The Definition of FDA 483

Why the FDA inspects

What is commonly referred to as FDA 483 is actually FDA Form 483, the form on which inspectors for the Food and Drug Administration detail unsatisfactory results of their inspection of manufacturing facilities for compliance with current good manufacturing practices (cGMP). The FDA inspects plants making human drugs (both prescription and over-the-counter drugs), animal and veterinary drugs, medical devices, food, radiation-emitting products, vaccines, blood and biological products and cosmetics for compliance with cGMP.

FD&C Act

The FDA's authority to inspect factories is detailed in Section 704 of the Federal Food, Drug and Cosmetic Act. The act authorizes officers or other employees of the FDA to enter any establishment in which "food, drugs, [medical] devices, or cosmetics are manufactured, processed, packaged, or held" in order to inspect the establishment and materials therein. Section 704 requires the inspector to provide the owner or operator with a report detailing deficiencies prior to leaving the establishment.

cGMP

The standards the FDA expects companies that manufacture either the ingredients for drugs (both active pharmaceutical ingredients and inactive ingredients such as excipients) or finished drugs (in their final dosage forms) are called cGMP. The cGMP for finished drugs are described in 21 C.F.R. Chapter 1 Section 211, which covers 58 topics, including quality control responsibilities, lighting, ventilation and equipment design and maintenance.

Inspections

The FDA is authorized to inspect plants at which active pharmaceutical ingredients (API) are manufactured in connection with its approval of the final drugs in which the API is used, and these plants are required to file what are called "drug master files" with the FDA. Because a number of manufacturers of both APIs and finished drugs are located outside the United States, the FDA is authorized to inspect both domestic plants and plants located outside the United States.

Form 483

Section 704 requires the inspector to provide the owner or operator with a report detailing deficiencies prior to leaving the establishment--namely a Form 483. A Form 483 will list the categories in which deficiencies have been found and provide observations detailing each such deficiency. For example, the Form 483 filed after inspection of a McNeil Consumer Products plant provides comments about the quality system, the labeling and packaging system, laboratory operations, the material system and facilities and equipment.

Dispute Resolution

If a drug manufacturer has FDA approvals pending for drugs manufactured at a facility for which a Form 483 letter has been issued, the FDA can withhold approval of the drugs pending satisfactory resolution of its concerns. The FDA has produced a document, or "Guidance for Industry," that details its formal dispute resolution system for scientific and technical issues related to cGMP, although the guidance suggests that the manufacturer try to reach agreement with the FDA inspector informally if possible.

References

• Food and Drug Administration: Federal Food, Drug, and Cosmetic Act
• Food and Drug Administration: Guidance for Industry: Formal Dispute Resolution: Scientific and Technical Issues Related to Pharmaceutical CGMP
• Food and Drug Administration: Form 483 (PDF)
• Code of Federal Regulations: 21 C.F.R. Section 211