Introduction

The regulation of clinical trials across the world is currently being reshaped by two forces: the progressive harmonisation of international governance standards and the integration of new technologies into trial design and conduct. Far from running in parallel, these forces are intricately connected. Harmonised standards are creating a shared framework within which digital tools, decentralised trials and new evidence models can be adopted consistently across borders. This is reshaping competition between jurisdictions seeking to attract clinical research activity.

This article examines both dimensions. We begin with the international regulatory landscape, focusing first on the harmonisation of good clinical practice standards through ICH E6(R3) and then on recent procedural and technological developments across the principal jurisdictions. We then turn to Australia and consider some structural nuances and the regulatory, legal and investment considerations that are shaping the Australian market.

Global trends in the regulation of clinical trials

Harmonisation of clinical trial governance: ICH E6(R3)

Globally, the uptake of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E6(R3) Guideline for Good Clinical Practice (ICH E6(R3)) across major jurisdictions reflects a convergence of standards for designing, conducting, recording and reporting clinical trials.

Founded in 1990, ICH develops guidelines that are intended to harmonise standards for the development of safe, effective and high-quality medicines. The guidelines are developed through scientific consensus and public consultation.¹

ICH E6(R3) was published by the ICH on 6 January 2025.² It is the third revision of the ICH’s Guideline for Good Clinical Practice (GCP) and was developed specifically for interventional clinical trials of investigational products. It provides a unified standard to facilitate the mutual acceptance of clinical trial data for ICH member countries.

Revisions of ICHE6(R3) from previous versions reflect evolving approaches to trial design and the emergence of new technologies. For example, ICH E6(R3) provides guidance on the handling and management of electronic data and the use of remote informed consent and is designed to be technology-neutral to enable the use of digital health technologies in clinical trials such as wearables and sensors.

ICH E6(R3) sets out overarching ‘Principles of GCP’ and an Annex 1 that provides guidance on the interpretation and application of those Principles. Since its publication, ICH E6(R3) has been adopted across most jurisdictions:

• European Union: The Principles and Annex 1 were adopted by the Committee for Human Medicinal Products on 12 December 2024, with legal effect from 23 July 2025.³ The EU legislation provides that sponsors and investigators must take appropriate account of ICH E6(R3) and that all trials submitted as part of a marketing authorisation in the EU must have been conducted in accordance with GCP.⁴
• United Kingdom: The Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025 formally implements ICH E6(R3) in the UK, with effect from 28 April 2026.⁵ Under the amended regulations, clinical trials must be conducted in accordance with the Principles of GCP set out in ICH E6(R3).⁶ The sponsor may be required to make modifications to a clinical trial approval if necessary to ensure that the Principles of GCP are satisfied.⁷ Sponsors and investigators are also required to give due regard to the annexes to ICH E6(R3); however, the Medicines and Healthcare products Regulatory Agency (MHRA) has indicated that compliance with the annexes will be evaluated in a proportionate and pragmatic manner.⁸
• Australia: Australia’s Therapeutic Goods Administration (TGA) adopted ICH E6(R3), with effect from 13 January 2026.⁹ The TGA has prescribed a 12-month transition period running to 13 January 2027, during which sponsors may comply with either the superseded E6(R2) or the new E6(R3).¹⁰ After that date, compliance with E6(R3) will be mandatory for all trials conducted under the CTN and CTA schemes, which we explore below.
• United States: The FDA published ICH E6(R3) (both the Principles and Annex 1) as a guidance document in September 2025.¹¹ FDA guidance documents are not binding and are provided as recommendations to industry.¹²

Sponsors conducting or planning trials in these jurisdictions should be actively reviewing their trial master files, investigator brochures, and monitoring plans against the new standard.

