FDA Warning Letter Report

GMP News No. 432

GMPNews
1 July 2004
 

FDA Warning Letter Report

 
Since 2000, CONCEPT HEIDELBERG creates the FDA Warning Letter Report ona yearly basis. In this news we present our systematic analysis of the findingsmentioned in the warning letters issued by FDA in the past Fiscal Year2003.

If one counts the citations of the individual paragraphs of 21 CFR(Code of Federal Regulations) Part 211 in the FDA warning letters, one getsan overview of the principal deficiencies found by FDA representativesduring inspections.

For the Fiscal Year 2003 (Oct. 2002 till Sept. 2003) we have finalisedthe analysis of all 42 warning letters citing the paragraphs of Part 211.Sorted by frequency, the deviations can be represented by the followinggraph:

The following table shows the exact titles of the paragraphs as well astheir assignment to the individual systems observed by FDA according toits system-based inspection approach, which became official in February2002 (see our GMPNews of 21 July 2003).

CFRParagraph

ExactTitle

Numberof Citations (Number ofCitations in FY 02)

System

211.100

Written procedures; deviations

Subpart F – Production and Process Controls

25(32)

Quality System

211.165

Testing and release for distribution

Subpart I – Laboratory Controls

24(22)

Quality System + Laboratory Control System

211.22

Responsibilities of quality control unit

Subpart B – Organization and Personnel

18(21)

Quality System

211.192

Production record review

Subpart J – Records and Reports

18(21)

Quality System

211.188

Batch production and control records

Subpart J – Records and Reports

17(20)

Production System

211.68

Automatic, mechanical, and electronic equipment

Subpart D – Equipment

16(8)

Facilities and Equipment System

211.160

General requirements

Subpart I – Laboratory Controls

16(22)

Quality System + Laboratory Control System

211.84

Testing and approval or rejection of components, drug productcontainers, and closures

Subpart E – Control of Components and Drug Product Containersand Closures

15 (11)

Materials System

211.25

Personnel qualifications

Subpart B – Organization and Personnel

14 (15)

Quality System

211.130

Packaging and labelling operations

Subpart G – Packaging and Labeling Control

11(7)

Packaging and Labeling System

211.186

Master production and control records

Subpart J – Records and Reports

11(7)

Production System

211.166

Stability Testing

Subpart I – Laboratory Controls

9(19)

Laboratory Control System

211.194

Laboratory records

Subpart J – Records and Reports

9 (10)

Laboratory Control System

211.67

Equipment cleaning and maintenance

Subpart D – Equipment

8 (21)

Facilities and Equipment System

211.110

Sampling and testing of in-process materials and drug products

Subpart F – Production and Process Controls

8(14)

Production System

211.122

Materials examination and usage criteria

Subpart G – Packaging and Labeling Control

8 (8)

Packaging and Labeling System

211.125

Labeling issuance

Subpart G – Packaging and Labeling Control

8(3)

Packaging and Labeling System

211.198

Complaint files

Subpart J – Records and Reports

8(10)

Quality System

From this compilation, it becomes clear that deficiencies in thequality system were the most frequent ones. As in the past year, the listis headed by § 211.100, which refers to the creation, approval andhandling of written procedures in the production area and to the handlingof deviations (see our GMPNews of 2 April 2004; the analysis given in that news relates to thecalendar year 2002, not to the fiscal year). The findings referred to thefact that there were no written procedures or that the existing procedureswere not followed - failures ascribed to the Quality Unit, just as in thefields "Testing and Release for Distribution"(211.165) and "Production Record Review" (211.192). Anotherthing often criticised by the FDA was the QU's failure to carry out itsresponsibilities and duties in an appropriate way.

As it was to be expected, the image of the higher positions of the topten deficiencies found in FY 2003 does not differ much from that of FY2002. According to the system-based inspection approach, the FDA takes anespecially critical look at the quality system in every inspection.

In contrast, there was a great increase in findings concerning thefacilities and equipment system with regard to the qualification,validation and calibration of production equipment (211.68) - as well asin the packaging and labeling system with regard to the handling andcontrol of labels (211.125).

The number of observations concerning "Equipment Cleaning andMaintenance" (211.67) and "Stability Testing" (211.166) hasfallen significantly; however, even if less frequent, these topics arestill to be found among the top ten.

Generally, the analysis of warning letters provides valuable clues tothe preparation of FDA inspections. One of the most important tasks to befulfilled prior to an FDA visit is to check the quality system forpossible gaps and to close them. As the other systems intersect with thequality system in several points, this approach should prove to be veryefficient.

Our analyses result in data collections containing the precisedescriptions of the findings in question. From now on, we will publishextracts of this very comprehensive data collection, which will deal withindividual deviations from the top-ten list.

Forthe members of the European Compliance Academy, we have made available thetables for the top 3 deviations in the members area (see item in the topmenu).
 

 
Author:
Dr Gerhard Becker
CONCEPT HEIDELBERG
   

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