Characterization of Protein Aggregates in Parenteral Drug with Imaging Particle Analysis

Protein Aggregates imaged by FlowCAMThe FlowCAM imaging particle analysis system allows you to simultaneously count and classify particles in your therapeutic protein formulations and vaccines - and provides you with the critical data you need to ensure product safety. The FlowCAM overcomes the limitation of particle counters, while giving additional particle information typically only found by using microscopy. Plus, imaging particle analysis provides a much more detailed look at the particulates than does classical light obscuration technologies used to comply with USP method <788>.

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 the identity and quantity of particles in protein therapeutics. Particle concerns are increasingly common in FDA submissions, and in some cases, particle matters have resulted in drug recalls.

Air Bubble versus Silicone Oil imaged by FlowCAMImage 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 particles produce a relatively lower count and concentration compared to “sharp” particles. Poor characterization creates a wider variation in measurements, and can lead to higher rates of false positives, false negatives, as well as a lower statistical confidence.

FlowCAM represents a powerful tool with unique features for detecting, counting, and characterizing protein aggregates and other particles in parenteral drug formulations.

Benefits of the FlowCAM

  • Superior Image Quality - Images from the FlowCAM are the sharpest in the industry, which allows you to distinguish the morphological differences associated with aggregated proteins. You are able to see the difference in morphological properties of protein aggregates, which may indicate bacterial or viral contamination.
  • Flexible and Configurable – Not all proteins look alike. The FlowCAM provides multiple objective / flow cell combinations, so you can optimize the system to suit the formulation under test. Both disposable flow cells and fixed field of view flow cells are available, plus 2X, 4X, 10X, and 20X objectives are also available.
  • High Sensitivity – The FlowCAM provides superior ability to detect particles with a low refractive index because you are able to set threshold limits for dark and light particles. Because protein aggregates can be transparent, there are instances where the aggregate will actually be lighter than the background intensity. FlowCAM allows you to optimize your threshold settings in order to properly capture, measure, and calculate concentration for protein aggregates found in therapeutic proteins, which is especially important when working with high concentration protein samples.
  • Small Sample Volume – The FlowCAM can provide reliable test results with a small sample volume. Our minimum sample volume is only 50 uL, which is especially important when working with precious samples that are in short supply.
  • Superior Software – FlowCAM and Visual Spreadsheet provide industry-leading data analysis capability including the ability to establish custom filters based on over 30 particle properties. Satellite software is also available, so post processing of FlowCAM data can be done at a remote location for added convenience and for sharing data with others.

Article Download

Characterizing Biologics Using Dynamic Imaging Particle Analysis >>
Published in BioPharm International

Compliance done with knowledge and understanding, not by rote: Contract lab solves biopharmaceutical challenges using imaging particle analysis >> 
Published in Processing Magazine

Poster Download

Flow Imaging of Subvisible Protein Particles: Moving Towards Best Practices >>
Presented at AAPS Biotech 2013

The Importance of Thresholding in Imaging Analysis of Protein Aggregates >>
Presented at WCBP 2014

Application Note Download

Detection of Protein Aggregates in Parenteral Drug Formulations >> 

See the FlowCAM in Action!

This quick video will show you how the FlowCAM works and acquires data!