Radiobiology Research Suite Expansion of the TriMetis GLP Vivarium at UTHSC - There is no radiation medical countermeasure (RCM) drug approved by the FDA that meets the criterion of a
gastrointestinal (GI) or lung radiomitigator – an agent that mitigates GI acute radiation syndrome (GI-ARS) or
lung-ARS when administered after the exposure. A critical barrier to progress in development of RCM drugs
is that a traditional human clinical trial is not an option. Therefore, FDA approval of a RCM is done under their
Animal Rule (21 CFR 314.600) that requires detailed understanding of its mechanism of action, demonstration
of safety and efficacy in animal models, including nonhuman primates (NHP), and its safety in humans. The
recent withdrawal of Altasciences Corp., the only GI-ARS qualified contract research organization from RCM
preclinical testing has created a critical shortage and a national strategic vulnerability in qualified drug
development sites in the USA. Although the NIH, DOD, BARDA, NASA and several pharmaceutical companies
are intensively pursuing RCM development projects there is no domestic test site currently available with an
established and validated NHP models for the evaluation of RCM drug candidates, particularly for GI-ARS.
This is compounded by the US dependence on foreign (PR Chinese) suppliers of rhesus macaques. The
University of Tennessee Health Sciences Center (UTHSC) has a unique resource: the TriMetis Life Sciences
Animal Facility (TAF). Since 2016, TAF has been operated and managed by UTHSC under its PHS Assurance
and AAALAC accredited program. The TAF is a state-of-the-art vivarium housing small- and large-animals,
including nonhuman primates, operated under FDA-approved Good Laboratory Practice (GLP), thereby meeting
the needs of academic and industry researchers both regionally and nationally. The purpose of this proposal
is to equip TAF with an radiation biology suite suitable for development of radiation countermeasure
(RCM), radioprotective and radiosensitizer drugs under the Animal Rule. Installation of an irradiation suite
at TAF will have a significant impact beyond the needs of RCM drug development: it will be optimal for the
evaluation of radiotherapy sensitizers for cancer treatment, including general preclinical research, and drug
testing with toxicology and pharmacokinetic studies. The UTHSC-owned Plough Center for Sterile Drug Delivery,
where GMP manufacturing and compounding of test articles is done, the Regional Biocontainment Laboratory,
where GLP radiation injury rodent models have already been in operation, are within a few hundred feet of the
TAF and provide an unparalleled comprehensive drug development infrastructure that will meet all national
academic and industry research and drug regulatory approval needs. The new state-of-the-art facility also
develop domestically bred cynomolgus monkey radiation models thereby eliminating the US dependence
on foreign suppliers.
