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Reviewing regulatory documents, such as 483 forms and Warning Letters, can aid in determining a facility’s inspection readiness, says Siegfried Schmitt, vice president, Technical at Parexel.
Q. Inspection readiness is a key performance indicator as part of our quality system. How can we make the best use of inspection information from regulatory agencies, such as FDA?
A. This is a very timely question, as FDA have just updated their Inspection Observation website (1). These are observations listed on an FDA Form 483 (commonly referred to as 483s) compiled into spreadsheets. The spreadsheets are available by fiscal year (FY) and the latest addition is the one for FY2023. Within the spreadsheets, the information is sorted by product and program areas (e.g., Biologics) on separate tabs, and further sorted within the tabs (e.g., by the cited regulation, and importantly, the frequency of the citation within 483s).
These spreadsheets provide a plethora of information and are of tangible benefit to industry for several reasons. Only a few Form 483s are published by FDA. Thus, access to the information as is presented here is almost impossible to attain any other way. Furthermore, FDA kindly provides the frequency of specific citations, which in turn is an indicator where FDA sees the most compliance lapses. FDA inspectors will thus pay particular attention to precisely these. Maybe unsurprisingly, the top spots held in the Biologics tab are failure to “Establish, maintain and follow manufacturing SOPs [standard operating procedures]” and failure to perform “thorough investigations”. It is not possible to know the precise circumstances that led to such an observation on a Form 483, but that is no hindrance to understanding the context of the observation as was discussed in a previous article (2).
The information from the spreadsheets should be used when preparing internal inspections, which in turn should form part of a firm’s inspection readiness program. Of course, caution is advised as every company is different and the circumstances, challenges, and compliance issues are unique. The data provided by FDA are, therefore, just indicators, and do not necessarily comprise all compliance/
Whereas not all Forms 483 get published on FDA’s website, Warning Letters are published (3). Paying attention to these is even more important, as they provide context not just to the observation (why FDA considered it a non-conformance with the laws and regulations), but also why FDA was not content with the response by the firm to the Form 483. It is not sufficient to understand what deficiencies have been encountered by FDA inspectors; it is essential to also understand how to remediate such deficiencies, and to remediate to the satisfaction of the agency.
These two sources on FDA’s website should provide you with lots of inspiration for testing your company’s inspection readiness. It would be really foolish if you failed to comply with any of those items at the top of FDA’s lists, as you know perfectly well that FDA will scrutinize these, and you have been warned.
Siegfried Schmitt is vice president, Technical at Parexel.
Volume 37, Number 1
When referring to this article, please cite it as Schmitt, S. Are You Ready for Inspection? BioPharm International 2024 37 (1).