The Crucial Role Of Sponsor Oversight In ICH E6 (R3)
By Inbal Hacmon and Rivka Zaibel, ADRES Bio
In the evolving landscape of clinical research, the International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines serve as the cornerstone for ensuring the ethical and scientific quality of clinical trials, safeguarding the rights, safety, and well-being of trial participants. The unveiling of the ICH E6 (R3) guideline revision marks a significant milestone, emphasizing enhanced sponsor oversight and stringent quality requirements. This article delves into the critical aspects of this new revision, shedding light on its implications for sponsor responsibilities in the realm of clinical trials.
The Evolution To Revision 3
Since its inception, the ICH E6 guideline has undergone revisions to adapt to the complexities of modern clinical research, integrating advancements in technology, regulatory expectations, and global health challenges. The transition from Revision 2 to Revision 3 underscores a proactive approach toward a quality-by-design framework, prioritizing risk management and comprehensive planning throughout the clinical trial process.
The Essence Of Sponsor Oversight
Sponsor oversight is a fundamental concept within the ICH E6 (R3) guideline, reinforcing the sponsor's pivotal role in ensuring trial integrity. This oversight is not merely a regulatory obligation but also a commitment to uphold the highest standards of quality and ethical conduct in clinical research. The guideline delineates clear expectations for sponsors to establish robust systems and processes that ensure continuous monitoring and management of trial quality, from inception to completion.
We at ADRES always have recommended this approach to our clients. The approach of relying completely on service providers, CROs, and laboratories with no oversight by the sponsor, according to our experience, leads to noncompliance issues, protocol deviations, and misinterpretation of the protocol and study plans. The level of sponsor oversight should be based on risk assessment of the service provided by the different stakeholders involved in the conduct of the study.
Quality Management: A Core Focus
At the heart of the ICH E6 (R3) guideline is an enhanced focus on quality management. This includes the integration of quality considerations at every stage of the trial process, emphasizing the identification, assessment, and mitigation of risks that could impact the reliability of trial results or participant safety. The guideline advocates for a systematic, proactive approach to quality, encouraging sponsors to adopt quality-by-design principles that anticipate potential issues and implement preventive measures.
Quality-by-design principles may include a review of clinical development plans for similar products and learning from early-stage study challenges and conduct when designing the pivotal studies. Develop a quality management plan to support the conduct of a study.
Risk-Based Approaches
A key innovation in the revised guideline is the endorsement of risk-based approaches to trial management and oversight. Sponsors are encouraged to tailor their strategies based on the complexity, scale, and inherent risks of the clinical trial. This flexible, adaptive framework allows for the efficient allocation of resources, focusing efforts where they are most needed to protect participants and ensure the integrity of trial data.
At ADRES, we have developed a risk management tool that includes all aspects of the clinical study, product characteristics, technologies and systems used for the conduct of the study, service providers, etc. This tool is a living document that can and should be updated during the conduct of the study.
Enhanced Transparency And Communication
The ICH E6 (R3) guideline places a strong emphasis on transparency and effective communication among all stakeholders involved in clinical trials, including sponsors, investigators, regulatory authorities, and participants. Sponsors are expected to foster an environment of openness, facilitating timely sharing of information and collaboration to address challenges and share best practices. This collaborative approach is essential for maintaining trust and ensuring the success of clinical trials.
The Role Of Technology
In recognizing the rapid advancements in technology and digital tools, the ICH E6 (R3) guideline acknowledges their potential to enhance trial efficiency, data quality, and oversight capabilities. Sponsors are encouraged to leverage innovative technologies for data collection, monitoring, and analysis, ensuring their use complies with regulatory standards and enhances trial integrity without compromising participant safety.
The approach to computerized systems validation, which is well known, controlled, and implemented in all other aspects of product development, is now a clear requirement also for clinical development.
Preparing For The Future
The ICH E6 (R3) revision is a forward-looking document that prepares the clinical research community for the challenges of the future. It emphasizes the need for ongoing education, training, and development for all individuals involved in clinical trials, ensuring that they are equipped with the knowledge and skills necessary to implement the guideline effectively.
The ICH E6 (R3) guideline emphasizes the importance and need for a well-designed quality system at the sponsor, ensuring the safety, efficacy, and quality of the clinical research.
ICH E6 (R3): A Renewed Focus On Oversight
The ICH E6 (R3) guideline is a testament to the evolving nature of clinical research, reflecting a collective commitment to enhancing the quality and reliability of clinical trials. The emphasis on sponsor oversight and quality management underscores the critical role sponsors play in safeguarding the integrity of clinical research. As the clinical trial landscape continues to evolve, the principles outlined in the ICH E6 (R3) guideline will serve as a guiding light, ensuring that trials are conducted ethically, scientifically, and with the utmost respect for participant welfare.
In embracing the spirit of this new revision, sponsors, and all stakeholders involved in clinical research are called upon to uphold the highest standards of quality and integrity. Through collaborative efforts, innovative approaches, and a relentless focus on quality, the clinical research community can continue to advance medical science while ensuring the safety and rights of participants worldwide. The journey toward excellence in clinical research is ongoing, and the ICH E6 (R3) guideline marks a significant step forward in this endeavor.
About The Authors:
Inbal Hacmon has over 15 years of experience in the pharmaceutical and biotechnology industry. She is experienced in the development, quality assurance, and regulatory affairs of drugs, biologics, devices, and combination products. Inbal is a subject matter expert in medical/clinical QA with extensive experience with global clinical trials in various stages, including GMP/GCP audit performance.
With over 35 years in biopharmaceutics and biotechnology, Rivka Zaibel has led an impressive number of multidisciplinary projects, supports startups globally, and has secured FDA and EMA approvals for recombinant proteins, vaccines, and medical devices. In 2019-2020, Rivka joined the Weizmann Institute of Science SPARK project as a mentor and also became a member of the advisory board and lecturer for a new master’s degree in regulatory and drug development at Tel Aviv University. In 2022, the ADRES team, led by Rivka, joined the BIODESIGN ISRAEL Rambam healthcare campus program as mentors. In 2023, Rivka was accepted as a mentor by EIT Health.