The Office of Critical Path Programs at FDA is soliciting grant proposals for programs to expedite the development of products used in the diagnosis, treatment and prevention of tuberculosis and other tropical diseases as defined in section 524(a)(3) of the Federal Food, Drug and Cosmetic act.

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The intent is to fund proposals for the developments and the running of collaborative partnerships involving a range of stakeholders for the purposes of (1) identifying, prioritizing and addressing gaps in the science and infrastructure needed to improve the diagnosis, treatment and prevention of TB and/or other tropical diseases as defined in section 524(a)(3) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C.

360n(a)(3)) and (2) developing and implementing a sustainable model for continued collaborative funding.

Parties eligible for this grant are listed in section 566 of the FD&C act which describes Critical Path public private partnerships.

They include institutions of higher education (as such term is defined in section 101 of the Higher Education Act of 1965 [20 USC § 1001]) or consortia of such institutions; or organizations described in section 501(c)(3) of the Internal Revenue Code of 1986 [26 USC § 501(c)(3)] and exempt from tax under section 501(a) of such Code [26 USC § 501(a)].

Proposals should provide a detailed plan for a collaborative partnership to address topics that may include but are not limited to those listed below.

Proposals should include a list of collaborators and their roles, as well as a proposed plan for developing additional funding mechanisms, such as consortia, to provide financial or in-kind support for the implementation of work streams identified in the proposal.

Letters from collaborators describing their roles should be included.

Projects may support the development of single product or products used in combination regimens.

1. Bridging the gap between discovery of new compounds and the testing of those compounds in man In many cases promising compounds for tuberculosis or tropical diseases are not viewed as profitable by industry, and clinical development has not occurred.

There is currently a need for organizations to support the generation of in vitro and animal data, as well as other scientific approaches to facilitate entry of candidate products into human clinical trials.

This effort involves planning, facilitation, and summary services for a program to address the “gap” between the discovery of compounds that are active in vitro against M tuberculosis or tropical diseases, and the testing of these compounds in man for the treatment of tuberculosis or tropical diseases.

Proposals are requested to develop and/or facilitate programs for nonclinical evaluation of toxicologic, pharmacologic, microbiologic (and immunologic in cases of vaccines) properties of newly discovered compounds and/or vaccines with potential activity in the treatment and prevention of tuberculosis or tropical diseases.

Applicants should consider addressing the funding of such a program, the collaboration of stakeholders in the drug discovery and drug development industries and practical strategies for initial exploration of the metabolic, toxicologic and microbiologic potential of newly discovered compounds.

2. Alternative uses of existing products Several products approved for diseases other than TB or tropical diseases have potential value in the treatment of TB or tropical diseases and in some instances are already used off label for these indications.

However, there is no financial incentive for sponsors to pursue FDA approval for these indications.

Proposals should address the development, funding and implementation of strategies to license existing products with potential activity against Mycobacterium tuberculosis or other tropical diseases for these indications.

Steps in this program might include a review of candidate products, an assessment of the current state of knowledge and a “gap” analysis, development of collaboration with appropriate stakeholders to fund needed clinical studies and sponsorship of a marketing application.

3. Biomarkers for global vaccine programs A significant challenge to the development of new TB or tropical disease vaccines is the absence of reliable immunological biomarkers for protective efficacy.

This program would involve 1) a review and evaluation of promising biomarkers for vaccine efficacy that already exist or are in development, 2) an assessment of the needs for such biomarkers, and 3) the formation of collaboration with stakeholders to fund and manage the discovery, standardization and validation of such biomarkers.

The program would address clinical trials and clinical specimens needed to validate new biomarkers.

4. Capacity building for clinical studies of TB and tropical diseases These diseases are typically most prevalent in the developing world where infrastructure for the conduct of clinical research is lacking.

Programs to build capacity in such sites may include:
• The development of an open source electronic case report form (eCRF) for investigators involved in studies in resource poor settings.

The case report form should use newly published CDISC/HL7 tuberculosis domain data standards and associated terminology.

The CRF should address inter-operability with open source clinical trial electronic Case Report Forms that are being developed and utilized in resource poor locations.

Applicants may consider addressing novel technologies for data transfer, e.g.

satellite communications and/or cell phones.

• Training in laboratory skills needed to support the conduct of high quality clinical trials.

Lack of laboratory infrastructure is an important limitation to the conduct of clinical trials at sites in resource poor settings.

A training program would be developed to assist such sites in developing the needed laboratory services to support a clinical trial in tuberculosis/ or other tropical diseases according to standards acceptable to the US Food and Drug Administration.

The program would consider optimal delivery of such training either at a central facility, web based training or on site training.

An appropriate collaboration of stakeholders would address the needs of such a program, the practical implementation, funding and sustainability.

5. Development of diagnostics A public workshop on TB diagnostics hosted by FDA, CDC and NIH will be held in June 201 0. Proposals are requested to extend the results of that workshop for the development and evaluation of • diagnostic biomarkers that will be reliable surrogates for determination of relapse-free cures and prediction of relapse in TB clinical trials • new rapid and reliable diagnostic tests for tuberculosis and for drug resistance which are practical for use in resource poor settings.

6. Combination therapy for tuberculosis This program will address in vitro and in vivo approaches to the selection of the most effective combination drug regimens for the treatment of drug-susceptible and/or drug-resistant TB.

The program will explore technologies and models to determine the most appropriate combinations of drugs and the required durations of therapy.

Timelines should be provided for milestones in each project.

Intermediate and final goals should be clearly identified in the program description.

Applicants should be able to describe specific short, medium and long term outcomes of public health relevance that will be reported as the program progresses.

It is expected that FDA will participate in the design of programs involving collaborative partnerships that may be formed as a result of this funding, and will provide oversight of the funded programs.