Why Do We Still Need Primate Toxicity Studies?
(Thursday, March 31, 2023)
Since the beginning of the pandemic, there has been an acute shortage of monkeys for non-clinical research. Recently, due to increase in smuggling of long-tailed macaques, federal regulator started blocking imports from Cambodia, further aggravating the shortage of animals and a resulting increase in the cost and delays in research. But how big is this crisis and why? There has been a regulatory acceptance across the globe to reduce, refine and replace (“the 3Rs”) animal studies in general and large animals, like primate, in particular. FDA has been talking about the principle of the 3Rs for the last few years. Primate experiments are not needed for the market approval of almost all small molecules. For biological molecules, primates are needed only if there are no alternatives such as for Developmental and Reproductive Toxicity (DART) studies. The core guidance document for non-clinical toxicity, ICH M3(R2), does not specifically mandate any given animal model. Rather it requires the developers to choose “suitable” small and large animal models for non-clinical toxicity investigations. FDA allows using other non-rodent species, conducting general toxicity studies only in rodents, and using fewer test groups to reduce the number of animals needed for each experiment. In its guidance to deal with the shortage of primates for non-clinical toxicity studies due to the pandemic, FDA suggested several alternates to primate research. The pandemic guidance addresses common questions the answers to which are still valid, post-pandemic. FDA also published peer-reviewed articles to suggest ways to reduce primate research. It is critical for companies to decrease their dependence on primate research when regulators have repeatedly indicated and opined that primate experiments are not needed in most cases, and even when needed, regulators accept alternates to primate experiments. The onus is on FDA to further revise its guidance for primate research, and clarify its policy, because there is still significant confusion in the industry about what FDA wants. Primate research should be highly reduced based on scientific logic; they are no longer the only option for investigating toxicity for new drugs.
Dr. Mukesh Kumar
Founder & CEO, FDAMap
Linkedin: Mukesh Kumar, PhD, RAC