In January 2025, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) published the final version of the “Guideline for Good Clinical Practice (GCP) E6(R3).” This release serves as an update from the previous 2016 E6(R2) Good Clinical Practice guideline. The ICH member countries are in the process of adopting the new E6(R3) principles, meaning its implementation timelines will differ globally depending on the member nation. The introduction of these updated Good Clinical Practice guidelines will lead to a significant transformation of the clinical research industry, affecting how clinical trials are conducted and managed by sponsors and CROs (Contract Research Organizations).  

The ICH E6(R3) guideline represents a refreshed approach to Good Clinical Practice in the conduct of clinical trials, addressing the complexities of modern clinical research while still maintaining the highest standards of the rights, safety and well-being of trial participants and the reliability of the trial results. This article will review key insights from this latest update, which reflect the industry-wide need to adapt to emerging technological advancements, evolving trial designs, essential proportionate and risk-based approaches to trial management, and many more. Read on to learn what the ICH E6(R3) Good Clinical Practice guideline means for your clinical trial! 

 

Overview of Key Changes in ICH E6(R3) Good Clinical Practice Guidelines 

According to the ICH E6(R3) Good Clinical Practice guideline published here, the document serves to build on the main concepts put forth in ICH E8(R1) General Considerations for Clinical Studies. This  guideline serves to describe international standards in the design and conduct of clinical trials. Clinical trials vary considerably due to a whole host of factors, all of which are associated with different risks that should be evaluated and managed to maximize efficiency and safety of new treatments. Key concepts from ICH E8(R1) carried over into ICH E6(R3) include promoting a culture of quality when planning clinical trials and drug development, implementing quality by design (QbD) approach, identifying critical to quality (CtQ) factors, engaging interested parties in trial design, and using a risk-proportionate approach.  

According to this summary from the Collaborative Institutional Training Initiative (CITI Program), the ICH E6(R3) guideline document describes general principles of ICH GCP, consideration for interventional trials in Annex 1, and additional considerations for interventional trials in Annex 2 that are based on the foundation established in Annex 1. Annex 2 should be read and implemented with ICH E6(R3) principles and Annex 1. Although, it should be noted that Annex 2 was not published with the final version of E6(R3). The key changes listed in these new ICH E6(R3) Good Clinical Practice guideline include the following:  

• Acknowledging the growing popularity of decentralized clinical trial designs 
• Emphasizing the use of Quality Management Systems to ensure trial quality 
• Encouraging transparency by clinical trial registration and result reporting 
• Introduction of a “fit for purpose” approach to quality-by-design 
• Encouraging the adoption of patient-centric clinical trials 
• Expanded guidance on the use of electronic systems 
• Recognizing the varied role of service providers (including CROs) 
• Including language to facilitate innovations in clinical trial design, health technology solutions and operational approaches  
• More detailed guidance on obtaining informed consent 

 

Promoting Unified Global Regulatory Standards in Clinical Development  

The ICH E6(R3) Good Clinical Practice guidance document states its objective is to “provide a unified standard to facilitate the mutual acceptance of clinical trial data for ICH member countries and regions by applicable regulatory authorities.”

This means the guidelines serve to establish common international quality standards that will enable regulatory authorities in different ICH member countries to accept and evaluate clinical trial data with confidence, regardless of where the trials were conducted. That is, unified regulatory standards imposed by global ICH E6(R3) Good Clinical Practice guidelines ensure that clinical trials conducted in one region can contribute to regulatory submissions in other ICH member regions. This could reasonably be expected to drive greater efficiency in resource utilization and promote faster access to new treatments. Furthermore, these latest standards help reduce the complexity, unnecessary burden for investigators and cost associated with conducting multi-regional clinical trials by establishing consistent requirements across participating countries.  

 

Enhanced Quality Management Through Quality by Design 

One of the key updates in the new ICH E6(R3) guideline emphasized the importance of integrating the “quality by design” principle, which involves focusing on critical to quality (CtQ) factors of the trial in order to increase its chances of meeting its objectives. Key factors crucial to the quality of a clinical trial, as introduced in ICH E8(R1), are recommended to be applied prospectively to ensure optimal patient protections and data integrity throughout the study lifecycle. Sponsors and CROs can use their expertise in clinical trials to implement several quality by design (QbD) strategies to mitigate the occurrence and the extent of any noncompliance issues. 

 

Proportionate and Risk-Based Approaches to Trial Management with CROs 

The recommended strategy for ensuring the concept of quality by design in the ICH E6(R3) document is implementing proportionate and risk-based approaches for trial management, a shift away from the previous traditional one-size-fits-all methodology. Experienced CROs are especially suited to help sponsors identify and manage risks early throughout the trial lifecycle to protect trial participants and ensure reliable trial results. The ultimate purpose of these strategies is to identify potential or actual causes of serious noncompliance issues, either with Good Clinical Practice, the protocol, and/or relevant regulatory requirements.  

Monitoring and data management processes are the main quality control activities in a clinical trial, meaning these proportionate and risk-based approaches should be applied to each stage of data handling. The ICH E6(R3) update also recommends adopting a tailored approach, where sponsors and CROs build specific risk profiles for each trial, based on its unique complexity, patient population, and investigational therapy characteristics.  

