Juvenile Nonclinical Safety Studies in Support of Pediatric Drug Development.

A pediatric assessment is now a required component of every drug marketing application in North America, Europe, and Japan, unless a waiver has been granted previously. Nonclinical juvenile toxicity studies are often required as part of this assessment. The protocols for juvenile toxicity studies are best devised in consultation with the regulatory authorities. It is important to submit the pediatric investigation plan (PIP) or pediatric study plan (PSP) early, in order not to delay the marketing authorization of the drug in adults. The choice of species and the design of juvenile toxicity studies are based on a series of complex considerations, including the therapeutic use of the drug, age at which children will be treated, duration of treatment, and potential age- or species-specific differences in efficacy, pharmacokinetics, or toxicity.

[Does a positive finding of tetrahydrocannabinol in the blood result from ingestion of Indian frankincense (Boswellia serrata)?]. / Führt die Einnahme von indischem Weihrauch zu einem positiven Tetrahydrocannabinolbefund im Blut?

The exculpatory statement that a positive THC finding in the blood is due to the consumption of hemp products or passive exposure to cannabis smoke has been disproved by the monitoring of hemp products and recent passive inhalation studies conducted in social settings, which showed that these conditions are unlikely to produce a positive result in the blood. The defense that the ingestion of Indian olibanum may result in a positive THC concentration in the blood is unusual; it is based on older publications where authors had speculated on a possible association of the synthetic pathways of THC from terpenoid precursors also being present in olibanum and the biogenesis of THC in hemp. It had further been speculated whether chemical or plant-derived pathways may also occur in humans. A thorough understanding of the different pathways and recently published results have outdated these speculations.

Value of juvenile animal studies.

The Developmental and Reproductive Toxicology Technical Committee of the ILSI Health and Environmental Sciences Institute has undertaken a project to address the impact of juvenile animal studies on pediatric drug development. A workshop, sponsored and organized by the Health and Environmental Sciences Institute Developmental and Reproductive Toxicity Technical Committee, was held on May 5-6, 2010, in Washington, DC, to discuss the outcome of a global survey and the value of juvenile animal studies in the development of drugs intended for use in pediatric patients. During this workshop, summary data from the 2009-2010 survey were presented, and breakout sessions were used to discuss specific case studies to try to assess the impact of juvenile animal studies performed to support specific pediatric drug development. The objectives of the Workshop on The Value of Juvenile Animal Studies were to (1) provide a forum for scientists representing industry, academia, and regulatory agencies to discuss the impact of juvenile animal studies on pediatric drug development, (2) evaluate summary data from the survey to understand how the juvenile study data are being used and their impact in labeling and risk assessment, (3) discuss selected case studies from the survey to highlight key findings, and (4) identify the areas of improvement for the designs of juvenile animal studies. The take home message that resonated from the workshop discussions was that well-designed juvenile animal studies have demonstrated value in support of certain pediatric drug development programs. However, it was also clear that a juvenile animal study is not always warranted.