QA, and data managers.

3. Responsibilities

• Principal Investigator (PI): Responsible for reviewing and signing off all protocol deviations and determining impact on subject safety and study integrity.
• Clinical Research Coordinator: Identifies, documents, and initiates deviation forms.
• Quality Assurance (QA): Reviews all reported deviations, assesses trends, and ensures CAPA implementation.
• Project Manager: Notifies sponsor, Ethics Committee, and regulatory authorities as applicable.

4. Accountability

The Head of Clinical Operations is accountable for ensuring all protocol deviations are handled in accordance with applicable regulations, GCP, and company policies.

5. Procedure

5.1 Identification of Protocol Deviations

1. Any deviation from the approved protocol, including:
   • Missed timepoints for PK sample collection
   • Incorrect dosing
   • Improper informed consent
   • Ineligible subject enrollment

   must be identified immediately by the involved staff.

2. Each deviation shall be reported within 24 hours of identification.

5.2 Documentation

1. Use Annexure-1: Protocol Deviation Report Form to record:
   • Study code
   • Subject ID
   • Date and nature of deviation
   • Immediate impact assessment
   • Corrective Action taken
2. Deviation form must be signed by the CRC and forwarded to the PI for review.

5.3 Classification of Deviations

1. Deviations are to be classified as:
   • Minor: No impact on subject safety or study outcome (e.g., vitals recorded 5 mins late)
   • Major: Potential impact on subject safety or data integrity (e.g., incorrect dosing, missed PK sample)
2. Major deviations must be escalated as per Section 5.4.

5.4 Escalation of Major Deviations

1. Major deviations shall be:
   • Reported to the Sponsor and Ethics Committee within 5 working days
   • Documented in Annexure-2: Deviation Escalation Log
2. Supporting documents such as subject notes, CRFs, and logs must be attached.

5.5 Corrective and Preventive Actions (CAPA)

1. For every deviation, a CAPA plan must be proposed in Annexure-3: CAPA Form including:
   • Root cause
   • Immediate corrective action
   • Long-term preventive measure
2. CAPA must be approved by QA and implemented within 7 days of deviation closure.

5.6 Review and Trending

1. QA shall conduct monthly reviews of all deviation logs to identify patterns or recurrent issues.
2. Deviations shall be trended by:
   • Study phase
   • Staff involved
   • Category (subject-related, procedure-related, documentation, etc.)
3. Results to be discussed in quarterly Quality Review Meetings.

5.7 Archival

1. All deviation records and CAPAs must be archived in the Trial Master File (TMF).
2. Retention period should follow applicable regulatory and sponsor-specific requirements (minimum 5 years).

6. Abbreviations

• BA/BE: Bioavailability/Bioequivalence
• PI: Principal Investigator
• CRC: Clinical Research Coordinator
• QA: Quality Assurance
• CAPA: Corrective and Preventive Action
• CRF: Case Report Form

7. Documents

1. Protocol Deviation Report Form – Annexure-1
2. Deviation Escalation Log – Annexure-2
3. CAPA Form – Annexure-3

8. References

• ICH E6(R2) – Good Clinical Practice
• Schedule Y – Drugs and Cosmetics Rules, India
• Institutional Ethics Committee SOPs

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 Deviation Report Form

Study Code	BA-BE-120
Subject ID	VOL1053
Date of Deviation	15/04/2025
Deviation Description	Sample collected 45 mins late
Impact	No impact on safety
Corrective Action	Retrained phlebotomist

Annexure-2: Deviation Escalation Log

Date	Study Code	Subject ID	Escalated To	Mode	Response
16/04/2025	BA-BE-120	VOL1053	Sponsor QA	Email	Accepted, no further action

Annexure-3: CAPA Form

Deviation	Missed PK sample at 4h
Root Cause	Phlebotomist skipped scheduled time
Corrective Action	One-on-one retraining conducted
Preventive Action	PK alerts implemented in scheduling software
Approved By	QA Manager

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/01/2022	1.0	Initial release	New SOP	QA Head
17/04/2025	2.0	Expanded escalation workflow and annexures	GCP alignment and inspection readiness	QA Head