title: The design of chronic toxicology studies of monoclonal antibodies: implications for the reduction in use of non-human primates.
abstract: The changing environment of monoclonal antibody (mAb) development is impacting on the cost of drug development and the use of experimental animals, particularly non-human primates (NHPs). The drive to reduce these costs is huge and involves rethinking and improving nonclinical studies to make them more efficient and more predictive of man. While NHP use might be unavoidable in many cases because of the exquisite specificity and consequent species selectivity of mAbs, our increasing knowledge base can be used to improve drug development and maximise the output of experimental data. Data on GLP regulatory toxicology studies for 58mAbs were obtained from 10 companies across a wide range of therapeutic indications. These data have been used to investigate current practice and identify study designs that minimise NHP use. Our analysis shows that there is variation in the number of animals used for similar studies. This information has been used to develop practical guidance and make recommendations on the use of science-based rationale to design studies using fewer animals taking into account the current regulatory guidance. There are eight recommendations intended to highlight areas for consideration. They include guidance on the main group size, the inclusion of recovery groups and the number of dose groups used in short and long term chronic toxicology studies.
authors.affiliation: National Centre for Replacement, Refinement and Reduction of Animals in Research, Gibbs Building, 215 Euston Rd., London NW1 2BE, UK. kathryn.chapman@nc3rs.org.uk
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Chapman
authors.forename: Laura
authors.initials: L
authors.lastname: Andrews
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Bajramovic
authors.forename: Paul
authors.initials: P
authors.lastname: Baldrick
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Black
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Bowman
authors.forename: Lorrene A
authors.initials: LA
authors.lastname: Buckley
authors.forename: Lee A
authors.initials: LA
authors.lastname: Coney
authors.forename: Jessica
authors.initials: J
authors.lastname: Couch
authors.forename: A
authors.initials: A
authors.lastname: Maggie Dempster
authors.forename: Lolke
authors.initials: L
authors.lastname: de Haan
authors.forename: Keith
authors.initials: K
authors.lastname: Jones
authors.forename: Nick
authors.initials: N
authors.lastname: Pullen
authors.forename: Anne Seitske
authors.initials: AS
authors.lastname: de Boer
authors.forename: Jennifer
authors.initials: J
authors.lastname: Sims
authors.forename: C
authors.initials: C
authors.lastname: Ian Ragan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D011323:Primates; D012107:Research Design; D036401:Toxicity Tests, Chronic / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal