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Codevelopment: BIO Comments on FDA Draft Guidance Principles for Codevelopment of an In Vitro Companion Diagnostic Device with a Therapeutic Product

Re: Docket No. FDA-2016-D-1703

Dear Sir/Madam:

The Biotechnology Innovation Organization (BIO) thanks the Food and Drug Administration (FDA) for the opportunity to submit comments on the “Principles for Codevelopment of an In Vitro Companion Diagnostic Device with a Therapeutic Product; Draft Guidance for Industry and Food and Drug Administration Staff” (Draft Guidance).”

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.

General Comments

BIO is supportive of FDA’s efforts to provide a practical regulatory guide for sponsors engaged in developing a therapeutic product and an accompanying IVD companion diagnostic (i.e. codevelopment).

In general, the Draft Guidance is helpful in describing general principles to guide codevelopment for contemporaneous therapeutic product and device marketing authorizations, regulatory requirements, administrative and clinical trial planning/execution considerations. BIO notes, however, that this draft guidance seems to also refer to the concept of a “complementary” diagnostic in the text.  In light of FDA’s recent approval of a device that belongs to this this new category, we request that the Agency reference “complementary” devices in the current draft, clarify regulatory requirements for approval of “complementary” diagnostics by issuing guidance devoted to the topic as well as discuss appropriate regulatory principles to compare and contrast to companion diagnostics.  Furthermore, the guidance should discuss the principles and criteria for making an assessment to distinguish between companion and complementary diagnostics.  This will allow industry to weigh the evidentiary requirements and provide input to the Agency.

Similarly, as we look forward to the future of Precision Medicine, some ‘companions’ are likely to be medical devices other than in vitro diagnostics (e.g., medical mobile application, wearables, etc.)  Either by footnote, as noted for future IDE guidance or in the guidance text, BIO believes that it would be beneficial for FDA to provide recommendations on similarities and differences between IVDs and other types of medical devices.

BIO notes that the document would benefit if some sections were expanded to provide additional information.  Namely, Section G, “Labeling Considerations”, should provide greater clarity to and information on labeling considerations for both companion and complementary diagnostics, refer to and potentially expand on other guidance documents that are salient to the subject (e.g. “In Vitro Companion Diagnostic Devices).  Although some detail is provided on adverse event reporting in the post-market setting, we think this guidance would benefit from a short discussion of these issues, including references to previous guidances that are relevant to these topics.

Similarly, it would be very helpful if the final guidance addressed some of the more challenging aspects of codevelopment such as multi-variate analyte CDx development, development and review considerations for “test system” IVDs (i.e. comprised of assay, instrument, software).  For example, the document could provide, among other considerations, more in-depth validation information for multi-variate companion diagnostics and/or provide reference to other guidance documents (i.e. Next Generation Sequencing-Based In Vitro Diagnostics draft guidance) and its relevance and application in the context of these important and novel technologies.

In the same vein, BIO suggests that the final guidance include a section on how clinical trial outcomes can affect IVD codevelopment and approvals in terms of possible outcomes (e.g. when the IVD does not result in a clear predictive outcome when employed in conjunction with a therapeutic in a clinical trial).

Lastly, BIO believes that harmonization of terminology is of great importance and benefit in this and other guidance documents.  Namely, the Biomarkers, Endpoints, and other Tools (BEST) Glossary, issued by FDA and NIH in January 2016, defined several types of biomarkers, including: predictive biomarkers, monitoring biomarkers, pharmacodynamic/response biomarkers, safety biomarkers as well as others.  We note that some of the terminology and concepts in the present guidance are not consistent with terms and concepts outlined in the BEST Glossary and strongly recommend harmonization between the two documents.

We provide additional, more specific comments on the draft guidance in the table following this text. We would be pleased to provide further input or clarification of our comments, as needed.