Approaches to Quality Risk Management When Using Single-Use Systems in the Manufacture of Biologics.
Biologics manufacturing technology has made great progress in the last decade. One of the most promising new technologies is the single-use system, which has improved the efficiency of biologics manufacturing processes. To ensure safety of biologics when employing such single-use systems in the manufacturing process, various issues need to be considered including possible extractables/leachables and particles arising from the components used in single-use systems. Japanese pharmaceutical manufacturers, together with single-use suppliers, members of the academia and regulatory authorities have discussed the risks of using single-use systems and established control strategies for the quality assurance of biologics. In this study, we describe approaches for quality risk management when employing single-use systems in the manufacturing of biologics. We consider the potential impact of impurities related to single-use components on drug safety and the potential impact of the single-use system on other critical quality attributes as well as the stable supply of biologics. We also suggest a risk-mitigating strategy combining multiple control methods which includes the selection of appropriate single-use components, their inspections upon receipt and before releasing for use and qualification of single-use systems. Communication between suppliers of single-use systems and the users, as well as change controls in the facilities both of suppliers and users, are also important in risk-mitigating strategies. Implementing these control strategies can mitigate the risks attributed to the use of single-use systems. This study will be useful in promoting the development of biologics as well as in ensuring their safety, quality and stable supply.
National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan. watabe@nihs.go.jp.
Akiko
A
Ishii-Watabe
National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
Akihiko
A
Hirose
National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
Noriko
N
Katori
National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
Norikata
N
Hashii
Sumitomo Bakelite Co., Ltd., 1-5, Murotani 1-Chome, Nishi-ku, Kobe, 651-2241, Japan.
Susumu
S
Arai
Nihon Pall Ltd., 6-5-1, Nishishinjuku, Shinjuku-ku, Tokyo, 163-1325, Japan.
Hirotoshi
H
Awatsu
Sekisui Seikei, Ltd., 2-1-9 Dojimahama, Kita-ku, Osaka, 530-0004, Japan.
Akira
A
Eiza
Sartorius Stedim Japan, 1-8-11 Kitashinagawa Shinagawa-ku, Tokyo, 140-0001, Japan.
Yoshiaki
Y
Hara
Dai Nippon Printing Co., Ltd., 1-1-1, Ichigaya Kagacho, Shinjuku-ku, Tokyo, 162-8001, Japan.
Hideshi
H
Hattori
MSD K.K., 2-3-7 Hiranomachi, Chuo-ku, Osaka, 541-0046, Japan.
Tomomi
T
Inoue
Chugai Pharmaceutical Co., Ltd., 5-1 Ukima 5-Chome Kita-ku, Tokyo, 115-8543, Japan.
Tetsuya
T
Isono
Manufacturing Technology Association of Biologics, 2-1-10 Shinkawa, Chuo-ku, Tokyo, 104-0033, Japan.
Masahiro
M
Iwakura
GE Healthcare Japan Corporation, Sanken Bldg., 3-25-1 Hyakuninchio, Shinjuku-ku, Tokyo, 169-0073, Japan.
Daisuke
D
Kajihara
Astellas Pharma Tech Co., Ltd., 160-2 Akahama, Takahagi-shi, Ibaraki, 318-0001, Japan.
Nobuo
N
Kasahara
Fujimori Kogyo Co., Ltd, 1-23-7 Nishi-Shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.
Hiroyuki
H
Matsuda
Hitachi, Ltd., 4-5-2 Higashi-Ikebukuro, Toshima-ku, Tokyo, 170-8466, Japan.
Sei
S
Murakami
Kyowa Hakko Kirin Co., Ltd., 1-6-1 Ohtemachi, Chiyoda-ku, Tokyo, 100-8185, Japan.
Taishiro
T
Nakagawa
Takeda Pharmaceutical Co., Ltd., 17-85, Jusohonmachi 2-chome, Yodogawa-ku, Osaka, 532-8686, Japan.
Takehiro
T
Okumura
Osaka University, U1E801, 2-1 Yamadaoka, Suita-shi, Osaka, 565-0871, Japan.
Takeshi
T
Omasa
Chugai Pharmaceutical Co., Ltd., 5-1 Ukima 5-Chome Kita-ku, Tokyo, 115-8543, Japan.
Shinya
S
Takuma
Merck Millipore, 1-8-1 Shimomeguro, Meguro-ku, Tokyo, 153-8927, Japan.
Iyo
I
Terashima
Kyowa Hakko Kirin Co., Ltd., 1-6-1 Ohtemachi, Chiyoda-ku, Tokyo, 100-8185, Japan.
Masayoshi
M
Tsukahara
Sumitomo Dainippon Pharma Co., Ltd., 1-3-45 Kurakakiuchi, Ibaraki-shi, Osaka, 567-0878, Japan.
Maiko
M
Tsutsui
Daiichi Sankyo Co., Ltd., 1-12-1, Shinomiya, Hiratsuka-shi, Kanagawa, 254-0014, Japan.
Takahiro
T
Yano
Yokohama City University, 1-7-29 Suehirocho, Tsurumi-ku, Yokohama-shi, Kanagawa, 230-0045, Japan.
Nana
N
Kawasaki
D001688:Biological Products / Q000009:adverse effects / Q000138:chemical synthesis* / Q000592:standards / Q000600:supply & distribution; D003257:Consumer Product Safety; D004209:Disposable Equipment / Q000592:standards; D004340:Drug Contamination / Q000517:prevention & control*; D004345:Drug Industry / Q000592:standards; D006801:Humans; D061214:Patient Safety; D011786:Quality Control; D018570:Risk Assessment; D012307:Risk Factors; D012308:Risk Management / Q000592:standards; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000592:standards
D001688:Biological Products
biologics; manufacturing technology; quality risk management; regulatory science; single-use system