Advanced therapy medicinal products development - from guidelines to medicines in the market.

In Europe, Advanced Therapy Medicinal Products (ATMPs) include medicines based on gene therapy, somatic-cell therapy, tissue-engineered products, and combined ATMPs. ATMPs constitute an emerging and innovative class of medicines used to treat multiple pathologies and are particularly relevant in pathologies where therapeutic options are limited and require high medical needs. These therapies act, among others, through the insertion of recombinant nucleic acids, including genes, to promote a therapeutic effect and through the restoration of cell functions, and repairing or replacing damaged cells and tissues impaired in pathological conditions. Despite their unique potential, these therapies face challenges related to scientific complexity, production processes, regulatory approval, and market access that hinder their development and availability. Based on official European guidelines, the present review explores the current regulatory framework for the non-clinical and clinical development of advanced therapies. We aimed to discuss the regulations applied to the different types of ATMPs, as well as the challenges associated with their development until these therapies reach the market. Accordingly, topics such as the implementation of proof-of-concept studies to provide evidence supporting the potential clinical effect; biodistribution studies to evaluate tissue distribution and persistence; and toxicology studies to assess potential undesirable effects, integration potential of viral vectors, tumorigenicity, and germline transmission, are discussed. This work also covers some of the ATMPs available to patients on the EU market.