FDA Form 483 & Warning Letter Q & A.
USing Form 483 / Warning Letter for contractor qualification.
Q. Are all FDA 483s followed by a Warning Letter? (It is my understanding that FDA 483s are issued immediately after an inspection and that a Warning Letter does not necessarily follow them.)
A. Your understanding is correct. Warning letters are only issued after agency review of all information pertinent to the findings of the inspection. This information includes the 483, inspection report (EIR) and any other information such as a response to the 483. Warning letters are reserved for the more significant cases of noncompliance where the final compliance classification is Official Action Indicated (OAI). Many inspections result in a 483 but do not result in a Warning letter.
Q. Are all Warning Letters in response to FDA 483s? Many Warning Letters (mostly from DDMAC) regarding labeling and promotional material are not included in FDA 483 violations.
A. Ordinarily Warning letters follow an inspection at which a 483 is issued. However, the agency has in house review functions, such as DDMAC's, in which a review of labeling for example can result in a Warning letter. Not all inspections result in a 483.
Q. Is it possible to obtain information on the total number of FDA 483s given to specific people and organizations?
A. The total number of 483s issued is really not very meaningful in trying to assess overall compliance of an industry sector. In general, you would need to make an FOI request asking for the 483 in question for the specific firms in question and would have to tally the numbers. Before you make such a request, please visit the FOI web page http://www.fda.gov/foi/foia2.htm for more information on how to get information through FOI Regarding 483s. In each of these lists you will notice a final classification of NAI, VAI, or OAI. You generally can assume that a 483 was issued for any inspection with a classification of VAI or OAI. 483s may have been issued for a NAI inspection but this is the exception rather than the rule.
Q. Is the FOI Reading Room a complete list of all FDA issued Warning Letters? Q3b Is it possible to limit searches to just GCP violations?
A. To search the Warning letters I suggest you search by subject. For example, for GCP inspections, search on each of the following "clinical investigator" "Institutional Review Board", "Sponsor".
Q. Is there a better regulatory mechanism (other than FDA 483s and Warning Letters) that could be used to measure compliance?
A. Yes there are better measures than a 483 alone.
First, the 483 should not be used alone in judging compliance. The 483 is a list of the inspector's observations which in the inspector's judgment represent deviations from the regulations which are significant. The decision as to whether a 483 observation is indeed a regulatory deviation is an agency decision made after review of all the facts as reported and documented in the EIR and from other sources such as correspondence from the inspected party. After each inspection, the Center, with responsibility for the inspection, will issue a post inspection correspondence, which communicates the agency's final decision on the compliance status of the site inspected. The Center will assign a final compliance classification as OAI, VAI, or NAI.
In general, when reviewing compliance data, determine the percent of inspections that fall into one of these three compliance classifications. You can develop your own compliance from that.
Warning letters are a form of post inspection correspondence, but they are only sent to the firms that are seriously noncompliant. Fortunately, this is only a small percentage of all firms inspected.