testing is conducted in accordance with the SOP, ensuring equipment calibration, and verifying test results.

4. Accountability

The Production Manager is accountable for ensuring that inline microbial testing is conducted as per this SOP and that the samples are collected at appropriate intervals. The QC Manager is responsible for overseeing the testing and reviewing the results. The Laboratory Supervisor is accountable for ensuring the proper calibration and functionality of microbial testing equipment.

5. Procedure

5.1 Pre-Production Setup

1. Ensure that all required equipment for microbial testing, such as petri dishes, agar media, incubators, and swab kits, are available and functional before the start of production.
2. Verify that the microbial testing equipment is calibrated according to the manufacturer’s instructions and complies with GMP requirements.
3. Review the Batch Manufacturing Record (BMR) to ensure the specific microbial testing points, sample sizes, and testing intervals are clearly outlined and understood by the production and QC teams.

5.2 Sample Collection for Microbial Testing

1. During production, collect microbial samples from designated points in the production process, such as during mixing, after heating, or before packaging, as specified in the BMR.
2. Use sterile sampling methods, including sterile swabs or containers, to ensure that the samples are free from external contamination.
3. Record the sample collection time, batch number, operator name, and other relevant details in the Microbial Testing Log (Annexure-1).
4. Ensure that the samples are properly labeled with batch numbers and sample points to ensure traceability.

5.3 Performing Microbial Testing

1. Test the collected samples for microbial contamination using appropriate methods, such as agar plate count, membrane filtration, or rapid testing methods, as per regulatory guidelines.
2. Incubate samples at the appropriate temperature and for the specified time, following the standard procedures outlined in the BMR.
3. Monitor the growth of microbial colonies on the agar plates or other testing media and record the results, including the number of colonies and any microbial identification, if applicable.
4. Compare the microbial count results to the acceptable limits outlined in the product specification and regulatory requirements.

5.4 Handling Deviations

1. If microbial contamination exceeds acceptable limits, stop production immediately and investigate the cause of the contamination.
2. Determine whether the contamination is due to equipment, raw materials, environmental factors, or personnel practices.
3. Take corrective actions to eliminate the source of contamination, which may include equipment sanitization, improving hygiene practices, or changing raw materials.
4. Document all deviations and corrective actions in the Deviation Report (Annexure-2) and ensure that the report is reviewed and signed by the QA team before production resumes.

5.5 Post-Production Activities

1. Once microbial testing is completed and all results meet acceptable limits, approve the batch for the next stage in production, such as packaging and labeling.
2. Ensure that all test results are documented in the Microbial Testing Log (Annexure-1) and reviewed for completeness and accuracy by the QC team.
3. Store all microbial test results for future reference and audits, maintaining records for at least two years or as required by regulatory guidelines.

5.6 Documentation and Record-Keeping

1. Document all microbial testing activities, including sample collection, testing results, corrective actions, and approvals, in the Microbial Testing Log (Annexure-1).
2. Ensure that any deviations from the microbial testing standards are documented in the Deviation Report (Annexure-2), with a description of the problem, corrective actions, and resolution.
3. Ensure that all records are reviewed by the QC team for accuracy and completeness. Store all documentation in compliance with GMP requirements for traceability and auditing purposes.

6. Abbreviations

• GMP: Good Manufacturing Practices
• QC: Quality Control
• QA: Quality Assurance
• BMR: Batch Manufacturing Record
• PPE: Personal Protective Equipment

7. Documents

1. Annexure-1: Microbial Testing Log
2. Annexure-2: Deviation Report

8. References

• Good Manufacturing Practices (GMP) Guidelines – 21 CFR Part 211
• International Conference on Harmonisation (ICH) Q7 – Good Manufacturing Practice for Active Pharmaceutical Ingredients
• FDA Guidance for Industry: Microbial Control in Pharmaceutical Manufacturing

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Microbial Testing Log

Batch Number	Sample Point	Collection Time	Test Method	Result	Operator	Remarks
12345	Mixing Tank	09:00 AM	Agar Plate Count	No Growth	John Doe	Within specifications
12345	Post-Heating	09:30 AM	Membrane Filtration	No Growth	Jane Smith	Within specifications
12345	Pre-Packaging	10:00 AM	Agar Plate Count	3 CFU	Michael Lee	Acceptable, corrective action not required
12345	Post-Packaging	10:30 AM	Agar Plate Count	12 CFU	Michael Lee	Above acceptable limit, batch rejected

Annexure-2: Deviation Report

Batch Number	Deviation Description	Corrective Action	Resolved By
12345	Microbial contamination detected in post-packaging sample	Batch rejected, cleaned equipment, re-sampled	QA Head

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
01/03/2024	1.0	Initial Version	New SOP Creation	QA Head
01/03/2025	2.0	Format Revision and Updates	Standardization of Document	QA Head