Overview of the Regulatory Oversight Implemented by the French Regulatory Authorities for the Clinical Investigation of Gene Therapy and Cell Therapy Products

Abstract

Advanced therapy medicinal products, a new class of products with promising therapeutic effects, have been classified as medicinal products and as such should be developed according to a well-structured development plan, to establish their quality, safety and efficacy profile and conclude, at the time of the marketing authorisation evaluation, on a positive risk/benefit balance for patients. An important part of this development plan is achieved through clinical trials, which have also to be approved according to a well-established regulatory process, prior any initiation. This chapter is dedicated to describe the regulatory pathway to be followed in France, before initiating any clinical trial with those investigational advanced therapy medicinal products. In France, to get the final authorisation to initiate a clinical trial, the legislation imposes to run in parallel two independent but complementary authorisation procedures. The first procedure is aimed at assessing the ethical aspect of the biomedical research, while the second has to review the safety and regulatory aspects. A third procedure has to be envisaged where in case the investigational product consists or contains a genetically modified organism. The French system herein described is in line with the EU regulation on clinical trial and follows the respective deadlines for granting the final approval. The complexity of the procedure is in fact more due to the complexity of the products and protocols to be assessed than to the procedure itself which is now very close to the well-known procedure applied routinely for more conventional chemical or biological candidate medicinal products.

ATMP Environmental Exposure Assessment in European Healthcare Settings: A Systematic Review of the Literature

“…PCR was used as a main technique to detect ATMP on work surfaces and the excreta or blood of a patient ( 26 , 28 , 31 – 33 , 36 , 38 , 45 , 46 , 48 , 49 , 52 , 54 ). The follow-up of a patient after treatment was approached by nine articles to evaluate the potential risk of dissemination of the ATMP ( 27 , 34 , 38 , 40 – 44 , 52 ). Yet, different ways of disposal were described to prevent the environmental shedding and quarantine of patients was mainly proposed ( n = 8; 16%).…”

“…Yet, different ways of disposal were described to prevent the environmental shedding and quarantine of patients was mainly proposed ( n = 8; 16%). Hygiene measures using the disinfectants to decontaminate and clean work surfaces and equipment as sodium hypochlorite, ethanol, or alkaline solutions following the use of ATMP were described ( 28 – 30 , 33 , 37 – 40 , 45 , 46 , 50 , 51 , 54 – 57 ). Waste sterilization and especially waste autoclaving was addressed within five articles ( 28 , 46 , 54 , 56 , 57 ).…”

“…Overall, 85% of the selected articles reported a potential environmental risk of dissemination following the use of ATMP. This risk was proven ( 26 , 32 , 34 – 37 , 41 ) or considered to be potential ( 28 – 31 , 38 , 40 , 42 – 49 , 52 – 57 ) and concerns mainly GMO.…”

Therapeutic nucleic acids: current clinical status

“…However, the above‐mentioned characteristics make them closer to new biological entities (NBEs) . Clinical trial regulations related to TNAs and subsequent approval for human use are more complex than for NCEs .…”