ICH Plan to Modernise Global Good Clinical Practice Guidance - "GCP Renovation"

Recommendation

5-7 November 2024
Hamburg, Germany

GMP meets Development
GMP and FDA Compliance in Pharmaceutical Development and IMP Manufacturing

The International Council for Harmonisation (ICH) consults with stakeholders on their plan to modernize the global good clinical practice guidance and has published a reflection paper on "GCP Renovation" on January 12, 2017.

The reflection paper contains the ICH proposal for further modernization of the ICH guidelines related to clinical trial design, planning, management, and conduct. The scope of the proposed renovation includes the current ICH E8 guideline (General Considerations for Clinical Trials) and further revision to the ICH E6 guideline (Good Clinical Practice), which is already undergoing modernization with the recent production of ICH E6(R2).

ICH says that the goal of the potential renovation is to provide updated guidance that is both appropriate and flexible enough to address the increasing diversity of study types and data sources that are being employed to support regulatory and other health policy decisions. The underlying principles of human subject protection and data quality would remain. ICH’s decision to invite stakeholder comment on the proposed renovations at this early stage, ahead of guideline development efforts, recognizes the considerable stake and relevant expertise in the research community beyond ICH.

In a February 2016 letter to ICH, stakeholders conveyed concerns that "the current ICH E6 guideline fails to sufficiently recognize variations in the level of risk for participants in different types of trials and allow corresponding flexibility in managing the risks. Another major concern was related to ICH E6’s limited scope. It was felt that a guideline entitled “good clinical practice” should more holistically address the planning and conduct of clinical trials."

The proposed revisions of ICH E6 include the following:

• The focus of the renovated E6 guideline will be retained compared to the focus of the current ICH E6 guideline regarding good clinical site practices and other key considerations. Recognizing that the most important tool for ensuring human subject protection and high-quality data is a well-designed and well-articulated protocol, the amended ICH E6 guideline will also refer to the proposed-to-be-revised ICH E8 guideline for a more comprehensive discussion of study quality considerations and relevant discussion and guidance in other ICH E guidelines.
• The main body of the renovated ICH E6 guideline should be revised to focus on overarching principles including key elements of human subject protection and data quality, using a risk-based approach to study oversight and monitoring. A number of available reference documents could be used to inform the development of these basic principles and list of candidate critical-to-quality (CTQ) factors including, for example, U.S. Food and Drug Administration (FDA) Guidance to industry: Oversight of Clinical Investigations—A Risk-Based Approach to Monitoring, the European Medicines Agency (EMA) Reflection paper on risk based quality management in clinical trials, and the Japanese Ministry of Health, Labour and Welfare (MHLW) administrative notice on Basic Principles of Risk-based Monitoring. Furthermore it should be taken into consideration that trial design and study objectives strongly influence the criticality of different factors.

Additionally, a set of more detailed annexes is proposed to be developed together with the new ICH E6 guideline:

• Proposed Annex 1: Traditional interventional trials of investigational unapproved or approved drugs (i.e., trials of unapproved drugs or of approved drugs for a new indication or use),
• Proposed Annex 2: Non-Traditional interventional trials and/or data sources,
• Proposed Annex 3: Non-Traditional trial designs.

The proposed renovation work will build on the important work of ICH E6(R2) and expand it, and it will bring even greater cohesiveness to the critical interplay of factors addressed in various ICH E guidelines. This includes - but is not limited to - the topics of Quality by Design (QbD) and related study quality considerations, statistical principles, and good clinical practices.

ICH points out that the seeking of stakeholder comments on the current reflection paper is seen as a first step in an enhancement of the ICH process with respect to public consultation for the revision of ICH E8 and ICH E6. The GCP Renovation reflection paper outlines additional steps that are also being considered to enhance stakeholder engagement. A 60-day comment period is being provided to enable time for the stakeholder review and response (Deadline is March 11, 2017). ICH will review the comments received to determine whether to make revisions to the currently proposed approach. The aim is to proceed with initiating needed renovation work as soon as practical, for example, within the next year.

For more detailed information please see the "ICH Reflection on “GCP Renovation”: Modernization of ICH E8 and Subsequent Renovation of ICH E6".