A European pharmaceutical company initiative challenging the regulatory requirement for acute toxicity studies in pharmaceutical drug development.
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.
Robinson
Sally
S
AstraZeneca, Alderley Park, UK. sally.robinson@astrazeneca.com
Delongeas
Jean-Luc
JL
Donald
Elizabeth
E
Dreher
David
D
Festag
Matthias
M
Kervyn
Sophie
S
Lampo
Ann
A
Nahas
Kamil
K
Nogues
Vicente
V
Ockert
Deborah
D
Quinn
Kirsty
K
Old
Sally
S
Pickersgill
Nigel
N
Somers
Kev
K
Stark
Claudia
C
Stei
Peter
P
Waterson
Lynne
L
Chapman
Kathryn
K
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*
D004364:Pharmaceutical Preparations