Nonhuman Primate Models in Biomedical Research State of the Science and Future Needs (2023) / Chapter Skim
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3 Current Landscape of Use and Availability of Nonhuman Primates for NIH-Supported Biomedical Research
3 Current Landscape of Use and Availability of Nonhuman Primates for NIH-Supported Biomedical Research
Pages 75-112
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From page 75... ...
In accordance with the committee's charge, the emphasis of this review of the NHP research landscape is on NIH and its extramural and intramural research programs; however, other stakeholders are briefly referenced within the context of the broader landscape of suppliers and users of NHP resources.
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From page 76... ...
Funding Mechanisms Common Activity Mechanism Description Codes* Research Project NIH-solicited or investigator-initiated awards for extramural R01, R21, R34, Grants health-related research projects or innovation research based on U01, U19 the mission of NIH Research Center Funds for large, multiproject efforts that include a diverse array P20, P30, P40, Grants of research activities P50, P51 Resource Grants Grant programs that provide research-related support or access R24, R45, X01 to resources Training, Fellowship, Funding programs that provide opportunities for training and T01, F30, F31, and Career Grants career growth F32, K01, K08, K24, R25, T32, U18, U24, K99/ R00 Research and Contracts between NIH and a contractor that are used to support N01 Development research in high-priority areas and to further progress toward a Contracts research goal Small Business Awards through the Small Business Innovation Research and R42, R44 Program Grants Small Business Technology Transfer programs that provide funds to small businesses Research Construction Support for construction or major remodeling to create new C06 Programs research facilities Cooperative Funding mechanism that acts as a hybrid of the grant and U42, U01, U18, Agreements contract mechanisms, used when substantial involvement of NIH U24 programs or scientific staff is required in an area of high research priority Intramural Research Funds supporting internal research programs within NIH ZIA, ZIC institutes, centers, and offices *
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From page 77... ...
and functions to advance NIH's broader research mission. NIH provides support for NHP research within both its intramural and extramural research programs, as well as support for the production and maintenance of NHP resources.
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From page 78... ...
Understanding the NIH-supported NHP research landscape specifically is further complicated at the stakeholder level by the complexities of contracts and awards from federal and nonfederal funders for the production and use of NHPs. An ICO-owned NHP breeding colony used for intramural research, for example, may be managed by a private contract research organization (CRO)
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From page 79... ...
Major Stakeholders Involved in the Supply and Use of NHP Resources for NIH-Supported Research As noted in the previous section, describing and quantifying NHP supply and use is complex, and the available data are insufficient to parse out, in a detailed manner, NHP production and use within the context of NIH-supported biomedical research. One aspect of this complex landscape is the diversity of stakeholders with key roles in the support and/ or conduct of NIH-funded NHP research.
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From page 80... ...
NOTES: In addition to the seven National Primate Research Centers, ORIP provides support via P40 awards and/or other funding mechanisms to four National Resources with nonhuman primate breeding colonies -- University of Texas MD Anderson Cancer Center, Caribbean Primate Research Center at the University of Puerto Rico, Wake Forest University School of Medicine, and The Johns Hopkins University School of Medicine -- and three Reagent Resources -- MassBiologics at the University of Massachusetts Chan Medical School, Trinity University, and University of Louisiana at Lafayette. HIV = human immunodeficiency virus.
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From page 81... ...
. Investigators at National Resources also actively conduct NHP research, some of which may be funded by NIH, and may purchase supplemental animals from the commercial market to 8 This reference refers to written responses to a committee information request received from each of the seven NPRCs (Washington NPRC, Oregon NPRC, California NPRC, Tulane NPRC, Emory NPRC, Wisconsin NPRC, and Southwest NPRC)
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From page 82... ...
