title: A European pharmaceutical company initiative challenging the regulatory requirement for acute toxicity studies in pharmaceutical drug development.
abstract: Regulatory guidelines indicate acute toxicity studies in animals are considered necessary for pharmaceuticals intended for human use. This is the only study type where lethality is mentioned as an endpoint. The studies are carried out, usually in rodents, to support marketing of new drugs and to identify the minimum lethal dose. A European initiative including 18 companies has undertaken an evidence-based review of acute toxicity studies and assessed the value of the data generated. Preclinical and clinical information was shared on 74 compounds. The analysis indicated acute toxicity data was not used to (i) terminate drugs from development (ii) support dose selection for repeat dose studies in animals or (iii) to set doses in the first clinical trials in humans. The conclusion of the working group is that acute toxicity studies are not needed prior to first clinical trials in humans. Instead, information can be obtained from other studies, which are performed at more relevant doses for humans and are already an integral part of drug development. The conclusions have been discussed and agreed with representatives of regulatory bodies from the US, Japan and Europe.
authors.affiliation: AstraZeneca, Alderley Park, UK. sally.robinson@astrazeneca.com
authors.forename: Sally
authors.initials: S
authors.lastname: Robinson
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Delongeas
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Donald
authors.forename: David
authors.initials: D
authors.lastname: Dreher
authors.forename: Matthias
authors.initials: M
authors.lastname: Festag
authors.forename: Sophie
authors.initials: S
authors.lastname: Kervyn
authors.forename: Ann
authors.initials: A
authors.lastname: Lampo
authors.forename: Kamil
authors.initials: K
authors.lastname: Nahas
authors.forename: Vicente
authors.initials: V
authors.lastname: Nogues
authors.forename: Deborah
authors.initials: D
authors.lastname: Ockert
authors.forename: Kirsty
authors.initials: K
authors.lastname: Quinn
authors.forename: Sally
authors.initials: S
authors.lastname: Old
authors.forename: Nigel
authors.initials: N
authors.lastname: Pickersgill
authors.forename: Kev
authors.initials: K
authors.lastname: Somers
authors.forename: Claudia
authors.initials: C
authors.lastname: Stark
authors.forename: Peter
authors.initials: P
authors.lastname: Stei
authors.forename: Lynne
authors.initials: L
authors.lastname: Waterson
authors.forename: Kathryn
authors.initials: K
authors.lastname: Chapman
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D003195:Computer Communication Networks; D003625:Data Collection; D004305:Dose-Response Relationship, Drug; D004345:Drug Industry / Q000592:standards*; D062787:Drug Overdose; D005062:European Union; D006801:Humans; D007880:Legislation, Drug / Q000592:standards*; D004364:Pharmaceutical Preparations / Q000592:standards*; D012107:Research Design; D018675:Toxicity Tests / Q000592:standards*
chemical_list: D004364:Pharmaceutical Preparations