A -- DEVELOPMENT OF A THIRD GENERATION ANTHRAX VACCINE

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 diseases. The NIAID, Division of Microbiology and Infectious Diseases (DMID), supports a comprehensive extramural research program focused on the prevention and control of diseases caused by virtually all infectious agents (with the exception of the Human Immunodeficiency Virus). This includes basic research, such as studies of microbial biology and physiology; applied research, including the development of vaccines, therapeutics and medical diagnostics; as well as clinical studies to evaluate experimental drugs and vaccines. Recent threats of the use of infectious agents as biological weapons have generated increased concern for the safety of the general American populace. Bacillus anthracis (B. anthracis) is the etiologic agent of anthrax. The ability to generate high titer anthrax spores using basic microbiological techniques combined with the ability of these agents to be disseminated by aerosolization, has made anthrax a primary bioterrorist and military threat. With the deliberate exposure of citizens of the United States to B. anthracis spores in 2001, there is an urgent need to stockpile appropriate and effective medical countermeasures to protect all U.S. citizens from the morbidity and mortality associated with infection from these instruments of terror. The NIAID has a requirement for the advanced development and testing of anthrax vaccine candidates which build upon the second generation vaccine, resulting in properties desirable for a biodefense vaccine to be stored in the Strategic National Stockpile (SNS). These properties include long-term stability (i.e., three years or longer) at room temperature, the ability to generate a protective immune response in one or two doses, and the ability to safely self-administer and/or rapidly inoculate into large numbers of people. Anthrax vaccine candidates eligible for support under this solicitation shall possess any one or all of the characteristics listed above while maintaining a superior safety profile to the currently U.S. licensed anthrax vaccine. Novel formulations/final vaccine presentation, new delivery platforms, adjuvants other than aluminum, and inclusion of antigens in addition to protective antigen (PA) may be components of candidate vaccines. The project involves: (1) manufacture and testing of anthrax vaccine candidates possessing any one or all of the characteristics listed above; (2) production of vaccine components and final product at pilot-lot scale; (3) characterization and testing including a stability program; (4) one or more pre-clinical safety studies required for the filing of an Investigational New Drug application (IND); and (5) non-clinical aerosol spore challenge studies using rabbit and non-human primate models. The Request for Proposal will include Mandatory Qualification Criteria that must be met at the time of receipt of the original proposal submission and they are as follows: Documentation must be provided to verify that the proposed anthrax vaccine candidate meets the following minimum development status criteria: a) As purified Protective antigen, (PA) has been shown to be efficacious against B. anthracis spore challenge in animal models, the proposed vaccine must contain a PA component; b) The PA component may be proteinaceous or nucleotide-encoded; c) Should the final vaccine presentation/inoculation strategy include a novel device, a Premarket Approval Application (PMA) or a Premarket Notification Form 510K must be currently filed with the FDA, and documentation provided in the Technical Proposal; and d) Data and results from a proof-of-concept study of the vaccine candidate in an anthrax spore challenge animal model which has demonstrated vaccine efficacy must be provided in the Technical Proposal. This may be in the form of a final study report or a peer-reviewed publication. If a novel device for vaccine delivery is proposed, contract funds may be utilized to suitably formulate the candidate vaccine for the device; however, funds may not be used for developing a device. This RFP will require that a Pre-market Approval Application (PMA) or a Premarket Notification Form 510K must be currently filed with the U.S. Food and Drug Administration (FDA) for such devices and documentation provided in the Technical Proposal. Potential offerors must also demonstrate and document the following in their technical proposal: (1) the vaccine candidate development status relating to established Good Manufacturing Practices (cGMP) pilot-scale production of clinical grade material suitable for use in Phase 1/2 clinical trials; (2) justification that further development of the proposed candidate vaccine as it relates to the objectives of this RFP (improved safety profile, rapid and robust titers in no more than two doses, elimination of cold chain/long-term stability, and ease of delivery for use in an emergency event) is warranted, while maintaining an improved safety/reactogenicity profile over the current licensed vaccine and at least equivalent efficacy; (3) documentation that the candidate contains, in part, a PA component; (4) demonstration of the availability and adequacy of facilities for cGMP drug substance (DS) and cGMP final drug product (FDP) manufacturing at pilot-lot manufacturing scale. For this RFP, pilot-scale DS fermentation is defined as a minimum of 30 liter working volume and/or sufficient DS to fill 2,000 doses of FDP. FDP is defined as a minimum of 2,000 final doses per single lot run. Potential sources proposing methodology for DS production other than fermentation must provide documentation to indicate that current yield is of equivalent quantity as above requirements. Pilot-lot scale processes must be readily transferable to large scale manufacture; (5) previous experience in developing and conducting non-clinical development plans to evaluate safety and efficacy of vaccine candidates that includes the conduct of all FDA required Investigational New Drug application (IND) enabling studies; and (6) previous experience in developing and executing clinical development plans to evaluate safety and immunogenicity of vaccine candidates. It is anticipated that one or more cost reimbursement, completion type contracts will be awarded for a three-year period of performance beginning on or about June 08, 2007, In addition, the contract will contain two Options. If executed, and will require the contractor to design and conduct a Phase 1 dose escalating clinical trial in healthy subjects ages 18 to 40 and up to two Phase 2 clinical trials in healthy subjects ages 18 to 55. It is estimated that the provision of FTEs will be approximately as follows: 13 FTE for Base Year 1 & 2; Reduced to 7.55 FTEs for Base Year 3; 2.1 FTEs for Year 3--Option 1; 2.1 FTEs per year in Option 2 (Years 4-7). The Option periods could increase the contract value and extend the contract by up to four years. Any responsible offeror may submit a proposal which will be considered by the Government. This RFP will be available electronically on/about June 19, 2006, and may be accessed through the NIAID Office of Acquisitions (OA) Home Page at http://www.niaid.nih.gov/contract and on FedBizOpps http://www.fedbizopps.gov/. This notice does not commit the Government to award a contract. No collect calls will be accepted. No facsimile transmissions will be accepted. See Government-Wide Numbered Note 26.