process.

2. Scope

This SOP is applicable to all QA personnel responsible for conducting or overseeing root cause investigations for any reported quality event at all stages of sterile injectable manufacturing, including R&D transfer, production, QC, and packaging.

3. Responsibilities

• QA Executive: Initiates and performs preliminary investigation and documents observations.
• Investigation Team: Conducts detailed root cause analysis using approved tools.
• QA Manager: Reviews investigation report and ensures effectiveness of RCA.
• Functional Heads: Provide subject matter expertise and ensure CAPA implementation.

4. Accountability

The Head of Quality Assurance is accountable for the timely execution, thoroughness, and closure of RCA activities for all reportable quality events in accordance with this SOP.

5. Procedure

5.1 Trigger for Root Cause Analysis

1. Initiate RCA when any of the following occurs:
   • Major deviation
   • OOS or OOT results
   • Customer complaint
   • Audit observation
   • Batch failure
2. Assign a unique Investigation Number and record in Investigation Log (Annexure-1).

5.2 Formation of Investigation Team

1. Team shall consist of members from relevant departments: QA, Production, QC, Engineering, and Warehouse as applicable.
2. Nominate a Lead Investigator who will coordinate the RCA activity.

5.3 Investigation Tools and Methods

1. Use one or more of the following methods for analysis:
   • 5 Whys Analysis
   • Fishbone Diagram (Ishikawa)
   • Fault Tree Analysis
   • Pareto Analysis
2. Document analysis outputs in Root Cause Analysis Report (Annexure-2).

5.4 Documentation Requirements

1. Capture the following in the report:
   • Background of the incident
   • Chronology of events
   • Initial containment actions
   • Identified root cause and supporting evidence
2. Define proposed Corrective and Preventive Actions (CAPA) and assign owners.

5.5 Review and Approval

1. QA Manager reviews RCA for completeness, logic, and accuracy.
2. Submit final report to Head QA for approval.
3. Approved CAPA shall be implemented with defined timelines and tracked via CAPA Tracker (Annexure-3).

5.6 Effectiveness Checks

1. After implementation of CAPA, QA shall perform effectiveness checks:
   • Verification audits
   • Review of trends for recurrence
   • System performance post-implementation
2. Update status in RCA Effectiveness Log (Annexure-4).

6. Abbreviations

• RCA: Root Cause Analysis
• CAPA: Corrective and Preventive Action
• QA: Quality Assurance
• OOS: Out of Specification
• OOT: Out of Trend

7. Documents

1. Investigation Log – Annexure-1
2. Root Cause Analysis Report – Annexure-2
3. CAPA Tracker – Annexure-3
4. Effectiveness Log – Annexure-4

8. References

• ICH Q10 – Pharmaceutical Quality System
• WHO TRS 996 Annex 5 – GMP for Sterile Pharmaceutical Products
• 21 CFR Part 211 – Subpart J: Records and Reports

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation	QA Executive	QA Manager	Head QA
Department	Quality Assurance	Quality Assurance	Quality Assurance

11. Annexures

Annexure-1: Investigation Log

Investigation No.	Date	Type of Issue	Department	Status
QA/INV/2025/016	20/06/2025	OOS in Assay	QC	Closed

Annexure-2: Root Cause Analysis Report

Investigation No.	QA/INV/2025/016
Tool Used	5 Whys
Root Cause Identified	Improper reagent storage
Evidence	Reagent stability compromised beyond allowable temperature

Annexure-3: CAPA Tracker

CAPA No.	Action	Owner	Due Date	Status
CAPA/QA/2025/044	Install reagent storage alarm	Sunita Reddy	30/06/2025	In Progress

Annexure-4: RCA Effectiveness Log

Investigation No.	Check Date	Result	Reviewer
QA/INV/2025/016	15/07/2025	No recurrence	Rajesh Kumar

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
10/05/2022	1.0	Initial Release	New SOP	QA Head
24/06/2025	2.0	Added Annexures and effectiveness log	Periodic Update	QA Head