Validated cleaning processes monitoring

The other document that the FDA will probably want to review during the course of the PAI is the validation master plan. It is important to note that at the very least a validation protocol must be in place at the time of the inspection (unless it is a sterile product, then full validation must be completed). The validation master plan should cover the cleaning, environmental monitoring, sterilization (when necessary) process, analytical, and computers. The role of validation in PAI has been reviewed in detail by Nash [5]. 

Once a cleaning process has been appropriately validated, steps should be taken to help insure that the cleaning process remains consistent and in control. Steps that are taken to help assure this include regular monitoring, a change control system, training, and revalidation. 

Other manufacturing procedures requiring validation include cleaning, decontamination and sanitation (CDS) procedures developed for specific items of equipment/processing areas. Of particular importance is the ability of such procedures to remove bioburden. This may be assessed by monitoring levels of microbial contamination before and after application of CDS protocols to the equipment item in question. 

The plutonium inventory monitoring system (PIMS) is a network of 142 He neutron detectors in moderating enclosures, which are installed in a plutonium-powder process area at fixed positions outside of process glove boxes and the ventilation system (Simpson et al. 1998 Parvin 2007 Whitehouse et al. 2004). The collected neutron counts are processed in a matrix approach to image the neutron field of the process area. Any change to the in-process inventory will be detected and can be accounted for on a near real-time basis. The PIMS will also be used to verify the clean out and to measure any residual material. The PIMS is operator-owned equipment used jointly with the inspectorate. Appropriate authentication measures are therefore in place to validate the measurement results. 

Mechanical cleaning is more reproducible and therefore better to validate. A disinfection step can be introduced by increasing the temperature to above 80 °C by the end of the cleaning phase, so the cleaned articles are germ-free after the procedure. The process can be monitored by measuring the temperature, the use of detergents and the conductivity of the... 

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