, broader which are important components for strengthening supply global health efforts such as universal health coverage (UHC) chain integrity and for thwarting the spread of substandard and and the attainment of the Sustainable Development Goal falsified medicines. (SDG) 3.8 2 are doomed to fail. 1 The consortium of partners includes the Pan-African Parliament, access to quality essential health care services, and access to safe, African Union Development Agency (AUDA-NEPAD), the World Health effective, quality, and affordable essential medicines and vaccines for Organization (WHO), Bill and Melinda Gates Foundation (BMGF), United all.” https://unstats.un.org/sdgs/metadata/?Text=&Goal=3&Target=3.8 Kingdom’s Foreign, Commonwealth and Development Office (formerly (accessed June 28, 2021). DFID), and the Clinton Health Access Initiative (CHAI). 2 Sustainable Development Goal (SDG) 3, Target 3.8 reads: “Achieve universal health coverage (UHC), including financial risk protection, Page 2 HNPGP Knowledge Brief The pathway from drug product development to a drug’s The World Bank Group’s comparative advantages in appropriate use by consumers is a complex, lengthy employing innovative financing strategies, pooling donor undertaking that is fraught with a high degree of funding, and driving projects through its field-based unpredictability. The value chain involves many touch points management capabilities were critical in getting the AMRH with regulatory authorities, including licensing of facilities and initiative off the ground in 2011. Starting with an initial personnel, clinical trial approvals, marketing authorization, contribution of US$12.5 million from the BMGF, the WBG set factory inspections, reporting and management of side effects, up the AMRH Trust Fund and quickly mobilized additional and post-approval changes. Each step in the process has the funding from other donors including the United Kingdom’s potential of compromising drug quality due to tampering or Foreign Commonwealth and Development Office, US delays if robust regulatory controls, within the context of an Government/President’s Emergency Plan for AIDS Relief appropriate legal framework, are not applied. (PEPFAR), and GAVI, increasing its programmatic budget from US$12.5 million to about US$35.0 million over the last National medicines regulatory authorities (NMRAs) are the decade. In 2012, the first grant was awarded to the East gatekeepers to the medicines regulatory system. Their African Community (EAC). Thereafter, the trust fund mandate is to ensure that drugs circulating in the market are expanded its support to four more regions by 2019, namely, of good quality and safe for use. However, baseline studies the Economic Community of West African States (ECOWAS), conducted in 2009 revealed that while some countries in Africa the Southern African Development Community (SADC), the have robust and functional NMRAs, others have regulatory Intergovernmental Authority on Development (IGAD), and the systems that are virtually nonexistent (Ncube, Dube, and Economic and Monetary Community of Central Africa Ward 2021). Thus, it is not surprising that marketing (CEMAC). Additionally, AUDA-NEPAD and WHO joined the authorization (MA) and clinical trials authorization (CTA) for WBG as program partners, bringing their global health products such as vaccines and medicines coordination/advocacy prowess and technical know-how, experience significant delays ranging from four to seven years respectively, to benefit the regions. Thanks to the unwavering in comparison to other more resourced regions of the world support of these program implementation partners, impressive (Ndomondo-Sigonda et al. 2018). It is this highly fragmented gains in improving medicines regulatory systems have been landscape that drug manufacturers must operate in, many of recorded. whom end up being deterred from entering the market in the first place. Achievements Launched in 2009, the AMRH initiative rightly focuses on Regional collaboration and information-sharing were improving the fragmented regulatory system for product significantly enhanced following the implementation of the registration in Africa by changing from a country-focused regulatory harmonization initiative. With AMRH Trust Fund approach to a collaborative-regional one (Ndomondo-Sigonda support, the regional projects succeeded in bringing together et al. 2018). With many NMRAs being underresourced and regulators in the different RECs and pooling resources and lacking the capacity to carry out essential regulatory tasks, expertise to assess pharmaceutical products dossiers and to AMRH’s medium of change is to bring regional entities such fast-track registration of essential medicines. As a result, as the RECs and regional health organizations (RHOs), steering committees have been established as platforms for alongside NMRAs, to harmonize technical requirements and ensuring regular dialogue among member states, for project guidelines for registration of medicines, and to conduct the oversight and approval of main decisions. This also ensures typical functions of regulators, such as joint regional dossier sustainability of the initiative even after donor support ends. assessments and Good Manufacturing Practices (GMP) Technical expert working groups in the different regulatory inspections. The goal is to have faster registration cycle times functions 3 were also created and harmonized regulatory starting with generics and extending to other product criteria through the development of guidelines and categories. Adopting harmonized regional approaches to procedures. Due to requirements standardization, medicines medicines regulations benefits all stakeholders because it registration timelines were significantly reduced, potentially offers NMRAs unique opportunities to share responsibilities accelerating access to essential medicines. For instance, in and to build capacities for the vast majority of processes and EAC and SADC, the timeline for registration greatly decreased functions needed. Most importantly, enhanced collaboration from 24 months on average to 10 to 12 months on average. 