level.

3. Responsibilities

• Principal Investigator (PI): Reviews and classifies protocol violations, ensures documentation, and initiates CAPA.
• QA Manager: Oversees protocol deviation tracking, supports root cause analysis, and verifies CAPA implementation.
• Study Coordinator: Documents deviations using the deviation report form and informs the PI and QA.
• Regulatory Affairs: Communicates reportable violations to Ethics Committees and regulatory authorities.

4. Accountability

The Head of Clinical Research and the QA Head are jointly accountable for ensuring protocol violations are properly classified, documented, addressed, and reported per GCP and regulatory standards.

5. Procedure

5.1 Identification of Protocol Violations

1. Any deviation from the approved protocol, GCP, or SOPs must be reported immediately by the staff member observing it.
2. Examples include:
   • Missed timepoints for blood draws
   • Enrollment of ineligible subjects
   • Failure to obtain consent
   • Unapproved dose substitution

5.2 Classification

1. Classify violations as:
   • Minor: No impact on subject safety or data integrity
   • Major: Potential impact on data integrity but no subject harm
   • Critical: Potential or actual impact on subject safety and/or trial validity
2. Document the classification in Annexure-1: Protocol Violation Log.

5.3 Documentation

1. Fill Annexure-2: Protocol Deviation Report Form within 24 hours of detection.
2. Each report should include:
   • Date and time of event
   • Volunteer ID
   • Description of deviation
   • Immediate corrective action

5.4 Root Cause Analysis and CAPA

1. QA and PI shall perform root cause analysis using Annexure-3: CAPA Worksheet.
2. Document:
   • Root cause
   • Corrective action taken
   • Preventive measures implemented to avoid recurrence

5.5 Review and Approval

1. PI to review and sign off the deviation and CAPA forms.
2. QA to verify and close the deviation after implementation of CAPA.

5.6 Reporting to Ethics and Regulatory Authorities

1. For critical violations:
   • Submit deviation report to Ethics Committee within 7 working days
   • Submit to CDSCO or relevant authority, if required
2. Maintain Annexure-4: Regulatory Submission Log for tracking communications.

6. Abbreviations

• BA: Bioavailability
• BE: Bioequivalence
• PI: Principal Investigator
• QA: Quality Assurance
• CAPA: Corrective and Preventive Action
• CDSCO: Central Drugs Standard Control Organization

7. Documents

1. Protocol Violation Log – Annexure-1
2. Protocol Deviation Report Form – Annexure-2
3. CAPA Worksheet – Annexure-3
4. Regulatory Submission Log – Annexure-4

8. References

• ICH E6(R2) – Good Clinical Practice
• Schedule Y – Drugs and Cosmetics Rules
• CDSCO Guidelines for Protocol Deviations

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Protocol Violation Log

Date	Volunteer ID	Violation Type	Classification	Status
15/04/2025	VOL-115-003	Missed 1hr sample	Major	Closed

Annexure-2: Protocol Deviation Report Form

Date	Study Code	Volunteer ID	Description	Immediate Action
15/04/2025	BE-115	VOL-115-003	Sample not collected at 1hr	Notified PI, noted in CRF

Annexure-3: CAPA Worksheet

Root Cause	Corrective Action	Preventive Action	Verified By
Scheduling oversight	Staff informed immediately	Updated sampling checklist	QA Officer

Annexure-4: Regulatory Submission Log

Date	Submitted To	Violation Summary	Response Received
16/04/2025	IEC	Major deviation: sample missed	Accepted with note

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
10/01/2022	1.0	Initial release	Regulatory Requirement	QA Head
17/04/2025	2.0	CAPA process and deviation classification added	Audit Recommendation	QA Head