Regulatory safety aspects of advanced therapy medicinal products (ATMPs)

Abstract

Advanced therapy medicinal products (ATMPs) such as gene-, cell- and tissue engineered therapies offer tremendous potential for treating unmet medical needs. Due to the novelty, complexity and technical specificity of such products, specially tailored and harmonized rules are needed to evaluate their safety and efficacy. Despite rapid progress in research and the wide range of ATMPs undergoing pre-clinical and clinical development, the number of licenced products still remains low. In order to determine the main factors, which complicate the translation from ATMPs research into patient access, the feedback from main stakeholders i.e. representatives of product manufacturers, regulatory authorities and patients’ associations was collected in semi-structured interviews. The main focus was on pre-clinical safety testing and the relevant regulatory considerations. Numerous factors have been identified as limitations preventing more rapid market authorization for ATMPs. The key challenges in pre-clinical development considered availability of the right animal model for the specific disease, current approaches in immunogenicity testing and insertional site analysis as well as determining appropriate dosing strategy. Concerns regarding the lack of validated (bio)analytical methods and insufficient programs for environmental risk monitoring were raised. A specific identified challenge for the ATMPs sector was the difficulty to meet all the requirements to obtain market authorization from regulatory authorities, especially for products developed for European and non-European markets simultaneously, and a great heterogeneity in the legal requirements at the national level for products developed for non-routine use. To address these knowledge gaps and regulatory challenges, numerous international collaboration projects and initiatives have been already undertaken. It is likely that the introduction of ATMPs will follow an incremental pattern of technological and regulatory change, building on existing drug development and regulation heuristics and experiences. A necessary open dialog and continuous collaboration between stakeholders is considered as key to learn and grow together in this new field and to design solid guidelines for the safe implementation of advanced therapies as medicinal treatment