FlowCam - Flow Imaging Microscopy Blog

Particles are ubiquitous in biotherapeutics and can drastically impact the efficacy of a given drug. Therefore, characterizing them is a critical step in biotherapeutic development, both to ensure samples meet particle limits set by regulations like USP <787/788>, and to maximize the safety and efficacy of the therapeutic.

New, innovative technologies may help researchers working with these therapies better understand the particles in their samples and, in turn, make more informed decisions about a sample’s quality. 

In microscope systems, the numerical aperture and the wavelength of the light determine how highly-resolved the images will be (in the case of microscopy, "resolved" refers to the minimum distance between particles where they can be recognized as distinct from one another). When using Flow Imaging Microscopy to analyze particles under 2 µm, clear images, accurate sizing, and consistent categorization are crucial, and all depend on the numerical aperture setting.

Many new types of biotherapeutic Active Pharmaceutical Ingredients (API) such as viruses, nanomedicines including virus-like particles and lipid nanoparticles, and cell-based medicinal products have recently experienced a significant surge in interest. Like proteins before them, formulations of these APIs contain particles that need to be characterized to ensure product quality and efficacy. Particle characterization technologies like FlowCam thus continue to play a critical role in developing and manufacturing safe biotherapeutics regardless of the API. 

We’re excited to announce the next-generation FlowCam Nano! The newest member of our FlowCam instrument family detects and images particles between 300 nm and 2 µm—the smallest objects visible by light microscopy.

FlowCam Nano can be used to determine the types of submicron particles present in samples, such as biotherapeutic particles or aggregates, drug delivery vehicles, bacterial cells, and other nanoparticles of interest. If not addressed, many of these smaller particles are prone to agglomeration into larger subvisible and visible particles. FlowCam Nano may be used to identify and mitigate these smaller particles before larger ones will form. Other species like bacterial cells inherently exhibit a size near or below the lower size limit of FlowCam 8000 and will only be detected by FlowCam Nano.

In a recent paper discussing particle counting and analytical techniques, the number and type of particles present in intravitreal injection formulations of three different drug agents used against vascular endothelial growth factor were investigated.

Last week, The-Scientist.com introduced their new Research Products blog. Their very first post discusses the capabilities of the FlowCam Nano:

Characterization of subvisible particles in protein therapeutics has become an increasingly important means to ensure the development of safe, stable, and effective medicines.  Many analytical techniques are available to identify and prevent not only protein aggregation, but to fulfill regulatory requirements. The purpose of this study by Danny Chou, President and Founder of Compassion BioSolution, LLC is to compare different techniques and their ability to identify subvisible particles and what relationship exists between the number of particles and different stress conditions imposed upon the protein drug products.

Flow Imaging Microscopy has been widely implemented for the analysis of particles ranging in size from 1-10µm. Yet, in recent years the FDA has highlighted the need for better analytical tools to fully understand how different stress conditions can impact the stability of the formulation. While light obscuration and membrane microscopy have been the primary methods to conduct USP testing for particles between 10µm - 25µm, regulators are now moving towards expecting orthogonal analytical methods to characterize and provide quantitative data on particles in the 2µm - 10µm range as well.

FlowCam Nano offers the ability to image and analyze particles ranging from 30µm down to as small as 300 nm.

The 4th Annual European Workshop on Protein Aggregation and Immunogenicity will be held in Salzburg-Wals, Austria on January 28 and 29.  This conference serves as a European summit for thought leaders and academic researchers to come together and discuss the issues of protein aggregation and its effects on the immunogenicity of therapeutic protein drug products. We are excited to attend and exhibit the FlowCam imaging particle analyzer with our German distributor, Anasysta.

Proteins and contaminants from a parenteral drug sample, imaged and analyzed by the FlowCam.

December 2018 — A recent study by researchers from the University of New England and University of New Hampshire has demonstrated that flow imaging microscopy is an accurate, more efficient, and more informative method of elastin-like polymer (ELP) coacervate analysis than standard methods. ELP coacervates are a class of molecules with promising applications in drug delivery vehicles, tissue engineering, environmental remediation, and more. ELP coacervate architecture is stimuli-responsive and highly tunable, making them ideal for the above-mentioned applications.  

The FlowCam continues to be an important instrument in biopharmaceutical research. The ability to image and characterize morphological features of particulate in parenteral formulations is an important aspect of ensuring quality and safety in injectable drug products.