An academic perspective on the EMA guidelines for medicines containing genetically modified cells

reNEW researchers have, in collaboration with the European Medicines Agency, published a commentary on the updated Guidelines for the development and evaluation of medicinal products containing genetically modified cells. The article, published in the British Journal of Clinical Pharmacology, presents a summary of the revised guidelines and a commentary on it from the academic developers’ point of view.

ATMPs in the clinic
Advanced Therapy Medicinal Products (ATMPs), such as those developed within reNEW, are a relatively new class of medicinal products that are mainly developed for the treatment of diseases for which currently insufficient treatment options exist. Over the last period, 28 ATMPs have been approved for clinical use by the European Medicines Agency (EMA), of which most are Gene Therapy Medicinal Products (GTMPs). GTMPs are biological medicinal products that fall in two categories: in vivo gene therapies and ex vivo gene therapies.

Updated guidelines
EMA first published a guideline on medicines containing genetically modified cells in 2012, to provide guidance around the development and evaluation of these medicinal products. Since, experience has been obtained with evaluation of the first GTMPs. In addition, technological advances in the field have been made. This new knowledge was incorporated in updated guidelines in 2021.

Academic perspective
In the present article, reNEW researchers Ana Hidalgo-Simon, Pauline Meij and Mara Tihaya teamed up with EMA to present an academic perspective on the updated guidelines. “It is important that EMA is aware of the challenges academic developers face. For this reason, we are in a constant dialogue,” says Hidalgo-Simon. Many of the GTMPs developed within an academic setting are inherently complex. Demonstrating the necessary positive risk-benefit balance is hence hindered by several challenges. Hidalgo-Simon explains: “Firstly, the products themselves consist of multiple components that are all subject to quality requirements. Besides, GTMPs are subject to EU regulations around genetically modified organisms.” She continues: “Most importantly, many of the GTMPs target ultra-rare orphan diseases which makes performing traditional randomized clinical trials merely impossible. In the absence of such a study, it is important that real-world data and registry data can support market authorization decisions.”

Flexibility is key
The EMA acknowledges that the uniqueness of each GTMP requires flexibility in development and evaluation of the end-product: both in an academic and commercial setting. A risk based approach should hence always be taken as a basis for setting quality controls and guiding non-clinical and clinical development to ensure successful market entry at the end of the process. Developers can always seek advice with EMA to receive guidance on their development programs and post-authorization evidence generation strategies. As extra support, EMA is currently developing a Guideline on the quality, non-clinical and clinical requirements for investigational ATMPs in clinical trials, which will be especially useful during early clinical development stages of novel ATMPs such as those developed within reNEW.

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