As proof of microdosing's potential in drug development, bioanalytical CRO, Xceleron, is to lead the European Union Microdose AMS Partnership Programme (EUMAPP) having additionally been awarded €2.1 million to further develop this technology.
The microdosing approach conducted with Accelerator Mass Spectrometry (AMS) offers new ways of developing drugs by bridging the gap between the laboratory and the clinic.
Working on the principle that 'the best model for man is man', the human microdosing concept, enabled by the ultra-sensitive analytical technology of Accelerator Mass Spectrometry (AMS), enables the safe introduction of sub-pharmacological doses of new drugs into man much earlier than ever before possible.
In this way, ADME/PK data in the target species (man) is gathered rather than relying on animal models that may well not prove to be of any use.
Essentially the adoption of human microdosing should allow better choices to be made in drug development, focusing resources on drug candidates that are more likely to succeed and killing early those compounds that will sap resources and waste time.
The 30-month EUMAPP project gathers together 10 organisations from 5 different countries (United Kingdom, Sweden, Netherlands, France and Poland) that aim to promote this technology as a viable experimental technique.
The programme aims to additionally certify high and low voltage AMS technologies as the most accurate in measuring microdosing values.
"This programme follows on from the successful CREAM trial and will add 7 more drugs to the growing portfolio of compounds tested by Xceleron," said Professor Colin Garner, Xceleron's CEO.
As many as one in three drugs fail in Phase I (healthy volunteer) clinical testing despite extensive pre-clinical screening of potential clinical candidates in animal and in vitro systems.
A high proportion of these failures can be attributed to sub-optimal pharmacokinetics (PK) leading to potential efficacy or safety issues in humans.
A spokesperson for Xceleron told DrugResearcher.com:: "There is little doubt that the current drug development paradigm needs to be updated as it costs around $1bn to develop a drug over many years."
"There is general recognition by the pharma industry that more clinical information needs to be gathered earlier than is currently practiced. Xceleron have worked with clients ranging from big pharma and the likes of GSK to the small innovative biotechs such as Speedel."
Human microdosing helps predict the ADME/PK properties of a new drug candidate at pharmacological dose levels in man that is currently achieved by modelling with animals and in vitro systems, which have tended to suffer from variable results.
While a distinct improvement on current techniques the common concern around human microdosing is that of predictivity from the microdose (at least 1/100th of the pharmacological dose) to the pharmacological dose.
"Theorists can think of a number of situations whereby the predictivity of microdosing might be questioned, however in practice and taking into account many 'difficult' cases Xceleron has shown that microdosing should have an 80 per cent plu level of predictivity," said the spokesperson.
"This was borne out by the CREAM trial which, instigated by Xceleron, looked at a number of drugs in which pharmacological PK in man has proven too difficult to predict," he added.
The issue with microdosing is that the body of public knowledge available to make a judgment on its utility is relatively small - hence the instigation of the CREAM trial and the recently announced EUMAPP project which is supported by EC monies under FP6.
Microdosing is not only making waves in the EU. While most of the world's experience of microdosing has been in Europe via Xceleron, microdosing has been discussed in regulatory terms in Europe since 2003 via an EMEA position paper on the subject.
However that seems likely to change with the advent of the US FDA's Exploratory IND guidance which was drafted in April last year and finalised in January 2006.
The Exploratory IND provides guidelines on what kind of conditions would be acceptable with regard to human microdosing studies - essentially they provide a very quick route into man with reduced toxicology and CMC requirements.
"The pharma industry is a big ship which takes time change direction - however we believe that the ship is turning as we have recently seen a huge increase in the level of interest in human microdosing, now translating to studies which will take place over the coming months," said the spokesperson.
"Whereas the US has created a potentially more favourable regulatory environment for microdosing studies, the experience and funding for such studies sits in Europe."