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Part 2- Embracing ICH E6 R3: Essential Steps to Level Up Quality Strategy 

Updated: Apr 25

 By Mamta Hunt, Associate Director QA Services, Americas

In the ever-evolving landscape of clinical research, staying abreast of regulatory updates is paramount for multinational organizations to maintain compliance and ensure the integrity of their trials. With the advent of ICH E6 R3, the latest revision of the International Council for Harmonisation's guideline on Good Clinical Practice (GCP), companies are presented with both challenges and opportunities to enhance their processes. Here, we delve into four crucial aspects that multinational organizations must address to prepare for ICH E6 R3.

1. Quality-by-Design (QbD) Process Implementation

One of the cornerstones of ICH E6 R3 compliance is the adoption of a Quality-by-Design (QbD) approach. This methodology emphasizes the proactive identifi cation of critical quality attributes and the design of processes to ensure their consistent achievement. For multinational organizations, this means not only identifying the QbD process but also ensuring that it permeates through every level of the clinical team.

This entails the development and execution of Standard Operating Procedures (SOPs) tailored to the QbD framework, accompanied by comprehensive training programs to educate all members of the clinical team. Additionally, selecting Contract Research Organizations (CROs) that embrace and implement the QbD approach is paramount. Collaborating with CROs that align with the organization's QbD principles facilitates seamless integration and fosters a culture of quality across all facets of the trial.

2. Transitioning from Computer System Validation to Computer System Assurance

In the digital age of clinical trials, the reliance on computerized systems for data management and analysis is ubiquitous. With ICH E6 R3, there is a paradigm shift from the traditional model of Computer System Validation (CSV) to a more dynamic approach known as Computer System Assurance (CSA).

Multinational organizations must adapt to this transition by reassessing their existing systems and processes to ensure alignment with CSA principles. This involves not only validating the functionality and performance of computer systems but also continuously monitoring and assuring their integrity throughout the trial lifecycle. Embracing CSA empowers organizations to leverage technology more effectively while maintaining the highest standards of data quality and compliance.

3. Incorporating Patient Experience into Clinical Data Gathering

ICH E6 R3 underscores the importance of incorporating patient experience as a fundamental component of clinical data gathering. Multinational organizations must recognize the invaluable insights that patients can provide and actively seek to understand their perspectives throughout the trial process.

By engaging patients in meaningful dialogue and soliciting feedback, organizations can gain valuable insights into the effi cacy, tolerability, and overall impact of investigational treatments. This information not only enriches the clinical data but also enables organizations to make informed decisions and implement protocol changes that prioritize patient-centricity. Integrating patient experience into the trial protocol ensures that the study design remains relevant and responsive to the needs of the individuals it aims to serve.

4. Establishing a Clinical Quality Assurance Team and Quality Management System (QMS)

Central to achieving ICH E6 R3 compliance is the establishment of a robust Clinical Quality Assurance team and a comprehensive Quality Management System (QMS). These entities serve as the cornerstone of the organization's commitment to maintaining the highest standards of quality and compliance throughout the trial lifecycle.

The Clinical Quality Assurance team is tasked with overseeing the implementation of GCP principles, conducting audits and inspections, and ensuring adherence to regulatory requirements. Complementing this is the QMS, which encompasses the policies, procedures, and processes designed to systematically manage quality across all aspects of the trial.

In addition, considering a separate clinical manual that is more inclusive of clinical needs can further streamline operations and enhance compliance eff orts. By consolidating clinical-specific requirements and best practices into a dedicated manual, multinational organizations can provide clearer guidance to their teams and foster a culture of excellence in clinical research.

The journey toward ICH E6 R3 compliance presents a myriad of challenges and opportunities for multinational organizations engaged in clinical trials. By embracing the principles of Quality-by-Design, transitioning to Computer System Assurance, incorporating patient experience into data gathering, and establishing robust Clinical Quality Assurance teams and QMS, organizations can navigate this regulatory landscape with confi dence and integrity, ultimately advancing the pursuit of safe and eff ective therapies for patients worldwide.


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 effi ciency. 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 eff ective 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.

Further to this the critical success steps to integration are:

1. Quality-by-Design process identifi ed, SOP and training executed to all clinical team- and select CRO that have the process

2. Move from Computer System Validation to Computer System Assurance

3. Understand patient experience as part of gathering clinical data and update/include changes to protocol based on the data

4. Have Clinical Quality Assurance team (and QMS) (may be have clinical manual separate and more inclusive of clinical needs)

How can Zigzag help? Reach out to start the conversation:

About Mamta Hunt

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.

For more information, please contact us here:


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