Form 483

The US FDA is authorized to perform inspections under the Federal Food, Drug, and Cosmetic Act, SEC. 704 (21 USC §374) "Factory Inspection". Form 483 , “Inspectional Observations,” is a form used by the FDA to document and communicate concerns discovered during these inspections. Also referred to as "Form FDA 483" or merely "483" , it states thereon that it

“...lists observations made by the US Food and Drug Administration (FDA) representative during the inspection of your facility. They are inspectional observations, and do not represent a final agency determination regarding your compliance.”

A recipient of a 483 should respond to the FDA, addressing each item, indicating agreement and either providing a timeline for correction or requesting clarification of what the FDA requires. This response must be submitted within 15 calendar days regardless of the number of observations, as of September 2009. While a response is not compulsory, a good response can usually help a company avoid receiving a Warning Letter from the FDA.

The FDA encourages resolution of issues through informal mechanisms prior to the issuance of a Form 483. After issuance, manufacturers can use a formal two-tiered dispute resolution process described in the FDA document Guidance for Industry - Formal Dispute Resolution: Scientific and Technical Issues Related to Pharmaceutical CGMP, and they have 30 calendar days to do so.

Form 483 content

Header information

The header identifies the FDA district office that performed the inspection, the date(s) of inspection, name and address of the facility that was inspected, a key contact for the facility, a brief description of the type of facility, and the facility's FEI (FDA Establishment Identification) number.

Observations

This section starts with a "disclaimer" that the form contains the observations of the inspector and does not necessarily "represent a final Agency determination regarding your compliance." Observations placed on a form 483 are the opinion of the FDA investigator and may be subject to review by other FDA personnel.

The Form 483 then has a large area for recording the observations. The FDA will typically include only significant observations that can be directly linked to a violation of regulations — not suggestions, guidance, or other comments. ("Significant" is somewhat arbitrary and may be subject to the bias of a particular inspector.) The Form 483 will not normally include actual regulatory references.

Signatures

The inspectors' names are printed and signed, and the date of issue is recorded in this section.

Public access to Form 483s

Form 483s are available under the Freedom of Information Act Amendments of 1996, but may be redacted to remove non-public information. The FDA publishes select Form 483s on their website at this location:

ORA FOIA Electronic Reading Room

As of 21-Nov-2009, the FDA is seeking 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's web site.

Recent trends in Form 483 observations

From 2002 to 2009, the dominant problem area documented on Form 483 was Investigations, which are integral to good CAPA programs. Investigations accounted for 27% of the observations in 2009. The next most problematic areas were Equipment/Facilities/Operations at 11% (2009) and Validation at 10% (2009).

External links

• US FDA
• Federal Food, Drug, and Cosmetic Act (FD&C Act)