International Council Finalizes Modernized Global Good Clinical Practice Guideline

In January 2025, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) adopted its updated Good Clinical Practice (GCP) guideline, also known as ICH E6(R3). The guideline has been drafted by regulators from, among others, the EU, U.S., Japan, Canada, and Switzerland, as well as industry representatives, and has been several years underway.

The updated guideline consists of a set of key principles and an Annex 1, which provides guidance on how these principles can be applied to clinical trials. An Annex 2, which is expected to be adopted in mid-2025, will address modern design aspects such as pragmatic clinical trials and decentralized clinical trials, as well as the incorporation of real-world data sources into trial designs. A public consultation process allows stakeholders to submit comments in the EU (link) until February 28, 2025.

ICH E6 is the cornerstone for ethical and scientific conduct of clinical trials and provides a unified standard to facilitate the mutual acceptance of clinical trial data. It sets the key principles on the roles and responsibilities of sponsors, investigators, and ethics committees in the conduct of clinical trials. It emphasizes the protection of participants’ rights, safety, and well-being, as well as the reliability and integrity of clinical trial results.

Why was it updated?

ICH E6 was updated to address the evolving clinical trial complexities by providing the necessary flexibilities and guidance regarding new clinical trial types and data sources. It was also rewritten to close gaps with existing ICH guidelines such as ICH E9 on statistical principles in clinical trials and its addendum ICH E9(R1) on estimands and sensitivity analysis in clinical trials.

What is new?

Key updates to the key principles and Annex 1 include:

1. Data governance and technology integration. With the increasing digitization of clinical trials globally, the guideline includes a new section on data governance, addressing data integrity and management expectations. It places increased emphasis on the validation and oversight of digital tools, including eConsent, wearables, and remote monitoring solutions.
2. Data integrity. The guideline contains a major revision of sections on essential records. The guidance uses the term “record” instead of the old term “documents” to reflect that the information required to assess the trial conduct also includes data. It also clarifies that the essential records, and therefore the content of the trial master file depend on the trial design and the application of risk-proportionate approaches to the trial.
3. Proportionality and proactive risk-based approach. While the previous version encouraged sponsors to apply a risk-based approach, the latest version further acknowledges that not all trials carry the same risks. It places a strong emphasis on proactively identifying and managing risks critical to participants’ safety and data reliability by integrating a “quality by design” principle into every stage of the trial process.
4. Service providers in the spotlight. The updated guideline refers to “service providers” instead of Contract Research Organizations (CROs) reflecting an increased use of (smaller) organizations to provide specific services or carry out specific trial activities, for example activities relating to electronic systems. Sponsors remain responsible for delegated activities, with the guideline now emphasizing the protection of the rights, well-being, and safety of trial participants. Service providers are also explicitly required to report to the sponsor any incident that could affect these rights and the reliability of the trial results. New text also requires the sponsor to assess the suitability of the services provided, signaling that authorities expect services provided to adhere to the same high standards as the sponsor.

What does this mean for sponsors?

ICH E6(R3) signals a shift in regulators’ approach in applying GCP towards modernized, flexible and patient-centric clinical trials.

The guideline invites sponsors to rethink how to design and conduct innovative clinical trials by focusing on flexibility, using risk-based approaches, and leveraging technology to streamline operations without compromising data integrity or patient safety. This may be achieved by adopting innovations, such as electronic informed consent and remote monitoring within the design and conduct of a trial. Simultaneously, sponsors are required to implement strong data integrity measures and proactively identify and manage risks throughout the trial lifecycle.

What are the next steps?

ICH E6(R3) – consisting of the key principles and Annex 1 – has been adopted by the European Medicines Agency (EMA) and will come into effect on July 23, 2025 for clinical trials conducted in the EU.

According to the ICH, additional annexes may be developed to respond to interested parties’ needs and to address emerging innovations in trial design and conduct.

What should sponsors do?

For clinical trial sponsors, understanding and preparing for this new GCP guideline and its changes is essential to ensure compliance, maintain trial quality, and ultimately bring new treatments to patients more efficiently. As the guideline will come into effect in July 2025, sponsors should start planning now how to adapt their internal procedures and clinical trials to meet the new expectations.

To prepare effectively, sponsors should:

• conduct a gap analysis to assess current processes against the new requirements to identify gaps;
• update internal procedures to reflect the changes in ICH E6(R3);
• consider new needs, such as investing in and adopting technical tools to support risk-based quality management, centralized monitoring, enhanced data management, etc.; and
• assess training needs (internally and externally) on the new guideline.