Standard Operating Procedure for Qualification of Filling Machines for Inhalers
1) Purpose
The purpose of this Standard Operating Procedure (SOP) is to define the process for qualifying filling machines used for the filling of inhaler products in pharmaceutical manufacturing. This SOP ensures that the filling machines are correctly installed, calibrated, and operate in compliance with the required specifications. The qualification process verifies that the filling machines meet the necessary operational parameters, including accurate dosing, container integrity, and batch consistency, ensuring that the inhaler products are filled and sealed according to regulatory and quality standards.
2) Scope
This SOP applies to the qualification of filling machines used for filling inhalers with active pharmaceutical ingredients (APIs) and excipients. The qualification includes Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ). This SOP is applicable to both new filling machines and those that have undergone significant repairs, upgrades, or relocations. The qualification ensures that the filling machine operates effectively, providing consistent fill accuracy, container integrity, and batch consistency under typical production conditions.
3) Responsibilities
Operators: Responsible for assisting in the IQ, OQ, and PQ processes, ensuring that the filling machine is operated according to the qualification protocols, and that
Quality Assurance (QA): Ensures that the IQ, OQ, and PQ of the filling machine are carried out in compliance with this SOP and meet 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 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 the filling machine meets all performance criteria.
Maintenance Personnel: Ensures that the filling machine is properly installed, calibrated, and maintained, 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 filling machines for inhalers:
1. Installation Qualification (IQ):
1.1 Review the filling machine’s specifications and manufacturer manuals to ensure that the equipment meets the necessary requirements for installation.
1.2 Verify that all required utilities (e.g., electrical power, compressed air, water, and gas) are available and meet the specifications required for operation.
1.3 Ensure that the installation site meets the required environmental conditions such as temperature, humidity, cleanliness, and space.
1.4 Confirm that all mechanical components are correctly installed, including the dosing system, valve filling mechanisms, and aerosol container handling systems.
1.5 Ensure that all electrical components, including sensors, actuators, control panels, and alarms, are correctly connected and functioning.
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 all operational controls, such as fill volume, fill speed, dosing accuracy, and system pressure, are properly set and calibrated.
2.2 Conduct a dry run of the filling machine to verify that it operates without issues. Monitor key parameters such as fill volume consistency, pressurization, and sealing mechanisms.
2.3 Test all control systems, ensuring that the start/stop, dosing, sealing, and system monitoring functions work correctly.
2.4 Inspect the filling process to ensure that the machine provides accurate fill volumes for each inhaler container and that the seals are intact.
2.5 Verify that the system can handle a range of container sizes and types without compromising the filling accuracy or the integrity of the product.
2.6 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., placebo or water) to monitor performance under typical production conditions.
3.2 Verify that the filling machine consistently delivers the required volume of product into each inhaler container, ensuring that there are no overfills or underfills.
3.3 Inspect the filled containers to ensure that they are properly sealed and that the integrity of each container is maintained.
3.4 Perform batch consistency tests to confirm that the dosage of the active ingredient is uniformly distributed across the batch.
3.5 Verify that the filling machine operates at the required throughput, meeting production speed without compromising product quality.
3.6 Document the results of the PQ, including fill volume consistency, container integrity, and any process deviations. 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 fill accuracy, container integrity, and product consistency.
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 filling process. This analysis should confirm that the filling machine operates consistently within predefined parameters and meets the acceptance criteria for dosage accuracy and batch uniformity.
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 filling machine’s performance.
5. Requalification:
5.1 Requalify the filling machine if significant changes are made to the equipment, such as replacing major components, relocating the machine, or modifying the filling process.
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
- Filling Process Records
- Container Integrity Inspection Logs
- Deviation and Corrective Action Reports
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: Filling Process Log
| Batch No. | Test Date | Fill Volume (mL) | Deviation (%) | Pass/Fail | Operator Initials |
|---|---|---|---|---|---|
| Batch Number | DD/MM/YYYY | Volume in mL | Deviation Percentage | Pass/Fail | Operator Name |
Template 3: Container Integrity Log
| Batch No. | Test Date | Seal Integrity (Pass/Fail) | Labeling Accuracy (Pass/Fail) | Operator Initials |
|---|---|---|---|---|
| Batch Number | DD/MM/YYYY | Pass/Fail | Pass/Fail | Operator Name |
