Preclinical and Clinical Resources for Antiviral Program for Pandemics Projects

NIAID provides access to preclinical and clinical resources through a suite of service contracts to support the development of therapeutics, vaccines, and diagnostics. These contract services are being leveraged to support promising antiviral therapeutics candidates through the Antiviral Program for Pandemics (APP). You may request access to these resources if you are an investigator in academia, a nonprofit organization, industry, or government in the United States or worldwide. You need not be a grantee of NIAID or another NIH Institute or Center. NIAID establishes the contracts with the service providers and covers the expenses for the requested studies. These established contracts provide protections for the confidential information and intellectual property of the organizations providing antiviral therapeutics candidates for these services. Results are returned to the requestor for use in advancing their product development efforts. Data must be provided to support requests and requirements are commensurate with the complexity/cost of the request, e.g., more data must be provided to support a clinical trial request than an in vitro assay. Many viruses are listed in the table below, though NIAID will prioritize testing across virus families.

The Antiviral Program for Pandemics (APP) is specifically focused on viral families of pandemic potential that require additional investment focused on new therapeutics discovery and development.

Use these links to jump to more information about preclinical and clinical resources that are available for your antiviral research project:

• Assessment of Antiviral Activity
• Nonclinical Therapeutics Profiling
• Synthesis and Manufacturing
• Early Clinical Trials

Assessment of Antiviral Activity

In vitro Antiviral Testing

In vitro antiviral assay methods vary by virus, but may include cytopathic effect, plaque assay, virus yield reduction and/or replicon assays. Product developers and NIAID staff can identify critical gaps in in vitro assay capabilities. NIAID can engage contractors to develop and standardize reproducible in vitro assays.

Standardized Animal Infection Models

NIAID preclinical services have capabilities for testing candidates in a wide range of viral infection models in rodents and non-human primates (NHP). Supportive maximum tolerated dose (MTD) and pharmacokinetics (PK) studies are available to inform study design.

Developing new animal infection models

Product developers and NIAID staff can identify critical gaps in animal model capabilities. NIAID can engage contractors to develop and standardize reproducible animal infection models.

The table below page lists viral pathogens typically available for in vitro and animal model testing (including the species commonly used). Please contact the NIAID staff for specific details since available models change periodically. Additional viral pathogens beyond those specifically in scope for APP are also available for assessing broader spectrum for candidates. Please ask for more details!

Table of viral pathogens typically available for in vitro and animal model testing

*Note that some animal models use a modified or adapted form of the virus. Please ask for more details, as needed.

Non-Clinical Therapeutic Profiling

A full suite of assays is available to support therapeutic product development at all stages, from lead identification to investigational new drug (IND)-enabling studies.  The scope of available assays is very broad and customizable to meet the needs of most drug development programs, so please ask NIAID staff for more information about available assays and capabilities.  The descriptions below are for typical screening assays used for lead series profiling for drug discovery programs in the lead identification and lead optimization phases. 

In vitro ADMET profiling

Contractors use a suite of in vitro assays to screen for desirable “drug-like” properties. A fixed panel of assays is available to examine the absorption, distribution, metabolism, excretion, and mammalian cell toxicity (AMDET) of a test article. In vitro safety panels, cytochrome P450 (CYP) induction, and CYP inhibition assays are also available. More customized assays are also available for a full range of in vitro ADMET profiling.

Screening pharmacokinetics (mouse, rat, hamster, and guinea pigs)

Contractors use liquid chromatography with tandem mass spectrometry (LC-MS/MS) to analyze the concentration of a test article in multiple biosamples (e.g. blood, ELF, tissues) across multiple timepoints after a single administration of the test article. Several routes of administration of the test article can be assessed in parallel. These screening studies are intended to inform the dosing route and schedule of the test article in follow-on studies.

Bioanalytical method development and qualification

Contractors develop, optimize, and/or validate a method to analyze the concentration of a test article in biological matrices. An appropriate bioanalytical method is required to detect test articles at low levels with high specificity. Once a bioanalytical method is developed, the method’s conditions can undergo further optimization and validation based on the phase of development.

Non-GLP and GLP pharmacokinetics/bioavailability

Contractors evaluate test article concentrations in plasma, blood, or other biosamples in rodent and non-rodent species to provide information to guide future animal and clinical studies.  Dose-range finding studies support pharmacokinetics study designs. Pivotal pharmacokinetic/bioavailability studies can be run in compliance with FDA good laboratory practice (GLP) regulations to support Animal Rule development and/or inform clinical dosing decisions.

Non-GLP and GLP safety and toxicology

Contractors can perform single- and repeat-dose toxicology studies for therapeutics conducted in rodent and nonrodent species, including non-GLP pilot and dose range-finding studies, and definitive pivotal toxicology studies conducted under GLP regulations and performed to meet the testing requirements of the FDA and the ICH M3 (Non-Clinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals) and other related International Council for Harmonisation (ICH) guidance. Also available are in vitro and in vivo genetic toxicology assays, cardiovascular telemetry, hERG, and respiratory assays.

Synthesis and Manufacturing

Small molecule synthesis and manufacturing

Service contracts supporting synthesis of small molecules and some peptides. Services include:

• Synthesis of intermediates or building blocks
• Singleton or library synthesis of analogs
• Process development and optimization
• Pilot and GMP manufacturing
• Formulation testing and optimization

Biopharmaceutical manufacturing

Service contracts supporting products containing recombinant proteins, peptides, and nucleic acids. Services include:

• Pilot and GMP manufacturing
• Assay development and product release testing
• Process development
• Formulation testing and optimization

Early Clinical Trial Contract Support

Service contracts are available to support early clinical trials for candidate therapeutics, including first-in-human, single-ascending dose (SAD), multiple-ascending dose (MAD) and other Phase 1 studies in healthy volunteers.

Support includes the design, development, and conduct of trials to generate safety and pharmacokinetics and/or pharmacodynamics (PK/PD) for candidate therapeutics.

After discussing with NIAID, a Clinical Trial Agreement delineating responsibilities will be signed. NIAID has the ability to support Phase 1 trials where the product sponsor holds the IND and performs bioanalytical assays, while NIAID contracts perform other trial activities. Alternatively, NIAID may sponsor the IND application for these trials, including providing safety oversight, clinical monitoring, data management, and regulatory management, in close collaboration with DMID’s preclinical and early product development programs, as well as external research partners.