Xceleron gives FDA document thumbs up

One particular approach detailed in the document, "Exploratory IND Studies," was the concept of human microdosing, an experimental technique that has been hailed as an answer to the escalating drug development times and especially costs.

The concept of human microdosing uses sensitive analytical technologies to track the sub-pharmacological drug doses given to humans in the drug development process. This allows human information to be determined much earlier than ever before possible, providing drug developers with a means to progress only the most promising drug candidates to further, more expensive clinical trials.

As many as one in three drugs fail in Phase I (healthy volunteer) clinical testing despite extensive pre-clinical screening of potential clinical candidates with a wide variety of in silico, in vitro, ex-vivo and animal models. A high proportion of these failures can be attributed to sub-optimal pharmacokinetics (PK) leading to potential efficacy or safety issues in humans.

"The approach could significantly reduce the time and resources spent during early drug development. The report further endorses our belief in ultra-sensitive Accelerator Mass Spectrometry (AMS) as the enabling technology for human microdosing studies,"​ commented Professor Colin Garner, CEO of Xceleron.

Using AMS it is possible to conduct a full human metabolism study after administration of as little as 0.1 milligram of drug substance, measuring drug concentrations in biological fluids up to 1000 times less than the levels one observed in Phase I clinical study.

The document defines a microdose as 1/100th of the dose calculated to yield a pharmacological effect with a maximum dose of 100 micrograms, as per the EMEA's position paper of June 2004. However, it differs from the EMEA paper in that no genetic toxicology tests are required, reflecting the fact that these studies are safe for human subjects at these microdose levels.

Xceleron has been a company at the forefront of using this experimental technique in its drug R&D. The success it has had bodes well for the industry as a whole as more and more pharmaceutical companies are sitting up and taking note of its advantages.

In February of this year results from a Consortium for Resourcing and Evaluating AMS Microdosing (CREAM) trial revealed that three of the five selected drugs resulted in predictive human pharmacokinetic data, which would have allowed the right decision to be made for further drug development.

Two of the drugs deviated from linear pharmacokinetic behaviour but nevertheless the microdose results gave useful insights into the properties of the drugs.

In September of last year, Xceleron​ struck a deal with GlaxoSmithKline GSK) which has resulted in the drug giants commissioning the pharmaceutical industry's first in-house Accelerator Mass Spectrometry (AMS) facility.

The FDA report is entitled: "Guidance for Industry, Investigators and Reviewers. Exploratory IND Studies Draft Guidance. Centre for Drug Evaluation and Research, Food and Drug Administration. US Department of Health and Human Services. April 2005."