BioWorld International Correspondent

LONDON - The UK is bringing in a new national accreditation scheme for Phase I clinical trial units, following the TGN1412 trial in which six healthy volunteers suffered life-threatening cytokine storms. The system will be policed by a beefed-up inspection regime, with units having until April to show they meet the new requirements.

The new rules cover the emergency and safety procedures that must be in place and the requirements for staff training in units conducting first-in-human trials of products with novel modes of action. A secondary, more stringent set of rules will apply if they also are complex biological molecules.

Dympna Starling, head of quality assurance at LCG Bioscience Ltd., of Cambridge, UK, which conducts clinical trials, welcomed the scheme saying, "The accreditation scheme provides much-needed formal guidance on the standards expected in a unit conducting first-in-human trials involving the administration of molecules where the risk may be difficult to predict."

Starling said the scheme will provide evidence that good practice is in place. "This initiative reinstates the UK as a world leader in early phase drug development."

The plan implements one of the main recommendations of the expert group that investigated what went wrong with the TGN1412 study on March 3, 2006. On the basis of the report, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) brought in stricter rules on the authorization of first-in-human trials in 2007. Following on from that the MHRA said the national accreditation scheme covering the conduct of such trials will, "maximize subject safety and create additional public confidence in the regulatory oversight of such trials."

The plan does not consider Phase I studies of ill patients conducted in hospitals, but does cover patient volunteer populations such as asthma sufferers.

Layered on top of the standard system is a supplementary scheme of stricter regulations to cover higher-risk agents. That includes biological molecules with long half-lives, and those directed against targets that are not expressed in healthy subjects.

Not only may absence of a target alter the way a molecule behaves, but animal studies may be of little value in predicting adverse reactions, as was the case with TGN1412.

Apart from not administering a product to all volunteers simultaneously, as happened in the TGN1412 trial, one of the main changes in trial design was a move from No Observable Adverse Effect as a measure for setting starting doses, to Minimum Anticipated Biological Effect Level. Using the latter measure, the starting dose in the disastrous TGN1412 trial would have been twentyfold lower.