While rarely associated directly with NIH-supported research using NHPs, industry-sponsored NHP research activities can impact the balance of supply, demand, and prices for NHP resources across the broader research landscape. Increases in NHP demand by pharmaceutical and biotechnology companies that cannot be met by importation or industry-owned colonies -- a situation experienced during the COVID-19 pandemic -- can result in increased competition and cost increases for the limited domestic NHP resources sought after by other stakeholders (Zhang, 2020)
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From page 83... ...
While the available supply of this research resource has always been limited because of high demand, recent geopolitical events and public health emergencies have directly impacted these dual pathways for the supply of NHPs and exacerbated the existing challenges of scarce NHP research resources. As discussed further in the sections that follow and in Appendix B, key findings11 related to NHP availability for NIH-supported extramural and intramural research include the following: • The absolute number of NHPs held or used for research purposes decreased over the past decade by more than 2,100 animals.
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From page 84... ...
Indeed, the committee heard from stakeholders that the steps NIH has taken to date in response to the ORIP report's recommendations are insufficient to address the needs of NHP researchers or those of the National Primate Research Centers and National Resources for maintaining NHP resources to support NIH-funded investigators (Flynn, 2022; Morrison et al., 2022)
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From page 85... ...
FIGURE 3-2 Nonhuman primates (NHPs) held or used for research purposes annually in the United States for fiscal years 2008–2021, based on data collected by the U.S.
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From page 86... ...
. Data collected by the committee show that low numbers of cynomolgus macaques are held and used by NPRCs and National Resources, which instead report high levels of use of rhesus macaques (National Resources Information Request, 202212; NPRC Information Request, 2022)
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From page 87... ...
. In addition to China's virtual absence of concentrated opposition from animal rights groups, investigators may be encouraged to move their NHP research to China by the greater availability of and access to NHPs, with some noting that less time is required to initiate preclinical trials for new drugs and medical devices using NHPs in China compared with the United States (Einhorn and Lew, 2022)
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From page 88... ...
. Domestic Breeding of NHP Resources The seven NPRCs and four National Resources together constitute a long-established network of highly specialized research facilities that are responsible for providing domestically produced NHPs for NIH-supported extramural research purposes (see Table 3-3 for a
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From page 89... ...
In some cases, academic and other institutions with breeding colonies (e.g., the Keeling Center at the MD Anderson Cancer Center and Wake Forest University) may maintain colonies supported by both NIH and other sources.
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From page 90... ...
National Resource data include information from Wake Forest University, MD Anderson Cancer Center, The Johns Hopkins University, and the Caribbean Primate Research Center. SOURCES: National Resources Information Request, 2022; NPRC Information Request 2022; ORIP, 2018a.
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From page 91... ...
. However, establishment of such colonies is a key recommendation of the 2018 ORIP report, and efforts were subsequently undertaken to establish a breeding population at the Wisconsin NPRC (NPRC Information Request, 2022)
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From page 92... ...
Given the predictions of NPRCs and National Resources that investigator demand for NHPs for use in NIH-supported research -- specifically for rhesus and cynomolgus macaques and marmosets -- will increase, efforts and investment to further expand existing breeding programs at NPRCs and National Resources are needed. Among the 258 NIH-supported investigators who responded to the committee's survey question about future demand for NHPs and reported expected NHP species needs for future NIH awards, rhesus macaques were overwhelmingly identified as the preferred NHP species (82 percent)
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From page 93... ...
NHP models are increasingly of value in research related to the development and testing of gene therapies. Investigator Demand and Access Challenges Timely access to NHP models is a concern widely reported by NIH-supported investigators and the ICOs for both extramural and intramural research (NIH, 2022a; NHP Investigators Survey, 2022)
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From page 94... ...
Challenges in securing NHP resources for intramural research activities were reported by the National Institute of Mental Health (NIMH) ; the National Eye Institute (NEI)
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. While it is impossible to compare changes in wait times since 2018 because of a lack TABLE 3-5 Nonhuman Primates (NHPs)
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NPRC = National Primate Research Center. SOURCE: NHP Investigators Survey, 2022.
