Characterizing Protein Aggregates in Biopharmaceuticals
Particulates in parenteral drug development have always been a serious issue. In biopharmaceuticals the issue is compounded by reported impacts of aggregates and particles on the product’s efficacy, safety, and immunogenicity. FDA regulations strongly recommend in-depth characterization of sub-visible particles in protein therapeutics. New recommendations are specifically targeted at the characterization of sub-visible particles between 2 and 10 microns.
Most protein therapeutics contain a variety of particles, including proteins, silicone drops, and contaminants that have a variety of shapes. Light obscuration, which is typically used to comply with USP <788>, cannot differentiate one particle from another, nor fully characterize particles because the technology assumes all particles are spherical. The FlowCAM imaging particle analysis system allows you to simultaneously determine particle shape, type, and size distribution, plus provides you with an image of each measured.
Image quality is extremely important when characterizing, identifying, and differentiating particles such as protein aggregates, silicone oil, air bubbles, and other contaminants, and it is essential for accurate sizing measurements. Blurry images lead to poor characterization of particles and can affect your particle size distribution.
The better the overall image quality, the easier it is for the instrument’s software to recognize patterns, and in turn characterize particles. Blurry images make it difficult to distinguish protein aggregates from silicone droplets and other contaminants, especially in the 2 - 10 µm range. Poor image quality also makes it difficult for the instrument to discriminate between a single protein amalgamation from several small proteins in close proximity to one another
If particles are not characterized correctly, your size distribution may not be ascertained reliably. Smaller or faint particles (such as those with a low refractive index) may be missed entirely, lowering particle counts. Large particles may be fractionated into smaller particles - reducing the number of large particles while increasing the number of small particles.
Only the FlowCAM dynamic image particle analysis system, has the image quality necessary to accurately count, size and classify particles in the 2 - 10 µm range.
Benefits of the FlowCAM
Learn the 5 important considerations when characterizing protein therapeutics with flow microscopy. Go to article now >>
Characterizing Biologics Using Dynamic Imaging Particle Analysis >>
Protein Sciences Corporation, Meriden, CT >>
AB BioTechnoloiges Inc., Bloomington, IN >>
Flow Imaging of Subvisible Protein Particles: Moving Towards Best Practices >>
The Importance of Thresholding in Imaging Analysis of Protein Aggregates >>
A Comparison of Methods for Quantifying Silicone Droplets in Biologics Using Dynamic Imaging Particle Analysis
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