Pediatrics: BIO Comments on FDA Draft Guidance Postapproval Pregnancy Safety Studies

The Biotechnology Innovation Organization (BIO) thanks the Food and Drug Administration (FDA or Agency) for the opportunity to submit comments to the Draft Guidance on Postapproval Pregnancy Safety Studies.

July 1, 2019

Re: Docket No. FDA-2018-D-4693: Postapproval Pregnancy Safety Studies

Dear Sir/Madam:

The Biotechnology Innovation Organization (BIO) thanks the Food and Drug Administration (FDA or Agency) for the opportunity to submit comments to the Draft Guidance on Postapproval Pregnancy Safety Studies.

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BIO appreciates the FDA’s efforts to develop the Draft Guidance on Post approval Pregnancy Safety Studies as it provides important information to both industry Sponsors and FDA reviewers regarding the FDA’s views on safety monitoring after a product is approved. We support the objective of enhancing the medical community’s knowledge of medicines’ effects in these populations through the inclusion of safety information in product labelling.

BIO commends the FDA for welcoming the use of other types of post approval studies, beyond pregnancy registries for monitoring the safety of a product, especially those using electronic data sources. These newer sources of data can provide studies with greater power more quickly and may allow for several different comparator groups. However, as written, the majority of the Draft Guidance is focused on pregnancy registries, implying that registries are the default mechanism for conducting pregnancy surveillance in the post-marketing setting. For example, the Draft Guidance refers to other types of pregnancy surveillance studies as “complementary” and discusses the strengths and limitations for pregnancy registries (Section IV); however, there is no discussion of strengths and limitations for electronic data sources, population-based surveillance, or population-based case control studies. Additionally, the Draft Guidance recommends that protocols should include a statistical analysis plan and a description of target sample size based on power calculation only for pregnancy registries; however, this recommendation should apply to other type of studies (e.g., insurance claims data) as well.

As the FDA is aware, pregnancy registries often take 10 years or more to conduct, significantly limiting their utility in informing the risks of exposure during pregnancy. Furthermore, they often encounter difficulty when recruiting and enrolling an adequate number of patients. With these limitations in mind, the FDA may consider amending this guidance and balancing discussion of all possible methods of pregnancy surveillance, including the use of retrospective studies using electronic data sources and real-world evidence, the strengths and weaknesses of each approach, statistical considerations, and the circumstances under which it is appropriate to utilize each approach.

BIO also requests that the FDA consider referencing the need to making better scientific use of existing systems to collect and evaluate pregnancy information, such as enhanced pharmacovigilance studies. Such studies can capture information on all pregnancies exposed to a drug focusing on collecting data prospectively (e.g., when the pregnancy is reported either before the end of pregnancy or before the detection of a congenital malformation), in a way that resembles a registry. The aim would be to provide a denominator and full and consistent data through a clear follow-up schedule with repeated attempts to obtain and correct data. In order to support increased consistency among studies, and therefore be able to use data from several registries to contextualize the findings from registries studies, there is a need to standardize definitions and to align among public partners, service providers and regulatory authorities.

BIO appreciates this opportunity to submit comments on the Draft Guidance on Postapproval Pregnancy Safety Studies. 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.