Non-Human Primate Husbandry and Impact on Non-Human Primates Health: Outcomes From an IQ DruSafe/3RS Industrial Benchmark Survey.

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.

FDA and industry collaboration: Identifying opportunities to further reduce reliance on nonhuman primates for nonclinical safety evaluations.

The nonhuman primate (NHP) has always been a limited resource for pharmaceutical research with ongoing efforts to conserve. This is due to their inherent biological properties, the growth in biotherapeutics and other modalities, and their use in small molecule drug development. The SARS-CoV-2 pandemic has significantly impacted the availability of NHPs due to the immediate need for NHPs to develop COVID-19 vaccines and treatments and the China NHP export ban; thus, accelerating the need to further replace, reduce and refine (3Rs) NHP use. The impact of the NHP shortage on drug development led DruSafe, BioSafe, and the United States (U.S.) Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) to discuss this issue at their 2021 annual meeting. This meeting identified areas to further the 3Rs in NHP use within the current nonclinical safety evaluation regulatory framework and highlighted the need to continue advancing alternative methods towards the aspirational goal to replace use of NHPs in the long term. Alignment across global health authorities is necessary for implementation of approaches that fall outside existing guidelines. This article captures the proceedings from this meeting highlighting current best practices and areas for 3Rs in NHP use.

Pharmaceutical industry perspective on combination toxicity studies: Results from an intra-industry survey conducted by IQ DruSafe Leadership Group.

Interest in developing combination products to overcome drug resistance and treat complex diseases is growing. However, ambiguity remains around the value of combination toxicity studies to support combination products. Therefore, the IQ* DruSafe Leadership Group surveyed member companies to evaluate industry experience with combination toxicity strategies, study designs and their impact on clinical development. Twenty companies responded, representing 79 combination programs. Combination toxicity studies were performed based on scientific rationale, regulatory agency request, or expected regulatory requirement. Combination toxicity study designs were varied (eg, group numbers, dose selection rationale and endpoints assessed) with no evidence that any one study design was superior. Studies were perceived as adding value when they fulfilled a regulatory requirement; avoided potential development delays; or when new or exaggerated toxicity or pharmacokinetic interactions were identified. Twelve percent of combination toxicity studies impacted clinical trial designs. The decision to conduct and the design of nonclinical combination toxicity studies should be based on sound scientific judgement with proactive engagement with regulatory agencies. Studies are not warranted when sufficient knowledge (eg, expected pharmacology, known mechanism of action, drug disposition, toxicity profile) is available to proceed safely in clinical development.