The reaction of the clinical research community to the issuance of these Form 483s borders on paranoia — paranoia at the prospect of an FDA audit resulting in the issuance of the dreaded Form 483, an action that some liken to the kiss of death for the recipient.

The recipient of a Form 483 should respond to the FDA, addressing each item, indicating agreement and either providing a timeline for correction or requesting clarification. Since September 2009, this response must be submitted within 15 working days, regardless of the number of observations. While a response is not compulsory, a good response can usually help a company avoid receiving a warning letter from the FDA, which may mean withholding of product approval, or plant shut-down.

The original intent of the Form 483 is to be an instrument of prompt notification to allow the inspected entity an opportunity for correction and improvement, not an instrument of punishment.

The US FDA has jurisdiction only within the US. However, the supply chain for pharmaceuticals often extends far beyond borders. The agency therefore performs foreign inspections and observations, which are also captured on a Form 483. Although they have no legal authority outside of the US they can restrict imports into the US.

References:

FDA. Regulatory information. FD&C Act SEC. 704. (21 USC §374) Factory Inspection

Federal Register: August 11, 2009 (Volume 74, Number 153) Notices [Page 40211-40212]