Utilities are essential support systems in pharmaceutical manufacturing, providing the necessary resources for production processes, research and development, and facility maintenance.¹ These systems, which include clean compressed air, steam, waste management, power backup, and various water and gas systems, must function reliably and consistently to ensure product quality, safety, and regulatory compliance. Operational Qualification (OQ) is a critical process that verifies and documents that these utility systems operate within pre-defined parameters, guaranteeing their effectiveness and reliability.² This article details the essential tests and acceptance criteria involved in the OQ of common utility systems (excluding HVAC and purified water, which are covered separately).

The Importance of Utilities in Pharmaceutical Manufacturing

Pharmaceutical manufacturing relies on a range of utilities to support its operations.³ These systems are crucial for:

• Providing Clean Air: Clean compressed air is essential for various processes, including product manufacturing, packaging, and equipment cleaning.⁴ It must be free from contaminants such as oil, moisture, and particulates.⁵
• Generating Steam: Steam is used for sterilization, cleaning, heating, and other processes.⁶ Its quality, including pressure, temperature, and purity, is critical.
• Managing Waste: Proper waste management is essential for the safe and compliant disposal of pharmaceutical waste materials, protecting personnel and the environment.⁷
• Ensuring Power Supply: Reliable power backup systems are crucial for maintaining continuous operations and protecting data integrity during power outages.⁸
• Maintaining Accurate Measurements: Calibrated instruments and sensors are essential for accurate monitoring and control of utility systems.
• Monitoring System Performance: Effective alarm and monitoring systems are necessary to detect deviations from defined parameters and trigger appropriate alerts.
• Supplying Process Gases: Gases like oxygen, carbon dioxide, and nitrogen are used in various pharmaceutical processes and must be supplied at the required purity and flow rates.⁹
• Providing Cooling and Heating: Chilled and hot water systems are essential for temperature control in various processes and for cleaning and sanitization activities.
• Maintaining Vacuum: Vacuum systems are used in various processes, including drying, filtration, and distillation.
• Dissipating Heat: Cooling towers are used to dissipate heat from various processes and maintain cooling water at the specified temperature.¹⁰
• Controlling Storage Conditions: Temperature and humidity mapping of storage areas ensures that pharmaceutical products are stored under appropriate conditions to maintain their stability and efficacy.¹¹

What is Operational Qualification?

OQ is a documented process that verifies and demonstrates that equipment (including utility systems) operates within its specified parameters throughout its intended operating ranges.¹² It focuses on the performance of the equipment itself, ensuring that it functions as designed and consistently delivers the desired output. In the context of utility systems, OQ confirms that the systems can consistently and reliably provide the required resources while maintaining the necessary quality and integrity.¹³

Tests and Acceptance Criteria for Utility System OQ

The OQ of utility systems involves a series of tests designed to evaluate their performance against pre-defined acceptance criteria.¹⁴ These tests cover various aspects of the systems’ operation, including air quality, steam quality, waste management procedures, power backup functionality, instrument calibration, alarm system effectiveness, gas purity and flow rates, water temperature and flow rates, vacuum levels, cooling tower efficiency, and storage area conditions. The specific tests performed and their acceptance criteria may vary depending on the specific utility system, the requirements of the pharmaceutical processes it supports, and applicable regulatory guidelines. The following tests are commonly included in the OQ of various utility systems:

1. Clean Compressed Air System:

• Acceptance Criteria: The compressed air system should meet the specified air quality standards, including the absence of oil, moisture, and particulate contaminants. Tests may include particle counting, dew point measurement, and oil mist analysis.

2. Steam System:

• Acceptance Criteria: The steam system should provide steam of the appropriate quality, meeting standards for pressure, temperature, and purity.¹⁵ Tests may include steam purity analysis, pressure and temperature monitoring, and condensate quality testing.¹⁶

3. Waste Management System:

• Acceptance Criteria: The waste management system should ensure the safe disposal of pharmaceutical waste materials in compliance with environmental regulations.¹⁷ OQ may involve reviewing waste disposal procedures, documentation, and training records.

4. Power Backup and Emergency Systems:

• Acceptance Criteria: Power backup systems, such as generators and UPS, should function correctly during simulated power outages to ensure continuous operations and data integrity.¹⁸ Tests should verify the automatic switchover, runtime, and load capacity of the backup systems.

5. Calibration of Instrumentation and Sensors:

• Acceptance Criteria: Instruments and sensors used in utility systems should be calibrated and show accuracy within specified limits. Calibration records should be reviewed and verified.

6. Alarm and Monitoring Systems:

• Acceptance Criteria: Alarm and monitoring systems for utilities should be tested to ensure they detect deviations from defined parameters and activate appropriate alerts. This includes testing alarm triggers, notification procedures, and operator responses.

7. Gas Supply System (e.g., Oxygen, Carbon Dioxide):

• Acceptance Criteria: The gas supply system should deliver gases of the specified purity and at the required flow rates without contamination or fluctuations. Gas purity analysis and flow rate measurements should be performed.

8. Chilled Water System:

• Acceptance Criteria: The chilled water system should provide water at the required temperature and flow rate to support cooling processes. Temperature and flow rate measurements should be performed.

9. Hot Water System:

• Acceptance Criteria: The hot water system should supply water at the specified temperature and pressure for various cleaning and sanitization activities. Temperature and pressure measurements should be performed.

10. Vacuum System:

• Acceptance Criteria: The vacuum system should demonstrate the ability to achieve the required vacuum levels for processes such as drying, filtration, and distillation. Vacuum level measurements should be performed.

11. Cooling Towers:

• Acceptance Criteria: Cooling towers should operate efficiently to dissipate heat from various processes and maintain cooling water at the specified temperature. Cooling tower performance should be evaluated through temperature measurements and efficiency calculations.

12. Temperature and Humidity Mapping of Storage Areas:

• Acceptance Criteria: Storage areas should be mapped for temperature and humidity to ensure that pharmaceutical products are stored under appropriate conditions.¹⁹ Mapping studies should demonstrate that temperature and humidity levels are within specified limits.

Documentation and Reporting

All tests and results from the utility system OQ must be thoroughly documented. A comprehensive OQ report should be generated for each utility system, including:

• The OQ protocol
• Descriptions of the tests performed
• The results obtained
• Any deviations from the protocol
• Conclusions regarding the system’s performance

These reports serve as evidence that the utility systems have been properly qualified and are suitable for use in pharmaceutical manufacturing.

Conclusion

Operational qualification of utility systems is a crucial step in ensuring the reliable and consistent supply of essential resources for pharmaceutical manufacturing. By rigorously testing the systems’ performance against pre-defined acceptance criteria, manufacturers can demonstrate and document that the equipment operates as intended, guaranteeing the quality and integrity of the utilities.²⁰ This process is essential for maintaining product quality, safety, efficacy, and regulatory compliance. The tests and acceptance criteria outlined in this article provide a framework for conducting a thorough and effective utility system OQ.