<1663> ASSESSMENT OF EXTRACTABLES ASSOCIATED WITH PHARMACEUTICAL PACKAGING/DELIVERY SYSTEMS 

SUMMARY

The completeness of an extractables assessment can only be judged against the overall goals of the assessment. For example, an extractables assessment accomplished solely for materials characterization might include one extracting solvent, one extraction technique, and one set of extraction conditions; along with a materials-based threshold (e.g., 10 ppm w/w). 

Such an extractables assessment might be considered complete if all extractables above the defined threshold were identified to the confident level (defined above) and quantitated. For an extractables assessment designed to establish a rigorous leachables–extractables correlation for a high risk drug product, where a challenging safety threshold might apply (e.g., 0.15 µg/day; see reference 5), good scientific practice and due diligence requires the following:

• Generation of extracts should be accomplished with
  1. Multiple solvents or extracting media with varying extracting power based on the known extracting power of the drug product vehicle;
  2. Multiple and complementary extraction techniques, including those with the capability for volatiles analysis;
  3. Extraction conditions that allow equilibrium to be achieved.

  
  

• Characterization of extracts should use
  1. Multiple and complementary analytical techniques;
  2. Careful sample preparation, keeping the analytical technique(s) in mind;
  3. A systematic process for identification and quantitation of extractables.