Standard Operating Procedure for Prevention of Cross Contamination during Drying in API Manufacturing
| Department | API Manufacturing |
|---|---|
| SOP No. | SOP/API/073/2025 |
| Supersedes | SOP/API/073/2022 |
| Page No. | Page 1 of 10 |
| Issue Date | 13/04/2025 |
| Effective Date | 15/04/2025 |
| Review Date | 13/04/2026 |
1. Purpose
To define the procedure for preventing cross contamination during drying processes of Active Pharmaceutical Ingredients (APIs) in the manufacturing facility, ensuring compliance with cGMP and product quality.
2. Scope
This SOP is applicable to all drying operations including tray drying, vacuum drying, fluid bed drying, and rotary drying performed in the API manufacturing areas.
3. Responsibilities
- Production Operator: Follow prescribed practices to prevent cross contamination.
- Production Supervisor: Verify adherence to preventive measures and perform risk assessments.
- QA Department: Ensure area cleanliness, review cleaning records, and validate preventive practices.
- Engineering Department: Maintain integrity of drying equipment and air handling units (AHUs).
4. Accountability
The Production Head is accountable for implementation of cross contamination prevention measures. QA Head is responsible for compliance monitoring and audit readiness.
5. Procedure
5.1 Equipment and Area Cleaning
- Ensure all drying equipment (FBD, tray dryer, vacuum dryer) is cleaned as per validated cleaning SOP before and after use.
- Verify cleaning status label is displayed as “Cleaned” with date and sign.
- Use dedicated cleaning tools for each drying area to prevent cross-use.
5.2 Batch and Product Segregation
- Do not dry different products or batches simultaneously in the same chamber or area.
- If multiple dryers are used in parallel, maintain physical separation and labeled identification of each dryer and batch.
- Implement scheduling to allow drying of only one product per session.
5.3 Environmental and Personnel Controls
- Ensure personnel wear product-specific PPE and change it when moving between product zones.
- Minimize human movement and material exposure during transfer to and from drying units.
- Monitor temperature, humidity, and particulate matter as per environmental control plan.
5.4 Equipment Integrity and Design
- Ensure all dryers are leak-free and have proper sealing mechanisms (e.g., door gaskets, clamps).
- Use HEPA filters where applicable, and monitor differential pressure in ducting to detect leaks.
- Perform regular maintenance and integrity testing of equipment and associated air handling units.
5.5 Line Clearance and Documentation
- QA must perform and document line clearance before and after each drying operation.
- Ensure that no remnants of previous batch/product remain in trays, ducts, or containers.
- Record preventive actions and inspections in “Cross Contamination Prevention Log” (Annexure-1).
5.6 Risk Mitigation and Validation
- Perform risk assessment for products with high cross-contamination potential (e.g., cytotoxics, beta-lactams).
- Validate cleaning processes and recovery limits for each product changeover.
- Review trends from environmental monitoring and product cross-checks in retained samples.
6. Abbreviations
- API: Active Pharmaceutical Ingredient
- SOP: Standard Operating Procedure
- FBD: Fluid Bed Dryer
- QA: Quality Assurance
- AHU: Air Handling Unit
- PPE: Personal Protective Equipment
7. Documents
- Cross Contamination Prevention Log (Annexure-1)
- Cleaning Checklist
- Environmental Monitoring Record
- Batch Manufacturing Record
8. References
- WHO TRS 986 Annex 2 – GMP for APIs
- EU Guidelines on Cross Contamination (Chapter 3 and 5)
- ICH Q9 – Quality Risk Management
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Cross Contamination Prevention Log
| Date | Dryer ID | Batch No. | Cleaning Verified | Line Clearance Done | Remarks | Checked By |
|---|---|---|---|---|---|---|
| 13/04/2025 | VCD-02 | API-20250413 | Yes | Yes | Clean & Clear |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 01/01/2022 | 1.0 | Initial SOP Release | New Compliance Requirement | QA Head |
| 13/04/2025 | 2.0 | Added Risk Assessment and Validation Elements | Regulatory Inspection Readiness | QA Head |