The '483 lists observations made by the FDA representative(s) during an inspection of a facility. These are inspectional observations and do not represent a final Agency determination regarding compliance.

A recipient of a 483 should:

• respond to the FDA,
• address each item,
  • indicating agreement and either
  • providing a timeline for correction or
  • requesting clarification of what the FDA requires.

This response (if prepared) must be submitted within 15 business days regardless of the number of observations. While a response is not required, a good response can usually help a company avoid

• receiving a Warning Letter from the FDA,
• withholding of product approval, or
• a facility shut-down.

Most expert consultants warn that responses should be:

• comprehensive,
• well-reasoned,
• well-documented,
• timely, and that
• each observation should be addressed individually.

The FDA encourages resolution of issues through informal mechanisms prior to the issuance of a 483. A formal two-tiered dispute resolution process is available and is described in the FDA document Guidance for Industry - Formal Dispute Resolution: Scientific and Technical Issues Related to Pharmaceutical CGMP, and 30 calendar days are allowed for this procedure.

Even though the U.S. FDA has jurisdiction only within the U.S., the supply chain for pharmaceuticals often extends far beyond the boundaries of the U.S., so the agency has an interest in assuring that the foreign operations part of the U.S. supply chain are in an appropriate state of control, even though they have no legal authority to do so. However, they can restrict importation into the U.S. The FDA does perform foreign inspections, and observations for these are also captured on a 483, written in English.

The "general contents" of the FDA 483 are as follows:

1. FDA Form 483 Content
    1.1 Header information
    1.2 Observations
          1.2.1 Annotation
    1.3 Signatures
    1.4 Reverse side
    1.5 Addenda/amendments
2. Public access to Form FDA 483s
3. Trends in Form FDA 483 observations
4. References
5. External links

Next week, the detailed explanation of the contents of the FDA 483 will be provided.