FDA Finalizes Guidance on Sex-Specific Data in Device Clinical Studies: What Changed from the January Draft?

In March 2025, the FDA issued its finalized guidance titled "Evaluation of Sex-Specific Data in Medical Device Clinical Studies", replacing the January 2025 draft that introduced sex- and gender-specific data considerations. Here’s how the final version evolved:

Shift from Gender-Inclusive to Sex-Focused Language

• The January draft broadened the scope to include gender-specific data, explicitly addressing transgender, nonbinary, and gender-diverse populations.

• The March final guidance reverts to a sex-specific focus, emphasizing biological differences (male/female) without incorporating gender identity. The term "gender" was removed from the title and throughout the text.

• Definitions and discussion of intersex, transgender, or nonbinary identities were omitted in the final version.

Refocused Intent and Scope

• The final guidance narrows its scope to biological sex and removes references to behavioral, psychosocial, or cultural aspects linked to gender.

• Applicable study types remain the same (IDE, PMA, 510(k), HDE, PAS, 522 PS), but the focus is squarely on improving sex-balanced enrollment and sex-specific statistical analysis.

Statistical Analysis Reframed

• While both documents emphasize sex-stratified analysis, the March version simplifies the statistical expectations.

• It maintains structured recommendations for premarket, postmarket, and comparative study designs, but omits gender-based heterogeneity testing discussed in the draft.

Key Takeaway for Sponsors

Sponsors should design studies to capture sex-specific differences in safety and effectiveness and ensure that sex-stratified outcomes are clearly reported in regulatory submissions. While the January draft signaled a broader push for inclusivity, the final guidance consolidates around well-established practices to enhance the statistical rigor and transparency of sex-based outcomes.

Polaris Biomedical Commentary

Risk Management: When Patients Use Gender, Not Sex

Even though the FDA’s final guidance limits its focus to biological sex, real-world users don’t always engage with medical devices through a binary lens. Patients—especially those who are transgender, nonbinary, or gender-diverse—may provide gender-based information during clinical use, intake, or digital interaction.

If a device’s performance or safety varies based on sex-linked traits, but the system assumes all users neatly fit into "male" or "female" categories, this creates a foreseeable risk under ISO 14971:2019.

Likewise, under 21 CFR Part 820, manufacturers are responsible for identifying and mitigating risks that arise from reasonably foreseeable misuse or user error, which includes mismatches between system expectations and actual patient behavior in the real world.

Bottom line: Even if gender-specific analysis is no longer expected by FDA, it is still good risk management practice to examine whether differences in gender identity or expression could impact how the device is used and whether that creates safety or effectiveness concerns.

Regulatory Trending

For those of us tracking regulatory trends, this reversal signals a more cautious institutional approach to inclusivity. While the draft's inclusion of gender was progressive—and in many ways aligned with EU MDR and WHO principles—the final guidance reaffirms FDA’s preference for incremental, evidence-based policy evolution.

From a strategic standpoint:

• Companies preparing for EU MDR should continue applying the broader gender-inclusive frameworks outlined in your QMS, risk analysis, and clinical evaluation processes.

• FDA-facing documentation can follow the finalized sex-based structure, but we recommend documenting internal rationale for any exclusion of gender-based subpopulations, especially if your device will later seek global clearance.

• At Polaris Biomedical, we believe that building inclusive medical devices, supported by robust clinical evidence, not only advances health equity but also strengthens business value by better serving diverse patient populations.

This outcome serves as a reminder: regulatory agility is not about chasing headlines or reacting to drafts, it’s about designing systems that can gracefully adapt as guidance evolves.

If you’d like help aligning your clinical evaluation, PMS, or quality processes to meet both FDA and EU expectations without duplicating effort, let’s talk. Polaris Biomedical specializes in translating regulatory ambiguity into compliant and scalable actions.