Nonclinical toxicology studies that are required to support human clinical trials of new drug candidates are generally conducted in a rodent and a non-rodent species. These studies typically contain a vehicle control group and low, intermediate, and high dose test article groups. In addition, a dosing-free recovery phase is sometimes included to determine reversibility of potential toxicities observed during the dosing phase and may include additional animals in the vehicle control and one or more dose groups. Typically, reversibility is determined by comparing the test article–related changes in the dosing phase animals to concurrent recovery phase animals at the same dose level. Therefore, for interpretation of reversibility, it is not always essential to euthanize the recovery vehicle control animals. In the absence of recovery vehicle control tissues, the pathologist’s experience, historical control database, digital or glass slide repositories, or literature can be used to interpret the findings in the context of background pathology of the species/strain/age. Therefore, in most studies, the default approach could be not to euthanize recovery vehicle control animals. This article provides opinions on scenarios that may or may not necessitate euthanasia of recovery phase vehicle control animals in nonclinical toxicology studies involving dogs and nonhuman primates.

The presence of health issues (diarrhea, poor body condition) in non-human primates can impact animal welfare, confound toxicity study data, and lead to animal exclusion from studies. A working group cosponsored by DruSafe and 3Rs Translational and Predictive Sciences Leadership Groups of the IQ Consortium conducted a survey to benchmark quarantine, pre-study screening, husbandry, and veterinary care practices and their impact on NHP health. Nineteen companies participated in the survey providing separate responses for studies conducted in-house and at Contract Research Organizations from 3 regions (North America (NA), Europe and Asia) for an aggregate of 33 responses. A majority of responding companies conducted studies at North America CROs (39%) or in-house (36%) using primarily Chinese (33%) or Cambodian (27%) and to a lesser extent Vietnam (18%) or Mauritian (15%) origin NHPs. Forty-Five percent of responses had pre-study health issues (fecal abnormalities, etc.) on ≥ 1 studies with the highest incidence observed in Vietnam origin NHPs (80%). The survey suggested variable pre-screening and quarantine practices across facilities. Husbandry practices including behavioral assessments, environmental enrichment and consistent diets were associated with a lower incidence of health issues. The survey also benchmarked approaches used to diagnose and manage abnormal feces in NHPs and has provided strategies to minimize impact on NHP health. The survey highlighted opportunities for harmonizing screening criteria across industry and for improving tracking and sharing of health screening results, leading to further refinement of NHP veterinary care practices, higher quality studies, and reduced NHP use.

Contract Research Organizations (CROs) conducting toxicology studies on behalf of biopharmaceutical sponsors and others routinely provide supportive care for animals to minimize pain and distress on studies. A large number of guidance documents govern the care of experimental animals, however there is currently no uniform approach on the communication between sponsor and their CRO partners in providing a standard definition of and strategies for administering supportive care in toxicity studies. This survey was conducted by the CRO Outreach Working Group (WG), a part of the 3Rs Translational and Predictive Sciences (TPS) Leadership Group of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ Consortium), to better understand the provision of supportive care on nonclinical studies. The survey aimed to define supportive care strategies, identify alternatives to supportive care, and understand regulatory feedback and implications about supportive care decisions. The survey was distributed to members of the 3Rs Leadership Group of the IQ Consortium and several CRO partners, representing 35 organizations as potential respondents. The results of the survey from 13 respondents provided positive feedback that helped in highlighting the existing best practices for supportive care. Areas of enhancements identified included greater consistency in the inclusion of sponsor veterinarians on project teams for externalized studies, the timing of initiation of supportive care, and increased sharing of regulatory outcomes. Suggested best practices include creating a plan of action for veterinary care prior to study start, and enhancing information sharing regarding expected toxicities from previous study findings. Improved communication regarding supportive care will pave the way for enhanced 3Rs initiatives, refining the existing animal care paradigm and helping to ensure the most ethical toxicology study designs.