The European Commission, together with the EMA and the expert group of the competent authorities of the EU Member States, has developed draft guidelines (the “Guidelines”) governing good clinical practice specific to advanced therapy medicinal products (“ATMPs”).
The purpose of the Guidelines is to adapt existing good clinical practice rules (“GCPs”) to ATMPs. This step is required by Article 4 of Regulation 1394/2007 on ATMP, which provides that the European Commission to draw up guidelines on GCPs specific to this category of medicinal products.
The document relates solely to ATMP and will apply in addition to the GCP Guidelines of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (“ICH”). The Guidelines also provide that investigational ATMPs must comply with the new guidelines on good manufacturing practice (GMP) specific to ATMPs.
The Guidelines discuss the areas in which specific rules would apply when a clinical trial is conducted in relation to an investigational ATMP.
By way of example:
- The clinical trial design should take account of the specific characteristics of ATMPs and the patient populations likely to consume these. Because of the novelty and scientific uncertainties relating to ATMPs the Guidelines provide, in particular, that there may be a need for subjects to be on long-term follow-up after treatment;
- Aspects of dosing and repeatability of treatment should be considered based on the specific characteristics of the product. Where the ATMP is expected to have long-term effects, dose escalation and repeated dosing should be considered with a view to control toxicity risks to the subject;
- The Guidelines describe specific requirements for ATMPs containing human cells or tissues used as starting materials. In these cases, the trial application dossier should contain confirmation that the donation, procurement and testing of cells and tissues are in compliance with EU legislation, and that there is a bidirectional traceability system in place from the point of donation to administration of the medicinal product in the clinical trial;
- The Guidelines underline that the quality of the investigational ATMPs may be highly dependent on their storage, transport and handling conditions. Sponsor should, therefore, provide investigators with detailed instructions concerning handling and storage of the investigational ATMPs;
- The administration procedure should be clearly explained by the sponsor. The level of documentation should take into account the complexity and the novelty of the procedure;
- The Guidelines acknowledge that in the case of ATMPs the retention of samples of the investigational medicinal product may be challenging due to scarcity of the starting materials. The general GCP rules requiring the sponsor to maintain sufficient quantities of the investigational product used in a trial to reconfirm specifications would not, therefore apply in the case of autologous ATMPs and certain allogeneic ATMPs (matched donor scenario).
The draft Guidelines can be found here and stakeholders are invited by the European Commission to comment on this consultation by 31 October 2018. The comments received will be taken into account by the European Commission in the finalisation of the Guidelines.