A proposed Annex 2 to ICH E6(R3) will cover clinical trial design, including ‘pragmatic’¹³ and ‘decentralised’¹⁴ clinical trials, and trials incorporating real-world data sources. Annex 2 will be finalised following a public consultation process.¹⁵

This is a significant development for sponsors running multi-jurisdictional programmes: harmonised standards simplify design, reduce duplication, and make data more transferable. They also, however, usually raise the compliance threshold in every participating country. Sponsors should not assume that existing trial procedures will meet the new standards.

As sponsors design trial programmes against the common baseline of good clinical practice, jurisdiction selection decisions turn on how efficiently that baseline can be implemented. Procedural efficiency, technological capability and trial infrastructure will become increasingly important variables for jurisdiction selection.

Procedural efficiencies

UK

In the UK, the amended regulations that take effect from 28 April 2026 are designed to strengthen patient safety and improve trial efficiencies, including by:

• introducing a combined regulatory and ethics review model, under which applications will be submitted through an Integrated Research Application System and reviewed by the MHRA and a research ethics committee in parallel;
• imposing statutory timelines requiring the MHRA and ethics committees to assess trial approvals within 30 days and amended requests for trial approvals within ten days.¹⁶

EU

In the EU, the Clinical Trials Regulation (CTR) has applied to all trials – including those ongoing before the CTR came into force – since 31 January 2025. The CTR establishes the Clinical Trials Information System (CTIS), which provides a single entry point for the submission and assessment of clinical trial applications in the EU.¹⁷ Under the CTR, all clinical trial sponsors, regardless of where they are based or which national competent authority or national ethics committee is involved, must use the same system and follow the same procedures when applying for authorisation of a clinical trial. Responsibility for the authorisation and supervision of clinical trials rests with EU/EEA Member States, while the European Medicines Agency (EMA) maintains CTIS and the European Commission oversees implementation of the CTR.

Further reform efforts in the EU are being directed to streamlining procedural timelines and making Europe a more attractive location for conducting strategic trials under the proposed Biotech Act and the FAST-EU pilot, including:¹⁸

• accelerating timelines for the review of clinical trial authorisation applications, from 75 to 47 days where no request for further information is required, and from 106 to 76 days where such a request is made;¹⁹
• reducing regulatory burden by allowing applicants to cross-refer to reviewed and approved data in dossiers from related trials;²⁰ and
• improving coordination and harmonisation between Member States by increasing reliance on the clinical trial authorisation assessment of a single ‘reporting Member State’. The Biotech Act includes proposed reforms to require a single, harmonised dossier format, reducing circumstances in which other Member States are unable to rely on the assessment of a reporting Member State because of differences in national dossier requirements.

New technologies and methods of data collection

The EMA and the FDA have jointly developed and in January 2026 published ten guiding principles of good AI practice in drug development. These principles address the use of AI in generating evidence across all phases of the medicines lifecycle, from clinical trials to post-market monitoring.²¹ The principles are intended to identify areas where international regulators and standards organisations can work together to advance good practice in drug development that best leverages AI enabled or embedded technologies.

Both the FDA and the EMA have also indicated a willingness to explore the use of digital twins to replace placebo control arms in clinical research.²² Digital twin technology uses AI to accumulate real-world patient data from placebo arms, active comparator arms, and failed intervention arms to create a digital patient profile that can be used in control arms.

The FDA has published guidance on the use of digital health technologies to acquire data from participants remotely, acknowledging that these technologies may improve the efficiency of clinical trials and increase opportunities for participation.²³ The guidance outlines a range of recommendations to facilitate the conduct of decentralised clinical trials. Key recommendations include that:

• sponsors choose digital health technologies that are fit for purpose: the FDA guidance recommends that sponsors select digital health technologies taking into account the clinical event or characteristic to be measured, the minimum technical and performance specifications needed, and whether participants can use the technology as intended in practice; and
• informed consent be tailored to the technology: the FDA guidance recommends that informed consent processes explain to patients the risk and potential discomfort associated with the use of digital health technologies, the information the technology will collect, how it will be used and monitored, who may access it, what privacy protections and restrictions  will be applied, and any added participation costs (such as data charges).

