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J Pharm Sci. 2018 Aug 16. pii: S0022-3549(18)30505-7. doi: 10.1016/j.xphs.2018.08.006. [Epub ahead of print]

Collaborative Study for Analysis of Subvisible Particles Using Flow Imaging and Light Obscuration: Experiences in Japanese Biopharmaceutical Consortium.

Author information

1
Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, 3-25-26, Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-9501, Japan.
2
Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, 3-25-26, Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-9501, Japan. Electronic address: h-shibata@nihs.go.jp.
3
Vaccine Operations, Global Vaccine Business Unit, Takeda Pharmaceutical Company Limited, 4720 Takeda, Mitsui, Hikari, Yamaguchi 743-0011, Japan.
4
U-Medico Inc., 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
5
Analytical and Quality Evaluation Research Laboratories, Daiichi Sankyo Co., Ltd., 1-12-1, Shinomiya, Hiratsuka, Kanagawa 254-0014, Japan.
6
Research Division, Formulation Development, Biomanufacturing Technology, JCR Pharmaceuticals Co., Ltd., 2-2-9 Murotani, Nishi-ku, Kobe, Hyogo 651-2241, Japan.
7
Supply Chain Management Division, Pharmaceutical Research Department, Production Technology, Mitsubishi Tanabe Pharma Corporation, 3-16-89, Kashima, Yodogawa-ku, Osaka-shi, Osaka 532-8505, Japan.
8
Biologics and New Modalities Development, Pharmaceutical Sciences, Takeda Pharmaceutical Company Limited, 4720 Takeda, Mitsui, Hikari, Yamaguchi 743-0011, Japan.
9
Bio Process Research and Development Laboratories, Kyowa Hakko Kirin Co., Ltd., 100-1, Hagiwara-machi, Takasaki, Gunma 370-0013, Japan.
10
Pharmaceutical Research Laboratories, Nippon Kayaku Co., Ltd., 3-31-12, Shimo, Kita-ku, Tokyo 115-0042, Japan.
11
Pharmaceutical Science and Technology Labs, Pharmaceutical Technology, Astellas Pharma Inc., 2-5-3 Tokodai, Tsukuba, Ibaraki 300-2698, Japan.
12
Pharmaceutical Laboratory, Mochida Pharmaceutical Co., Ltd., 342 Gensuke, Fujieda, Shizuoka 426-8640, Japan.
13
CMC Regulatory and Analytical R&D, Ono Pharmaceutical Co., Ltd., 1-1, Sakurai 3-chome, Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan.
14
CMC Analysis Laboratory, Toray Research Center, Inc., 9-1, Oe-cho, Minato-ku, Nagoya, Aichi 455-8502, Japan.
15
Pharmaceutical Technology Division, Quality Development Department, Chugai Pharma Manufacturing, 5-1, Ukima, 5-chome, Kita-ku, Tokyo 115-8543, Japan.
16
Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.

Abstract

The evaluation of subvisible particles, including protein aggregates, in therapeutic protein products has been of great interest for both pharmaceutical manufacturers and regulatory agencies. To date, the flow imaging (FI) method has emerged as a powerful tool instead of light obscuration (LO) due to the fact that (1) protein aggregates contain highly transparent particles and thereby escape detection by LO and (2) FI provides detailed morphological characteristics of subvisible particles. However, the FI method has not yet been standardized nor listed in any compendium. In an attempt to assess the applicability of the standardization of the FI method, we conducted a collaborative study using FI and LO instruments in a Japanese biopharmaceutical consortium. Three types of subvisible particle preparations were shared across 12 laboratories and analyzed for their sizes and counts. The results were compared between the methods (FI and LO), inter-laboratories, and inter-instruments (Micro Flow Imaging and FlowCam). We clarified the marked difference between the detectability of FI and LO when counting highly transparent protein aggregates in the preparations. Although FlowCam provided a relatively higher number of particles compared with MFI, consistent results were obtained using the instrument from the same manufacturer in all 3 samples.

KEYWORDS:

image analysis; microparticle(s); particle size; protein aggregation; standards

PMID:
30121316
DOI:
10.1016/j.xphs.2018.08.006
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