278:'Upon completion of any such inspection of a factory, warehouse, consulting laboratory, or other establishment, and prior to leaving the premises, the officer or employee making the inspection shall give to the owner, operator, or agent in charge a report in writing setting forth any conditions or practices observed by him which, in his judgement, indicate that any food, drug, device, cosmetic in such establishment (1) consists in whole or in part of any filthy, putrid, or decomposed substance or (2) has been prepared, packed, or held under insanitary conditions whereby it may have become contaminated with filth, or whereby it may have been rendered injurious to health. A copy of such report shall be sent promptly to the Secretary.'
22:
178:
This section starts with a "disclaimer" that the form contains the observations of the inspector and does not necessarily "represent a final Agency determination regarding your compliance." Observations placed on a 483 are the opinion of the FDA investigator and may be subject to review by other FDA
183:
This document 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. If you have an objection regarding an observation, or have implemented, or plan
169:
that performed the inspection, the date(s) of inspection, name and address of the facility that was inspected, the name and title of the individual to whom the 483 is issued to (usually the most responsible individual physically present in the facility), a brief description of the type of facility,
144:
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
287:
It is possible that an error is discovered by the inspector(s) after issuing the 483. If the 483 was generated via Turbo EIR, then an amendment is created within that system. Else, an addendum is created. If possible, the investigator(s) will personally deliver the addendum/amendment to the firm.
196:
The 483 then have a large area for recording the observations, which may be continued on several pages. The observations should be ranked in order of significance. If an observation made during a prior inspection has not been corrected or is a recurring observation, that may be noted on the 483.
184:
to implement, corrective action in response to an observation, you may discuss the objection or action with the FDA representative(s) during the inspection or submit this information to FDA at the address above. If you have any questions, please contact FDA at the phone number and address above.
242:
The actual annotation of the 483 occurs during the final discussion with the firm's management; if the firm prefers no annotation, then annotation will not be performed. The annotations may be after each observation, at the end of each page, or at the bottom of the last page prior to the
102:
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
324:
As of 21-Nov-2009, the FDA is seeking input from the public "on whether inspection reports should be re-designed to separate out a summary or key findings page that could be made available to the public quickly." Responses from the public can be submitted on the FDA's web site.
251:
The investigators' names are printed and signed, and the date of issue is recorded in this section. Titles for the investigators may also be included. If the 483 is multiple pages, the first and last pages have full signatures while the intervening pages are only initialed.
212:
of a particular inspector.) Observations of questionable significance should not be on the 483, but should have been discussed with the firm's management so that they understand how uncorrected problems could become a violation. The 483 will not normally include actual
190:
The observations noted in this Form FDA-483 are not an exhaustive listing of objectionable conditions. Under the law, your firm is responsible for conducting internal self-audits to identify and correct any and all violations of the quality system
107:
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.
94:... 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
90:, "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
133:, 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
145:
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.
461:
225:
As of 1997, the FDA established an annotation policy for medical device inspections. The investigator(s) should offer to annotate the 483 with one or more of the following:
404:
569:
291:
Addenda/amendments are not normally used for adding observations to a 483 after the inspection has been closed out and the investigator(s) have left the premises.
661:
650:
111:
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
300:
827:
920:
153:
The content of a 483 may be handwritten, typed, completed in a PDF file and printed, or completed via the FDA's computer system called Turbo EIR.
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observations that can be directly linked to a violation of regulations — not suggestions, guidance, or other comments. ("
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75:
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2. To assist firms inspected in complying with the Acts and regulations enforced by the Food and Drug
Administration.
425:; "Guidance for Industry - Formal Dispute Resolution: Scientific and Technical Issues Related to Pharmaceutical CGMP"
98:
A recipient of a 483 should respond to the FDA, addressing each item, indicating agreement and either providing a
120:
Guidance for
Industry - Formal Dispute Resolution: Scientific and Technical Issues Related to Pharmaceutical CGMP
726:
896:
651:
Shapiro, Jeffrey K., and
Wesoloski, Brian J. "FDA’s Regulatory Scheme for Human Tissue A Brief Overview
543:, "INSPECTIONAL ANNUAL REVIEW, A Decade of FDA Form 483 Notices of Deficiency" (Volume 15, Issue 1) p. 5
264:
The observations of objectional conditions and practices listed on the front of this form are reported:
747:"Guidant Corporation, 483 Inspectional Observations, St Paul, Minnesota, dated 12/15/2005 - 02/09/2006"
712:
687:"Investigations Operations Manual", SUBCHAPTER 1.1 - ENGLISH LANGUAGE REQUIREMENT FOR FDA DOCUMENTS
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to remove non-public information. The FDA publishes select 483s on their website at this location:
162:
112:
104:
83:
614:
557:
630:
610:
553:
501:
130:
115:
601:, "News You Can Use: Reading Between the Lines of FDA Letters" (Volume 16, Issue 4/5) p. 2.
321:
Some third parties query the FDA and publish a listing of Form FDA 483s issued since 2000.
