Preapproval inspections manufacturing process

Eventually the point will be reached at which the development of a product is complete the formulation is finalized, the equipment has been selected, the analytical methods are validated, the development transfer report has been issued, and the Preapproval Inspection (PAI) is anticipated. Now is the time to consider validation of both the manufacturing and cleaning processes. Although some process validation may have also been completed or a process validation protocol may have been prepared and approved, it is likely that very little has been finished that would enable us to state that the cleaning process is fully validated. 

Preapproval inspections can be very comprehensive in nature. Firms therefore need to be well prepared before the arrival of the FDA investigators. The field investigator will in all likelihood audit development data during the course of the inspection for authenticity as well as for accuracy. Additionally, he or she will determine if the facilities, personnel, equipment, and laboratory methods adequately support the manufacturing process in the NDA. The items likely to be reviewed by the FDA investigator(s) during the course of the inspection are shown inTable 2. 

In a well-designed validation program, most of the effort should be spent on facilities, equipment, components, methods, and process qualification. In such a program, the formalized, final three-batch validation sequence provides only the necessary process validation documentation required by the FDA to show product reproducibility and a manufacturing process in a state of control. Such a strategy is consistent with the FDA preapproval inspection program directive. ... 

Prepared for preapproval inspections (PAI) is not a trivial matter, as significant observations may delay the approval of the corresponding applications usually the PAI takes place after all other aspects of the application have been reviewed and found suitable for approval. Although GMP issues may arise, the principal objective of the PAI is to determine the soundness of the manufacturing process relative to the process described in the application. Some golden rules that can do no harm are ... 

Preapproval inspection (PAI) An inspection by the FDA of the facilities that are proposed as the manufacturing, packaging, and testing sites in the NDA. The PAI normally occurs during the review process. Besides inspecting the facilities, the documentation will be reviewed for compliance to GMPs, SOPs and to verify the integrity of the data in the submission. 

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