National Institutes of Health, National Heart, Lung, and Blood Institute, Contracts Operations Branch, 6701 Rockledge Drive, Room 6100, MSC 7902, Bethesda, MD 20892

A -- REFINEMENT OF NEW ASSAYS FOR DIRECT DETECTION OF VIRAL NUCLEIC ACIDS IN DONATED ORGANS SOL NHLBI-HB-99-10 POC Lynda A. Bindseil, Contracting Officer, (301) 435-0355 WEB: Click here to download a copy of the RFP., http://www.nhlbi.nih.gov/nhlbi/rafs/rfas.htm#rfp. E-MAIL: Click here to contact the Contracting Officer via, bindseil@nih.gov. The Division of Blood Diseases and Resources (DBDR) has a requirement for a Contractor to refine nucleic acid-based assays to identify infection of organ/tissue donors by blood-borne viruses, most notably human immunodeficiency virus (HIV) and hepatitis C virus (HCV). The major objectives of this program are: 1) to refine for use in clinical laboratories, one or more nucleic-acid based techniques that will be feasible for the direct detection of blood-borne viruses in donors of organs for transplantation to reduce the antibody-negative window period between infectivity and detection to the shortest possible time and, when possible, obviate the need for indirect antibody tests; and 2) to file for investigational new drug exemption (INDs) with the Food and Drug Administration (FDA), and submit and obtain approval for product license applications (PLAs). Presently available information indicates that the first detectable evidence for infection with HIV is a burst of viral RNA in circulating plasma about 7-10 days after the infecting episode. Hence, the solicitation calls for a test to detect this viral RNA. Unless the test proposed is 100% specific for the virus target, an offeror must propose an approach to a confirmatory test. Present information also indicates that there is a prolonged period of HCV viremia before clinical disease (including laboratory tests, such as ALT) and HCV antibodies develop. The availability of an assay to detect HCV RNA could reduce transplantation transmission of that virus by reducing the infectious, test-negative (antibody) window by several weeks. Accordingly, a companion test, multiplexed with one for HIV RNA, must also be developed and brought to clinical availability. As with the HIV RNA assay system, an offeror must also propose an approach to a confirmatory test for HCV. Furthermore, the offerors must provide suitable evidence that patent issues surrounding RNA testing for HCV have been acceptably addressed and resolved. The most promising technologies appear to be nucleic acid amplification systems such as polymerase chain reaction, ligase chain reaction, nucleic acid-based sequence amplification, strand displacement amplification, branched DNA, and transcription-mediated amplification. Innovative adaptations of these gene amplification and detection methods are expected to lead to efficient and reliable assays suitable for fool-proof performance at odd hours, one by one, by less practiced staff. The major focus is on HIV-1, although a test to detect HCV is also an important requirement. Multiplexing the detection of HIV-1 and HCV in the same reaction is desirable. The preclinical phase for refinement of an organ donor assay shall be completed within 12 months from contract award. All clinical studies conducted at approved clinical trial sites must be completed and the results submitted to the Center for Biologies Evaluation and Research (CBER) within a period of 20 months from receipt of the investigational new drug (IND). An additional 4 months will allow for review of data by CBER officials and, ultimately, licensure of the procedure. It is anticipated that one (1) award will be made from this solicitation and that the award will be made on or about September 30, 1999. A cost-sharing, cost reimbursement completion contract with a term of three (3) years is anticipated. This is not a Request for Proposals (RFP). RFP No. NHLBI-HB-99-10 will be released on or about December 28, 1998 on the NHLBI web page at http://www.nhlbi.nih.gov/nhlbi/rafs/rfas.htm#rfp. There are no paper copies. Interested organizations should review and download the streamlined RFP designated as RFP No. NHLBI-HB-99-10 which will appear under the list of RFPs for the National Heart, Lung, and Blood Institute. Further instructions and forms for proposal submission are located at the menu selection entitled "Streamlined RFP References" which is located at the web page for the NIH Request for Proposals Directory, http://www4.od.nih.gov/ocm/contracts/rfps/mainpage.htm. Posted 12/09/98 (W-SN278728). (0343)

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