As discussed in our introductory blog post for FDA’s Benefit-Risk Framework for NDAs and BLAs, the FDA developed and utilizes a structured benefit-risk assessment framework to streamline their decision-making process regarding approval or licensure decisions of New Drug Applications (NDAs) and Biologics License Applications (BLAs). FDA’s Benefit-Risk Framework is the presentation for communicating the assessment of the benefits and risks based on the therapeutic context, available evidence and uncertainties for the product in development. The overall presentation of the benefit-risk assessment in the marketing application should align with the FDA’s guidance, as outlined in Figure 1, which considers 1) the therapeutic context, 2) the evidence, 3) the uncertainties, and 4) the regulatory options to manage risk and reduce uncertainties.

Figure 1:  FDA’s Benefit-Risk Framework¹

AEs = adverse events; REMS = risk evaluation and mitigation strategy
¹Food and Drug Administration. Guidance for Industry: Benefit-Risk Assessment for New Drug and Biological Products. October 2023.

Given that the FDA’s clinical review team completes the benefit-risk framework in this structured format, Rho highly encourages sponsors to use this tabular format as part of the benefit-risk assessment preparation and presentation in Module 2.5 Clinical Overview (Guidance for Industry: ICH M4E(R2)).  As noted in our introductory blog post for FDA’s Benefit-Risk Framework for NDAs and BLAs, sponsors are encouraged to build the benefit-risk framework throughout development, starting with drafting the Target Product Profile (TPP) to inform the therapeutic context and provide a road map for the development of your product. Critical sources of your product’s benefits, risks, and uncertainties are the comprehensive integrated analyses of efficacy and safety presented in the Integrated Summaries of Effectiveness and Safety in a marketing application; as such, it is important that the sponsor ensures the appropriate data are collected throughout development, especially in later stage development, to be able to effectively communicate why the benefits of the product outweigh the risks.

In collaboration with the sponsor, Rho experts support the development of the benefit-risk assessment for Module 2.5 and full content for marketing applications. We have found our approach to benefit-risk planning early in preparation of the marketing application is helpful both in terms of developing the key messages for the benefit-risk assessment and developing the framework with the sponsor’s assessment of their product’s benefits and risks. For marketing applications Rho has supported, we have had success in the FDA utilizing and incorporating significant Rho developed content in the structured benefit-risk assessments (Module 2.5.6 and tabular presentation) into the Agency’s own Summary Basis of Approvals. Reach out to our experts at Rho to help with your benefit-risk assessment for your marketing application.

Kimberly Koehn, Ph.D., Regulatory Scientist, has 10 years of experience in writing and editing scientific documents and publications across a variety of chemistry, biological, clinical, and regulatory fields. At Rho, she leads and manages regulatory and scientific authoring teams and has participated in the authoring and preparation of modules for regulatory submissions (IND, NDA, BLA, etc.), briefing packages to support regulatory meetings, clinical study protocols and reports, and other regulatory documents.