The European Commission and its Scientific Committee on Health, Environmental and Emerging Risks (SCHEER) released a preliminary opinion earlier this month reiterating that, when alternatives do not exist, the appropriate use of non-human primates (NHPs) remains essential to some biomedical and biological research, as well as for pharmaceutical safety assessments.
The opinion is part of a process to reevaluate the same conclusion from 2009 that “recognised that animals should only be used in medical research when it is unavoidable and validated alternative methods are not available.”
The commission’s opinion notes that NHPs are predominantly used in the development and safety testing of pharmaceuticals and medical devices; treatment and prevention of infectious diseases; neuroscience; ophthalmology and (xeno)transplantation, “with the largest fraction of NHPs used in the EU for safety assessment studies, performed to meet regulatory requirements.”
For 2014, a total of 8,898 uses (uses includes reuse of the same NHP and “does not refer to the total number of animals”) of NHPs were reported by European member states. Species most frequently used were cynomolgus monkeys (7,098, 79.7%), marmoset and tamarins (743, 8.4%) and rhesus monkeys (612, 6.9%).
But the numbers have been declining in recent years. According to the latest available statistics of the EU from 2011, around 11 million animals were used in scientific procedures in the EU, and of these, approximately 6,000 were NHPs, compared to almost 10,000 in 2008.
“Arguments against phasing out NHPs in safety testing of pharmaceuticals are therefore similar in many ways to those regarding using rodents for toxicity testing, i.e. incomplete knowledge of integrated body systems and pathophysiology, poor representation of pharmacokinetics by in vitro systems,” the opinion notes.
And ICH safety guidelines, which seek to prevent duplicative studies, say such trials should be performed in “relevant species,” though pivotal studies for risk assessment of pharmaceuticals, such as repeated dose toxicity testing, usually must be performed in two species, one of which must be a non-rodent.
ICH guideline S6 (R1) on preclinical safety evaluation of biotechnology-derived pharmaceuticals, in force since December 2011, also emphasizes the use of in vitro alternative methods for safety evaluation and opens the way to replacing the current standard methods.
“To progress towards complete replacement of NHPs in drug safety testing, it will be necessary to gain new insights into molecular biology, including a better understanding of signalling pathways, modelling and bioinformatics and further research into integrated testing strategies,” the opinion says.
Additional work is needed on new models for investigating abuse potential, assessment of reproductive toxicity and characterization of the safety of biopharmaceuticals.
While recognizing the public concern about NHP research, the opinion says that some regulators have adopted ethical limits or boundaries on their use, but “the close phylogenetic relationship of NHPs with humans makes them the best available animal models for addressing particular research questions.”
A number of factors determine the timetable for complete replacement of NHP use, according to the opinion, including:
- Availability of funding and resources for developing alternatives to NHP models and ensuring they are fit for purpose
- Progress in the validation of alternative test methods within the regulations
- Lack of regulatory and guideline harmonization both within and across sectors, and the condition that is often included that an alternative method must be formally validated and accepted by regulators before it can be used
- New demands for NHP use in science, such as emergence and re-emergence of infectious diseases where NHPs are the only relevant model
- Biosimilars for which NHPs have been advocated as better models because they have a higher tolerance for human proteins
This latest opinion highlights not only why non-human primates are essential in such cases, but the many scientific approaches that could significantly contribute to the replacement, reduction and refinement (3Rs) of NHP studies and tests.
On 14 March, the SCHEER will organize a public hearing in Luxembourg to discuss the preliminary opinion.
Preliminary Opinion on “The need for non-human primates in biomedical research, production and testing of products and devices” (update 2017)