The EMA is also developing a reflection paper on the use of external controls for evidence generation in regulatory decision-making.²⁴ External control data may be derived from sources such as other clinical trials or real-world data and is used where data is collected under a clinical trial protocol that does not use a randomised control arm. Between 2016 and 2021, 17 per cent of EMA-approved cancer drugs were assessed based on trials that used external controls, 37 per cent of which were sourced from real-world data.²⁵

Against this backdrop of converging standards and evolving trial methods, Australia has emerged as an attractive jurisdiction for both early-phase and late-phase clinical trials.

Australia as a jurisdiction for clinical trials

Structural advantages

Australia has emerged as one of the world’s leading destinations for early-phase and late-phase clinical trials, a status founded on regulatory efficiency, fiscal incentives, and the quality of its clinical infrastructure.

Central to Australia’s appeal is its dual-pathway regulatory framework, administered by the TGA. Sponsors may proceed under the Clinical Trial Notification (CTN) scheme, which requires only notification to the TGA and permits commencement immediately once Human Research Ethics Committee (HREC) approval is obtained – often within weeks.²⁶ This contrasts sharply with jurisdictions that require formal pre-approval from a central medicines authority before a trial may begin. Under the alternative Clinical Trial Approval (CTA) scheme, the TGA will review the scientific data prior to approval being granted and the trial commencing. This provides an additional layer of regulatory scrutiny that is appropriate for higher-risk products.²⁷ The availability of two pathways provides an approach that can be calibrated by sponsors.

	CTN Scheme	CTA Scheme
Mechanism	Notification only – sponsor submits online form to TGA	Formal application – sponsor submits scientific data to TGA for review and approval prior to commencement
TGA role	Receives notification; does not assess the application	Actively reviews scientific and clinical data; may seek further information
Pre-submission	Not required	Optional pre-submission advice available from TGA
HREC approval	Required before commencement; drives the practical timeline	Required; obtained after TGA approval
Typical timeline	Weeks (HREC approval is the critical path)	Longer; TGA review adds a substantive assessment phase
Appropriate for	Most lower risk commercial trials; unapproved therapeutic goods on lower-risk protocols	Higher-risk products or protocols where advance TGA scientific endorsement is warranted

Table 1: Comparison of CTN and CTA Schemes

Australia’s Research and Development (R&D) Tax Incentive that was introduced in XXX a significant incentive for research and development, and clinicals in particular, to be conducted in Australia that has manifested in significant growth in the sector. Eligible companies with an annual aggregate turnover below AU$20m can access a refundable tax offset of up to 43.5 per cent on qualifying R&D expenditure, including clinical trial costs.²⁸ Larger companies receive a non-refundable offset.

A 2022 regulation made clear that clinical trial activities (Phase 0 through Phase III) that satisfy TGA registration requirements are deemed to constitute ‘core R&D activities’. This provided sponsors with greater certainty when structuring their arrangements and making claims.²⁹ Notably, there is no requirement for the intellectual property generated to be held in Australia, and sponsors need not be headquartered there.³⁰ The combined effect is a substantial reduction in the cost of conducting trials in Australia compared with comparable jurisdictions.

Recent regulatory and legal developments

The Australian clinical trials regulatory landscape has undergone a number of developments over the past year, in a regulatory environment that is both mature and continuing to evolve.

ICH E6(R3) adoption

As noted above under ‘Harmonisation of clinical trial governance’, ICH E6(R3) took effect in Australia from 13 January 2026, with a 12-month transition period to 13 January 2027. After that date, compliance with E6(R3) will be mandatory for all trials conducted under the CTN and CTA schemes. HREC members, sponsors and investigators operating in Australia should review their current practices against the new standard during the transition period.

