Biomarkers: BIO Submits Comments on FDA Draft Guidance Biomarker Qualification: Evidentiary Framework

February 11, 2019

Re: Docket No. FDA-2018-D-4267: Biomarker Qualification: Evidentiary Framework; Draft Guidance for Industry and Food and Drug Administration Staff.

Dear Sir/Madam:

The Biotechnology Innovation Organization (BIO) thanks the Food and Drug Administration (FDA or Agency) for the opportunity to submit comments regarding the Draft Guidance on Biomarker Qualification: Evidentiary Framework.

BIO is the world's largest trade association representing 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.

BIO recognizes the FDA’s efforts to provide clarity around the evidentiary standards required for biomarker qualification. The Draft Guidance outlines a stepwise process to qualify drug development tools for use in drug development. While the process that a Sponsor may follow is outlined, we find that the Draft Guidance should provide information such as timelines that the Agency will follow when making determinations regarding whether a submission will be reviewed, when Sponsors may expect to receive feedback from the Agency, and information regarding how Sponsors may interact or engage with the Agency regarding their qualification submission. Such information will be important for successful qualification of biomarkers moving forward.

BIO appreciates that the FDA indicates in the Draft Guidance that many of the principles discussed in the guidance could also be appropriate for supporting the use of a biomarker in an individual drug development program (e.g., investigational new drug application, new drug application, or biologics license application submissions). We find this language very helpful and commend the FDA for making note of this in the Draft Guidance. However, in some cases, such as in the context of rare diseases, where there are limited patient populations, it may not be feasible for a Sponsor to qualify a new biomarker. While BIO acknowledges that the Draft Guidance provides a few examples (e.g., lines 385-387), where the Agency may provide flexibility for rare diseases, it would be helpful for the Draft Guidance to make note of other such areas where flexibility may be provided in the context of rare diseases, both in the context of qualification but also in the context of biomarker use for an individual drug development program. Additionally, information in the Draft Guidance regarding how qualified biomarkers may be used to support drug labeling and/or individualized/personalized medicine would also be helpful to include.

BIO also requests the FDA to consider including information in the Draft Guidance pertaining to the qualification of a biomarker that already has an established specific context of use (COU). For example, it would be helpful for the FDA to include information regarding whether a Sponsor can build upon a specific COU or whether a separate biomarker qualification submission would be required. Additionally, a single biomarker may serve multiple utilities. For example, pre-treatment levels of a biomarker may be predictive of response to a treatment and the same biomarker may also provide insights regarding treatment efficacy. To this end, we ask the FDA to clarify as to whether each proposed biomarker utility would require its own specific COU and a separate qualification submission. To encourage biomarker qualification, BIO encourages the FDA to take an approach that is not overly burdensome.

BIO also notes that the PDUFA VI Commitment Letter indicates that the Agency will establish a pilot program to engage external experts to support the review of biomarker qualification submissions. BIO views the use of such external experts as integral to ensure additional insight into emerging areas and thus the efficient review of qualification submissions and BIO encourages the Agency to use experts qualified in specific therapeutic areas, product development specialists as well as clinical researchers since they all have unique contributions to make. BIO is looking forward to hearing more from the Agency about the pilot program as well as other innovative approaches for accessing external experts for input into biomarker qualification. Additionally, the 21st Century Cures Act and FDARA Legislation include requirements that FDA share information about the biomarker qualification submissions, including those that result in qualification. This information will be extremely valuable to entities engaging in biomarker development. It will help biomarker developers better understand the range of studies needed for qualification of different types of biomarkers and different contexts of use. Therefore, we suggest that language be included in the Draft Guidance reminding readers of these requirements along with a link to the appropriate website(s). Additionally, the FDA might also consider putting some examples or case studies of successful biomarker qualification into the Draft Guidance as an appendix in order to provide additional clarity into the FDA’s thinking.

In addition to the comments above, we have also included several line edits that can be found on the following pages. BIO appreciates the opportunity to submit comments regarding FDA’s Draft Guidance, Biomarker Qualification: Evidentiary Framework. We would be pleased to provide further input or clarification of our comments, as needed.