As mandated in Article 4 of Regulation (EC) No 1394/2007 on Advanced Therapy Medicinal Products (ATMPs), the European Commission has published guidelines on good clinical practice (GCP) specific to ATMPs. The 15-page document should be read in conjunction with ICH E6 Guidelines on GCP, which are also applicable to ATMPs.

Due to the complexity of ATMPs, there is a likelihood of significant deviations from standard development paths. Lack of appropriate animal models, for instance, might rule out execution of meaningful nonclinical pharmacology studies. In addition, ATMPs are often characterized by manufacturing constraints and a short shelf-life, which require implementation of additional logistics controls. As the administration of ATMPs (e.g. gene therapy) often involves a complex surgical procedure, placebo controls may be deemed unethical. And documentation of long-term / life-long therapeutic effects of certain products can demand complex arrangements for patient follow- up.

The new ATMP GCP guideline contains sections on: clinical trial design, nonclinical studies, quality of the investigational ATMPs, the safe conduct of the clinical trial, upstream interventions on subjects and administration procedures, traceability, retention of samples, protection of trial samples, safety reporting and monitoring.

While it is emphasized that the specific content of the Cover Letter, Protocol, Investigators Brochure (IB), and Investigators Medicinal Product Dossier (IMPD) has been laid down previously (Regulation (EU) No 536/2014), the new ATMP guideline clearly specifies which aspects of ATMP-specific information are expected to be included in these regulatory documents. Two examples:

  • Nonclinical: Comprehensive information about the nonclinical development program should be provided in the IB; the IMPD can subsequently cross-refer to the relevant IB sections. Potentially significant findings from nonclinical studies should then be summarized in the Protocol.
  • If the ATMP incorporates a medical device, the IMPD and Protocol should contain information on the characteristics, performance and intended use of the device. In addition, the Protocol should contain information on the device’s regulatory status and the IMPD should contain information on compliance of the medical device with safety and performance requirements. The Cover Letter should state whether the medical devices are CE-marked for the intended use.

As these two examples show, the new ATMP GCP guideline aims to promote high-quality CTA dossiers, which is beneficiary to all stakeholders – Regulators, Industry and Patients. EUDRAC is experienced in CTA submissions and in working with ATMPs; please contact us directly for queries on how EUDRAC can assist you with your ATMP applications.

1 November 2019