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Top 10 FDA Warning Letter Findings for Finished Pharmaceuticals in 2015

This is a historical document describing the Top 10 FDA Warning Letter Findings for finished pharmaceuticals in the Year 2015.

After reviewing the 27 warning letters issued for finished pharmaceuticals in 2015 (a decrease from the 33 issued letters in 2014) the following top 10 hit list has been assembled.

#10 Subpart J: Records and Reports 211.194 (a)

Laboratory records: Data Integrity

Frequency: 3


  • Incomplete batch documentation
  • Falsification of data on batch documentation
  • Data/test results deemed to be “trial” data and eliminated from released batch documentation without adequate justification
  • Relevant data pages torn off from laboratory logs and found in trash bags


#9 Subpart D: Equipment 211.68 (b)

Automatic, mechanical, and electronic equipment: Access control

Frequency: 4


  • Passwords to computer systems/database shared between multiple operators
  • Audit trial features disabled in key data collection software
  • Data files deleted without alternative record or justification
  • Data files modified without record or traceability


#8 Subpart B: Organisation and Personnel 211.22 (d)

Responsibilities of quality control unit: Documentation

Frequency: 4


  • Failure to document procedures and roles and responsibilities applicable Quality Control Unit (QCU)
  • Failure to follow written procedures


#7 Subpart I: Laboratory Controls 211.165 (a)

Testing and release for distribution: Finished product testing

Frequency: 6


  • Failure to test all APIs in the finished product at the time of batch release


#6 Subpart F: Production and Process Controls 211.113 (a)

Control of microbiological contamination

Frequency: 6


  • Inadequate scientific data to establish that aseptic process hoods provide protect from lower quality surrounding air
  • Use of non-sterile cleaning wipes
  • Inadequate/lack of dynamic airflow studies in controlled environments
  • Failure to validate aseptic processing equipment
  • Poor aseptic processing techniques


#5 Subpart I: Laboratory Controls 211.167 (a)

Specific testing requirements: Finished product testing

Frequency: 7


  • Inadequate sterility testing on finished products, containers or closures


#4 Subpart B: Organisation and Personnel 211.28 (a)

Personnel responsibilities: Gowning

Frequency: 7


  • Not replacing gowns at the required frequency
  • Use of non-sterile gowns in aseptic processing areas
  • Exposed skin
  • Improper storage of sterile gowns


#3 Subpart C: Buildings and Facilities 211.42 C (10) (v)

Design and construction features: Cleaning Validation

Frequency: 8


  • Failure to sanitize/sterilize all equipment before being transported into the controlled environment
  • Failure to use appropriate sterilization agents e.g. sporicidal


#2 Subpart I: Laboratory Controls 211.166 (a)

Stability Testing

Frequency: 9


  • Failure to conduct finished product stability testing for all APIs in the product
  • Un-validated stability test methods


#1 Subpart C: Buildings and Facilities 211.42 C (10) (iv)

Design and construction features: Environmental Monitoring System (EMS)

Frequency: 13


  • Inadequate EMS system in place to monitor aseptic processing areas
  • Inadequate scientific studies/data to establish cross-contamination prevention
  • Inadequate justification for sampling plans (location, frequency, method) for EMS
  • Failure to follow established sampling plans


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