Standard Operating Procedure for Equipment Cleaning and Validation in Solvent Units in API Manufacturing
| Department | API Manufacturing |
|---|---|
| SOP No. | SOP/API/058/2025 |
| Supersedes | SOP/API/058/2022 |
| 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 validated cleaning procedure for all equipment used in solvent handling, storage, and recovery to ensure removal of residues, prevent cross-contamination, and comply with cGMP and regulatory requirements.
2. Scope
This SOP applies to all reactors, pipelines, condensers, storage tanks, filters, pumps, and associated solvent-handling equipment used in the API manufacturing solvent area.
3. Responsibilities
- Production Staff: Execute cleaning as per procedure and fill logs.
- Maintenance Team: Assist with dismantling and reassembling of parts, if required.
- QA Department: Review and approve cleaning validations.
- QC Department: Perform swab and rinse sampling for validation analysis.
4. Accountability
The Production Head is accountable for implementation of cleaning practices. QA Head is responsible for ensuring cleaning validations are approved and compliant.
5. Procedure
5.1 Cleaning Procedure
- Ensure equipment is empty and disconnected from solvent supply.
- Flush with 10–20 L of potable water to remove residual solvents.
- Use 1% NaOH solution (or suitable detergent) for alkaline wash, followed by thorough rinsing.
- Rinse with purified water until conductivity is below 10 µS/cm.
- Use final rinse with IPA (Isopropyl Alcohol) or suitable grade solvent where required to displace water.
- Dry equipment using compressed air or hot air blower.
- Label as “Cleaned” with status tag and mention cleaning date and expiry.
5.2 Cleaning Validation
- Perform validation for each equipment type and cleaning method.
- Prepare “Cleaning Validation Protocol” outlining:
- Worst-case solvent/product
- Acceptance criteria (NMT 10 ppm residue or NMT 0.002 mg/cm² surface)
- Sampling locations
- Analytical method
- Collect swab/rinse samples post-cleaning (Annexure-1: Swab Sampling Form).
- Send samples to QC for analysis and attach report to the validation summary.
5.3 Cleaning Frequency
- Clean equipment:
- After each batch or campaign
- If idle for more than 7 days
- Before product changeover
- Maintain “Equipment Cleaning Record” (Annexure-2) for each cleaning cycle.
5.4 Revalidation
- Revalidate if:
- Equipment is modified
- Change in cleaning procedure
- Failure of initial validation
- Prepare a new validation protocol and perform full cycle study again.
6. Abbreviations
- SOP: Standard Operating Procedure
- QC: Quality Control
- QA: Quality Assurance
- IPA: Isopropyl Alcohol
- µS/cm: Microsiemens per centimeter
- NMT: Not More Than
7. Documents
- Swab Sampling Form (Annexure-1)
- Equipment Cleaning Record (Annexure-2)
- Cleaning Validation Summary Report
8. References
- ICH Q7 – Section 5.21: Cleaning Validation
- US FDA Guidance for Industry – Process Validation
- EU GMP Annex 15 – Qualification and Validation
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Swab Sampling Form
| Equipment ID | Surface Area (cm²) | Swab Location | Sample ID | Date | Analyst |
|---|---|---|---|---|---|
| STV-101 | 100 | Inlet Valve | SWB-0425 | 13/04/2025 |
Annexure-2: Equipment Cleaning Record
| Date | Equipment ID | Product Last Used | Cleaning Method | Cleaned By | Checked By |
|---|---|---|---|---|---|
| 13/04/2025 | STV-101 | Methanol | Alkaline Wash |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 01/01/2022 | 1.0 | Initial SOP Release | GMP Compliance | QA Head |
| 13/04/2025 | 2.0 | Included Rinse Sampling and Revalidation Triggers | Audit Observation | QA Head |