Background
The European regulatory landscape for advanced therapy medicinal products (ATMPs) is complex and the approval pathway depends on product classification. The EMA’s Committee for Advanced Therapies (CAT) is responsible for providing scientific recommendations on the classification of ATMPs as either gene therapy medicinal products (GTMPs), somatic cell therapy medicinal products (sCTMPs), tissue-engineered products (TEPs), or combinations thereof. However, product classification may not always be clear-cut given the proliferation of novel approaches to ATMP development.
Approval times for an initial clinical trial in Europe varied widely from fewer than 30 days to more than a year, with an average approval time of three to six months, according to a survey of Alliance of Regenerative Medicine members. These timelines vary widely by country and are longer for trials with gene therapies due to the additional regulatory submissions and permits required for products sub-categorized as genetically modified organisms (GMOs).
Objective
A European ATMP developer engaged Premier Research for assistance with planning a Phase 2a study in six countries within the European Economic Area, which is regulated by European Union (EU) gene therapy legislation. The investigational medicinal product (IMP), a genetically modified naked DNA plasmid, was given the outcome of an ATMP/GTMP by the CAT. Given the borderline nature of the IMP and the potential regulatory hurdles associated with GTMPs sub-categorized as GMOs, Premier Research worked with the sponsor and regulators to reduce the number of submissions required and accelerate study start-up timelines.
Reducing regulatory burden and accelerating study start-up
In each of the six countries involved in the clinical trial, additional regulatory submissions and permits would have been required if the IMP was classified as a GMO, lengthening the development timeline and delaying study start-up. To address this hurdle, Premier Research developed a regulatory approach to perform a documented risk assessment and rationale for classification of the IMP such that the GMO Authorities in each country would be persuaded that additional GMO approvals were not required for this non-viral based product.
We provided a written position statement to the respective GMO Authorities indicating that the IMP did not fall under the GMO sub-category per definitions defined in relevant EU directives as the plasmid does not have any biological entity capable of replication or transfer of genetic material. In four of the six countries, it was negotiated that no additional GMO approvals were required.
Consequently, we were able to move forward with only ATMP reviews, shortening the timeline for regulatory approvals by one to three months and accelerating study start-up, site initiation visits, and patient enrollment. Eliminating the requirement for GMO approval also broadened the range of sites that could participate in this clinical trial, as GMO accreditation and permits were no longer needed in these countries.
Takeaway
When planning a gene therapy trial in the EU, it is critical to understand the nuances of country-specific regulatory guidelines. Partnering with a team with experience in developing flexible, creative approaches to navigating the complex regulatory landscape for these advanced therapies can streamline the process, accelerating study start-up.
Premier Research has conducted more than 60 gene and cell therapy trials in the past five years in multiple therapeutic areas, including oncology, hematology, neurology, and rare disease. Contact us to schedule a consultation with our gene therapy experts. For more information on ATMP and GMO regulation, click here.