RT Journal Article
SR Electronic
T1 Challenges in the Manual Visual Inspection of the Interior Surfaces of Single-Use Systems for the Presence of Particulate Matter
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP pdajpst.2020.012211
DO 10.5731/pdajpst.2020.012211
A1 Wormuth, Klaus
A1 Benoit, Olivier
A1 Kateb, Dounia
A1 Laruelle, Dany
YR 2021
UL http://journal.pda.org/content/early/2021/02/19/pdajpst.2020.012211.abstract
AB 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 (fluid-contacting) surfaces of the single-use system could potentially release and contaminate the drug product. Risk reduction requires methods which 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 (2D 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 single-use system type and size, but the POD for 2000 μm fibers was marginal to poor. Overall, POD decreased as bag size or tubing line length increased. An attribute Gage R&R 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 highlight the challenges in reliably detecting particulate matter in a visual inspection of the interior surfaces of single-use systems.