Objectives

Regulators must balance medicine benefits and risks while ensuring consistency, transparency, and efficiency in decision-making and the aim of this study was to assess UMBRA’s impact on SAHPRA to determine if a structured approach enhances benefit-risk assessment quality and consistency.

Methods

A qualitative study applied the UMBRA framework to six NCEs reviewed by SAHPRA. Three assessors documented decision contexts, weighted benefits and risks, and interpreted the benefit-risk balance. Results were compared to prior reviews, with feedback gathered through questionnaires and discussions.

Results

The study assessed the impact of the UMBRA framework when applied to SAHPRA’s benefit-risk evaluations through retrospective and prospective analyses. In the retrospective study, three products: tofacitinib; brexpiprazole; and venetoclax were reviewed using the UMBRA templates, revealing greater transparency, structured decision-making, and alignment with global regulatory authorities. Assessors identified the key benefits and risks, assigned relative weightings, and compared the results to prior SAHPRA assessments. Tofacitinib and venetoclax showed favorable benefit-risk profiles, aligning with global approvals, while brexpiprazole’s assessment raised questions on indication approval. The prospective study applied UMBRA to icatibant, neratinib, and cabozantinib. UMBRA facilitated systematic identification of benefits and risks, enhancing assessors’ ability to justify decisions. Icatibant demonstrated a rapid onset of symptom relief, fulfilling an unmet medical need. Neratinib showed improved disease-free survival but had safety concerns requiring further local population studies. Cabozantinib addressed a regional oncology treatment gap, but additional data were requested before final approval. The assessors provided feedback on UMBRA’s advantages, citing improved objectivity, consistency, and transparency in benefit-risk evaluations. The structured format complemented narrative assessments, helped highlight critical safety issues, and encouraged reliance on international regulatory decisions. Challenges included retrospective implementation and aligning industry submissions with the framework. Overall, utilization of the UMBRA framework enhanced clarity, reproducibility, and decision-making transparency at SAHPRA, supporting its integration into the routine regulatory practices of new active substances.

Conclusion

This study demonstrated that a structured, systematic approach to benefit-risk assessment enhances consistency, transparency, and decision-making quality at SAHPRA. Using the UMBRA framework helped assessors clearly document decisions, justify benefit-risk balances, and align evaluations with global regulatory standards. By reducing subjectivity and providing a reproducible methodology, the UMBRA supports evidence-based regulatory decisions. Assessors found the framework valuable for identifying key clinical benefits and risks, assigning relative weightings, and ensuring thorough evaluations. It also enables better regulatory reliance, allowing African authorities to adopt globally accepted standards while addressing local needs. Applying a universal benefit-risk framework fosters regulatory harmonization, public trust, and clear communication of decisions through the publication of public assessment reports (PARs). The UMBRA’s structured methodology can guide the African Medicines Regulatory Harmonization (AMRH) initiatives and support joint reviews across regulatory agencies. Furthermore, with the advent of the African Medicines Agency (AMA), proliferation of a structured and systematic approach to benefit-risk assessment into a continental best-practice would allow the AMA to publish clearly substantiated PARs, detailing the scientific rationale for authorizing a product for use within the African population. The recommendations include integrating the UMBRA framework into routine regulatory assessments of innovative medicines, utilizing it to train new reviewers, and adopting it for reliance strategies to improve efficiency. By encouraging structured industry submissions, aligned with UMBRA, the methodology could further enhance decision-making consistency. Ultimately, the study underscores the importance of a systematic benefit-risk evaluation in ensuring equitable and transparent medicine approvals, benefiting the industry, regulators and patients.

This poster by Lorraine Danks, Boitumelo Semete-Makokotlela, Donald Chuma, John Joseph Borg, Star Khoza, Stuart Walker & Sam Salek was presented at the 2025 DIA Global Annual Meeting, 16-20 June 2025, Washington DC, USA.

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