FDA Amends GCP Guideline to Emphasize Quality Responsibilities
​​[Posted on: Thursday, March 1, 2018]

Today FDA released an addendum to ICH E6 (R2), the GCP Guidelines, to include several provisions for quality management responsibilities of the sponsors of clinical trials. These additional requirements apply to any trials conducted under an IND or IDE and used to support a US market approval application. Some important additions include a whole section on the sponsor’s responsibilities for implementing a Quality Management System (QMS) in clinical trials. Specifically the sponsor should create a risk-based QMS in clinical trials that starts with identification of critical processes and data during planning, and includes extensive risk management practices such as risk identification, evaluation, control, communication, review and reporting requirements. Throughout the ICH E6 documents, FDA added several provisions to emphasize the QMS and general quality practices expected of clinical trials. Important additions include definition of certified copies of documents, and computer system validation. The investigator and the institutions they belong to are responsible to supervise all personnel and maintain complete, accurate and unaltered source documents, and audit trails. The sponsor is expected to supervise its CRO, ensure the validation of electronic data and databases via processes described in comprehensive SOPs. Sponsors are also strongly encouraged to use risk-based monitoring and remote monitoring practices to identify and correct most data related issues and conduct targeted on-site monitoring based on defined criteria. Monitors should create monitoring reports for all remote monitoring activities in addition to on-site visits per the detailed monitoring plan that should emphasize the monitoring of critical data and processes. Root cause analyses should be conducted for all noncompliance incidences with the protocol, SOPs, GCP, and/or applicable regulatory requirement(s) by an investigator/institution, or by member(s) of the sponsor's staff and appropriate corrective and preventive actions should be implemented. The sponsor and the site should maintain a record of the location(s) of their respective TMF components including source documents. The storage system used during the trial and for archiving (irrespective of the type of media used) should provide for document identification, version history, search, and retrieval. Essential documents for the trial should be clearly defined. The sponsor should ensure that the investigator has control of and continuous access to the CRF data reported to the sponsor. The sponsor should not have exclusive control of those data. Only certified copies can replace an original document (e.g., source documents, CRF). The investigator/institution should have control of all essential documents and records generated by the investigator/institution before, during, and after the trial. All these additions are intended to suggest measures to address deficiencies identified during FDA’s GCP audits.