outside the specified limits, indicating a potential stability failure.

3. Responsibilities

• QC Stability Analyst: Identifies and reports the failure promptly.
• Quality Assurance (QA): Coordinates investigation and initiates CAPA.
• Regulatory Affairs: Evaluates the regulatory impact and informs authorities if required.
• Formulation Development (FD): Assists in root cause analysis for formulation-related failures.

4. Accountability

The Head – Quality Assurance is accountable for timely resolution and regulatory compliance of all stability failure investigations.

5. Procedure

5.1 Detection of Stability Failure

1. QC analyst identifies a parameter that has deviated from approved specifications (OOS/OOT).
2. Data is immediately reported to QA and documented in the stability tracking logbook.
3. A preliminary assessment is made to confirm the validity of the result.

5.2 Preliminary Investigation

1. Repeat testing of the sample as per OOS SOP to confirm failure.
2. If confirmed, QA initiates a formal investigation using the Stability Failure Investigation Form (Annexure-1).
3. Investigate potential laboratory errors, sample integrity, and storage condition deviations.

5.3 Root Cause Analysis

1. QA, QC, and FD jointly perform root cause analysis (RCA).
2. Use tools like fishbone diagram, 5 Whys, and CAPA matrix to identify possible causes.
3. Evaluate raw materials, process variables, packaging, and environmental factors.

5.4 Corrective and Preventive Actions (CAPA)

1. Define CAPA based on investigation findings (e.g., reformulation, packaging change).
2. Implement corrective actions under QA supervision.
3. Verify effectiveness of CAPA through follow-up studies or trending of future batches.

5.5 Regulatory Reporting

1. Regulatory Affairs evaluates whether the stability failure impacts shelf-life or label claims.
2. If required, file a variation or notify regulatory agencies (e.g., CDSCO, USFDA, EMA).
3. Document the communication and response in the regulatory tracking log.

5.6 Documentation and Closure

1. Compile all investigation data, reports, and CAPA in a consolidated Stability Failure Dossier.
2. QA Head reviews and signs off for closure.
3. Store records for a minimum of 5 years or as per regulatory requirement.

6. Abbreviations

• OOS: Out of Specification
• OOT: Out of Trend
• CAPA: Corrective and Preventive Action
• QA: Quality Assurance
• QC: Quality Control

7. Documents

1. Stability Study Report
2. OOS/OOT Report – Annexure-1
3. Root Cause Analysis Form – Annexure-2
4. CAPA Implementation Log – Annexure-3

8. References

• ICH Q1A(R2): Stability Testing of New Drug Substances and Products
• WHO TRS 1010 Annex 2
• PharmaSOP OOS Handling SOP

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation	Jr. Production Chemist	QA Executive	Head – Manufacturing
Department	Gel Manufacturing	Quality Assurance	Manufacturing

11. Annexures

Annexure-1: Stability Failure Investigation Form

Product Name
Batch No.
Study Condition	25°C/60%RH / 40°C/75%RH
Parameter Failed
Date of Observation
Initial Result
Repeat Result
Investigation Initiated By
Remarks

Annexure-2: Root Cause Analysis Form

Potential Cause Category	Details	Verified?
Material		Yes / No
Method		Yes / No
Machine		Yes / No
Man		Yes / No
Environment		Yes / No
Conclusion

Annexure-3: CAPA Implementation Log

CAPA ID	Action	Owner	Planned Date	Completion Date	Status
					Open/Closed

Revision History

Revision Date	Revision No.	Change Description	Reason	Approved By
14/04/2022	1.0	Initial Issue	New SOP	QA Head
02/06/2025	2.0	Added detailed RCA and CAPA templates	Annual Review	QA Head