By Joy McElroy, Maynard Consulting Company
Regulations require equipment, systems, and utilities used for GMP manufacture or services to demonstrate suitability for the intended use and to operate according to their design and functional specifications. In order to meet these requirements, qualification protocols must be written for installation, operational, and performance verification. These protocols have to verify proper installation, adequate support utilities, operation over its entire range, and acceptable performance according to established SOPs and operational set points. Protocols must be in place, be based on user and functional specifications, and be approved prior to execution. Many times, companies fail to execute appropriate protocols, or protocols are found to lack necessary information and often fall short of providing the necessary tests for suitability and functional design specifications.
The FDA requires verification that equipment specifications have been met. Verification is the confirmation by examination and provision of objective evidence that specified requirements have been fulfilled. Validation is the confirmation by examination and provision of objective evidence that the particular requirements for a specific intended use can be consistently fulfilled. Whenever the results cannot be fully verified by subsequent verification and tests, the equipment has to be validated with a high degree of assurance and approved according to facilities’ established procedures.
Manufacturing and analytical equipment is validated by performing equipment qualifications. Qualifications are the actions of proving through documented evidence that any premise, system, and items of equipment work correctly and lead to expected results. Therefore, installation qualifications (IQs), operational qualifications (OQs), and performance qualifications (PQs) have to be written properly and effectively.
IQs demonstrate that the process or equipment meets all specifications, is installed correctly, and all required components and documentation needed for continued operation are installed and in place.
The installation qualification ensures the equipment/system and its components are installed correctly according to the original manufacturer’s specifications. All calibrations of major and accessory equipment must be performed during the IQ as well. Other things to consider are equipment design features, safety features, environmental conditions, and supplier documentation for preventive maintenance.
Design features included in an IQ include equipment, process piping, environment, valves, lubricants, safety devices, alarms, instrumentation, and utilities.
IQ sections and requirements are as follows:
Operational Qualification (OQ)
The OQ is the documentation of objective evidence showing that the equipment operates according to manufacturer’s specifications. In the OQ, tests are performed on the critical parameters of the system/process. These are usually the independent and/or manipulated variables associated with the system/equipment. All tests’ data and measurements must be documented in order to set a baseline for the system/equipment.
OQ sections and requirements include the following:
Performance Qualification (PQ)
The PQ is the third and final phase of equipment qualification. This phase tests the ability of the equipment to perform consistently over long periods of time within tolerance deemed acceptable by the manufacturing process as a whole. This phase may be performed in conjunction with the process validation. During the PQ stage of process validation, the process design is evaluated to determine if it is capable of reproducible consistent commercial manufacture.
The PQ involves verifying that utility systems and equipment operate in accordance with the process requirements in all anticipated operating ranges. This should include challenging the equipment or system functions while under load comparable to that expected during routine production. It should also include the performance of interventions, stoppage, and start-up as is expected during routine production. Operating ranges should be shown capable of being held as long as would be necessary during routine production.
The PQ combines the actual facility, utilities, equipment, and the trained personnel with the commercial manufacturing process, control procedures, and components to produce commercial batches. A successful PQ will confirm the process design and demonstrate that the commercial manufacturing process performs as expected. The approach to PQ should be based on sound science and the manufacturer’s overall level of product and process understanding and demonstrable control. The cumulative data from all relevant studies (designed experiments; laboratory, pilot, and commercial batches) should be used to establish the manufacturing conditions in the PQ. To understand the commercial process sufficiently, the manufacturer will need to consider the effects of scale. It is not typically necessary to explore the entire operating range at commercial scale if assurance can be provided by process design data. Previous credible experience with sufficiently similar products and processes can also be helpful. Firms should employ objective measures (e.g., statistical metrics) wherever feasible and meaningful to achieve adequate assurance. In most cases, PQ will have a higher level of sampling, additional testing, and greater scrutiny of process performance than would be typical of routine commercial production.
The level of monitoring and testing should be sufficient to confirm uniform product quality throughout the batch. The increased level of scrutiny, testing, and sampling is to establish levels and frequency of routine sampling and monitoring for the particular product and process as the facility moves into actual manufacturing.
Considerations for the duration of the heightened sampling and monitoring period could include, but are not limited to: volume of production, process complexity, level of process understanding, and experience with similar products and processes.
Writing effective IQ/OQ/PQ protocols is a must for following the regulations required by the FDA for equipment, systems, and utilities to demonstrate suitability for the intended use and to operate according to their design and functional specifications. In order to prove the requirements are met, qualification protocols have to be written and followed. These protocols are documented evidence that manufacturing firms are in compliance with cGMPs. Following these guidelines, your facility’s IQ/OQ/PQ protocols will be effective and provide adequate proof of compliance.
About The Author:
Joy McElroy is the founder and principal consultant at Maynard Consulting Company, which provides services in validation engineering, process engineering, quality control, and quality assurance. McElroy began her career in the pharmaceutical industry performing environmental monitoring and sterility testing, and then moved into a supervisory role overseeing quality control. From there, she moved into quality assurance, and then into equipment qualification and process validation. In addition to consulting, she also develops and delivers webinars, on-site training, and seminars in areas such as technical writing, equipment qualification, cleaning validation, FDA audit preparation, and more.