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) as priority areas for current NHP research (National Resources Information Request, 2022; NIH, 2022b; NHP Investigators Survey, 2022; NPRC Information Request, 2022)
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From page 98... ...
. Demand for NHP Resources by Research Domain and Species: Intramural Research Information on demand for NHP models within the NIH intramural research program, based on current intramural research activities, shows overall concordance with high-demand domains in extramural research -- including neuroscience and neurological disorders, and infectious disease and immunology (Denny, 2022)
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From page 99... ...
Data provided by ICOs that carry out intramural research using NHPs show that macaques account for 75 percent of all NHPs used (Denny, 2022) , a proportion consistent with that described in the 2018 ORIP report.
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From page 100... ...
NIAID indicated that the price of cynomolgus macaques, the supply of which was strongly impacted by the Chinese export ban, had increased by 500 percent. Cost increases apply to all NHP species used in intramural research, even those for which demand is not typically high and whose supply was largely unaffected by the knock-on effects of shortages of macaques, as seen with the doubling in price of African green monkeys.
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From page 101... ...
. Domestically, U.S.-based NHP research is increasingly relying on ground transportation in response to the lack of air travel options.
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From page 102... ...
. STATE OF CURRENT NHP RESEARCH INFRASTRUCTURE: GAPS AND NEEDS Physical Research Infrastructure In response to concerns related to the difficulties of NPRCs and National Resources in continuing to provide adequate numbers of NHPs for NIH-supported research and the need to invest in the maintenance of existing NHP research resource infrastructure, the 2018 ORIP report includes a recommendation that ORIP provide greater support for NHP research resources that support NIH's extramural grant programs (ORIP, 2018b)
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From page 103... ...
has been sustained. This persistent budgetary shortfall limits the ability of NPRCs to carry out their critical dual role as both major providers of NHP resources and physical centers of biomedical research services and expertise as they attempt to meet increasing demand for NHP resources.
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SOURCE: NIH RePORTER, 2023a. FIGURE 3-5 P40 research center awards for National Resources, fiscal years 2012–2022, adjusted for inflation.
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From page 105... ...
These shortfalls in operational budgets have also been felt by NHP investigators at academic institutions with their own NHP resources, who have experienced shortages of space or NHP housing that have resulted in research delays and higher daily operational costs. Ultimately, dedicated, consistent funding for existing research infrastructure would limit the strain on NHP resources and allow for recovery and planning for future public health needs.
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From page 106... ...
However, each individual ICO holding or using NHPs for intramural research purposes tracks the number of animals and NHP species held to assess its own NHP resource maintenance and infrastructure needs, to monitor colony health, and to determine per diem cost allocations (NIH, 2022b)
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From page 107... ...
Thus, it is essential to address the staffing challenges outlined above not only to maintain the caliber of research currently being carried out, but to also meet the needs of NIH-supported NHP research for the future. CONCLUSIONS The committee's assessment of the current state of the NIH-supported research landscape since the publication of the 2018 ORIP report showed that NHP resources remain insufficient to meet the demands of the NIH-supported biomedical research ecosystem.
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From page 108... ...
Conclusion 3-6: Inadequate coordination of nonhuman primate (NHP) resources and research programs at the national level contributes to missed opportunities and diminished opportunities for efficient use of limited NHP resources.
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From page 109... ...
2021. Nonhuman primate models for SARS-CoV-2 research: Managing demand for specific-pathogen-free (SPF)
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From page 110... ...
2021. Nonhuman primate models for SARS-CoV-2 research: Infrastructure needs for pandemic preparedness.
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From page 111... ...
Document provided to the Com mittee on the State of the Science and Future Needs for Nonhuman Primate Model Systems on November 15, 2022. Available by request through the National Academies' Public Access Records Office.
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From page 112... ...
2022. Nonhuman primate model systems: State of the science and future needs.
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