title: Micro-CT imaging: Developing criteria for examining fetal skeletons in regulatory developmental toxicology studies - A workshop report.
abstract: During the past two decades the use and refinements of imaging modalities have markedly increased making it possible to image embryos and fetuses used in pivotal nonclinical studies submitted to regulatory agencies. Implementing these technologies into the Good Laboratory Practice environment requires rigorous testing, validation, and documentation to ensure the reproducibility of data. A workshop on current practices and regulatory requirements was held with the goal of defining minimal criteria for the proper implementation of these technologies and subsequent submission to regulatory agencies. Micro-computed tomography (micro-CT) is especially well suited for high-throughput evaluations, and is gaining popularity to evaluate fetal skeletons to assess the potential developmental toxicity of test agents. This workshop was convened to help scientists in the developmental toxicology field understand and apply micro-CT technology to nonclinical toxicology studies and facilitate the regulatory acceptance of imaging data. Presentations and workshop discussions covered: (1) principles of micro-CT fetal imaging; (2) concordance of findings with conventional skeletal evaluations; and (3) regulatory requirements for validating the system. Establishing these requirements for micro-CT examination can provide a path forward for laboratories considering implementing this technology and provide regulatory agencies with a basis to consider the acceptability of data generated via this technology.
authors.affiliation: GlaxoSmithKline, King of Prussia, PA, United States.
authors.forename: Howard M
authors.initials: HM
authors.lastname: Solomon
authors.affiliation: U.S. Environmental Protection Agency, National Center for Environmental Assessment, Washington, DC, United States. Electronic address: makris.susan@epa.gov.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Makris
authors.affiliation: GlaxoSmithKline, King of Prussia, PA, United States.
authors.forename: Hasan
authors.initials: H
authors.lastname: Alsaid
authors.affiliation: ILSI Health and Environmental Sciences Institute, Washington, DC, United States.
authors.forename: Oscar
authors.initials: O
authors.lastname: Bermudez
authors.affiliation: Sanofi U.S. Inc., Bridgewater, NJ, United States.
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Beyer
authors.affiliation: Merck Research Laboratories, Kenilworth, NJ, United States.
authors.forename: Antong
authors.initials: A
authors.lastname: Chen
authors.affiliation: ILSI Health and Environmental Sciences Institute, Washington, DC, United States.
authors.forename: Connie L
authors.initials: CL
authors.lastname: Chen
authors.affiliation: U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of New Drugs, Silver Spring, MD, United States.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Covance Laboratories, Greenfield, IN, United States.
authors.forename: Gary
authors.initials: G
authors.lastname: Chmielewski
authors.affiliation: Novartis Pharmaceutical Corporation, East Hanover, NJ, United States.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: DeLise
authors.affiliation: Janssen R&D, Beerse, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: de Schaepdrijver
authors.affiliation: Merck Research Laboratories, Kenilworth, NJ, United States.
authors.forename: Belma
authors.initials: B
authors.lastname: Dogdas
authors.affiliation: Morphology Consulting Ltd., Staffordshire, United Kingdom.
authors.forename: Julian
authors.initials: J
authors.lastname: French
authors.affiliation: U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of New Drugs, Silver Spring, MD, United States.
authors.forename: Wafa
authors.initials: W
authors.lastname: Harrouk
authors.affiliation: Stage 2 Innovations, Framingham, MI, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Helfgott
authors.affiliation: The Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: R Mark
authors.initials: RM
authors.lastname: Henkelman
authors.affiliation: InviCRO, Boston, MA, United States.
authors.forename: Jacob
authors.initials: J
authors.lastname: Hesterman
authors.affiliation: Takeda Pharmaceutical Company, Deerfield, IL, United States.
authors.forename: Kok-Wah
authors.initials: KW
authors.lastname: Hew
authors.affiliation: Charles River Laboratories, Preclinical Services, Horsham, PA, United States.
authors.forename: Alan
authors.initials: A
authors.lastname: Hoberman
authors.affiliation: University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Cecilia W
authors.initials: CW
authors.lastname: Lo
authors.affiliation: U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of New Drugs, Silver Spring, MD, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: McDougal
authors.affiliation: U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of New Drugs, Silver Spring, MD, United States.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Minck
authors.affiliation: Charles River Laboratories, Preclinical Services, Horsham, PA, United States.
authors.forename: Lelia
authors.initials: L
authors.lastname: Scott
authors.affiliation: ApconiX, Macclesfield, Cheshire, United Kingdom.
authors.forename: Jane
authors.initials: J
authors.lastname: Stewart
authors.affiliation: National Toxicology Program/NIEHS, Research Triangle Park, NC, United States.
authors.forename: Vicki
authors.initials: V
authors.lastname: Sutherland
authors.affiliation: Covance Laboratories, Greenfield, IN, United States.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Tatiparthi
authors.affiliation: Pfizer Worldwide Research & Development, La Jolla, CA, United States.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Winkelmann
authors.affiliation: Independent Teratologist, Philadelphia, PA, United States.
authors.forename: L David
authors.initials: LD
authors.lastname: Wise
authors.affiliation: Merck Research Laboratories, Upper Gwynedd, PA, United States.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Wood
authors.affiliation: Sanofi U.S. Inc., Cambridge, MA, United States.
authors.forename: Xiaoyou
authors.initials: X
authors.lastname: Ying
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000000981:diagnostic imaging*; D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities / Q000000981:diagnostic imaging* / Q000187:drug effects; D032921:Consensus; D015509:Developmental Biology / Q000379:methods* / Q000592:standards; D005333:Fetus / Q000002:abnormalities / Q000000981:diagnostic imaging* / Q000187:drug effects; D017408:Guidelines as Topic; D006801:Humans; D015588:Observer Variation; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D018675:Toxicity Tests / Q000379:methods* / Q000592:standards; D055114:X-Ray Microtomography / Q000592:standards
keywords: Concordance criteria; Developmental toxicology; GLP validation; Imaging; Micro-CT; Skeletal evaluation