title: Cracking the Egg: Potential of the Developing Chicken as a Model System for Nonclinical Safety Studies of Pharmaceuticals.
abstract: The advance of perinatal medicine has improved the survival of extremely premature babies, thereby creating a new and heterogeneous patient group with limited information on appropriate treatment regimens. The developing fetus and neonate have traditionally been ignored populations with regard to safety studies of drugs, making medication during pregnancy and in newborns a significant safety concern. Recent initiatives of the Food and Drug Administration and European Medicines Agency have been passed with the objective of expanding the safe pharmacological treatment options in these patients. There is a consensus that neonates should be included in clinical trials. Prior to these trials, drug leads are tested in toxicity and pharmacology studies, as governed by several guidelines summarized in the multidisciplinary International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use M3 (R2). Pharmacology studies must be performed in the major organ systems: cardiovascular, respiratory, and central nervous system. The chicken embryo and fetus have features that make the chicken a convenient animal model for nonclinical safety studies in which effects on all of these organ systems can be tested. The developing chicken is inexpensive, accessible, and nutritionally self-sufficient with a short incubation time and is ideal for drug-screening purposes. Other high-throughput models have been implemented. However, many of these have limitations, including difficulty in mimicking natural tissue architecture and function (human stem cells) and obvious differences from mammals regarding the respiratory organ system and certain aspects of central nervous system development (Caenorhabditis elegans, zebrafish).This minireview outlines the potential and limitations of the developing chicken as an additional model for the early exploratory phase of development of new pharmaceuticals.
authors.affiliation: Department of Pathology, Oslo University Hospital HF, Ullevål, Oslo, Norway (S.B., B.R.); Institute of Clinical Medicine (B.R.), Department of Pharmaceutical Biosciences, School of Pharmacy (L.P.E.A., R.E.P.), and NDEVOR, Section of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences (J.C.G.), University of Oslo, Oslo, Norway; and Norwegian Center for Stem Cell Research, Department of Immunology and Transfusion Medicine, Oslo University Hospital HF, Rikshospitalet, Oslo, Norway (J.C.G.).
authors.forename: Sigrid
authors.initials: S
authors.lastname: Bjørnstad
authors.affiliation: Department of Pathology, Oslo University Hospital HF, Ullevål, Oslo, Norway (S.B., B.R.); Institute of Clinical Medicine (B.R.), Department of Pharmaceutical Biosciences, School of Pharmacy (L.P.E.A., R.E.P.), and NDEVOR, Section of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences (J.C.G.), University of Oslo, Oslo, Norway; and Norwegian Center for Stem Cell Research, Department of Immunology and Transfusion Medicine, Oslo University Hospital HF, Rikshospitalet, Oslo, Norway (J.C.G.).
authors.forename: Lars Peter Engeset
authors.initials: LP
authors.lastname: Austdal
authors.affiliation: Department of Pathology, Oslo University Hospital HF, Ullevål, Oslo, Norway (S.B., B.R.); Institute of Clinical Medicine (B.R.), Department of Pharmaceutical Biosciences, School of Pharmacy (L.P.E.A., R.E.P.), and NDEVOR, Section of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences (J.C.G.), University of Oslo, Oslo, Norway; and Norwegian Center for Stem Cell Research, Department of Immunology and Transfusion Medicine, Oslo University Hospital HF, Rikshospitalet, Oslo, Norway (J.C.G.).
authors.forename: Borghild
authors.initials: B
authors.lastname: Roald
authors.affiliation: Department of Pathology, Oslo University Hospital HF, Ullevål, Oslo, Norway (S.B., B.R.); Institute of Clinical Medicine (B.R.), Department of Pharmaceutical Biosciences, School of Pharmacy (L.P.E.A., R.E.P.), and NDEVOR, Section of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences (J.C.G.), University of Oslo, Oslo, Norway; and Norwegian Center for Stem Cell Research, Department of Immunology and Transfusion Medicine, Oslo University Hospital HF, Rikshospitalet, Oslo, Norway (J.C.G.).
authors.forename: Joel Clinton
authors.initials: JC
authors.lastname: Glover
authors.affiliation: Department of Pathology, Oslo University Hospital HF, Ullevål, Oslo, Norway (S.B., B.R.); Institute of Clinical Medicine (B.R.), Department of Pharmaceutical Biosciences, School of Pharmacy (L.P.E.A., R.E.P.), and NDEVOR, Section of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences (J.C.G.), University of Oslo, Oslo, Norway; and Norwegian Center for Stem Cell Research, Department of Immunology and Transfusion Medicine, Oslo University Hospital HF, Rikshospitalet, Oslo, Norway (J.C.G.) r.e.paulsen@farmasi.uio.no.
authors.forename: Ragnhild Elisabeth
authors.initials: RE
authors.lastname: Paulsen
mesh_terms: D000818:Animals; D002642:Chick Embryo / Q000187:drug effects*; D002645:Chickens / Q000502:physiology*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D057166:High-Throughput Screening Assays; D006801:Humans; D010063:Ovum / Q000187:drug effects*; D011247:Pregnancy