Perspectives on the Evaluation and Adoption of Complex In Vitro Models in Drug Development: Workshop with the FDA and the Pharmaceutical Industry (IQ MPS Affiliate)

被引：67

作者：

Baran, Szczepan W. ^{[1
]}

Brown, Paul C. ^{[2
]}

Baudy, Andreas R. ^{[3
]}

Fitzpatrick, Suzanne C. ^{[4
]}

Frantz, Christopher ^{[5
]}

Fullerton, Aaron ^{[6
]}

Gan, Jinping ^{[7
]}

Hardwick, Rhiannon N. ^{[8
]}

Hillgren, Kathleen M. ^{[9
]}

Kopec, Anna K. ^{[10
]}

Liras, Jennifer L. ^{[11
]}

Mendrick, Donna L. ^{[12
]}

Nagao, Ryan ^{[5
]}

Proctor, William R. ^{[6
]}

Ramsden, Diane ^{[13
]}

Ribeiro, Alexandre J. S. ^{[14
]}

Stresser, David ^{[15
]}

Sung, Kyung E. ^{[16
]}

Sura, Radhakrishna ^{[17
]}

Tetsuka, Kazuhiro ^{[18
]}

Tomlinson, Lindsay ^{[19
]}

Van Vleet, Terry ^{[20
]}

Wagoner, Matthew P. ^{[21
]}

Wang, Qin ^{[21
]}

Arslan, Sevim Yildiz ^{[22
]}

Yoder, Gorm ^{[23
]}

Ekert, Jason E. ^{[24
]}

机构：

[1] Novartis Inst BioMed Res, Emerging Technol, Cambridge, MA 02139 USA

[2] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Silver Spring, MD USA

[3] Merck & Co Inc, ADME & Discovery Toxicol, Kenilworth, NJ USA

[4] US FDA, Ctr Food Safety & Appl Nutr, Off Ctr Director, College Pk, MD USA

[5] Seagen, Translat Sci, Seattle, WA USA

[6] Genentech Inc, Safety Assessment, San Francisco, CA USA

[7] Bristol Myers Squibb Res & Dev, Pharmaceut Candidate Optimizat, Princeton, NJ USA

[8] Theravance Biopharma US Inc, Translat Safety Sci, San Francisco, CA USA

[9] Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA

[10] Pfizer Inc, Drug Safety Res & Dev, Groton, CT 06340 USA

[11] Pfizer Inc, Pharmacokinet Dynam & Metab, Cambridge, MA USA

[12] US FDA, Natl Ctr Toxicol Res, Off Ctr Director, Silver Spring, MD USA

[13] Takeda Pharmaceut Int Co, Global Drug Metab & Phannacokinet, Cambridge, MA USA

[14] US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol,Div Appl Regulatory Sci, Silver Spring, MD USA

[15] AbbVie Inc, Drug Metab Phannacokinet & Bioanal, N Chicago, IL USA

[16] US FDA, Ctr Biol Evaluat & Res, Off Tissues & Adv Therapies, Div Cellular & Gene Therapies, Silver Spring, MD USA

[17] AbbVie Inc, Global Preclin Safety, N Chicago, IL USA

[18] Astellas Phanna Inc, Anal & Phannacokinet Res Labs, Tsukuba, Ibaraki, Japan

[19] Pfizer WRD, Global Pathol DSRD, Cambridge, MA USA

[20] AbbVie Inc, Chicago, IL USA

[21] Takeda Pharmaceut Int Co, Drug Safety Res & Evaluat, Cambridge, MA USA

[22] Astellas Pharma Inc, BioAnal Appl Res Management & Biomed Sci AMS, Northbrook, IL USA

[23] Aimmune Nestld Hlth Sci, Brisbane, Qld, Australia

[24] GlaxoSmithKline, In Vitro In Vivo Translat Res Pharmaceut R&D, Collegeville, PA USA

来源：

ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION | 2022年 / 39卷 / 02期

关键词：

MICROPHYSIOLOGICAL SYSTEMS MPS; INDUCED LIVER-INJURY; SAFETY; RISK; CELL; TOXICITY; SCIENCE; TOOL;

D O I：

10.14573/altex.2112203

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Complex in vitro models (CIVM) offer the potential to improve pharmaceutical clinical drug attrition due to safety and/ or efficacy concerns. For this technology to have an impact, the establishment of robust characterization and qualification plans constructed around specific contexts of use (COU) is required. This article covers the output from a workshop between the Food and Drug Administration (FDA) and Innovation and Quality Microphysiological Systems (IQ MPS) Affiliate. The intent of the workshop was to understand how CIVM technologies are currently being applied by pharmaceutical companies during drug development and are being tested at the FDA through various case studies in order to identify hurdles (real or perceived) to the adoption of microphysiological systems (MPS) technologies, and to address evaluation/qualification pathways for these technologies. Output from the workshop includes the alignment on a working definition of MPS, a detailed description of the eleven CIVM case studies presented at the workshop, in-depth analysis, and key take aways from breakout sessions on ADME (absorption, distribution, metabolism, and excretion), pharmacology, and safety that covered topics such as qualification and performance criteria, species differences and concordance, and how industry can overcome barriers to regulatory submission of CIVM data. In conclusion, IQ MPS Affiliate and FDA scientists were able to build a general consensus on the need for animal CIVMs for preclinical species to better determine species concordance. Furthermore, there was an acceptance that CIVM technologies for use in ADME, pharmacology and safety assessment will require qualification, which will vary depending on the specific COU.

引用

页码：297 / 314

页数：18

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