title: Recommendations from a global cross-company data sharing initiative on the incorporation of recovery phase animals in safety assessment studies to support first-in-human clinical trials.
abstract: An international expert group which includes 30 organisations (pharmaceutical companies, contract research organisations, academic institutions and regulatory bodies) has shared data on the use of recovery animals in the assessment of pharmaceutical safety for early development. These data have been used as an evidence-base to make recommendations on the inclusion of recovery animals in toxicology studies to achieve scientific objectives, while reducing animal use. Recovery animals are used in pharmaceutical development to provide information on the potential for a toxic effect to translate into long-term human risk. They are included on toxicology studies to assess whether effects observed during dosing persist or reverse once treatment ends. The group devised a questionnaire to collect information on the use of recovery animals in general regulatory toxicology studies to support first-in-human studies. Questions focused on study design, the rationale behind inclusion or exclusion and the impact this had on internal and regulatory decisions. Data on 137 compounds (including 53 biologicals and 78 small molecules) from 259 studies showed wide variation in where, when and why recovery animals were included. An analysis of individual study and programme design shows that there are opportunities to reduce the use of recovery animals without impacting drug development.
authors: UK National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs), Gibbs Building, 215 Euston Road, London NW1 2BE, UK. Electronic address: fiona.sewell@nc3rs.org.uk.
authors: Fiona
authors: F
authors: Sewell
authors: UK National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs), Gibbs Building, 215 Euston Road, London NW1 2BE, UK.
authors: Kathryn
authors: K
authors: Chapman
authors: Covance Laboratories Ltd, Otley Road, Harrogate HG3 1PY, UK.
authors: Paul
authors: P
authors: Baldrick
authors: Vertex Pharmaceuticals Inc., 50 Northern Avenue, Boston, MA 02139, USA.
authors: David
authors: D
authors: Brewster
authors: Huntingdon Life Sciences Ltd, Occold, Eye, Suffolk IP23 7PX, UK.
authors: Alan
authors: A
authors: Broadmeadow
authors: Food and Drug Administration (FDA), 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
authors: Paul
authors: P
authors: Brown
authors: Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA.
authors: Leigh Ann
authors: LA
authors: Burns-Naas
authors: Biogen Idec, Cambridge, MA 02142, USA.
authors: Janet
authors: J
authors: Clarke
authors: Infinity Pharmaceuticals, 780 Memorial Drive, Cambridge, MA 02139, USA.
authors: Alex
authors: A
authors: Constan
authors: Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors: Jessica
authors: J
authors: Couch
authors: Bayer Pharma AG, Müllerstrasse 170, 13353 Berlin, Germany.
authors: Oliver
authors: O
authors: Czupalla
authors: Charles River Laboratories, Preclinical Services, Tranent, Edinburgh EH33 2NE, UK.
authors: Andy
authors: A
authors: Danks
authors: Merck, 770 Sumneytown Pike, Mailstop WP45-201, West Point, PA 19486, USA.
authors: Joseph
authors: J
authors: DeGeorge
authors: MedImmune, Granta Park, Cambridge CB21 6GH, UK.
authors: Lolke
authors: L
authors: de Haan
authors: Austrian Agency for Health and Food Safety, Traisengasse 5, 1200 Vienna, Austria.
authors: Klaudia
authors: K
authors: Hettinger
authors: Novartis Institutes for BioMedical Research (NIBR), Basel, Switzerland.
authors: Marilyn
authors: M
authors: Hill
authors: Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, CH - 4070 Basel, Switzerland.
authors: Matthias
authors: M
authors: Festag
authors: Food and Drug Administration (FDA), 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
authors: Abby
authors: A
authors: Jacobs
authors: Food and Drug Administration (FDA), 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
authors: David
authors: D
authors: Jacobson-Kram
authors: Celgene, 86 Morris Avenue, Summit, NJ 07901, USA.
authors: Stephan
authors: S
authors: Kopytek
authors: AbbVie Deutschland GmbH & Co. KG, Knollstrasse, 67061 Ludwigshafen, Germany.
authors: Helga
authors: H
authors: Lorenz
authors: Novo Nordisk A/S, Novo Nordisk Park, Maaloev, Denmark.
authors: Sophia Gry
authors: SG
authors: Moesgaard
authors: Huntingdon Life Sciences Ltd, Alconbury, Huntingdon, Cambridgeshire PE28 4HS, UK.
authors: Emma
authors: E
authors: Moore
authors: University of Eastern Finland, Faculty of Health Sciences, School of Pharmacy, Kuopio, Finland.
authors: Markku
authors: M
authors: Pasanen
authors: Pfizer Drug Safety Research and Development, 455 Eastern Point Rd., Groton, CT 06340, USA.
authors: Rick
authors: R
authors: Perry
authors: Board member, NC3Rs, Gibbs Building, 215 Euston Road, London NW1 2BE, UK.
authors: Ian
authors: I
authors: Ragan
authors: AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
authors: Sally
authors: S
authors: Robinson
authors: Paul-Ehrlich-Institute, Federal Agency for Vaccines and Biomedicines, Langen, Germany.
authors: Petra M
authors: PM
authors: Schmitt
authors: Allergan, Drug Safety Evaluation, 2525 Dupont Dr, RD-2A, Irvine, CA 92612-1599, USA.
authors: Brian
authors: B
authors: Short
authors: iMED, UL, University of Lisbon, Portugal.
authors: Beatriz Silva
authors: BS
authors: Lima
authors: Millenium: The Takeda Oncology Company, 40 Landsdowne St., Cambridge, MA, USA.
authors: Diane
authors: D
authors: Smith
authors: GlaxoSmithKline, Park Road, Ware, Hertfordshire SG12 0DP, UK.
authors: Sue
authors: S
authors: Sparrow
authors: Janssen Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
authors: Yvette
authors: Y
authors: van Bekkum
authors: Medicines Healthcare Products Regulatory Agency (MHRA), UK.
authors: David
authors: D
authors: Jones
mesh_terms: D000818:Animals; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D007391:International Cooperation; D023421:Models, Animal; D012107:Research Design; D011795:Surveys and Questionnaires; D013997:Time Factors; D014116:Toxicology / Q000379:methods*
keywords: 3Rs; Dog; Non-clinical; Primate; Recovery; Reduction; Regulatory toxicology; Repeat-dose studies; Reversibility; Rodent