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Procedure Development for Repeat Infusions in Juvenile NHPs

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Authors: N. Lalayeva, J. Reynolds, G. Aylor, J. Forget, and T. Rogers. Altasciences, Seattle, WA.

With the increase of pediatric pharmaceuticals in preclinical studies, the ability to learn and adapt to the use of a younger and smaller test model is necessary to assure process evolution and stress reduction on the research animals. The cynomolgus macaque is a commonly used non-human primate in research. Method development for a repeated-infusion dose in juvenile non-human primates required a united effort to create a concise study and equipment design, with animal welfare at the forefront of all considerations. The routine method for infusion restraint included the use of a procedure cage where all limbs were secured, providing limited movement. This method would be highly stressful for the animals under a year of age needed for the proposed study (juvenile animals 6 to 9 months of age at initiation of dosing). To avoid stress, the “snuggle wrap” method was developed to allow young animals to remain immobile while still feeling comforted by a hugging-like sensation. Stress behaviors were noticeably reduced when using the snuggle wrap compared to manual holding as a restraint method. The snuggle wraps were designed for vein accessibility, while the remaining limbs were secure and comfortable. Given that social pairs needed to remain in proximity, the “snuggle board” was also developed. Animals were implanted with RFID chips, and the wrapped juveniles were labeled with temporary ID cards to allow for easy identification once snuggled and placed on the board. These boards held 4 snuggled animals closely together which kept social pairs in visual and auditory contact during dose administration. Following catheter placement, dosing limbs were secured with Velcro straps for the dose duration. Animals were visually monitored, provided treats, juice, light projections, and chewing toys throughout dose duration by trained technicians. The snuggle board restraints were used for ~13 weeks, until the animals were over a year old and large enough for the procedure cage. This method was also successfully implemented in animals as young as 3 months

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