Call for More Effective Regulation of Clinical Trials with Advanced Therapy Medicinal Products Consisting of or Containing Genetically Modified Organisms in the European Union

Advanced Therapy Medicinal Products' Translation in Europe: A Developers' Perspective

“…Consequently, delays due to the variations in GMO regulation across MS result in a less-competitive and less-attractive environment for stakeholders to realize multicenter clinical trials with investigational gene therapies in Europe and has been issued by multiple stakeholders ( 18 ). Together with national competent authorities, they demand to exempt ATMPs containing or consisting of GMOs from the GMO legislation, as it has been temporarily adopted by the EU for IMPs treating or preventing COVID-19 in human ( 19 ).…”

Impact of genetically modified organism requirements on gene therapy development in the EU, Japan, and the US

“…Furthermore, each member state still requires additional supportive documentation, 25 some of which is needed in the local language, adding further complexity to the submission. 19 …”

“…In addition to documentation differences, national agencies have variable review timelines, differing languages, and differing views on the classification of products (deliberate or contained use). 7 , 8 , 19 , 25 A further complexity in some member states is that the competent authority reviewing the GMO and CTA may be the same (e.g., Germany, Italy, and Sweden), while in other member states, it is different (e.g., France, Spain, and Belgium). 25 A report by the Alliance for Regenerative Medicine published in October 2019 highlighted that these burdensome requirements have made Europe less competitive in attracting new advanced-therapy medicinal product (ATMP) clinical trials.…”

“…The EC and industry have recognized that the clinical development of GMOs is slowed by the current regulatory framework governing GMOs. 19 , 28 , 29 The recent decision to temporarily exempt coronavirus disease 2019 (COVID-19) treatments from GMO requirements 28 , 29 was made to “accelerate the authorization and availability of successful vaccines against COVID-19.” 29 The topic of permanent exemption is part of the ongoing discussion on the EC’s pharmaceutical strategy. 30…”

“…In the EU and Japan, where the requirements for GMO risk assessment must be met before initiating clinical trials, the regulatory process can create significant delays for starting a clinical trial. 14 , 18 , 19 Therefore, for product developers planning to conduct multi-regional clinical trials (MRCTs), it is critically important to consider the time required for both the preparation of the required documents and for the review of both clinical trial applications (CTA) and GMO submissions in each target country when planning development strategies.…”