A recent article by Shashi Amur and FDA colleagues on the future of biomarker development (Biomarker Qualification: Toward a Multiple Stakeholder Framework for Biomarker Development, Regulatory Acceptance, and Utilization) provides a solid foundation for ongoing development and review process for biomarker qualification. FDA should be applauded for their progress in agency collaboration with the Critical Path Institute (in biomarker consortia development), the recent total kidney volume and plasma fibrinogen prognostic marker approvals, and sponsorship of interactive sessions such as the recent CERSI meeting at University of Maryland, as well as their EMA partnership to facilitate collaborative review of drug development tool qualification.
We would encourage additional measures to hasten biomarker development, including:
- Maximizing Expert Resources: FDA needs adequate resources to provide advice and oversee review and decision-making. One solution is to partner with an external entity (an Intramural Biomarker Consortium-IBC) to develop early advice and serve as an expert sounding board for nascent biomarker efforts. The IBC could be a required or voluntary resource in the review process, especially for initial data package reviews. This approach would allow FDA staff to focus on their primary role of product review and regulatory oversight.
- Refined Evidentiary Considerations: The product development and research community should collaborate to support FDA in developing a framework for the proper level of evidentiary substantiation required for qualification and the criteria used to evaluate them – such that FDA can issue guidance -standards which do not exist today. The IBC could be charged with overseeing relevant workshops and the drafting of initial guidance documents (consistent with FDA’s Good Guidance Practice recommendations and provided FDA is actively participating and has final approval).
- Qualification Plan: FDA should clarify the components of individual qualification plans and judge submitted data packages against them. Decisions not to qualify a proposed biomarker for a particular context should be accompanied by an explanation of the evidentiary gaps between the agreed plan and the submitted qualification package. IBC could work with biomarker developers to build these plans and perform initial data package reviews.
- Enhance Learning: Give FDA the authority to share information about biomarker qualification programs that are being advanced through collaborative efforts. Much can be learned by reviewing successes and failures across ongoing biomarker programs, and would inform the broader research community to enable refined evidentiary standards.
- Timeliness: FDA must clarify and communicate timelines for the qualification process in order to foster predictability and encourage participation. Such resources could be provided via PDUFA VI.
FDA can further solidify its place squarely in the center of the innovation ecosystem by fostering collaborative alliances with all stakeholders, enhancing qualification planning, sharing developmental endeavors, and clarifying standards.
Peter J. Pitts
President, Center for Medicines in the Public Interest
Former FDA Associate Commissioner
Timothy R. Franson, M.D.
Chief Medical Officer – YourEncore
Immediate Past President- US Pharmacopeial Convention