Form 483 is the most common enforcement tool for all FDA-regulated products. FDA Form 483, or Inspectional Observations, are a list of observations of possible small and significant violations made by field investigators during an inspection.
An FDA Form 483 is issued to firm’s management at the conclusion of an inspection when an investigator(s) has observed any conditions that in their judgment may constitute violations of the Food Drug and Cosmetic (FD&C) Act and related Acts. FDA investigators are trained to ensure that each observation noted on the FDA Form 483 is clear, specific and significant. Observations are made when in the investigator’s judgment, conditions or practices observed would indicate that any food, drug, device or cosmetic has been adulterated or is being prepared, packed, or held under conditions whereby it may become adulterated or rendered injurious to health.
The FDA Form 483 does not constitute a final Agency determination of whether any condition is in violation of the FD&C Act or any of its relevant regulations. The FDA Form 483 is considered, along with a written report called an Establishment Inspection Report, all evidence or documentation collected on-site, and any responses made by the company. The Agency considers all of this information and then determines what further action, if any, is appropriate to protect public health.
The U.S. Food and Drug Administration (FDA) is authorized to perform inspections under the Federal Food, Drug, and Cosmetic Act, Sec. 704 (21 USC §374) "Factory Inspection".Form FDA 483, "Inspectional Observations," is a form used by the FDA to document and communicate concerns discovered during these inspections. Also referred to as "Form 483" or merely "483", it states thereon that it
"...lists observations made by the FDA representative(s) 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 business 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, withholding of product approval, or plant shut-down. Most experts warn that responses should be comprehensive, well-reasoned, well-documented and 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. 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.
The FDA refers to cellular and tissue-based products as "human cells, tissue (biology), and cellular or tissue-based products" (HCT/Ps). To protect the health of consumers, the agency also inspects these facilities and documents observations on a 483. The authority to do so is granted by 21 CFR 1271 Subpart F.
The U.S. FDA has jurisdiction only within the United States. However, the supply chain for pharmaceuticals often extends far beyond the boundaries of the U.S., so the agency has an interest in assuring that 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 — although they can restrict importation into the U.S. The agency therefore performs foreign inspections, and observations for these are also captured on a 483. Regardless of the local language, the 483 will be written in English.