Animal Testing – from Mandatory to Optional to Last Resort

July 11, 2023

A lot is happening with the regulations directing the use of animal studies for drug development. New Approach Methodologies (NAMs) are being encouraged by regulatory authorities, calling for an increased effort to implement the 3Rs, aiming to replace, reduce and refine animal testing.   

In December of 2022, US President Joe Biden signed the FDA Modernization Act 2.0, enacting the bill into law. In April of 2023, the European Commission followed by adopting a proposal for a new Directive and Regulation, that is, to replace the existing European pharmaceutical legislation. The proposal is now up for scrutiny and will have to be agreed upon within the European Parliament before becoming law, a process which may take a couple of years. This means that now is the time for experts and stakeholders to provide their input and help shape the future of drug development.  

So, what does the proposal suggest when it comes to the use of NAMs? Read on for a recap of the FDA Modernization Act 2.0 and the European Commission Proposal.   


FDA Modernization Act 2.0 – from Mandatory to Optional

The FDA Modernization Act 2.0 amends the Federal Food, Drug, and Cosmetic Act (FFDCA) and authorizes authorises sponsors of novel drugs to make use of “certain alternatives to animal testing”.

The reference in the FFDCA to “preclinical tests (including tests on animals)” has been replaced by “nonclinical tests” – that are to be “conducted in vitro, in silico, or in chemico, or a nonhuman in vivo test, that occurs before or during the clinical trial phase of the investigation of the safety and effectiveness of a drug”. 

Of note, the terms preclinical and nonclinical are still used interchangeably within the industry, and although the FDA is switching to nonclinical only, the EMA continues to use both terms.   

Nonclinical tests, according to the FDA Modernization Act 2.0, may include the following:  

  • Cell-based assays  
  • Organ chips and microphysiological micro physiological systems  
  • Computer modeling modelling  
  • Other nonhuman or human biology-based test methods, such as bioprinting  
  • Animal tests 

The FDA Modernization Act 2.0 marks an important step, transferring animal testing from being mandatory, to being optional! 

US Senator Booker commented on the new law, saying that it “will avoid the needless suffering of countless animals, now that experimental drug testing can be done with modern non-animal alternatives that are more scientifically relevant.”  


European Commission Proposal – from Optional to Last Resort 

After adjustments have been made, the European Commission’s proposal will The proposal from the European Commission will, after adjustments have been made, replace current European pharmaceutical legislation. The use of NAMs instead of animal studies is encouraged throughout the proposal.

Article 6 of the proposal states that the marketing authorisation applicant must do the following:   

  • The use of the 3Rs must be demonstrated: The applicant “shall demonstrate that the principle of replacement, reduction and refinement of animal testing for scientific purposes has been applied in compliance with Directive 2010/63/EU with regard to any animal study conducted in support of the application”. 
  • Animal testing can only be used as a last resort: The applicant “shall not carry out animal tests in case scientifically satisfactory non-animal testing methods are available”. 

Article 12 then states that animal-based validation studies must be replaced by non-animal counterparts wherever possible: 

If an opinion is favourable to the granting of the relevant marketing authorisation, a document shall be annexed: where appropriate, to carry out medicinal product-specific validation studies to replace animal-based control methods with non-animal-based control methods.” 

Preamble 46 of the proposal states that the 3Rs of replace, reducereduce, and refine animal testing must be used in accordance with the European law on the protection of animals (Directive 2010/63/EU): 

“Any study involving the use of live animals, which provides essential information on the quality, safety and efficacy of a medicinal product, should take into account those principles* of replacement, reduction and refinement, where they concern the care and use of live animals for scientific purposes, and should be optimised in order to provide the most satisfactory results whilst using the minimum number of animals. The procedures of such testing should be designed to avoid causing pain.” 

*as stated in the Directive 2010/63/EU (Editor’s remark) 

Implementing the proposal from the EU Commission will take regulations even further than animal testing being optional, to them being a last resort when no other option is available!  

The proposal also outlines where the European Medicinal Agency (EMA) should focus their its efforts to help support further implementation of the 3Rs and the use of NAMs. 

Objectives for the EMA according to the proposal:  

  • Cooperate with EU decentralised agencies and other scientific authorities for the “development of coherent scientific methodologies, including replacing, reducing or refining animal testing”.  
  • Provide regulatory support and scientific advice for, andfor and facilitate the development of, validation and regulatory uptake of NAMs. 
  • Facilitate joint non-clinical studies between applicants and holders to avoid unnecessary duplication of animal studies.   

It will be exciting to follow the revisions of the EU Commission Proposal for new pharmaceutical legislation and the implementation of the new law, which we at Immuneed hope will happen soon!


If you want to know more about how Immuneed’s services align with the 3Rs and how we can help you with your non-clinical immunotoxicity testing!  Contact us here



FDA Modernization Act 2.0:

European Commission Proposal:

Editor: Jessica Norberg
Regulatory Reviewer: Wing Cheng

Publication Date: 2023-07-11 Last Reviewed: 2023-08-08