Award Notice for Hollow Fiber Studies and Mathematical Modeling to Determine the Dosage and Frequency of Administration of Amoxicillin for Anthrax Prophylaxis for Pregnant Women and Children

The Food and Drug Administration (FDA) intends to solicit proposals for a contractor to fulfill a requirement for a program entitled - Hollow Fiber Studies and Mathematical Modeling to Determine the Dosage and Frequency of Administration of Amoxicillin for Anthrax Prophylaxis for Pregnant Women and Children. The NAICS Code is 541712, with a small business size standard of 500 employees. A. Background: In 2001, an intentional release of anthrax spores in New York City, Washington, D.C, and Florida through the U.S. postal system resulted in 22 confirmed cases of anthrax, 11 cases of inhalational anthrax and 5 fatalities. Over 10,000 people were prescribed a 60 day course of antibiotics for exposure prophylaxis. The optimal dosage and frequency of administration of antibiotics for prophylaxis and treatment of inhalational anthrax is unknown, although available animal studies and human case reports suggest that the current recommendations for ciprofloxacin and doxycycline may be adequate for the general population. However, women who are pregnant are a special subgroup in whom treatment with doxycycline and ciprofloxacin are to be avoided unless no other antibiotic options are available (ie: the benefit of these drugs outweighs the risks to mother and fetus), and alternative therapies are needed for children. Amoxicillin has been used successfully for treatment and prophylaxis against B. anthracis in animal studies and in human case studies, where the pathogen is known to be susceptible to this drug. Amoxicillin is a category A drug, deemed safe for mother and fetus. However, the optimal dose and dosing frequency for amoxicillin to treat anthrax is unknown. Furthermore, since the distribution and elimination of drugs often differ in pregnant and non-pregnant women, it is unknown whether an amoxicillin regimen that is shown to be efficacious in non-pregnant persons will maintain its efficacy in women who are pregnant. In addition, modeling is needed to determine the optimal Amoxicillin dosing strategy for children based on pharmacokinetic data. B. Objectives: The specific programmatic goals of this requirement are to use the hollow fiber model of B. anthracis infection (using the ?Sterne strain): 1. To conduct dose-fractionation studies in the hollow fiber system to determine the pharmacodynamic parameter linked with the efficacy of amoxicillin for the treatment of B. anthracis infection. 2. To conduct dose-ranging studies in the hollow fiber infection model to determine the intensity of exposure associated with optimal amoxicillin efficacy. 3. To determine the pharmacodynamically-optimized amoxicillin dosage and frequency of dosing that prevents emergence of resistance during therapy. 4. Using the data derived from these hollow fiber studies together with human PK data, apply mathematical modeling (population PK analysis, Monte Carlo simulations, and Target Attainment analysis) to develop amoxicillin regimens that should provide optimal benefit to pregnant and non-pregnant women and pediatric populations for prophylaxis against anthrax. C. Scope of Work : Independently, and not as an agent of the U.S. Federal Government, the offeror shall furnish the necessary personnel, materials, services, facilities, and otherwise do all things necessary for or incident to conduct studies to determine the dosage and frequency of administration of amoxicillin for anthrax prophylaxis for pregnant women and children. The offeror will perform hollow fiber dose-fractionation studies and establish peak concentrations, time above the MIC and AUC for q12h, q6h and q3h dosing given for 14 days. Hollow fiber dose-ranging studies will be performed. Amoxicillin assays and susceptibility testing with mutation frequency studies will be obtained. Population analyses will be performed and the results used for Monte Carlo simulations to identify the optimal Amoxicillin dose for pregnant women and children. D. Additional Information: It is anticipated that one (1) contract will be awarded with a period of performance of approximately 26 weeks. FDA intends to solicit this requirement as Full and Open Competition. This announcement is not a request for proposal (RFP). FDA anticipates release of the RFP on or around May 26, 2008 and it will be available on the Federal Business Opportunities (FedBizOpps) website. The anticipated award date for this effort is on or before September 1, 2008.