Pre-Clinical Models of Infectious Diseases
Introduction The National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), of the Department of Health and Human Services (DHHS) supports research related to the basic understanding of microbiology and immunology leading to the development of vaccines, therapeutics, and medical diagnostics for the prevention, treatment, and diagnosis of infectious and immune-mediated diseases. The NIAID, Division of Microbiology and Infectious Diseases has a requirement to provide and develop animal models in order to advance our understanding of infectious diseases as well as advance the development of therapeutics and vaccines for infectious diseases. Description The National Institute of Allergy and Infectious Diseases (NIAID) supports and facilitates research that focuses on understanding, treating and, ultimately, preventing infectious, immunologic, and allergenic diseases. The NIAID Division of Microbiology and Infectious Diseases (DMID) supports and facilitates research to understand, control and prevent human disease caused by infectious agents. Basic, applied and translational research to develop and assess therapeutics, vaccines, and diagnostics is supported tough research grants, cooperative agreements, and contracts. In turn, DMID further supports and facilitates research ongoing under these funding mechanisms and tough other programs via an array of preclinical and clinical resources and services to support multiples stages of the product development pipeline. These resources and services include genomic and gene sequencing services, provision of high quality biological materials, biocontainment facilities, and pre-clinical and clinical translational research resources (https://www.niaid.nih.gov/research/resources). The current NIAID Preclinical Models of Infectious Diseases IDIQ contract program is one of DMID’s preclinical services resources and supports the development and refinement of animal models and animal replacement models of infectious diseases, models that subsequently are used to evaluate candidate medical countermeasures against these diseases. In addition, these contracts facilitate regulatory submissions, patents, and other intellectual property applications by extramural investigators who request evaluation of their products. This program serves the DMID mission of supporting investigator-initiated research by providing critical data needed to apply for grant or other funding. Finally, these contracts enable product developers and sponsors to make key go/no-go decisions for candidate therapeutics, vaccines, and diagnostics. In addition to meeting the needs of extramural researchers, this program provides crucial data to our DHHS agency partners. These data will facilitate the advancement of promising candidate medical countermeasures against priority biodefense and emerging infectious agents to approval or licensure, and, in some cases, eventual deposit in the Strategic National Stockpile. As background, In 2017, 32 institutions were awarded base contracts under the Preclinical Models of Infectious Diseases IDIQ contract program. This program was a re-competition of her Animal Models of Infectious Diseases IDIQ contract program, and its overarching goal was to provide capability in a broad range of animal and animal replacement models for use in evaluating promising candidate countermeasures (vaccines, therapeutics, diagnostics) against the broad range of infectious agents that are in the purview of DMID. The breadth of the existing contractor pool has enabled a rapid and effective response to emerging infectious diseases, such as COVID-19, and emergency preparedness priorities. Awarded contracts were divided into 3 model-specific pools: Part A – Small animal models of infectious diseases Part B – Non-human primate models of infectious diseases Part C – Non-traditional animal models and animal replacement models of infectious diseases The Preclinical Models of Infectious Diseases program will continue to provide the capability and capacity to develop and employ animal and animal replacement models (e.g., organ-on-a-chip technology) of infectious diseases for screening and product evaluation and addresses a critical stage in this pipeline by bridging in vitro testing and eventual clinical evaluation, including as needed, studies conducted under the guidance of 21 CFR 58, “Good Laboratory Practices”. In addition, for candidate products that are unable to be assessed for clinical efficacy in phase II or III trials for ethical or practical reasons, contracts awarded under this solicitation will enable regulatory approval or licensure via the guidance of the FDA’s Animal Efficacy Rule (21 CFR 314.610 and 601.91). This anticipated solicitation will award multiple IDIQ base contract awards to successful offerors proposing a general approach to the requirements under one Contractor pool. Successful Offerors will have qualified for the pool to compete for eventual task order awards in one or more of