Review of form 483s and warning letters to pharmaceutical manufacturers issued by USFDA

Abstract

Regular inspections are carried out to ensure system conformity by the Food and Drugs Regulatory Authority (FDA) of the United States one of the most stringent regulatory authorities in the world. The inspectors send Form 483 to the management after the inspection, detailing the inappropriate conditions. Because the FDA guidelines are difficult to comply with, a company can contravene the regulations. If any significant infringements can affect the protection, quality, effectiveness, or public health of the drug is identified, the FDA issues advice to the company. Warning Letters (WL) shall be an official notification of non-compliance with federal law within a period to be issued by manufacturer, clinician, distributor, or responsible person in the company. The delivery of a letter has a considerable impact on the company's reputation and position in the market. Inadequate WL reactions could lead to a refusal, import denial, memorandum or even conviction and order. A brief study was conducted in this document of Form 483 and WL for four years (2017–2020) on an understanding the regulatory provisions.

Keywords

Warning letter drug safety FDA inspections enforcement public health

Get full access to this article

View all access options for this article.

References

https://www.fda.gov/ (accessed 26 May 2021).

https://thelawreviews.co.uk/title/the-life-sciences-law-review/usa (accessed 26 May 2021).

https://www.fda.gov/animal-veterinary/animal-food-feeds/product-regulation (accessed 26 May 2021).

National Research Council (US) Committee on Drug Use in Food Animals. The use of drugs in food animals: benefits and risks. Washington (DC): National Academies Press (US); 1999. 2, Food-Animal Production Practices and Drug Use, https://www.ncbi.nlm.nih.gov/books/NBK232573/ (accessed 26 May 2021).

Fleming

Demets

McShane

LM.

Discussion: the role, position, and function of the FDA – the past, present, and future. Biostatistics 2017; 18: 417–421.

Wax

PM.

Elixirs, diluents, and the passage of the 1938 federal food, drug and cosmetic act. Ann Intern Med 1995; 122: 456–461.

Teff

Drug approval in England and the United States. Am J Comparat Law 1985; 33: 567–610.

Lauer

Barker

Solano

, et al. FDA device regulation. Mo Med 2017; 114: 283–288.

Rägo

Sillo

‘T Hoen

, et al. Regulatory framework for access to safe, effective quality medicines. Antivir Ther 2014; 19: 69–77.

10.

https://www.contractpharma.com/issues/2017-06-01/view_fda-watch/warning-letters-close-out-letters/49675 (accessed 26 May 2021).

11.

https://www.fda.gov/files/science%20%26%20research/published/9-45.–-11-00-Investigator-Responsibilities-%E2%80%93-Regulation-and-Clinical-Trials.pdf (accessed 26 May 2021).

12.

https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/about-warning-and-close-out-letters (accessed 26 May 2021).

13.

https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-references/fda-form-483-frequently-asked-questions (accessed 26 May 2021).

14.

Investigations Operations Manual, 2021, FDA, https://www.fda.gov/media/113432/download (accessed 26 May 2021).

15.

https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-classification-database (accessed 26 May 2021).

16.

https://www.fda.gov/about-fda/fda-basics/what-does-fda-inspect (accessed 26 May 2021).

17.

DiGIulio

FDA’s Pre-Approval inspection (PAI) program and how to prepare for a successful outcome, https://www.fda.gov/media/94064/download (2015, accessed 26 May 2021).

18.

Mozzachio

AM.

Post-Approval & Surveillance Inspection Programs for Pharmaceutical Manufacturers, https://www.fda.gov/media/88492/download (accessed 26 May 2021).

19.

Patel

DS.

The FDA cGMP inspection is coming: make the best of it, IVT. https://www.ivtnetwork.com/article/fda-cgmp-inspection-coming-make-best-it (accessed 26 May 2021).

20.

https://www.accessdata.fda.gov/scripts/cderworld/index.cfm?action=compliance.:main&unit=2&lesson=1&topic=4 (accessed 26 May 2021).

21.

Ohanian

Understanding the 4 types of FDA inspections. Halloran Consulting Group, https://www.meddeviceonline.com/doc/understanding-the-types-of-fda-inspection-0001 (accessed 26 May 2021).

22.

Waters

VanDerslice

Porucznik

, et al. The effect of follow-up inspections on critical violations identified during restaurant inspections. J Environ Health 2015; 77: 8–12.

23.

https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-references/inspection-observations (accessed 26 May 2021).

24.

https://datadashboard.fda.gov/ora/cd/inspections.htm (accessed 26 May 2021).

25.

https://www.law.cornell.edu/cfr/text/21/part-211 (accessed 26 May 2021).

26.

https://www.law.cornell.edu/cfr/text/21/part-312 (accessed 26 May 2021).

27.

FMD- 86, Establishment inspection report conclusions and decisions, FDA-ORA. https://www.fda.gov/media/87643/download (accessed 26 May 2021).

28.

Nahler

Establishment inspection report (EIR). In: Dictionary of pharmaceutical medicine. Vienna: Springer, 2009, pp. 67–68. DOI: 10.1007/978-3-211-89836-9_506.

29.

Bablani

Janodia

MD.

Analysis of FDA warning letters issued to Indian pharmaceutical and medical device companies: a retrospective study. Ther Innov Regul Sci 2019; 54(4): 925–931.

30.

https://www.gmp-compliance.org/gmp-news/fda-warning-letters-structure-and-the-lessons-learnt-effect (accessed 26 May 2021).

31.

Symonds

Hackford

Abraham

A review of FDA warning letters and notices of violations issued for patient-reported outcomes promotional claims between 2006 and 2012. Value Health 2014; 17: 433–437.

32.

FEDERAL FOOD, DRUG, AND COSMETIC ACT, https://uscode.house.gov/ (accessed 26 May 2021).

33.

https://www.fda.gov/consumers/health-fraud-scams/fraudulent-coronavirus-disease-2019-covid-19-products (accessed 26 May 2021).

34.

https://www.drugabuse.gov/drug-topics/opioids/opioid-overdose-crisis (accessed 26 May 2021).

35.

https://www.raps.org/news-and-articles/news-articles/2020/9/wide-swath-of-online-opioid-sellers-warned-by-fda (accessed 26 May 2021).

36.

https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/compliance-actions-and-activities/warning-letters (accessed 26 May 2021).

37.

https://www.fda.gov/industry/import-program-food-and-drug-administration-fda/actions-enforcement (accessed 26 May 2021).