Morphologically-Directed Raman Spectroscopy as an Analytical Method for Subvisible Particle Characterization in Therapeutic Protein Product Quality

Journal Article · 22 November 2023 · Scientific Reports

DOI: https://doi.org/10.1038/s41598-023-45720-0 · OSTI ID:2217559

Kim, Minkyung ^[1]; Ma, Youlong ^[1]; Srinivasan, Charudharshini ^[1]; O’Connor, Thomas ^[1]; Telikepalli, Srivalli N. ^[2]; Ripple, Dean C. ^[2]; Lute, Scott ^[1]; Bhirde, Ashwinkumar ^[1]

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1. US Food and Drug Administration (USFDA), Silver Spring, MD (United States). Center for Drug Evaluation and Research
2. National Inst. of Standards and Technology (NIST), Gaithersburg, MD (United States)

ubvisible particles (SVPs) are a critical quality attribute of injectable therapeutic proteins (TPs) that needs to be controlled due to potential risks associated with drug product quality. The current compendial methods routinely used to analyze SVPs for lot release provide information on particle size and count. However, chemical identification of individual particles is also important to address root-cause analysis. Herein, we introduce Morphologically-Directed Raman Spectroscopy (MDRS) for SVP characterization of TPs. The following particles were used for method development: (1) polystyrene microspheres, a traditional standard used in industry; (2) photolithographic (SU-8); and (3) ethylene tetrafluoroethylene (ETFE) particles, candidate reference materials developed by NIST. In our study, MDRS rendered high-resolution images for the ETFE particles (> 90%) ranging from 19 to 100 μm in size, covering most of SVP range, and generated comparable morphology data to flow imaging microscopy. Our method was applied to characterize particles formed in stressed TPs and was able to chemically identify individual particles using Raman spectroscopy. MDRS was able to compare morphology and transparency properties of proteinaceous particles with reference materials. The data suggests MDRS may complement the current TPs SVP analysis system and product quality characterization workflow throughout development and commercial lifecycle.

• Research Organization: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
• Sponsoring Organization: USDOE Office of Science (SC); USFDA; National Institute of Standards and Technology (NIST); USDOE
• Grant/Contract Number: SC0014664
• OSTI ID: 2217559
• Alternate ID(s): OSTI ID: 2471324
• Journal Information: Scientific Reports, Vol. 13, Issue 1; ISSN 2045-2322
• Publisher: Nature Publishing GroupCopyright Statement
• Country of Publication: United States
• Language: English