Final ICH E6(R3) Guideline on GCP released

The ICH E6(R3) Good Clinical Practice (GCP) Guideline provides a unified standard to facilitate the mutual acceptance of clinical trial data for ICH member countries and regions by competent regulatory authorities. The guideline comprises of principles and annexes providing specific details for different types of clinical trials. Moreover, it contains lots of information about requirements to data governance and computerised systems.

Annex 1, including its Appendices, is intended to provide information on how the principles can be appropriately applied to clinical trials. Annex 2 will focus on examples of trials that incorporate decentralized & pragmatic elements and/or Real-World Data (RWD). According to the ICH, "additional annexes may be developed to respond to interested parties' needs and address emerging innovations in trial design and conduct".

Good Manufacturing Practice

Investigational medicinal products (IMPs) used in a clinical trial should be manufactured in accordance with applicable Good Manufacturing Practice (GMP) standards and be managed in accordance with the product specifications and the trial protocol. Processes should be in place for the handling, shipping, storage, dispensing, returning and destroying (or alternatively disposing) of the IMP. The sponsor should ensure that the IMP (including active controls and placebo) is characterised as appropriate to the development stage of the IMP, is manufactured in accordance with any applicable GMP and is coded and labelled in a manner that protects the blinding. In addition, the labelling should comply with applicable regulatory requirements. The IMP should be packaged to prevent contamination and unacceptable deterioration during transport and storage. The sponsor should determine acceptable storage temperatures, storage conditions (e.g., protection from light) and shelf life for the IMP, appropriate reconstitution fluids and procedures, and devices for product administration. In addition, the sponsor should inform all involved parties (e.g., monitors, investigators, pharmacists, storage managers) of these determinations.

Data Governance & Computerised Systems

Guidance is provided to the responsible parties (i.e., investigators and sponsors) on appropriate data management (i.e., data integrity, traceability and security). Procedures should be in place to cover the full data life cycle. Systems are designed to permit data changes in such a way that the initial data entry and any subsequent changes or deletions are documented, including, where appropriate, the reason for the change. Procedures for review of trial-specific data, audit trail review and other relevant metadata should be in place. The review "should be a planned activity, and the extent and nature should be risk-based, adapted to the individual trial and adjusted based on experience during the trial". Sponsors have to justify their approach.
The responsibilities of the sponsor, investigator and the activities of other parties with respect to computerised systems used in clinical trials should be clear and documented. They should ensure that validation documentation is maintained and retained. Validation should demonstrate that the system conforms to the established requirements for completeness, accuracy and reliability and that its performance is consistent with its intended purpose. The approach to validation should also be based on a risk assessment.

Further information, including the Guideline and the draft Annex 2, can be found on the ICH E6(R3) page.