Pre-approval inspections

Preparing for FDA Pre-Approval Inspections, edited by Martin D. Hynes III... 

Pre-approval inspection (PAI) issues of a forthcoming product/process... 

Duffell, W. Industry perspectives of pre-approval inspections. PMA-RAC Meeting, Washington, DC, May 16, 1991. 

Lee, J. Y. Documentation requirements for pre-approval inspections. Pharm Techn March 154-164 (1993). 

There has been a major impact on the need for firms to be ready for the preapproval inspection (PAI) earlier than ever because of the increased number of FDA reviewers and the greatly reduced review times. Firms do not have the lag time that they had become accustomed to and typically used to focus on and prepare their facilities for inspection. Prior to PDUFA, the industry was accustomed to submitting its applications and subsequently having a long lead time before FDA initiated the pre-approval inspection. Lack of planning results in lengthy FDA-483 at the PAI because firms are simply not ready for the inspection at the time of the submission of the marketing application. 

FDA Compliance Program Guidance Manual, Pre-Approval Inspections/Investigations (Program 7346.832), October 1990... 

Hynes, M.D. III. Developing a strategic approach to preparing for a successful pre-NDA approval inspection. Hynes, M.D. Ill (ed.). Preparing for FDA Pre-Approval inspections. New York Marcel Dekker, 1998 pp. 11-29. 

Every batch of clinical trial material is not necessarily included in stability studies however, because so many factors that can affect stability (e.g., formulation, manufacturing, container-closure) change during product development, many if not most clinical trial materials are included in some form of stability study. The results of the stability studies and the rationale for not conducting stability studies should be documented and organized appropriately in anticipation of regulatory review during pre-approval inspections (PAIs). 

M.D. Hynes, III, Preparingfor FDA Pre-Approval Inspections Throughout the Drug Development Process Gearing Up for Pre-Approval Inspections. Presented at the Institute for International Research, Miami, FL, February, 1999. 

The Pre-Approval Inspection (PAI)—The Development Report, Technology Transfer and Validation... 

Before and following the NDA tiling, many other activities are going on which are pertinent to regulatory matters and preparatory to the FDA Compliance Branch s Pre-Approval Inspection (PAI). The most important activities are the writing of the Development Report, Technology Transfer, and Validation of the operation. 

As indicated by the above enantiomeric purity assay, the quality of the DBTA salt prepared according to Scheme 8 was often borderline (ca. 97%). A process was registered (as an IND update) for occasional use in which the salt was split back to the base (in -butanol) and the DBTA salt formation step repeated. As time passed, it became apparent that it would be better, from an operations and economics standpoint, to seek a higher first crop yield (by cooling to ca. 0°C) and to recrystallize the wet first crop routinely. This position became the subject of criticism during the FDA s pre-approval inspection (q.v.). 

At the time of the FDA s pre-approval inspection (our first) of the Chemical Development dilevalol DBTA manufacturing operation (dilevalol hydrochloride itself was manufactured in Schering s Ireland facility), Chemical Development received an FDA 483 notification stating that the full-time use of the butanol/water recrystallization process for dilevalol DBTA salt was in violation of the NDA. The NDA stated that the recrystallization process was registered for use only when the first crystallization of the DBTA salt gave a product outside specification the FDA interpreted this to mean no more than about 10% of the time. Since the process had evolved... 

J Lee. GMP compliance Clinical supplies to pre-approval inspections. Presentation in Fort Lauderdale, FL, February 1993. 

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