Global Regulatory Updates on Clinical Trials (September 2025)

There were several regulatory updates issued by global Health Authorities in September, impacting many sponsors currently conducting clinical trials and developing therapeutic treatments to combat various diseases around the world. Caidya’s Regulatory & Strategic Development (RSD) team has included a high-level summary of Guidelines issued by the US FDA, EMA (European Union), NMPA (China), TGA (Australia), Health Canada, and ICH (International Council for Harmonisation) which are important for stakeholders. 

FDA (United States) 

Final Updates 

• ICH E6(R3) Good Clinical Practice (Final Guidance) – FDA issued the final ICH E6(R3) GCP guidance, which introduces flexible, risk-based approaches and embraces modern innovations in trial design, conduct, and technology. (This update modernizes global GCP principles to support a broader range of trial designs while maintaining participant protection and data quality.) FDA Guidance Page 

Draft Updates 

• Expedited Programs for Regenerative Medicine Therapies (Draft Guidance) – FDA (CBER) released a draft guidance for sponsors developing regenerative medicine therapies for serious or life-threatening conditions, detailing how to utilize expedited development and review pathways (including RMAT designation and accelerated approval) to speed patient access. (It outlines available expedited programs and clinical development considerations for cell and gene therapies designated as RMATs.) FDA Draft Guidance 

• Post approval Data Collection for Cell/Gene Therapies (Draft Guidance) – FDA (CBER) proposed guidance on methods to capture post-approval safety and efficacy data for cell and gene therapy products. Given these therapies’ long-lasting effects and small trial populations, the draft emphasizes robust long-term post-market monitoring to gather safety and effectiveness data over time. (The guidance discusses approaches for long-term follow-up of patients to inform ongoing safety and benefit after approval.) FDA Draft Guidance 

• Innovative Trial Designs for Small Populations (Draft Guidance) – FDA (CBER) issued a draft guidance for cell and gene therapy trials in rare disease populations, recommending novel trial designs and endpoints to support product licensure in small populations. It describes FDA’s requirements and considerations for flexible trial design strategies to demonstrate effectiveness when studying therapies for rare conditions. (Sponsors are encouraged to use innovative statistical designs and surrogate endpoints to efficiently generate evidence in small or underserved patient groups.) FDA Draft Guidance 

European Medicines Agency (EMA) 

Final  

• No final EMA guidance updates specific to drug/biologic clinical trials have been published in this timeframe. (EMA’s recent activities have focused on draft guidance development and consultation.) 

Drafts  

• Reflection Paper on Patient Experience Data (Draft) – EMA, 29 Sept 2025: The reflection paper is intended for medicine developers, patient groups, researchers and other decision-makers. It encourages medicines’ developers to gather and include data reflecting patients’ real-life perspectives and preferences throughout the lifecycle of medicines (i.e. during pre-authorisation, benefit-risk evaluation and post-authorisation), and describes general principles on how to generate, collect and analyse this data. 

• While detailed methodological guidance is outside the scope of the paper, EMA is working with the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) to harmonise existing methodological guidelines globally. In this context, the reflection paper provides a complementary framework to ICH work and focuses on general principles to include patient experience data in medicine development programmes and regulatory submissions in the European Union (EU). 

• Guideline on the clinical evaluation of medicinal products intended for treatment of Hepatitis B – Revision 1 (Draft)
  EMA, 30 Sept 2025: Start of public consultation
  Clinical evaluation of medicinal products intended for treatment of hepatitis B – Scientific guideline | European Medicines Agency (EMA)
  First revision of EMA’s guideline on clinical evaluation of drugs for the treatment of Hepatitis B, replacing the current effective version dating back to 2006.
  In recent years, there have been several new products and treatment strategies aimed at achieving functional cure, including finite and combination treatment regimens. Furthermore, there has been development of new antiviral and immunomodulatory treatment options with mechanisms of action different to those of nucleos(t)ide analogues (NUCs) or peg-interferon alfa-2a (PEG-IFN), which are covered by the current effective guidance. Therefore, a revision of the guideline has been initiated to reflect these new developments and the implications for clinical development programs. 

• Guideline on clinical investigation of medicinal products for the treatment of Psoriatic Arthritis– Revision 1 (Draft)
  EMA, 30 Sept 2025: Start of public consultation
  Clinical investigation of medicinal products for the treatment of psoriatic arthritis – Scientific guideline | European Medicines Agency (EMA)
  This draft revision of the EMA guideline, which came into effect in 2007, considers that clinical practice has been subject to significant evolution since publication of the previous guideline. Relevant treatment goals, general design of clinical studies, definition of study population, and study endpoints in terms of efficacy and safety were updated in the light of the currently available treatment options for psoriatic arthritis (PsA).  

• Concept paper on new Guidance on the clinical investigation of medicinal products for the treatment of idiopathic pulmonary fibrosis (IPF)
  EMA, 30 Sept 2025: Start of public consultation
  Clinical investigation of medicinal products for the treatment of idiopathic pulmonary fibrosis (IPF) – Scientific guideline | European Medicines Agency (EMA)
  As there is currently no scientific guidance from EMA on the clinical investigation of medicinal products for the treatment of idiopathic pulmonary fibrosis (IPF), EMA released this concept paper proposing a new guideline in order to facilitate development and support marketing authorization applications for this condition. The concept paper outlines issues related to the design of development programs for the treatment of IPF, which will be addressed in the new guidance document, e.g. the choice of primary and secondary endpoints for confirmatory and dose finding studies, relevance and limitations of outcome measures commonly used in IPF development programs (e.g. lung function testes, exercise capacity), key patient selection criteria for IPF studies considering stage of the disease at enrolment, or the number of pivotal studies recommended for approval also considering the rarity of the condition. 