4 and coordination benefits patients by ensuring that the best Furthermore, regulators participated in joint activities such as possible science, standards, and practice drive the regulatory joint assessments 5 of medicines’ dossiers and joint GMPs process, resulting in improved safety, innovation, and access inspections. 6 For example, the Southern African Development to medicines. Community Medicines Regulatory Harmonization (SADC 3 According to the WHO, the main pharmaceutical functions are (i) 6 Good Manufacturing Practices (GMPs) are the practices required to product registration; (ii) licensing of manufacturing, importation, and conform to the guidelines recommended by agencies that control the distribution; and (iii) control of medicine promotion and information. authorization and licensing of the manufacture and sale of 4 World Bank, “EAC Implementation Completion Report,” August 2018. pharmaceutical products. They are set by the International Consortium 5 Joint assessments are defined as collaboration among member states for Harmonization (ICH). in regions to assess quality, efficacy, and safety of medicines before granting marketing authorization. Page 3 HNPGP Knowledge Brief • MRH) project jointly approved 18 pharmaceutical products for The AMRH program as a platform for regulatory registration in the region, while IGAD granted a positive exchanges has proven to be key for African countries to recommendation for four products. These main regulatory collaborate on critical issues such as the fight against activities aim to guarantee that drug development complies substandard and falsified medicines but also in terms of with international standards and brings safe, good quality, and pandemic preparedness. AMRH has been an important efficacious products to the market. Moreover, the WBG is player in pooling together relevant expertise on the continent closely working with the RECs to develop a regional in an effort to accelerate the registration and deployment of information management system (IMS) for regulators to share new COVID-19 tools and interventions. At the onset of the confidential information about assessments, inspections, and pandemic, the AMRH platform used its strong convening pharmacovigilance and to avoid potential duplication of power to enable NMRAs across the continent to meet and efforts. share information quickly to address the effects of the disease. During these key interchanges, perspectives and Support from the AMRH Trust Fund played a critical role learning on the effective regulation, quality, and safety in strengthening governance and institutions, efficiency, assurance of in vitro diagnostic (IVD) devices, personal and transparency at the national level. Through the protective equipment (PPE), along with preparations for implementation of Quality Management Systems 7(QMS), clinical trials of prospective vaccines in member countries NMRAs’ efficiency and transparency significantly improved. were discussed. The forum helped to hasten steps in the As a result, quality of work and information-sharing with approval of various products, address drug and medical manufacturers and the public increased, leading to better supply shortages, and reduce any existing barriers that could accountability. The program supported QMS implementation negatively impact supply. It also enabled the quick adoption of in several NMRAs such as the Gambia, Ghana, Kenya, WHO COVID-19-related guidelines and boosted support for Tanzania, Uganda, and Zanzibar, all of which have become local production in the various member countries as an ISO-certified. In a customer survey, these countries also additional interventionary measure. reported improvements in the quality of services, better clarity of timelines for every stage of the process for medicines Outside regional projects, the WBG has also been regulation, as well as inputs and outputs for each regulatory supporting work in thematic areas that contribute to function. Efficiency and transparency were also enhanced as overall improvements in the pharmaceutical governance countries started using IMS at the national level. Regulatory sector. In 2019, the Global Steering Committee (GSC) for systems were assessed in more than 20 countries in CEMAC, Quality Assurance of Health Products received support from IGAD, and SADC using the WHO Global Benchmarking Tool, the trust fund. The GSC serves as a voluntary coalition of their maturity levels were determined, and institutional major health development and financing agencies working development plans were prepared for governments to act on. together to enhance supply chain integrity and to combat the Although, most regulatory authorities were ranked at maturity challenges associated with falsified and substandard level 1 (out of 4), the program supported the Ghana Food and medicines in low- to middle-income countries. Also, the WBG Drug Authority (FDA) in reaching maturity level 3. recruited a consultancy firm in 2019 to review the existing Furthermore, assessments of the respective legislative AMA Business Plan and Institutional Framework with a view environments led to the development of draft legislations to to develop recommendations for a five-year strategy and align outdated countries’ laws with the AU Model Law, paving revised the business plan for the operationalization of AMA. the way toward the establishment of autonomous medicines The review successfully addressed many outstanding regulatory authorities. Some countries in CEMAC have also questions surrounding the precise size, scope, scale, been using the legislative assessment to advocate for the governance, and functioning of the AMA, including its ratification of the Treaty for the Establishment of the African financing model; the product and functional scopes; and the Medicines Agency (AMA). operational transitioning of AMRH activities, structures, and governance to the AMA. Regulators’ capacity was strengthened in all the RECs through the support of the AMRH Trust Fund. In collaboration Lessons Learned with the WHO, training workshops, curricula in the different Some of the core elements for achieving more consistent