WHO Guidelines on Reducing Animal Testing

Just recently, the NIH (National Institutes of Health) in the USA announced at an NIH and FDA workshop on reducing animal testing that the biomedical authority will no longer award funding for new grant applications that rely exclusively on animal testing.
Now the WHO is following suit with new guidelines entitled ‘Guidelines on the replacement or removal of animal tests for the quality control of biological products’ and the global trend of reducing or completely replacing animal testing wherever possible.

Importance

At the beginning of the new document, the WHO emphasises that: "The recommendations contained in this document regarding the use of in vitro tests and, in a broader sense, the replacement or abolition of animal testing, should be considered superior to all corresponding quality control requirements in WHO documents published before 2025. Product developers, manufacturers and other stakeholders should not wait for individual WHO documents to be updated, but should instead actively and immediately promote the development, validation and implementation of animal-free in vitro approaches to quality control of biological products – in close consultation with and after approval by the respective NRA."
This makes it clear that the 3Rs principle is given high priority and that passages from other older guideline documents do not exempt one from the responsibility to seek alternative options to existing animal experiments or to use alternatives for new approvals.

Objectives

In the introduction and objectives, the WHO states that animal testing has traditionally been central to the development and quality control of biological medicines, as it provided crucial information about their mechanisms of action, safety and efficacy. However, it is now often considered scientifically inferior to in vitro methods. The WHO therefore recommends replacing or removing animal testing in quality control with valid, scientifically sound in vitro tests wherever possible.

Since 2019, the WHO has had all animal testing-related requirements in its guidelines reviewed by the British NC3Rs. Of 81 WHO documents, 63 contained animal-based tests, e.g. for potency, pyrogenicity or neurovirulence. The review resulted in recommendations for wording adjustments and a call for the development of general WHO guidelines for animal-free quality control.

The WHO advocates the rapid implementation of animal-free testing methods in close consultation with authorities. Where replacement is not yet possible, animal testing should be reduced, refined or used only once at critical points.

Therefore, already in the development phase of new products, it should be examined whether in vitro tests can be established for quality control. Early implementation facilitates the evaluation of batch consistency and compliance with clinical requirements.

The ‘Quality by Design’ concept supports this approach through defined product goals, a deep understanding of manufacturing processes and a sound risk assessment. New biological products are increasingly being developed and controlled using in vitro methods, particularly because modern processes are based on high-purity components and do not use animal ingredients.

Older (legacy) products, on the other hand, are often still tested using in vivo tests, which is complicated by regulatory hurdles. Manufacturers should critically question the necessity of such animal testing and work with regulatory authorities (NRAs) to develop and validate alternative, animal-free methods.

Further details can be found in the complete WHO guideline.

In addition, PharmaLab 2025 on 25/26 November 2025 offers the opportunity to meet experts from the British NC3Rs in person to discuss the 3Rs, e.g. in connection with the MAT as an alternative pyrogen test, and to discuss alternative methods in this area with experts from industry, laboratories and authorities such as EDQM, PEI, etc.