Standard Operating Procedure for IQ/OQ/PQ of Cryogenic Storage Systems

1) Purpose

The purpose of this Standard Operating Procedure (SOP) is to define the process for the Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ) of cryogenic storage systems used in pharmaceutical manufacturing. This SOP ensures that cryogenic storage systems are correctly installed, calibrated, and operate in compliance with regulatory and operational requirements. The qualification process verifies that the cryogenic systems are capable of maintaining the required low temperatures for the safe storage of temperature-sensitive products, such as biologics, vaccines, and other pharmaceuticals, ensuring product integrity and stability.

2) Scope

This SOP applies to the qualification of cryogenic storage systems used for the long-term storage of temperature-sensitive pharmaceutical products. The qualification includes Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ). This SOP is applicable to both new cryogenic storage systems and those that have undergone significant repairs, upgrades, or relocations. The qualification ensures that the cryogenic systems maintain the required temperatures, have functional safety systems, and are compliant with GMP and regulatory standards for storage.

3) Responsibilities

Operators: Responsible for assisting in the IQ, OQ, and PQ processes, ensuring that the cryogenic storage system is operated according to the qualification protocols, and that critical parameters are monitored and recorded during testing.
Quality Assurance (QA): Ensures that the IQ, OQ, and PQ of the cryogenic storage system 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 cryogenic system 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 cryogenic storage system meets all performance criteria.
Maintenance Personnel: Ensures that the cryogenic storage system 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 cryogenic storage systems:

1. Installation Qualification (IQ):
1.1 Review the cryogenic storage system specifications and manufacturer manuals to ensure that the equipment meets the necessary installation requirements.
1.2 Verify that all required utilities (e.g., electrical power, liquid nitrogen supply, or other cryogenic gases) 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 temperature monitoring systems, refrigeration units, cryogenic gas tanks, and safety systems.
1.5 Ensure that all electrical components, including controllers, alarms, sensors, and temperature data loggers, 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 temperature settings, gas flow, and system alarms, are correctly set and calibrated.
2.2 Conduct a dry run of the cryogenic storage system to verify that it operates without issues. Monitor key parameters such as temperature, gas flow, and the system’s response to alarms.
2.3 Test all control systems, ensuring that the temperature regulation, alarm systems, and safety cut-offs work correctly.
2.4 Inspect the cryogenic storage system to ensure that it consistently maintains the specified temperature ranges under different operational conditions.
2.5 Verify that the system can handle a range of operating conditions, including changes in load and environmental conditions.
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 a test run of the cryogenic storage system with actual product or simulated product (e.g., temperature sensors or frozen vials) to monitor performance under typical storage conditions.
3.2 Verify that the cryogenic storage system consistently maintains the required storage temperatures, including assessing temperature uniformity across different areas within the storage system.
3.3 Test the system’s response to environmental fluctuations or potential system failures, such as loss of liquid nitrogen supply or a power failure.
3.4 Perform microbiological testing or stability testing (where applicable) to verify that the storage process maintains product integrity and sterility over time.
3.5 Verify that the system maintains the required low temperatures over extended periods, ensuring that stored products remain within their stability limits.
3.6 Document the results of the PQ, including temperature profiles, product 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 temperature, pressure, and storage conditions.
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 cryogenic storage system. This analysis should confirm that the system operates consistently within predefined parameters and meets the acceptance criteria for product storage.
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 cryogenic storage system’s performance.

5. Requalification:
5.1 Requalify the cryogenic storage system if significant changes are made to the equipment, such as replacing major components, relocating the system, or modifying the storage parameters.
5.2 Periodically perform requalification to ensure that the system 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
• Temperature and Pressure Logs
• Product Integrity Test 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

Template 2: Cryogenic Storage Log

Template 3: Product Stability Log