FDA publishes advice on animal testing alternatives

New draft guidance from the FDA is urging pharma companies to accelerate efforts to transition from animal testing to non-animal alternatives.

The document is intended to help companies validate 'new approach methodologies' (NAMs) based on systems that more closely reflect human biology, such as organ-on-chip devices, human cell lines, organoids, and computer modelling techniques.

It is the latest stage in the FDA's roadmap for reducing animal testing over the next three to five years, published in April last year, and follows other measures such as the recent publication of guidance aimed at reducing or stopping toxicity studies of monoclonal antibody-based drugs in non-human primates (NHPs).

The overall aim is to move away from the current default of using animal models toward more human-centric technologies that can more reliably predict human drug reactions prior to the clinical testing stages of development.

As the FDA released its draft guidance, the NIH said it will invest $150 million in human-based research to develop the tools needed to reduce the use of animal models, the first awards under the recently announced Complement Animal Research in Experimentation (Complement-ARIE) programme.

In a statement, the US regulator said the NAMs guidance is a "major milestone" on that path and "reflects the FDA's commitment to moving away from using animal testing as the default method for gaining drug safety information."

It sets out a series of general recommendations on the things drug developers will have to consider when validating their NAMs, such as defining the context of use clearly, explaining the relevance to human biology and how they can assess toxicity, providing reliable and reproducible technical characterisation data, and demonstrating that it is fit-for-purpose – in other words, showing that it assists the FDA's Center for Drug Evaluation and Research (CDER) in regulatory decision-making.

The guidance notes that a fit-for-purpose NAM could replace an animal study or fill a data gap not addressed by animal-based methods, or provide additional information when traditional non-clinical models are unavailable. For example, an in vitro NAM might justify why certain animal species may not yield useful information, according to the document, which is open for comment until 18th May.

It does not address specific methodologies or drug discovery applications, and the FDA is encouraging drug developers to consult with its experts on the specifics of "indication-, disease-, organ-, and endpoint […] applications."

"Technological advances are allowing us to move beyond animal testing in drug development, which has a poor track record of predicting safety and efficacy in humans," said FDA Commissioner Marty Makary. "This guidance will facilitate the adoption of modern alternatives to animal testing in regulatory submissions."

Image by Tibor Janosi Mozes from Pixabay