Classified and controlled environments. Similar in some ways to the utility systems described above, these systems provide a condition rather than a specific material at a well-defined state. The equipment-qualification side of these systems fits the guidance model reasonably well. Because the systems perform in essentially the same manner at all locations and for nearly all applications, development in the sense required in the guidance does not apply at all. A design phase certainly exists, but its elements are not at all like those related to formulation or synthesis processes.
The simplest of these systems (e.g., cold boxes, incubators, and similar items) require little performance qualification, and the use of statistics is hardly warranted. At the other extreme, aseptic processing areas, the evaluation of successful performance is subject to numerous external influences, so these systems can't be considered performance qualified at all, at least not in an independent manner. Acceptable results in an aseptic processing environment result more from diligence in manual routine decontamination, housekeeping practices, operator gowning, and the like. It would be inappropriate to suggest that once the environment is properly qualified, the activities performed inside it would always be successful. Success simply can't be guaranteed, at least not in any manned environment. The application of the guidance to classified environments without adjustment is not feasible.
In-process inspection of product attributes. The inspection of pharmaceutical products is an important part of the overall process for their preparation. The purpose of the inspection is to identify and remove nonconforming units before further processing or final release. Inspection processes are quite varied. They include:
- Inspection of filled parenteral containers for visible particulates
- Inspection of uncoated and coated tablets
- Lot-number and expiry-date inspection for printed materials.
The design and development of inspectional systems can be a hybrid of process development and equipment design. The use of DOE practices can be effective in establishing the inspection parameters for automated systems. When the inspection is performed by qualified personnel, a certain amount of that evaluation is possible, but because the operator's inherent diligence and visual acuity are perhaps of greater importance than the controllable inspection parameters, statistical inferences are less useful. Initial and ongoing qualification of these systems is reconfirmation of the optimized inspection parameters in commercial settings with real-world defects. The life-cycle model for process validation appears to fit inspectional systems reasonably well.