Understanding European Union Medicines for All (EU M4All) and its Role in Health Product Security in Africa.
Background
Low and middle-income countries (LMICs), particularly in Africa, face substantial hurdles in attaining health product security, essential to ensuring access to affordable, safe, and effective medicines. Africa bears 25% of the global disease burden, with a disproportionate burden of tuberculosis (TB), malaria, and HIV/AIDS, alongside an increasing prevalence of non-communicable diseases (NCDs). Individuals in Africa encounter significant barriers in accessing essential health products contributing to poor health outcomes across the region. According to the Pharmaceutical Manufacturing Plan of Africa, among the key challenges the continent contends with in achieving health product security include fragmented and weak regulatory systems, low investments in research and development as well as intellectual property, and inadequate human capacity. Strong regulatory systems are crucial to ensuring reliable access to quality-assured healthcare products and technologies in any country. Yet only 8 of the 55 National Regulatory Medicines Agencies (NMRAs) in Africa having attained the World Health Organization Maturity Level 3 status, which underscores gaps in regulatory capacities. These make it challenging for many countries to respond effectively to public health needs, particularly in times of health emergencies, and highlight the urgent need for continued investment in regulatory resilience and capacity-building across the region. To address these challenges, African governments are making efforts to enhance health products accessibility through regulatory harmonization initiatives like the African Medicines Regulatory Harmonization (AMRH) and, more recently, the African Medicines Agency (AMA). These initiatives aim to harmonize regulatory processes and strengthen regulatory systems across the continent. These have been through regional economic communities (RECs) joint assessment procedures such as East Africa Community Medicines Regulatory Harmonization (EAC MRH) and West Africa Health Organization (WAHO).
To support regulatory systems strengthening in Africa, international agencies such as the World Health Organization (WHO), Swissmedic, European Medicines Agency (EMA) have also developed and implemented alternative regulatory pathways such as EU Medicines for All (EU M4All), WHO Collaborative Registration Procedures, among others. Exploration of these pathways is crucial to attaining health product security in Africa as they are designed to bolster regulatory capacity and expedite access to essential health products. In collaboration with the European Medicines Agency (EMA) we hosted an industry discussion forum on November 7, 2024, targeting industry players, development partners, and NMRAs.
The objectives of these industry discussion forums were to:
- Create awareness about the European Union Medicines for All EU M4All procedure to industry, national regulatory authorities and development partners interest in medicines regulatory procedures in Africa.
- Outline the benefits and requirements for industry to use such a pathway in medicines registration
- Outline the features and process involved in medicines registration through the procedure with focus on how African national medicines regulatory authorities can participate in the program.
Methodology
Considering the burden of infectious diseases and compounding burden of non-communicable diseases (NCDs) in Africa, it is imperative to facilitate timely and reliable access to novel therapeutics in the continent. One mechanism of making this a possibility is to draw on expertise and foster strategic engagements to expedite the registration pathway for medicines in the continent. Cognizant of this need, we designed the project in the following format:
· We did cross-sectional literature review to establish the regulatory bottlenecks and opportunities to unlock these possibilities to make therapeutics accessible in the continent. Through this we established that registration timelines serve as a barrier to market entry for industry in the continent. However, it was also evident that interventions were being put in place to address this. These were however not achieving their expected outcomes due to:
a. Limited knowledge and understanding of the procedures by industry professionals and other stakeholders who could use them. They were therefore not being considered during regulatory strategy development phase for new product registrations.
b. Limited knowledge and openness to these procedures by national medicines regulatory authorities which was making it challenging for industry to adopt the same as the success of the same was not guaranteed.
· We further conducted document analysis with focus on case reviews of existing regulatory pathways to establish the available regulatory pathways that could be utilized to reduce registration timelines while driving access to therapeutics in the continent. Through this we reviewed Swissmedic MAGHP, European Union Medicines for All (EU M4all), WHO Prequalification (WHO PQ), Joint Assessment Procedures (JAPs) such as East Africa Community Medicines Regulatory Harmonization (EAC-MRH), WHO Collaborative Registration Procedure (WHO CRP), Regulatory Reliance among others.
· Guided by the above findings we prioritized the procedures for which to facilitate industry discussion forums starting with Swissmedic MAGHP and EU M4All. The criteria for selection were based on companies from the domicile country with innovations of need in Africa, responsiveness of the regulatory officers we approached.
