US FDA Guidance for Industry July-Sept 2025

DateTitle of guidance and link to documentType and level
of guidance		About the guidance
26 Sep 2025E20 Adaptive Designs for Clinical TrialsDraft, Level 1This document provides guidance on confirmatory clinical trials with an adaptive design intended to evaluate a treatment for a given medical condition within the context of its overall
development program.

The focus of this guideline is on principles for the planning, conduct, analysis, and interpretation of trials with an adaptive design intended to confirm the efficacy and support the benefit-risk assessment of a treatment. The emphasis is on principles that are critical to ensuring the trials produce reliable and interpretable information and that require specific considerations
with use of an adaptive design.

The scope of this guideline does not include trials with unplanned modifications to the design, such as a protocol amendment proposed by an independent data monitoring committee (IDMC) based on unexpected interim results. It also does not include design changes based entirely on emerging information from a source external to the trial. Routine monitoring of operational aspects such as the enrollment rate, data quality, or extent of participant withdrawal is also out of scope.
19 Sep 2025Safety Labeling Changes—Implementation of Section 505(o)(4) of the FD&C ActDraftThis guidance provides information on the implementation of section 505(o)(4) of the FD&C Act (21 U.S.C. 355(o)(4)). Section 505(o)(4) authorizes FDA to require application holders for certain drugs to make labeling changes based on new safety information (NSI) (including information related to reduced effectiveness) that becomes available after approval of the drug that FDA determines should be included in the labeling of the drug. This draft guidance revises the guidance for industry Safety Labeling Changes— Implementation of Section 505(o)(4) of the FD&C Act issued in July 2013. After it has been finalized, this guidance will replace the July 2013 guidance. Significant changes from the 2013 version include the addition of information related to Congress’ 2018 changes to the statutory definition of adverse drug experience regarding reduced effectiveness, and a description of how FDA reviews and acts on safety labeling changes (SLCs) when NSI applies to multiple application holders and the SLC is issued to multiple applicants. Furthermore, the guidance clarifies when FDA may disclose SLC notification and order letters. Finally, additional changes were made to reflect current SLC processes and procedures that have been updated since the SLC guidance was issued in 2013.
11 Sep 2025Alternative Tools: Assessing Drug Manufacturing Facilities Identified in Pending ApplicationsFinal, Level 1The purpose of this guidance is to provide information to applicants on how FDA intends to use alternative tools to assess drug manufacturing facilities identified in a marketing application (i.e., an NDA, an ANDA, a BLA, or a supplement to any of these types of applications). As part of the negotiations relating to the reauthorization of the Prescription Drug User Fee Act (PDUFA) and the Biosimilar User Fee Act (BsUFA), as described in “PDUFA Reauthorization Performance Goals and Procedures Fiscal Years 2023 Through 2027” (PDUFA VII commitment letter) and “Biosimilar Biological Product Reauthorization Performance Goals and Procedures for Fiscal Years 2023 Through 2027” (BsUFA III commitment letter),5 FDA agreed to issue guidance on the use of alternative tools to assess manufacturing facilities named in pending applications and to incorporate best practices from the use of such tools during the Coronavirus Disease 2019 (COVID-19) pandemic.
10 Sep 2025Development of Non-Opioid Analgesics for Chronic PainDraft, Level 1This guidance is intended to address two Agency priorities:
(1) fostering the development of novel analgesic products and
(2) decreasing opioid analgesic exposure and preventing new addiction.

This guidance also responds to the statutory requirements of section 3001(b) of the Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment for Patients and Communities (SUPPORT) Act, which directs FDA to issue or update existing guidance to help address challenges to developing non-opioid medical products to treat pain.

Further information on the guidance is available here.
8 Sep 2025Development of Therapeutic Protein Biosimilars: Comparative Analytical Assessment and Other Quality-Related Considerations Guidance for IndustryFinalThis guidance describes the Agency’s recommendations on the design and evaluation of comparative analytical studies intended to support a demonstration that a proposed therapeutic protein product is biosimilar to a reference product licensed under section 351(a) of the Public Health Service Act (PHS Act). Additionally, this guidance is intended to provide recommendations to sponsors on the scientific and technical information for the chemistry, manufacturing, and controls (CMC) portion of a marketing application for a proposed product
submitted under section 351(k) of the PHS Act.
8 Sep 2025E6(R3) Good Clinical Practice (GCP)Final, Level 1The objective of this ICH GCP guidance is to provide a unified standard to facilitate the mutual acceptance of clinical trial data for ICH member countries and regions by applicable regulatory authorities.

