On February 28, 2018, the FDA released E6(R2) Good Clinical Practice: Integrated Addendum to ICH E6(R1): Guidance for Industry, which can be found here. Other than a few minor clerical differences, the guidance was implemented in entirety from the ICH E6(R2) Addendum, which can be found here. The notice of the draft guidance was published in the Federal Register on September 29, 2015 and was open to comments until November 30, 2015. The final draft was submitted to ICH Assembly and the regulatory agencies endorsed it in November 2016.
Additions in the ICH E6 R2 addendum include:
- Definitions of certified copy, monitoring plan, and validation of computerized systems were added.
- Records include electronic as well as paper. E6 was written when paper-based records were commonly used, but electronic records are now more common.
- The focus of clinical trials should be on human subject protection and “reliability of trial results.”
- Prior to delegating tasks, the investigator is responsible for ensuring that the entities have the needed qualifications to carry out the duties. Also, the delegated entities should have procedures in place ensuring data integrity, and the investigator should supervise their activities.
- Source data should follow ALCOA-C, and changes to data should leave an audit trail.
- Sponsors should implement a Quality Management System that utilizes a risk-based approach.
- Sponsors must provide sufficient oversight of others that carry out sponsor-related tasks, such as CROs.
- Validation of computerized systems, SOPs describing the correct use of the computerized systems, and systems that ensure data integrity should be implemented.
- Monitoring may be on-site, centralized, or a combination, if the method chosen is justified.
- Monitoring plans should be customized for each trial to ensure human subject protection and data integrity.
- The sponsor should conduct a root cause analysis (RCA) and implement appropriate corrective and preventive actions (CAPA) when noncompliance affects or may affect human subject protection or data integrity.
- Document storage systems should allow for version control, identification, and retrieval.
- Certified copies may be used in place of original documents.
The purpose of ICH E6(R2) Addendum is to improve clinical trial efficiency and oversight while continuing to ensure human subject protection and data integrity. The new guideline modernizes Good Clinical Practices with the way clinical trials are conducted today, including delegation of tasks, risk-based monitoring, and relying on computerized systems. The FDA’s implementation of ICH E6(R2) Addendum in entirety suggests harmonized methods to conduct clinical trials with sufficient oversight, reduced costs, and increased efficiency within the United States.
Some key areas to consider for new or improved skills that need training and practice are: 1) certified copies and validated methods, 2) supervision of direct and third-party delegates by the investigator, 3) RCA and CAPA, 4) ALCOA-C, 5) Quality Risk Management. Let us know how we can help with the integration into your company standards and training.
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