Standard Operating Procedure for Microbial Testing of Injectable Products
| Department | Sterile Injectable Manufacturing |
|---|---|
| SOP No. | SOP/SIM/068/2025 |
| Supersedes | SOP/SIM/068/2022 |
| Page No. | Page 1 of 13 |
| Issue Date | 18/06/2025 |
| Effective Date | 20/06/2025 |
| Review Date | 18/06/2026 |
1. Purpose
To establish a standardized procedure for performing microbial testing of sterile injectable products, including sterility, bioburden, and microbial limits testing, in accordance with pharmacopeial guidelines.
2. Scope
This SOP applies to all finished injectable products manufactured in the sterile injectable facility requiring microbial testing as part of in-process,
finished product, or stability testing programs.
3. Responsibilities
- Microbiology Analyst: Conducts microbial tests according to validated procedures.
- QC Manager: Reviews data and ensures adherence to pharmacopeial requirements.
- QA Officer: Verifies documentation and reviews OOS or abnormal results.
4. Accountability
The Head of Quality Control is accountable for ensuring proper execution and documentation of microbial testing activities.
5. Procedure
5.1 Sample Collection
- Collect representative samples in sterile containers under aseptic conditions.
- Ensure that sample volume and container type meet testing requirements.
- Record details in the Sample Receipt Log (Annexure-1).
5.2 Sterility Testing
- Perform testing as per USP <71>, IP, or EP monograph.
- Use membrane filtration method or direct inoculation depending on product characteristics.
- Incubate media:
- Fluid Thioglycollate Medium (FTM): 30–35°C
- Soybean Casein Digest Medium (SCDM): 20–25°C
- Monitor for microbial growth for 14 days and document observations.
5.3 Bioburden Testing
- Determine microbial load prior to sterilization using:
- Membrane filtration
- Pour plate or spread plate method
- Calculate CFU/mL and compare with predefined acceptance criteria.
5.4 Microbial Limits Testing (MLT)
- Conduct MLT for non-sterile intermediates or stability samples.
- Perform Total Aerobic Microbial Count (TAMC), Total Yeast and Mold Count (TYMC), and tests for specified pathogens.
5.5 Result Interpretation and Documentation
- Document results in the Microbial Testing Report (Annexure-2).
- Compare observations against specifications as per pharmacopeia.
- Report OOS/OOT results to QA and initiate investigation.
5.6 Handling of Positive Results
- In case of microbial growth in sterility tests:
- Perform identification of organism.
- Initiate a deviation report and risk assessment.
- Repeat testing only upon justified approval by QA.
6. Abbreviations
- SOP: Standard Operating Procedure
- QC: Quality Control
- QA: Quality Assurance
- CFU: Colony Forming Units
- USP: United States Pharmacopeia
- MLT: Microbial Limit Testing
7. Documents
- Sample Receipt Log – Annexure-1
- Microbial Testing Report – Annexure-2
- Sterility Test Observation Log – Annexure-3
8. References
- USP <71> Sterility Tests
- Ph. Eur. 2.6.1, 2.6.12, 2.6.13
- WHO TRS 961 Annex 6
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | QC Microbiologist | QA Executive | Head QA |
| Department | Quality Control | Quality Assurance | Quality Assurance |
11. Annexures
Annexure-1: Sample Receipt Log
| Date | Batch No. | Product Name | Test Type | Received By |
|---|---|---|---|---|
| 15/06/2025 | INJ-2025-001 | Amikacin Injection | Sterility | Sunita Reddy |
Annexure-2: Microbial Testing Report
| Batch No. | Test Type | Result | Specification | Remarks |
|---|---|---|---|---|
| INJ-2025-001 | Sterility | No growth | No growth for 14 days | Pass |
Annexure-3: Sterility Test Observation Log
| Date | Batch No. | Medium | Incubation Temp. | Result | Tested By |
|---|---|---|---|---|---|
| 16/06/2025 | INJ-2025-001 | FTM | 30–35°C | No growth | Rajesh Kumar |
| 16/06/2025 | INJ-2025-001 | SCDM | 20–25°C | No growth | Rajesh Kumar |
Revision History
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 01/06/2022 | 1.0 | Initial version | New SOP | QA Head |
| 18/06/2025 | 2.0 | Added microbial limits section | Periodic Review | QA Head |