The selection of marmoset monkeys (Callithrix jacchus) in pharmaceutical toxicology

Abstract

Prior to controlled clinical trials in human volunteers or patients it is required that novel pharmaceuticals are evaluated for pre-clinical safety in a rodent and a non-rodent ('second') species. In most cases the rodent species used has been the rat and the second species has been the dog or macaque (usually cynomolgus or rhesus) monkey. However, there is an increasing trend within the United Kingdom (UK) pharmaceutical industry to use the common marmoset (Callithrix jacchus) for pre-clinical toxicology programmes. This paper examines the practicality of using the common marmoset (henceforth referred to as 'the marmoset') in toxicological testing and reviews metabolic and pharmacodynamic similarities between this species and humans. It then discusses some of the advantages and disadvantages of the use of this species when compared with two other alternatives to the dog and macaque, namely the ferret and minipig. In particular, the marmoset has clear advantages over the macaque in terms of animal welfare and practicality. There is regulatory acceptance of this species for Investigational New Drug (IND), Clinical Trial Exemption (CTX), New Drug Application (NDA) and Marketing Authorization Application (MAA) registrations. Whilst the dog is likely to be maintained as the primary non-rodent species in toxicology, the marmoset has been, and will likely continue to be, adopted as an additional non-rodent species in pre-clinical toxicology programmes where appropriate.