Deviations and Failure Investigation - CAPA in the light of FDA Inspections

Deviations and Failure Investigation – CAPA in the light of FDA Inspections

GMP News
28 March 2007
 

Deviations and Failure Investigation – CAPA in the light of FDA Inspections


As indicated in ECA’s Warning Letter Report (see GMP
News from 10 January 2007), production record review is one of the most frequent GMP deviations made by the FDA. In the fiscal year 2006, observations regarding this subject were No.2 in the ranking of cited GMP deficiencies. In the previous period, production record review deviations were observed more than any other issue.

After a closer look at these citations, it becomes obvious that most observations are caused by failures in deviation management and CAPA. In most cases, deviations were noticed by the pharmaceutical company but no sound investigation was performed and no consequences were defined. Below you will find an excerpt from the FDA Warning Letters Report*:

The FDA Warning Letters Report

Finished Pharmaceuticals
Top Nine Citations in Fiscal Year 2006 – Abstracts of the original wording

Date of Issue:
1 November 2006

 211.192Subpart J  Records and Reports Production Record Review
(Nr. 2 of the Top Nine in FY 2006)

Original Wording

Company / Date

Failure to thoroughly investigate failures of finished drug products or drug product components to meet established specifications. Specifically, finished product samples that test positive for microbial growth are retested on new media; no investigation into the first positive result is conducted, as required.
[21 CFR 211.192].

Diversified Manufacturing Corporation;

Newport, Minnesota; 20.10.05

There is a failure to investigate a batch that did not meet specifications.
[21 CFR § 211.192].

Cody Laboratories, Inc.;

Cody, Wyoming;
07.04.06

Unexplained discrepancies of a batch or any of its components were not always thoroughly investigated. The investigations did not always extend to other batches of the same drug product and other drug products that may have been associated with the specific failure or discrepancy. 21 CFR 211.192

Pliva Croatia Ltd.;

Zagreb Croatia;
28.04.06

Failure to thoroughly investigate the unexplained discrepancies or out of specification results in batches of … tablets manufactured at your site as required under 21 CFR 211.192.

Wyeth Pharmaceuticals Company;

Madison, NJ;
08.05.06

Written records are not always made of investigations into unexplained discrepancies, nor did investigations of unexplained discrepancies extend to other batches of the same drug product or other drug products that may have been associated with the specific failure or discrepancy
[21 CFR § 211.192]
.

Specifically

a) Product samples tested in conjunction with a complaint loose caps on Nitroglycerin tablets lot … produced out-of-specification results for assay and content uniformity. There was no examination of product retains or a review of the batch record. The sample results were invalidated due to product damage from environmental exposure although there was no provision for this in your firm’s written procedure.

 b) Product samples tested in conjunction with complaints regarding tablets not dissolving … were tested for all release specifications except assay. There was no justification for omission for this test, nor was there any evidence of an examination of stability lots, retained samples, or a review of the batch records.

 c) The reference standard injection following assay and content uniformity testing of Hyoscyamin Sulfat Tablets, lot … failed to show any peaks due to a leaking column. There was no documented investigation of this deviation, there was no assessment of the impact of the leaking column…

 d) There was no documented investigation regarding HPLC malfunctions requiring external repair. … there is no documentation regarding whether the malfunctions impacted any analyses, and if so, what the corrective actions were regarding those analyses.

Concord Laboratories, Inc. ;

 

Fairfield, New Jersey;
11.07.06

FDA’s recently published Quality System Guide and those Warning Letter citations clearly emphasise the increasing relevance of a proper deviation management and CAPA.

* Find out more about the

FDA Warning Letters Report.

 

To get more information on the US authority, please see the 2-day ECA education coursefrom 26 - 27 April 2007 in Prague, Czech Republic

Learn more about the regulatory requirements and how to run your documentation and quality systems efficiently and GMP-compliant in the following ECA course:


from 22 – 23 October 2007 in Copenhagen, Denmark

 
Author:
Wolfgang Schmitt
On behalf of the European Compliance Academy (ECA)
  

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