by Ali Said Faqi
One area where this is especially true is juvenile toxicity testing. We know there are profound differences between adults and children in drug disposition and effect; yet most drugs prescribed to children have not been adequately studied in the young.
Fortunately, the pharmaceutical industry and regulatory agencies are starting to address this issue. Drug companies are deliberately focusing on juvenile data. Since 2006, the United States, the European Union and Japan have issued guidelines for evaluating the safety of pediatric medicines.
Generating such data begins in preclinical development. Juvenile animal studies at this stage can assist in identifying postnatal development toxicities or other adverse effects that may not be adequately assessed in routine rapid adult studies or in standard pediatric clinical trials.
As more juvenile toxicology studies are undertaken, we’re learning many important lessons:
Study design is key. Safety data are useful only if generated from the most appropriate species at the most relevant age and comparable organ development. This means studies are designed case by case, in discussion with regulatory guidelines and mimicking the pediatric trial as much as possible. A well-designed study will address the complex logistical and technical issues involved while avoiding costly delays.
Selecting Animal Species. Rodents, rabbits, dogs and non-human primates (NHP) are all appropriate models, but each has limitations. Endpoints may be the limiting factor in any given study. So might maturation (particularly reproductive assessments in juvenile NHP), locomotion, skeletal development, blood volume and other elements. In short, there may be a few exceptions to the one-species standard depending on the data sought.
A better determination of age comparison is needed. In order to draw relevant conclusions, the stage of development in the animal being studied must be comparable to that in the intended pediatric population. The tools that exist aren’t adequate in all cases.
Regulatory authorities are increasingly interested in pediatric assessment. Both the United States and the European Union require assessment plans, known as the Pediatric Investigation Plan (PIP) for the European Medicines Authority, and pediatric assessment under the U.S. Pediatric Equity Research Act.
Safety concerns are paramount. When designing a juvenile toxicity study, appropriate safety concerns of the intended pediatric drug must be carefully addressed.
The latter lesson, of course, is the most important. While juvenile toxicity testing might be vital for product approval or pediatric indications, its greatest role is assuring that the medicines we give to our children are as safe and effective as they can be.
Ali Said Faqi, DVM, Ph.D., D.A.B.T., Fellow ATS, is Senior Director, Developmental & Reproductive Toxicology, at MPI Research. Dr. Faqi gave a presentation on juvenile toxicity testing at the recent Society of Toxicology Annual Meeting. To find out more about juvenile toxicity testing at MPI Research, contact us at firstname.lastname@example.org.