Microbiological Stability Testing of Liposomes
1) Purpose
The purpose of this SOP is to outline the procedure for conducting microbiological stability testing on liposome formulations. This testing ensures that the liposomes remain free from microbial contamination during storage, thereby maintaining product quality and safety over the defined shelf life.
2) Scope
This SOP applies to personnel involved in the microbiological testing of liposomal formulations, including quality control and microbiology teams. It covers the evaluation of microbial contamination over time and ensures compliance with regulatory standards for sterile or non-sterile formulations.
3) Responsibilities
- QC Microbiology Team: Responsible for performing microbiological tests at specified intervals and documenting the results.
- QA Team: Responsible for reviewing and approving the test results and ensuring compliance with GMP standards.
- Formulation Scientists: Responsible for preparing sterile samples for microbiological testing and ensuring that the production process complies with microbial control procedures.
4) Procedure
4.1 Sample Preparation
- 4.1.1 Prepare liposomal formulations in sterile containers, ensuring that samples are representative of the production batch.
- 4.1.2 Label the samples with the batch number, preparation date, and storage conditions.
- 4.1.3 Store samples under controlled conditions as required by the stability testing protocol (e.g., 25°C/60% RH, 40°C/75% RH).
4.2 Microbiological Testing Parameters
The following microbiological tests should be performed at specified
intervals to monitor contamination levels:
- 4.2.1 Total Aerobic Microbial Count (TAMC): Perform microbial enumeration to determine the total number of viable aerobic microorganisms in the liposomal formulation.
- 4.2.2 Total Yeast and Mold Count (TYMC): Perform microbial enumeration to determine the total number of viable yeast and mold colonies.
- 4.2.3 Pathogen Detection: Test for the presence of specific pathogens (e.g., Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli) using selective media.
4.3 Testing Schedule
- 4.3.1 Initial Test: Conduct microbiological tests immediately after formulation preparation to establish a baseline for contamination levels.
- 4.3.2 Interim Tests: Perform microbiological testing at specified intervals (e.g., 1 month, 3 months, 6 months) during storage under various conditions.
- 4.3.3 Final Test: Conduct a final microbiological test at the end of the stability study (e.g., 12 months) to confirm product sterility or bioburden.
4.4 Data Recording and Analysis
- 4.4.1 Record all test results in the Microbiological Stability Test Report (see Annexure 1 for the template).
- 4.4.2 Compare the results against the baseline and regulatory limits to assess microbiological stability over time.
- 4.4.3 Analyze any trends in microbial growth to determine the risk of contamination and evaluate the effectiveness of the preservation system.
4.5 Acceptance Criteria for Microbiological Stability
The liposomal formulation is considered microbiologically stable if the following criteria are met throughout the study:
- 4.5.1 The total aerobic microbial count (TAMC) remains within acceptable limits (as defined by regulatory guidelines).
- 4.5.2 The total yeast and mold count (TYMC) remains within acceptable limits.
- 4.5.3 No specific pathogens are detected during the study period.
5) Abbreviations
- TAMC: Total Aerobic Microbial Count
- TYMC: Total Yeast and Mold Count
- QC: Quality Control
- QA: Quality Assurance
6) Documents
- Microbiological Stability Test Report
- Batch Manufacturing Record (BMR)
- Microbial Enumeration Test Report
- Pathogen Detection Report
7) References
- USP <61>: Microbiological Examination of Non-Sterile Products
- ICH Q6A: Specifications for New Drug Substances and Products
8) SOP Version
Version 1.0
Annexure
Annexure 1: Microbiological Stability Test Report Template
| Time Point | Storage Condition | TAMC (cfu/mL) | TYMC (cfu/mL) | Pathogens | Operator Initials |
|---|---|---|---|---|---|
| Initial | 25°C/60% RH | Below Limit | Below Limit | None | Operator Name |
| 1 Month | 40°C/75% RH | Below Limit | Below Limit | None | Operator Name |
| 3 Months | 40°C/75% RH | Below Limit | Below Limit | None | Operator Name |