Preclinical drug candidate safety assessment

The topic of preclinical assessment of a clinical candidate has been reviewed in Chapter 29. The topic is mentioned here because the decision as to whether it is safe to take a candidate drug into humans is ultimately a medical judgment that can only be made by individuals responsible for clinical drug development. Preclinical safety assessments are designed to provide the knowledge needed to decide whether it is reasonably safe to study a drug candidate in humans. The term reasonably safe is used in this context because that is what an FDA reviewer must answer when reviewing an IND application. 

The paradigm in drug development is sequentially divided into several phases starting with preclinical assessment. After selection of a drug candidate based on preclinical studies, clinical Phase 1 studies are initiated to characterize the safety, tolerability, biomarker, and pharmacokinetic profiles of the candidate, typically in healthy subjects. Phase 2 studies test the drug efficacy hypothesis in patients and explore dose range, and Phase 3 studies aim to demonstrate efficacy in the intended patient population in a statistically robust manner. 

A discussion of regulatory requirements for the preclinical safety assessment of drug candidates intended for use in humans would require significant detail. The reader is referred to excellent resources and websites (www.ich.org, www.fda.gov, and www.emea.com) for detail and additional information. 

It has become accepted that the main pharmaceutical areas where metabonomics is impacting include validation of animal models of disease, including genetically modified animals preclinical evaluation of drug safety studies allowing ranking of candidate compounds assessment of safety in humans in clinical trials after product launch, quantitation, or ranking of the beneficial effects of pharmaceuticals. 

PRECLINICAL SAFETY ASSESSMENT OF DRUG CANDIDATE-INDUCED PANCREATIC TOXICITY FROM AN APPLIED PERSPECTIVE... 

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