National Statement on Ethical Conduct in Human Research 2025

The National Health and Medical Research Council (NHMRC) released the National Statement on Ethical Conduct in Human Research 2025, which is scheduled to take effect in early 2026 (the precise date remaining to be confirmed).³¹ The 2025 National Statement updates guidance on research involving participants at elevated risk, introduces more detailed provisions for specific population cohorts, and includes new provisions governing research conducted during natural disasters or public health emergencies.³² HREC members and clinical trial sponsors operating in Australia should familiarise themselves with the revised framework ahead of its commencement, in particular its updated provisions on participant vulnerability and emergency-context research.

Updated investigational product requirements

From early 2025, updated investigational product requirements apply following the TGA’s 2024 adoption of the 2022 PIC/S Guide to Good Manufacturing Practice. These requirements govern the manufacture and handling of investigational medicinal products used in Australian trials and align Australia’s manufacturing standards more closely with those of its international counterparts.³³

Foreign investment considerations

Foreign sponsors looking to conduct clinical trials in Australia, or who are considering investment in Australian clinical infrastructure should be aware that the activity may trigger notification and review under the Foreign Acquisitions and Takeovers Act 1975 (Cth). Mandatory filing obligations (with a zero monetary threshold) apply to acquisitions of a ten per cent or greater direct interest in a ‘national security business’, and health data assets have attracted growing scrutiny from the Foreign Investment Review Board (FIRB). Where approval is required in health-sector transactions, the Treasurer’s established practice has been to impose data security conditions on the acquirer – including restrictions on offshore access to Australian patient data – that go beyond the baseline requirements of the Privacy Act 1988 (Cth).

Conclusion

The two forces examined in this article – harmonisation and technological change – are mutually reinforcing. The progressive adoption of ICH E6(R3) across the EU, the UK, Australia and the US creates a common baseline for good clinical practice across the world’s principal research jurisdictions.

Accelerated pathways, innovative trial designs, and new methods of data collection offer faster routes to evidence, but they depend on sound governance, transparent methodologies and credible long-term oversight to withstand regulatory scrutiny. The willingness of regulators in the EU and the US to explore digital twins, external controls and AI-assisted evidence generation is a notable development, but those frameworks remain in early development, and sponsors moving early should expect to engage closely with regulators.

Australia is well positioned within this global movement. Its structural advantages – efficient regulatory pathways, fiscal incentives, and internationally accepted data – are supported by a domestic reform programme that aligns Australian practice with the global standard. Sponsors, institutions, and investors operating in this sector should monitor these developments closely and seek specialist legal advice before committing to trial programmes or investment structures that engage any of the regulatory and commercial frameworks discussed in this article.

 

