Particle Detection and Characterization for Biopharmaceutical Applications: Current Principles of Established and Alternative Techniques

Abstract

Detection and characterization of particles in the visible and subvisible size range is critical in many fields of industrial research. Commercial particle analysis systems have proliferated over the last decade. Despite that growth, most systems continue to be based on well-established principles, and only a handful of new approaches have emerged. Identifying the right particle-analysis approach remains a challenge in research and development. The choice depends on each individual application, the sample, and the information the operator needs to obtain. In biopharmaceutical applications, particle analysis decisions must take product safety, product quality, and regulatory requirements into account. Biopharmaceutical process samples and formulations are dynamic, polydisperse, and very susceptible to chemical and physical degradation: improperly handled product can degrade, becoming inactive or in specific cases immunogenic. This article reviews current methods for detecting, analyzing, and characterizing particles in the biopharmaceutical context. The first part of our article represents an overview about current particle detection and characterization principles, which are in part the base of the emerging techniques. It is very important to understand the measuring principle, in order to be adequately able to judge the outcome of the used assay. Typical principles used in all application fields, including particle–light interactions, the Coulter principle, suspended microchannel resonators, sedimentation processes, and further separation principles, are summarized to illustrate their potentials and limitations considering the investigated samples. In the second part, we describe potential technical approaches for biopharmaceutical particle analysis as some promising techniques, such as nanoparticle tracking analysis (NTA), micro flow imaging (MFI), tunable resistive pulse sensing (TRPS), flow cytometry, and the space- and time-resolved extinction profile (STEP®) technology.

FtsZ Interactions and Biomolecular Condensates as Potential Targets for New Antibiotics

“…Tunable resistive pulse sensing (TRPS) is an emerging sizing method applicable to a wide variety of particles ranging from single molecules to whole cells within 40 nm–10 μm in size [ 84 ]. It measures current fluctuations produced by the species passing through a dynamically resizable pore, allowing simultaneous determination of size and concentration of the species present in polydisperse samples [ 85 ]. TRPS is a highly accurate and precise method potentially useful to detect and quantitate the effect of drugs on FtsZ polymerization.…”

Recent Progress in Spectroscopic Methods for the Detection of Foodborne Pathogenic Bacteria

“…Pathogen detection has been carried out using DLS, in which the pathogens are considered microparticles. Different pathogens exhibit unique scattering of light based on different sizes, shapes, and characteristics of the microbes [ 87 , 88 , 89 , 90 , 91 ].…”

Stress Factors in Primary Packaging, Transportation and Handling of Protein Drug Products and Their Impact on Product Quality

“…Appropriate analytical methods for assessing the effect of the stresses of different manufacturing processes are discussed in USP chapters <1787>, <1788>, <1790>, and several excellent review articles. 2,[18][19][20][21][22] For subvisible particle analysis, it is highly advisable to apply analytical methods that are sensitive to protein particles, which are often translucent and not well detected by the compendial methods (i.e., light obscuration). The panel of analytical methods used in development should include those that can also differentiate proteinaceous particles from other types of particles which may originate from the device or the formulation components.…”