the following areas: Task Area A – Small Animal Models of Infectious Diseases Task Area B – Non-Human Primate Models of Infectious Diseases Task Area C – Animal Replacement and Non-traditional Animal Models of Infectious Diseases Task Area D – Generation and Distribution of Specialized Reagents Contracts are anticipated to organizations that represent the best value to the Government for the full suite of services. For the purposes of this solicitation, the following definitions apply: Animal replacement tissue technologies derived from human or animal tissue (in particular lung, liver, immune system, brain, skin/soft tissue or gastrointestinal tissues): Organoids Organs on chips Artificial complex cell systems Microphysiological systems Tissue technologies derived from animals, in particular, non-human primates (for the purposes of bridging data from in vivo models with clinical data) Evaluation: encompasses advanced testing after a product has been screened and demonstrated as efficacious in the same or lower animal models; activities include dose refinement, measurement of host response, pharmacokinetics (in infected animals), pharmacodynamics (in infected animals), and therapeutic efficacy or immune protection against challenge. Model development: a novel systematic effort to reproduce a clinical syndrome caused by an infectious agent in an animal species following challenge with the agent and includes median lethal and/or infectious dose determination, natural history of infection, and serial pathogenesis studies. Model refinement: a systematic effort to improve the performance of an existing animal model that reproduces a clinical syndrome caused by an infectious agent; to adapt an existing animal model that reproduces a clinical syndrome caused by one infectious agent to a different, but related, infectious agent; to adapt an existing animal model to optimize its ability to support product screening or evaluation following challenge with the infectious agent. Non-human primate models: new and old-world species, including but not limited to Macaca, spp. (cynomolgus, Rhesus, pig-tailed); Chlorocebus, spp. (African green monkeys, vervets); Aotus, spp.; Papio, spp.; Callitix, spp. (marmosets) Non-traditional animal models including but not limited to: Domestic livestock: horses, cattle, goats, sheep, fowl Wildlife species: marmots, wild rodents, deer, bats Invertebrates: snails, parasitic nematodes, parasitic protozoa, insect vectors of human disease Aquatic: zebrafish HFIM Pathogens: infectious bacteria, viruses, parasites, fungi, toxins, and other agents such as prions that cause clinical syndromes in humans (surrogate human pathogen/animal combinations may be used for diseases where human pathogens cannot be studied in animal models) Products: agents for the prevention of infectious diseases such as vaccines or microbicides; therapeutics targeting the host or the pathogen, including conventional drugs, immunotherapeutics, and therapeutic vaccines; and diagnostics (Also referred to as candidate medical countermeasures or countermeasures.) Reagents: biochemical, genomic, molecular, cellular, and immunologic materials integral to research on pathogens, including the pathogenic agent or toxin itself requiring an in vivo model for production (e.g., hybridomas, monoclonal antibodies, otherwise unculturable organisms, live vectors) Screening: encompasses early-stage or first-in-animal testing for product effectiveness in animals; activities include rudimentary testing of product effectiveness after challenge, determination of maximum tolerated dose, and minimum effective dose. Small animal models: includes but is not limited to traditional laboratory rodent species (mice, rats, hamsters, gerbils (including jirds), guinea pigs), transgenic, humanized knock-out, and knock-in mouse strains, cotton rats, laboratory rabbit varieties, and laboratory ferrets The services encompass the following: Small animal models: development of new and refinement of existing models amenable for evaluating candidate countermeasures; evaluation of candidate countermeasures, including but not limited to, maximum tolerated dose, minimum effective dose, safety, efficacy, pharmacokinetics, pharmacodynamics Non-human primate models: development of new and refinement of existing models amenable for evaluating candidate countermeasures; evaluation of candidate countermeasures, including but not limited to, maximum tolerated dose, minimum effective dose, safety, efficacy, pharmacokinetics, pharmacodynamics Animal replacement models and non-traditional animal models: development of new and refinement of existing models amenable for evaluating candidate countermeasures; evaluation of candidate countermeasures, including but not limited to, maximum tolerated dose, minimum effective dose, safety, efficacy, pharmacokinetics, pharmacodynamics studies to bridge animal and animal replacement model Generation and Distribution of Specialized Reagents including but not limited to: Production