• Product-Specific Bioequivalence Guidances (Drafts) for:   

• • Eltrombopag film-coated tablets 12.5 mg, 25 mg, 50 mg, 75 mg and powder for oral suspension 25 mg
    EMA, 25 Sept 2025: Start of public consultation 

• • Melatonin prolonged release tablets 2 mg 
    EMA, 25 Sept 2025: Start of public consultation 

Product-specific bioequivalence guidance | European Medicines Agency (EMA) 

These two product-specific draft guidance documents outline (prospective) requirements for the demonstration of bioequivalence for generic versions of the respective drug products, including study design, definition of the analyte, and parameters for the bioequivalence assessment. 

NMPA (China) 

Final Updates 

• Revised Clinical Trial Policies to Streamline Development – NMPA, effective 2 Sept 2025: China’s NMPA implemented revisions to its clinical trial regulations aimed at accelerating drug development and shortening trial approval timelines by ~30%. The new policy allows use of adaptive trial designs (with real-time protocol modifications) under stricter patient safety oversight, mandates public trial registration and results disclosure for transparency, and generally aligns China’s GCP standards closer to international normshttps://www.pacificbridgemedical.com/news-brief/chinas-nmpa-implements-revisions-to-clinical-trial-policies-to-streamline-development/. (These changes are intended to reduce administrative delays, encourage innovation in trials (especially for biologics and personalized medicines), and attract global sponsors by facilitating mutual acceptance of Chinese trial data.) NMPA Policy Update (Summary) 

Draft Updates 

• No specific draft guidance in this period. (NMPA’s recent trial-related guidance activity before September included a draft cell therapy change evaluation guidance in July 2025, focusing on CMC changes over the  lifecycle of a cell therapy productcisema.comcisema.com) 

TGA (Australia) 

Final Updates 

• Adoption of GVP Module I (Pharmacovigilance Systems) – TGA, 9 Sept 2025: The TGA formally adopted the EMA’s Good Pharmacovigilance Practices (GVP) Module I guideline, which outlines requirements for pharmacovigilance systems and quality systems for sponsors. (This adoption updates Australia’s post-market safety monitoring standards, aligning them with EMA’s framework for MAH pharmacovigilance system quality.) TGA Notice – GVP Module I 

• Adoption of ICH E9(R1) (Estimands in Clinical Trials) – TGA, 9 Sept 2025: TGA adopted ICH E9(R1) (Addendum on Estimands and Sensitivity Analysis in Clinical Trials)tga.gov.au. (This introduces the “estimand” framework into Australian trial guidance, clarifying how trial objectives, endpoints, and intercurrent events should be defined and handled statistically to improve clarity in Phase II–III trial design and analysis.) TGA Notice – ICH E9(R1) 

Draft Updates 

• No new draft guidance specific to clinical trials was issued by the TGA during this period. (TGA’s regulatory consultations in late 2025 focused on other areas, such as AI in medical devices and unapproved cannabis product use, which are outside the scope of drug clinical trial design.) 

Health Canada 

Final Updates 

• No final clinical trial guidance has been issued since Sept 1, 2025. (Health Canada’s key initiatives in this period have been at the draft/consultation stage, as noted below.) 

Draft Updates 

• Biosimilar Biologic Drugs – Revised Draft Guidance – Health Canada, Draft released 10 June 2025 (consultation closed 8 Sept 2025): Health Canada proposed significant revisions to its biosimilar approval guidance, most notably removing the routine requirement for Phase III comparative efficacy trials. Under the draft, a biosimilar submission “in most cases” would not require a comparative clinical efficacy/safety study, relying instead on analytical comparability plus pharmacokinetic, immunogenicity, and safety data collected in comparative PK/PD studies smartbiggar.ca. (Sponsors would only conduct a confirmatory efficacy trial if specifically justified, aligning Canada’s policy with recent EMA moves to streamline biosimilar development.) Draft Guidance – Information and Submission Requirements for Biosimilar Biologic Drugs 
• Good Pharmacovigilance Practices (GVP) Inspection Guidelines (Draft Update) – Health Canada, 15 Sept 2025: Health Canada opened a consultation on updated GVP guidelines for industry, which include a revised Good Pharmacovigilance Practices (GUI-0102) guide and an updated risk classification guide (GUI-0063) for PV inspection findings https://www.canada.ca/en/health-canada/programs/consultation-guidance-document-updates-good-pharmacovigilance-practices-gvp-inspections.html. (These drafts, once finalized, will replace the 2013 versions, providing more current guidance on maintaining compliant pharmacovigilance systems and explaining how Health Canada will categorize and follow up on PV inspection observations.) Consultation Notice – GVP Guidance Update 

International Council for Harmonisation (ICH) 

Final Updates 

• ICH E2D(R1) – Post-Approval Safety Data (Step 4 Guideline) – ICH, 24 Sept 2025: The E2D(R1) guideline “Post-Approval Safety Data: Definitions and Standards for the Management and Reporting of Individual Case Safety Reports” reached Step 4 (final). (This revised pharmacovigilance guideline updates the definitions and standards for post-market individual case safety reports (ICSRs), improving the clarity and harmonization of how adverse event data are collected, managed, and reported across regions in the post-approval phase.) ICH News Release – E2D(R1) Adoption 

Draft Updates 

• No new ICH efficacy guideline drafts were released in this period. (Notably, ICH E2D(R1) was finalized as above. Earlier in 2025, ICH did endorse the draft E20 (Adaptive Clinical Trials) guideline, which was under consultation through mid-2025, but no additional draft guidelines related to clinical trial phases I–IV were published after September 1, 2025.)