FDA updates guidance language, forms to align with Trump executive order

Life Sciences | By Amanda Conti, Laura DiAngelo, MPH

Feb. 03, 2025

During the past week, the FDA has quietly been making changes to important forms and guidance documents to align with a new executive order that directs agencies to “use the term ‘sex’ and not ‘gender’ in all applicable Federal policies and documents.” These changes to FDA documents appear to be still in progress, but here AgencyIQ walks through which documents have been changed so far, and what those changes are.

Quick Background: Rollout of Trump’s executive orders

  • President DONALD TRUMP issued a flurry of executive orders (EOs) to start his second term. As AgencyIQ previously discussed, these include EOs on topics related to the federal workforce, federal hiring, the issuance of regulatory policy, artificial intelligence, and diversity-related policies – all of which have specific implications for the FDA and its regulated industries. As a top-of-mind example, the FDA pulled its draft guidance on Diversity Action Plans (DAPs) and several other diversity-related projects following issuance of the EO to roll back diversity, equity and inclusion (DEI) policies at the federal level. Since AgencyIQ’s last update on Jan. 30, an additional diversity-related guidance has been taken down: the 2020 final guidance on “ Enhancing the Diversity of Clinical Trial Populations – Eligibility Criteria, Enrollment Practices, and Trial Designs.”
  • Another Jan. 20 EO, EO 14168, “recognize[s] two sexes, male and female” at the federal level and directs agencies to “use the term ‘sex’ and not ‘gender’ in all applicable Federal policies and documents.” Notably, following the issuance of this EO, the FDA removed a January 2025 draft guidance on sex- and gender-based differences in device development that had just been issued by the Center for Devices and Radiological Health (CDRH). As AgencyIQ noted on Jan. 30, additional guidance documents from the FDA do refer to “gender” and would likely also soon be updated. [ Read Agency’s status check on FDA’s diversity-related policies here.]
  • Over the past few days, FDA has begun updating its documents to reflect the policy under EO 14168, modifying wording to use “sex” and not “gender” in “all applicable Federal policies and documents.” Updates include both guidance documents and FDA forms.

First: FDA has formally released new editions of nine forms to halt collection of information on gender identity.

  • FDA develops forms to streamline submission of certain information to the agency. As of January 31, 2025, FDA’s forms database listed over 300 of these documents, which have a diverse array of functions across FDA’s product centers. A few examples include certain supplements, certifications and reports.
  • The agency has issued new editions of nine forms since Jan. 20, the majority of them related to the agency’s MedWatch program for post-market safety monitoring. As a refresher, stakeholders have different avenues to provide information to FDA in the post-market setting. Healthcare professionals and patients can submit voluntary reports to the FDA via MedWatch, while drug manufacturers submit reports to the FDA via the FDA Adverse Event Reporting System (FAERS). The recent update involves seven Form 3500 MedWatch documents geared toward voluntary, mandatory, and consumer reporters. The documents have been updated in both English and Spanish, and in multiple file formats.
  • The change: Questions regarding the patient’s gender identity have been removed from the forms. An archived version instructed the respondent to “Enter the patient’s current gender (how the patient thinks of themself).” The new version says, “Section Removed.” The prior question, which asks for “Sex: Enter the patient’s sex at birth (the sex that a person has or was assigned to at birth),” has also undergone changes. While the archived version shows options for “undifferentiated” or “decline to answer,” the Jan. 2025 version only provides “male” and “female” checkboxes. Industry should take note of this change, which is expected to have downstream effects on the granularity of post-market safety monitoring information about various populations.
  • The other two forms with new editions are the instructions and content of Form 3926, the Individual Patient Expanded Access Investigational New Drug Application (IND). As described in an Oct. 2017 final procedural guidance, the program allows licensed physicians to use an investigational new drug for a single patient outside of a trial, or use an approved drug “where availability is limited by a risk evaluation and mitigation strategy (REMS), for an individual patient who has a serious or immediately life-threatening disease or condition and there is no comparable or satisfactory alternative therapy.” When compared to the archived April 2024 version of the document, the Jan. 2025 edition makes one change: swapping the word “gender” for “sex.” More changes like this will likely be made in the coming weeks, AgencyIQ will continue to monitor their scope and implications.

