MHRA sets out how it will weigh non-clinical data from outside the OECD MAD system

What the MHRA has said

On 4 November 2026 the MHRA published guidance on how it will assess non-clinical data generated outside the OECD Mutual Acceptance of Data (MAD) system. According to the agency's announcement, the guidance explains when UK clinical trial applications that rely on non-OECD MAD safety data may be considered. It also describes enhanced assessment in limited circumstances and a programme of test facility inspections.

The summary available to us is short. It does not say which circumstances trigger enhanced assessment, which facilities or countries will be inspected, or how inspection findings will feed into trial application decisions. Sponsors should read the full guidance before drawing conclusions about their own packages.

Why the OECD MAD question matters for trial applications

In general terms, the OECD MAD system lets participating countries accept non-clinical safety data generated under Good Laboratory Practice (GLP) in line with OECD principles, without repeating the studies. A first-in-human application normally rests on that non-clinical package: toxicology, safety pharmacology and related studies that support the proposed starting dose and monitoring plan.

If part of that package comes from a test facility outside the MAD system, the regulator has less automatic assurance about how the data were generated. The MHRA's guidance appears to set a route for those cases rather than closing the door. The record says such applications 'may be considered', which suggests case-by-case treatment, not a blanket acceptance or rejection.

The inspection programme is the notable signal

The announcement pairs the assessment approach with a programme of test facility inspections. For sponsors, this means the regulator intends to build its own evidence on non-OECD MAD facilities rather than relying only on documents submitted with an application. How that programme will operate, and whether sponsors will be asked to help facilitate access, is not stated in the record.

The change sits alongside other MHRA activity on inspection. On 6 November the agency updated its guidance page on GCP inspections for clinical trials of medicines. That page sets out risk-based and triggered inspections, dossier requests and the inspection process, and names ICH E6(R3) as the reference standard. It covers clinical conduct, not non-clinical laboratories, so the two should not be conflated. Still, together they show a regulator paying close attention to data provenance and quality at both ends of development.

How this compares with developments in the US

The US is moving on early-phase speed. On 4 November the FDA's CBER said it had closed applications to its Expedited IND pilot after more than 100 submissions, with selections due by 18 December. The pilot, run under HHS Operation TrialBlazer, will test whether outside expert institutions and rolling review can speed first-in-human trials without lowering safety or oversight standards.

CBER also described the structure. Sponsors in the pilot submit discipline-specific components during pre-IND development, and a QRI vets each component before the 30-day review begins. Most activity therefore happens before the formal IND.

The two approaches are different, and no record links them. Even so, both put weight on how early evidence is assembled and checked before a first-in-human decision. A sponsor planning parallel UK and US starts will need to manage both the speed ambitions in the US and the provenance questions in the UK.

Who is affected and what to watch

The most exposed groups are sponsors, CROs and non-clinical project teams that have commissioned or plan to commission safety studies at facilities outside the OECD MAD system, particularly where those studies underpin a UK first-in-human application. Teams that use only OECD MAD-compliant facilities may see little direct change, though they should confirm this against the guidance text.

The wider development landscape shows why timing matters. Xencor said on 4 November that it plans to meet the FDA in the first half of 2027 on a possible accelerated approval route for XmAb819. Arvinas, in its Q3 2026 results, reported dosing the first patients with ARV-6723 in a Phase 1/2 solid tumour trial and planned EU and UK filings for ARV-102 in PSP. The records say nothing about where those companies generated their non-clinical data, so there is no suggestion they are affected. They simply illustrate how many programmes are moving through early development and regulatory interactions at once.

Open questions for the coming months include how the MHRA defines 'limited circumstances' for enhanced assessment, how soon inspections begin, and whether any applications face delays as a result. None of these is answered in the available record.