Particle risk questions rarely have a one-size-fits-all answer, but a few come up often enough that it's worth having clear, direct responses on hand. We asked KBI Biopharma's Kylee Harris (Scientist II/Project Leader), Madison Connor (Scientist II/Project Leader), and Sarah Dickerson, PhD (Director, Biophysical and Particle Characterization Core) to weigh in .
Dickerson: They really pair nicely together. Simulating an in-use study may generate particles under the conditions as observed in the clinic. This could be a result of a specific hold time, bag, or device. There is an art in designing an appropriate clinical in-use (CIU) study, and there are two unique capabilities we offer at KBI that make this a complete story for our clients. One, we evaluate samples using a comprehensive analytical panel that includes our KBI-owned particle classification machine learning tool (PICTS) for accurate and speedy identification. Two, we have a team of experts who specialize in particle forensics. If a particle is observed during CIU simulation, we can identify it and trace it to the source.
Harris: As early as possible, ideally before filing their IND. That's early enough to de-risk the program without a major hit to timelines. Follow-on studies can always expand scope, but starting early means you have the information you need, on formulation, device, and dosing, to inform an IND package.
Harris: It really depends on the molecule; every modality behaves differently, which is exactly why representative, molecule-specific studies matter. But if we had to pick one, it's dilution compatibility combined with handling. We've seen cases where dilution of excipients, or shifting ionic strength or pH, leads to large protein aggregates forming with very little agitation involved.
Harris: Not automatically. It really depends on the in-clinic preparation and handling, for example, whether the product is reconstituted, diluted, or held for any length of time between preparation and administration. If you are holding prepared samples at room temperature for 8 hours or more, microbial challenge testing is recommended.
Dickerson: Yes. We support clinical in-use studies and particle forensics across antibodies, bispecifics, ADCs, viral vectors, and LNPs. We've even supported clients outside of the pharma field for particle forensics. The specific risks depend on the modality, but the team has experience with a broad range of molecules.
Connor: Identification can be quite specific depending on the particle and material. For some therapeutics, surfactants may be of interest, at which point we can distinguish between PS80, P188, etc. Unique chemical composition enables specific identification by vibrational spectroscopy techniques like Raman and FTIR. Custom reference libraries take it further, tying an ID to the exact source component rather than a broad material category (e.g., IV bag port versus polyethylene).
Connor: We can be fairly confident, even at the single-particle level. Based on particle morphology and material class, we can usually narrow down an origin like a container, device, or administration pathway. A custom reference library takes that from a generic origin to an exact source. This same forensic approach isn't limited to biopharma and drug products, either. We’ve supported clients in industries ranging from aerospace to cosmetics to agriculture. The applications of spectroscopy are endless!
Connor: That's where SEM-EDS comes in. If a material doesn't produce a robust vibrational spectrum, which is often the case with metallic components or dried buffer residue, elemental analysis can identify what's present even without a unique spectral fingerprint.
Connor: More often than you'd think. One of my favorite analyses involved an eye-dropper device. It looked simple, but it had about ten different components within the cap alone. While many of the components were unique polymers, a few were identified as polyethylene and, as luck would have it, so was the particle of interest. We were able to determine which polyethylene source was responsible for the particulate based on subtle spectral shifts, colorant peaks, and particle morphology.
Go deeper: Watch the on-demand webinar to learn how to assess particle risk before it impacts product quality or patient safety, identify the source of unexpected particles with advanced forensic techniques, build regulator-ready evidence to support confident development decisions, and accelerate investigations through KBI's STAT portal.
Kylee holds a degree in Chemical and Biological Engineering from Colorado State University and has been with KBI since 2022. She leads a team specializing in clinical in-use studies, particle characterization, and IV bag/device compatibility testing, supporting the development of gene therapies, ADCs, and protein therapeutics. Passionate about patient safety, she helps ensure drug products are both effective and ready for clinical use.
Madison earned her degree in Molecular, Cellular, and Developmental Biology from the University of Colorado Boulder and has been with KBI since 2018. She leads a team specializing in particle characterization and forensic particle analysis, using advanced techniques to identify particulate matter and support drug product quality, manufacturing improvements, and patient safety.
Sarah earned her PhD in Biochemistry from the University of Colorado Boulder and brings more than 10 years of industry experience, primarily in gene therapies. She specializes in analytical development, product characterization, and CMC strategy, helping clients implement robust early characterization approaches that reduce risk to their programs.
Every microbial development program presents unique technical and business challenges.
If you're evaluating expression strategies, optimizing an existing process, or preparing for scale-up, KBI's microbial development experts can help identify the development approach best suited to your molecule and your program objectives.
Explore KBI's flexible microbial development capabilities or connect with one of our scientific experts to discuss the strategy best suited for your molecule.
KBI Biopharma is a biologics-focused CDMO with a heritage in analytical sciences. KBI offers integrated analytical, formulation, and manufacturing services from early development through commercial supply reducing risk for biopharmaceutical developers.