Date: June 3, 2026
The Regulatory Members of the ICH Assembly endorsed Annex 2 of E6(R3), the guideline for good clinical practice, under Step 4 on June 3, 2026, and ICH consolidated the principles, Annex 1 and Annex 2 into a single E6(R3) document dated June 16, 2026 that also incorporates error corrections made since January 2025. The principles and Annex 1 reached Step 4 on January 6, 2025 and came into effect in the EU on July 23, 2025. EMA lists January 15, 2027 as the date Annex 2 comes into effect, after CHMP adoption on June 25, 2026. FDA issued the principles and Annex 1 as final guidance in September 2025; as of October 26, 2026, its Annex 2 page still shows the December 2024 draft.
Annex 2 covers trials with decentralized and pragmatic elements and the use of real-world data. It “should be read in conjunction with the Principles and Annex 1,” and its data considerations in Section 3.5 refer back to Annex 1 Sections 3.16.1 and 4.
Annex 1 Section 4 sets data governance expectations for the investigator and the sponsor. Its data life cycle elements (4.2) include relevant metadata and audit trails, review of data and metadata, data corrections, and data transfer, exchange and migration, and its computerized systems subsection (4.3) covers security, validation, system release, system failure and user management, among other topics.
What it means for calibration
In practice, a laboratory that analyzes trial samples for a sponsor generates trial data, and the sponsor’s data handling duties in Annex 1 Section 3.16.1 apply to those data. The sponsor should focus quality assurance and quality control activities, including data review, “on data of higher criticality and relevant metadata” (3.16.1(b)). Calibration determines every reported concentration, so the regression model and weighting, excluded calibration standards with their reasons, and reintegration events are among the metadata a risk-based sponsor review is likely to examine.
Section 3.16.1(x)(ii) asks the sponsor to ensure that requirements for computerized systems, such as validation, audit trails, user management, backup, disaster recovery and IT security, are addressed in proportion to the importance of the system, and 3.16.1(x)(v) calls for a process for service providers and investigators to inform the sponsor of system defects. For the CDS and LIMS that hold calibration data, laboratories should expect sponsors to ask for validation status, audit trail configuration and user access records, and to write defect reporting into service agreements.
Source: ich.org, E6(R3) Guideline for Good Clinical Practice, consolidated final version (June 16, 2026)
Also see: ema.europa.eu, ICH E6 Good clinical practice, scientific guideline page; ema.europa.eu, ICH E6(R3) Guideline for Good Clinical Practice, Annex 2, Step 5 (EMA/CHMP/ICH/495903/2024); ich.org, E6(R3) Guideline for Good Clinical Practice (Step 4, January 6, 2025); fda.gov, E6(R3) Good Clinical Practice (GCP) (final guidance, September 2025); fda.gov, E6(R3) Good Clinical Practice (GCP), guidance document (September 2025); federalregister.gov, E6(R3) Good Clinical Practice; International Council for Harmonisation; Guidance for Industry; Availability (September 9, 2025); fda.gov, E6(R3) Good Clinical Practice: Annex 2 (draft guidance, December 2024)
Part of the WLTR ICH M10 guide for pharmaceutical and bioanalytical labs. This is a plain-language summary, not regulatory advice. Confirm requirements with the issuing agency and your quality unit. Questions or a different read on this change? Leave a comment below.