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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*:
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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 |
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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 |
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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 |
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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 |
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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.
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