• 3.1.7. Refine or enhance existing technologies to improve the sensitivity, specificity, and robustness of testing methods used to measure MCM potency, in-process characteristics, and final drug substance characteristics (for example, in-line sensors and process analytical technologies)

• 3.1.8. Advance broadly-applicable, commercially-ready (manufacturing readiness level [MRL] 4-6) tools, technologies, and platforms that improve manufacturing efficiency, consistency, quality, and speed of MCMs to bolster the MCM supply chain; for example, “plug-and-play” modular unit operations applicable for downstream processing, or continuous manufacturing 

• 3.1.9. Investigate the effects in supply chain of implementing advanced manufacturing for specific types of medical products, especially such as biologics, vaccines and medical devices. Topics may include:

  • 3.1.9.1. Supply chain resilience to disruption
  • 3.1.9.2. Increased access
  • 3.1.9.3. Personalization
  • 3.1.9.4. Decreased reliance on foreign supply chains

Submitters interested in Research Area 3.1 may want to review the FDA web page Advanced Manufacturing.

• The Animal Rule is defined under 21 CFR 314.600/21 CFR 601.90. Accelerated Approval of Biological Products for Serious or Life-Threatening Illnesses is defined under 21 CFR Part 601, Subpart E. Accelerated Approval of New Drugs

• 7.1.1. Advance the capability to conduct natural history studies necessary to support MCM development under the Animal Rule (e.g., further the understanding of the pathophysiological mechanisms of toxicity, species specificity, or virulence of challenge agents)

• 7.1.2. Develop improved in-silico models to extrapolate pharmacokinetic/pharmacodynamic (PK/PD) data from animals to humans (e.g., PK modeling, PK/PD modeling, physiologically-based pharmacokinetic (PBPK) modeling, or population modeling)

• 7.1.3. Develop, qualify, and/or facilitate innovative analytical technology or quantitative imaging modality assessments of tissues/cells infected with emergent diseases and biological threats in order to advance characterization and further scientific understanding of pathophysiological mechanisms of infection, disease progression, susceptibility, or virulence;

• 7.1.4. Identify and qualify biomarkers and immune correlates of protection that enhance the understanding of the mechanism of action of MCMs, support appropriate clinical dosing of MCMs, and enable comparisons to be made between animal models and humans;

• 7.1.5. Develop and qualify in vitro systems (e.g., microphysiological systems) that can accurately predict in vivo responses in humans and/or animals to support the assessment of the safety and efficacy of MCMs

• 7.1.6. Identify and evaluate biomarkers and predictors of harm, susceptibility, latency, or virulence of biological threat agents of concern using innovative analytical technologies, imaging modalities, and other advanced approaches (e.g., omics).
• 7.1.7. Develop and/or advance the capability to conduct in vitro or in vivo assessments with threat agents, at greater than or equal to Biosafety level 3 containment, in order to:
  • 7.1.7.1. Further scientific understanding of the pathogenesis of disease or exposure and the pathophysiological mechanisms of disease, toxicology, progression, susceptibility, or virulence; 
  • 7.1.7.2. Investigate pathogenesis and pathophysiological mechanisms in alternative models of special populations, such as juveniles and patients with underlying medical conditions or rare diseases;
  •  7.1.7.3. Identify potential biomarkers of harm, toxicological effects, susceptibility/resistance, latency, or virulence

• 7.2.1. Enhance capabilities to rapidly assess the safety, efficacy and/or effectiveness of MCMs used during public health emergencies including:

  • 7.2.1.1. Develop and refine tools and methodologies to collect, monitor, track, and analyze real-world data and real-world evidence to support regulatory decision making

  • 7.2.1.2. Develop capabilities to inform or support multisite/multi-center clinical studies during public health emergencies including pre-positioned protocols, rapid and flexible clinical trial designs, novel statistical methods for analysis of clinical data, and clinical trial networks Also see: Medical Countermeasure Monitoring and Assessment

• 7.2.2. Develop and validate reference materials to facilitate the development and availability of vaccines, therapeutics, and diagnostics related to threat agents of concern

• 7.2.3. Develop new tools and methodologies to leverage large, unstructured data sets for analysis of MCM-relevant safety and efficacy endpoints

• 7.2.4. Develop technologies that can rapidly detect counterfeit, substandard, or adulterated MCMs

• 7.2.5. Develop technologies that can support the rapid assessment of MCMs for shelf-life extension

• 7.2.6. Develop technologies and methods to monitor and predict disruptions in medical device/medical product supply chain security due to technological or CBRN threats (see BAA Area 3.1.2)

• 7.3.1. Develop and validate rapid testing methods to speed characterization, in-process testing, and/or lot release for MCMs (e.g. sterility, immunogenicity, neurovirulence, mycoplasma, etc.)

• 7.3.2. Develop technologies and methods to accelerate collection and assessment of MCM-relevant clinical safety and efficacy endpoints

• 7.3.3. Develop methods using digital design and manufacturing data to increase efficiency of review

• 7.3.4. Develop technologies to support the adoption of advanced manufacturing technologies for MCMs (see BAA Area 3.1.7 and 3.1.8);

• 7.3.5. Evaluate methods for facilitating and incentivizing the production and development of MCMs or bolstering the MCM supply chain within the U.S (see BAA Area 3.1.9).

• 7.3.6. Develop and/or advance the capability to conduct in vitro or in vivo assessments with biological threat agents, at greater than or equal to Biosafety level 3 containment, in order to:

  • 7.3.6.1. Identify measurable characteristics of toxicological effects, safety and efficacy when evaluating therapeutic regimens and/or interventions to enable translational comparisons between animal model species and humans and to support clinical dosing; or

  • 7.3.6.2. Identify interactions between therapeutics, characteristics of alternative models of special populations, and disease variables influencing efficacy and adverse event outcomes.