title: Safety assessment of biopharmaceuticals: Japanese perspective on ICH S6 guideline maintenance.
abstract: Safety assessment of biopharmaceuticals in preclinical studies is guided by the ICH S6 guideline issued in 1997. Along with enormous experiences and knowledge on safety assessment of some classes of biopharmaceuticals over the last decade, the necessity and feasibility of updating the guideline has been discussed. According to a recommendation by safety experts at the ICH meeting in Chicago in 2006, regional discussions of ICH S6 were held in the USA, EU and Japan. The meeting to clarify the values, challenges and recommendations for ICH S6 from Japanese perspective was held as a part of the first Drug Evaluation Forum in Tokyo on August 10, 2007. Of utmost importance, the "case-by-case" approach must be preserved as the basic principle of the ICH S6 guideline. It is our opinion that oligonucleotides, siRNA, aptamers and related molecules should be excluded from ICH S6 and may be more appropriate for separate guidance. However, based on experiences and accumulated knowledge, there are a number of issues that can be updated including new types of biopharmaceuticals such as bioconjugates, use of homologous proteins and transgenic animals, reproductive/developmental toxicity studies in non-human primates, in vitro cardiac ion channel assay and alternative approaches for carcinogenicity assessment. Preliminary recommendations for some of these topics were outlined at the meeting. The overall Japanese recommendation is that the ICH S6 guideline should be updated to address these topics.
authors.affiliation: Japan Pharmaceutical Manufacturers Association, Drug Evaluation Committee, Non-clinical Evaluation Subcommittee, Tokyo. nakazawa_takahiro@lilly.com
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Misao
authors.initials: M
authors.lastname: Kurokawa
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kimura
authors.forename: Akihiro
authors.initials: A
authors.lastname: Wakata
authors.forename: Shigeru
authors.initials: S
authors.lastname: Hisada
authors.forename: Tadashi
authors.initials: T
authors.lastname: Inoue
authors.forename: Fumio
authors.initials: F
authors.lastname: Sagami
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Heidel
authors.forename: Koji
authors.initials: K
authors.lastname: Kawakami
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Shinoda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Onodera
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kumagai
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohno
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kawamura
authors.forename: Tsuneyoshi
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Tohru
authors.initials: T
authors.lastname: Inoue
mesh_terms: D000818:Animals; D001688:Biological Products / Q000633:toxicity*; D001709:Biotechnology / Q000379:methods*; D015197:Carcinogenicity Tests; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005333:Fetus / Q000187:drug effects; D017408:Guidelines as Topic; D006801:Humans; D007391:International Cooperation; D007564:Japan; D012098:Reproduction / Q000187:drug effects; D012449:Safety
chemical_list: D001688:Biological Products