Amid the COVID-19 pandemic, the EU is allowing trials to start before the requirements of directives dating back as far as 2001 have been met.
It is not often that regulation of clinical trials is eased. Usually the tendency is for rules to be tightened up—but necessity has proved the mother of invention in the case of clinical trials for products to combat COVID-19. The European Parliament rushed through an exemption from the onerous European Union requirement for prior environmental risk assessment in the case of products making use of genetically modified organisms—which, with the multiple current approaches using attenuated viruses or live vectors, is a scenario increasingly likely in vaccine development.
The exemption will permit clinical trials to start before the requirements of directives dating back as far as 2001 have been met. This legislation, notorious among sponsors of clinical trials, obliges sponsors to obtain written consent in advance from each of the member states where a trial is planned, on the basis of a case-by-case review of an environmental risk assessment. As the parliament resolution drily remarks, “experience shows that, in clinical trials with investigational medicinal products containing or consisting of genetically modified organisms (GMOs), the procedure to achieve compliance with the requirements of Directives 2001/18/EC and 2009/41/EC as regards the environmental risk assessment and consent by the competent authority of a member state is complex and can take a significant amount of time.”
Worse still are the impediments to multi-center trials. “The complexity increases greatly,” states the resolution, with multiple requests for authorization to multiple competent authorities in different member states in parallel—and with national requirements and procedures that “vary greatly from one member state to another.” Some countries require a single request for authorization to a single competent authority, but in others parallel requests need to be submitted to different authorities.
As if that were not challenging enough, “some member states apply Directive 2001/18/EC, others apply Directive 2009/41/EC, and there are member states that apply either Directive 2009/41/EC or 2001/18/EC depending on the specific circumstances of a clinical trial.” And other member states apply both directives simultaneously to different operations within the same clinical trial. There are also variations between national requirements as to the content of the technical dossier.
In consequence, “it is not possible to determine a priori the national procedure that is to be followed,” the resolution says. Attempts to streamline the process through informal coordination between member states’ competent authorities have been unsuccessful, and “it is therefore particularly difficult to conduct multi-center clinical trials with investigational medicinal products that contain or consist of GMOs involving several member states.”
Since the pandemic has created an unprecedented public health emergency and claimed the lives of thousands, as well as inflicting major disruptions to national economies and the EU, the plan is to ease that requirement so that remedies can be developed and be made available as soon as possible, the parliament reasons. And so that trials are not delayed “due to the complexity of differing national procedures put in place by member states,” it is necessary to grant a temporary derogation from the requirements concerning a prior environmental risk assessment and consent. This will last for the duration of the pandemic—or as long as COVID-19 is a public health emergency.
However, sites where the genetic modification of wild-type viruses and related activities take place will still be required to comply withthe legislation, so the manufacturing of medicinal products containing or consisting of GMOs intended to treat or prevent COVID-19, including investigational medicinal products, will be excluded from the temporary derogation.
Sponsors will also be required to minimize negative environmental impacts. And the environmental impact of exempt products “will continue to be assessed by the EMA in parallel with the evaluation of the quality, safety, and efficacy.” Compliance with ethical requirements and good clinical practice in the conduct of clinical trials continues to be mandatory as well as compliance with good manufacturing practice in the manufacture or importation of investigational medicinal products containing or consisting of GMOs.
Peter O'Donnell is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium