Does Geographical Origin of Long-Tailed Macaques (Macaca fascicularis) Matter in Drug Safety Assessment?: A Literature Review and Proposed Conclusion

Abstract

Long-tailed macaques are the predominant nonhuman primate species for the nonclinical safety testing of biopharmaceuticals. This species comprises 9 subspecies with Macaca fascicularis fascicularis naturally occurring in Southeast Asia. Since the 17th century, M. f. fascicularis also occurs on Mauritius. Cynomolgus macaques do not naturally occur in China, but are bred in many farms across the country. The current shortage in animal supply raises the question whether geographical animal origin matters and if animals from different geographical regions can be combined on a drug development program or even a single experiment. This article reviews geographical animal origin in relation to selected endpoints that are relevant in nonclinical drug safety testing. Animals from different countries within Asia mainland do not appear to show any meaningful difference. Very little data are available for animals from Asia island. Mauritian animals show consistent differences from Asian animals in several clinical and anatomical pathology parameters. For developmental parameters, animals from Mauritius and Asia are comparable with the exception that Mauritian animals mature faster. In the authors’ view, differences between the geographical clusters can be accounted for as long as baseline and reference data are available.

Genetic Variability of the Long-Tailed Macaque (Macaca fascicularis) Populations in Urban Habitat in Padang City, West Sumatra, Indonesia

“…In addition to elucidating the genetic variation of particular populations, genetic analysis can be used in guiding conservation initiatives (Farias et al 2015). This database of DNA sequences may be adopted in diverse domains, including biomedical and biogeographical investigations (Yao et al 2017;Weinbauer and Mecklenburg 2022).…”

Special Issue on the Pathobiology of Laboratory Nonhuman Primates: A Review of Species, Substrain, Geographical Origin, Age, and Modality-Related Factors

“…6,8 An investigation into the influence of geographical origin on several selected toxicology study endpoints indicated that mainland Asian animals from different countries such as China, Cambodia, and Vietnam do not appear to demonstrate any substantive differences in toxicologic endpoints, while NHPs from Mauritius have consistent differences from Asian animals in several of the typical study endpoints. 8,9,10,11 The absence of major relevant baseline differences between cynomolgus macaques sourced from the mainland Asia (also known as continental) provides evidence to support the interchangeable use of animals from these geographical regions within a development program. However, while animals from Mauritius and mainland Asia were shown to be comparable for developmental and reproductive parameters, NHPs from Mauritius appeared to mature faster, reaching sexual maturity earlier than Asia mainland animals, 11 and attaining comparably higher body weights 10 relative to their mainland Asia counterparts.…”

“…8,9,10,11 The absence of major relevant baseline differences between cynomolgus macaques sourced from the mainland Asia (also known as continental) provides evidence to support the interchangeable use of animals from these geographical regions within a development program. However, while animals from Mauritius and mainland Asia were shown to be comparable for developmental and reproductive parameters, NHPs from Mauritius appeared to mature faster, reaching sexual maturity earlier than Asia mainland animals, 11 and attaining comparably higher body weights 10 relative to their mainland Asia counterparts. The higher body weight in Mauritian animals correlated with higher absolute organ weights in this subpopulation, when compared with Asian mainland macaques.…”

The Histology of Background Pathological Processes in Cynomolgus Monkeys (Macaca fascicularis) from Control Groups in Toxicology Studies

“…The aim of this work was to describe the background histopathological findings in tissues from control cynomolgus monkeys received from the breeding facilities of the Sochi Research Institute of Medical Primatology, Russia, as well as primates imported from Vietnam. Since previous toxicology studies most often evaluated histological abnormalities in the internal organs of primates primarily from Mauritius, China and Vietnam, [5,6] it seems relevant to analyze the morphology of background lesions in monkeys used in preclinical studies conducted in the Russian Federation, followed by a comparative assessment between animals grown in the breeding facilities of Sochi and primates obtained from Vietnam.…”