PT  - JOURNAL ARTICLE
AU  - Wang, Bo
AU  - Zhang, Shanshan
AU  - Chen, Mengyi
AU  - Lei, Ming
AU  - Gao, Tian
AU  - Fan, Wei
AU  - Huang, Jincui
AU  - Cao, Xiaolin
TI  - Identification and Root Cause Analysis of the Visible Particles Commonly Encountered in the Biopharmaceutical Industry
AID  - 10.5731/pdajpst.2023.012894
DP  - 2024 Sep 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - 586--603
VI  - 78
IP  - 5
4099  - http://journal.pda.org/content/78/5/586.short
4100  - http://journal.pda.org/content/78/5/586.full
SO  - PDA J Pharm Sci Technol2024 Sep 01; 78
AB  - Visible particle is an important issue in the biopharmaceutical industry, and it may occur across all the stages in the life cycle of biologics. Upon the occurrence of visible particles, it is often necessary to conduct chemical identification and root cause analysis to safeguard the safety and efficacy of the biotherapeutic products. In this article, we present a number of typical particles and relevant root cause analysis in the categories of extrinsic, intrinsic, and inherent particles that are commonly encountered in the biopharma industry. In particular, the optical images of particles obtained both in situ and after isolation are provided, along with spectral and elemental information. The particle identification was carried out with multiple microscopic and microspectroscopic techniques, including stereo optical microscopy, Fourier-transform infrared microscopy, confocal Raman microscopy, scanning electron microscopy, and energy dispersive X-ray spectroscopy. Both commercial and in-house spectral databases were used for comparison and identification. In addition to particle identification, we placed significant efforts on the root cause analysis of the addressed particles with the intention to provide a relatively whole picture of the particle-related issues and practical references to particle mitigation for our peers in the biopharmaceutical industry.