Preclinical Testing for a New Excipient

The preclinical safety evaluation of a new excipient generally commences after initial in vitro pharmacy work to demonstrate the material s proposed role. Additionally, some in vivo investigations (often a short exposure study in the rodent) may occur, for example, comparing the new proposed material in a drug formulation versus a marketed drug formulation. Enhanced drug exposure and/or a reduced toxicity profile (through the use of lower-dose levels or excipient protection) may be a study end point. 

Guidance Initial Short-term clinical use Midterm clinical use Longer-term clinical use 

IPEC-US (intended clinical route)a Acute oral and dermal toxicity, skin and eye irritation, and skin sensitization. Bacterial gene mutation and chromosome damage. ADME (intended route). 28-day toxicity (2 species by intended clinical route) Short-term use studies. 90-day toxicity (most appropriate species). Teratology (rat and/or rabbit). Genotoxicity assays. Additional assays (conditional) 1 Short-/midterm studies. One-generation reproduction. Chronic toxicity (rodent and nonrodent) and carcinogenicity (conditional) 

FDA (intended Standard safety Acute toxicity (rodent and Short-term use studies Short-/midterm studies 

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