ICH: BIO Comments on FDA Draft Guidance ICH E19 Optimisation of Safety Data Collection

September 25, 2019

Re: Docket ID: FDA-2019-D-1828: E19 Optimisation of Safety Data Collection; International Council for Harmonisation

Dear Sir/Madam:

The Biotechnology Innovation Organization (BIO) thanks the Food and Drug Administration (FDA) for the opportunity to submit comments on E19 Optimisation of Safety Data Collection; International Council for Harmonisation.

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 document on the optimization of safety data collection and support the goal to provide internationally harmonized guidance regarding when it would be appropriate to use a selective approach to safety data collection in some late-stage pre-marketing or post-marketing studies, and how such an approach would be implemented. Although we believe the guidance is well written, we have provided general comments below for FDA’s consideration, as well as detailed comments in the annexed table.

  • This guideline should be applicable to pharmaceuticals, biological and vaccines, and not applicable to advanced therapies or gene therapies. More specifically, consideration should be given to exclude certain classes of products from this guidance (e.g., advanced therapy medicinal products [ATMP] and gene therapies). With such limited experience of such products, the collection of comprehensive safety data should be required in order to fully elucidate the safety profiles for these products. It would not be justified to reduce data collection where no long-term benefit-risk assessment has been determined. This argument might be extended to all new chemical entities, and biologicals or vaccines subject to a novel manufacturing process. Hence it should be carefully considered whether exemptions from data collection may be granted to products under additional monitoring.
  • It is appreciated that this guideline provides further guidance for safety data collection and outlines the scenarios where reduced safety data collection might be acceptable, reducing burden to all parties involved. It would be desirable to explicitly extend the current scope (interventional and non-interventional studies) to other solicited sources of adverse events (e.g., Patient Support Programmes) to reduce administrative burden and to ensure collected safety data are valuable for protection of patients.
  • Exclusion from data collection, or enhanced data collection based on the presence of a specific biomarker, or biomarkers, should be considered. Where a specific biomarker is present (or absent), the safety profile of a medicinal product will change. Thus, there is an opportunity to specify that if a relevant biomarker is detected, then either additional testing may be required, or such testing may be rendered irrelevant.
  • Although the draft guidance provides details on when selective safety data collection may be considered, it would also be beneficial to understand the quantity or range of data to be accepted as “sufficient safety data” to justify utilizing selective safety data collection. A clear example or description would be helpful. It would also be helpful to provide additional guidance when it is appropriate for a sponsor to approach the regulatory agency to consider selective data collection since industry and regulatory agencies may have different thresholds.
  • BIO suggests FDA consider adding to the guidance how to address any bias when selective data collection occurs in a study where comprehensive safety data collection occurs for a specific subset of the population (i.e., paediatrics) or when some regulators/countries allow selective safety data collection. Conducting analysis of ADRs in these scenarios may lead to identification of false signals, therefore suggest adding this consideration in the guidance.
  • Specific references should be made to potential risks specified within the Risk Management Program or Risk Evaluation and Mitigation Strategy. In this case, it would seem prudent to ensure that the collection of safety data that might contribute to the evaluation and assessment of such risks should always be collected.

BIO appreciates this opportunity to submit comments on E19 Optimisation of Safety Data Collection; International Council for Harmonisation. 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.