Standard Operating Procedure for Microbial Limit Testing for Capsules

Department	Capsule Manufacturing
SOP No.	SOP/CM/185/2025
Supersedes	SOP/CM/185/2022
Page No.	Page 1 of 9
Issue Date	01/02/2025
Effective Date	05/02/2025
Review Date	01/02/2026

1. Purpose

This SOP defines the procedure for conducting microbial limit testing on capsules to ensure that the product complies with microbiological standards and is safe for consumer use.

2. Scope

This SOP applies to the microbial limit testing of all capsule batches to ensure compliance with the regulatory limits for microbial contamination.

3. Responsibilities

• Quality Control (QC) Team: Responsible for performing the microbial limit testing and ensuring that the capsules meet the defined microbiological specifications.
• Quality Assurance (QA) Team: Ensures the test criteria and methods comply with regulatory requirements and approves the results.
• Production Team: Provides capsule samples for microbial limit testing at the appropriate stages of production and ensures proper handling during the sampling process.

4. Accountability

The QA Manager is responsible for ensuring the microbial limit testing process complies with GMP and regulatory standards. The QC Supervisor is responsible for the proper execution of the microbial testing procedure. The Production Supervisor ensures proper sampling of capsules for microbial testing.

5. Procedure

5.1 Pre-Testing Setup

Before initiating microbial limit testing, the following steps should be completed:

1. Review Microbial Testing Criteria
   1. Review the microbial limits based on regulatory requirements (e.g., USP, EP). The limits must be approved by the QA department before initiating testing.
2. Prepare Testing Equipment
   1. Ensure all microbiological testing equipment (e.g., incubators, petri dishes, sterile tools) is clean and calibrated. Document calibration in the Equipment Calibration Log (Annexure 1).
3. Prepare Sample Collection
   1. Collect a representative sample of capsules, ensuring that the sample is randomly selected. Typically, 10-20 capsules are required for testing.

5.2 Microbial Limit Testing Procedure

Follow these steps for conducting microbial limit testing:

1. Sample Preparation
   1. Carefully open each selected capsule and remove the fill material. Weigh the material if necessary and transfer it to a sterile container or broth for testing.
2. Microbial Culturing
   1. Inoculate the sample with an appropriate medium to allow microbial growth. Incubate the samples at the required temperature for the specified time as per the testing standard (e.g., 37°C for 48 hours for total aerobic microbial count).
3. Microbial Identification
   1. After incubation, examine the culture plates for microbial growth. Perform microbial identification (e.g., using Gram staining, biochemical tests) if necessary to confirm the type of contamination.
4. Quantification of Microbial Content
   1. Count the number of colonies that have grown. Compare the microbial load with the predefined acceptance criteria (e.g., no more than 100 CFU/g for total aerobic bacteria).
5. Document Results
   1. Record the results of microbial testing in the Microbial Limit Testing Log (Annexure 2). Document the number of colonies, any deviations, and the corrective actions taken.

5.3 Post-Testing Activities

After completing microbial limit testing, ensure the following actions are performed:

1. Review Results
   1. The QA Manager reviews the test results and ensures that the capsules comply with the defined microbial limits. If any capsules exceed the limits, initiate an investigation into the cause.
2. Corrective Actions
   1. If microbial contamination exceeds acceptable limits, investigate the source of contamination (e.g., raw materials, environment, equipment) and implement corrective actions such as adjusting manufacturing processes or sterilization procedures.
3. Training and Feedback
   1. If errors are identified in the process, provide feedback and additional training to the operators to ensure that the procedures are followed correctly.
4. Record Keeping
   1. Ensure that all records related to microbial testing, including the test logs, results, and corrective actions, are archived according to regulatory and company requirements.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QA: Quality Assurance
• QC: Quality Control
• CFU: Colony Forming Units
• USP: United States Pharmacopeia
• EP: European Pharmacopeia

7. Documents

1. Annexure 1: Equipment Calibration Log
2. Annexure 2: Microbial Limit Testing Log
3. Annexure 3: Corrective Action Report

8. References

• FDA Guidance on Microbial Limit Testing
• Good Manufacturing Practice (GMP) Guidelines
• USP <61> – Microbiological Examination of Nonsterile Products
• EP 2.6.12 – Microbial Limit Tests

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure 1: Equipment Calibration Log

Equipment ID	Calibration Date	Operator	Calibration Details	Next Calibration Due
Incubator 502	01/02/2025	John Doe	Calibration of temperature range	01/02/2026

Annexure 2: Microbial Limit Testing Log

Capsule ID	Test Date	Microbial Count (CFU/g)	Acceptable Limit	Result	Remarks
Batch 001	02/02/2025	50	100 CFU/g	Pass	No contamination

Annexure 3: Corrective Action Report

Batch ID	Deviation	Corrective Action	Responsible Person	Completion Date
Batch 001	Excess microbial contamination	Investigation and equipment cleaning	Production Supervisor	03/02/2025

12. Revision History

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
01/01/2024	1.0	Initial version of SOP	Creation of SOP for microbial limit testing	QA Head
01/02/2025	2.0	Updated microbial limit testing method	Refined testing process and record keeping	QA Head