 

Integration of Digital Health Technologies with Support from CROs 

The ICH E6(R3) update also expanded its guidance on the use of electronic systems, particularly digital health technologies (DHTs) and electronic sources (eSource). Examples of DHTs include interactive response technologies (IRTs), electronic clinical outcome assessments (eCOAs), including electronic patient-reported outcomes (ePROs) and wearable devices. The guideline recognizes that these technologies enable the use of a variety of relevant data sources in clinical trials. To maximize efficient and quality data collection, DHTs should be integrated to fit the trial’s unique participant characteristics and study design. Sponsors and CROs is also responsible for taking steps to ensure the security and validation of these systems, per the ICH E6(R3) Good Clinical Practice recommendations. 

 

Promoting Diversity and Inclusion Throughout Clinical Development 

Another key update from ICH E6(R3) is the emphasis on making clinical development processes for the design and conduct of a clinical trial more inclusive [2]. Specifically, the guidelines state that sponsors are required to ensure their participant selection process is representative of the study’s target population groups. During the design of a clinical trial, researchers are reminded to carefully consider the scientific goal and purpose to avoid unnecessarily excluding certain patient populations. This ensures the trial’s results are generalizable across the broader population.  

 

Strengthened Focus on Patient Rights and Safety with Patient-Focused Trials 

The rights, safety and well-being of the participants are the most important considerations when conducting a clinical trial, and should always be prioritized over all other interests. The 2025 update to the ICH E6(R3) Good Clinical Practice guidelines reinforced the importance of maintaining clear communication with trial participants, including enhancement of the comprehensive informed consent process that account for DHTs and remote trial conduct. For example, while electronic systems are permitted to be used to obtain informed consent, patients should also be given the option to use a paper-based approach as an alternative. Furthermore, the latest ICH E6(R3) update encourages sponsors to conduct patient-centric clinical trials by inviting the perspectives of patients and their communities, patient advocacy groups and healthcare professionals throughout the study lifecycle. The ICH E6(R3) recognizes that their input can help to reduce unnecessary complexity, improve feasibility and increase the likelihood of meaningful trial outcomes.  

 

Embracing Innovative Trial Designs and Methodologies with Expertise from CROs 

Finally, the 2025 ICH E6(R3) guidelines state that “the use of innovative trial designs and technologies may enable the inclusion of a wider and more diverse population of participants and thereby broaden the applicability of trial outcomes.”

Although not published with the final version of the latest Good Clinical Practice guidelines, Annex 2 is dedicated to providing guidance on additional considerations for interventional trials to address recent emerging innovations in trial design and conduct, including variety of trial designs and data sources, where applicable. This will include: 

1. Decentralised elements, where some or all trial-related activities occur at locations other than traditional clinical trial sites (e.g., patient homes, mobile trial units, local outpatient clinics) and data collection may occur remotely. 
2. Pragmatic elements, reflecting trials that closely resemble routine clinical practice. 
3. Real-world data (RWD) sources (e.g., the use of registries, electronic health records (EHR), hospital data, pharmacy and medical claims data or wearables). 

It is recommended that any trial design being considered should be operationally feasible to avoid unnecessary complexity. Additionally, protocols, data acquisition tools and other key documents should all be fit for purpose, clear, concise and consistent to ensure the study is not placing excessive burden on patients and investigators.  

 

How TFS is Seamlessly Guiding the Adoption of ICH E6(R3) in Clinical Development 

TFS HealthScience CRO has over 25 years of experience in clinical research and regulatory compliance, making the company a pioneering partner in helping sponsors navigate the implementation of ICH E6(R3). TFS’s in-house Quality Management System is well-suited to align with the new guidelines’ emphasis on Quality by Design principles, ensuring that quality measures are embedded throughout the trial lifecycle. The CRO also offers a team of experts with a deep understanding of risk-based approaches to help sponsors develop tailored quality and risk management strategies based on their trial’s specific risk profile. With the expanded guidance on DHTs in ICH E6(R3), TFS has already established a robust technological infrastructure that can help sponsors seamlessly integrate these digital tools, while still maintaining the highest standards of data security and privacy compliance.  

Furthermore, the company’s global presence across Europe and North America ensures sponsors worldwide can benefit from their dedicated training programs for these latest requirements. Finally, TFS’s underlying mission aligns perfectly with the emphasis on diversity and inclusion in the new ICH E6(R3). Read more about how TFS is promoting improved patient diversity in recruitment for clinical trials here, and strategically driving gender diversity in leadership in this article. Overall, TFS is the ideal CRO partner for sponsors seeking to implement the new ICH E6(R3) Good Clinical Practice standards effectively and efficiently. To learn more about their quality management systems, visit their Drug Safety & Pharmacovigilance CRO.  

 

Conclusion 

In conclusion, the ICH E6(R3) guideline, published here, represent a significant evolution in Good Clinical Practice and clinical trial ecosystem. The latest standards aim to balance the need for innovation with the fundamental principles of patient safety and reliability or trial results. As the year goes on and ICH E6(R3) becomes fully implemented across all ICH member nations, these new requirements will help provide a crucial framework for conducting high-quality modern clinical trials to advance medical research more effectively.  

 

About TFS HealthScience Drug Safety & Pharmacovigilance CRO 

TFS HealthScience’s global Drug Safety & Pharmacovigilance division delivers comprehensive pharmacovigilance (PV) solutions throughout the entire drug development lifecycle and post-marketing period. What sets us apart is our integrated approach with expert regulatory, medical, and clinical teams to ensure comprehensive oversight from start to finish, supported by our Quality Management System to guarantee the highest standards of compliance and data integrity. The global capabilities of TFS Drug Safety & Pharmacovigilance CRO include end-to-end PV services, comprehensive clinical safety services, and robust post-approval support.  

If you’re looking for a partner who can provide fully integrated, end-to-end pharmacovigilance strategies, services, and systems, visit our website or connect with a TFS representative today!