In the past 9 years as senior clinical scientist, I have been challenged many times by working with new and innovative drugs. Sometimes, unraveling the best study design to study novel drugs is not the only challenge I encounter.
Last year I got the opportunity to work with GMO’s (genetically modified organisms). More specifically: genetically modified vaccines and a gene therapeutic. For this type of interventions there is – next to the regular guidelines for clinical trials – additional legislation. As it is likely that we will encounter more of these types of interventions in the future, I find it worthwhile to use this blog as the opportunity to share my experiences with overcoming some of the legal and administrative hurdles associated with GMO’s in early phase clinical development.
In short, for the evaluation of clinical gene therapy research different aspects come together;
1) genetic modification,
2) environmental aspects and
3) clinical research.
As a result, also a whole bunch of different legal regimes based on European directives, come together. Unfortunately, the implementation of the directives into Dutch legislation contain aspects that still are not converged sufficiently.
Generally in the Netherlands, besides ethical approval, the institute that wants to work with the GMO needs a license from the Ministry of Environment. This implicates that next to the CCMO as reviewing committee and the Ministry of Health as competent authority (laid down by The Medicines Evaluation Board), the Ministry of Environment is involved as well. Furthermore, COGEM (the Netherlands Commission on Genetic Modification; http:// www. cogem.net) acts as advisory committee for obtaining the environmental license and bureau GGO (Bureau of genetically modified organisms; http://www.ggo-vergunningverlening.nl/) is involved for all administration regarding the license. Thus, there are many legal instances that the researcher need to involve and provide with the right documentation. However, the researcher can always get help from “Loket Gentherapie” that streamlines the processes and communication between the different bodies and is always of help when a researcher is lost in legislation.
There are only some minor differences for the clinical trial application for gene therapy studies to the EC/CA compared to a ‘regular’ clinical trial application. It is the application for the environmental license that makes the process complicated, or more accurately: lengthy.
For the license, the Ministry of Environment focuses in particular on the environmental aspects and the environmental risk analysis of the application. Just like a normal permit for installing for example your roof top terrace, the permit is available for public inspection (2 times, 6 weeks). The whole process takes at least 120 days, with clock stops for addressing the public objections. In practice, it takes months before you have the permission to start your clinical trial.
I’m puzzled by the idea that the general public would be able to judge the environmental risks of applying gene therapeutics in a clinical trial. These risk analyses are complicated matter and not common practice, even for the researchers involved. In my opinion, this makes the procedure unnecessarily lengthy and it does not automatically make the studies any safer. Do not get me wrong; of course, these clinical studies should only be executed if they are safe for both the volunteer and the environment. However, I do not understand why the environmental risk assessment cannot be incorporated in the CCMO assessment. COGEM/ministry of health experts could be additionally be involved if deemed necessary. This could make the whole process much shorter and further build on the reputation of the Netherlands as an attractive country for the innovative pharmaceutical industry to perform their gene therapy studies.
Anyway, I am happy that I have had this challenge and that I was able to scrutinize Dutch law regarding gene therapy studies. And now we have adapted all applicable CHDR SOPS according the current legislation we are ready to start our first clinical gene therapy studies!
by Ingrid de Visser, Senior Clinical Scientist