Standard Operating Procedure for Qualification of Granulators (High-Shear and Oscillating)
1) Purpose
The purpose of this Standard Operating Procedure (SOP) is to define the process for qualifying high-shear and oscillating granulators used in pharmaceutical manufacturing. This SOP ensures that the granulators are installed, operate according to specifications, and perform consistently under normal production conditions, ensuring effective granulation of pharmaceutical powders. The qualification process includes verifying critical parameters such as granulation time, mixing speed, and product uniformity to guarantee that the granulation process yields products that meet regulatory and quality standards.
2) Scope
This SOP applies to the qualification of both high-shear and oscillating granulators used in the pharmaceutical industry for granulating active pharmaceutical ingredients (APIs), excipients, and other formulations. It covers the qualification process at all stages: Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ). The SOP is applicable to both new granulators and those that have undergone major repairs, upgrades, or relocations. The SOP includes the verification of mechanical and electrical components, operational parameters, and granulation performance during qualification runs.
3) Responsibilities
Operators: Responsible for assisting in the IQ, OQ, and PQ processes, ensuring that the granulators are operated according to the qualification protocol and that critical process parameters are monitored during testing.
Quality Assurance (QA): Ensures that the IQ, OQ, and PQ of the granulators are carried out in compliance with this SOP and meet all regulatory requirements. QA is also 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 equipment operates within specified parameters.
Validation Team: Responsible for developing the qualification protocols, executing the IQ, OQ, and PQ runs, and analyzing the results to ensure the granulators meet performance criteria.
Maintenance Personnel: Ensures that the granulators are 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 high-shear and oscillating granulators:
1. Installation Qualification (IQ):
1.1 Review equipment specifications and manufacturer manuals to ensure that the granulator meets the necessary requirements for installation.
1.2 Verify that the necessary utilities (e.g., electrical, compressed air, cooling water, etc.) are available and meet the specifications required for proper equipment 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 granulation chamber, mixing blades, and drive mechanisms.
1.5 Ensure that all electrical components are installed properly and that control systems, alarms, and emergency stops are functional.
1.6 Perform a visual inspection to confirm that the equipment is installed according to the manufacturer’s instructions and regulatory requirements.
1.7 Complete the IQ documentation, including checklists and equipment manuals, and ensure that all information is recorded and signed by responsible personnel.
2. Operational Qualification (OQ):
2.1 Verify that all operational controls, such as mixing speed, granulation time, and temperature (if applicable), are properly set and calibrated.
2.2 Conduct a dry run of the granulator to verify that it operates without issues. Monitor key parameters like mixing efficiency, vibration, and noise levels.
2.3 Test all control systems, ensuring that the start/stop, mixing speed, temperature control (if applicable), and emergency stop functions work correctly.
2.4 Inspect the mixing process during operation. Verify that the granulator is producing a uniform mixture and that there are no signs of clumping, segregation, or excessive heat buildup.
2.5 Check that the granulator produces consistent particle size during operation and that granulation is completed within the specified time.
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 granulation process using product or simulated product (such as inert powder) and monitor the performance under typical production conditions.
3.2 Measure the uniformity of the granulation process. Ensure that the blend consistency and homogeneity meet predefined criteria for the finished product.
3.3 Perform sampling during the granulation process and analyze the granule size distribution, moisture content, and particle shape.
3.4 Verify that the granulation process is producing consistent results across multiple cycles. Ensure that granules meet the required size range, moisture content, and uniformity.
3.5 Evaluate the granulation efficiency by comparing the results of the granulation uniformity and quality attributes against predefined specifications.
3.6 Document the results of the PQ, including sample results, any process 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 granulation uniformity, granule size, moisture content, and mixing speed.
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 granulation process. This analysis should confirm that the granulator operates consistently and produces granules that meet 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 granulator’s performance.
5. Requalification:
5.1 Requalify the granulators if significant changes are made to the equipment, such as replacing major components, relocating the machine, or modifying control systems.
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
- Granulation Process Records
- Granule Size Distribution Test Records
- Moisture Content and Uniformity Test Logs
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: Granulation Process Test Log
| Test Date | Granule Size (µm) | Moisture Content (%) | Granulation Time (minutes) | Uniformity (Pass/Fail) | Operator Initials |
|---|---|---|---|---|---|
| DD/MM/YYYY | Granule Size | Moisture Percentage | Granulation Time | Pass/Fail | Operator Name |
Template 3: Equipment Calibration and Maintenance Log
| Equipment Name | Calibration Date | Maintenance Performed | Next Calibration Date | Operator Initials |
|---|---|---|---|---|
| Granulator Model | DD/MM/YYYY | Maintenance Tasks | DD/MM/YYYY | Operator Name |
