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Clinical Trials: Scientific and Ethical Considerations for Inclusion in Clinical Trials

June 8, 2018

Re: Docket No. FDA-2018-D-1201: FDA Draft Guidance on Pregnant Women: Scientific and Ethical Considerations for Inclusion in Clinical Trials Guidance for Industry.

Dear Sir/Madam:

The Biotechnology Innovation Organization (BIO) thanks the Food and Drug Administration (FDA or Agency) for the opportunity to submit comments regarding FDA Draft Guidance, Pregnant Women: Scientific and Ethical Considerations for Inclusion in Clinical Trials Guidance for Industry.

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BIO supports the FDA’s work to develop the Draft Guidance titled Pregnant Women: Scientific and Ethical Considerations for Inclusion in Clinical Trials Guidance for Industry. We see this as an important step in ensuring that information regarding the safety and efficacy of therapies that may be used by pregnant women is available to patients and providers. Below we have included general comments regarding the Draft Guidance as well as more detailed comments beginning on page three of this letter for the FDA’s consideration. 

General Comments:

BIO views the Draft Guidance as being applicable to how and when to include pregnant women in drug development clinical trials. We interpret clinical trials to mean controlled interventional studies (with one or more arms) for drugs, biologics, or devices that are subject to FDA regulation. We ask the FDA to indicate whether the guidance also applies to post-marketing registries. Furthermore, we also ask the FDA to clarify whether the Draft Guidance applies to open label trials (where treatment assignment is clear) as well as blinded studies, where a pregnant woman may be assigned to placebo. Finally, we ask the FDA to clarify the applicability of the Draft Guidance to multinational and non-U.S. studies.

Throughout the Draft Guidance BIO requests that the FDA clarify if they view the term “nonpregnant women” to be used synonymously with “women of reproductive potential”.  For example, depending on the drug being evaluated, nonpregnant women could include post-menopausal women, or women deemed clinically infertile (e.g., post-hysterectomy).

BIO believes that guidance from the Agency regarding issues pertaining to the inclusion of lactating women in clinical studies is also of high importance for industry Sponsors. To this end, BIO asks that the Agency either include information pertaining to the inclusion of lactating women in this Draft Guidance or develop additional guidance that will specifically address issues pertaining to the inclusion of lactating women in clinical trials.

The number of pregnant women enrolled in clinical trials is expected to be small, except for medical products that are specifically indicated for pregnant women. BIO suggests the Agency provide guidance regarding how to analyse and interpret data obtained from pregnant women in clinical trials that are not indicated for pregnant women and how data obtained in pregnant women may be incorporated into the product label. Given that the number of pregnant women in clinical trials for products that are not indicated for pregnant women will be small, the Draft Guidance would also benefit from the inclusion of information regarding the use of innovative trials designs. For example, in Section C of the Draft Guidance, the FDA could provide information regarding the use of adaptive trial designs for the collection of pharmacokinetic data in pregnant women in cases where the product is not specifically indicated for pregnant women. In addition, given the small numbers enrolled in trials, the assessment of risk of a given product should also include information collected from off-label use of the product or from clinical experience with other products in the same class.

Finally, BIO also recommends that FDA consider including relevant statements in the Introduction and/or Background sections of the Draft Guidance regarding the use and importance of patient-focused drug development as it relates to clinical trials containing pregnant women. 

As the Agency continues to develop considerations for research in pregnant women BIO encourages the FDA to provide clear opportunities for Sponsors to discuss such research with appropriate review divisions. BIO appreciates this opportunity to submit comments regarding FDA’s Draft Guidance. We would be pleased to provide further input or clarification of our comments, as needed.