1. Purpose

To define identification, classification, documentation, reporting and prevention of protocol deviations and violations.

2. Scope

Applies to all departures from the IRB-approved protocol, applicable regulations or site SOPs, whether or not they affect subject safety or data integrity.

3. Responsibilities

• All Personnel: Report a suspected deviation to the Principal Investigator and Quality Assurance on the day it is identified.
• Principal Investigator: Assesses subject safety and data impact and signs the deviation report.
• Regulatory Affairs: Submits reportable deviations to the IRB and sponsor and maintains the deviation log.
• Quality Assurance: Classifies deviations, monitors trends, and initiates CAPA for major or recurring deviations.

4. Definitions

Deviation

Any departure from the approved protocol, consent process, regulations or site procedures.

Major deviation (violation)

A deviation that affects subject safety, rights or welfare, or the integrity of the study data.

Minor deviation

A deviation with no effect on subject safety, rights, welfare or data integrity.

Serious non-compliance

A deviation that is wilful, repeated, or presents a substantive risk, requiring prompt IRB reporting.

5. Procedure

1. Report the suspected deviation to the Principal Investigator and Quality Assurance on the day of identification, in writing, using the site deviation form.
2. Take immediate action to protect subject safety, including medical evaluation, unblinded medical care where necessary, and notification of the treating physician.
3. Document the factual description: what happened, when, which subject or subjects, which protocol requirement was affected, and how it was discovered.
4. Classify the deviation as minor, major or serious non-compliance with documented Quality Assurance and investigator input.
5. Determine whether the deviation constitutes an unanticipated problem involving risks to subjects, and if so process it also under CON-001 and REG-002.
6. Notify the sponsor according to the protocol and clinical trial agreement, and report to the IRB within the timeframe set by the IRB's policy for major deviations and serious non-compliance.
7. Assess whether the affected subject may continue in the study and document the investigator's decision and rationale.
8. Determine the root cause and record immediate corrective action; escalate major and recurring deviations to the CAPA process under QA-002.
9. Record the deviation in the study deviation log with a unique identifier, dates, classification, reporting dates and resolution status.
10. Reconcile the deviation log with the sponsor's log at each monitoring visit and at study close-out.
11. Review deviation trends by type, study and department at the monthly quality management review, and use them to target training and process change.
12. Never conceal, retroactively correct or omit a deviation from the log; the record is maintained for inspection.

6. References

• 21 CFR Part 312.60 — General responsibilities of investigators
• 21 CFR Part 56 — Institutional Review Boards
• ICH E6(R3) Good Clinical Practice
• QA-002 Corrective and Preventive Action (CAPA)
• CON-001 Adverse Event & Serious Adverse Event Reporting

7. Revision History

• v2.0 · Aug 08, 2022 — Added serious non-compliance classification.
• v3.0 · Jul 07, 2025 — Added trend review and mandatory same-day reporting.