BIO Submits Comments on Advancing the Use of Biomarkers and Pharmacogenomics
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The Biotechnology Industry Organization (BIO) thanks the Food and Drug Administration (FDA) for the opportunity to submit comments on “Advancing the Use of Biomarkers and Pharmacogenomics; Notice of Public Meeting; Request for Comments.” BIO appreciates the Agency’s commitment to advancing biomarker science and agrees that biomarkers offer the potential to realize much greater efficiency in, and a more personalized approach to, drug development.</p>
There are significant challenges for Sponsors of individual drug development programs seeking to utilize biomarkers, surrogate biomarkers and, particularly, alternative endpoints within their specific drug development programs. The processes through which advice/consultation can be sought from additional FDA offices and staff (i.e., Office of Translational Sciences, Study Endpoints and Labeling Development staff, etc.) to augment the experience/expertise of the FDA review divisions is not transparent. Additionally, the lack of timelines for receiving input or decisions from those support offices or staff makes it difficult for Sponsors to plan their drug development programs. Finally, there is no formal mechanism through which external scientific expertise can be leveraged by FDA to evaluate novel biomarkers, surrogate biomarkers and, particularly, alternative endpoints proposed early during drug development.
The current FDA Biomarker Qualification Program that supports regulatory qualification of biomarkers across drug development programs also presents significant challenges.Chiefly, there are no timelines or responsiveness requirements associated with the steps of the Qualification Process for Drug Development Tools
, creating unpredictability for biomarker sponsors. Also, rather than prospective evidentiary standards, the program relies upon a Consultation and Advice stage that is designed to align FDA and submitters on the standards for qualification to be used in each qualification submission (i.e., achieve regulatory consensus). The transit time through the Consultation and Advice stage of the process is long, and the outcomes from this stage are unpredictable. Qualification submissions since the inception of this process have been challenged to move beyond this stage, and this stage often re-evaluates (and contradicts) scientific consensus previously achieved through external scientific expertise and collaboration. Specifically, as of 2013, FDA had received 23 submissions to the Biomarker Qualification Program, with only three of those submissions receiving regulatory qualification. More concerning, though, is the fact that nearly 60% of those submissions (13) are mired in the Consultation and Advice stage of the Biomarker Qualification process, unable to align scientific consensus with regulatory consensus for qualification.
While these challenges are important, the overarching problem central to both processes is the lack of prospective evidentiary standards for biomarker acceptance or qualification. Without guiding, prospective evidentiary standards tied to context of use, it is impossible to have a consistent, coherent view of biomarker acceptance or qualification, regardless of access to external expertise or review timelines. Once prospective evidentiary standards for biomarker acceptance or qualification have been developed, their employment with appropriate risk-benefit calculus can be monitored through a transparent process, such as an Advisory Committee.
