CLARK MERCHANT,1 DEEPAK K. SHARMA,1 DAVE KING,1 PETER OMA1
1ProteinSimple Technologies Inc., 115 Terence Matthews Cr., Ottawa, Ontario, Canada, K2M2B2
ABSTRACT: The detection and isolation of particle populations in parenterals is an invaluable process for quality control and diagnostics during development and commercialization of formulations. USP <788> does not consider intrinsic sources of particulate matter such as protein aggregates, silicone oil droplets or air bubbles, whose populations can vary significantly lot-to-lot and mask the population of interest (whether foreign or proteinaceous) . The presence of air bubbles usually causes an over-counting of particulate in the formulation, creating false positives during quality control testing. Silicone oil has a far greater impact on quality control, being a possible cause of protein aggregation which can potentially render a product clinically unacceptable due to potential for immune response in the patient.
An inherent challenge for quantification of silicone oil droplets and air bubbles from protein aggregates in biopharmaceutical formulations is the difficulties in detecting and differentiating these populations. Micro-Flow Imaging (MFI) utilizes a precision optical system in a bright-field configuration to provide high-contrast images and morphological information of particles in a solution. Through appropriate morphological filter development, results show successful differentiation of well over 90% between protein aggregates, air bubbles and silicone oil in a PBS buffer solution for particles within USP <788> size limits.
PRESENTED AT:
IBC’s 5th Annual Biophysical Analysis for Bioprocessing, San Francisco CA, USA
2010 ProteinSimple_Differentiation of Particles using MFI.pdf
2010 ProteinSimple_Differentiation of Particles