While those forms received formal updates, FDA has quietly swapped language in multiple guidance documents

  • FDA’s revisions to existing draft or final guidance documents are customarily accompanied by a Federal Register notice and update to the issue date listed on the document. Now, the agency is varying from this practice as it updates documents to comply with EO 14168. In some updated guidance documents, FDA has added new footnotes to the cover pages with links to SharePoint files internal to the agency (see example here, with more information below. These documents have undergone editing to replace the word “gender” with “sex.” In another unusual move, the FDA has not provided any formal announcement accompanying these changes – and not all updated guidance documents include the footnote.
  • One updated guidance includes FDA’s version of the foundational 2001 ICH M4S safety guideline from the International Council for Harmonisation, which “primarily addresses the organization of the information to be presented in the Safety section of an application for new pharmaceuticals (including biotechnology-derived products),” according to the document. In a side-by-side comparison of the new document to the previous, the word “gender” has been swapped for “sex” on pages 9 and 11. No additional content changes were made apart from a note on the cover page that reads: https://fda my.sharepoint.com/personal/jennifer_clampet_fda_gov/Documents/Desktop/Updated Guidances-Jan 2025/48_M4S The CTD Safety/!4539S_Jan 2025 update.doc 01/31/25” The HHS employee directory indicates that the name included in the link belongs to a Senior Tech Writer/Editor in CDER’s Office of Regulatory Policy (ORP) This user’s name is also in the Sharepoint link referenced above.
  • Changing the text of an ICH document is particularly notable given the intent of these documents: To harmonize submissions to global regulators. –
  • Sponsors may notice other documents are missing. Over the weekend, CDRH’s Clinical Decision Support (CDS) software guidance document was taken down, but as of Monday, Feb. 3 it has been re-uploaded to FDA’s repository unchanged except for the deletion of the word “gender” in the two instances it previously appeared in the document. This document does not include the footnote indicating it was updated in 2025.

Analysis and what’s next

  • It appears that this work is ongoing: For example, two guidance documents on real-world evidence (RWE) are currently missing from the guidance repository, one each on the use of electronic health records (EHR)/claims data and registry data. However, both of these guidance documents remain included on FDA’s list of its RWE-related guidance documents, which indicates that they aren’t being pulled or withdrawn. From a keyword search, these two documents, one addressing EHR/claims data and the other registry data, are the only two documents in the RWE guidance dossier that include(d) the word “gender.” It’s thus likely that they will be replaced with slightly amended versions eliminating that term, as the FDA carries out word-replacement directive of EO 14168.
  • Similarly, the diversity guidance cited above (“ Enhancing the Diversity of Clinical Trial Populations – Eligibility Criteria, Enrollment Practices, and Trial Designs”) that has been taken down from FDA’s online guidance repository also included extensive references to “gender.” For now, it’s not clear if that guidance will be re-uploaded without references to “gender,” or if it will be removed from the FDA’s repository in to comply with the terms of the separate EO directing agencies to halt their DEI work.
  • Practically, this means that sponsors might be collecting data that FDA is no longer going to be looking for, as the agency deletes references to “gender” from guidance, and removes the term from forms. Further, it also likely creates a bit of a divergence from what other regulators are looking for, as in the FDA-specific change to the ICH document. This means that sponsors and researchers may need to adjust their internal processes to account for these changes. The disappearance of these data fields may result in a disruption in data collection going forward, which could impact future research into demographic subgroup differences.
  • The discreet actions to comply with EO 14168 may clash with another EO. During Trump’s first term, he issued Executive Order (EO) 13891 (Promoting the Rule of Law Through Improved Agency Guidance Documents) on October 9, 2019. This order asserts that “the public frequently has insufficient notice of guidance documents, which are not always published in the Federal Register or distributed to all regulated parties” and describes procedures for issuing guidance and soliciting feedback. The order was revoked by former President JOE BIDEN on January 20, 2021, through EO 13992 (Revocation of Certain Executive Orders Concerning Federal Regulation). On the first day of his second term, Trump’s EO 14148 revoked Biden’s EO 13992, reinstating the policy of his first term.
  • According to an Office of Personnel Management (OPM) memorandum issued January 29, 2025, agencies have been instructed to provide updates on implementation of EO 14168 by noon on Friday, February 7, 2025. This means we may see a flurry of additional guidance language changes this week – and researchers will need to stay aware of what is changing as the FDA quietly updates its documents.

Featuring previous research by Laura DiAngelo.

To contact the authors of this item, please email Amanda Conti ( aconti@agencyiq.com) and Laura DiAngelo ( Ldiangelo@agencyiq.com).
To contact the editor of this item, please email Kari Oakes ( koakes@agencyiq.com).

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