A -- In Vitro Testing Resources For AIDS Therapeutics Development

The Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), funds a comprehensive portfolio of grant and contract resources to discover and develop novel agents for the prevention and treatment of infections caused by the human immunodeficiency virus (HIV) and AIDS-associated opportunistic pathogens, including tuberculosis. Investigators at academic institutions and small biotechnology/pharmaceutical companies who identify new therapeutic or prevention agents frequently do not have the expertise or financial resources to conduct many of the additional studies needed to convert promising leads into pharmaceutical agents suitable for Phase I clinical evaluation. To facilitate further development of promising leads, DAIDS supports a portfolio of in vitro, animal model, and drug development contracts to assist these investigators by providing the pharmaceutical-grade materials and preclinical data needed to support submission of an Investigational New Drug (IND) application to the Food and Drug Administration (FDA). Several contracts in this research and development portfolio are being recompeted for award in fiscal year 2007, including: (a) Tissue-based Small Animal Model for HIV Drug Discovery; (b) Pharmaceutical and Chemical Resources for AIDS Drug Development; (c) Safety Evaluation of Anti-AIDS Agents; and (d) Management of Information Resources for AIDS Drugs. Through this Request for Proposals (RFP), DAIDS is recompeting contracts for the development and conduct of in vitro assays to assess the potential of drug substances for further development as anti-HIV agents. Proposals are solicited in two distinct areas, each to result in the award of a separate contract: Part A: Confirmatory In Vitro Evaluations of HIV Therapeutics Part B: Specialized In Vitro Virological Assays for HIV Therapeutics and Topical Microbicides Proposals may be submitted for Part A alone, Part B alone, or both Part A and Part B; however, separate Technical and Business Proposals are required for each part. Any proposal which combines both Part A and Part B will be returned to the Offeror without review or further consideration. If an Offeror is awarded both Part A and Part B, NIAID will consider merging the two awards into a single contract. PART A: CONFIRMATORY IN VITRO EVALUATIONS OF HIV THERAPEUTICS Part A shall provide for in vitro confirmatory testing of drug substances submitted to the DAIDS Preclinical Therapeutics Development Committee (DPTDC) for further development as potential anti-HIV therapies. The goal of this contract resource is to independently confirm the initial observation of anti-HIV activity of promising drug substances and then examine the spectrum of in vitro activity in multiple cell types against panels of laboratory and/or primary HIV isolates representing different co-receptor usage, clade classification, and drug sensitivity. In addition, potential drug-drug interactions shall be examined and drug-resistant HIV isolates shall be made for the most promising drug substances. Part A will NOT support primary screening of new drug substances for anti-HIV activity. Drug substances for evaluation under Part A are submitted to DAIDS by academic institutions, private biotechnology/pharmaceutical companies, and government sources. Drug substances shall be provided to the Contractor in a blinded fashion and shall include small molecules, peptides, oligonucleotides, or polymeric substances. Each drug substance shall have different evaluation needs that will be dependent on the nature of the drug substance, the proposed mode of action, and the needs of the provider of the drug substance. Over 250 unique drug substances have been evaluated by the incumbent contractor employing a variety of assays, including: assays that use multiple isolates of HIV-1 and HIV-2; acute and chronic infection assays; virus inactivation assays; p24, reverse transcriptase, and tetrazolium dye reduction as virologic endpoints; and tetrazolium dye reduction and tritiated thymidine incorporation as cytotoxicity endpoints. Drug substances submitted to DAIDS for in vitro evaluation have originated 20% from academia, 40% from small biotechnology/pharmaceutical companies, and 40% from government sources. PART B: SPECIALIZED IN VITRO VIROLOGICAL ASSAYS Part B shall provide for biochemical, cell-based, and tissue-based assays to be performed to evaluate the efficacy and toxicity of potential topical microbicides submitted to the DAIDS Topical Microbicide Working Group (DTMWG), and anti-HIV therapeutics submitted to the DPTDC. Support shall also be provided for the development of new, and the improvement of existing, assays. High throughput screening capabilities are necessary. The drug substances to be submitted to the Contractor for analysis or assay development shall include small molecules, peptides, oligonucleotides, or polymeric substances. Biological samples submitted for analysis shall not contain infectious agents, but could be derived from once infectious material inactivated via chemical or thermal means prior to submission. In support of topical microbicide development, the assays to be performed include: (1) evaluation of potential topical microbicides for the ability to inhibit the transmission of HIV from infected to uninfected cells, or to inhibit the replication of HIV in relevant primary cells, established cell lines and tissue/organ cultures; (2) monitoring the effect of seminal plasma on the effectiveness of potential topical microbicides; (3) monitoring the toxicity of potential topical microbicides on hydrogen peroxide-secreting Lactobacillus; (4) mimicking the effect of pH transition that occurs during coitus on potential topical microbicides; and (5) determining the mechanism(s) of action of potential topical microbicides. In support of anti-HIV therapeutic development, the assays to be performed shall include biochemical and cell-based assays to access the impact of potential inhibitors on the action of HIV proteins and relevant host cell factors. Cytotoxicity and mechanism of action assays shall be also employed. It is anticipated that two seven year cost-reimbursement, completion type contracts will be awarded, beginning approximately July 23, 2007. Any responsible Offeror may submit a proposal which will be considered by the Government. RFP-NIH-NIAID-DAIDS-07-25 will be available electronically on or about September 6, 2006 with a closing date tentatively set for December 6, 2006. The RFP may be accessed through the NIAID Contract Management Program (CMP) Home Page at http://www.niaid.nih.gov/contract and on FedBizOpps web site located at http://www.fedbizopps.gov/ . This notice is for information and planning purposes only and does not commit the Government to award a contract now or in the future. This is not a request for proposals. The Government does not intend to award a contract based on responses under this announcement. No collect calls will be accepted. No facsimile transmissions will be accepted. Points of Contact: Eileen Webster-Cissel, Phone 301-496-0349, Fax 301-402-0972, Email: ewcissel@niaid.nih.gov; Nancy Hershey, Contract Specialist, Phone 301-496-0193; Fax 301-402-0972, Email: nhershey@niaid.nih.gov.