Standard Operating Procedure for Heavy Metal Testing of Capsule Materials

Department	Capsule Manufacturing
SOP No.	SOP/CM/186/2025
Supersedes	SOP/CM/186/2022
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 performing heavy metal testing on capsule materials to ensure that the levels of potentially toxic metals, such as lead, mercury, arsenic, and cadmium, do not exceed the acceptable limits.

2. Scope

This SOP applies to the testing of all capsule raw materials and finished products to ensure that they comply with regulatory standards for heavy metal contamination.

3. Responsibilities

• Quality Control (QC) Team: Responsible for performing heavy metal testing on raw materials, intermediate, and finished capsule products. QC ensures the tests are conducted accurately and documented properly.
• Quality Assurance (QA) Team: Reviews test results, ensures compliance with regulatory standards, and approves or rejects capsule batches based on the results.
• Production Team: Provides raw material and capsule samples for heavy metal testing at the specified intervals.

4. Accountability

The QA Manager is accountable for ensuring that the heavy metal testing procedure complies with GMP and regulatory standards. The QC Supervisor is responsible for the execution of heavy metal testing, ensuring that sampling and testing are carried out accurately. The Production Supervisor ensures that the required samples are collected and submitted to QC in a timely manner.

5. Procedure

5.1 Pre-Testing Setup

Before starting the heavy metal test, ensure the following:

1. Review Test Criteria
   1. Review the heavy metal limits as per regulatory guidelines (e.g., USP, EP) for the raw materials and capsules. These limits must be approved by the QA department before testing.
2. Prepare Testing Equipment
   1. Ensure all laboratory equipment, such as atomic absorption spectrometers (AAS) or inductively coupled plasma mass spectrometers (ICP-MS), is calibrated and functioning properly. Record calibration in the Equipment Calibration Log (Annexure 1).
3. Prepare Sample Collection
   1. Obtain representative samples of raw materials or finished capsules according to the sampling plan (usually 10-20 capsules or a specified weight of raw material).

5.2 Heavy Metal Testing Procedure

Follow these steps to perform heavy metal testing:

1. Sample Preparation
   1. Open the capsules and remove the fill material, if necessary. Weigh a sufficient quantity of material (e.g., 1g of capsule fill) and transfer it into a clean container.
2. Digestion of Sample
   1. Digest the sample using an appropriate acid mixture (e.g., nitric acid) in a digestion vessel. The digestion process should break down the sample and make the heavy metals soluble in solution.
3. Analyze for Heavy Metals
   1. Perform the analysis using atomic absorption spectroscopy (AAS) or inductively coupled plasma mass spectrometry (ICP-MS) to detect and quantify heavy metals (e.g., lead, arsenic, mercury, cadmium) in the sample.
4. Compare to Acceptance Limits
   1. Compare the results with the predefined regulatory limits. The concentration of each heavy metal must not exceed the allowable limits as specified by the regulatory authority (e.g., USP, EP).
5. Document Results
   1. Record the test results in the Heavy Metal Testing Log (Annexure 2), including the sample details, heavy metal concentration, and any deviations from the limits.

5.3 Post-Testing Activities

After completing the heavy metal testing, ensure the following:

1. Review Test Results
   1. The QA Manager reviews the test results to ensure compliance with regulatory limits. If any heavy metals exceed the acceptable limits, the batch will be rejected, and an investigation will be initiated.
2. Corrective Actions
   1. If the heavy metal test fails, the production team must identify the source of contamination (e.g., raw material, equipment) and implement corrective actions to prevent recurrence.
3. Training and Feedback
   1. If deviations are identified in the testing process, provide feedback to the operators and provide additional training to ensure that the procedures are followed properly.
4. Record Keeping
   1. Ensure all heavy metal testing records are properly filed and archived, including test logs, corrective actions, and batch details, as per regulatory requirements.

6. Abbreviations

• SOP: Standard Operating Procedure
• GMP: Good Manufacturing Practice
• QA: Quality Assurance
• QC: Quality Control
• ICP-MS: Inductively Coupled Plasma Mass Spectrometry
• AAS: Atomic Absorption Spectrometry

7. Documents

1. Annexure 1: Equipment Calibration Log
2. Annexure 2: Heavy Metal Testing Log
3. Annexure 3: Corrective Action Report

8. References

• FDA Guidance on Heavy Metal Testing for Pharmaceutical Products
• Good Manufacturing Practice (GMP) Guidelines
• USP <231> – Heavy Metals
• EP 2.4.8 – Heavy Metals Test

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
ICP-MS 303	01/02/2025	John Doe	Calibration of mass spectrometer	01/02/2026

Annexure 2: Heavy Metal Testing Log

Capsule ID	Test Date	Heavy Metal (Lead) (mg)	Heavy Metal (Mercury) (mg)	Result	Remarks
Batch 001	02/02/2025	0.05	0.02	Pass	No contamination

Annexure 3: Corrective Action Report

Batch ID	Deviation Type	Corrective Action	Responsible Person	Completion Date
Batch 001	Excessive heavy metal contamination	Investigated raw material source and adjusted process	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 heavy metal testing	QA Head
01/02/2025	2.0	Updated testing methods and limits	Enhanced test methods and compliance	QA Head