900:
683:
607:
549:
235:
Promised to correct (may be appended with "by xxx date" or "within xxxx days or months").
805:
333:
Tabulations of the most-cited issues tend to be relatively stable from year to year.
275:
Section 704(b) of the
Federal Food, Drug, and Cosmetic Act (21 USC §374(b)) provides:
909:
524:
141:
802:: "Tell Us Your Ideas: How Should FDA Inform the Public About Inspection Results""
334:
126:
776:
214:
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1. Pursuant to
Section 704(b) of the Federal Food, Drug and Cosmetic Act, or
597:
539:
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The U.S. FDA has jurisdiction only within the United States. However, the
894:
List of FDA-issued 483s from 2000 through
January 2013 (Source: FDAzilla)
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The fifth listed item in FY2012 (211.110(a)) had dropped to #12 by 2019.
99:
574:; "FDA Begins Enforcing Deadlines on Form 483 Responses" (15-Sep-2009)"
375:
221.42(c), "facilities shall include defined areas of sufficient size"
134:
828:"FDA CDER Most Frequent Form FDA 483 Observations Fiscal Year 2012"
361:
211.110(a), Control procedures to monitor and validate performance
170:
893:
462:"Goebel, Paul W.; Whalen, Matthew D.; and Khin-Maung-Gyi, Felix.
662:
U.S. Code of
Federal Regulations, Title 21, Part 1271, Subpart F
338:
209:
673:
Coukell, Allan. "Protecting Consumers from Adulterated Drugs"
15:
529:; "Glossary of Terms - Form 483" (Volume 12, Number 3) p. 83
345:
211,22(d), Procedures not written, or are not fully followed
348:
211.192, Poor investigations of discrepancies or failures (
125:
The FDA refers to cellular and tissue-based products as "
883:
39:
443:; "Ignore a form 483? Not wise say FDA" (26-Feb-2009)
78:(FDA) is authorized to perform inspections under the
855:"FDA FY2019 Drug Inspection Observations And Trends"
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211.160(b), Scientifically sound laboratory controls
889:
Federal Food, Drug, and Cosmetic Act (FD&C Act)
208:" is somewhat arbitrary and may be subject to the
730:; "(OEI) Development and Maintenance Procedures"
716:"Investigations Operations Manual", EXHIBIT 5-5
466:; "What a Form 483 Really Means" (01-Sep-2001)"
341:shows that the top five items of concern were:
408:, "Sec. 704. (21 USC §374) Factory Inspection"
739:
737:
627:"FDAzilla | How to Respond to a Form FDA 483"
8:
260:The reverse side of the form has this text:
122:, and they have 30 calendar days to do so.
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415:
355:211.100(a), Absence of written procedures
62:Learn how and when to remove this message
179:personnel. The full text is as follows:
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498:; "Why Fear Form-483?" (24-Nov-2008)"
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7:
761:; "ORA FOIA Electronic Reading Room"
520:
518:
200:The FDA will typically include only
80:Federal Food, Drug, and Cosmetic Act
329:Trends in Form FDA 483 observations
853:Unger, Barbara (6 December 2019).
826:Friedman, Barry (April 24, 2013).
299:Form 483s are available under the
14:
884:U.S. Food and Drug Administration
229:Reported corrected, not verified.
314:ORA FOIA Electronic Reading Room
20:
496:About.com: Biotech / Biomedical
381:221.166(a), "stability testing"
365:By FY2019, the top items were:
921:United States government forms
773:"FDAzilla's 483s index search"
464:Applied Clinical Trials Online
295:Public access to Form FDA 483s
118:described in the FDA document
1:
243:investigator's signature(s).
916:Food and Drug Administration
337:2012 data compiled by FDA's
86:§374) "Factory Inspection".
76:Food and Drug Administration
937:
832:Barry A. Friedman, PhD LLC
441:in-Pharma Technologist.com
384:211.100(a), was #3 in 2012
301:Freedom of Information Act
378:211.160(b), was #4 in 212
34:may need to be rewritten
369:221.22(d), same as 2012
232:Corrected and verified.
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194:
186:
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859:Pharmaceutical Online
372:221.192, same as 2012
262:
187:
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494:"Phillips, Theresa.
238:Under consideration.
149:Form FDA 483 content
167:FDA district office
899:2013-02-02 at the
606:2009-07-05 at the
548:2009-07-05 at the
283:Addenda/amendments
157:Header information
113:dispute resolution
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137:1271 Subpart F.
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38:Please help
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31:lead section
206:Significant
202:significant
127:human cells
910:Categories
812:2010-04-05
783:2010-09-09
637:2011-03-04
599:BioQuality
584:2010-04-05
541:BioQuality
508:2010-04-05
476:2010-04-05
392:References
247:Signatures
221:Annotation
215:regulatory
615:1090-2759
558:1090-2759
74:The U.S.
52:June 2019
897:Archived
604:Archived
546:Archived
305:redacted
100:timeline
116:process
865:22 Dec
838:22 Dec
834:(Blog)
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135:21 CFR
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350:CAPA
339:CDER
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