Food and Drug Administration researchers hope new simulation methods will be able to show whether animal drugs under development are equivalent to approved drugs without the need for studies involving animal deaths.
If they validate their simulation methods, drug companies could potentially secure approval for some generic animal drugs and reformulations without performing terminal studies. FDA information indicates those companies instead would use the simulations.
In a statement published this fall, FDA commissioner Scott Gottlieb, MD, said the FDA is trying to reduce, replace, or refine the use of animals in research.
"Before approving an animal drug, the FDA must have data to understand how a drug behaves in an animal's body," Dr. Gottlieb's announcement states. "As one part of generating these data, animal drug developers perform bioequivalence studies, which compare pharmaceutical products (i.e., an original approved product and proposed generic version) to see if they are similar enough to link them in terms of safety and effectiveness."
This fall, FDA officials plan to start a nine-month study during which they will test three formulations of ivermectin and praziquantel, ingredients in Iverhart Max. The formulations will have different dissolution rates for the two drugs.
Ivermectin is used to treat dogs with heartworm, and praziquantel is used to treat dogs with tapeworms.
Agency researchers will administer tablets containing all three formulations, in different orders, to 27 dogs and draw blood for testing. They also will create a physical model to simulate dissolution of the same drugs in a dog's gastrointestinal tract.
Siobhan DeLancey, who is a spokeswoman for the FDA Center for Veterinary Medicine, provided a statement that said the live animal studies will provide the data needed to validate the simulations, which the researchers will use to predict whether the drugs are equivalent.
"If the collected data support the study hypothesis, animal drug sponsors may then use these data to aid in the design of in vitro studies used as a surrogate for certain trials using animal subjects," she said. "Instead of using animals, sponsors would be able to use the in vitro dissolution data to extrapolate how their generic or reformulation functions in the body as compared to the original approved product."
The FDA's study design could, for example, help researchers avoid using dogs to check the equivalence of two anti-parasitic drugs that have local, rather than systemic, action and absorption, according to the concept paper and Dr. Gottlieb's announcement. Today, that probably would require terminal studies with large numbers of dogs.
"In short, our goal is to do one single study involving a small number of dogs—where the dogs will only be subject to minimally invasive blood sampling and adopted as pets at the completion of the short trial—to eliminate the need for the use of dogs in certain types of future studies, some where they might have been euthanized," Dr. Gottlieb's announcement states.
DeLancey said the FDA has started encouraging drug companies to develop and validate alternatives to animal testing, including in vitro dissolution tests and computer modeling. But developing some drugs may still require live animal studies, including terminal studies. She cited as an example toxicological studies in support of a new animal drug.