Manufacturers of pharmaceuticals have come under growing pressure to perform sensitive and accurate analytical studies to detect, identify, and quantify low level extractable and leachable compounds (E&Ls), which may be potentially toxic or have otherwise undesirable effects on the efficacy of drugs. When it comes to E&L analysis, there are at least two critical analytical workflows involved, each with its own unique requirements. The first is extractables profiling which provides the first pass assessment and profiling of the worst-case leachables which may be encountered in the final dosage form or manufacturing process. The second is the actual testing of the final drug product or bioprocessing/manufacturing steps for targeted or suspected leachables or to identify any new leachables that weren’t previously expected. In this seminar, we will present an optimized analytical strategy for these E&L analysis workflows in some detail and with relevant real world examples.

First, we will present an analytical strategy for the qualitative assessment of extractables during profiling experiments with an emphasis on LC/MS and GC/MS for organic extratables profiling. Second, we will present a workflow suitable for laboratories performing leachables testing while operating under GMP compliance. This workflow enables the fully automated targeted and suspect screening and quantitation. The workflow is seamless and uniform for both LC/MSD and GC/MSD platforms. The workflow enables browsing through results from multiple manufacturing lots with ease and fully integrating calculations. We will illustrate this workflow with a leachables study performed on an ophthalmic drug product. The application provided quantitative information for leachables found to be above Analytical Evaluation Threshold (AET) and used spectral libraries with UV and MS spectra to aid identification of unexpected leachables.

• Speakers ▼

  

  Maggie Ostrowski, Ph.D.,
  Single Quadrupole Product Manager,
  GC/MS & LC/MS,
  Agilent Technologies, Inc.
  

  

  Syed Latif,
  Applications Engineer,
  Agilent Technologies, Inc.
  

  

  Smriti Khera, Ph.D.,
  Global Pharma Segment Marketing Manager,
  Agilent Technologies, Inc.
  

  

  Linda Wang,
  Senior Editor,
  C&EN