New data strengthens case to replace animals in lab tests with
24 June 2008
The European Union Microdose AMS Partnership Programme (EUMAPP)
consortium has announced the preliminary results of a 30-month, €2m
project studying the use of microdosing in drug development. The
findings were presented at the European Federation for Pharmaceutical
Sciences (EUFEPS) Conference in Bad Homburg, Germany on 16 June.
The compounds selected for EUMAPP were chosen to rigorously test the
predictability of human microdosing by studying drugs that exhibited
properties in humans that are difficult to predict in animal or in vitro
models and drugs with properties that, it was suspected, might be
difficult to predict at a therapeutic dose from microdose data.
On reviewing the preliminary EUMAPP data Dr Colin Garner, President
and CEO of Xceleron and Chair of the EUMAPP steering committee
commented: “The outputs of the programme need to undergo rigorous
scrutiny and detailed interpretation, but the early indications are that
results strongly endorse the ability of microdosing to provide valuable
human data at the earliest stages of exploratory clinical development.”
Dr Roeline Jochemsen, Director of Clinical Pharmacokinetics &
Pharmacometrics at Institut de Recherches Internationales Servier
observed that “The EUMAPP study provides increased confidence in the
predictivity of Microdosing”.
Professor Malcolm Rowland, Scientific Advisor to the EUMAPP
consortium said: “Generally the EUMAPP results are sufficiently
encouraging to continue to support the view that, applied intelligently,
microdosing coupled with AMS, offers an additional tool to facilitate
earlier than otherwise possible decisions in candidate selection”.
Recently Xceleron announced that it has developed a database of 25
compounds with data on both microdose and pharmacological dose that show
80% predictability of pharmacokinetic parameters over dose ranges of a
hundred-fold and more (in some cases many thousand-fold) for a diverse
range of compounds.
Microdosing involves giving ultra-low, safe, doses of new compounds
to human volunteers and responses can then be analysed by Accelerator
Mass Spectrometry (AMS).
AMS is able to directly count individual atoms and is so sensitive
that it has the ability to detect a compound even after one litre of it
has been diluted in a volume of liquid equivalent to the world’s oceans.
Many agree that the TGN1412 drug disaster could have been avoided by
this approach — in this drug trial human volunteers suffered terrible
side effects that were not predicted in monkeys given doses 500 times
The use of micro-dosing as an animal test replacement would be a huge
boost to the National Anti Vivisection Society (NAVS) campaign to end
primate tests and to secure improved rules for animal experiments in
NAVS Chief Executive, Jan Creamer, said: “The European Commission is
currently reviewing Directive 86/609/EEC on the use of animals in
experiments, and is expected to make proposals for a revision this year.
We have been very actively involved in this process, with the adoption
of our Declaration to end primate tests with the signatures of 432 MEPS
and numerous presentation to the Parliament and Commission. With
cosmetics tests we showed that with the right commitment these tests
could be replaced, the time is now right for a major shift in how
regulatory testing is undertaken. The adoption of modern human-based
techniques will be good news for animals and good news for consumers.”