Parexel

PAREXEL International is a company based in Waltham, Massachusetts with offices all around the world, founded in 1983 by Josef H. von Rickenbach (still current CEO) and Anne Sayigh, that provides services for companies in the pharmaceutical, biotechnology and medical device industries, including consulting and clinical studies. The name PAREXEL comes from Paracelsus, a Swiss physician considered as the father of modern toxicology. PAREXEL employs more than 6,500 people worldwide and is one of the most important pharmaceutical services companies.

TeGenero Clinical Trial
In March 2006, a PAREXEL-run trial on behalf of TeGenero, the now bankrupt German biotechnology firm, on its anti-inflammatory drug TGN1412 to treat rheumatoid arthritis, multiple sclerosis or leukaemia, unexpectedly caused severe inflammation and multiple organ failure in six healthy volunteers at a facility based at Northwick Park Hospital in London.

The drug had been previously successfully tested on animals. However, a documentary shown in the UK on 28th September, 2006 featuring journalist Brian Deer as part of Channel 4's Dispatches series exposed uncertainty about the existence of data that should mandatorily have been submitted by TeGenero to the Medicines and Healthcare products Regulatory Agency (MHRA) prior to the trial indicating whether TGN1412 had been adequately tested on human blood in vitro. Concerns were also raised about whether a safe human dosage was properly obtained by TeGenero.

However, it should be noted that other opinion leaders believe that PAREXEL acted within all the current guidelines that exist for clinical trials (and this is also the conclusion of the MHRA investigations - see below), and that it is the guidelines that are at fault rather than PAREXEL or TeGenero per se. The unfortunate events at Northwick Park may lead to an examination of the whole range of drug testing regulations in the UK.

Conclusion of the MHRA
The MHRA published on 25 May 2006 a final report on these events which concluded that even if there were some  discrepancies in the procedure, they did not cause the adverse effects which were observed:
 * This investigation indicates that the adverse incidents did not involve errors in the manufacture of TGN1412 or in its formulation, dilution or administration to trial participants. The MHRA therefore concludes that an unpredicted biological action of the drug in humans is the most likely cause of the adverse reactions in the trial participants. Monoclonal antibodies are a relatively new type of biological drug although there are a number of them already licensed and in use. However, TGN1412 is a new class of monoclonal antibody which has a stimulatory mode of action affecting certain types of cell in the immune system. In this case the resulting activity seen in humans was not predicted from apparently adequate pre-clinical testing. This is a complex scientific issue which raises important scientific and medical questions about the potential risks associated with this type of drug and how to make the transition from pre-clinical testing to trials in humans. (Conclusion of the final report)

The discrepancies concerned contracts and insurance procedures, failure to update the medical history file of a subject, permission given to the two placebo subjects to leave the hospital without checking that there were really the ones who were given the placebo, as this was a double-blinded trial (but the incident made this precaution unnecessary), and no system to provide a 24h medical cover.