Medical Biological Defense (SDD)

Abstract

This project supports Engineering and Manufacturing Development and Low Rate Initial Production (EMD/LRIP) of medical countermeasures, development of reagents, assays, diagnostic equipment, biosurveillance and supporting efforts. Efforts included in this project are: (1) Coronavirus Disease Point of Care Diagnostics (COVID POC DX) (2) Coronavirus Disease Repurposed Therapeutics (COVID TX) (3) Antiviral Therapeutics Program (AV TX) (4) Botulinum Monoclonal Antibodies (BOT MAB) (5) Countering Emerging Threats Rapid Acquisition and Investigation of Drugs for Repurposing (CET RAIDR) (6) Chem Bio Incident Preparedness and Response - Advanced Development and Manufacturing (CBIPR - ADM) (7) Countermeasures for Multi-Drug Resistance-Bacterial (CMDR-B) (8) Defense Biological Products Assurance Program (DBPAP) (9) Joint Mobile Emerging Disease Intervention Clinical Capability (JMEDICC) (10) Medical Countermeasure Platform Technologies (MCMPT) (11) Next Generation Diagnostic System 2 (NGDS 2) (12) NGDS 2 Chemical Diagnostic (NGDS 2 CHEMDX) (13) NGDS 2 Man Portable Diagnostic System (NGDS 2 MPDS) (14) Botulinum Vaccine (VAC BOT) (15) Plague Vaccine (VAC PLG) (16) Botulinum and Plague Vaccine Storage and Stability Testing (Congressional Interest Item - CONG) (17) Antiviral Prophylaxis Studies (Congressional Interest Item - CONG) (18) Special Immunizations Program (VAC SIP) The COVID POC DX program is utilizing Coronavirus Aid, Relief, and Economic Security (CARES) Act funds to evaluate Commercial-Off-The-Shelf (COTS) POC devices for diagnosing COVID-19 at DoD locations that could benefit from reduced logistical burden of more complex diagnostic devices. The evaluation of these devices will enable moving testing capability closer to the patient in order to more efficiently and quickly identify the infected, implement treatment decisions and break the chains of disease transmission through non-pharmaceutical interventions. With this effort the CBDP is generating critical enabling data that will inform diagnostic use cases to refine testing strategies for the DoD to more efficiently address COVID response. The COVID TX program is utilizing CARES Act funds to support the development of Food and Drug Administration (FDA) approved therapeutics for the treatment of COVID-19. The AV TX program will develop and deliver FDA approved antiviral therapeutics for the warfighter. Based on the current gap in defense to the warfighter, the initial therapeutic candidate is now for a treatment against the Marburg virus in lieu of Ebola Zaire to follow for approval of a PanFilo therapeutic. Other pathogens on the biological warfare threat lists, including viruses of interest from Filoviridae, Arenaviridae, Bunyaviridae, and Flaviviridae, are targets of future interest. Developed broad spectrum antiviral therapeutics will be employed after suspected or confirmed exposure to the relevant threat agents and AVTX Medical Countermeasures (MCMs) will ameliorate the effect of threat agents to the warfighter. In the event of a natural occurring outbreak, antiviral therapeutics can be provided to ensure freedom of operation. In FY22 AV TX in the Engineering Manufacturing Design (EMD) phase will initiate efficacy studies with Non-Human Primates (NHPs) infected with Marburg virus towards animal rule FDA approval. The BOT MAB program will provide an anti-botulinum neurotoxin monoclonal antibody (mAB) cocktail that protects the warfighter against exposure to BOT A&B serotypes. It will provide prophylaxis and therapy for Warfighter exposure to aerosolized botulinum neurotoxin serotypes A and B and is intended for intramuscular route of administration. This capability is complementary to botulinum vaccine and therapeutics and will provide a continuum of protection against botulinum toxins. BoNT Advanced Development and Manufacturing of Antibody Technology (ADAMANT) leverages the advanced platform technology developed within the DoD's Advanced Development Manufacturing (ADM) facility that was initiated by the Medical Countermeasure Platform Technologies (MCMPT). In FY22 BOT MAB continues Botulinum monoclonal antibody platform development with manufacturing runs to produce product for pivotal animal studies and phase 2/3 clinical studies. The CET RAIDR program will develop repurposed drugs as medical countermeasures towards known, potential, and unknown and emerging threats, bridging the gap from when a threat is identified until targeted countermeasures such as vaccines are available. CET RAIDR will leverage lessons learned in Coronavirus Aid, Relief, and Economic Security (CARES) Act funded efforts under COVID TX and address advanced development portion of Science and Technology (S&T) efforts from Defense Threat Reduction Agency (DTRA) Joint Science and Technology Office (JSTO) Development of Medical Countermeasures Against Novel Entities (DOMANE) and Layered Integrated Medical Countermeasures Intervention Technologies (LIMIT) programs for new and emerging threats. In FY22, CET RAIDR continues nonclinical studies and Phase 2 and 3 trials, and on-going COVID activities to conduct advanced development of repurposed drugs. The CBIPR-ADM program is the capability building effort at the DoD ADM to establish and enhance proven biopharmaceutical and vaccine manufacturing technologies and accelerate the delivery of medical countermeasures as part of a medical integrated layered defense. The CBIPR-ADM enables an increased