Standard Operating Procedure for Rework and Reprocessing Guidelines in API Manufacturing
| Department | API Manufacturing |
|---|---|
| SOP No. | SOP/API/039/2025 |
| Supersedes | SOP/API/039/2022 |
| 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 GMP-compliant procedure for managing rework and reprocessing of non-conforming API batches, ensuring product quality, process traceability, and regulatory oversight.
2. Scope
This SOP applies to all Active Pharmaceutical Ingredients (APIs) manufactured in-house that require rework or reprocessing due to non-compliance with predefined specifications during or after production.
3. Responsibilities
- Production Personnel: Identify non-conformance and propose rework/reprocessing plans.
- QA Department: Review and approve rework/reprocessing proposals and oversee execution.
- QC Department: Perform analytical testing before and after rework/reprocessing.
4. Accountability
The QA Head is accountable for approving rework/reprocessing procedures and ensuring regulatory compliance. The Production Head is responsible for execution as per approved protocol.
5. Procedure
5.1 Definitions
- Rework: Subjecting non-conforming product to one or more processing steps different from original manufacturing process.
- Reprocessing: Repeating one or more steps of the original manufacturing process.
5.2 Identification of Non-Conformance
- Identify deviations in physical, chemical, or microbiological specifications during IPC or final QC testing.
- Record findings in the Batch Manufacturing Record (BMR) and notify QA.
5.3 Proposal and Approval
- Production team shall prepare a “Rework/Reprocessing Proposal Form” (Annexure-1).
- Include:
- Batch details
- Root cause
- Proposed method
- Justification
- Risk assessment
- QA reviews the proposal with QC and approves if compliant with regulatory guidelines and internal quality risk management practices.
5.4 Execution of Rework/Reprocessing
- Execute only after QA approval.
- Follow instructions outlined in the approved plan.
- Document all activities separately in “Rework/Reprocessing Execution Log” (Annexure-2).
- Label material appropriately during each stage of reprocessing (e.g., “Under Rework”).
5.5 Testing and Disposition
- Submit samples to QC for complete analysis after rework/reprocessing.
- Compare test results with original specifications and document in the COA.
- Only QA shall approve release or rejection of the batch after reprocessing.
- Retain full documentation in batch file and deviation records.
5.6 Regulatory and Stability Considerations
- If reprocessing/rework is included in approved regulatory filing, no further approval is needed.
- If not included, regulatory affairs shall be consulted before execution.
- Perform stability studies if reprocessing has potential to impact product shelf life.
6. Abbreviations
- SOP: Standard Operating Procedure
- QA: Quality Assurance
- QC: Quality Control
- IPC: In-Process Control
- BMR: Batch Manufacturing Record
- COA: Certificate of Analysis
7. Documents
- Rework/Reprocessing Proposal Form (Annexure-1)
- Rework/Reprocessing Execution Log (Annexure-2)
- QC Report Post-Reprocessing (Annexure-3)
8. References
- ICH Q7 – Good Manufacturing Practice for Active Pharmaceutical Ingredients
- 21 CFR Part 211 – Subpart F & J
- WHO GMP Guidelines – Rework and Reprocessing Section
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Rework/Reprocessing Proposal Form
| Batch No. | Product | Issue Observed | Proposed Method | Justification | Approved By |
|---|---|---|---|---|---|
| API-202504 | API-X | Low Assay | Recrystallization | Restores potency |
Annexure-2: Rework/Reprocessing Execution Log
| Date | Batch No. | Executed Step | Performed By | Observed Results |
|---|---|---|---|---|
| 13/04/2025 | API-202504 | Repeat Crystallization | Clear crystals formed |
Annexure-3: QC Report Post-Reprocessing
| Batch No. | Parameter | Result | Limit | Status |
|---|---|---|---|---|
| API-202504 | Assay | 99.2% | 98.0–102.0% | Pass |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 01/01/2022 | 1.0 | Initial SOP Release | New GMP Process | QA Head |
| 13/04/2025 | 2.0 | Added regulatory filing considerations | Audit Requirement | QA Head |