Everything you need to know about the new ICH E6 GCP (R3): updates and how to be prepared

What is Good Clinical Practice (GCP)?

Good Clinical Practice (GCP) is an international standard that ensures the ethical and scientific conduct of clinical trials. It protects the rights, safety, and well-being of participants while generating reliable data for healthcare advancement.

The Evolution of ICH E6

• 1996: The International Council for Harmonisation (ICH) establishes the first GCP standards (ICH E6 (R1)).
• 2016: ICH E6 (R2) is released, emphasizing risk and quality management.
• 2023 (May): A draft of ICH E6 (R3) is unveiled, reflecting the ever-evolving clinical research landscape.

What is ICH E6 (R3)?

ICH E6 (R3) is the latest revision of the International Council for Harmonisation's Good Clinical Practice (GCP) guideline. It serves as an internationally recognized standard for conducting ethical and scientifically sound clinical trials. This revision aims to modernize GCP practices by addressing the evolving complexities of clinical research.

Why is ICH E6 (R3) Important?

ICH E6 (R3) isn't just an update; it's a transformation. It addresses the complexities of modern clinical trials by:

• Modernizing: Aligning with advancements in technology, trial designs, and data capture methods.
• Harmonizing: Ensuring consistency and streamlined processes across regulatory bodies worldwide.
• Adapting: Addresses the growing complexities of clinical research while prioritizing participant safety and data integrity.

Key Changes in ICH E6 (R3):

• Focus on Quality by Design (QbD): The guideline promotes a proactive approach to risk management and quality assurance. This means identifying critical risks and quality factors at the outset of the trial to ensure patient safety and data reliability.
• Data Governance: ICH E6 (R3) places significant emphasis on data integrity, highlighting the importance of secure electronic systems and processes to safeguard data throughout the trial lifecycle.
• New Trial Designs: The revision acknowledges the increasing use of novel trial designs like decentralized and pragmatic trials, offering guidance for conducting them ethically and efficiently.
• Risk-Based Approach: The guideline advocates for a risk-based approach, focusing resources on processes and data points with the most significant impact on patient safety and trial outcomes. This lean approach aims to accelerate evidence generation without compromising quality.
• Data Reliability: The focus is on data integrity to ensure confident decision-making for informed healthcare decisions.
• Future-Proof Framework: E6 (R3) accommodates the rise of data-driven technologies, decentralized trials, and innovative trial designs.

What Does ICH E6 (R3) Apply To?

• Interventional clinical trials for investigational products intended for regulatory submissions.
• May still be relevant for non-marketing authorization trials (consult the guideline for details).

Timeline for ICH E6 (R3) Implementation:

ICH E6 (R3), in its finished form, will comprise 3 sections:

1) Overarching 'principles' document

2) Annex 1: considerations for interventional trials

3) Annex 2: further considerations for 'non-traditional interventional' trials

Here's a breakdown of the expected release schedule:

• Initial Draft (May 2023): Released, comprising the core principles document and Annex 1 related to interventional trials.
• Draft Annex 2 (Expected Mid 2024): This annex will address considerations for "non-traditional interventional" trials.
• Final Draft for Public Consultation (Expected March-September 2024): Once both Annexes are drafted, the entire guideline will be released for public feedback.
• Final Live Version (Estimated 2025): Following public consultation, the final ICH E6 (R3) guideline is expected to be released sometime in 2025.

Until then, ICH E6 (R2) remains the live, valid and applicable GCP guideline for quality-focused clinical businesses to work to.

Preparing Your Team for the Future

While the final release of ICH E6 (R3) is anticipated in 2025, proactive steps can be taken today:

• Familiarize your team with the draft: Familiarize yourself with the current draft of E6 (R3) and Annex 1 (interventional trials). A thorough understanding of the core principles and proposed changes will allow you to identify areas where your current practices may need adjustments. Consider how the revisions might impact your clinical operations.

• Conduct a Risk Assessment: Identify critical risks specific to your trials that could jeopardize patient safety or data integrity. Develop risk mitigation strategies aligned with the principles of E6 (R3). Develop strategies to mitigate these risks based on the principles of QbD
• Conduct a QbD-based risk assessment: Identify critical risks to patient safety and data integrity in your trials. Develop risk mitigation strategies aligned with QbD principles.
• Review and update SOPs and protocols: Revise standard operating procedures (SOPs) to reflect the emphasis on quality by design, risk management, and data governance. Ensure your Standard Operating Procedures (SOPs) and clinical trial protocols are aligned with the evolving principles of ICH E6 (R3).
• Invest in training: Ensure your team receives training on the key updates of E6 (R3). Equip them with the knowledge and skills necessary to implement the new requirements effectively. Training on risk management, data integrity, and QbD principles is crucial.
• Embrace New Technologies: Explore and implement technology solutions that can enhance data management, risk mitigation, and overall trial efficiency.

The Future of Clinical Research is Here

The arrival of ICH E6 (R3) marks a significant turning point in clinical research. By embracing the new framework, we can usher in a new era of safe, ethical, and efficient clinical trials that pave the way for better healthcare solutions and improved patient outcomes.

Key Principles of GCP (ICH E6 (R3))

The guideline outlines 11 core principles, including:

• Informed consent
• Ethical conduct
• Scientific soundness
• Qualification of personnel
• Quality assurance throughout the trial
• Proportionate processes
• Clear and concise protocols
• Reliable data generation
• Defined roles and responsibilities
• Good Manufacturing Practice (GMP) for investigational products

Looking Ahead: The Future of Clinical Research

By embracing the ICH E6 (R3) framework, we can create a new era of clinical research characterized by:

• Safety: Prioritizing participant well-being throughout the trial process.
• Ethics: Upholding ethical principles and informed consent.
• Efficiency: Streamlined and optimized trials for faster evidence generation.
• Reliability: Generating trustworthy data for informed healthcare decisions.

Conclusion:

ICH E6 (R3) marks a significant step towards safer, more ethical, and efficient clinical research. It is recommended that important key stakeholders review the draft and understand the main updates. Although the paper has not been adopted yet, now is a good moment to start planning and implementing changes.

By embracing this transformative framework, we can pave the way for better healthcare solutions and improved patient outcomes.