Standard Operating Procedure for Qualification of Isolators in Aseptic Areas
1) Purpose
The purpose of this Standard Operating Procedure (SOP) is to define the process for qualifying isolators used in aseptic areas within pharmaceutical manufacturing. This SOP ensures that the isolators are properly installed, calibrated, and operate according to the required specifications. The qualification process verifies that the isolators meet necessary parameters, including environmental control, sterility, and containment requirements, to ensure that aseptic processes are maintained and that the product is produced under controlled and sterile conditions in compliance with regulatory and quality standards.
2) Scope
This SOP applies to the qualification of isolators used in aseptic areas for the containment of sterile processes such as filling, compounding, or other critical operations involving sterile drug products. The qualification includes Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ). This SOP is applicable to both new isolators and those that have undergone significant maintenance, repairs, or relocations. The qualification ensures that the isolator functions effectively to protect against contamination and maintain the required aseptic environment during pharmaceutical manufacturing operations.
3) Responsibilities
Operators: Responsible for assisting in the IQ, OQ, and PQ processes, ensuring that the isolator is
Quality Assurance (QA): Ensures that the IQ, OQ, and PQ of the isolator 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 isolator 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 isolator meets all performance criteria.
Maintenance Personnel: Ensures that the isolator 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 isolators in aseptic areas:
1. Installation Qualification (IQ):
1.1 Review isolator 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, vacuum, nitrogen) 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 glove ports, air handling units, decontamination systems, and filtration systems.
1.5 Ensure that all electrical components, including control panels, sensors, and alarms, are correctly connected and functioning.
1.6 Perform a visual inspection to confirm that the isolator 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 airflow, pressure, temperature, and humidity, are properly set and calibrated.
2.2 Conduct a dry run of the isolator to verify that it operates without issues. Monitor key parameters such as airflow patterns, pressure differentials, and decontamination processes.
2.3 Test all control systems, ensuring that the start/stop, decontamination, and pressure regulation systems work correctly.
2.4 Inspect the isolator to ensure that it maintains the required sterility and containment levels, and that the airflow pattern is consistent throughout the chamber.
2.5 Verify that the isolator maintains the necessary pressure differential between the sterile and non-sterile zones.
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 isolator operation under typical production conditions using inert products or simulated product (e.g., sterile water or placebo solutions) to monitor performance.
3.2 Verify that the isolator maintains the required sterility and containment levels during the operation.
3.3 Perform microbiological testing to verify that the isolator effectively maintains a sterile environment during the processing of the product.
3.4 Test the isolator’s effectiveness at maintaining a controlled environment during simulated production runs.
3.5 Measure the environmental control system’s response to challenges such as air leaks or failures in filtration or pressure maintenance.
3.6 Document the results of the PQ, including microbial testing, sterility levels, and any deviations from expected performance. 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 sterility, containment, and environmental control.
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 isolator’s performance. This analysis should confirm that the isolator operates consistently within predefined parameters and meets the acceptance criteria for sterility and containment.
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 isolator’s performance.
5. Requalification:
5.1 Requalify the isolator if significant changes are made to the equipment, such as replacing major components, relocating the isolator, or modifying the aseptic 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
- Environmental Control Logs
- Microbial Testing Logs
- Decontamination Records
- 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: Environmental Control Log
| Batch No. | Test Date | Temperature (°C) | Pressure (Pa) | Humidity (%) | Operator Initials |
|---|---|---|---|---|---|
| Batch Number | DD/MM/YYYY | Temperature | Pressure | Humidity | Operator Name |
Template 3: Microbial Test Log
| Batch No. | Test Date | Microbial Load (CFU/mL) | Pass/Fail | Operator Initials |
|---|---|---|---|---|
| Batch Number | DD/MM/YYYY | Microbial Load | Pass/Fail | Operator Name |