consistency, and regulatory compliance.

2. Scope

This SOP applies to all manufacturing personnel, QA staff, and QC analysts involved in analyzing, reviewing, and trending of data across sterile injectable manufacturing operations.

3. Responsibilities

• Production Operators: Report any abnormal or unexpected results immediately to supervisors.
• Production Supervisor: Initiate initial assessment and notify QA for further evaluation.
• Quality Assurance (QA): Evaluate and determine OOT status, perform impact analysis, and initiate CAPA if required.
• Quality Control (QC): Provide historical data for comparison and assist in investigation.
• Head – QA: Review and approve conclusions, risk assessments, and ensure timely closure of OOT events.

4. Accountability

The Head of Quality Assurance is accountable for ensuring all OOT events are thoroughly investigated, documented, and resolved as per regulatory and company standards.

5. Procedure

5.1 Definition of OOT

1. OOT is defined as a result that falls within the specification limits but is inconsistent with historical trends, previous batches, or established statistical limits.
2. Examples of OOT occurrences:
   • Sudden shift in pH of solution during batch preparation
   • Abnormal weight gain in vial filling, though within tolerance
   • Significant variation in LAF airflow pattern readings

5.2 Detection and Initial Notification

1. Any personnel identifying a potential OOT shall immediately inform their supervisor and QA.
2. The result shall be clearly marked as “Suspected OOT” in the batch manufacturing record or relevant logbook.

5.3 Initial Review and Verification

1. QA shall verify:
   • Correct sampling technique was followed
   • Equipment calibration status
   • Environmental conditions at the time of observation
2. If all above are satisfactory, classify the result as confirmed OOT.

5.4 OOT Investigation

1. Initiate OOT Investigation Form (Annexure-1).
2. Gather historical batch data for the same product, process, or equipment from QC.
3. Interview relevant operators and document findings.
4. Evaluate:
   • Trends over last 10 batches
   • Any equipment alarms or deviations logged
   • Materials used, especially new lot numbers

5.5 Impact Assessment

1. QA shall assess:
   • Impact on product quality
   • Regulatory compliance
   • Release status of affected batch
2. If necessary, quarantine affected material or products pending resolution.

5.6 Corrective and Preventive Actions (CAPA)

1. Root cause to be identified through tools like fishbone diagram or 5-Whys technique.
2. Implement CAPA measures such as retraining, equipment recalibration, or SOP revision.
3. Track CAPA effectiveness over a defined period.

5.7 Documentation and Closure

1. Compile all records including investigation form, historical data, and impact report.
2. Head QA to review and approve final OOT report.
3. Update OOT Register (Annexure-2) for future trend review.

6. Abbreviations

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

7. Documents

1. OOT Investigation Form – Annexure-1
2. OOT Register – Annexure-2

8. References

• ICH Q9 – Quality Risk Management
• ICH Q10 – Pharmaceutical Quality System
• EU GMP Annex 15

9. SOP Version

Version: 2.0

10. Approval Section

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

11. Annexures

Annexure-1: OOT Investigation Form

OOT No.	OOT/2025/012
Date Identified	21/06/2025
Batch No.	INJ/145/2025
Parameter	pH
Observed Value	6.95
Historical Range	6.70–6.80
Investigator	Rajesh Kumar
Preliminary Remarks	Requires further review

Annexure-2: OOT Register

OOT No.	Date	Batch	Parameter	Conclusion	Status
OOT/2025/012	21/06/2025	INJ/145/2025	pH	Accepted with justification	Closed

Revision History

Revision Date	Revision No.	Details	Reason	Approved By
01/07/2022	1.0	Initial release	New SOP	QA Head
24/06/2025	2.0	Expanded investigation and CAPA sections	GMP enhancement	QA Head