Equipment cleaning operational qualification

Quality systems require that facilities and equipment should be appropriate to the activities undertaken. Surfaces that are easy to clean and maintain in hygienic condition are a requirement in many situations. For example, cloth-backed chairs would not be acceptable in a laboratory that handled potentially biohazardous materials. Equipment should be checked at installation to demonstrate that it can perform its desired function. This is frequently done using an Installation Qualification, Operational Qualification and Performance Qualification (IQ /OQ/PQ) commissioning process. Routine maintenance and calibration programmes are then required to ensure that equipment continues to deliver the specified performance. 

Finally, during the qualification of the facility, all systems are tested, calibrated, and cleaned. The mechanical and service infrastructure must be qualified. The operational qualification will involve practice runs. All documentation must be finalized. This includes standard operating procedures, batch records, and equipment logs. 

Equipment—proper design and sizes for the project, use and cleaning records, documentation to show proper installation and operational qualification (equipment qualification EQ), and in some cases performance qualification documents, validated computer systems, preventive maintenance program, records of equipment repairs and upgrades and subsequent requalification documentation, etc. 

The first component of a successful clinical trial manufacturing program is the area or facility used for the production of clinical trial batches. This facility should have limited access and be segregated from other activities where the danger of cross contamination is removed and the control of materials, product, waste, and personnel flow can be achieved. Preparation of vector batches requires rooms where a controlled environment can be maintained. Here, under class 10,000 and class 100 environments, batches can be produced, purified, and vialed for use in trials. HVAC and other equipment used within the manufacturing facility requires annual calibration, initial installation, and operational qualification, and appropriate preventive maintenance programs. Written procedures for the use, cleaning, and maintenance of the facility, and the equipment must also be written and followed by appropriate personnel. 

Design Qualification (DQ) is the first validation element of a new facility system or equipment, where adherence to the user s specifications and to GMP rules is demonstrated. Installation Qualification (IQ) follows with the verification of adequacy of the area, installation of equipment pipelines, utilities, instrumentation, and conformity of the material used to the project specifications. At the Operational Qualification (OQ) phase, carried out after installation of all equipment, it is verified whether the system, when in operation, complies with the acceptance criteria defined in the validation plan. Once the OQ phase is successfully finalized it is possible to proceed with the calibration procedures, operation and cleaning, operator training, and preventive maintenance program. After IQ and OQ are concluded, it is time for the Performance Qualification (PQ), with the aim of verifying that what was designed, built, and operated results in a product that meets the expected specifications. Production and QC personnel are specially trained for these assessments. The tests can be done with the product of interest or a placebo, and are related to all operations, from raw material reception to product release (EC, 2001). 

Systems and equipment should be released for routine use after completion of operational qualification, provided that all calibration, cleaning, maintenance, training and related tests and results were found to be acceptable. 

Critical processes other than the actual product manufacturing process — such as sterilization, component washing, and equipment cleaning — require prevalidation cycle development work. This may include establishment of appropriate sterilization cycle types, cleaning agents, etc. This test work is performed during or after Operational Qualification. 

For personnel working with radiopharmaceuticals, training and qualification should cover general principles of GMP and radiation protection. This includes also personnel in charge of cleaning premises and equipment used for this type of production. All manufacturing operations should be carried out under the responsibility of a QP with additional competence in radiation protection. 

A significant aspect of compliance is validation of the process through qualifications of the equipment installation and operation, process validation and, recently, the development of a cleaning validation. There are summaries describing how to qualify the installation and operation of equipment, piping, valves and instruments [84], The process validation requires evaluating the critical steps, which effect the quality and purity of the final active drug substance [85]. This involves development of a protocol, which states how the validation is to be conducted and defines the data to be collected. The most important part of the protocol is the development of acceptance criteria for the results. 

---