Top-down measurement uncertainty for subvisible particles by light obscuration in injections - Uncertainties from precision and recovery studies.

The subvisible particle counting by light obscuration is a critical quality control test in injectable drug products. Incorrect conformity decisions, particularly false acceptance of non-compliant batches, may result in significant health risks to patients. This study evaluates the measurement uncertainty associated with subvisible particle quantification using the light obscuration test, as described in USP < 788 > . A top-down approach was applied, integrating precision and recovery data. Four intravenous drug products (linezolid, fluconazole, metronidazole and ciprofloxacin) were analyzed under different sampling volumes and discard flow rates. Results demonstrated that measurement uncertainty is magnitude dependent. Particles count in the range < 10, 10-100, 100-1000, 1000-10000, and > 10000 presented relative uncertainty values of 275%, 53%, 21%, 16%, and 11% respectively. Precision uncertainty contributions dominate at low counts, while bias uncertainty contributions become progressively more influential at higher subvisible particle range. Uncertainty estimation integrated contributions from precision and trueness supported by recovery studies using an independent particle counter. The application of a top-down enhances the reliability of conformity decisions, reducing the risk of false acceptance or rejection of injectable drugs and supports robust pharmaceutical quality control practices.