he COVID-19 pandemic exposed significant challenges in the pharmaceutical global supply chain, leading to severe shortages of drugs and vaccines worldwide. This resulted in a pronounced inequity in distribution, particularly disadvantaging the Global South. This disparity is largely due to the dependency of low- and middle-income countries (LMICs) on pharmaceutical manufacturing in more industrialized nations. To mitigate this inequity and ensure supply of medicinal products across the globe, manufacturing of medicinal products needs to be decentralized through the establishment of manufacturing sites in LMICs.
Overcoming Dependency on Vaccine-Manufacturing Countries
This approach involves local production of essential medicinal products to address the urgent needs of the LMIC. A major challenge in this process is the development of a pharmaceutical industry in regions with nonexistent or very basic regulatory systems, while ensuring high-quality production of pharmaceuticals.
We propose a model of parallel technology and regulatory (Tech and Reg) transfer, through which manufacturing technology alongside regulatory control mechanisms are transferred from developed regions with established pharmaceutical industries to LMICs. This model is a good entry point for any country that has a less experienced national regulatory agency, as it ensures that pharmaceutical production adheres to the highest international standards.
As a starting point, products to be manufactured in LMICs must already be authorized by mature agencies. This approach requires that the manufacturing sites located in LMICs be included in the marketing authorization issued by a mature agency. In this way, national regulatory agencies in LMICs can use reliance schemes to execute the necessary regulatory functions—for instance, by recognizing marketing authorizations or Good Manufacturing Practice (GMP) licensure issued by mature regulatory agencies.
Building on this concept, the precedent for a Tech and Reg transfer was set through a collaborative effort known as Vaccine Equity for Africa. This led to the BioNTech Comirnaty SARS-CoV-2 mRNA vaccine technology being transferred to Rwanda based on the European Community Marketing Authorisation of this product. The BioNTech Kigali facility was opened in December 2023, an important step in making the African continent more independent from global vaccine manufacturers in the north. In the near future, in addition to the SARS-CoV-2 mRNA vaccine and others licensed in the EU or other mature regulatory regions, this approach will focus on the manufacture of vaccines that are mainly needed for Africa and not necessary for more industrialized nations. The ultimate goal of this Rwandan approach is to address as many unmet medical needs of the continent as possible and to provide equitable access to globally needed vaccines.
Prerequisites for Regulatory Systems to Establish a Pharmaceutical Industry
To successfully implement a Tech and Reg transfer model, several foundational elements must be in place.
First, a basic but nonetheless robust regulatory framework must be established in accordance with World Health Organization (WHO) principles. Central to this is the creation of an independent national regulatory agency that is mandated by law to oversee all regulatory functions in the LMIC as outlined in the WHO global benchmarking tool (GBT). Its independence from political decision-making is crucial for impartiality and effectiveness.
Second, a contemporary drug law in accordance with international standards should be in place to regulate domestically manufactured products. All regulatory functions should be covered in the legal framework with the primary focus on reliance schemes. Reliance on established, highly mature regulatory authorities is of particular importance because it ensures that the quality, safety, and efficacy of pharmaceuticals meet high international standards.
After an independent national regulatory agency and basic drug law have been created, it is easier to attract investors to establish manufacturing facilities. However, to attract medicinal product developers and manufacturers, LMICs will need to operate under the highest possible standards and gradually advance their maturity level according to WHO standards. Steps to prepare for local manufacturing should include undergoing training to perform future site inspections, to issue GMP certificates and manufacturing licenses, and to carry out oversight activities.
Training to support drug product manufacturing should focus on enabling the regulatory authority to monitor GMP facility construction and review relevant manufacturing processes and QC procedures to ensure that their implementation at the facility is GMP compliant. Additionally, personnel should be trained on the specifics of aseptic manufacturing and control. When it comes to site inspection, practical training, such as participation in inspection activities performed by mature regulatory agencies or by experienced third-party GMP consultants, should be included. The focus should be on products or product types relevant for the LMIC in question and aligned with that country’s or region’s plans to attract specific manufacturers.
To ensure a diverse and comprehensive supply of medicinal products, strategic collaborations and alliances with other manufacturing countries in the Global South should be established. Such partnerships could facilitate the sharing of responsibilities, expertise, and resources, thereby enhancing the collective capacity for pharmaceutical production and regulation—for example, monoclonal antibodies (mAbs), chemical active pharmaceutical ingredients, mRNA vaccines and related products, and antibiotics could be manufactured in different countries, each specializing in certain types of medicines. Such a strategy not only optimizes the regulatory framework but also promotes a more equitable and efficient distribution of medical resources, leveraging the unique strengths and expertise of each participating country or region.
Parallel Tech and Reg Transfer as Entry Point for Regulatory System Development
This proposed model of a parallel Tech and Reg transfer offers a low-threshold entry point for LMICs with limited regulatory systems to establish and control pharmaceutical manufacturing in the country according to the highest possible standards.
With the approach of a parallel Tech and Reg Transfer, less experienced National Regulatory Authorities could learn how to regulate medicinal products starting with simple regulatory reliance schemes. Over time, these skills and expertise could be expanded further to gradually develop independence and local expertise. To achieve greater regulatory maturity, collaboration with experienced stakeholders such as WHO, EMA, the US FDA, or other mature health authorities should be considered to provide support with specific training programs, twinning initiatives that pair an LMIC regulatory body with a mature regulatory authority, and practical experience sharing. Rwanda FDA (RFDA) provides a great example of quick progression in terms of maturity and autonomy. The RFDA has recently built an extensive network of collaborators and twinning partners, including several leading agencies from the Global North such as ANSM of France and PEI of Germany, and has also fostered collaboration within the continent with agencies such as Ghana FDA, which has already reached maturity level 3 (ML3) (out of 4) according to the WHO GBT.
Similar collaborative models are currently being adapted by other regions and countries. For example, Barbados Drug Service, representing the Caribbean region, has recently officially introduced a White Book describing the regulatory models appropriate for that country.
Model for the Future
Adoption of decentralized pharmaceutical manufacturing in the Global South is a critical step toward addressing the inequities in global pharmaceutical access. By integrating parallel Tech and Reg transfers, these nations can be empowered to not only meet their immediate healthcare needs but also contribute to a more balanced and resilient global healthcare system.
This approach calls for a collaborative effort, demanding commitment from international stakeholders to ensure its success and sustainability. Ultimately, this will ensure that access to essential medicines is a universal reality, bridging gaps and fostering global health equity.