Responding to

FDA 483s
Strategies for Successfully
Obtaining Closeout

From the Editors of

The Executive Briefing Series

Copyright © 2013 by Washington Business Information Inc. All rights reserved. The Executive Briefing Series from The Food
& Drug Letter (ISSN 0362-6466), is an in-depth analysis of regulations and issues affecting the pharmaceutical and biologics
industries. The series is published monthly, 12 issues per year, for $4,995. Photocopying or reproducing in any form, includ-
ing electronic or facsimile transmission, scanning or electronic storage is a violation of federal copyright law and is strictly
prohibited without the publisher’s express written permission. Subscribers registered with the Copyright Clearance Center
(CCC) may reproduce articles for internal use only. For more information, contact CCC at www.copyright.com or call
(978) 750-8400. For site licenses for multiple users or to purchase multiple copies, contact Nelly Valentin at (703) 538-7656.
 Responding to FDA 483s:
Strategies for Successfully Obtaining Closeout

Table of Contents
Introduction
Inspection Trends: ʻThe Enforcement Storyʼ 5
New Enforcement Policies 9
Preparing for Inspections 12
What to Expect: Observations 15
Responding to the Form 483 and Warning Letter 18
FAQs 24
Conclusion 27
Appendices
Appendix A: Key Components for Effective 483 and Warning Letter
Responses
Appendix B: FDA Announcement Regarding Timely Issuance of
Warning Letters
Appendix C: Example of a Closeout Letter
Introduction
The FDA’s inspection process and the receipt of a Form 483 or warning letter has always been
a serious matter. And the importance of sending an appropriate response is essential. A compa-
ny must show the FDA that an effective corrective action plan has been established, and ade-
quately spell out the plan in a response to the agency.
The response has always been critical, but the timeliness of that response has not been as criti-
cal. In the past, some companies have submitted multiple written responses to Form 483 obser-
vations, sometimes over many months. The FDA would review these responses as they came in
before deciding on whether to issue a warning letter. Thus, the entire process of writing
responses and reviewing them delayed enforcement and compliance.
That sometimes-lengthy process of sending responses has come to an end, however. The FDA
has begun to enforce a program that calls for a more timely review of its Form 483 inspection
observations. As of Sept. 15, 2009, six new policies became effective, including one that states
a company has 15 days to respond to a Form 483 before the FDA decides whether to issue an
official warning letter.
The FDA’s new strategy was described by FDA Commissioner Margaret Hamburg as “swift,
aggressive and effective” enforcement of the FDA’s laws and regulations. The FDA is also con-
tinuing to beef up its heretofore slim resources, hiring more inspectors and establishing more
international bases.
And, while the FDA is planning to be tougher, there is an upside for companies within this new
strategy. Companies that fix problems cited by the FDA in a 483 and/or warning letter could
receive a “closeout letter,” which is something like being issued a clean bill of health. This can
be a positive sign to investors looking for reassurance.
With these new policies, the FDA hopes to make the best use of its resources and to encourage
companies to correct violations in a timely manner. The agency has stated that the ultimate goal
is not to necessarily look for more violations, but to emphasize the protection of the public’s
health and safety.
This management report is based in part on an FDAnews audioconference conducted by
Frederick H. Branding, partner in the health law group of McGuireWoods LLP in Chicago,
Illinois, and Cathy L. Burgess, senior counsel for regulatory law at the American Red Cross.

4 Responding to FDA 483s: Strategies for Successfully Obtaining Closeout

  
 
 
 
This is a sample. 
 
Subscribe to 
The Executive Briefing Series 
to view the entire report.