Standard Operating Procedure for Handling of Process Deviations in API Manufacturing
| Department | API Manufacturing |
|---|---|
| SOP No. | SOP/API/034/2025 |
| Supersedes | SOP/API/034/2022 |
| Page No. | Page 1 of 11 |
| Issue Date | 13/04/2025 |
| Effective Date | 15/04/2025 |
| Review Date | 13/04/2026 |
1. Purpose
To define the procedure for identifying, documenting, evaluating, and resolving process deviations during the manufacturing of Active Pharmaceutical Ingredients (APIs), ensuring product quality and regulatory compliance.
2. Scope
This SOP applies to all planned or unplanned process deviations occurring during any manufacturing activity (production, in-process testing, material handling, equipment operation, etc.) within the API manufacturing department.
3. Responsibilities
- Production Operator: Immediately report any observed deviation to the supervisor or QA.
- Production Supervisor: Record preliminary details, assess immediate impact, and initiate deviation form.
- QA Department: Lead the investigation, ensure risk assessment, and track deviation closure.
- Quality Head: Review deviation trend reports and approve CAPA (Corrective and Preventive Actions).
4. Accountability
The Production Manager is accountable for execution and timely reporting of deviations. The QA Manager is responsible for investigation, documentation, and closure of all deviations as per GMP guidelines.
5. Procedure
5.1 Identification of Deviation
- Any departure from an approved manufacturing instruction, parameter, or condition shall be considered a deviation.
- Examples include:
- Deviation from temperature/time range
- Failure in equipment settings
- Sampling delay or missed step
- Immediately inform the supervisor and QA upon identifying a deviation.
5.2 Documentation of Deviation
- Record the deviation in the “Deviation Notification Form” (Annexure-1) within 1 hour of observation.
- Include batch number, process step, observed vs expected parameter, date, time, and initial remarks.
- Submit the form to QA for further investigation.
5.3 Investigation and Impact Assessment
- QA will coordinate a root cause analysis using tools such as 5 Whys or Fishbone Diagram.
- Evaluate impact on:
- Product quality
- Yield and purity
- Regulatory and validation requirements
- If required, QA may initiate sample analysis or request additional tests.
- Document findings in “Deviation Investigation Report” (Annexure-2).
5.4 Classification and Disposition
- Classify deviation as:
- Minor: No direct impact on quality, yield, or compliance
- Major: Potential or actual impact on product quality or process control
- Based on the investigation, disposition could be:
- Continue with processing
- Reprocess or rework
- Reject batch and investigate further
5.5 Corrective and Preventive Action (CAPA)
- Determine immediate corrections, root-cause-based corrective action, and long-term preventive action.
- Assign target dates and responsibilities.
- QA to verify implementation and effectiveness before deviation closure.
5.6 Closure and Trending
- QA shall approve and close deviation in “Deviation Closure Record” (Annexure-3).
- Maintain deviation trend reports monthly and review in quality meetings for repetitive issues.
6. Abbreviations
- SOP: Standard Operating Procedure
- QA: Quality Assurance
- CAPA: Corrective and Preventive Action
- GMP: Good Manufacturing Practice
- BMR: Batch Manufacturing Record
7. Documents
- Deviation Notification Form (Annexure-1)
- Deviation Investigation Report (Annexure-2)
- Deviation Closure Record (Annexure-3)
8. References
- ICH Q10 – Pharmaceutical Quality System
- 21 CFR Part 211 – Subpart J: Records and Reports
- WHO GMP Guidelines – Section on Deviations
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Deviation Notification Form
| Date | Batch No. | Step Involved | Description of Deviation | Initial Action Taken |
|---|---|---|---|---|
| 13/04/2025 | API-202504 | Crystallization | Temp exceeded 45°C | Cooled immediately |
Annexure-2: Deviation Investigation Report
| Deviation ID | Root Cause | Investigation Tool | Impact Assessment | QA Comments |
|---|---|---|---|---|
| DEV-034-25 | Operator error | 5 Whys | Minor | Training Scheduled |
Annexure-3: Deviation Closure Record
| Deviation ID | CAPA Summary | Effectiveness Verified | Closed On | QA Reviewer |
|---|---|---|---|---|
| DEV-034-25 | Process refresher training | Yes | 18/04/2025 |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 01/01/2022 | 1.0 | Initial Issue | New SOP | QA Head |
| 13/04/2025 | 2.0 | Revised investigation and classification process | Compliance Enhancement | QA Head |