Capsule: SOP for Process Validation for Multi-Layer Capsule Filling – V 2.0

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Capsule: SOP for Process Validation for Multi-Layer Capsule Filling – V 2.0

Standard Operating Procedure for Process Validation for Multi-Layer Capsule Filling

Department Capsule Manufacturing
SOP No. SOP/CM/154/2025
Supersedes SOP/CM/154/2022
Page No. Page 1 of 8
Issue Date 01/02/2025
Effective Date 05/02/2025
Review Date 01/02/2026

1. Purpose

The purpose of this SOP is to provide detailed instructions for the validation of the multi-layer capsule filling process. Multi-layer capsules are used to deliver active pharmaceutical ingredients (APIs) in layers, which can be critical for specific release profiles. This SOP ensures that the multi-layer filling process is consistently reproducible and meets the required quality attributes, including uniformity, stability, and dosage accuracy.

2. Scope

This SOP applies to the process of filling multi-layer capsules in the manufacturing environment. It covers the validation of the equipment, materials, and processes involved in the multi-layer filling process. This SOP ensures that all parameters are optimized and validated to ensure the capsules meet the desired specifications.

3. Responsibilities

  • Production Operators: Responsible for executing the multi-layer capsule filling process as per SOP and ensuring that all process parameters are maintained during the validation runs.
  • Quality Control (QC) Team: Conducts quality tests on the capsules to ensure they meet uniformity, content, and release specifications. The QC team also ensures that the validation results are documented and meet the established criteria.
  • Quality Assurance (QA) Team: Reviews and approves the validation plan, ensures that the process complies with GMP standards, and verifies that the validation results are documented correctly.
  • Engineering Team: Ensures that the capsule filling machines and related equipment are calibrated, maintained, and set up correctly for the validation process.

4. Accountability

The Capsule Manufacturing Supervisor is responsible for ensuring that the multi-layer filling process is validated according to this SOP. The QA Manager is responsible for reviewing and approving the validation results to ensure compliance with GMP standards.

See also  Capsule: SOP for Operating Capsule Filling Machines - V 2.0

5. Procedure

5.1 Preparation for Multi-Layer Capsule Filling Validation

Before starting the validation, ensure the following preparations are made:

  1. Review Validation Plan

    1. Ensure that the multi-layer capsule filling validation plan includes the objectives, materials, equipment, process parameters, and the criteria for validation acceptance. The validation plan should be reviewed and approved by the QA department.
  2. Gather Materials and Equipment

    1. Ensure that all materials, including active pharmaceutical ingredients (APIs), excipients, and capsule shells, are available and meet the quality specifications for the validation study.
    2. Verify that the capsule filling machine is prepared and calibrated for multi-layer filling. Ensure that all equipment such as weighing scales, mixing units, and encapsulation machines are ready for use and documented in the Equipment Calibration Log (Annexure-1).
  3. Calibrate Equipment

    1. Ensure that the capsule filling machine is properly calibrated according to the required parameters for multi-layer filling, including layer separation, fill volume, and uniformity. Calibration details should be recorded in the Equipment Calibration Log (Annexure-1).

5.2 Multi-Layer Capsule Filling Validation Process

Follow these steps to perform the multi-layer capsule filling validation:

  1. Perform Pre-Validation Setup

    1. Set up the capsule filling machine according to the SOP for equipment operation. Verify that the machine is properly configured to fill capsules with multiple layers of API and excipients.
    2. Ensure that the environment in which the filling process is carried out is controlled, with stable temperature, humidity, and air quality. Record environmental conditions in the Environmental Monitoring Log (Annexure-2).
  2. Initiate Multi-Layer Filling Process

    1. Initiate the filling process by loading the prepared materials into the capsule filling machine. Ensure that the layers are being filled as per the specified weight and volume for each layer.
    2. Monitor the machine for any irregularities such as blockages, uneven filling, or incorrect layer separation. Record observations in the Filling Process Log (Annexure-3).
  3. Monitor Key Process Parameters

