Amber Raises the Bar on Product Quality with Micro-Flow Imaging (MFI)

STATE OF THE ART PARTICLE CHARACTERIZATION

KBI Biopharma is a contract development and manufacturing organization specializing in commercial-scale mammalian and bacterial expression of drug substances. Amber Fradkin, Ph.D., is the Associate Director of their
Particle Characterization Core Facility. Her group does contract testing for specialized particle characterization and identification and works with biologics, small molecules, vaccines, NBCDs and materials on a regular basis. The facility uses a state-of-the-art suite of particle technologies to investigate and develop new particle analysis methods on their client’s products and for routine analyses.

YES/NO ANSWERS WITH LO NOT ENOUGH

The Particle Characterization Core Facility handles a wide range of projects like forensic ID, comparability/biosimilarity, device/IV bag compatibility, method development/validation, stability testing, batch release testing and
product/process characterization. Standard light obscuration (LO) methods weren’t cutting it for particle analysis as it only told them if they did or didn’t have particles. To fully characterize particles in all their biologic samples, they needed to know exactly what those particles were and also make sure they didn’t miss translucent ones in the process — LO couldn’t do either.

In 2011, KBI responded to the biopharmaceutical industry’s understanding of how subvisible particles affected injectable product quality by getting its first MFI instrument, the DPA 4200 system. But their sample demand quickly
outpaced the capacity of this manual system.

RAMPING UP PARTICLE CHARACTERIZATION

Amber’s group was one of the first to upgrade to the MFI 5200 + Bot1 autosampler when it launched. When doing particle analysis on their biologics, cell therapies, vaccines and even materials, they found flow imaging gave them a plethora of information they weren’t able to get before. They used the images provided by MFI to perform more in-depth analyses of particle profiles to identify trends, evaluate stability and understand if a sample was outside of ‘what is normal’ for a product. They were also able to couple the images they got with MFI with images from automated Raman microscopy to classify and identify the chemical identity of particles.

On top of the incredible amount of information MFI provided, the team found the system robust and reliable, and really easy to operate. They could analyze several milliliters of sample to get a good understanding of the
particle population(s) present, and customize orthogonal methods and instrument parameters/operation from there to specifically target one or more populations for characterization. Plus with the MFI 5200 system + Bot1,
they were able to keep up with their sample load without a backlog.

BETTER UNDERSTANDING OF PRODUCTS

MFI is generally the first step in understanding subvisible particles in products at the core facility now. Many of the novel techniques they use require finessing to operate, so understanding a little more about the sample prior to doing more specialized techniques gives them a huge advantage. They’re able to do extended analysis with images they get with MFI and bridge that data with other techniques to identify and rapidly classify particles in solution. At the end of the day, KBI Biopharma can help clients understand their products better, which also ensures patients only get the highest quality products.

They’ve since added more MFI 5200 units at both their Durham, NC and Boulder, CO facilities. All their instruments are qualified, and each has its own calibration logbook. Amber’s group has developed generic protocols and custom, client-specific protocols using different algorithms for particle quantitation and characterization. They’ve also developed automated cleaning protocols with tight specifications for their Bot1 autosamplers to make sure background counts stay low for accurate sample analysis.

Amber expects MFI to give her team an even stronger understanding of products. Because subvisible particles present in a product are very specific to the formulation and stress conditions the product experiences, she’s envisioning that subvisible particle populations will at some point be characterized specifically for every product — almost like a thumb print for a human.

Amber’s inspired by continuous improvement, and doesn’t like stagnation or accepting that ‘this is how we always do it’. She always likes to find ways to be better and do things more efficiently. Increased efficiency in the lab also leaves more time for her other love, music.