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Real World Evidence: BIO Submits Comment Letter to FDA Draft Guidance on Submitting Documents Using Real-World Data and Real-World Evidence to the Food and Drug Administration for Drugs and Biologics

The Biotechnology Innovation Organization (BIO) thanks the Food and Drug Administration (FDA) for the opportunity to submit comments to the Draft Guidance on Submitting Documents Using Real-World Data and Real-World Evidence to the Food and Drug Administration for Drugs and Biologics.

Re: Docket No. FDA-2019-D-1263: Submitting Documents Using Real-World Data and Real-World Evidence to the Food and Drug Administration for Drugs and Biologics

Dear Sir/Madam:

The Biotechnology Innovation Organization (BIO) thanks the Food and Drug Administration (FDA) for the opportunity to submit comments to the Draft Guidance on Submitting Documents Using Real-World Data and Real-World Evidence to the Food and Drug Administration for Drugs and Biologics.

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BIO welcomes this procedural draft guidance from FDA. We believe this document establishes a simple and reliable mechanism for identifying submissions with Real World Data (RWD), and that this procedural step is an important one in the implementation of this new area of regulatory science and policy at FDA. We hope that FDA uses the checklist provided in the Appendix as a tool to connect intention to action. Specifically, FDA leadership has established a foundation of receptivity to data sources like RWD, but this intention to embrace innovation may be delayed or impeded by practical implementation challenges or lack of experience with RWD at the review division level. BIO encourages efforts to understand resources needed across FDA’s review divisions, in particular as they learn to assess novel data sources and applications of such data.

BIO encourages the Agency consider how Real World Evidence (RWE) or RWD tracking efforts could be utilized by the Agency to generate publicly available information (e.g., public summaries[1]), as this information will benefit sponsors, researchers, as well as the Agency in advancing use of RWD for regulatory decision-making. For example, FDA could periodically publish aggregate, deidentified data on the number of RWE submissions made, context-of-use, study design, data type, and therapeutic area. Similar metrics have been made available to track the implementation of the Breakthrough Therapies Program and have been found generally helpful by the research community.

The draft guidance also describes submitting documents containing RWD/E in submissions that are either INDs, NDAs, and BLAs. In addition, the Agency encourages that Sponsors request early feedback in the form of Type B or C meetings if a Sponsor is considering the use of RWD/E in an IND, NDA, or BLA. Therefore, we suggest that the FDA consider internal tracking of pre-submission feedback (i.e., Type B and C meetings) that may be related to the regulatory use of RWD/E, since these meetings provide context on Agency’s acceptance/denial for the use of RWD/E within an IND, NDA or BLA.

Furthermore, in order to better promote the collection and utilization of RWD/E for regulatory purposes, BIO recommends the Agency include, in this, or future guidance:

  1. a description of FDA’s process to determine whether the Agency agrees/disagrees with the Sponsor’s classification of RWD/E as included in the cover letter accompanying a submission;
  2. information on whether and how RWD/E was used to inform the regulatory decision;
  3. additional recommendations on the most appropriate mechanism for seeking FDA feedback pertaining to RWD/E;
  4. additional examples to those in Section III of the draft guidance which provide information on regulatory submissions that could include RWD and/or RWE and which ones the Agency intends to track or not. The RWD/E examples provided should be expanded to provide additional clarity on when to flag a submission that is used for supporting a regulatory approval or satisfy a post approval study. This would help ensure accuracy in achieving the stated objectives and better inform the use of RWD/E; and
  5. consider a common data structure and electronic data submission system. As there is currently no standard format for submitting RWD/E to the Agency, we recommend that the Agency work with industry and other relevant stakeholders to develop a common data structure for these submissions. Additionally, given that submissions containing RWD/E may include large datasets that cannot be submitted electronically due to FDA server restrictions, we recommend that the Agency address these capacity concerns regarding its technological infrastructure and logistics around the accessibility of these datasets to FDA reviewers.

Lastly, BIO suggests that FDA consider expanding the guidance to address inter-center harmonization on submission and use of RWE, in general, between Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER) and the Center for Devices and Radiological Health (CDRH). Namely, this draft guidance has been developed and issued by CDER and CBER only, while the final guidance issued August 2017 titled “Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices” covers CBER and CDRH. Neither the latter nor this draft guidance contain recommendations on how to indicate submitting RWD/E to CDRH, which could lead to inconsistency in tracking and informing the RWE program on medical device and combination product submissions containing RWE in support of regulatory decisions regarding safety and/or effectiveness. Furthermore, as FDA receives tracking information and develops best practices to inform the program, BIO encourages the Agency to share learnings and best practices (i.e., process and content via MAPPs) with other regulators (e.g., EMA, PMDA) to enable early harmonization and convergence.

BIO appreciates this opportunity to submit comments on the Draft Guidance on Submitting Documents Using Real-World Data and Real-World Evidence to the Food and Drug Administration for Drugs and Biologics. We provide additional specific, detailed comments to improve the clarity of the Draft Guidance in the following chart. We would be pleased to provide further input or clarification of our comments, as needed.