EU M4All Procedure
The EU M4All initiative supports regulatory systems and exemplifies an international collaborative approach, combining the expertise of EMA with non-EU regulators and WHO to provide scientific opinions on high priority medicines intended for use outside the EU. This facilitates faster registration and approval processes for health products, ultimately improving access to health products in resource-limited settings such as Africa. EU M4All can be performed in parallel to a centralized procedure for products intended for use in EU and non-EU countries to accelerate medicines access at a global scale. Through EU M4All, approved medicines can be added to the WHO Prequalification List via the ‘alternative listing procedure,’ allowing them to bypass additional review by the WHO Prequalification Program. The procedure involves two main phases;
- Pre-submission Phase
- Scientific Opinion Phase
Pre-Submission Phase
During the development phase, developers can seek scientific advice at any stage of development. EU M4All offers scientific and regulatory guidance to applicants, outlining the appropriate tests and studies required during the development of a medicine. Applicants can also consult on the adequacy of pharmacovigilance practices and risk minimization measures to be implemented in the target countries where the product will be marketed. This support ensures that medicines meet rigorous safety standards, and that post-market surveillance aligns with local needs, promoting safer and more effective access to health products.
Eligibility of Products
Applicants are encouraged to seek eligibility for EU M4All at least 7 months before the intended submission date of the dossier. In accessing eligibility, EU M4All takes into consideration health products, including medicines and vaccines, that address a major public health interest for markets outside the European Union. They include, but are not limited to: Vaccines that are or could be used in the WHO Expanded Program on Immunization (EPI).
- Vaccines for protection against a WHO public health priority disease.
- Vaccines that are part of a WHO-managed stockpile for emergency response.
- Medicinal products for WHO target diseases such as human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), malaria, tuberculosis, lymphatic filariasis (elephantiasis), trachoma, leishmaniasis, schistosomiasis, African trypanosomiasis (sleeping sickness), onchocerciasis (river blindness), dengue fever, Chagas disease, leprosy and intestinal helminths.
Eligible products may also include new formulations, new pharmaceutical forms or routes of administration of medicinal products already authorized in the European Union, fixed-dose combination products and generic products.
The eligibility of the product is jointly determined by the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) in collaboration with the World Health Organization (WHO). Once eligibility is granted, a product lead and rapporteurs are appointed to oversee the review process. These rapporteurs consist of two specialized technical committees:
- Committee for Medicinal Products for Human Use (CHMP) rapporteur and co-rapporteur: CHMP members (national experts) responsible for assessing quality, non-clinical and clinical safety and efficacy aspects of a particular medicine
- Pharmacovigilance Risk Assessment (PRAC) rapporteur and co-rapporteur: PRAC members (national experts) responsible for assessing the pharmacovigilance plan, risk minimizations measures and safety follow-up
Simultaneously, the WHO will nominate WHO headquarters staff and NMRAs to participate as in the review process. These NMRAs will include representatives from target countries where the product is intended for use, as well as from WHO Member States. The selection of these experts is strategically based on their scientific expertise, to complement the EU assessment teams. This collaborative approach ensures a comprehensive and contextually relevant evaluation, aligning with the local needs where the product will be marketed. Moreover, participation of NMRAs not only builds trust in the process but also strengthens their capacities, enhancing their ability to regulate health products effectively within their own countries.
Role of WHO and NMRA Experts in EU M4All
- Act as scientific experts to contribute to scientific advice or evaluation.
- Share their comments on the assessment reports. Participate in PRAC/CHMP plenary meetings, ad-hoc expert groups, working parties or scientific advisory groups (SAG), as appropriate.
- Participate in Good Clinical Practice and Good Manufacturing Practice inspections, where possible to ensure compliance and the highest scientific and regulatory standards.
- Expedited approvals for NMRA as their participation provides awareness of scientific issues that are identified during assessment.
Note: NMRAs retain full independence in their final decision-making process regarding the granting of market authorization approvals following the scientific opinion.
Scientific Opinion Phase
Applicants may apply in parallel for an EU marketing authorization under the centralized procedure and an opinion under EU M4All for their medicine to be used outside the EU. For this simultaneous evaluation process, applicants will be required to submit two separate applications with the technical dossier for both applications being identical. While pre-submission meetings are not mandatory, they can be requested to provide valuable guidance and feedback on key considerations that applicants should address when preparing their application for initial marketing authorization. Successful pre-submission meetings should enable applicants to submit applications that conform to legal and regulatory requirements and that can be validated speedily. The applicant needs to identify the type of application at the time of submission, each associated with specific data requirements.
Submission should be made according to the requirements for the type of application selected with some requirements that do not apply;
· Paediatric Legislation
· Orphan Incentives
· 5-Year Renewal NRG consultation for the invented name and EU translations
· There is no obligation for the applicant to be established in the European Economic Area (EEA).
