Global Regulatory Updates on Clinical Trials (November 2025)

Several regulatory updates were issued by global health authorities in November, affecting sponsors conducting clinical trials and developing drugs and biologics worldwide. Caidya’s Regulatory & Strategic Development (RSD) team has compiled a high-level summary of guidance and updates from the FDA (USA), EMA (European Union), NMPA (China), TGA (Australia), Health Canada, and ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) that are relevant for stakeholders involved in Phase I–IV clinical trials. 

Food and Drug Administration (FDA – USA) 

Final Updates 

• None identified in November 2025 — No new final clinical trial guidance specific to Phases I–IV was listed on FDA’s “Clinical Trials Guidance Documents” page. 

Draft Updates 

• Q3E Guideline for Extractables and Leachables — The FDA announced a draft guidance (Docket No. FDA-2025-D-4678) that provides a comprehensive, riskbased framework for the assessment and control of extractables and leachables (E&L) in pharmaceutical products — including drug and biologic formulations used in clinical trials. The draft also includes supporting documentation: “Class 3 Leachable Monographs.” This guidance builds on previous impuritycontrol guidance under the harmonised International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) framework (Q3A–D, M7), and applies to drug products including combination drugdevice products and advanced therapies Guideline for Extractables and Leachables (Draft, November 2025) — The FDA announced a draft guidance (Level 1) for industry on extractables and leachables (E&L) assessment and control for pharmaceutical products, which would apply to drug/biologic formulations used in clinical trials and beyond. 

European Medicines Agency (EMA – EU) 

Final / Operational Updates 

• CTIS Sponsor Handbook v6.1 — EMA published an updated version of the Sponsor Handbook for its Clinical Trials Information System (CTIS) on 07 November 2025.
  The CTIS sponsor handbook provides sponsors of clinical trials with the operational guidance they need to create and submit clinical trial information to the member states of the European Union/European Economic Area (EU/EEA) through the CTIS in compliance with the Clinical Trial Regulation No. 536/2014..  

• Guidance for applicants: the ETF scientific advice that facilitates clinical trial authorisations (SA-CTA) – new guidance issued by EMA on 17 November 2025
  EMA’s Emergency Task Force (ETF) is improving its approach to scientific advice for the most promising medicines and vaccines under development for public health threats. Under the new process, which is explained in the scope of this new guidance, developers of medicines falling within the scope of the ETF’s activities, including medicines for antimicrobial resistance (AMR) and other health threats that have the potential to cause public health emergencies, can apply for combined scientific advice from EMA, as well as clinical trial and ethics experts at national level. 

• Guidance for stepwise PIPs (sPIPs) — updated guidance issued by EMA on 28 November 2025
  By definition, a paediatric investigation plan (PIP) is a research and development programme aimed at ensuring that the necessary data are generated determining the conditions in which a medicinal product may be authorised to treat the paediatric population. A stepwise PIP would apply to cases where there is a lack of crucial information needed to decide on certain parts of the paediatric investigation plan, such as whether a clinical study for a whole age group is necessary.
  This guidance provides an overview of the application for and modification of a stepwise PIP. 

Draft / Consultation Stage Updates 

• Draft “Guideline on non-inferiority and equivalence comparisons in clinical trials” – Start of public consultation on 13 November 2025

This guideline lays out general principles for the design and analysis of confirmatory clinical trials that include non-inferiority or equivalence comparisons. It replaces the “Guideline on the choice of the non-inferiority margin” from 2005 (EMEA/CPMP/EWP/2158/99) and the “Points to consider on switching between superiority and non-inferiority” from 2000 (CPMP/EWP/482/99). It addresses all the topics that were addressed in the two previous guidelines, with updated recommendations to reflect current EMA positions and the concepts introduced in the framework (ICH E9 R1). Deadline for comments is 31 May 2026. 

• In parallel, the draft of  “Q3E Guideline for Extractables and Leachables”(see above under FDA) remains under public consultation via EMA/ICH — the guideline is listed on EMA’s scientific guideline page. The deadline for comments is 18 December 2025.  

There were no guidance updates in the month of November for NMPA (China), TGA (Australia), Health Canada or ICH.