Clinical trials with investigational medicinal products consisting of or containing genetically modified organisms: implementation of Clinical Trials Regulation EU 536/2014

Although originally applicable to genetically modified crops, advanced therapy medicinal products (ATMPs), such as gene therapies, that consist of or contain genetically modified organisms (GMOs) and also viral-based vaccines, need to comply with the European Union (EU) GMO legislation, as implemented in each EU Member State before a clinical trial can commence. Under the European Clinical Trials Regulation 536/2014 (CTR) due to go live on 31st January 2022, a single electronic clinical trial application dossier will need to be submitted to all the Member States involved in the trial, via the European submission portal (Clinical Trials Information System, CTIS). However, national documents, such as informed consent forms, will still need to be submitted, as part II of the dossier, to each Concerned Member State, also via CTIS. There will be a single coordinated and harmonized assessment of the clinical trial application between the involved Member States, with one country leading the coordination of the assessment (the Reporting Member State). The CTR has as yet not addressed GMO documentation (ERA, common application form, etc) required for an IMP with a genetic component. There is no defined interplay between the CTR and the current GMO legislative framework. There is no specified procedure, nor structure for submission of a GMO application via CTIS, as part of the new single submission and coordinated evaluation procedure for clinical trials defined by the CTR. Upcoming challenges to clinical trial sponsors under the CTR across Member States are identified in this article. Further, national GMO competent authorities are called upon to adopt a pragmatic and simple approach as a first step to facilitate the GMO assessment and its coordination with approval of a clinical trial application.