Timelines for the Procedure
The assessment of an application for a new medicine takes up to 210 active days for EMA experts to evaluate the evidence provided. This time is interrupted by one or two ‘clock-stops’ during which the applicant prepares the answers to any questions raised by the CHMP/PRAC. The assessment time may be reduced to 150 days, in case of ‘accelerated assessment’. This is applicable for medicines of major public health interest such as those that target a condition for which there is no treatment option and that have the potential to address the unmet medical need.
Scientific Opinion Phase
The pharmacovigilance systems and risk management plans (RMPs) requirements have to be tailored to the specific needs of the patient populations and healthcare systems in the countries where the medicinal product is intended for authorization. An updated RMP should be submitted to EMA upon request and/or whenever the risk management system is modified. EMA will keep an oversight of the post authorization life-cycle and may request the opinion holder to submit further post-authorization measures. The opinion holder is responsible for notifying EMA of any changes related to their medicine following the Committee for Medicinal Products for Human Use (CHMP) opinion and submitting variations in accordance with the regulatory requirements.
WHO Collaborative Registration Procedure (CRP)
The national registration process of a product assessed under EU M4All pathway can be done independently country by country or via the WHO CRP. This approach accelerates national approval, particularly in countries with limited regulatory resources, by leveraging the regulatory work already performed by Stringent Regulatory Authorities (SRAs) such as EMA. This facilitates quicker access to essential medicines for patients, improving global health.
EMA’s involvement in the WHO CRP occurs at the request of a marketing authorization holder, once they obtain the EU M4All scientific opinion. For national authorities to assess the medicinal product, the following documents are required:
- Product dossier used for EMA’s assessment.
- EMA’s assessment report – The CHMP assessment report applies for products that have gone through the centralized and EU M4All procedures and comprises
- The quality information summary to confirm sameness.
- A Good Manufacturing Practice (GMP) certificate or inspection report that verifies the applicant’s capability to consistently produce high quality pharmaceutical products, in compliance with the standards established by the European Medicines Agency (EMA). The GMP certificates are available in the EudraGMDP public database which contains:
- Manufacturing and importation authorizations for EEA Sites.
- Good Manufacturing Practice (GMP) certificates for EEA + 3rd Country Sites issued by EEA or MRA partners.
- Statements of non-compliance with GMP for EEA + 3rd Country Sites issued by EEA or MRA partners.
Industry Discussion Forum Participation
A total of 201 participants attended the discussion from 27 countries spanning Africa, Europe, Australia and Asia. Represented countries include Kenya, Eswatini, Egypt, South Africa, United Kingdom, Germany, Tanzania, Switzerland, Denmark, Zimbabwe, Botswana, France, Burundi, Uganda, Belgium, Morocco, Netherlands, Ghana, Ethiopia, Somalia, Senegal, Sudan, India, Rwanda, Ireland, Spain, and Australia. The participants comprised professionals from various sectors with the pharmaceutical and healthcare industries, including pharmacists, Regulatory Affairs and Pharmacovigilance Specialists, Quality Assurance Specialists, Project and Program Officers, Operations Specialists, Academicians, Clinical Researchers, and Pharmaceutical Consultants. Also in attendance were representatives from 9 NMRAs including Egyptian Drug Authority (EDA), Ethiopian Food and Drugs Authority (EFDA), Pharmacy and Poisons Board (PPB) of Kenya, Danish Medicines Agency, Botswana Medicines Regulatory Authority (BOMRA), Uganda National Drug Authority (NDA), National Medicines and Poisons Board (NMPB) of Sudan, Somalia National Medicines Regulatory Authority, and Burundi National Medicines Regulatory Authority (ABREMA).
Conclusion
Given the limited resources across Africa, it’s essential for stakeholders in the pharmaceutical industry to adopt and harness innovative approaches that promote faster, more reliable access to high-quality, safe health products and technologies. The rising demand for health products, driven by an escalating disease burden, underscores the need for efficient resource utilization while exploring sustainable solutions, such as bolstering local manufacturing capacity. Effective resource management begins with a clear understanding of what is available. Industry discussion forums, like this one, play a crucial role in building the capacity of industry professionals and regulatory authorities alike, fostering collaboration, and sharing knowledge to strengthen regulatory systems at national and regional level. As such, we recommend that NMRAs in attendance actively adopt and integrate the EU M4All pathway into their regulatory frameworks. In doing so, NMRAs should ensure that industry stakeholders have access to the necessary regulatory tools, guidance, and capacity-building initiatives to effectively leverage this mechanism.