Notes

1. ICH, Harmonisation for better health: available at www.ich.org/page/mission.
2. ICH, ICH E6(R3) (6 January 2025): available at www.ich.org/page/e6r3-good-clinical-practice.
3. EMA, ICH E6 Good clinical practice – Scientific guideline: available at www.ema.europa.eu/en/ich-e6-good-clinical-practice-scientific-guideline.
4. EMA, European Commissioner, HMA, ACT EU workshop on ICH E6(R3) Principles and Annex 1 (19–20 February 2025).
5. See www.legislation.gov.uk/uksi/2025/538.
6. The Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025 (UK), Amendment to Schedule 1.
7. Ibid, reg 21.
8. Clinical trials for medicines: guidance on compliance with ICH E6 good clinical practice (GCP) in the United Kingdom (Guidance, 27 March 2026).
9. TGA, ICH E6(R3) Guideline for Good Clinical Practice (effective 13 January 2026): available at www.tga.gov.au/resources/resources/international-scientific-guidelines-adopted-australia/ich-e6r3-guideline-good-clinical-practice.
10. TGA, ICH E6(R3) Consultation (August 2025) – transition period to 13 January 2027.
11. FDA, E6(R3) Good Clinical Practice (GCP) (September 2025): available at www.fda.gov/regulatory-information/search-fda-guidance-documents/e6r3-good-clinical-practice-gcp.
12. FDA, Guidance (17 January 2025).
13. Pragmatic clinical trials test the effectiveness of drugs in real-world settings that reflect the settings in which the intervention will be implemented, by contrast to the highly controlled conditions of randomised controlled trials.
14. A decentralised clinical trial is a clinical trial in which some or all trial-related activities occur remotely rather than at a centralised research site.
15. A draft version of Annex 2 is available at www.ich.org/page/e6r3-good-clinical-practice.
16. MHRA, ‘Clinical trials regulations: six-month countdown begins’ (28 October 2025); MHRA, ‘UK-specific annotations to ICH E6(R3)’ (updated 9 March 2026); MHRA, ‘MHRA to streamline clinical trial approvals in biggest overhaul of trial regulation in 20 years’ (21 March 2023); The Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025 (UK).
17. EMA, Clinical Trials Regulation becomes fully applicable (31 January 2025): available at www.ema.europa.eu/en/news/clinical-trials-regulation-becomes-fully-applicable.
18. European Commission, ‘Questions and answers on the European Biotech Act’ (15 December 2025); EMA, ‘Clinical Trials Regulation becomes fully applicable’ (31 January 2025); EMA/ACT EU, ‘Launch of revised CTIS transparency rules’ (22 April 2024); Federal Institute for Drugs and Medical Devices, ‘A fast-track approach for the authorization of multinational clinical trials in the EU/EEA will be launched as test’ (3 December 2025).
19. See https://ec.europa.eu/commission/presscorner/api/files/document/print/en/qanda_25_3079/QANDA_25_3079_EN.pdf.
20. European Commission, Opening remarks by Commissioner Várhelyi – Exchange of views on the Biotech Act with the European Parliament’s SANTE-ITRE Committee (19 March 2026).
21. EMA & FDA, ‘Guiding principles of good AI practice in drug development’ (Guidance, January 2026).
22. Li, ‘A New Regulatory Road in Clinical Trials: Digital Twins’ (Applied Clinical Trials, 2024).
23. FDA, ‘Digital Health Technologies for Remote Data Acquisition in Clinical Investigations’ (Guidance and related materials, December 2023).
24. EMA, ‘Development of a reflection paper on the use of external controls for evidence generation in regulatory decision-making – Scientific guideline’ (Guidelines, 25 July 2025).
25. Wang et al, ‘Current perspectives for external control arms in oncology clinical trials: Analysis of EMA approvals 2016–2021’ (Journal of Cancer Policy, 2023).
26. Therapeutic Goods Administration, ‘Clinical Trial Notification (CTN) Scheme’, available at https://www.tga.gov.au/resources/resource/guidance/clinical-trial-notification-ctn-scheme.
27. JETRO, ‘Guidebook for Clinical Trials in Australia’ (March 2024), pp 1–2, available at www.jetro.go.jp/ext_images/_Reports/02/2024/f6172b819d209c83/Guidebook_for_Clinical_Trials_in_Australia_202403_En.pdf.
28. Clinical Trials Queensland, ‘Value – R&D Tax Incentive’: available at www.clinicaltrialsqld.com/value.
29. business.gov.au, ‘R&D Tax Incentive: Clinical Trials Determination Guide’, available at https://business.gov.au/grants-and-programs/research-and-development-tax-incentive/assess-if-your-randd-activities-are-eligible/clinical-trials-determination-guide.
30. Silicon Valley Bank, ‘The Advantage of Oz: Offshore Tax Rebates for Life Science R&D in Australia’: available at www.svb.com/industry-insights/healthcare-life-science/the-advantage-of-oz-offshore-tax-rebates-for-lshc-rd-in-australia.
31. NHMRC, ‘National Statement on Ethical Conduct in Human Research 2025’: available at www.nhmrc.gov.au/about-us/publications/national-statement-ethical-conduct-human-research-2025.
32. NIH ClinRegs, ‘Australia – Clinical Research Regulation’ (updated November 2025): available at https://clinregs.niaid.nih.gov/country/australia.
33. TGA, PIC/s Guide to Good Manufacturing Practice (GMP): manufacturing principles for medicines, APIs and sunscreens (14 June 2025).