ICH E6(R3) GCP: Quality by Design, Data Governance and Investigational Product
Identify what is critical to quality, keep systems fit for purpose and keep investigational product records blinded.
In Short
- Adopted 6 January 2025.
- Quality by design from protocol.
- IP made under applicable GMP.
ICH E6(R3), the Good Clinical Practice guideline, was adopted at Step 4 on 6 January 2025. It is organised as principles plus annexes and applies to interventional clinical trials of investigational products intended for submission to regulators. Each region adopts it on its own timetable; regional implementation notices were not opened for this guide. This summary covers the principles, data governance and investigational product sections relevant to manufacturers and sponsors; it is orientation, not legal advice. Sources checked 4 Oct 2026.
Quality by Design
Principle 6 says quality should be built into the scientific and operational design and conduct of trials. Quality means fitness for purpose.
Worked Example: Critical-to-Quality Factors for Trial CT-204
| Factor | Why critical | Control |
|---|---|---|
| Informed consent | Participant rights | Consent version check at visit |
| Primary endpoint measurement | Result reliability | Calibrated device, trained raters |
| Blinding of kits | Bias | Coded labels; restricted list |
- Informed consent
- Why critical
- Participant rights
- Control
- Consent version check at visit
- Primary endpoint measurement
- Why critical
- Result reliability
- Control
- Calibrated device, trained raters
- Blinding of kits
- Why critical
- Bias
- Control
- Coded labels; restricted list
More on quality by Design
Factors critical to quality should be identified prospectively: the attributes fundamental to participant protection and reliable results. Principle 6.3 asks for strategies to avoid, detect, address and prevent recurrence of serious noncompliance. For a sponsor this is a documented exercise at protocol design, revisited as the trial runs, rather than a checklist added after monitoring finds problems.
Proportionate Processes
Principle 7 asks for processes proportionate to the risks to participants and the importance of the data, avoiding unnecessary burden. Risks to critical-to-quality factors should be managed proactively and adjusted when new issues arise.
More on proportionate Processes
Principle 7.4 says trial processes should be operationally feasible and avoid unnecessary complexity and data collection. The sponsor quality management section (3.10) builds on this, including pre-specified acceptable ranges for important parameters that, when exceeded, prompt evaluation of whether action is needed.
Computerised Systems and Records
Principle 9.3 says computerised systems used in trials should be fit for purpose, for example through risk-based validation where appropriate, with factors critical to their quality addressed in their design. Section 4 on data governance covers metadata including audit trails and procedures for computerised systems.
More on computerised Systems and Records
The sponsor sections ask sponsors to keep a record of important systems, their validation status and who is responsible, and to ensure requirements for validation, audit trails, user management and backup are proportionate. Principle 9.5 requires essential records to be retained securely for the required period under applicable regulation.
Investigational Product
Section 3.15.2 asks the sponsor to ensure investigational product, including comparators and placebo, is characterised appropriately for its development stage, made under applicable GMP, and coded and labelled to protect blinding where applicable, with labelling meeting regulatory requirements. The sponsor determines storage conditions and shelf life and informs those involved.
Investigational product handover (3.15.2)
More on investigational Product
Packaging must prevent contamination and unacceptable deterioration in transport and storage. Blinded trials need processes to prevent and detect inappropriate unblinding and to identify product rapidly in a medical emergency.
Worked Handover: Supply Lot IP-0931
Illustrative only. A CDMO packs blinded kits for lot IP-0931.
More on worked Handover: Supply Lot IP-0931
The batch record shows manufacture under GMP; the label proof carries kit numbers without treatment identity; the randomisation list stays with the unblinded team; storage at 2 to 8 °C is specified by the sponsor and shipping uses qualified packaging. The sponsor's quality person reviews the lot documentation and the emergency unblinding arrangement before release to sites. Any temperature excursion is assessed by named people before kits are used.
Questions
When was ICH E6(R3) adopted?
ICH adopted E6(R3) at Step 4 on 6 January 2025. Each region sets its own implementation date, which this guide did not verify.
Does E6(R3) require validated computerised systems?
Principle 9.3 says systems should be fit for purpose, for example through risk-based validation where appropriate, with critical quality factors addressed.
What does quality by design mean in E6(R3)?
Identifying factors critical to trial quality prospectively and focusing design and conduct on them, under Principle 6.
Must investigational product be made under GMP?
Section 3.15.2 asks sponsors to ensure it is manufactured in accordance with any applicable GMP and labelled to protect blinding where applicable.
Practical orientation, not legal advice. Rules differ by jurisdiction; your quality and compliance team decides what applies.
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