The FDA has published new guidance aimed at reducing or stopping toxicity studies of monoclonal antibody-based drugs in non-human primates (NHPs), in the latest stage of an ongoing effort to reduce animal testing of new medicines.
The new draft guidance removes the requirement for single-target or ‘monospecific’ antibodies to be tested for six-month toxicity in NHPs like cynomolgus macaque or rhesus monkeys and marmosets.
Instead, antibody developers can extrapolate from three-month studies on nonrodent species like NHPs, dogs, and mini-pigs, supplemented by a weight-of-evidence (WoE) risk assessment based on data from similar antibodies.
The eight-page document notes that, unlike small-molecule drugs, antibodies are not metabolised through ‘biotransformation’ in the liver so do carry the same risk of generating potentially toxic metabolites.
The guidance does not, however, apply to multispecific antibodies, antibody-drug conjugates, or drugs based on antibody fragments, according to the FDA.
Earlier this year, the regulator said it intends to reduce or replace animal testing of various medicines, including antibodies, with other methods that it hopes will be more relevant to human physiology.
Among the alternatives under consideration are artificial intelligence (AI) and computational methods that could predict safety in silico, human cell lines, and ‘organoids’ – organ-like structures made from human cells and tissues – that could serve as lab models.
Similar efforts to reduce animal testing of medicines have also been announced recently by the EU and the UK.
“We are delivering on our roadmap commitment to eliminate animal testing requirements in drug evaluation and our promise to accelerate cures and meaningful treatments for Americans,” said FDA Commissioner Marty Makary.
“Modern science has given us far more effective and humane ways of evaluating drug safety than animal testing.” He added. “This reform may reduce the amount of time it takes to bring a drug to market and lower research and development costs, which can translate into lower drug prices.”
The FDA estimates that a typical nonclinical programme with a monoclonal antibody product could include more than 100 NHPs, incurring costs of approximately $50,000 per animal. However, many products that clear toxicity testing in animals do not receive FDA approval, predominantly due to safety or efficacy issues in humans.
Richard Pazdur, who is reported to be retiring from his role of director of the FDA’s Center for Drug Evaluation and Research shortly after just a few weeks in the job, said that a knowledge-based risk assessment of toxicity “reflects both scientific progress and our responsibility to use the most effective tools for drug evaluation.”
Photo by Matthijs Photography on Unsplash
