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Part 1-Revolutionizing Clinical Trials: ICH E6 R3 and Quality by Design

By Mamta Hunt, Assocoate Director, QA Services, Americas


In the dynamic landscape of clinical research, the pursuit of innovation and efficiency is constant. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E6 R3 guideline represents a transformative framework aimed at elevating the quality and effectiveness of clinical trials. This blog explores the profound impact of ICH E6 R3 on Quality by Design (QbD) principles, revolutionizing the way trials are designed and conducted.


Risk-Based Approach in Design & Conduct of Study:

ICH E6 R3 continues to champion a risk-based approach to clinical trial design and conduct, reshaping traditional methodologies. By understanding the risks identified in the protocol before an audit, sponsors can tailor their strategies to prioritize areas crucial for patient safety and data integrity. This proactive approach ensures resource optimization and enhances trial quality from the outset.

Data Quality & Integrity:

With all the technologies that are used in modern day of clinical research, maintaining the quality and integrity of trial data is paramount for generating reliable outcomes. ICH E6 R3 mandates stringent protocols for data management, emphasizing robust measures to ensure data security and chain of custody processes. By upholding the highest standards of data quality and integrity, sponsors can instill confidence in the reliability of trial results.

Informed Consent:

ICH E6 R3 underscores the importance of informed consent processes that are both simple and detailed, ensuring participant comprehension and autonomy. Audits focus on the content of informed consent forms, verifying their adherence to regulatory standards and effectiveness in conveying study details. Moreover, audits assess the method of consent capture, ensuring that participant rights are upheld throughout the trial.

Quality Management System:

A robust quality management system (QMS) is another essential area of focus for overseeing all aspects of clinical trial conduct. ICH E6 R3 mandates comprehensive quality oversight, encompassing deviations, corrective and preventive actions (CAPAs), and rigorous audits. By implementing an effective QMS, sponsors can identify and address issues proactively, thereby safeguarding trial integrity and regulatory compliance.

Patient-Focused Approaches:

ICH E6 R3 places a heightened emphasis on patient-centricity within clinical trials, reshaping the traditional trial paradigm. Audits scrutinize the incorporation of patient experiences into electronic medical records (eMRs), ensuring that patient perspectives are integrated into trial documentation. Moreover, audits may evaluate the inclusion of patient feedback in trial design, fostering greater patient engagement and satisfaction.

Safety Reporting:

Timely and accurate reporting of adverse events (AEs) is critical for safeguarding participant safety. ICH E6 R3 addes mandate around robust safety reporting mechanisms, ensuring compliance with regulatory requirements. Audits review the auditee's processes for documenting, assessing, and reporting AEs, verifying that appropriate measures are in place to mitigate risks and uphold patient welfare.

Clinical Protocol Design:

The design of the clinical protocol is pivotal for trial success, and ICH E6 R3 encourages greater flexibility and innovation in this regard. Audits assess protocol design elements to ensure they reflect a QbD approach, emphasizing risk management and optimization. Additionally, audits may involve reviewing protocol addendums and evaluating sponsor oversight to ensure protocol compliance and optimization.

Greater Flexibility (Quality by Design):

Flexibility in trial design and execution is essential for adapting to evolving regulatory requirements and scientific advancements. ICH E6 R3 promotes greater flexibility through a QbD approach, enabling sponsors to tailor study protocols to specific patient populations and therapeutic areas. This flexibility fosters innovation and efficiency, ultimately accelerating the development of new treatments and therapies.

Check out Part 2 for more on QbD!

Electronic Systems:

The integration of electronic systems into clinical trial processes offers numerous benefits, including enhanced data capture, analysis, and management. ICH E6 R3 mandates the effective utilization of electronic systems, ensuring compliance with regulatory standards. Audits assess the auditee's electronic systems to verify their effectiveness in maintaining data security and integrity, thereby enhancing trial efficiency and compliance.

Role of Sponsor:

Sponsors play a pivotal role in ensuring trial quality and compliance, and their oversight is integral to the success of clinical trials. ICH E6 R3 mandates sponsor involvement in in-study audits, underscoring their responsibility for trial oversight. Audits assess sponsor oversight to ensure active participation in trial conduct and optimization, thereby upholding the highest standards of integrity and patient care.



In conclusion, ICH E6 R3 represents a paradigm shift in clinical trial design and conduct, embracing Quality by Design principles to enhance trial quality and efficiency. By prioritizing a risk-based approach, maintaining data integrity, and fostering patient-centricity, sponsors can revolutionize the way trials are conducted, ultimately accelerating the development of safe and effective treatments for patients worldwide. As the clinical research landscape continues to evolve, adherence to ICH E6 R3 guidelines will be essential for driving forward innovation and excellence in clinical trials.


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Mamta Hunt PhD, is a true global expert in several GxP areas including GCP, GcLP , GMP, GVP, and GLP Quality. With 325 years of direct quality experience in industry, Mamta has spent the majority of her career in Executive Quality Managaement. She moved through increasing levels of seniority within clinical quality assurance with multiple domains of experiences in Quality management systems, Quality strategies and has an extensive experience auditing in global locations including: the United States, Canada, United Kingdom, Eastern and Western Europe, The Middle East, China, Japan, South Korea, Vietnam, the Philippines, Thailand, India, Australia, and New Zealand. Her vast experience enables a uniquely global perspective in bringing quality best practices to our clients.


About Zigzag Associates:


Zigzag is a United Kingdom headquartered consulting firm, with global office locations, specializing in pharmaceutical research quality and compliance. With a team of experienced professionals and deep industry expertise, we provide comprehensive consulting services to pharmaceutical companies, helping them navigate regulatory requirements, optimize quality systems, and ensure compliance throughout the drug development process.


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