The Biotechnology Industry Organization (BIO) thanks the Food and Drug Administration (FDA) for the opportunity to submit comments on the International Conference on Harmonisation proposed guideline on E2C(R2) Periodic Benefit-Risk Evaluation Report.
BIO represents more than 1,200 biotechnology companies, academic institutions, state biotechnology centers and related organizations across the United States and in more than 30 other nations. BIO members are involved in the research and development of innovative healthcare, agricultural, industrial and environmental biotechnology products, thereby expanding the boundaries of science to benefit humanity by providing better healthcare, enhanced agriculture, and a cleaner and safer environment.
A. Indication Specific Benefit/Risk Evaluation
The guidelines suggest that the benefit-risk profile is specific to an indication and population. Thus, a separate benefit-risk is required for each indication. We request clarification on the type of documents that need to be submitted – is a separate report required for each indication or one single report with separate benefit-risk assessments?
It should be noted that a separate report for each indication represents significant challenges and potentially increased burden for industry to prepare and submit separate reports for each indication.
B. Methodologies for Benefit/Risk Evaluation
Additionally, the only advice on what constitutes a “benefit-risk assessment” in the guidelines is to “provide a clear explanation of the methodology and reasoning used to develop the benefit-risk evaluation.” For a guideline purporting to provide the structure for a report on benefit-risk assessment there is a noticeable lack of discussion regarding the methods of benefit-risk assessment. We request further clarification and discussion of benefit/risk methodologies in the context of this guidance.
We believe that methodology can change based on standard of care, indication, and jurisdiction. In regard to jurisdiction, should the detail of the PBRER also be dependent on the approval status in a given region/country? It seems that writing the same benefit-risk assessment for a product recently marketed in one region would be inappropriate for a region where it is not yet approved.
It is unclear how a MAH/sponsor should prepare a benefit-risk assessment common to all ICH regions when the benefits may vary by region as a function of the indications/uses approved by that region. The benefit-risk varies for population corresponding with each approved indication. To this end, should the sponsor include information on all indications approved regardless, or only those approved in all ICH regions, etc.? We ask that this be identified in the E2C guidance.
Furthermore, what may be considered “off-label” in one region could be on-label by another region, steps needed to take for risk-minimization activities could vary by region, affecting the conclusions and recommendations in the benefit-risk assessment.
BIO appreciates this opportunity to comment on “E2C(R2) Periodic Benefit-Risk Evaluation Report.” Specific, detailed comments are included in the following chart. We would be pleased to provide further input or clarification of our comments, as needed.