Nonclinical Development

V. Extended nonclinical development these parallel activities will include... 

Snodin DJ, Ryle PR. Understanding and applying regulatory guidance on the nonclinical development of biotechnology-derived pharmaceuticals. Bio Drugs 2006 20 25-52. 

One of the primary issues repeatedly arising from the guideline and from the very nature of the complexities of process development, scale up, and eventual large-scale manufacture of biologies is what material is appropriate to use during the various stages of nonclinical development. As stated above, the material should be representative of the anticipated clinical material. This needs to be supported by data, namely identity, purity, stability, and potency. See Table 38.2 for suggested analytical tests for test article used in preclinical studies. 

EMEA Drafts Guideline on the Nonclinical Development of Fixed Combinations of Medicinal Product... 

Unless justified from pharmacokinetic results from humans, additional animal pharmacokinetic are not usually conducted during nonclinical development. Types of animal pharmacokinetics that might be performed include (a) multi-... 

Turner JR, Durham TA. Nonclinical Development Integrated Cardiac Safety Assessment Methodologies for Non-cardiac Drugs in Discovery, Development, and Postmarketing Surveillance. John Wiley Sr Sons Inc. Hoboken, New Jersey. 2009 111-134. 

Farmacia hospitalaria (Sociedad Espanola de Farm-acia Hospitalaria, 1990). ° Edited in 1990, this book compiles all activities, clinical and nonclinical, developed by an hospital pharmacist. Due to the success of the first edition, two years later, the contents were reviewed, and a second edition was published, including more details about clinical contribution of the pharmacist on patient s pharmacotherapy. 

While a nonclinical development program is informative and important, no amount of nonclinical research can predict precisely what will happen once the candidate drug is given to humans. Therefore, a clinical development program is also necessary. The clinical development program builds in many meaningful ways on the results from the nonclinical development program. 

If a candidate drug successfully makes it through the nonclinical development program, the safety and efficacy of the investigational drug will be tested in humans in a series of clinical trials that comprise the clinical development program. Each study that is conducted will test a particular aspect or facet of the drug, and the overall... 

V. Clinical Drug Development Stage (Conducted Concurrently with Nonclinical Development)... 

From a practical perspective, species cross-reactivity should be considered an important criterion for lead candidate selection. In the absence of cross-reactivity, there are limited options for assessing the potential safety risks during nonclinical development, which in turn impacts the conduct of the clinical trials (Muller et al., 2009). Ideally, a lead candidate with both rodent and nonrodent cross-reactivity would be identified, as this enables the molecule to be evaluated in pharmacology studies and if needed early rodent toxicology studies. However, if not possible, all available protein engineering efforts should be undertaken to identify a lead with NHP CToss-reactivity (Doria-Rose and Joyce, 2015). 

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