Form FDA 483

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".[1] Form FDA 483,[2] "Inspectional Observations", is a form used by the FDA to document and communicate concerns discovered during these inspections. Also referred to as "Form 483"[3][4][5][6] or merely "483",[4][7] 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.[4] This response must be submitted within 15 business days regardless of the number of observations, as of September 2009.[8][9] While a response is not compulsory, a good response can usually help a company avoid receiving a Warning Letter from the FDA,[3] withholding of product approval, or plant shut-down.[6] Most experts warn that responses should be comprehensive, well-reasoned, well-documented and timely, and that each observation should be addressed individually.[10]

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.[2]

The FDA refers to cellular and tissue-based products as "human cells, tissue (biology), and cellular or tissue-based products" (HCT/Ps).[11] 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.[12]

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[13] — 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.[14]

  1. ^ FD&C Act, "Sec. 704. (21 USC §374) Factory Inspection"
  2. ^ a b FDA; "Guidance for Industry - Formal Dispute Resolution: Scientific and Technical Issues Related to Pharmaceutical CGMP"
  3. ^ a b Taylor, Nick . in-Pharma Technologist.com; "Ignore a form 483? Not wise say FDA" (26-Feb-2009)
  4. ^ a b c "Goebel, Paul W.; Whalen, Matthew D.; and Khin-Maung-Gyi, Felix. Applied Clinical Trials Online; "What a Form 483 Really Means" (01-Sep-2001)". Archived from the original on 2011-07-11. Retrieved 2010-04-05.
  5. ^ "Phillips, Theresa. About.com: Biotech / Biomedical; "Why Fear Form-483?" (24-Nov-2008)". Archived from the original on 2011-04-07. Retrieved 2010-04-05.
  6. ^ a b Roth, Gil Y. Contract Pharma; "Glossary of Terms - Form 483" (Volume 12, Number 3) p. 83
  7. ^ BioQuality, "INSPECTIONAL ANNUAL REVIEW, A Decade of FDA Form 483 Notices of Deficiency" (Volume 15, Issue 1) p. 5 Archived 2009-07-05 at the Wayback Machine. ISSN 1090-2759
  8. ^ "Rios, Maribel. PharmTech Talk; "FDA Begins Enforcing Deadlines on Form 483 Responses" (15-Sep-2009)". Archived from the original on 2010-04-06. Retrieved 2010-04-05.
  9. ^ BioQuality, "News You Can Use: Reading Between the Lines of FDA Letters" (Volume 16, Issue 4/5) p. 2. Archived 2009-07-05 at the Wayback Machine ISSN 1090-2759
  10. ^ "FDAzilla | How to Respond to a Form FDA 483". Archived from the original on 2011-04-27. Retrieved 2011-03-04.
  11. ^ Shapiro, Jeffrey K., and Wesoloski, Brian J. "FDA’s Regulatory Scheme for Human Tissue A Brief Overview
  12. ^ U.S. Code of Federal Regulations, Title 21, Part 1271, Subpart F
  13. ^ Coukell, Allan. "Protecting Consumers from Adulterated Drugs"
  14. ^ FDA: "Investigations Operations Manual", SUBCHAPTER 1.1 - ENGLISH LANGUAGE REQUIREMENT FOR FDA DOCUMENTS