FDA Issues New Guidance on Sex and Gender Considerations in Medical Device and Drug Development

The U.S. Food and Drug Administration has issued several new draft guidances aimed at improving how sex and gender differences are addressed in medical product development, signaling a significant shift in the agency's approach to ensuring medical products are safe and effective for all populations.

On January 7, 2025, the FDA released a draft guidance titled "Evaluation of Sex-Specific and Gender-Specific Data in Medical Device Clinical Studies," which encourages science-driven consideration of both biological sex and gender when designing clinical studies for medical devices. This guidance, when finalized, will update and replace the agency's 2014 policy that focused primarily on sex-specific data.

"Differences in physiology between females and males can lead to differences in disease manifestation, pharmacokinetics, pharmacodynamics, and response to treatment," the FDA noted in its announcement. The agency is accepting public comments on this draft guidance until April 7, 2025.

Comprehensive Approach to Sex and Gender in Clinical Research

The FDA simultaneously issued a companion draft guidance, "Study of Sex Differences in the Clinical Evaluation of Medical Products," which provides recommendations for increasing female enrollment in clinical trials, analyzing sex-specific data, and including sex-specific information in regulatory submissions.

Dr. Richard Pazdur, director of the FDA's Oncology Center of Excellence (search)Search term and acting director of the Office of Oncologic Diseases in the FDA's Center for Drug Evaluation and Research (search)Search term, emphasized the importance of these guidances: "This new draft guidance builds on the agency's ongoing efforts to enhance clinical trials by providing recommendations to improve participant safety and further clinical research."

The agency also released a draft guidance on "Considerations for Including Tissue Biopsies in Clinical Trials," developed in collaboration with the Office for Human Research Protections. This guidance addresses the use of tissue biopsies in adults and children participating in clinical trials evaluating investigational medical products.

Updated HCT/P Donor Eligibility Criteria

In a significant policy shift, the FDA issued four draft guidances and two final guidances on human cells, tissues, and cellular and tissue-based products (HCT/Ps) regarding donor eligibility determinations. These guidances aim to expand the pool of eligible donors while maintaining appropriate safeguards against disease transmission.

Dr. Peter Marks, director of the FDA's Center for Biologics Evaluation and Research (search)Search term, stated, "The FDA continues to work diligently to ensure that HCT/P donor-eligibility recommendations are grounded in the best available science and data."

Notable changes include:

• Revising recommendations for donor screening by reducing certain time-based risk factors and conditions
• Eliminating screening questions specific to men who have sex with men (MSM) and women who have sex with MSM
• Implementing individual risk-based questions relevant to HIV, HBV, and HCV for every donor regardless of sex or gender

Accelerated Approval and Confirmatory Trials

The FDA also issued a draft guidance on "Accelerated Approval and Considerations for Determining Whether a Confirmatory Trial is Underway." This guidance clarifies the agency's interpretation of when a confirmatory trial is considered "underway" for drugs granted accelerated approval.

For drugs approved through the accelerated pathway, sponsors must conduct post-approval confirmatory studies to verify the anticipated clinical benefit. The guidance outlines factors the FDA will consider when determining whether a confirmatory trial meets the "underway" requirement prior to accelerated approval.

Optical Imaging Drug Development

Another draft guidance released on January 7 focuses on "Developing Drugs for Optical Imaging." This document provides recommendations to drug companies on designing clinical trials for optical imaging drugs used with imaging devices during surgery to detect tumors or delineate normal anatomical structures.

Medical Device Manufacturing Notifications

The FDA finalized guidance on "Notifying FDA of a Permanent Discontinuance or Interruption in Manufacturing of a Device Under Section 506J of the FD&C Act." This guidance clarifies when manufacturers must notify the FDA about interruptions in device manufacturing that could lead to supply disruptions during public health emergencies.

The agency will host a webinar on March 4, 2025, for stakeholders interested in learning more about these notification requirements.

Commitment to Diversity in Clinical Trials

These guidances align with the FDA's broader efforts to enhance diversity in clinical trials. On January 7, the agency submitted its report to Congress, "Diversity Action Plans Summary: FY 2023 and FY 2024," summarizing diversity plans received during that timeframe as required by the Food and Drug Omnibus Reform Act of 2022.

While the requirement to submit Diversity Action Plans will apply to certain studies for which enrollment begins after the publication of final guidance, the FDA noted that some sponsors have already begun voluntarily submitting diversity plans for clinical studies.

The comprehensive set of guidances reflects the FDA's commitment to advancing scientific understanding of how medical products affect different populations and ensuring that clinical research adequately represents the diverse patients who will ultimately use these products.