BioWorld International Correspondent

LONDON - The FDA set out draft guidelines indicating it will allow microdosing studies in man without the full range of animal testing or any of the genetic toxicology tests that now are required before therapeutic doses can be administered in Phase I trials.

The guidelines refer to "Exploratory Studies" that involve very limited human exposure to the compound being tested and have no therapeutic intent.

The agency said the potential risks of those types of studies are less than for a traditional Phase I, and therefore the investigational new drug applications "can be less detailed and more flexible than for traditional [Phase I] IND studies."

The guidelines aim to stop the waste of time and money involved in animal tests of drug candidates that turn out to have unacceptable profiles in humans.

That's good news for UK company Xceleron Ltd., which has pioneered the technique of microdosing. It administers radiolabeled drugs at microdoses (a maximum dose of 100 micrograms) and subsequently assesses ADME characteristics using its Accelerator Mass Spectrometer. Xceleron recently completed human trials validating the technology.

In the trial, five compounds with known and different pharmacokinetic characteristics were administered as microdoses. Three of the five resulted in predictive pharmacokinetic data, which would have allowed the right decision to be made for further development. Two of the drugs deviated from linear pharmacokinetic behavior, but the microdose results provide useful insights into the properties of the drugs.

The trial, sponsored by F. Hoffmann-La Roche Ltd., Eli Lilly and Co., Servier Laboratories SA and Schering AG, selected the five drugs on the basis of their difficult pharmacokinetic properties - for example, showing good bioavailability in dogs and rats and very poor bioavailability in humans.

Jeremy Hague, Xceleron's European business development manager, told BioWorld International more data are needed on a wider range of compounds to clarify how useful the technique is. "We can only tee this up; industry has to hit the ball. It's a valuable piece of technology, let's see what we can do with it," he said.

York-based Xceleron estimated microdosing could cut 12 to 18 months from development programs. Hague said getting human bioavailability data before having to pay for full Phase I trials could be of particular value to cash-starved biotechnology companies. It is possible to rank candidates on the basis of ADME characteristics in advance of full toxicology and animal studies, and cut down on the current 30 percent failure rate in Phase I.

The FDA guidelines follow on the Critical Path Report in March 2004, which called for tools to be developed for eliminating unsuitable candidates early in the development process. The European Medicines Evaluation Agency set out a similar position on microdosing in May.