The Value of Juvenile Animal Studies What Have We Learned From Preclinical Juvenile Toxicity Studies? II

Recent changes in the regulations from the FDA and EMA have shifted the focus of juvenile toxicity studies more to the safe use of all pharmaceuticals and the absence of label or safety information for the pediatric population. Unlike other regulatory guidance, the need or design of these animal studies is not specified. Ideally these should be decided case-by-case based on the patient population, pharmacology, existing toxicological and clinical data, dosing regimen, and developing system impact. Following the publishing of a small intercompany survey (Bailey and Marien, 2009), a more extensive survey was commissioned by the ILSI/HESI DART Technical Committee to clarify what has been learned for the safety assessment for pediatrics. Contributions from 24 companies totaling 241 studies (84% rat and 14% dog) were received. In 12 of 82 programs (15%) were the existing adult preclinical or clinical data considered a sufficient safety prediction for pediatric trials. Clinical/preclinical correlates were observed in 17.2% (rat) and 42.9% (dog) of the studies and a lack of predictability from the pharmacology or the adult toxicity data was seen in 25% of rat and 14.3% of dog studies. Many of the studies were large, lengthy, complex, included parameters that mirrored the adult studies and yielded no new or useful information. We should avoid conducting complex or inappropriate studies and Contract Research Organisations and regulatory agencies have a role in encouraging more targeted designs. Only with appropriate designs can we adequately identify safety or pharmacokinetic issues, suggest clinical endpoints, and contribute to the product label. Birth Defects Res (Part B) 92:273-291, 2011. (C) 2011 Wiley-Liss, Inc.