An Analysis of the Regulatory Requirements for the Registration of Biosimilar Medicines in Six African Countries with WHO ML3 Status as of July 2024

Abstract

Introduction Biosimilars are medicines of biological origin that contain a highly similar version of the active biological ingredient in a registered biological medicine (innovator), and might cost much less. Biosimilars are gaining importance in Africa as they are included in the priority medicine list published by the African Union Development Agency-New Partnership for Africa’s Development and will therefore undergo preferential evaluation in countries that support the African Medicines Regulatory Harmonisation Initiative. Biosimilar registration guidelines are constantly updated as new scientific information supporting the development and assessment of biosimilars becomes available. Biosimilars must demonstrate high similarity to the reference product, with no clinically meaningful differences in safety, purity, and potency. The review of biosimilar registration guidelines in African countries with matured regulatory systems is an important and necessary step to guide applicants on the latest regulatory requirements. Aim and objective The aim of this study was to review the biosimilar guidance documents of six selected countries in Africa, with the purpose of identifying similarities and differences. The countries weres elected on the basis of achieving World Health Organization Maturity Level 3 status or higher, as of the end of July 2024. The similarities and differences identified across these guidelines was used to develop a comprehensive checklist to promote regulatory compliance and alignment with the requirements of multiple territories in Africa. Requirements unique to individual country guidelines can be integrated into a single dossier, enabling a more comprehensive and robust submission. The ultimate goal is to facilitate the reduction of review deficiencies and streamline the registration process to support faster market authorization and simultaneous access across multiple target markets in Africa. Method A qualitative content analysis of the guidance documents for registration of biosimilar medicines from six African countries was performed. The selected countries were Egypt, Ghana, Nigeria, South Africa, United Republic of Tanzania, and Zimbabwe. Biosimilar registration guidelines implemented and updated over a period of 11 years, i.e., from 2014 to 2025, were reviewed thematically according to pre-determined categories. Results The review of the biosimilar guidance documents has shown an overall similarity of 69,01 % in the requirements for biosimilar medicine registration. Quality, nonclinical and clinical comparability studies are required in 100,00 % of the test population. The quality studies requirements show a range in similarity of 33,33 % (molecular weight, chemical modification, and aggregate formation) to 100,00 % (primary and higher order structure) in the test population. The non-clinical studies requirements range from 33,33 % (single-dose toxicity study) to 83,33 % (repeatdose toxicity study, Pharmacokinetic/Pharmacodyamic [PK/PD], and immunogenicity studies) in the test population. The clinical studies requirements range from 33,33 % (data on all investigated indications and interaction studies / data in special populations) to 83,33 % (PK/PD, immunogenicity studies, safety monitoring, and extrapolation of safety and efficacy across indications) in the test population. Reliance, as recognised in 100,00 % of the study population, will effectively contribute to work sharing and maximising the use of scarce resources at National Medicine Regulatory Authorities. Substitution and interchangeability of biosimilars and reference products still differs great across the study population with these concepts only accepted in 50,00 % of the countries investigated. Conclusion The guidance documents are mostly similar in terms of the requirements for registration of biosimilars, however variability persists in specific procedural, administrative, post-approval pharmacovigilance requirements, and interchangeability provisions. A harmonised checklist assists in closing this gap, by clarifying where a single, robust dossier could satisfy multiple jurisdictions' core scientific requirements.