Safety Risk Categorization of Organic Extractables Associated with Polymers used in Packaging, Delivery and Manufacturing Systems for Parenteral Drug Products

To develop and justify a Risk Evaluation Matrix for estimating the safety risk associated with extractables from plastic materials used in pharmaceutical applications and to apply that matrix to approximately 510 extractables to assess the risk that they would accumulate in drug products at levels sufficiently high to affect patient safety. The Risk Evaluation Matrix considers toxicological, availability and solubility characteristics of extractables. Safety Risk categories were established based on certain scaled values for these characteristics, Total Risk Scores were calculated for each extractable and the extractables were categorized with respect to their safety risk based on these calculations. The Total Risk Scores were normally distributed around a value of 20 to 23, corresponding to safety risk categories of moderate and intermediate risk. The range in Risk Scores defined by the mean +/- one standard deviation encompassed the entire region of moderate and intermediate risk. Approximately 15% of the extractables were categorized as lowest risk while 3% of the extractables were categorized as highest risk. Categorization of extractables could facilitate the selection of materials for use in pharmaceutical systems, the analytical testing of extracts and the selection of target extractables.