    1. During the validation runs, monitor key parameters such as layer fill weight, capsule integrity, and layer separation. Ensure that these parameters are within the acceptable limits specified in the validation plan.
    2. Monitor capsule weight, content uniformity, and fill volume, and ensure that they meet the predetermined specifications. Record results in the Capsule Filling Validation Log (Annexure-4).
  4. Conduct Quality Control Testing

    1. After each batch, perform QC testing on the capsules to assess their uniformity, weight, fill content, and integrity. Perform dissolution, disintegration, and other relevant tests to ensure that the multi-layer capsules meet the required specifications.
    2. Record all test results in the Multi-Layer Capsule QC Report (Annexure-5) and compare them with the acceptance criteria outlined in the validation plan.
  5. Assess Results and Approve Validation

    1. Review the results from the validation runs, ensuring that all process parameters and quality attributes meet the established criteria. If results are satisfactory, approve the process for routine use in production.
    2. If any deviations or non-conformances are identified, take corrective actions and revalidate the process as necessary.
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5.3 Post-Validation Documentation

Ensure proper documentation of the validation process:

  1. Validation Report

    1. Prepare a comprehensive Process Validation Report (Annexure-6) that includes the results of the validation activities, the performance of the equipment, and the outcomes of the quality control tests.
  2. Validation Approval

    1. Have the validation report reviewed and approved by the QA Manager to ensure that the multi-layer capsule filling process is compliant with GMP and regulatory standards.

5.4 Documentation

Ensure that all steps of the multi-layer filling process are properly documented for traceability and regulatory compliance:

  1. Process Validation Log

    1. Document all validation activities, including setup, filling, and testing, in the Process Validation Log (Annexure-4).
  2. Filling Process Log

    1. Document the operational parameters and any deviations observed during the filling process in the Filling Process Log (Annexure-3).
  3. Quality Control Report

    1. Document the quality control test results in the Multi-Layer Capsule QC Report (Annexure-5).
  4. Process Validation Report

    1. Complete the Process Validation Report (Annexure-6) and ensure it is signed and approved by the QA Manager.
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6. Abbreviations

  • SOP: Standard Operating Procedure
  • GMP: Good Manufacturing Practice
  • QC: Quality Control
  • QA: Quality Assurance
  • PPE: Personal Protective Equipment
  • API: Active Pharmaceutical Ingredient
  • RPM: Revolutions Per Minute

7. Documents

  1. Process Validation Report (Annexure-6)
  2. Process Validation Log (Annexure-4)
  3. Filling Process Log (Annexure-3)
  4. Quality Control Report (Annexure-5)
  5. Equipment Calibration Log (Annexure-1)

8. References

  • USP <1163> – Pharmaceutical Dosage Forms: Capsules
  • FDA Guidelines for Capsule Manufacturing
  • 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-4: Process Validation Log

Batch ID Validation Date Operator Test Parameters Results
Batch 001 02/02/2025 John Doe Layer weight, fill volume Pass

Annexure-3: Filling Process Log

Batch ID Process Date Operator Parameters Monitored Corrective Actions
Batch 001 02/02/2025 Jane Smith Layer separation, uniformity No corrections

Annexure-5: Multi-Layer Capsule QC Report

Batch ID QC Test Date Test Results Remarks
Batch 001 02/02/2025 Pass All tests passed within specification

Annexure-6: Process Validation Report

Batch ID Validation Date Operator Validation Criteria Results
Batch 001 02/02/2025 John Doe Layer weight, fill content, capsule integrity Pass

Annexure-1: Equipment Calibration Log

Equipment ID Calibration Date Operator Calibration Details Next Calibration Due
Capsule Filler 001 02/02/2025 Jane Smith Weight calibration for multi-layer capsules 02/02/2026

Revision History:

Revision Date Revision No. Revision Details Reason for Revision Approved By
01/01/2024 1.0 Initial version New SOP Creation QA Head
01/02/2025 2.0 Updated multi-layer capsule validation procedure Improved validation criteria QA Head
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