Standard Operating Procedure for Handling Raw Materials with Special Microbiological Testing Requirements
| Department | Quality Control / Quality Assurance / Microbiology |
|---|---|
| SOP No. | SOP/RM/084/2025 |
| Supersedes | SOP/RM/084/2022 |
| Page No. | Page 1 of 15 |
| Issue Date | 01/02/2025 |
| Effective Date | 05/02/2025 |
| Review Date | 01/02/2026 |
1. Purpose
This Standard Operating Procedure (SOP) outlines the guidelines for handling raw materials that require special microbiological testing, ensuring their integrity and preventing contamination throughout the quarantine and testing processes. This SOP aligns with Good Manufacturing Practices (GMP) and regulatory guidelines.
2. Scope
This SOP applies to all raw materials received and stored in the quarantine area that require microbiological testing, including but not limited to, sterile APIs, excipients sensitive to microbial contamination, and materials requiring bioburden or endotoxin testing.
3. Responsibilities
- Warehouse Personnel: Ensure proper storage and labeling of materials requiring microbiological testing.
- Quality Control (QC) and Microbiology Personnel: Conduct microbiological testing, ensure aseptic sampling techniques, and maintain sterile environments.
- Quality Assurance (QA): Review procedures for compliance with microbiological standards and approve deviations if necessary.
4. Accountability
The Microbiology Manager is responsible for ensuring that microbiological testing and aseptic handling procedures are followed correctly. The QA Manager
ensures compliance with regulatory standards and approves any deviations from standard procedures.
5. Procedure
5.1 Identification and Classification of Materials
- Materials Requiring Special Testing:
- Sterile Active Pharmaceutical Ingredients (APIs)
- Excipients prone to microbial contamination
- Water-sensitive materials requiring endotoxin testing
- Herbal and natural products requiring bioburden testing
- Labeling Requirements:
- Clearly label materials with the following:
- Material Name
- Batch/Lot Number
- “Requires Microbiological Testing” indicator
- Special storage instructions (e.g., “Store in sterile conditions”)
- Clearly label materials with the following:
5.2 Storage Procedures
- Storage Conditions:
- Store materials in a dedicated, temperature-controlled quarantine area designed for microbiological-sensitive products.
- Ensure materials are kept in sealed, sterile packaging until sampling.
- Document storage details in the Microbiological Material Storage Log (Annexure-1).
- Segregation of Materials:
- Segregate materials requiring microbiological testing from non-sensitive raw materials.
- Label storage zones accordingly to prevent cross-contamination.
5.3 Sampling Procedures
- Preparation for Sampling:
- Perform sampling in a dedicated cleanroom or aseptic sampling booth.
- Use sterile, single-use sampling tools to prevent contamination.
- Ensure all sampling equipment is pre-sterilized and documented in the Equipment Sterilization Log (Annexure-2).
- Sampling Process:
- Wear appropriate PPE, including sterile gloves, gowns, masks, and face shields.
- Disinfect the outer packaging before opening in the cleanroom.
- Collect the sample using aseptic techniques and transfer it to sterile containers.
- Seal and label the sample containers immediately after collection.
- Document sampling details in the Microbiological Sampling Log (Annexure-3).
5.4 Microbiological Testing Procedures
- Types of Tests:
- Bioburden Testing: Determine the microbial load of the material using standard plate count methods.
- Endotoxin Testing: Use the Limulus Amebocyte Lysate (LAL) test for endotoxin detection in water-sensitive materials.
- Sterility Testing: Perform sterility tests on materials labeled as sterile, following pharmacopeial guidelines.
- Documentation of Test Results:
- Record all test results in the Microbiological Test Result Log (Annexure-4).
- Report any out-of-specification (OOS) results immediately to the QA Manager.
5.5 Handling Deviations in Microbiological Testing
- Deviation Reporting:
- Document any deviations in sampling, storage, or testing procedures in the Microbiological Deviation Report (Annexure-5).
- Report OOS results to the QA Manager immediately for investigation.
