FDA Warning Letters in 2010 for GCP Failures

FDA Warning Letters GCP

FDA Maintains Pace for GCP Warning Letters
in 2010

After a significant rise in Warning Letters issued for GCP failures the past few years, FDA seems to have leveled off in the number of Warning Letters issued in 2010. I have not seen FDA metrics for Fiscal Year 2010 but my own review of Warning Letters issued to clinical investigators in 2010 doesn’t show a sharp increase, only more of the same. In particular, the primary deficiency categories are quite similar as they were 15 years ago when I attended my first FDA Bioresearch Monitoring course. Although the terminology has modernized over the years it can be summed up in four words: protocol adherence and recordkeeping.

UPDATE: I have posted below the BIMO FY-2010 Metrics below, courtesy of the Office of Good Clinical Practice- FDA/OC (many thanks). They are the people responsible for the Clinical Trials link on the FDA website. The metrics essentially confirm some of the conclusions of this post.

When looking at an FDA Warning Letter I am always curious about the very first charge that is listed. You will note that FDA does not use categories such as Critical, Major, or Minor as many company QA departments do. MHRA, the United Kingdom’s regulatory agency for health products, also uses a rating system, Major, Minor, and “Other.” However, FDA lists violations in the order of significance and the first item listed on either a Warning Letter or Form FDA 483, Inspectional Observations, is supposed to be the most significant. In ten Warning Letters I reviewed that were issued to clinical investigators in 2010 “failure to follow the investigational plan” was listed first on Warning Letters issued by the Center for Drugs four times. “Failure to conduct the investigation according to the signed agreement, the investigational plan, and FDA regulations was listed first in two Warning Letters issued by the Center for Devices and Radiological Health. The lesson here is that FDA pays close attention to protocol adherence.

FDA Warning Letters GCP

Keeping on Top of Records and the TMF

Recordkeeping violations were listed first on one Warning Letter but were included on eight of the ten Warning Letters I reviewed. Perhaps this is one of the reasons for the strong interest in the trial master file, the TMF. This pattern of violations has been happening a very long time. The first article I wrote after leaving FDA (six years ago) was called, “Protocol Adherence and Recordkeeping: The Twin Pillars of GCPs.” A typical Warning Letter was issued on 30 September 2010 (there is a link below). So the good news is that many researchers are paying attention to the increase in FDA Warning Letters the past few years and are instituting changes. The bad news is that there are still some people that keep repeating the same mistakes.

FDA GCP Warning Letter: 30 SEP 10

BIMO metrics – FY-2010

A new feature from FDAzilla on FDA 483s

Read the Press Release on 483s


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GxP Perspectives LinkedIn Group

Visit the TMF Page at the Top Right of the Blog! I am trying to assemble resources for those of us concerned with the Trial Master File. I welcome any contributions you might have of interesting articles and resource documents.


In news from GxP Perspectives.

On the Blogroll: Catalyst Biomedical – A blog that I recently discovered and that you may find of interest

Two Important New GCP Documents: There is a new Final Rule on required elements of Informed Consent. You can read the Federal Register Announcement here that includes FDA comments in the preamble. The exact change in 21 CFR Part 50 is:

“Sec. 50.25 Elements of informed consent.

* * * * *
(c) When seeking informed consent for applicable clinical trials,
as defined in 42 U.S.C. 282(j)(1)(A), the following statement shall be
provided to each clinical trial subject in informed consent documents
and processes. This will notify the clinical trial subject that
clinical trial information has been or will be submitted for inclusion
in the clinical trial registry databank under paragraph (j) of section
402 of the Public Health Service Act. The statement is: “A description
of this clinical trial will be available on
http:[sol][sol]www.ClinicalTrials.gov, as required by U.S. Law. This
Web site will not include information that can identify you. At most,
the Web site will include a summary of the results. You can search this
Web site at any time.”

Your comments are welcome on FDA Warning Letters

One Response to FDA Warning Letters in 2010 for GCP Failures

  1. Jon Nugent says:

    Companies whose products must meet regulatory and ISO guidelines know how to produce and they know how to control their output.

    Companies simply know what works and they stick to it. FDA regulated industries are subject to the fact that habits—when left unchanged—have a nasty way of turning the tables on good fortune.

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