Monday, 19 June 2023 11:47

Animal-free drug development in the U.S.: Addressing NAMs builds confidence Featured

An article from Nature Medicine provides a good insight into the current debate about the recognition of results from animal-free methods in drug development.

At the end of December 2022, U.S. President Joe Biden signed the FDA Modernization Act 2.0. Under this law, the safety of drugs no longer necessarily has to be tested on animals to receive approval from the U.S. Food and Drug Administration to start a clinical trial.

The FDA Modernization Act 2021 "... allows manufacturers and sponsors of a drug to use alternative test methods to animal testing to study the safety and effectiveness of a drug, ..." As a result, in the bill, the text "animal" was deleted and replaced with "nonclinical test or nonclinical study." The term "nonclinical test or nonclinical study" means a test or study conducted in vitro, in silico, in chemico, or in vivo before or during the clinical trial phase. The so-called New Approach Methodologies (NAMs), which are predominantly human-specific methods without animal testing such as cell-based assays, organ-on-a-chips, microphysiological systems, computer models, and other non-animal-based testing methods, have developed rapidly in recent years. Being based on human physiology, they are very meaningful and provide more precise information than animal experiments. Only when ultimately investigative questions cannot be answered using these methods is an animal experiment considered.

It is increasingly recognized that in some cases animal models are simply not informative for understanding the efficacy and safety of new drugs, Nicole Kleinstreuer, PhD, director of the National Toxicology Program's Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), is quoted.1 According to the FDA, more than 90% of drugs already tested in preclinical trials fail to demonstrate either safety or efficacy when tested in humans. So better methods are desirable.

In addition, it would be attractive for drug development companies to be able to omit the time-consuming and expensive procedures on animals. According to the experience of manufacturers of animal-free methods, they are showing increasing interest in the new methods as a result of the new American legal situation and are investing here.

This does not immediately put an end to animal testing, but the regulatory authorities must first definitely deal with the results from the new methods, become familiar with them and learn about their performance, expressed a former Sanofi manager recently - the group that was the first to obtain approval from the FDA for a clinical trial. However, additional safety data should also had been present from previous animal studies with the drug for an earlier induction.1

International drug companies definitely have an interest in the new methods: recently, the head of the Darmstadt-based Dax company Merck, Belén Garijo2, spoke out in favor of significantly reducing the number of animal tests for the development and product safety of drugs and chemicals in the coming years. Roche also wants to significantly expand the use of NAMs. The German Society for Endocrinology (DGE), for example, also made a clear statement. Animal testing must be further reduced because non-animal methods are improving all the time, said DGE Vice President Jan Tuckermann.3

Fears are already circulating that regulatory authorities may be subject to lobbying by biotech and drug companies. This may underestimate the regulatory authorities. They conduct their own research on NAMs in their own laboratories since years and cooperate with the National institutes of Health (NIH) for validation. Researchers such as Prof. Donald Ingber, founding director of the Wyss Institute for Biologically Inspired Engineering at Harvard University, also currently see their developments as a way to reduce animal testing, i.e. to use them before they are turned into final animal tests to investigate unexpected side effects in the whole body. After all, the new American Modernization Act 2.0 does not exclude animal testing totally.

1 Moutinho, S. Researchers and regulators plan for a future without lab animals. Nat Med (2023).