SHANNON SOUTHALL, CHARLENE E. BRISBANE, AMOL KETKAR
Biopharmaceutical Technologies, Biopharmaceutical Development, GlaxoSmithKline Pharmaceutical R&D, King of Prussia PA, USA
Posted with permission from Shannon Southall
Purpose:
To evaluate Micro-Flow Imaging (MFI) technology by exploring its particle detection and enumeration capabilities. Additionally, to implement MFI technology in formulation screening by comparing the propensities of protein formulations to form particles upon application of shear stress.
Methods:
Experiments were conducted using the ProteinSimple DPA-4100 Flow Microscope to assess: (1) analytical variability; (2) particle size and morphology analysis capabilities; and (3) advantages over traditional light obscuration methods. In addition, particle formation in two protein formulations was monitored as a function of continuous application of shear over a 24 hour period.
Results:
Instrumental variability was measured using PolyStyrene standards and found to be less than 5%. Increased variability was observed when measuring protein samples; however, optimization of sample handling and sample introduction lowered this variability to 7%. MFI enabled the use of significantly smaller sample volumes (2 mL), compared to light obscuration (20mL). In addition to conserving sample, the ability to capture images during a sample run allowed for further analysis of particles based on size, shape, and relative intensity. Using this capability, air bubbles or silicone droplets could also be detected and quantified. Finally, the instrument was able to reveal significant differences in particle formation (10 fold) between different sample formulations under shear stress conditions, confirming its utility for formulation screening.
Conclusion:
MFI has potential to be a valuable aid during biopharmaceutical product formulation development due to its unique capability for discreet particle detection and quantitation, as well as particle size and morphology characterization.
PRESENTED AT:
2009 AAPS National Biotechnology Conference, San Francisco CA, USA
2009 AAPS NBC_GSK_Particle investigation in BioPharm formulations using MFI.pdf
2009 AAPS NBC GSK Particle investigation