What changed in E6(R3)
ICH finalised E6(R3), its revised Good Clinical Practice guideline, in January 2025, and it has applied in the EU since 23 July 2025. The revision is less a new rulebook than a change of emphasis. The themes that affect sponsor procedures most are:
- Quality by design and proportionality. Identify the factors critical to quality in each trial and size your controls to the risk, rather than applying the same checks everywhere.
- Risk-based thinking across the whole trial, not only monitoring.
- Sponsor oversight of delegated activities. You can delegate tasks, but you remain responsible, and your oversight has to be planned and evidenced.
- Data governance. Clearer expectations for computerised systems, audit trails, metadata and the full data lifecycle.
- Flexibility in how trials run, including decentralised elements, remote activities and electronic consent.
The SOPs most likely to need revision
- Risk management
- Service provider selection and management, and any CRO oversight procedure
- Monitoring and oversight of monitoring, to allow risk-based and centralised approaches
- Data management and computerised systems
- Trial master file, which E6(R3) frames as essential records
- Deviations, quality events and CAPA, with a sharper focus on important deviations
- Training, which should be role-based and proportionate
- Informed consent, where electronic and remote consent are used
The SOPs that usually stand
Document control, good documentation practice, translations and medical writing procedures normally need terminology and cross-reference updates rather than new content.
How to approach the update
- Run a gap assessment of each procedure against the E6(R3) principles and Annex 1. Our gap analysis does this clause by clause.
- Prioritise the procedures that govern risk, oversight and data first.
- Revise, train your team, and retire superseded versions under document control, keeping a record of what changed and why.
- Update the forms and templates that go with each SOP, which are easy to miss.
If your procedures are several years old, it can be quicker to adopt an E6(R3)-aligned set and tailor it than to revise line by line. See whether to refresh or replace old SOPs, or look at our E6(R3)-aligned SOP library.