Quality by Design
Critical-to-quality factors — the data and processes that matter most — are identified prospectively and protected throughout the trial.
The international ethical, scientific and quality standard for trials involving human participants — rewritten around quality by design, risk-proportionate oversight and modern data governance. Below is a structured summary by the KG Hospital Clinical Research Centre.
“Good Clinical Practice (GCP) is an international, ethical, scientific and quality standard for the conduct of trials that involve human participants.” ICH E6(R3), Section I — Introduction
Trials run to this standard help assure that participants’ rights, safety and well-being are protected, that conduct is consistent with the Declaration of Helsinki, and that results are reliable. “Trial conduct” covers everything from planning and initiation to recording, oversight, analysis and reporting.
The guideline builds on ICH E8(R1): fostering a quality culture, designing quality into trials from the start, identifying factors critical to quality, engaging interested parties and using a proportionate, risk-based approach.
Applies to interventional clinical trials of investigational products (drugs, medicines, vaccines and biological products) intended for submission to regulatory authorities. Its principles may also apply to other interventional trials in line with local requirements.
E6(R3) is restructured into overarching Principles and Annexes that explain how to apply them — flexible enough to stay relevant as trial designs and technology evolve.
Critical-to-quality factors — the data and processes that matter most — are identified prospectively and protected throughout the trial.
Processes and oversight scale to the risks to participants and the importance of the data, avoiding unnecessary burden on participants and investigators.
Written to accommodate digital health technologies such as wearables and sensors, remote consent and on-site or remote monitoring.
A dedicated chapter covers the full data life cycle, audit trails, blinding safeguards and computerised-system validation and security.
Input from patients, communities and advocacy groups is encouraged to reduce complexity and improve feasibility.
Participant selection should represent the populations the product is intended to benefit, so results generalise more broadly.
Timely registration in public databases, public posting of results and objective, non-promotional communication of results to participants.
Sponsors and investigators may transfer or delegate activities but retain overall responsibility and must maintain oversight.
The principles are interdependent and should be considered in their totality to assure ethical trial conduct and reliable results. Select a principle to see its key provisions.
Sponsors manage risks to critical-to-quality factors before and throughout the trial — across trial design, participant selection, consent, randomisation, blinding, product administration, data handling and service-provider activities.
Risks with meaningful impact on critical-to-quality factors, including computerised systems.
Likelihood of harm, how detectable it is, and its impact on participants and results.
Proportionate mitigation through protocol design, monitoring plans, agreements and training.
Document and share risks and mitigations with those who act on or are affected by them.
Periodically check that controls remain effective as knowledge and experience grow.
Summarise important quality issues and remedial actions in the clinical trial report (ICH E3).
Quality tolerance limits: where relevant, sponsors set pre-specified acceptable ranges at trial level. When a range is exceeded, an evaluation determines whether there is a systemic issue and whether action is needed.
Investigators and sponsors share responsibility for data integrity, traceability and security across the full data life cycle — irrespective of the media used.
Changes must be traceable through an audit trail, must not obscure the original entry and should be explained where necessary. Investigators define source records and data-capture methods before the trial starts and avoid unnecessary transcription. Read our ALCOA++ guide →
Data collected through validated, fit-for-purpose methods.
Who changed what, when and why — retained and reviewable.
Risk-based review of data and metadata; documented corrections.
Integrity preserved when data moves between systems.
Data sets locked prior to analysis, with blinding safeguarded.
Secure retention for the required period, then controlled destruction.
Annex 1 and its appendices explain how to apply the principles. Alternative approaches may be used if they are justified and achieve the intended purpose.
Our Clinical Research Centre aligns every trial with ICH-GCP E6(R3), the New Drugs & Clinical Trials Rules 2019 and continuous Ethics Committee oversight.
Informed consent in English and Tamil, documented rights and responsibilities, and on-site emergency and critical care for participant safety.
Protocol compliance and safety reporting are managed proportionately, with proven readiness for sponsor audits and a DCGI (CDSCO) site inspection in September 2022.
Essential records and source data are maintained to ALCOA+ principles and retained to support inspection readiness at all times.
Step 2 approval; released for public consultation.
Step 4; recommended for adoption by ICH regulatory bodies.
Post-Step 4 editorial corrections.
Integrated addendum adopted under Step 4.
Step 2 endorsement; public consultation.
Step 4 — final version adopted.
Download the official ICH E6(R3) document, or return to the Clinical Research Centre for more GCP, NDCT and participant resources.
Source: ICH Harmonised Guideline for Good Clinical Practice E6(R3), final version adopted 06 January 2025 © International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). This page is an adapted summary prepared by KG Hospital Clinical Research Centre and is not endorsed or sponsored by ICH. Refer to the official document for complete and authoritative text.