Presolicitation Notice

Introduction

The goal of this contract is to support the research and development of biodosimetry approaches to assess and medical countermeasures (MCMs) to mitigate/treat acute and/or delayed radiation injuries. 
This Broad Agency Announcement (BAA) serves as the RNCP's only mechanism to solicit investigator-initiated ,advanced development research directed toward Investigational New Drug application (IND) or Investigational Use Only (IUO)-enabling efforts for the development of medical countermeasures and biodosimetry approaches.

The goals of this BAA are two folds; the first goal is the development of safe and effective MCMs to mitigate and/or treat normal tissue injuries arising from exposure to ionizing radiation from a radiological or nuclear incident, thereby leading to a reduction in radiation-associated mortality and major morbidities.  The second goal of research interest that follows is the advancement and translation of biodosimetry biomarkers and/or devices to inform triage and treatment strategies for a mass casualty radiation incident.

MCMs Development

1. The lead MCM must already have demonstrated efficacy (i.e., clinically-relevant and statistically significant reduction in mortality and/or major morbidity in appropriate laboratory animal models of acute or delayed radiation injury predictive of the human response following a mass casualty scenario) when administered at least 24 hours after radiation exposure (or 48 h and later post-exposure for mitigation of H-ARS).
2. The lead MCM must have a demonstrated favorable safety profile in animal studies and/or in human clinical studies for another indication. This is critical, because MCMs could be used in cases where appropriate biodosimetry is not available to confirm the radiation dose received prior to initiating treatment.
3. The lead MCM must have a target product profile, including:
a. Preliminary data to support the selection of the MCM, specifically animal studies that demonstrate efficacy when delivered 24 hours or later (48 h or later if MCM is for H-ARS) after radiation exposure, using appropriate animal models and assays.
b. The intended use/indication of the lead MCM and the biodefense/public health gap that the product is intended to fill.
c. The performance specifications and features that the MCM will meet in order to provide therapeutic benefit.
d. The following information, if available:
i. Results from pharmacokinetics/pharmacodynamics (PK/PD) studies.
ii. Physicochemical characteristics, current formulation, and a mechanism of action.
iii. Documentation of communications with the FDA’s Center for Drug Evaluation and Research (CDER), or Center for Biologics Evaluation and Research (CBER) that are relevant to development activities for the proposed therapeutic product. Note that offerors need not have previously met with the FDA to be responsive to this solicitation.  

Bio-Dosimetry Development

1.  Point-of-care biodosimetry signature/device (e.g., for field triage use) must be able to 
distinguish between exposed and unexposed populations, and with a
sample-to-answer time of 30 min or less.

2.  Research focusing on diagnosis of the absorbed dose must measure the extent and intensity of 
radiation injuries to aid in determining the type of medical intervention that is needed within a 
time-window of 7 days post-exposure. They also should have demonstrated the ability to accurately 
and precisely measure absorbed radiation exposure levels to the body and/or tissues within ±0.5 Gy. 
Assay time for definitive care devices (e.g., medical-center based) should be 4 h or less from 
sample-to-answer.
3.  Research to predict outcomes of radiation exposure (e.g., predictive biodosimetry) must 
evaluate and characterize biomarkers of radiation injury to major organs and tissues to allow for 
timely and appropriate administration of treatments before the onset of overt radiation 
sub-syndromes. Biomarkers should be linked to relevant clinical outcomes, such as organ failure, 
other major morbidities, and/or mortality (e.g., febrile neutropenia, pneumonitis, renal fibrosis, 
cardiac events, etc.). Assay time can range from 0.5 to several hours, depending on the intended 
use of the assay.
4.  Biodosimetry assay/device must demonstrate medical benefit and broad, practical use of the 
biodosimetry signature and/or device in a mass casualty setting (e.g., time required for assay, 
process for testing accuracy of the signature and/or device, and confounders, such as time since 
exposure, gender, age, health status, co-morbidities, or health conditions), as demonstrated with 
the use of appropriate animal models, human clinical samples, or in ex vivo cellular assays.
5.  A target product profile for the lead biodosimetry signature and/or device that must include:
a. Intended use of the biodosimetry signature and/or device in a mass casualty setting; specify if 
use will be for preliminary, point-of-care triage purposes (within 72 hours), for definitive dose 
medical management in a hospital setting, or for later post-exposure times (for dose assessment and 
predicting outcome).
b. Performance specifications, features, and diagnostic benefit of the biodosimetry signature 
and/or device.
c. Description and specification of biodosimetry signature used, specimen type, selected 
population, assay limitations, established performance characteristics, demonstrated accuracy, 
analytical range, and possible confounders of the assay.
d. Meeting minutes detailing communication with the FDA, if available, that are relevant to 
development activities for the proposed biodosimetry signature or device. Note that offerors need 
not have met with the FDA to be responsive to this solicitation.