On 14 July 2026, Bellberry and ASCEPT released the draft of their NAMs HREC Review Checklist: a risk-proportionate, hybrid-model guide for Australian Human Research Ethics Committees for first-in-human trials supported by New Approach Methodologies. The draft guidance is open for comment until 31 August.
It is, to my knowledge, the first guidance document anywhere in the world that tells reviewers precisely how to assess a NAMs-supported clinical trial application. I believe this is this is a critical step to the widespread adoption of NAMs globally, and one that positions Australia to be a world leader in human-relevant clinical trial initiations.
Why This Guidance Is Different
There is no shortage of NAMs documents. The FDA has its draft NAMs guidance. The European Commission has its Roadmap. But these are often structured as a series of considerations, recommendations, or plans. These are typically non-binding and lack certainty drug sponsors need. None of them answer the question that matters most at the point of clinical trial initiation: how to evaluate a submission where NAMs replace or reduce conventional animal data?
The Bellberry/ASCEPT Checklist answers that question directly. It is structured, scoreable, and designed to be used in actual human research ethics committee (HREC) meetings. Every item can be rated Acceptable, Conditional, Unacceptable, or Not Applicable based on defined expected evidence. Core items must reach at least Conditional before a trial can proceed.
But the audience is not just ethics committees. Drug sponsors planning a NAMs-supported submission can and should cross-reference this Checklist when assembling their evidence package. It tells you what the committee will be looking for: Context of Use statements, validation summaries, weight-of-evidence assessment, uncertainty characterisation, and trial safeguards calibrated to NAMs-derived risk.
NAMs developers should also take note. The Checklist specifies the technical characterisation, domain of applicability, and fit-for-purpose evidence that reviewers will expect. If your platform cannot supply these elements in a format an HREC can assess, your technology is not submission-ready. Having these elements prepared and ready for clients makes your technology a plug-and-play option for nonclinical studies.
Risk Tiering Defines Approach
The Checklist introduces a four-tier risk framework (Tier 0 to Tier 3) that calibrates the depth of review to the role NAMs play in the submission. This is the single most important design decision in the document.
The risk matrix cross-references three dimensions: the modality and indication risk (lower, moderate, higher), the scope of NAMs use (support/complement, fill gap/partially replace, fully replace), and the resulting tier assignment. This means the barrier to entry is proportionate. If using NAMs instead of animals poses minimal additional patient risk, the pathway is straightforward. The Checklist does not treat all NAMs submissions as high-risk by default. The need for external review and the stringency applied to the evaluation of NAMs data will be set by the risk tier.
Weight of Evidence: How Multiple NAMs Tell a Story
One of the most practically important features of the Checklist is combining data from different NAMs to better inform specific scientific questions. Most real-world NAMs submissions will not rely on a single method. They will combine in vitro systems, in silico modelling, PBPK predictions, and possibly limited animal data into an integrated evidence package.
The Checklist requires sponsors to explain how individual NAMs combine into a coherent package. It asks whether the methods converge, complement one another, or provide orthogonal support for the same decision. It requires an integrated weight-of-evidence table mapping each safety question to its supporting lines of evidence and residual gaps. It requires an explicit uncertainty statement covering known unknowns, limits of extrapolation, and the consequences if assumptions prove wrong.
This is what will convince an HREC that a drug is reasonably safe to test in humans. Not a single NAM replacing a single animal study. A structured, transparent argument showing how multiple lines of human-relevant evidence address the key safety questions, where the gaps remain, and how trial design manages the residual uncertainty.
Parallels with FDA Guidance, Practically Expanded
The Checklist has parallels with key concepts from the FDA NAMs draft guidance, including Context of Use, fit-for-purpose validation, and weight-of-evidence integration. But it goes further in in a key aspect: it operationalises these concepts for a specific decision point.
The FDA guidance describes what good NAMs evidence looks like. The Bellberry/ASCEPT Checklist tells a reviewer how to score it, when to escalate, and what determination to reach. It includes templates for validation summaries, weight-of-evidence tables, uncertainty statements, and minimum evidence packages. These are tools a committee can use on the day.
What This Means for NAMs-Based Trial Initiation in Australia
This guidance dramatically lowers the practical barrier to initiating NAMs-supported clinical trials in Australia.
Until now, the single biggest obstacle to NAMs adoption in the clinic was not regulatory hostility. It was uncertainty. Sponsors did not know how an ethics committee would evaluate their NAMs data. Committees had no shared framework to evaluate it. The result was a circular problem: sponsors hesitated to submit NAMs because committees had no precedent for reviewing them, and committees had no precedent because sponsors never submitted them.
The Checklist changes that. It gives sponsors a clear target for what to prepare. It gives committees a structured process for how to review it. It gives both sides a shared language of Context of Use, risk tiering, weight of evidence, and proportionate safeguards.
For the right applications, Australia is now the most practical jurisdiction in the world to run a NAMs-informed first-in-human trial. The CTN scheme already offers faster initiation timelines and lower regulatory overhead than the US IND or EU CTA pathways. This Checklist adds a structured, transparent ethics review process calibrated specifically for NAMs. Drug sponsors with strong NAMs packages should be actively considering Australia for their next FIH programme. The infrastructure is ready.
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