DEEPAK K. SHARMA,1 PETER OMA,1 MUPPALLA SUKUMAR2
1ProteinSimple Technologies Inc., 115 Terence Matthews Cr., Ottawa, Ontario, Canada, K2M2B2
2Biopharmaceutical Research and Development, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285
ABSTRACT: The need to monitor, measure and control sub-visible proteinaceous particulates in bio-pharmaceutical formulations has been emphasized in recent publications and commentaries. Some of these particulates can be highly transparent, fragile and unstable. For much of the size range of concern, no practical measurement method with adequate sensitivity and repeatability has been available. Micro-Flow Imaging™ (MFI) has been shown to provide high sensitivity in detecting and imaging transparent protein particles.
The focus of current study was to investigate the accuracy of MFI to size and count proteinaceous particles, in high concentration opalescent protein solutions. Protocols were developed to generate proteinous particles of a mAb which were used to investigate precision and linearity of detection by MFI or to access accuracy by comparison to light obscuration and manual microscopy.
Results showed that MFI can detect proteinaceous particles, even in the context of opalescent formulations. The sizing and concentration accuracy of MFI for polystyrene and glass particles, was unaffected by the opalescence of the medium. MFI also demonstrated a high degree of linearity for quantifying proteinaceous particles in opalescent solutions over a wide range of particle concentrations. These particles were significantly underestimated by LO and manual microscopic technique, particularly in sub-visible size range.
PRESENTED AT:
2010 IBC’s Formulation Strategies for Protein Therapeutics, Providence RI, USA
2010_ProteinSimple_sbVP Analysis in high conc protein form using MFI.pdf
2010 ProteinSimple_sbVP Analysis in high conc