The division is home to one of the largest medical countermeasure (MCM) programs in the world. It has the necessary technical capabilities, infrastructure, and resources to conduct preclinical efficacy screens in a range of small and large animal models against acute radiation sickness (ARS) and delayed effects of acute radiation exposure (DEARE). All studies are conducted in compliance with the U.S. Food and Drug Administration (FDA) Good Laboratory Practice (GLP) regulations. The division, through partnerships with:

• National Institutes of Allergy and Infectious Disease (NIAID)/National Institutes of Health (NIH)
• Biomedical Advanced Research and Development Authority (BARDA)
• Industry
• and Academia

has made significant advances in the development of new pharmacotherapeutics and repurposing of existing therapies for use as MCMs.

Director of Medical Countermeasures for DTRS

Erika W. Davies, PhD, MS (she/her)
Assistant Professor 
Director of Medical Counter Measures for DTRS
Department of Radiation Oncology

Discovering New Treatments for Radiation Exposure from a Nuclear Incident or Attack

The MCM program is comprised of a powerful team of individuals with extensive and long-term experience with product development leading to FDA approval under the Animal Rule regulatory pathway. Models developed within the MCM program are designed to satisfy the objectives of the FDA Animal Rule criteria (21 CFR § 314.610, drugs; § 601.91, biologics) for pivotal efficacy testing and product approval. The MCM team is highly experienced and capable in performing studies to further product development, including determining the best route of administration, dose, duration, timing, and therapeutic index.

The division’s models of acute radiation syndrome (ARS)/ delayed effects of radiation exposure (DEARE) are thoroughly described in published literature and copies of relevant publications can be provided upon request. Preclinical studies control for all factors that may influence data interpretation and outcomes including dosimetry, strain differences, animal gender/age, supportive care, infection, stress, batch effects, and survival (a soft endpoint) through rigorous quality assurance/quality control, and strict adherence to study protocols as well as intensive training of all staff and personnel assigned to studies.

Results-driven approach to research and development

Key deliverables over the past three years include but are not limited to the following:

• Conducts studies in multiple animal models of radiation injury to advance development of potential mitigators of ARS and DEARE, with quantitative endpoints, that are linked across syndromes and species;
• Collaborates with government agencies, including BARDA, NIAID/NIH, and NASA through contracts and grants to develop medical countermeasures against ARS and DEARE;
• Contracts with multiple companies to perform pre-clinical and IND-enabling studies as part of their drug development pathways;
• Achieved concurrence of animal models of ARS and DEARE at Type B and C meetings as appropriate for candidate MCM screening in support of product approval through the U.S. Food and Drug Administration (FDA) Animal Rule (AR);
• Generated the source data in a GLP-compliant preclinical trial leading to the first drug approvals by the FDA for the treatment of myelosuppression resulting from ARS;
• Published >50 peer-reviewed research articles related to model development, MCMs, and mechanism of radiation damage in tissue with significant short and long-term impact to aid in defining the indication and treatment regimen for radiation countermeasures.

Capabilities within the MCM program include, but are not limited to the following:

• Relevant existing small and large RadNuc models with established dose–response relationships and defined dose- and time-dependent incidence, severity, and latency of H-ARS, GI-ARS, DEARE-lung, cutaneous radiation injury (CRI) in the context of a nuclear terrorist event;
• Established ARS/DEARE animal model research platform that addresses many of the critical knowledge gaps associated with successful adherence to FDA AR criteria required for product licensure or EUA considerations;
• Collaboration with imaging/biomarker team led by Dr. Maureen Kane in the UMB School of Pharmacy focused on molecular analysis and tissue imaging using matrix-assisted laser desorption ionization (MALDI) and imaging mass spectrometry (IMS) that is linked to cellular analysis and biomarker discovery (genomic, proteomics, metabolomics);
• Capability to link molecular and cellular analysis to animal signs that reflect morbidity and mortality along the time course of organ-specific dysfunction and recovery;
• Sophisticated noninvasive endpoints for evaluating pathogenesis of injury, including respiratory function, MR/SPECT/PET/CT imaging and ultrasound/echocardiography;
• Incorporation of quantitative pharmacology in trial design and data analysis through collaboration with Dr. Joga Gobbaru, Director, Center for Translational Medicine;
• All studies comply with the USDA Animal Welfare Act, 9 Code of Federal Regulations, Parts 1,2, and 3; the Guide for the Care and Use of Animals, National Research Council, National Academic Press, Washington, D.C., 1996, and UMSOM Institutional Animal Care and Use Policies; and
• All GLP studies comply with 21CFR, Part 58, Good Laboratory Practices for Nonclinical studies for FDA.

Data Quality and Transparency

The division adheres to a quality plan that complies with the U.S. Food and Drug Administration Good Laboratory Practice regulations and industry-standards for preclinical contract research. To ensure adequate design, conduct, and reporting of MCM studies, the division has a programmatic management team of administrators, quality assurance and regulatory personnel, and data and document management groups to oversee, manage, and track contract objectives and deliverables, allowing us to keep our efforts on budget, within scope, and on schedule. Research is conducted in a purpose-built research facility dedicated to MCM screening that is fully equipped with state-of-the-art equipment and animal housing plus office space for research staff, administration, and regulatory personnel.

The MCM program utilizes an adaptive trial design to minimize the total number of animals required for estimation of the dose-modifying effects of candidate MCMs on major morbidity/mortality. Through collaborations with investigators within the University of Maryland School of Pharmacy, the division conducts animal toxicology and safety studies and performs pharmacokinetic/pharmacodynamic modeling and simulation design. The program is supported by four full-time board-certified medical physicists as well as additional support from dedicated dosimetrists. Further details are available under Contract Research Services.