The Biotechnology Industry Organization (BIO) thanks the Food and Drug Administration (FDA) for the opportunity to submit comments on the “Draft Guidance for Industry on Enrichment Strategies for Clinical Trials to Support Approval of Human Drugs and Biological Products.” BIO commends FDA on the release of this Draft Guidance, which will help to increase the efficiency of clinical research and, ultimately, to facilitate the development of therapies with better defined benefit-risk relationships for relevant patient populations.
BIO represents more than 1,100 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A. Improving the Utility of the Draft Guidance
In general, the Draft Guidance is very helpful and well written, providing useful examples and references to illustrate the important principles underlying each section. BIO believes, however, that the overall utility of the Draft Guidance would be enhanced by more explicit and deliberate discussions of the labeling implications for the specific enrichment strategies presented, as well as a discussion that identifies the common factors that prevent achievement of various enrichment goals and provides recommendations to address them. Additionally, there is confusion and concern with the definition offered for “prognostic enrichment,” which is highlighted in several specific questions and comments in the table below.
B. Broadening the Scope of the Draft Guidance
BIO suggests that several sections of the Draft Guidance should broaden their focus beyond pivotal registration trials and point out relevant enrichment approaches for non-registration Phase 1 and 2 trials. The distinction between registration and non-registration studies is important, particularly for co-development of a drug with a predictive biomarker. In non-registration programs, all studies will generally be purely inductive in nature until both the dose(s) and population for registration studies are selected. Often the selection will not be achieved until the end of Phase 2b studies. This sets non-registration programs apart in that there is typically not an expectation that Phase 2 studies would be used to support registration of the drug, and this may permit greater flexibility with respect to enrichment programs.
C. Highlighting the Relationship to Other, Relevant Guidance Documents
BIO shares the Agency’s commitment to modernizing the conduct and improving the efficiency of clinical research, while ushering in an era of more personalized care to patients. To advance this commitment, BIO enthusiastically supports efforts by the FDA to address regulatory aspects of Adaptive Design Clinical Trials, Drug Development Tools, In Vitro Companion Diagnostic Devices, and related guidance documents and encourages FDA to cross-reference, where appropriate, these and other important guidance documents to provide a more cohesive view of the Agency’s current regulatory policies related to clinical research and development of more personalized therapies for patients.
BIO appreciates this opportunity to comment on the “Draft Guidance for Industry on Enrichment Strategies for Clinical Trials to Support Approval of Human Drugs and Biological Products.” Specific, detailed comments are included in the following chart. We would be pleased to provide further input or clarification of our comments, as needed.