results that show atypical shifts compared to historical data, even when they are within specifications.

3. Responsibilities

• QC Analyst: Monitor and flag unusual results during testing and document OOT observations.
• QC Reviewer: Evaluate trends against historical data and determine the need for investigation.
• QA Officer: Review investigation findings, approve CAPA, and assess potential impact on product quality.

4. Accountability

The Head – QC is accountable for ensuring all OOT events are captured, investigated, and documented in accordance with regulatory guidelines and data integrity standards.

5. Procedure

5.1 Definition and Identification of OOT

1. An OOT result is a test result that is within specification limits but inconsistent with historical data or trends.
2. OOT conditions may include:
   • Sustained upward or downward shifts in assay or impurity values
   • Sudden spike in moisture, pH, or impurity profiles
   • Changes in UV absorbance or color over batches
3. OOT trends can be detected through statistical tools or visual trend charts maintained in the QC department.
4. All OOT observations must be documented using the OOT Notification Form (Annexure-1).

5.2 Preliminary Assessment

1. Verify analytical method performance and system suitability results.
2. Check sample preparation steps, instrument calibration, reagent validity, and environmental conditions.
3. If no assignable cause is found, escalate to QA for a detailed OOT investigation.

5.3 Full-Scale Investigation

1. QA initiates the OOT Investigation Form (Annexure-2) and assigns a unique OOT investigation number.
2. Evaluate:
   • Production batch records and process parameters
   • Stability or degradation trends
   • Analytical method robustness
   • Related past OOT or OOS events
3. Conduct interviews and collect supporting evidence.
4. Perform re-testing only if scientifically justified and approved by QA.
5. Conclude investigation with root cause identification (if applicable) and propose CAPA.

5.4 Data Trending and Review

1. Document trending of critical quality attributes monthly using control charts or run charts.
2. QA to review all trends quarterly and report to management during Quality Review Meetings.
3. Update trend analysis tools when methods or specifications change.

5.5 Disposition

1. Decide final batch status based on investigation outcome:
• Acceptable variation – batch approved
• Unacceptable variation – batch rejected or reprocessed
2. QA to record disposition in the OOT Disposition Log (Annexure-3).

6. Abbreviations

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

7. Documents

1. OOT Notification Form (Annexure-1)
2. OOT Investigation Form (Annexure-2)
3. OOT Disposition Log (Annexure-3)
4. Batch Manufacturing Records
5. Trend Analysis Sheets

8. References

• ICH Q9 – Quality Risk Management
• US FDA Guidance on OOS Investigations
• 21 CFR Part 211
• ICH Q10 – Pharmaceutical Quality System

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: OOT Notification Form

Date	Batch No.	Test	Observed Result	Previous Avg.	Remarks
13/04/2025	API-20250413	Assay	97.5%	99.8%	Trend deviation noted

Annexure-2: OOT Investigation Form

OOT No.	OOT/026/2025
Investigation Date	13/04/2025
Investigated By	QC Supervisor
Root Cause	Degradation due to prolonged exposure to ambient light
CAPA	Reinforce storage practices, retrain staff

Annexure-3: OOT Disposition Log

Date	OOT No.	Batch No.	Disposition	QA Sign
14/04/2025	OOT/026/2025	API-20250413	Accepted with justification	QA Head

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/01/2022	1.0	Initial Release	GMP Requirement	QA Head
13/04/2025	2.0	Added trend review, annexures	Audit Suggestion	QA Head