Preapproval inspections

Laboratory notebooks—It may be debatable to consider laboratory notebooks as text documents, but they should be mentioned here because of their importance in preclinical development. Laboratory notebooks are used to record experimental procedures, observations, raw data, and other important information. Although laboratory notebooks are rarely used for submission to regulatory agencies directly, they are available for inspection by the authorities in the Preapproval Inspection (PAI) and other GMP/GLP-related inspections. Currently, most of the major pharmaceutical companies still use paper-based laboratory notebooks. Electronic-based notebook systems are being developed and commercialized, which are discussed in Chapter 9. 

M. D. Hynes, Preparing for FDA Preapproval Inspections. New York Marcel Dekker, Inc., 1998. 

Until recently, CBER was the only center doing postlicensure inspections and remains the only center engaged in preapproval inspections. CBER surveillance of licensed products was described in 1998 as the inspection of manufacturing facilities for compliance with regulations, verification that product lots conform to preapproval standards and product consistency prior to their release into distribution, and evaluation of surveillance reports, such as adverse experience reports and blood fatality reports (Sensabaugh, 1998, p. 1012). 

The stability data that should available at the time of preapproval inspection include... 

The formal validation is often completed after the PAI, where three-batch process validation will be conducted in accordance with the protocol approved during the preapproval inspection. The primary objective of the formal process validation exercise is to establish process reproducibility and consistency. Such validation must be completed before entering the market. The formal validation studies continue through packaging and labeling operations (in whole or in part), so that machinability and stability of the finished product can be established and documented in the primary container-closure system. 

While validation as a discipline is widely known across the pharmaceutical industry, there are still a significant number of instances in which preapproval inspection results or product recalls identify an insufficient validation program as the root cause of the difficulty. Continued awareness of validation requirements and a diligent application of validation principles will thus help to ensure that pharmaceutical products will be able to be developed and produced with the quality and reproducibility required from regulatory agencies across the world. 

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