The Dog as a Second Species for Toxicology Testing Provides Value to Drug Development.

ABSTRACT

The objective of the pharmaceutical industry is to develop new drugs that are safe for human use. In many cases, the accepted approach codified in guidance from regulatory authorities to assess the nonclinical safety profile of potential pharmaceuticals is to perform toxicity testing in two species. However, the use of a second species to establish the safety of new pharmaceuticals has been the subject of much scrutiny in recent years and the industry has been repeatedly challenged to reduce, refine, or replace some or all of the animals used to establish the safety of these pharmaceutical candidates. Specifically, the value of the dog in this testing paradigm has been questioned. Publications reviewing available data for marketed drugs suggest that for many drugs, the dog does not identify unique toxicities critical to human safety. The weakness of this approach, however, is that many of the cases where the dog (or any other species) has the greatest impact on drug development are cases for which development decisions based on safety concerns are not shared publicly. The European Federation of Pharmaceutical Industries and Associations (EFPIA) Preclinical Development Expert Group (PDEG) decided to share case studies collected from its membership and the literature to illustrate the value of the dog in drug development decision-making and clinical monitoring practices to protect the safety of trial subjects.