root cause and take appropriate corrective and preventive actions (CAPA).

2. Scope

This SOP applies to all personnel involved in QC testing of sterile injectable products, including raw materials, in-process, finished goods, and stability samples, where OOS results are obtained for any validated analytical method.

3. Responsibilities

• QC Analyst: Identifies and reports any OOS result immediately and documents preliminary details.
• QC Supervisor: Reviews the OOS result and initiates Phase I investigation.
• QA Department: Reviews the investigation, evaluates the impact on product quality, and approves the closure of the investigation.
• Department Head: Ensures implementation of CAPA and final decision on batch disposition.

4. Accountability

The Head of Quality Control is accountable for ensuring compliance with this SOP and regulatory expectations outlined in FDA 21 CFR 211, WHO TRS 986, and other applicable guidelines.

5. Procedure

5.1 Identification of OOS

1. Any result that falls outside the predetermined specification range during analytical testing shall be treated as a potential OOS result.
2. The analyst shall not repeat the analysis without notifying the QC Supervisor.
3. Record the result in the raw data sheet and inform the supervisor immediately.

5.2 Phase I – Laboratory Investigation

1. QC Supervisor and analyst jointly review raw data, calculations, chromatograms, instrument settings, standard preparations, and sample integrity.
2. Check the performance and calibration status of instruments used.
3. Verify that correct method was followed and reagents/standards used were within expiry.
4. If any clear laboratory error is identified (e.g., dilution error, weighing mistake), it should be documented and justified with evidence.

5.3 Hypothesis Testing (if applicable)

1. If the error is not obvious, perform a hypothesis test under controlled conditions to determine if the result can be reproduced.
2. Document all hypothesis testing separately in Annexure-2.

5.4 Phase II – Full-Scale Investigation

1. If no assignable laboratory error is identified, initiate a Phase II investigation in coordination with QA.
2. Review batch manufacturing records, equipment logs, environmental data, and personnel training records.
3. Interview personnel involved in sample collection and handling.
4. Perform a risk assessment to determine if other batches or products are impacted.

5.5 Retesting

1. Retesting may only be permitted if justified in Phase I and approved by QA.
2. Retesting should be conducted on the same sample (if available) and not on a new sample from the batch.
3. Results of retesting must be evaluated along with original data; averaging results is not acceptable.

5.6 Resampling

1. Permissible only if it is demonstrated that the original sample was mishandled or compromised.
2. Requires prior QA approval and full documentation.

5.7 Conclusion and Final Decision

1. Summarize findings and root cause in the OOS Investigation Report (Annexure-1).
2. Determine batch disposition (release, rework, reject) based on investigation outcomes.
3. Implement appropriate CAPA to prevent recurrence.

5.8 Documentation

1. All documents related to OOS investigation must be maintained with traceability to batch number and analyst ID.
2. Ensure entries in Annexure-1 are completed and reviewed by QA before closing the report.

6. Abbreviations

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

7. Documents

1. OOS Investigation Report – Annexure-1
2. Hypothesis Testing Log – Annexure-2
3. Retesting Approval Form – Annexure-3

8. References

• FDA Guidance for Industry – Investigating OOS Test Results for Pharmaceutical Production
• 21 CFR Part 211
• WHO TRS 986
• ICH Q10 – Pharmaceutical Quality System

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation	QC Analyst	QA Executive	Head QA
Department	Quality Control	Quality Assurance	Quality Assurance

11. Annexures

Annexure-1: OOS Investigation Report

Date	Batch No.	Test Parameter	OOS Result	Initial Observation	Investigator
20/06/2025	INJ-950	Assay	87.2%	Low result on first run	Rajesh Kumar

Annexure-2: Hypothesis Testing Log

Date	Test Conducted	Control Used	Result	Remarks
21/06/2025	Repeat dilution with fresh standard	Cal std A	99.2%	Test passes; lab error suspected

Annexure-3: Retesting Approval Form

Date	Analyst	Justification	QA Approval	Remarks
21/06/2025	Sunita Reddy	Suspected standard degradation	Approved	Retesting permitted once

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/04/2022	1.0	Initial version	New SOP	Head QA
24/06/2025	2.0	Updated with detailed investigation flow and annexures	Annual Review	Head QA