GCP Consultant Australia: 20 Good Clinical Trial Updates for 2025 That Should Be Shared

Introduction

Clinical trial regulation changed more in 2025 than in any single year since ICH E6 was first adopted. The four central authorities—FDA, EMA, MHRA, and TGA—each released significant guidance or implemented new systems that affect how sponsors, CROs, and sites conduct research.

These GCP updates for 2025 share common themes: faster pathways for lower-risk studies, stricter oversight for novel technologies, and greater flexibility in trial design. Regulators are moving from pandemic-era adaptation toward permanent frameworks that formalise decentralised elements, adaptive designs, and AI-assisted evidence generation.

Australian sponsors operating globally now face a patchwork of deadlines and requirements that demand careful attention. The CTIS transition is complete in Europe. ICH E6(R3) is now mandatory for new EU trials. The UK is piloting streamlined notification schemes ahead of the April 2026 implementation. And the TGA is strengthening its oversight of high-risk device trials while consulting on AI regulation.

This article summarises the twenty most significant regulatory changes, organised by authority, with audit-relevant implications for each. Whether you are a sponsor, CRO, or investigator site, understanding these updates is essential for maintaining compliance across jurisdictions.

FDA Updates: Streamlined Approvals and Modern Trial Designs

The FDA’s 2025 agenda focused on reducing barriers to patient access while formalising expectations for AI and adaptive trials. These seven updates signal a shift toward greater flexibility—provided sponsors can demonstrate rigorous evidence quality.

1. Single Pivotal Trial Policy

In late 2025, FDA leadership publicly signalled interest in shifting evidentiary expectations toward reliance on a single pivotal study in some contexts, subject to robust design and statistical rigour. This was not yet formalised in guidance at the time of reporting [Source].

2. Enhancing Participation Guidance (Final)

Final guidance addressed eligibility criteria and enrolment practices to promote diversity and inclusion. The practical impact is clear: sponsors must document their rationale for restrictive criteria and demonstrate active efforts to broaden participation in underrepresented populations [Source].

3. Adaptive Designs Framework (ICH E20)

The FDA removed a major hurdle to using RWE in applications by allowing aggregated, de-identified data from real-world sources without requiring individual patient-level data in all cases. This policy change (Dec 2025) enables sponsors to leverage large databases (e.g. disease registries, EHR networks) to support drug and device approvals, potentially accelerating development [Source].

4. Inclusion of Pregnant and Breastfeeding Women (ICH E21)

ICH E21 addresses a longstanding data gap by providing a framework for including these populations in clinical trials. Ethics committees will look for explicit justification of inclusion or exclusion decisions, with documented risk-benefit assessments. Draft Guidance [Source].

5. Biosimilar Trial Requirements Update

In Oct 2025, the FDA released a draft guidance re-examining when comparative clinical efficacy trials are needed for biosimilars. The guidance suggests that if analytical and functional similarity to the reference product is convincingly demonstrated, a confirmatory efficacy trial may be unnecessary. This potential shift could streamline biosimilar development by reducing redundant late-phase trials in some instances [Source].

6. Innovative Trial Designs for Gene/Cell Therapies

The FDA’s Centre for Biologics Evaluation and Research (CBER) issued a draft guidance in Sept 2025, encouraging the use of adaptive and novel trial designs in small populations (e.g., rare diseases) for cell and gene therapies. The guidance outlines the use of various trial designs and endpoints to efficiently generate evidence for licensure in trials with extremely limited patient numbers [Source].

7. AI for Regulatory Decision-Making

The January 2025 draft guidance establishes a risk-based framework for AI/ML that generates regulatory evidence. Sponsors must demonstrate “model credibility”—reliable, reproducible, and fit-for-purpose outputs with documented validation and ongoing performance monitoring [Source].

EMA Updates: CTIS Enforcement and Transparency Mandates

The EMA’s 2025 was defined by hard deadlines and binding transparency requirements. The transition period is over—compliance is now mandatory.

8. Full CTIS Transition (January 2025)

As of 31 January 2025, all EU clinical trials must be managed through CTIS. Trials that failed to transition from the legacy Directive are now legally non-compliant. This is an enforcement deadline, not a grace period. Sponsors must verify their migration status immediately [Source].

9. ICH E6(R3) Effective Date (July 2025)

ICH E6(R3) Principles and Annex 1 came into effect on 23 July 2025, modernising GCP for quality-by-design and risk-based approaches. New trials initiated after this date must comply with R3 requirements. Existing trials should plan their transition pathway [Source].

10. CTIS Clinical Trial Map Launch

The EMA launched the CTIS Clinical Trial Map in March 2025, a public tool showing trial locations across the EU/EEA. This transparency initiative means sponsor data is publicly visible—inaccuracies reflect poorly on organisational credibility and data management capability [Source].