This guidance builds on key concepts outlined in the ICH guidance for industry E8(R1) General Considerations for Clinical Studies (April 2022).This includes fostering a quality culture and proactively designing quality into clinical trials and drug development planning, identifying factors critical to trial quality, engaging interested parties, as appropriate, and using a proportionate risk-based approach.
18 Aug 2025Oncology Therapeutic Radiopharmaceuticals: Dosage Optimization During Clinical DevelopmentDraftThis guidance is intended to assist sponsors in identifying an optimized dosage(s) (administered activity and schedule) for radiopharmaceutical therapies (RPTs) for oncology indications during clinical development and prior to submitting a marketing application for a new indication and usage.
18 Aug 2025Approaches to Assessment of Overall Survival in Oncology Clinical TrialsDraftThe purpose of this guidance is to provide recommendations to sponsors on the assessment of overall survival in randomized oncology clinical trials conducted to support marketing approval of drugs and biological products, with an emphasis on the analysis of overall survival as a prespecified safety endpoint.
18 Aug 2025Marketing Submission Recommendations for a Predetermined Change Control Plan for Artificial Intelligence-Enabled Device Software FunctionsFinalSpecifically, this guidance provides recommendations on the information to include in a Predetermined Change Control Plan (PCCP) in a marketing submission for a device that includes
one or more AI-DSFs. This guidance recommends that a PCCP describe the planned AI-DSF modifications, the associated methodology to develop, validate, and implement those modifications, and an assessment of the impact of those modifications. FDA reviews the PCCP as part of a marketing submission for a device to ensure the continued safety and effectiveness of the device without necessitating additional marketing submissions for implementing each modification described in the PCCP.
25 Jul 2025Study of Sex Differences in the Clinical Evaluation of Medical ProductsDraftThis guidance provides recommendations for increasing enrollment of females in clinical trials, analyzing and interpreting sex-specific data, and including sex-specific information in regulatory submissions of medical products. When finalized, this guidance will replace the guidance entitled “Guideline for the Study and Evaluation of Gender Differences in the Clinical Evaluation of Drugs” issued in July 1993.
18 Jul 2025E21 Inclusion of Pregnant and Breastfeeding Women in Clinical TrialsDraft, Level 1The objective of this guideline is to provide recommendations for the appropriate inclusion and/or retention of pregnant and/or breastfeeding women in clinical trials and facilitate the generation of robust clinical data that allow for evidence-based decision making on the safe and effective use of medicinal products by these women and their healthcare providers (HCPs).

The scope of this guideline includes pre- and postmarketing clinical trials of investigational products (see ICH E6(R3)) for indications in the general population and indications specific to pregnant or breastfeeding women.
18 Jul 2025Formal Meetings Between the FDA and Sponsors or Applicants of BsUFA Products Guidance for IndustryFinalThis guidance:
• provides recommendations to industry on formal meetings between the FDA and sponsors or applicants relating to the development and review of proposed biosimilar, including interchangeable biosimilar, products regulated by the CDER or CBER
• discusses the principles of good meeting management practices and describes standardized procedures for requesting, preparing, scheduling, conducting, and documenting such formal meetings
• finalizes the draft guidance of the same name issued in August 2023.
16 Jul 2025Development of Cancer Drugs for Use in Novel Combination – Determining the Contribution of the Individual Drugs’ EffectsDraftThis guidance:
• provides recommendations for characterizing the safety and effectiveness of individual drugs for use in a novel combination regimen in treating cancer
• is intended for sponsors developing drugs for use in combination for the treatment of cancer
• reflects FDA’s current thinking regarding the use of clinical data for demonstration of contribution of effect for the following types of novel combinations in oncology:

1) Two (or more) investigational drugs that have not been previously approved by FDA for any indication

2) An investigational drug with a drug(s) approved for a different indication

3) Two (or more) drugs approved for a different indication(s)

This guidance does not address:
• contribution of effect in settings where an investigational drug is being developed in combination with a drug approved for the same indication for the purposes of comparing the approved drug to the combination (i.e., “add-on” trials to standard of care (SOC)) or to fixed combinations of previously approved drugs for the approved indication(s).
• safety or dosing considerations when designing trials to study two or more drugs when used in combination. Nor does it address the evaluation of
safety data to support the benefit-risk of two or more drugs when used in combination. For more information on these concepts, refer to the 2013 Co-development Guidance.