title: In Vivo Predictive Dissolution (IPD) and Biopharmaceutical Modeling and Simulation: Future Use of Modern Approaches and Methodologies in a Regulatory Context.
abstract: The overall objective of OrBiTo, a project within Innovative Medicines Initiative (IMI), is to streamline and optimize the development of orally administered drug products through the creation and efficient application of biopharmaceutics tools. This toolkit will include both experimental and computational models developed on improved understanding of the highly dynamic gastrointestinal (GI) physiology relevant to the GI absorption of drug products in both fasted and fed states. A part of the annual OrBiTo meeting in 2015 was dedicated to the presentation of the most recent progress in the development of the regulatory use of PBPK in silico modeling, in vivo predictive dissolution (IPD) tests, and their application to biowaivers. There are still several areas for improvement of in vitro dissolution testing by means of generating results relevant for the intraluminal conditions in the GI tract. The major opportunity is probably in combining IPD testing and physiologically based in silico models where the in vitro data provide input to the absorption predictions. The OrBiTo project and other current research projects include definition of test media representative for the more distal parts of the GI tract, models capturing supersaturation and precipitation phenomena, and influence of motility waves on shear and other forces of hydrodynamic origin, addressing the interindividual variability in composition and characteristics of GI fluids, food effects, definition of biorelevant buffer systems, and intestinal water volumes. In conclusion, there is currently a mismatch between the extensive industrial usage of modern in vivo predictive tools and very limited inclusion of such data in regulatory files. However, there is a great interest among all stakeholders to introduce recent progresses in prediction of in vivo GI drug absorption into regulatory context.
authors.affiliation: Department of Pharmacy, Uppsala University , Uppsala, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Lennernäs
authors.affiliation: Medical Products Agency , Uppsala, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Lindahl
authors.affiliation: Janssen Research and Development, Janssen Pharmaceutica NV , Turnhoutseweg 30, 2340, Beerse, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Van Peer
authors.affiliation: Sanofi US , 55 Corporate Drive, Bridgewater, New Jersey 08807, United States.
authors.forename: C
authors.initials: C
authors.lastname: Ollier
authors.affiliation: AstraZeneca R&D , Macclesfield, U.K.
authors.forename: T
authors.initials: T
authors.lastname: Flanagan
authors.affiliation: Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, Food and Drug Administration , 10903 New Hampshire Avenue, Silver Spring, Maryland 20993, United States.
authors.forename: R
authors.initials: R
authors.lastname: Lionberger
authors.affiliation: Medical Products Agency , Uppsala, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Nordmark
authors.affiliation: Faculty of Pharmaceutical Sciences, Setsunan University , Nagaotoge-cho 45-1, Hirakata, Osaka 573-0101, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yamashita
authors.affiliation: Food and Drug Administration, Center for Drug Evaluation and Research , Silver Spring, Maryland 20993, United States.
authors.forename: L
authors.initials: L
authors.lastname: Yu
authors.affiliation: College of Pharmacy, University of Michigan , Ann Arbor, Michigan 48109-1065, United States.
authors.forename: G L
authors.initials: GL
authors.lastname: Amidon
authors.affiliation: Drug Metabolism and Pharmacokinetics, Research & Development, AbbVie , North Chicago, Illinois 60064, United States.
authors.forename: V
authors.initials: V
authors.lastname: Fischer
authors.affiliation: Department of Pharmacy, Uppsala University , Uppsala, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Sjögren
authors.affiliation: Sanofi US , 55 Corporate Drive, Bridgewater, New Jersey 08807, United States.
authors.forename: P
authors.initials: P
authors.lastname: Zane
authors.affiliation: Pharmaceutical Development, GlaxoSmithKline , New Frontiers Science Park, Harlow, Essex CM19 5AW, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: McAllister
authors.affiliation: AstraZeneca R&D , Gothenburg, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Abrahamsson
mesh_terms: D000284:Administration, Oral; D001702:Biopharmaceutics / Q000379:methods; D065569:Gastrointestinal Absorption / Q000502:physiology; D041981:Gastrointestinal Tract / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism*; D012995:Solubility
chemical_list: D004364:Pharmaceutical Preparations
keywords: Biopharmaceutics Classification System; PBPK; bioequivalence; biorelevant dissolution; generic drugs; in vivo predictive dissolution; intestinal drug absorption; theoretical modeling