11. High-Risk Medical Device Trial Guidance

EMA established a permanent procedure (Feb 2025) for manufacturers of specific high-risk medical devices to obtain scientific advice on their clinical development plans. Following a successful pilot, device sponsors (Class III and select Class IIb devices) can now consult expert panels via an EMA-coordinated process at different trial stages. This formal medical device trial advice framework is intended to foster innovation and patient safety. [Source]

12. New Pharmaceutical Legislation Agreement

As part of the ACT EU (Accelerating Clinical Trials in the EU) initiative, EMA and partners addressed clinical trial processes in health emergencies throughout 2025. Regulators worked on regulatory and technical flexibilities to facilitate faster trial assessment/approval during crises. They also began evaluating the benefits of a centralised EU ethics committee for public health emergency trials. [Source]

MHRA Updates: Risk-Proportionate Regulation Takes Shape

The UK’s new Clinical Trials Regulations represent the most significant overhaul in two decades. Throughout 2025, the MHRA piloted key mechanisms before full implementation.

13. New Clinical Trials Regulations (April 2026)

The Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025 were signed into law, with full implementation set for 28 April 2026. Combined regulatory/ethics review timelines are locked in, and the legal framework for streamlined pathways is established. [Source]

14. MHRA End-of-Trial Reporting Requirements: 

In Oct 2025, MHRA issued revised guidance on ending clinical trials (effective with the 2025 regulations) to clarify sponsors’ obligations. Key updates include mandatory timelines for notifying authorities when a trial concludes (90 days for a standard end, 15 days if a trial is terminated early). [Source]

15. Route B Notification Pilot

To prepare stakeholders for the new regulations, MHRA launched a Route B Substantial Modification pilot program (Oct 1, 2025 – Mar 31, 2026) to streamline trial amendment approvals. Under the upcoming law, certain substantial protocol modifications that meet pre-specified criteria will be eligible for automatic approval by MHRA (no waiting for explicit authorisation). The pilot allowed sponsors to submit eligible trial changes and receive MHRA feedback within 14 days. [Source]

16. Simplified Consent for Low-Risk Trials

The HRA in 2025 worked on principles to implement a new allowance in UK law for simplified consent processes in specific low-intervention trials. For clinical studies using approved medicines (and hence lower risk), regulators aim to enable streamlined consent documentation and procedures while maintaining ethical safeguards. [Source]

TGA Updates: Device Scrutiny and Ethics Alignment

The TGA’s focus in 2025 centred on high-risk devices, AI/SaMD, and ethics committee coordination. For Australian sponsors, these updates signal increased regulatory engagement during trial conduct.

17. HREC and TGA Discussion Forum
The TGA established regular meetings with Human Research Ethics Committees (HRECs) to improve alignment on clinical trial matters. This coordination signals that sponsors should expect greater consistency between ethics and regulatory expectations—and reduced tolerance for discrepancies. [Source]

18.  Adoption of ICH GCP R3 (with Transition): 

The TGA began aligning with the new ICH E6(R3) Good Clinical Practice guideline in 2025. Following a public consultation, TGA announced it will adopt ICH GCP R3 (Principles and Annex 1) effective 13 January 2026, with a 12-month transition period for implementation. [Source]

19. Enhanced GCP Inspection and Device Trial Oversight

In 2025, TGA strengthened its Good Clinical Practice (GCP) Inspection Program with particular focus on high-risk trials. New guidance was published to clarify the inspection process and enable proactive monitoring of high-risk medical device trials. TGA’s inspection reports for 2023–24 highlighted efforts to oversee first-in-human implantable device trials and other advanced interventions. [Source]

20. AI and Medical Device Software Report

The July 2025 report concluded that current exclusions for consumer health software may need to be amended to capture high-risk AI diagnostic tools. Sponsors developing AI-based devices should monitor consultation outcomes and prepare for potential regulatory expansion. [Source]

Practical Implications: What This Means for Your Organisation

The volume of change creates operational challenges for clinical operations and quality teams.

Compliance Readiness Checklist:

• Review active and planned trials against ICH E6(R3) requirements
• Verify CTIS migration status for EU trials initiated under the Directive
• Assess eligibility criteria documentation for FDA diversity expectations
• Update SAP templates for ICH E9(R1) estimand requirements
• Classify UK trials by risk level for notification scheme eligibility
• Document AI/ML model credibility for systems generating regulatory evidence
• Review high-risk device monitoring plans against TGA proactive oversight

What Happens Next

Several updates will be developed further in 2026. The MHRA’s full implementation in April brings notification schemes into mandatory operation. The EMA’s pharmaceutical legislation will move to practical guidance. The TGA’s AI/SaMD consultation will likely result in amended requirements.

For Australian sponsors, international harmonisation continues, but each authority maintains distinct requirements and timelines. Quality systems that flex across jurisdictions while maintaining inspection-ready documentation will be best positioned.

Next Step: Review current SOPs for clinical trial conduct, statistical analysis, and quality management, and assess each relevant update. Prioritise remediation based on proximity to the deadline and the impact on patient safety.