Toxicology non-clinical

Dixit, R., What non-clinical toxicology and safety pharmacology data are needed to accelerate phase I—II clinical trials , Am. Pharm. Outsourcing, 5, 30-37, 2004. 

The design and the execution of safety pharmacology studies are focused upon the safety of human volunteers and patients in clinical trials. ICH S7A and may be soon S7B strive for effective integration of safety pharmacology results with those of the non-clinical (toxicology) and clinical safety databases. 

Generally accepted 28 consecutive daily doses in rodents. Adaptations of immunotoxicity assays have been described using non-rodent species. The species, strain, dose, duration, and route of administration used in immune function assays should be consistent, where possible, with the non-clinical toxicology study in which an adverse immune effect was observed. 

Supporting the choice of test species and treatment regimen for non-clinical toxicology studies... 

The nature, timing and extent of the initial non-clinical toxicology program depend on the clinical development plan that it must support. The ICH guidelines further specify the extent and duration of nonclinical studies that are required to initiate or continue clinical studies (Federal Register, November 1997, and see below). Therefore, it is important that the clinical development plan, at least the initial stages, be clearly delineated. 

GLP regulations require confirmation of the potency of all formulations used in non-clinical studies. Furthermore, current ICH guidelines also require toxicokinetic data (i.e. animal pharmacokinetics determined at one or more time points during a non-clinical toxicology study). Both the potency and toxicokinetic assays require an analytical... 

In Japan, if there are no Phase II clinical trials of equivalent duration to the proposed Phase III trials, then non-clinical toxicology studies of the durations shown in Table 6.2 should be considered. 

Non-clinical toxicology studies required to support Phase II and Phase III stages of the program depend upon a variety of factors. First, as shown in Tables... 

The European Community, and other countries, require several expert reports in each dossier, one of which examines the non-clinical toxicology of the new drug. These documents are typically about 20-30 pages long and summarize all the toxicology data, as well as the clinical implications. 

---