The FDA has authority to perform inspections under the Federal Food, Drug, and Cosmetic Act (FFDCA). Form FDA 483 is referred to as “Notice of Inspectional Observations.” The 483 is issued by an FDA field investigator after an on-site inspection; it lists deficiencies in your quality system. The observations contained in every Form 483 are based on the inspector’s evaluation of your operation and their interpretation of the regulations and how they relate to your operational GMP quality system.

The FDA 483 states, “ This document lists observations made by the FDA representative during the inspection of your facility. They are inspectional observations, and do not represent a final Agency determination regarding your compliance.”

The field inspector will submit the finalized 483 to his/her superiors and based on the severity of the findings, an FDA warning letter may be issued to your firm.  The Warning Letter is official notification of a violation of the law.

A recipient of form 483 should respond to the FDA, addressing each item, indicating  whether you agree or disagree and providing corrective action taken and/or planned. This response must come within 15 calendar days. A good response can avoid a Warning Letter, or withholding of product approval or plant shutdown.

The FDA encourages resolution of issues through an informal mechanism prior to the issue of a 483. After a 483 issue, manufacturers can use a formal two-tiered dispute resolution process[dlt3] and they have 30 calendar days to do so.

The content of the form 483 is specifically designated. It contains:

• Header Information: that identifies the FDA district office and:

o   Name and address of the facility

o   A key contact for the facility

o   A brief description of the type of facility

o   The facility’s FEI (FDA Establishment Identification) number

• Observations: This section starts with a “disclaimer” that the 483 does not necessarily “represent a final agency determination regarding your compliance.” Observations are the opinion of the FDA investigator and may be subject to review by other FDA personnel. There is a large area for recording observations and it may be several pages in length. The observations should be ranked in order of significance. A recurring observation will be so noted. Questionable observations should not be on the 483.
• Annotation: As of 1997, the FDA implemented an annotation policy for medical device inspections. There are four choices:

o   Report corrected, not verified

o   Corrected and verified

o   Promised to correct (by a given date)

o   Under consideration

• Signatures: The investigator’s signature on the first and last pages and initials on the middle pages.
• Converse side: Cites the legal precedence for the inspection.
• Addenda/amendments: For errors that occur after the issuance of the 483. It is not used for adding observations.

Under the Freedom of Information Act Amendments of 1996 the FDA 483 form is available to the public. The FDA publishes select 483s in their electronic reading room. In November of 2009, the FDA asked for input from the public “on whether inspection reports should be re-designed to separate out a summary or key findings page that could be made available to the public quickly.” Responses from the public can be submitted on the FDA web site.

Written by: Margaret Stenerson

10 4 2010