In the previous two fiscal years the number of warning letters issued to drug
manufacturers remained static. In comparison this number clearly dropped in
2007. This trend can also be noticed for manufacturers of blood and biologic
products. The number of warning letters relative to medical device manufacturers
is still quite large and remained in the same range as last year.
|
FY 2006 |
FY 2007 |
WLs regarding Part 211 (Drugs) |
20 |
13 |
WLs regarding Part 600, 606, 610, 630, 640, 680 (Blood, Blood
Products, Biologicals) |
10 |
6 |
WLs regarding Part 820 (Medical Devices) |
79 |
78 |
Wirth regard to topics and frequency there is almost no difference compared to
the last year. The following paragraphs in the Code of Federal Regulations (CFR)
were violated the most:
-
Laboratory Controls, general requirements (211.160)
-
Production record review (211.192)
-
Responsibilities of quality control unit (211.22)
-
Testing and release for distribution (211.165)
-
Control of microbiological contamination (211.113)
Alike in the years before, there were frequent deficiencies in
the areas quality control and respectively labs in the current fiscal year. They
range from inadequate calibration of lab instruments to disregarded OOS results
and not conducted impurity analyses to not representative sampling. Following a
few representative quotes:
Failure to maintain complete records of the periodic calibration of
laboratory instruments
Our investigators also uncovered numerous instances where out-of-specification
test results obtained during the testing of your firm's drug products were not
adequately investigated. Instead, additional testing was conducted and the
original results were discarded without any documented justification.
Drug products manufactured by your firm have not been evaluated for the
presence of impurities and degradation products.
Samples taken of drug products for a determination of conformance to written
specifications are not representative.
Obviously the FDA frequently finds violations of important GMP basics in its
inspections of labs. Moreover, important duties in quality insurance as, for
instance, the clearing of deviations in the production process are often
disregarded. A typical keyword that can be found in the most warning letters is
unexplained discrepancy. The following quotes clarify the particular
circumstances:
Failure to conduct and document a thorough investigation of any unexplained
discrepancy or failure of a drug product batch to meet its specifications or to
extend the investigation to other batches that may been associated with the
specific failure or discrepancy.
Failure to thoroughly review any unexplained discrepancy and the failure of
a batch or any of its components to meet any of its specifications, whether or
not the batch has been already distributed.
The following table shows the five most frequent deficiencies in the fiscal
years 2006 and 2007.
The five most frequent GMP Deficiencies in Warning Letters in the Fiscal Years
2006 and 2007
Top List No |
Fiscal Year
2006 |
Fiscal Year
2007 |
1 |
211.22
Subpart B Organization and Personnel
Responsibilities of quality control unit |
211.160
Subpart I Laboratory Controls
General requirements
211.192
Subpart J Records and Reports
Production record review |
2 |
211.192
Subpart J Records and Reports
Production record review |
211.22
Subpart B Organization and Personnel
Responsibilities of quality control unit |
3 |
211.67
Subpart D Equipment
Equipment cleaning and maintenance
211.166
Subpart I Laboratory Controls
Stability Testing |
211.165
Subpart I Laboratory Controls
Testing and Release for Distribution
|
4 |
211.100
Subpart F Production and Process Controls
Written procedures; deviations
211.160
Subpart I Laboratory Controls
General requirements
211.165
Subpart I Laboratory Controls
Testing and Release for Distribution
211.194
Subpart I Laboratory Controls
Laboratory Records |
211.113
Subpart F Production and Process Controls
Control of microbiological contamination
|
5 |
211.25
Subpart B Organization and Personnel
Personnel qualifications
211.84
Subpart E Control of Components and Drug Product Containers and Closures
Testing and approval or rejection of components, drug product containers,
and closures
211.137
Subpart G Packaging and Labeling Control
Expiration dating
|
211.42
Subpart C Buildings and Facilities
Design and construction features
211.67
Subpart D Equipment
Equipment cleaning and maintenance
211.68
Subpart D Equipment
Automatic, mechanical, and electronic equipment
211.188
Subpart J Records and Reports
Batch production and control records
211.194
Subpart I Laboratory Controls
Laboratory Records |
The analysis shows, that again the authority punished fundamental violations in
the areas lab control systems and quality systems last year. Although the total
number of warning letters decreased, this trend seems to remain.
Based on comprehensive data, quotes in warning letters from the last fiscal
years (2002-2007) were systematically analysed. This analysis is available on
the CD FDA Navigator. To find out more, please visit
http://www.gmp-compliance.com/eca_gmppublication.html
|