level of preparedness and responsiveness (i.e. operational readiness) to rapidly counter current and emerging biological threats including pandemic response. By establishing and enhancing these new proven MCM manufacturing technologies, the DoD ADM accelerates rapid development of MCMs at all stages of development. The MCMs impacted by these efforts include: Vaccines for Viral and Bacterial Agents and Toxins, monoclonal antibodies for prophylactic and/or therapeutic indications, and antibody conjugates for use across all agent classes. In FY22 CBIPR-ADM continues activities to maintain the DoD ADM's capabilities in a state of readiness to support Medical Countermeasure (MCM) development and manufacturing. The CMDR-B program develops Medical Countermeasures (MCM) for Service members to protect against Multiple Drug Resistance (MDR) bacteria, including Biological Warfare Agents (BWAs) and organisms that are genetically modified to be MDR and resulting bio-toxins. The resulting product(s) will be US Food and Drug Administration (FDA)-approved to prevent or minimize effects of MDR bacterial exposures. The candidates are transitional product from S&T that showed efficacy against plague, anthrax, and other BW agents. The regulatory approach of the program is to pursue development of products to FDA approval under the Animal Rule. The program conducted animal studies to confirm efficacy for plague and melioidosis. In FY20 Pharmacokinetic study on non-human primates Good Laboratory Practice (GLP) study report was completed for the plague indication and results were analyzed against threat indication. In FY21 and beyond, the Defense-Wide Review reduced this program for higher priorities. Execution of program closeout in FY20. The DBPAP program facilitates new technology transition to advanced development, efficient production, and timely distribution. DBPAP consists of a Critical Assays and Reagents team, which serves as the principal resource for biological assays and reagents, and the Targeted Acquisition of Reference Materials Augmenting Capabilities (TARMAC) team, which generates data on biodefense pathogens to inform product development. DBPAP establishes a core research and development capability by developing biological threat agent reference materials (strains, antigens, antibodies and nucleic acids) and detection/diagnostic assays for biothreat agent detection. These reagents/assays are leveraged across multiple programs to meet the requirements of the Warfighter and Joint biological defense systems and support the biological defense community. Through the TARMAC initiative, the DBPAP will use a systematic approach to the introduction of new materials and information into MCM development. This includes advanced platform technologies within the DoD's ADM facility. In FY22 DBPAP continues development/expansion of biological threat agents reference materials to known and emerging threats. The JMEDICC program is a collaboration between United States and Ugandan research and outbreak response entities intended to enable clinical trials for filovirus (Ebola and Marburg) therapeutics during an outbreak. The JMEDICC effort provides a platform of advanced supportive care, scientific rigor, laboratory and logistical capacity, mobility, and rapid response to test new therapeutics or MCM in a filovirus outbreak setting. The JMEDICC effort is a project whose resulting capability offers a mechanism to greatly accelerate the development of life-saving products for future outbreaks. The performer received approval of an emergency access protocol for the use of the Remdesivir drug in the country of Uganda. The MCMPT program establishes enabling technologies and pre positioning platform systems at the DoD's Advanced Development Manufacturing (ADM) facility using standardized discovery, design, manufacturing, and testing processes to reduce the medical countermeasure (MCM) development risks. Efforts will center on leveraging the ADM's facility and developing robust manufacturing processes. MCMPT will leverage platform technologies to streamline and accelerate the MCM delivery to the Force by reducing developmental risk. A subset of these technologies will be adapted to deliver a rapid response capability to novel and emerging threats. Through the Advanced Development and Manufacturing Antibody Technologies (ADAMANT) and Rapid Response platforms, MCMPT will deliver an enduring capability from which future candidates can be manufactured. The Agile Medical Paradigm (AMP) is the CBDP's strategic framework to accelerate the delivery of MCMs. To achieve this goal the DoD is establishing a medical countermeasures platform technology (MCMPT) capability. The NGDS program is a family of systems providing increments of diagnostic capabilities over time that address varied chemical, biological and radiological (CBR) threats across the different echelons of the Combat Health Support System. The mission of the NGDS is to provide CBR threat and infectious disease identification and FDA-cleared diagnostics to inform individual patient treatment and CBR situational awareness and disease surveillance. NGDS 2 will provide additional capability for diagnosis of CBR-induced diseases, suitable for use in far forward environments, by developing lightweight, portable, and simple-to-use instruments and test kits. In FY21 NGDS Increment 2 transitions into two programs of record; NGDS 2 MPDS Program and NGDS 2 CHEMDX Program. The NGDS 2 CHEMDX