The now infamous TeGenero clinical trial - six patients fell critically ill from an investigational biologic — occurred, ironically, after the EU Clinical Trials Directive had been implemented in the UK in May 2004. Biotechs in the Netherlands, it seems, were adjusting to the adoption of the EU Clinical Trials Directive into national law on March 1, 2006 when the TeGenero incident occurred (March 13). Before that, healthy volunteer trials in the UK had been unregulated.

At the recent Applied Clinical Trials European Summit in Amsterdam, one speaker talked about the long shadow the TeGenero trial will cast not only on the Netherlands but on the entire European Union. Even though the Medicines and Healthcare Products Regulatory Agency’s (MHRA) final report from May identified some Good Clinical Practice discrepancies, the main cause of the severe reactions in the six trial volunteers was an “unexpected biological effect.”...

In the same report, the MHRA called it “a very complex scientific issue” and said that the agency is having it reviewed by an independent, expert scientific group appointed by the Secretary of State for Health.

Seeking outside expertise for the kinds of clinical trials biotechs run may be the wave of the future. Clearly the MHRA does not want to be caught off guard again, nor does any other EU regulatory agency. The sense is that biotechs are going to have to jump through a lot more hoops now before they can test biologicals on humans.

According to the speaker, the Netherlands was one of the more efficient EU countries to seek gene therapy clinical trial approvals before the Directive was passed. The adoption of the Directive has changed the situation there “drastically”, according to one of the speakers at the Summit, due in no small part to the increased number of documents and attendant bureaucracy required for a clinical trial application. In fact, there have been no new biotech product trials started in the Netherlands since the Directive was passed.

Biotechs often are at the forefront of developing orphan drugs — drugs for diseases that have an incidence of fewer than 200,000 in the U.S. and have no chance of becoming blockbusters. Sometimes, biotechs find only one person in a country with the disease they are studying and they generally want to recruit every patient they can find, no matter where they live. But the speaker at the ACT European Summit contended that submitting an entire clinical trial application for a single patient in the Netherlands was a lot of work, compared with other EU countries.

The central question attendees at this conference left with was ‘Will regulators in the EU have the experience necessary to review highly innovative products?’ Trying to avoid another TeGenero is certainly uppermost in every regulator’s mind, but at the same time that shouldn’t prevent biotechs from studying innovative treatments for rare diseases. Regulators in the Netherlands are specifically instructed to consult outside expertise, and it was strongly suggested that the biotech industry and regulators need to collaborate closely. For the sake of future biotech innovations, let’s hope they do.