of live life cycle stages for parasitic infections (e.g., eggs, pupae, larvae, adult stage parasites) Production of live vectors that support life cycle stages of parasitic infections (e.g., mosquitoes, ticks, fleas, black flies, sand flies, tsetse flies, reduviid bugs) Tissues required for isolation of otherwise unculturable infectious agents or toxins that can be distributed as reagents Production of monoclonal and polyclonal antibodies and hybridomas in mice Model species that are not listed with the individual Task Areas above, but are requested for development or demonstrated as necessary for testing medical countermeasures following award, will be taken under advisement by the Government, and task order requirements involving these model species may be developed on a case-by-case basis as long as they are determined to represent benefit to the Government. The services shall be directed at, but not be limited to, the following areas of emphasis: RNA viruses with the potential to cause pandemics from the following viral families: Bunyaviridae Coronaviridae Enteroviridae (in particular, EV-D68 and EV-71) Filoviridae Flaviviridae (in particular dengue and West Nile viruses) Paramyxoviridae (in particular Hendra and Nipah viruses) Togaviridae Antimicrobial resistant and multi-drug resistant infections, including Methicillin- Resistant Staphylococcus aureus, Vancomycin-Resistant Enterococcus, Carbapenem-Resistant Enterobacteriaceae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Clostridium difficile Diseases caused by pathogens and toxins on the National Institute of Allergy and Infectious Diseases (NIAID) Emerging Infectious Diseases/Pathogens list: http://www.niaid.nih.gov/topics/biodefenserelated/biodefense/pages/cata.aspx ; in particular, influenza, viral hemorrhagic fevers (including artopod-borne viruses), artopod-borne encephalitis viruses, rabies, and Mycobacterium tuberculosis (including MDR and XDR strains), Bordetella pertussis, Group A Streptococcus; Fungal diseases, including invasive aspergillosis, candidiasis, coccidioidomycosis, cryptococcosis, mucormycosis , pneumocystis pneumonia; Non-Biodefense Bacteria, including Chlamydophila pneumonia, Haemophilus, spp., Legionella, spp, non-tuberculous Mycobacterial spp., Streptococcus pneumoniae, Non-Biodefense Viruses, including: adenoviruses Hepatitis B and C viruses, Herpesviruses (HSV 1 and 2, CMV, VZV, HHV-6/7), human metapneumovirus, respiratory syncytial virus, papillomaviruses, parainfluenza virus; Neglected tropical diseases, including: filariasis, leprosy, schistosomiasis, trachoma, trichomoniasis; and Sexually transmitted infections, including bacterial vaginosis, chlamydia, and gonorrhea The NIAID recognizes that a single organization or institution may not have the full spectrum of expertise or facilities required to perform all activities set forth in the Statement of Work. Contractors shall perform the work described in one or more Task Areas. Contractors may need to be supported to a certain extent by the expertise and resources of other organizations or persons tough consortia agreements, partnerships, subcontracts, and/or consultants. However, contractors shall be responsible for ALL work performed and shall be responsible for project planning, initiation, implementation, management, and communication; evaluation, selection, and management of subcontractors; and for all deliverables specified in this contract and each awarded Task Order. Any responsible Offeror may submit a proposal which will be considered by the Agency. This RFP will be available electronically on February 15, 2023 and may be accessed tough sam.gov. Please note: After opening/downloading the solicitation in the Come browser, click the down arrow and select "Open with system viewer" to view the RFP in Adobe Acrobat. This process will allow the links in Section J of the RFP to work properly. This notice does not commit the Government to award a contract. No collect calls will be accepted. No facsimile transmissions will be accepted. For this solicitation, the NIAID requires proposals to be submitted online via the NIAID electronic Contract Proposal Submission (eCPS) website. The content of the disc and online proposals must be identical. Submission of proposals by facsimile or e-mail is not acceptable. For directions on using eCPS, go to the website https://ecps.niaid.nih.gov and then click on "How to Submit." To submit online using eCPS, offerors must have a valid NIH electronic Research Administration (eRA) Commons account, which provides authentication and serves as a vehicle for secure transmission of documents and communication with the NIAID. The eRA Commons registration process may take up to 4 weeks. For more information, please see https://www.era.nih.gov/register-accounts/register-in-era-commons.htm.” NIHAI75N93023R00003 Department of Health and Human Services National Institutes of Health National Institute of Allergy and Infectious Diseases
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