Standard Operating Procedure for Handling Discrepant IPC Observations in API Manufacturing
| Department | API Manufacturing |
|---|---|
| SOP No. | SOP/API/116/2025 |
| Supersedes | SOP/API/116/2022 |
| Page No. | Page 1 of 10 |
| Issue Date | 13/04/2025 |
| Effective Date | 15/04/2025 |
| Review Date | 13/04/2026 |
1. Purpose
To establish a procedure for managing discrepancies observed in IPC (In-Process Control) data during API manufacturing, including unusual, inconsistent, or unexpected results, ensuring timely identification, investigation, correction, and documentation as per cGMP.
2. Scope
This SOP applies to all IPC parameters monitored during the production of APIs and intermediates, where observed results deviate from expected trends or show inconsistencies due to operator error, equipment fault, or sampling issues.
3. Responsibilities
- Production Chemist: Immediately report any discrepant observation to QA and document the initial finding in the IPC sheet.
- QC Analyst: Assist in confirmation and repeat testing (if justified), and provide analytical insight.
- QA Officer: Initiate deviation process, perform investigation, and ensure resolution of discrepancy.
4. Accountability
The QA Head is accountable for the review, classification, and closure of discrepant IPC observations. The Production Head is accountable for ensuring timely notification and execution of corrective actions.
5. Procedure
5.1 Identification of Discrepant Observation
- A discrepant observation is defined as:
- Sudden variation in result from previous trend
- Fluctuating readings within a short interval
- Unusually high/low readings despite correct process settings
- Observation not matching batch behavior (e.g., visual, pH, temperature)
- On identification, halt further processing of the affected stage until QA is notified and assessment is performed.
5.2 Immediate Actions
- Document the discrepancy in the IPC logbook with:
- Date and time
- Parameter and equipment used
- Observation details
- Operator signature
- Notify the QA team and shift supervisor immediately.
- Place equipment “On Hold” if malfunction is suspected.
5.3 Investigation and Classification
- QA will initiate deviation as per SOP/API/115/2025 and conduct a root cause analysis (RCA).
- Determine potential causes:
- Sampling error
- Instrument calibration or functionality error
- Environmental influence
- Operator error
- Classify the discrepancy as:
- Minor (no impact on product quality)
- Major (requires CAPA, may affect next stage)
- Critical (impact on product quality or safety)
5.4 Retesting Criteria
- Retesting shall be permitted only if:
- There is clear evidence of error in sampling or instrument use
- QA has approved the justification for retesting
- Retesting is documented in Deviation Form and IPC Sheet
5.5 Corrective Action
- Implement appropriate action based on investigation outcome, such as:
- Retraining of staff
- Repair or recalibration of equipment
- Procedure revision
- Process adjustment (if deviation is accepted with impact evaluation)
- Record action taken in Deviation Report and obtain QA approval for closure.
6. Abbreviations
- IPC: In-Process Control
- SOP: Standard Operating Procedure
- QA: Quality Assurance
- QC: Quality Control
- RCA: Root Cause Analysis
- CAPA: Corrective and Preventive Action
7. Documents
- Discrepant IPC Observation Report (Annexure-1)
- Deviation Register
- IPC Logbook
8. References
- ICH Q10 – Pharmaceutical Quality System
- 21 CFR Part 211 – cGMP for Finished Pharmaceuticals
- WHO TRS 986 – GMP Guidelines
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Discrepant IPC Observation Report
| Date | Batch No. | Parameter | Observed Value | Expected | Suspected Cause | Action Taken | QA Comments |
|---|---|---|---|---|---|---|---|
| 13/04/2025 | API-20250413 | Temperature | 42°C | 30–35°C | Equipment sensor drift | Sensor Replaced | Approved for closure |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 01/01/2022 | 1.0 | Initial SOP Release | Regulatory Requirement | QA Head |
| 13/04/2025 | 2.0 | Added structured classification and retesting rules | Audit Recommendation | QA Head |