and regulatory areas, post-marketing surveillance, Integrated sustainable impact in MRH activities are as follows: Management Systems (IMS), and Quality Management • Prioritize deeper engagement with countries. Efforts to Systems (QMS) were organized. As a result, 1,433 regulators engage countries to drive the decision-making process and health personnel across the continent benefitted from need to be constantly prioritized, as ultimately the success these capacity-building activities and had the opportunity to of the regional activity depends on them. Strong NMRA disseminate knowledge in their respective agencies. commitment and ownership, especially the involvement of Strengthening capacity across the continent was critical to the heads of agencies, are key to strengthening minimizing disparities among countries, as it allowed countries regulatory activities, such as integrating MRH activities to better collaborate, build trust, and move toward a future of into the overall work plan and deliverables of the country’s mutual recognition of regulatory assessments and decisions. regulatory agency for better workflow and staffing 7 Quality Management Systems (QMS) can be defined as a set of interacting elements based on procedures, policies, resources, and objectives that are established collectively to guide an organization. Page 4 HNPGP Knowledge Brief support. For example, AUDA-NEPAD has been at the forefront of • Allocate additional resources for institutional formalizing and operationalizing many of the AMRH’s strengthening in less-resourced NMRAs to facilitate institutional structures and procedures, including the AU their eventual full participation in the harmonized Model Law and AMA. Where AMRH donors and international system over the long term. Although, significant support organizations are concerned, the opportunity to engage was provided for several capacity-building and twinning directly with the regions creates new channels for initiatives, additional time and investments in human communication and collaboration. Finally, given the extensive resources and infrastructure, along with securing the operational and technical knowledge and network built over necessary political will and support, were necessary to the last decade, both at global and regional levels, the WBG bridge the gap between less-resourced NMRAs and the is also uniquely placed to continue supporting AMRH through stronger NMRAs. collaboration with governments and the donor community. • Encourage regular, open dialogues with stakeholders Moving forward, a key priority for improving access to such as the pharmaceutical industry to increase medicines in Africa would be to strengthen their accountability and to make the process more transparent. pharmaceutical manufacturing capacity. Through the support of the International Finance Corporation (IFC), the WBG is well-positioned to support the continent toward achieving Conclusion greater independence in the supply of quality medicines. Taken together, the WBG partnership under the AMRH Trust Fund has contributed immensely to strengthening systems and to improving the overall efficiency of the medicines References regulatory landscape in Africa. With the dedicated support of Ncube, B. M., A. Dube, and K. Ward. 2021. “Establishment of the African WHO and AUDA-NEPAD, it has built important partnerships Medicines Agency: Progress, Challenges and Regulatory with public and private stakeholders and created a vibrant Readiness.” J of Pharm Policy and Pract 14 (29). community of regulatory harmonization advocates in the https://doi.org/10.1186/s40545-020-00281-9. region. During the COVID-19 pandemic, RECs adjusted Ndomondo-Sigonda, M., J. Miot, S. Naidoo, A. Ambali, A. Dodoo, and H. quickly to carrying out their essential work activities, despite Mkandawire. 2018.”The African Medicines Regulatory the very challenging context. For example, joint assessments Harmonization Initiative: Progress to Date.” Medical Research and inspections transitioned completely to a virtual Archives 6, no. 2 (February). environment and innovative solutions were used to quickly https://esmed.org/MRA/mra/article/view/1668 share information and to connect with other stakeholders. This WHO (World Health Organization). 2004. The World Medicines level of dedication speaks volumes about the regions’ Situation, 2nd ed. Geneva. commitment to the long term and about the sustainability of https://apps.who.int/iris/bitstream/handle/10665/68735/WHO_ the AMRH program. Despite these impressive gains, more EDM_PAR_2004.5.pdf?sequence=1&isAllowed=y work needs to be done to fully realize the benefits of regulatory harmonization. For example, there needs to be a standardized ———. 2020. “Access to Medicines: Making Market Forces Serve the electronic submission portal for each region; national Poor.” https://www.who.int/publications/10-year- review/chapter-medicines.pdf. regulators need to be more reliable in fast-tracking approval for jointly reviewed products; communication between World Bank. 2013. “The Global Burden of Disease: Main Findings for regulators and manufacturers can be improved; and national- Sub-Saharan Africa.” level capacity needs to be strengthened, to name a few https://www.worldbank.org/en/region/afr/publication/global- priorities. Additionally, a major milestone for achieving a burden-of-disease-findings-for-sub-saharan-africa (accessed on June 27, 2021). mature regulatory environment is the establishment of AMA, which is yet to be realized. World Bank. 2018. “EAC Implementation Completion Report.” World Bank report. On October 31, 2021, the WBG officially closed its projects https://documents1.worldbank.org/curated/en/1188915341825 and activities under the AMRH Trust Fund. This planned 37235/pdf/ICR-for-the-African-Medicines-Regulatory- Harmonization-Project-P128332-Final-08082018.pdf closure presents many opportunities for redefining the donor and coordinating landscape for MRH in Africa. With their growing capacity and ownership of the MRH agenda, African institutions are poised to capitalize upon this new opportunity and to keep the current momentum to ensure sustainability. Page 5