Capsule: SOP for Conducting Residual Solvent Testing for Capsules – V 2.0

Standard Operating Procedure for Conducting Residual Solvent Testing for Capsules

Department	Capsule Manufacturing
SOP No.	SOP/CM/194/2025
Supersedes	SOP/CM/194/2022
Page No.	Page 1 of 8
Issue Date	01/02/2025
Effective Date	05/02/2025
Review Date	01/02/2026

1. Purpose

This SOP outlines the procedure for testing residual solvents in capsules to ensure that any solvent residues from the manufacturing process are within acceptable limits to comply with safety and regulatory standards.

2. Scope

This SOP applies to all capsule batches that require residual solvent testing to ensure they meet specified safety and quality standards, particularly concerning solvent residues from gelatin preparation or encapsulation processes.

3. Responsibilities

Quality Control (QC) Team: Responsible for conducting residual solvent testing on capsule samples and documenting the results.
Quality Assurance (QA) Team: Reviews the test results to ensure compliance with specified limits and regulatory requirements.
Production Team: Ensures that the capsule manufacturing process does not exceed the allowable limits for residual solvents and that capsules are properly sampled for testing.

4. Accountability

The QA Manager is accountable for ensuring the SOP’s adherence to regulatory standards. The QC Supervisor ensures the proper execution of residual

solvent testing, and the Production Supervisor ensures the quality of the manufacturing process and timely sample provision.

5. Procedure

5.1 Pre-Testing Setup

Before beginning residual solvent testing, ensure the following:

Review Residual Solvent Specifications
1. Review the residual solvent specifications based on regulatory guidelines (e.g., USP, EP) and the internal quality standards. These should be approved by the QA department before testing.
Prepare Testing Equipment
1. Ensure that the equipment used for testing residual solvents (e.g., gas chromatograph) is calibrated and in proper working condition.
2. Verify that all necessary solvents and standards are available for use in the testing procedure.
Prepare Sample Collection
1. Collect a representative sample of capsules, typically 10-20 capsules per batch, for testing. Ensure that the sample represents the entire batch and is randomly selected.

5.2 Residual Solvent Testing Procedure

Follow these steps to perform the residual solvent test:

Prepare Solvent Extraction
1. Extract the residual solvents from the capsules using an appropriate solvent, such as water, methanol, or ethanol, based on the solvent’s properties and the expected residuals.
2. Ensure that the extraction procedure is done under conditions that ensure maximum solvent recovery (e.g., shaking, heating if necessary).
Perform Gas Chromatography (GC) or Other Analytical Testing
1. Analyze the extracted sample using gas chromatography (GC) or another approved analytical technique (e.g., high-performance liquid chromatography – HPLC) to detect and quantify the residual solvents.
2. Ensure that the equipment used is calibrated according to standard protocols, and the analysis follows the relevant pharmacopoeial methods (e.g., USP <467> for residual solvents).
Record Results
1. Record the concentration of each residual solvent detected and calculate the total residual solvent content in the capsules.
2. Compare the results against the specified limits outlined in the applicable pharmacopoeia and internal quality standards.

5.3 Post-Testing Activities

After completing the residual solvent test, ensure the following:

Review Results
1. The QA Manager reviews the results to ensure that the residual solvent levels are within the specified limits. If the solvent levels exceed the allowable limits, the batch should be rejected.
Corrective Actions
1. If any capsules fail the residual solvent test, the root cause should be investigated (e.g., improper drying of gelatin, inadequate encapsulation process). Corrective actions, such as adjusting the process parameters, should be implemented.
Reporting
1. If required, report the residual solvent levels to the regulatory authorities, especially in cases of high residual levels or non-compliance.
Record Keeping
1. Ensure that all records related to residual solvent testing, including raw data, test results, and corrective actions, are properly stored and archived according to GMP and regulatory guidelines.

6. Abbreviations

SOP: Standard Operating Procedure
GMP: Good Manufacturing Practice
QA: Quality Assurance
QC: Quality Control
HPLC: High-Performance Liquid Chromatography
GC: Gas Chromatography
USP: United States Pharmacopeia
EP: European Pharmacopeia

7. Documents

Annexure 1: Equipment Calibration Log
Annexure 2: Residual Solvent Testing Log
Annexure 3: Corrective Action Report

8. References

USP <467> – Residual Solvents
European Pharmacopoeia 2.4.24 – Residual Solvents
Good Manufacturing Practice (GMP) Guidelines

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
GC System 205	01/02/2025	Jane Doe	Calibration of solvent detection and quantification system	01/02/2026

Annexure 2: Residual Solvent Testing Log

Capsule ID	Test Date	Solvent Detected	Solvent Level (ppm)	Result
Batch 008	02/02/2025	Ethyl acetate	15 ppm	Pass

Annexure 3: Corrective Action Report

Batch ID	Deviation	Corrective Action	Responsible Person	Completion Date
Batch 008	Excess residual solvent	Adjusted drying time and encapsulation parameters	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 residual solvent testing	QA Head
01/02/2025	2.0	Updated testing procedure and log format	Improvement of testing accuracy and compliance	QA Head