The Food and Drug Administration(FDA) is the federal agency responsible for approval of new drugs in the U.S. In December 2022, The FDA Modernization Act 2.0 was signed into law by President Biden.
The FDA Modernization Act 2.0 amends the Federal Food, Drug and Cosmetic Act instated in 1938. The 1938 bill mandated testing using animal-based methods to improve quality and safety assessments preceding approval of new drugs and medical devices. Since then, development of animal-free test methods has taken enormous leaps, and the FDA Modernization Act 2.0 now enables implementation of alternative non-animal methods for approval of new drugs.
The nonclinical tests approved by the new bill are tests conducted
in vitro, in silico, in chemico
and also includes non-human
in vivo
test methods. The test methods may include animal tests, non-animal tests or human biology-based tests.
In summary, the animal-based test methods are no longer mandatory for approval of newdrugs but can, and will, still be used. Furthermore, the requirement of using animal testing for licensing of a drug that is biosimilar or interchangeable with another biological product is also removed by the implementation of the FDA Modernization Act 2.0.
S.5002 - FDA Modernization Act 2.0 (congress.gov)
The question is, however, what impact the FDA Modernization Act 2.0 will have on drug approval and animal testing, both in the U.S. and globally.
The Swedish context
We asked
Camilla Svensson, Scientific director in pharmacology and toxicology at the Swedish Medical Products Agency, for a comment.
Will the implementation of the FDA Modernization Act 2.0 have any impact on drugapproval in Sweden?
In our perspective, we do not expect any effects on drug approval in Sweden as we follow legislation instituted by the Swedish government and the European Union. The signing of the FDA Modernization Act 2.0 is rather an adjustment to how both the FDA and European authorities approving new drugs are already implementing new, improved methods and the 3Rs.
For example, there is an increase in the development of human-specific products, where use of alternative non-animal methods for testing and approval are clearly motivated. It is, however, of great importance that new approach methods (NAM’s) are being thoroughly evaluated and accepted by authorities such as the European Medicines Agency (EMA) to be approved for regulatory testing. That will ensure that the use of alternative non-animal test methods will result in similar, or even better, evaluation of drug efficacy and safety EMA offers consultation regarding qualification of alternative methods, and the implementation of the FDA Modernization Act 2.0 could possibly increase the interest also in Europe for method developers to proceed with new methods.
It should be noticed, though, that many years will pass before alternative methods have been established that can replace the in vivo studies required within regulatory testing today.
Will the implementation affect legislation regarding animal testing for drug approval globally?
FDA is setting the tone as a powerful agency globally, and it is not impossible that the implementation of the new bill will affect legislation in other regions or countries over time.
Are there any possible drawbacks with the amendment regarding animal testingand the future use of alternative methods?
In our perspective, it depends on how the changes will be implemented in future updates of international guidelines that in more detail will describe which studies that need to be performed to verify efficacy and safety of new drugs.
Most importantly, robust and relevant data has to be produced to verify efficacy and safety of new drugs, to ensure that implementation of new methods do not compromise the health of humans or animals.
It is also of importance that the future updated guidelines do not prohibit the use of animal models in specific settings, such as toxicity studies to evaluate specific risks, and in cases where animal testing is considered to be the best alternative to generate reliable data.
Another reflection regarding possible negative consequences by this new legislation is that it can be percieved as a signal that animal studies are considered irrelevant. This could possibly have negative effects on, for example, allocation of grants to projects based on animal studies. That would disfavour research and scientific development dependent on animal models which, in a longer perspective, could affect health in both humans and animals.
Possible future effects on the use of laboratory animals in the U.S.?
Difficult to say, the decrease in animal use within regulatory testing will probably be limited to specific products, such as biosimilars. The use of animal testing will also decrease in cases where animal models can be replaced as considered irrelevant or when evaluation can be based on other types of data produced by non-animal methods. The effects might also be seen globally, as some of the companies perform studies and testing outside the U.S., including Europe.
