시판 후 바이오의약품의 비가시성 미립자 생성 원인 및 분석법

Abstract

The aggregation and formation of subvisible particles in biopharmaceuticals can occur at various stages, including bioprocesses such as mixing, stirring, pumping, transportation, and even immediately before and even during administration. These particles have the potential to adversely affect product quality, leading to unforeseen side effects, particularly severe immune responses. This review explores reported cases of adverse effects linked to subvisible particles, as well as recent studies that clarify the mechanisms behind particle formation in post-marketing biopharmaceuticals. Furthermore, it compares the analytical methods and devices applied, drawing on the guidelines provided by the Korean Pharmacopoeia (KP) and the United States Pharmacopeia (USP). Additionally, the review suggests the introduction of flow-imaging microscopy (FI) as a method for analyzing transparent particles that are challenging to detect using conventional methods such as light obscuration (LO). In conclusion, selecting appropriate methods to monitor subvisible particles during product development and optimizing hospital preparations can reduce the particle delivery to patients, thereby enhancing patient care.