The release of the ICH Guideline for Good Clinical Practice (E6 R2) in November of 2016 has, for the first time in over a decade, put new guidelines and regulations in front of clinical trial Sponsors and Investigators.
ICH E6 R2 brings a new set requirements and a particularly intense focus on Clinical Trial activities to ensure higher quality studies. These new regulations have a major impact on CROs, software vendors, auditors, and quality professionals alike.
Addressing Over a Decade of Change
Clinical Trials have undergone many significant changes since the last ICH/GCP guidance — E6 R1 2001 — was released over 15 years ago. New regulations, larger scale trials, higher costs, and greater complexity surrounding the ways trials are planned and conducted have all had a major impact.
Today, the reliance on paper based data collection and reporting has diminished. New digital technologies like EDC and direct-to-computer data collection, along with enhanced risk assessment process have created new opportunities to make Clinical Trials far more efficient than before.
Here are four significant changes and/or clarifications made in the new guidance that impact Good Clinical Practices (GCP).
1. Implementation of a Quality Assurance and Risk Assessment Process
To ensure the safety, rights, well-being of subjects are protected while taking advantage of new opportunities for efficiency, the new addendum calls on Sponsors and Investigators to implement additional quality assurance safeguards — specifically, a risk assessment process covering trial conduct and the responsibilities of the Investigator and Sponsor.
2. Expanded Definitions
The glossary section of the new addendum offers more comprehensive definitions around key terms, such as:
• What constitutes a Certified Copy
ICH E6 R2 clarifies that a certified copy must either have been signed and dated or generated using a documented validated process.
• Central Monitoring
As Sponsors increasingly use Central Monitoring, the new addendum requires they develop a report to show that this type of monitoring was in fact performed.
• Validation of Computerized Systems
Risk assessment is now a required component of computer system validation. Sponsors must also establish a documented process showing requirements are consistently followed all the way from design to a decommissioning or a transition to a new system.
More specifically, risk assessment is required for evaluating the intended use of the clinical trial system and any potential risk to the subjects within the trial or the reliability of the data generated.
3. Additional Responsibilities for Sponsors and Investigators
Responsibilities for Clinical Trial Investigators
The Investigator is now solely responsible for confirming the qualifications and supervising any individual or group that they have delegated trial related duties. In addition, they must implement documented procedures to ensure these duties and all functions of the trial are performed with integrity and the data that is generated from those activities is accurate and credible.
Other direct Investigator responsibilities include:
• Ensuring trial records are timely, accurate, complete, accessible, and compliant with protocols.
• Ensuring the data integrity for all information reported to the Sponsor in CRFs and required reports.
• Generating trial documentation. Part of this responsibility is ensuring records are available for review by an auditor, monitor, IRB/IEC, or other regulatory authority when requested.
Responsibilities for Clinical Trial Sponsors
Sponsors are now responsible for implementing a robust risk-based quality management system (QMS) across the entire life of the study.
This QMS must extend risk-based components to areas such as:
• Critical Process and Data Identification
• Risk Identification, Evaluation, Control, Communication, Review, and Reporting
When reporting risk, Sponsors must include a documented description of the specific approach to quality management being implemented in the study along with an explanation of any deviations from the quality expectations defined before the study began as well as any remediation actions taken to correct them.
Sponsors are also now required to demonstrate adequate vendor oversight CROs, including those sub-contracted to another party by the Sponsor CRO(s).
4. Monitoring Plan Components
The new addendum offers specific instructions for central monitoring performed by the Sponsor and identifies what should be included in the plan as well as the importance that must be placed on monitoring critical data and processes and any aspects of the trial that are not part of routine clinical practice — particularly areas that may require more training. Validation of clinical data systems and supporting SOPs have also been extended.
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The ICH/GCP E-6 (R2) 2016 addendum offers a number of challenges.
• Investigators will need processes to show they are managing all staff members that perform trial activities.
• Investigators will also need to make documents available during any monitoring visit, audit, or regulatory inspection.
• Sponsors must now implement a formal risk-based approach across the study, develop quality agreements, and collect metrics to show there is ongoing quality management of the trial.
• Sponsors will need to identify processes and data that are critical to ensure subject protection and the reliability of trial results throughout the life of the study.
Need expert assistance preparing to meet these expanded GCP requirements? Contact us today.