In the first half of 2020 and as a direct consequence of the ongoing pandemic, China issued a ban on the export of non-human primates (NHPs), including those used for pharmaceutical research. As this affected COVID-19 research, the NIH later issued a Notice of Limited Availability in an effort to prioritize studies requiring NHPs and minimize the impact of the resulting shortage.
At this point, there is no information on when Chinese exports will resume. However, given that even domestic researchers are having difficulty obtaining the animals, it could be some time before the supply of NHPs from China returns to pre-pandemic levels. Large pharmaceutical companies have the power to reserve the limited number of monkeys available in advance, leaving emerging biopharma companies all over the world with a very real and pressing supply chain issue.
NHPs are an important species, particularly for biologics research.
Safety studies in animals are an integral piece of the development and eventual approval of news drugs, as they are required by all regulatory agencies around the world. Selecting the correct species is a crucial decision for sponsors that must be made at the latest when IND-enabling toxicology studies start.
Monkeys are commonly used due to their genetic and physiological similarities with humans. They are particularly prevalent in studies involving biologics, which are best researched in organisms with similar immune systems as humans. While there are many species of monkeys to choose from, macaques are the most common. Specifically, rhesus macaques are primarily used in early research, and cynomolgus macaques are primarily used in later drug development. Around 75,000 NHPs are imported to the US each year. By comparison, Canada imports closer to 5,000 NHPs each year, mostly cynomolgus macaques used for pharmaceutical research by CROs such as those used by the Camargo Research Group to conduct toxicology studies.
A large percentage of NHPs are bred in China.
Between 80% and 90% of all NHPs available worldwide are bred in Asia, including 60-80% bred in China, since China offers (sub)tropical climates and can provide NHPs with the most suitable growth environment until they are ready to be shipped to scientific institutions all over the world. This has led to the accumulation of an abundance of relevant scientific data regarding Chinese-origin NHPs, so sponsors generally prefer them. The below figure summarizes the species available from one of the world’s leading providers of monkeys along with their origin, size, and prevalence in research publications.
Sponsors can consider alternative animal models for their nonclinical research.
Although each nonclinical (or preclinical) program has its own specific needs, Camargo can suggest several alternatives to Chinese-origin NHPs that those affected by the shortage should consider.
Other Sources of Cynomolgus Macaques
So far, only China has issued a ban on the export of NHPs, so cynomolgus macaques coming from other Asian countries and from the Republic of Mauritius are still available (though the demand is quite a bit larger than the supply at this point). Research is available comparing physiological and pharmacological parameters and the genetic composition of cynomolgus monkeys from various origins. For example, Mauritius NHPs tend to mature faster than Chinese monkeys and to be more homogeneous, likely an effect of the geographical isolation of the island. This may well be the best mid-term solution for a sponsor that has not begun safety testing.
Marmosets are an up and coming NHP species alternative now being considered by biomedical researchers. More primitive than macaques, they may therefore be the more ethical choice. They are also much smaller, with a weight close to that of a rat, which could potentially lead to large manufacturing savings as a result of reduced product volume needs. However, more animals may be needed per study to obtain the same toxicokinetic information.
Given that data on marmosets continues to accumulate, the species may prove useful in diversifying the nonclinical research industry supply chain long-term.
Alternatives to NHPs
Certain companies may need to revise their species selection processes in response to the temporary NHP shortage. Many small molecules are still tested in NHPs, when alternative non-rodent species could be valid options.
- Minipigs are still very underused in the industry, likely due to more burdensome test item requirements.
- Beagle dogs are often 5-10 kg at the start of a study, so here too is a greater CMC strain. Regardless, they have been the default non-rodent species for many years.
- Although NHPs are often the obvious choice for biotherapeutics, homologous targets in rodents or transgenic mice can be considered as alternatives for safety testing.
Program Delay or Reprioritization
It is always an option to indefinitely delay a program—for example, by reprioritizing the development of another molecule for which other species are more appropriate. Of note, CROs cannot at this point guarantee either the future availability or the future prices of any NHPs, and the situation could still worsen. Therefore, in the meantime, reevaluating program timelines could be a solution depending on business considerations.
With deep nonclinical expertise, Camargo provides solutions to help you design, execute, and manage your nonclinical program. If the global shortage is impacting your development timeline or budget, the experts at Camargo Research Group and our network of CROs can help you to determine which alternatives to Chinese NHPs could be viable options for your studies. Contact us to start a conversation today.