Product Development Support Services (PDSS) for Medical Countermeasures Against Chemical Threats

• Demonstrate pilot proof-of-principle efficacy of MCM candidates against the lethal and/or non-lethal effects of chemical threat agents in established and novel models of chemical intoxication.
  • Threat agents available under the CCRP PDSS include unrestricted and restricted chemicals, e.g., choking, blister, blood, and nerve agents.
• All phases of nonGxP preclinical product development, including Absorption, Distribution, Metabolism, Elimination, Toxicity (ADMET) studies.

If approved, studies are performed at no cost to the applicant. Investigators seeking these services receive no funding from NIAID, but instead receive products or information generated by NIH-funded contractors on their behalf. NIH will deliver a final study report to the investigator at the end of the study. 

Resources are limited, the CCRP PDSS is not intended to sustain the entire spectrum of chemical MCM discovery, research, and development and should not be the sole source of support. Preliminary evidence of compound efficacy, i.e., biological response, against the actual threat agent OR an acceptable surrogate model is required. 

The CCRP PDSS provides centralized resources for the following services to facilitate chemical toxicity research and MCM discovery and early product development:

• Pilot studies to facilitate discovery and/or characterization of MCM candidates to prevent chemically induced mortality and/or treat serious morbidities, include but not limited to:
  • Development of novel and/or refinement of established models of chemical intoxication
  • Exploratory proof-of-principle efficacy evaluation in established small laboratory animals models of chemical intoxication, such as:
    • Sulfur Mustard (SM) Pulmonary Toxicity
      • Toxidromes include acute lung injury, acute respiratory distress syndrome, pulmonary fibrosis
    • SM Ocular Toxicity
      • Toxidromes include corneal fibrosis, neovascularization, limbal stem cell deficiency
    • SM Hematological Toxicity
      • Toxidrome includes myelosuppression
    • Soman (GD) Neurotoxicity  
      • Toxidromes include refractory status epilepticus, neurodegeneration
• Preclinical Development Activities, include but not limited to:
  • Initial non-GLP ADMET Services
    • Determination of maximum tolerated dose and no observed effect levels (NOEL)
    • Acute and subchronic toxicity; single and repeated dose toxicity studies
    • Determination of relevant pharmacokinetic/toxicokinetic parameters
    • Bioavailability studies
    • Biotransformation assays conducted in vitro
    • Absorption, distribution, metabolism, and excretion studies
    • Various toxicity studies (e.g. genotoxicity, carcinogenicity, reproductive, cytotoxicity, immunotoxicity)
    • Behavioral pharmacology
    • Cell permeability
  • Chemistry and Manufacturing Services
    • Developing and performing analytical methods to characterize lead therapeutic agent(s)
    • Formulation and manufacture of lead compounds for in vivo studies
    • Synthesis, resynthesize, or acquisition of reagent grade or clinical grade lead compounds
    • Manufacture laboratory-scale of small quantity and non-GxP quantities of lead MCM candidate(s)
  • Preclinical Development, Planning, and Evaluation
    • Development/Review of preclinical and/or product development plans

• PDSS is available to any U.S.-based applicant with promising MCM candidates (and appropriate supporting preliminary data) responsive to the CCRP mission
  • Applicants from foreign institutions and non-U.S. components of U.S. organizations are not eligible to apply
• Need not be a grantee of NIAID nor another National Institutes of Health Institute or Center
• Applicants may consult with NIH to determine eligibility. 

Step 1–Discuss the potential request informally

Contact the Office of Biodefense Research and Surety (OBRS) to schedule an informal, exploratory discussion of your preliminary data and the suitability of your proposed studies for support. Depending on the areas of interest, OBRS may coordinate with scientifically-pertinent HHS officials to participate in the discussions.

Your request will be evaluated as follows:

1. Are the proposed studies within the OBRS/NIAID mission?
2. Are the proposed studies within the scope of and/or technology provided by awarded contracts?
3. Are sufficient quality and/or quantity of products to be evaluated available?
4. Is the proposed work supported by other funding sources?
5. Has the requestor previously used CCRP resources for assessment of the same or similar product? (Repeat use of CCRP resources may only be undertaken with strong justification.)
6. Are preliminary data adequate to support the request to advance the product to the proposed next step?
7. What is the likelihood that services will contribute significantly to the eventual development and/or evaluation of a product as a MCM candidate?
8. What is the purported public health impact?
9. What improvements in health benefits are offered beyond current standard of care or MCM(s)?
10. Does the requestor have a plan advancing the product beyond completion of the services requested?

Informal requests are reviewed and approved at the branch/office level, where they may be considered in relation to branch/office priorities and availability of funds.

Step 2–Submit a formal Study Pre-Proposal (by invitation only)

1. If the initial discussions of your request are judged to be promising, OBRS staff will invite you to submit a formal Study Pre-Proposal (SPP) request for approval.
2. CCRP staff will provide a complete set of SPP instruction and/or application.  
3. Formal SPPs are reviewed by the trans-NIH CCRP team and approved by OBRS, where they are considered in relation to CCRP priorities.

All information provided to the CCRP PDSS will be treated as confidential. The potential MCM may be coded throughout the study by request, so that experiments are performed under blind procedures. Participants will retain custody of and have primary rights to the data developed, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

Before, during, and subsequent to the evaluation, the U.S. Government is not required to obtain for the participants any proprietary rights, including intellectual property rights, or any materials needed by the applicant to perform the project. Participants may wish to establish a separate Material Transfer Agreement with the PDSS laboratory before commencing any studies, if desired.

PDSS are supported by contracts with Battelle Memorial Institute (Columbus, OH) and SRI International (Menlo Park, CA) under interagency agreements between the NIH Office of the Director and the Department of Defense and/or the Department of Health and Human Services.