program will provide a rapid, hand-held, point-of-care device. It utilizes an electrochemical assay for the quantitative detection of acetyl cholinesterase (AChE) activity in finger stick and venous whole blood samples of individuals suspected of being exposed to cholinesterase inhibiting substances, such as nerve agents. NGDS 2 CHEMDX diagnostic capabilities will be employed in Army, Air Force, Navy, Marines and SOCOM (Roles 1-3), with applicability to routine healthcare at higher echelons. NGDS 2 CHEMDX test results are to be used to aid in the diagnosis of cholinesterase inhibition in an individual suspected of having exposure to NTAs and his/her treatment decision with an Antidote Treatment Nerve Agent, Autoinjector (ATNAA): self-aid; buddy aid; combat lifesaver; or medic. In FY22 NGDS 2 CHEMDX continues Engineering & Manufacturing Development. The NGDS 2 MPDS program will provide a simple-to-use, portable diagnostic device capability that can be used in far-forward and austere battlefield environments to assist in the diagnosis of infectious diseases and biological warfare agents in symptomatic individuals. The MPDS will enable earlier patient diagnosis by its placement on the battlefield. Concepts of Employment support use by small teams and medical providers at Role 1 and Role 2 echelons of care. Earlier diagnosis of infectious diseases improves decision support for treatment and evacuation, improves command situational awareness, and mitigates the effects of exposure to unknown infectious disease and biological agents. In FY22 NGDS 2 MPDS concludes hardware, software, assay development, and two clinical trials; continues development of third assay panel; and management of hardware and software configurations. The DoD provides for the development of vaccines that are directed against validated biological warfare (BW) weapons to include bacteria, viruses, and toxins of biological origin. Effective medical countermeasures are urgently needed to negate the threat of these BW agents. Vaccines have been identified as the most efficient countermeasure against the validated threat of BW weapons. Products under development in this budget item include Recombinant Botulinum A/B (VAC BOT) and Plague (VAC PLG) vaccines. Efforts to be conducted during the Engineering Manufacturing Development (EMD) Phase include the development of large scale manufacturing process and validation of that process, nonclinical studies, demonstration of manufacturing consistency, and expanded clinical human safety studies. The results of these efforts, and those conducted during the EMD phase, will be used to submit a Biologics License Application (BLA) to the FDA for product licensure. To evaluate vaccine effectiveness, pivotal animal studies will be conducted concurrently with the Phase 3 clinical trial to satisfy the requirements of the FDA's "Animal Rule". Congressional Interest Item - The Botulinum and Plague Vaccine Storage and Stability Testing (VSST) program utilizes Congressional directed funding for the Botulinum and Plague vaccines. DoD has the mission to maintain the existing vaccine material in Good Manufacturing Practice (GMP) storage and to conduct the periodic potency and stability testing of these materials to support submissions to the FDA and potential future emergency response. In FY21, VSST continues storage, distribution, and stability testing of VAC BOT and VAC PLG materials, and initiates a Phase 2 clinical trial evaluating the use of a biological response modifier (BRM) co-administered with the VAC PLG drug product to identify avenues for faster onset and longer duration of protection. Congressional Interest Item - The Antiviral Prophylaxis Studies program will manage the development of TPOXX as Post-Exposure Prophylaxis (PEP) for Smallpox. TPOXX is only approved as treatment for clinically evident smallpox, which is usually diagnosed 12 to 14 days post-exposure, but as late as 17 days post-exposure. The warfighter is therefore exposed to a "window of vulnerability" in the progression of smallpox for which no treatment options are approved by the FDA. This effort will complete all required nonclinical and clinical studies necessary to submit a supplemental New Drug Application (sNDA) or New Drug Application (NDA) seeking approval of TPOXX as a post-exposure prophylaxis. The funding supports a regulatory pathway to provide a Post-Exposure Prophylactic to close the "window of vulnerability" by providing a treatment option for smallpox after vaccination ceases to be effective and prior to clinically evident disease. The SIP continually manages, updates, and executes the INDs of selected prophylaxis, treatments and diagnostics development products which provide additional protection to individuals that are at high risk of exposure to CBRN agents. These vaccines will be used to provide additional levels of protection to laboratory workers conducting research. DoD has the mission to maintain IND vaccines in Good Manufacturing Practice (GMP) storage and to conduct the periodic potency and stability testing of these materials to support submissions to the FDA. In FY22 SIP continues storage, distribution, potency testing, and biosurety compliance activities.

Document Details

• Document Type: Project
• Publication Date: Oct 01, 2022
• Source ID: MB5_0604384BP_5_0400_PB_2022

Tags

Readers

• Critical Infrastructure Protection in CBRN and WMD Threats.
• Infectious Disease/Epidemiology

Technology Areas

• Biotechnology