Vertex Pharmaceuticals, Boston, Massachusetts (N.H.); Genentech, South San Francisco, California (J.R.K.); Novartis Pharmaceuticals, Florham Park, New Jersey (H.E.); Eli Lilly and Company, Indianapolis, Indiana (M.M.); Boehringer Ingelheim, Ridgefield, Connecticut (D.R.); Merck and Co., Kenilworth, New Jersey (J.P.), Amgen Inc., Thousand Oaks, California (J.D.), Pfizer Global Research and Development, Groton, Connecticut (O.A.F.); Sanofi Pharmaceuticals, ChillyMazarin, France (M.P.); Eisai Pharmaceuticals, Andover, Massachusetts (A.Y.S.); Glaxo SmithKline, King of Prussia, Pennsylvania (L.C.); Bristol-Myers Squibb, Wallingford, Connecticut (M.S.); AstraZeneca, Mölndal, Sweden (B.J.); EMD Serono, Billerica, Massachusetts (R.W.);Janssen R&D, Spring House, Pennsylvania (S.D.); Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceuticals Co., Cambridge, Massachusetts (S.K.B.); Corning Life Sciences; Woburn, Massachusetts (G.Z.); XenoTech LLC, Lenexa, Kansas (D.B.); Merck and Co., West Point, Pennsylvania (D.T.)
Vertex Pharmaceuticals, Boston, Massachusetts (N.H.); Genentech, South San Francisco, California (J.R.K.); Novartis Pharmaceuticals, Florham Park, New Jersey (H.E.); Eli Lilly and Company, Indianapolis, Indiana (M.M.); Boehringer Ingelheim, Ridgefield, Connecticut (D.R.); Merck and Co., Kenilworth, New Jersey (J.P.), Amgen Inc., Thousand Oaks, California (J.D.), Pfizer Global Research and Development, Groton, Connecticut (O.A.F.); Sanofi Pharmaceuticals, ChillyMazarin, France (M.P.); Eisai Pharmaceuticals, Andover, Massachusetts (A.Y.S.); Glaxo SmithKline, King of Prussia, Pennsylvania (L.C.); Bristol-Myers Squibb, Wallingford, Connecticut (M.S.); AstraZeneca, Mölndal, Sweden (B.J.); EMD Serono, Billerica, Massachusetts (R.W.);Janssen R&D, Spring House, Pennsylvania (S.D.); Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceuticals Co., Cambridge, Massachusetts (S.K.B.); Corning Life Sciences; Woburn, Massachusetts (G.Z.); XenoTech LLC, Lenexa, Kansas (D.B.); Merck and Co., West Point, Pennsylvania (D.T.).
Drug Metab Dispos. 2017 Oct;45(10):1049-1059. doi: 10.1124/dmd.116.074567. Epub 2017 Jun 23.
The European Medicines Agency (EMA), the Pharmaceutical and Medical Devices Agency (PMDA), and the Food and Drug Administration (FDA) have issued guidelines for the conduct of drug-drug interaction studies. To examine the applicability of these regulatory recommendations specifically for induction, a group of scientists, under the auspices of the Drug Metabolism Leadership Group of the Innovation and Quality (IQ) Consortium, formed the Induction Working Group (IWG). A team of 19 scientists, from 16 of the 39 pharmaceutical companies that are members of the IQ Consortium and two Contract Research Organizations reviewed the recommendations, focusing initially on the current EMA guidelines. Questions were collated from IQ member companies as to which aspects of the guidelines require further evaluation. The EMA was then approached to provide insights into their recommendations on the following: 1) evaluation of downregulation, 2) in vitro assessment of CYP2C induction, 3) the use of CITCO as the positive control for CYP2B6 induction by CAR, 4) data interpretation (a 2-fold increase in mRNA as evidence of induction), and 5) the duration of incubation of hepatocytes with test article. The IWG conducted an anonymous survey among IQ member companies to query current practices, focusing specifically on the aforementioned key points. Responses were received from 19 companies. All data and information were blinded before being shared with the IWG. The results of the survey are presented, together with consensus recommendations on downregulation, CYP2C induction, and CYP2B6 positive control. Results and recommendations related to data interpretation and induction time course will be reported in subsequent articles.
欧洲药品管理局（EMA）、药品医疗器械管理局（PMDA）和食品药品监督管理局（FDA）发布了药物相互作用研究的指南。为了专门考察这些监管建议在诱导方面的适用性，一组科学家在创新和质量（IQ）联盟药物代谢领导小组的支持下，成立了诱导工作组（IWG）。由来自 IQ 联盟 39 家制药公司中的 16 家和 2 家合同研究组织的 19 名科学家组成的团队，对这些建议进行了审查，最初重点是当前的 EMA 指南。IQ 成员公司提出了一系列问题，要求进一步评估指南的哪些方面。然后，EMA 被要求就以下方面提供其建议的见解：1）下调的评估，2）CYP2C 诱导的体外评估，3）使用 CITCO 作为 CAR 诱导 CYP2B6 的阳性对照，4）数据解释（mRNA 增加 2 倍作为诱导的证据），以及 5）用试验药物孵育肝细胞的时间。IWG 对 IQ 成员公司进行了一项匿名调查，以查询当前的做法，重点关注上述关键点。收到了来自 19 家公司的回复。在与 IWG 共享之前，所有数据和信息均被屏蔽。本文介绍了调查结果，并就下调、CYP2C 诱导和 CYP2B6 阳性对照提出了共识建议。与数据解释和诱导时间过程相关的结果和建议将在后续文章中报告。
