A New Bill in the US Congress Aims to Reduce Animal Testing. Will it Work?
(Thursday, October 6, 2022)
This week the US Congress unanimously cleared the Bill S.5002 which requires FDA to allow alternatives to animal testing for drug and biological applications. While there is a strong bi-partisan political support in the US for this bill, in practicality it may have minimal impact on the animal tests required by FDA. Animal testing is the current gold standard for evaluating the toxicity of new drugs and biologics before they can be tested in clinical trials. Animal toxicity studies are strictly regulated and described in various guidance documents. The requirements for animal tests are not limited to the US; the principle of extrapolating animal toxicity experience to human subjects is universally accepted and described in ICH guidance documents adopted by almost all countries in the World. Over the years, several laws were passed to reduce or defer animal testing. Current FDA standard is to require bare minimum animal experiments to initiate first-in-human clinical studies and defer most large animal studies to later stages of development. For example, certain animal tox studies such as the carcinogenic potential, neonatal, reproductive, and other special toxicity studies are not needed till immediately prior to the market approval application by which time the clinical safety and effectiveness is established and the tox studies complement the missing safety profile information that cannot be collected from human subjects. The main challenge to eliminating animal toxicity is not regulatory but scientific. There are very few if any alternatives to evaluating the complete toxicity profile of a new drug or biologic prior to its approval for use in humans. Cell culture experiments cannot represent the toxic effects of a molecule at the tissue level. The in-silico models for tissue, and in vitro systems such as the organ-on-a-chip model have not evolved to the level where they can replace or even complement animal studies. Animal studies still represents the fastest, cheapest, and most reliable method to evaluate the bigger safety questions about a given drug or biologic. The efficacy studies in animals, on the other hand, are not required by the FDA in almost all cases, at least explicitly, and hence significant flexibility exists for doing reducing or eliminating non-toxicology studies in animals. For that reason, large animal studies and non-human primate studies have almost disappeared from the toxicity profile of most new drugs, and for good reason. The most reliable source of efficacy evaluation is human clinical trials. So, while the new bill describes the political will to change animal study requirements, all it does is replace the word “animal” in the law to “non-clinical”. It will likely have no practical impact on what FDA would keep requiring in IND, NDA and BLA applications for new drugs and biologics.
Dr. Mukesh Kumar
Founder & CEO, FDAMap
Linkedin: Mukesh Kumar, PhD, RAC