On 23 July 2025, a part of the Good Clinical Practice Guideline, GCP E6 (R3), promulgated by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)1 comes into force. The development of new technologies, the rapidly evolving clinical trial (CT) ecosystem, and the need to respond quickly to deviations in CT processes have prompted the revision of the current version of GCP ICH E6(R2), which is valid until 22 July 2025.
The content of the guideline is presented in an updated structure, and includes key sections on GCP principles and the responsibilities of the key roles in CT - Institutional Review Board/Independent Ethics Committee (IRB/IEC), the investigator and the sponsor. Specific attention is given to guidance for responsible parties on the proper data governance.
Updated principles:
The document sets out 11 framework principles that should be considered throughout the life cycle of a CT. Some of the GCP principles have not changed, however, based on a comparative analysis of the current and the new version of the guidelines - the framework principles have been significantly supplemented and clarified:
1. ethical conduct: CTs should be conducted in accordance with the ethical principles laid down in the Declaration of Helsinki and consistent with the GCP and applicable regulatory requirements, and ensure the rights, safety and well-being of CT participants;
2. informed consent: voluntary informed consent is a mandatory element of the ethical conduct of CTs;
3. supervision and approval of CT: CTs should be carried out with prior approval from (IRB/IEC), and with the possibility of periodic review;
4. scientific validity: CT should be scientifically sound with the possibility of updating the CT protocol when new scientific information becomes available;
5. Qualified Individuals: all phases of CTs should be conducted only by qualified individuals with appropriate education and experience;
6. quality by design: implementation of strategies to prevent, detect, eliminate and avoid recurrence of GCP violations, test protocols and regulatory requirements and other factors important to the quality of the CT during the design phase;
7. justification of CT risks: CTs should be conducted commensurate with the risks to participants and the importance of the data collected, without placing additional risks on CT participants and investigators - the risks should be proportional to the purpose of the CT;
8. clarity of CT protocol: CTs should be clearly and concisely spelt out in the CT protocols;
9. reliability of CT results: CTs should generate reliable results, this principle includes several aspects:
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the quality, suitability and amount of information generated in the CT,
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the suitability for the purposes of the CT of using computerised systems and other systems and processes to manage and analyse the CT data,
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the effectiveness of the record management and data protection processes of the TRC,
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transparency, objectivity and public availability of the results of the CT;
9. clear distribution of roles and responsibilities: roles and responsibilities in CT should be clearly defined and appropriately documented. Responsibility for delegated activities remains with the sponsor and the researcher respectively;
10. recording and following the rules and procedures for handling the products being tested: investigational products must be manufactured in accordance with applicable Good Manufacturing Practice (GMP) standards and managed in accordance with the product specifications and test protocol.
Key aspects of the new revision:
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quality by design: GCP E6 (R3) supports a proactive approach to risk management and CT quality assurance that promotes early detection of risks and deviations, as well as ensuring the safety of CT participants and the reliability of the results obtained;
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CT data governance: GCP E6 (R3) contains a separate guidance section on CT data governance. The development and implementation of documented key processes should accompany the entire lifecycle of CT data (from registration to destruction) on both the sponsor and investigator side, namely:
(a) processes that protect the confidentiality of the data of the CT participants;
(b) processes for managing the computerized systems used for the purposes of the CT;
(c) processes that guarantee important elements of the CT - randomisation, blinding and dose adjustments;
(d) processes that support key decisions making (e.g. changes in CT design).
The new revision provides detailed guidance on data processing as well as the use of automated systems in CT. In order to produce reliable CT results, considerable attention is given to data integrity and quality, and to controlling the protection of computerized systems in CT throughout the life cycle
- risk-based approach and clear allocation of responsibilities: it is recommended to use a risk-based approach at all stages of the CT from planning to completion.
Potential impact of the new version of GCP on Russia and the EAEU.
We would also like to remind you that from 01.09.2024 in order to harmonise national regulation with the EAEU legislation in the Russian Federation the national rules of good clinical practice were cancelled (Order of the Ministry of Health of Russia from 29.05.2024 № 274n). At the level of EAEU regulation, the EAEU Rules of Good Clinical Practice are in force2, which are subject to regular review in case of changes in international rules for conducting CTs.
The Concept of Development of the Common Market of Medicines, approved by Decision of the EEC Council No. 19 of 21.02.20253, supports ongoing to harmonise EAEU legislation with international approaches to regulation of the pharmaceutical industry in order to ensure the optimal market entry of safe, effective and high-quality medicines. The integral system of good pharmaceutical practices of the EAEU, which ensures the unity of regulation of the main stages of the life cycle of medicinal products, is formed and harmonised with the practices of the WHO, ICH, OECD and the European Union (EU).
Thus, the new edition of GCP ICH E6 R(3) will be taken into account by the EEC – a corresponding draft amendment to the EAEU Rules of Good Clinical Practice should be expected. Despite the retention of key concepts, in connection with the upcoming entry into force of GCP ICH E6 R(3), sponsors, investigators and CROs should review their documented procedures for the participation, organisation and conduct of clinical trials in order to bring their current processes into line with the new rules.
1ICH E6 Good clinical practice - Scientific guideline | European Medicines Agency (EMA).
2Decision of the EEC Council of 03.11.2016 No. 79 "On the Approve of the Rules of Good Clinical Practice of the Eurasian Economic Union".
3Decision of the EEC Council of 21.02.2025 No. 19 "On the Draft Order of the Eurasian Intergovernmental Council "On the Concept of Development of the Common Market of Medicines within the Eurasian Economic Union".