Standard Operating Procedure for Qualification of Capsule Filling Machines
1) Purpose
The purpose of this Standard Operating Procedure (SOP) is to define the process for qualifying capsule filling machines used in pharmaceutical manufacturing. This SOP ensures that the capsule filling machines are installed, operated, and perform consistently under normal production conditions, ensuring that the process of filling capsules with powders, granules, or other formulations meets the required regulatory and quality standards. The qualification includes verification of mechanical components, operational parameters, and performance during typical production runs.
2) Scope
This SOP applies to the qualification of all capsule filling machines used in pharmaceutical manufacturing for filling capsules with active pharmaceutical ingredients (APIs) and excipients. It includes the Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ) processes. The SOP is applicable to both new machines and those that have undergone significant repairs, modifications, or relocations. It covers the verification of critical process parameters such as filling accuracy, capsule weight, and fill uniformity.
3) Responsibilities
Operators: Responsible for assisting with the IQ, OQ, and PQ processes, ensuring that the capsule filling machines are operated in compliance with the qualification protocols and that critical parameters are monitored and recorded during
Quality Assurance (QA): Ensures that the qualification of the capsule filling machines is carried out in compliance with this SOP and meets all regulatory requirements. QA is responsible for reviewing and approving all qualification reports and documentation.
Production Supervisors: Oversee the qualification processes to ensure that operators follow the protocol and that the capsule filling machine operates within the specified parameters.
Validation Team: Responsible for developing the qualification protocols, executing the IQ, OQ, and PQ runs, and analyzing the results to ensure that the capsule filling machine meets all performance criteria.
Maintenance Personnel: Ensures that the capsule filling machine is properly installed, maintained, and calibrated, and that all mechanical and electrical systems are functioning correctly during the qualification process.
4) Procedure
The following steps should be followed for the IQ, OQ, and PQ of capsule filling machines:
1. Installation Qualification (IQ):
1.1 Review equipment specifications and manufacturer manuals to ensure that the capsule filling machine meets the necessary requirements for installation.
1.2 Verify that all required utilities (e.g., electrical, air, vacuum, and water systems) are available and meet the specifications required for machine operation.
1.3 Ensure that the installation site meets the required environmental conditions such as temperature, humidity, cleanliness, and space requirements.
1.4 Confirm that all mechanical components are correctly installed, including the hopper, dosing systems, capsule handling mechanisms, and filling stations.
1.5 Ensure that all electrical components are properly connected, and that control systems, alarms, and emergency stop functions are in place and operational.
1.6 Perform a visual inspection to confirm that the equipment is installed according to the manufacturer’s instructions and that all components are intact.
1.7 Complete the IQ documentation, including checklists, equipment manuals, and relevant installation records, ensuring that all information is recorded and signed off by responsible personnel.
2. Operational Qualification (OQ):
2.1 Verify that the operational controls, including capsule loading, dosing, filling, sealing, and ejection systems, are properly set and calibrated.
2.2 Conduct an empty run of the capsule filling machine to verify that it operates without issues. Monitor key parameters such as motor function, capsule alignment, and filling speed.
2.3 Test all control systems, ensuring that the start/stop, filling controls, capsule alignment, and emergency stop functions are working correctly.
2.4 Inspect the filling process to ensure that the capsules are being filled accurately. Check that the dosage meets the specified limits for weight and uniformity.
2.5 Verify the consistency of capsule filling by checking the weight of filled capsules and inspecting for any missing or overfilled capsules.
2.6 Ensure that the capsule filling machine operates without excessive vibrations, abnormal noise, or overheating during the run.
2.7 Document the results of the OQ, noting any deviations or issues encountered and corrective actions taken.
3. Performance Qualification (PQ):
3.1 Conduct the filling process using product or simulated product (e.g., inert powder) and monitor the performance under typical production conditions.
3.2 Perform sampling during the filling process to measure the weight of the filled capsules. Ensure that the capsule weight falls within the acceptable range as specified in the product formula.
3.3 Verify that the capsule fill weight is consistent across multiple runs and that the machine operates efficiently within predefined fill times.
3.4 Perform fill uniformity testing to assess the consistency of the fill weight across all capsules in a batch. This may include checking the fill weight variance and ensuring it meets predefined acceptance limits.
3.5 Conduct a final inspection to confirm that no capsules are damaged, broken, or improperly sealed during the process.
3.6 Document the results of the PQ, including sample results, any deviations, and corrective actions taken. Ensure that all records are signed and reviewed by responsible personnel.
4. Documentation and Reporting:
4.1 Record all data during the IQ, OQ, and PQ processes, including batch records, equipment logs, process parameters, and inspection results for capsule weight, fill uniformity, and capsule integrity.
4.2 Ensure that all forms, reports, and certificates are completed and signed by responsible personnel.
4.3 Perform statistical analysis on the collected data to assess the consistency and reliability of the capsule filling process. This analysis should confirm that the machine operates consistently within the predefined parameters and meets the acceptance criteria.
4.4 Prepare a final qualification report, summarizing the results of the IQ, OQ, and PQ, including any deviations, corrective actions, and conclusions regarding the capsule filling machine’s operational capabilities.
5. Requalification:
5.1 Requalify the capsule filling machine if significant changes are made to the equipment, such as replacing major components, relocating the machine, or modifying the filling system.
5.2 Periodically perform requalification to ensure that the equipment continues to perform as expected and remains in compliance with regulatory requirements.
5) Abbreviations
- IQ: Installation Qualification
- OQ: Operational Qualification
- PQ: Performance Qualification
- QA: Quality Assurance
- SOP: Standard Operating Procedure
6) Documents
- IQ/OQ/PQ Protocol
- Equipment Manufacturer Specifications
- Installation and Setup Reports
- Calibration Records
- Capsule Filling Process Records
- Capsule Weight Testing Logs
- Fill Uniformity Test Records
7) Reference
- FDA Guidance for Industry: Equipment Qualification
- International Council for Harmonisation (ICH) Q7: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
- ISO 9001: Quality Management Systems – Requirements
- USP Chapter 1151: Pharmaceutical Dosage Forms
8) SOP Version
Version 1.0 – Effective Date: DD/MM/YYYY
Annexure
Template 1: IQ/OQ/PQ Test Record
| Date | Time | Operator Initials | Test Type (IQ/OQ/PQ) | Test Results | Comments |
|---|---|---|---|---|---|
| DD/MM/YYYY | HH:MM | Operator Name | IQ/OQ/PQ | Pass/Fail | Comments |
Template 2: Capsule Weight and Fill Uniformity Log
| Batch No. | Test Date | Weight (mg) | Uniformity (Pass/Fail) | Operator Initials |
|---|---|---|---|---|
| Batch Number | DD/MM/YYYY | Capsule Weight | Pass/Fail | Operator Name |
Template 3: Capsule Inspection and Performance Log
| Batch No. | Inspection Date | Inspection Method | Result | Operator Initials |
|---|---|---|---|---|
| Batch Number | DD/MM/YYYY | Method | Pass/Fail | Operator Name |