- Corrective Actions:
- Conduct a root cause analysis to identify sources of contamination or procedural lapses.
- Implement corrective actions and document them in the Corrective Action Log (Annexure-6).
5.6 Training and Compliance
- Personnel Training:
- All personnel involved in handling and testing microbiological-sensitive materials must be trained in aseptic techniques and microbiological testing procedures.
- Document training in the Training Log (Annexure-7).
- Compliance Monitoring:
- QA must conduct periodic audits of microbiological handling procedures to ensure compliance.
- Document audit findings in the Compliance Audit Log (Annexure-8).
6. Abbreviations
- SOP: Standard Operating Procedure
- GMP: Good Manufacturing Practice
- QA: Quality Assurance
- QC: Quality Control
- PPE: Personal Protective Equipment
- OOS: Out-of-Specification
- LAL: Limulus Amebocyte Lysate
7. Documents
- Microbiological Material Storage Log (Annexure-1)
- Equipment Sterilization Log (Annexure-2)
- Microbiological Sampling Log (Annexure-3)
- Microbiological Test Result Log (Annexure-4)
- Microbiological Deviation Report (Annexure-5)
- Corrective Action Log (Annexure-6)
- Training Log (Annexure-7)
- Compliance Audit Log (Annexure-8)
8. References
- 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals
- ICH Q7 – Good Manufacturing Practice for Active Pharmaceutical Ingredients
- USP <61>, <62>, <85> – Microbiological Examination of Non-Sterile Products, Endotoxin Testing
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Microbiological Material Storage Log
| Date | Material Name | Batch Number | Storage Location | Stored By |
|---|---|---|---|---|
| 01/02/2025 | Sterile API-X | API-X-2025-001 | Sterile Storage Area A | Ravi Kumar |
Annexure-2: Equipment Sterilization Log
| Date | Equipment Name | Sterilization Method | Sterilized By | Verified By (QA) |
|---|---|---|---|---|
| 01/02/2025 | Sampling Pipette | Autoclaving | Sunita Sharma | Anjali Mehta |
Annexure-3: Microbiological Sampling Log
| Date | Material Name | Batch Number | Sampled By | Verified By (QA) |
|---|---|---|---|---|
| 02/02/2025 | Sterile API-X | API-X-2025-001 | Ajay Singh | Anjali Mehta |
Annexure-4: Microbiological Test Result Log
| Date | Material Name | Batch Number | Test Performed | Result | Tested By |
|---|---|---|---|---|---|
| 03/02/2025 | Sterile API-X | API-X-2025-001 | Bioburden Testing | Within Limits | Sunita Sharma |
Annexure-5: Microbiological Deviation Report
| Date | Material Name | Batch Number | Deviation Description | Reported By |
|---|---|---|---|---|
| 03/02/2025 | Sterile API-X | API-X-2025-001 | Microbial Contamination Detected | Ajay Singh |
Annexure-6: Corrective Action Log
| Date | Deviation Description | Corrective Action | Implemented By | Verified By (QA) |
|---|---|---|---|---|
| 04/02/2025 | Microbial Contamination | Revised Aseptic Sampling Procedure | Ravi Kumar | Anjali Mehta |
Annexure-7: Training Log
| Date | Training Topic | Trainer | Attendee Name | Signature |
|---|---|---|---|---|
| 05/02/2025 | Aseptic Sampling and Microbiological Testing | Health & Safety Officer | Sunita Sharma |
Annexure-8: Compliance Audit Log
| Date | Audit Type | Findings | Corrective Actions Taken | Audited By |
|---|---|---|---|---|
| 06/02/2025 | Microbiological Compliance Audit | Non-Sterile Equipment Detected | Revised Equipment Sterilization SOP | Anjali Mehta |
Revision History:
| Revision Date | Revision No. | Revision Details | Reason for Revision | Approved By |
|---|---|---|---|---|
| 01/01/2024 | 1.0 | Initial Version | New SOP | QA Head |
| 01/02/2025 | 2.0 | Updated Microbiological Testing and Handling Procedures | Regulatory Compliance | QA Head |