Semiquantitative sensitization safety assessment of extractable and leachables associated with parenteral...

Extractable and leachables (E&Ls) associated with parenteral pharmaceutical products should be assessed for patient safety. One essential safety endpoint is local or systemic sensitization. However, there are no regulatory guidelines for quantitative sensitization safety assessment of E&Ls. A semiquantitative sensitization safety assessment workflow is developed to refine the sensitization safety assessment of E&Ls associated with parenteral pharmaceutical products. The workflow is composed of two sequential steps: local skin sensitization and systemic sensitization safety assessment. The local skin sensitization step has four tiers. The output from this step is the acceptable exposure level for local sensitization (AEL_ls) and this safety threshold can be used for local sensitization safety assessment. From the derived AEL_ls, the systemic sensitization safety assessment at step 2 proceeds in 2 tiers. The output from this workflow is the derivation of acceptable exposure level for systemic sensitization (AEL_ss). When the estimated human daily exposure (HDE) is compared with the AEL_ss, the margin of exposure is calculated to determine the sensitization safety of E&Ls following parenteral administration. The current work represents an initial effort to develop a scientifically robust process for sensitization safety assessment of E&Ls associated with parenteral pharmaceutical products.