Warning Letters Report 2007 Frequent Deficiencies in Quality Control Labs and in the Clearing of Deviations in Production

GMP News
05 March 2008
 

Warning Letters Report 2007
Frequent Deficiencies in Quality Control Labs and in the Clearing of Deviations in Production

 
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

 


Author:
Dr. Gerhard Becker
On behalf of the European Compliance Academy (ECA)
 

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