Opportunities to minimise animal use in pharmaceutical regulatory general toxicology: A cross-company review

Society of Toxicologic Pathology Position Paper on Best Practices on Recovery Studies

“…Although preclinical toxicities associated with most biologics are often a result of exaggerated intended pharmacological activity or inherent immunogenicity (Baldrick 2011;Sparrow et al 2011;Tabrizi et al 2009;Weinberg et al 2005), nonspecific effects can occur (Sparrow et al 2011). Some biopharmaceuticals (e.g., monoclonal antibodies) have lengthy half-lives resulting in continued exposure following the end of the dosing period (Dong et al 2011;Lobo, Hansen, and Balthasar 2004).…”

Functional Assessments in Nonhuman Primate Toxicology Studies to Support Drug Development

“…The standard duration of regulatory toxicology studies run before human exposure is 28 days of dosing (termed 1-month studies), which permits dosing of the same duration in humans [1][2][3][4]; they are required in a rodent and a nonrodent species and are conducted according to the principles of Good Laboratory Practice [3]. These 1-month studies are preceded by maximal tolerated dose (MTD)/dose range-finding (DRF) studies.…”

“…Longer-term toxicology studies (longer than 1 month in duration) are conducted in parallel to early clinical trials to enable the dosing of patients over longer periods [1][2][3][4]. In addition to these general toxicology studies, specialized repeat-dose toxicity studies are also required and include rodent carcinogenicity, reproductive toxicology, and juvenile toxicity studies [3,[7][8][9][10][11][12][13].…”

Incorporation of capillary microsampling into whole body plethysmography and modified Irwin safety pharmacology studies in rats

“…Following a short period in a warming chamber and minimal handling, blood volumes as low as 25e32 ml are accurately collected (Jonsson et al, 2012a(Jonsson et al, , 2012b, and as such, the impact on the animal, both in terms of welfare and on volumedepletion effects on clinical pathology parameters are much improved (Powles-Glover et al, 2014). This introduces the opportunity for serial sampling within the same animal for small rodent species, reducing the requirement of satellite animals merely to provide sufficient volumes to support toxicokinetic profiling (Sparrow et al, 2011;Chapman et al, 2013Chapman et al, , 2014Powles-Glover et al, 2014). Furthermore, the provision of pharmacokinetic data from the same animal as the functional, toxicological or histopathological endpoints provides additional scientific robustness and allows interpretation of individual data as part of the overall interpretation of results (as is the case in non-rodent studies).…”