Challenges in the Manual Visual Inspection of the Interior Surfaces of Single-Use Systems for the Presence of Particulate Matter.

Abstract

Single-use systems find increasing application downstream of final filters in the production of antibody, vaccine, gene, and cell therapy drug products. For such critical applications, particulate matter attached to the interior (product-contacting) surfaces of the single-use system could potentially be released and contaminate the drug product. Risk reduction requires methods that reliably detect particulate matter on the inside of single-use systems. Here we describe the results from the development and validation of a manual visual inspection method for the detection of particulate matter inside transparent single-use systems. Test kits consisted of single-use systems (2 D bags, tubing lines, and bag/tubing assemblies) internally seeded with test particles (black, clear, or fiber) ranging from 100 to 2000 µm in size. A designed experiment determined the optimal light intensity, inspection time, and time between inspector breaks required to maximize the probability of detection (POD) for particles. POD > 70% for black and clear particles started at particle sizes exceeding 400 to 1000 µm depending on the single-use system type and size, but the POD for 2000 µm fibers was marginal to poor. Thus, for single-use systems, the particle size to achieve POD > 70% shifted to significantly larger sizes than the 150-250 µm particle size typically detectable in drug products. Overall, the POD decreased as the bag size or tubing line length increased. An attribute gage repeatability and reproducibility study using three inspectors validated the inspection method for reliable detection of black and clear particles ≥ 1000 µm in size over the entire size range of single-use assemblies and tubing lines examined. Fibers of length 1000 and 2000 µm were not reliably detected. The results highlighted the challenges in reliably detecting particulate matter in a visual inspection of the interior surfaces of single-use systems.