The US Food and Drug Administration looks set to back away from a proposal that would have exempted manufacturers of investigational new drugs destined for Phase I clinical trials from having to fully validate their manufacturing process.

The volte face comes after vocal opposition from a number of groups, including the Biotechnology Industry Association, the Parenteral Drug Association and consumer group Public Citizen, which claim relaxing the rules could increase the risk of volunteers being injured by drug candidates.

The Direct Final Rule – a type of guidance that bypasses the usual notice, comment and review system at the FDA and is intended to ease through changes to the rulebook that are not ‘substantive’ - was released in January 2006 and created a distinction between small-scale laboratory production of investigational human drug products (including biologics) and large-scale commercial manufacture of pharmaceuticals.

At that time, FDA Deputy Commissioner for Operations Janet Woodcock said the exemption was intended to recognise that regulations designed for manufacturing do not really fit laboratory production. It does not apply to drugs in Phase II or III testing.

Under current regulations, even clinical trial materials used in Phase I drug studies must go through extensive GMP requirements, and bypassing this would reduce the cost of early-stage trials, and help tackle the issue of declining R&D productivity in the pharmaceutical industry.

But Public Citizen maintains that the move also makes the drug industry less accountable and there is no evidence that current system acts as a brake on new drugs starting clinical trials. Moreover, deputy director of the Health Research Group at the organisation, Peter Lurie, commented: “All barriers do (or at least should) serve a social purpose – in this case, preventing those incapable of following or unwilling to follow GMPs from administering investigational products to humans.”

While Public Citizen is well known for challenging the drug industry and FDA, groups representing biopharmaceutical manufacturers, including the BIO, have voiced their concerns with the guidance.

In a statement, the BIO notes that as it stands the exemption will not reduce the burden on drugmakers, and could in fact increase it by asking for information that isnot currently required. Most companies use the same facilities to make Phase I and Phase II clinical trial materials, it points out, and what is needed is a new set of GMP guidance that specifically covers manufacturing for trials, ideally an incremental system that is less stringent than those for manufacturing during investigational product development.

The initiative is part of the FDA’s Critical Path programme, which aims to streamline drug development by identifying promising new therapies early. The GMP exemption was announced alongside draft guidance on exploratory INDs, a stripped down application to start clinical trials based on techniques such as micro-dosing, which exposes patients to sub-therapeutic doses of a drug.