ATMPs (Advanced Therapy Medicinal Products) are medicinal products based on gene therapy, somatic cell therapy or tissue engineering. Regulation (EU) 1394/2007 has been designed to ensure the free movement of ATMPs within the EU to facilitate their access to the EU market and to foster the competitiveness of European pharmaceutical companies while guaranteeing the highest level of health protection for patients.
As ATMPs post specific challenges to developers, manufacturers, regulators, and clinicians in terms of complexity and risk profile, distinct rules have been developed for the production and clinical testing of ATMPs.
Article 4 of Regulation 1394/2007
Requires the EC to establish GCP guidelines specific to ATMPs. The stakeholder consultation performed for this purpose, however, has not addressed the qualification of clinical trial sites and investigators.
Clinical Sites and Investigators and ATMP Competencies and Readiness
It remains to be seen how clinical trial sites and investigators using ATMPs can give documented evidence of their specific qualification, and how Ethics Committees can draw on the expertise needed to assess this special group of innovative medicines.
Methods, Results & Conclusion
Chimeric antigen receptor (CAR)-transduced cells highlight the challenges in the qualification of trials sites and investigators. With patients in desperate need, clinicians have put growing pressure on regulators and politicians to render these promising therapies more rapidly available, irrespective of existing gaps in infrastructure, clinical expertise, and concepts for covering costs.
What is the ATMP Site Qualification Checklist?
- A risk-benefit analysis that addressed the characteristics of the respective ATMP specifically and appropriately
- The capacity to monitor, grade, manage and document acute toxicity inherent in this approach
- The infrastructure needed to handle these toxicities
- A data registry and repository for adverse events related to use of ATMPs in humans
- A recognizable network of collaborating centers who exchange knowledge, share training and help each other in this challenging and important field.
Increasingly ethics committees (ECs) will count on independent experts in ATMPs, especially high-risk (and high demand) products, to provide guidance in assessing clinical centers and investigators as qualified for these special medicines. Consensus statements by professional medical organizations are important.
Research Center Participants
- TUMCells, TUM School of Medicine, Munich Germany
- Ethics Committee of the State of Berlin, Berlin, Germany
- Institute of Clinical Chemistry and Pathobiochemistry, Blood Depot, TUM School of Medicine