A -- Proper Dosage, Bridging Studies and Criteria for alternate modes of drug administration

This is a combined synopsis/solicitation for commercial items or services prepared in accordance with the format in FAR Subpart 12.6 as supplemented with additional information included in this notice. This announcement constitutes the only solicitation and a written solicitation will not be issued. This solicitation is issued as a Request for Quote (RFQ) No. D88340. These solicitation clauses and provisions are those in effect through Federal Acquisition Circular 97-27. The Standard Industrial Classification (SIC) Code for this acquisition is 7389 and the North American Classification System (NAICS) Code is 541710. The FDA intends to issue a purchase order for the following three projects. 1. Criteria used in the approval or alternate modes of administration of oral dosage forms in special populations i.e. pediatric and elderly patients. Objective: systematically examine and analyze the in-house and published data (in vitro, in vivo in the form of bioavailability and/or clinical data or a combination) with the goal of standardizing the regulatory requirements for future submissions. Deliverable: Survey and analysis of currently existing in-house and published clinical and biopharmaceutics data to establish the criteria used in different applications to specify acceptable means of administering the drug other than as the manufactured dosage form. The range of foods allowed will be identified and the basis for the selections will be determined. 2. Proper Dosage Adjustment in Subpopulations. The objectives: to examine and validate the assumption that exposure-response relationship is similar between adults and children in selected therapeutical drug classes, to provide a list of conditions where the assumption is valid, and to explore the methodology for future studies in aspects. Contractor will use the PK/PD modeling analysis focused on the relationship and explain why similarity is not seen, or in what concentration or dose range the similarity may be apparent. 3. Proper Dosage Adjustment in Subpopulations. The objective is to provide a method for integrating all factors that significantly affect the drug PK and/or PD and generate reasonable dosage recommendations for the labeling. Results should enable the agency to guide the industry and in making decisions regarding the benefit of integration of multiple factors on dosage. This is NDA data collection and survey-based with in-depth data analysis. Deliverables: Pharmacokinetic information, clinical safety and efficacy information along with demographic, pathologic and disease variables from clinical trials in various drug classes will be extracted from 10 newly approved NDA?s. Data will be analyzed for covariate effect on drug total body clearance (CL) and volume of distribution through mixed effect modeling analysis. Identify independent, interactive and confounding factors that have impact on the pharmacokinetics properties of the drug. Proposals for dose selection considering integrated factors for some hypothetical subjects will be defined. Proposals of dose selection based on current best practice will also be determined. Plasma drug concentrations for each proposal will be simulated based on the known pharmacokinetic properties and subject specific variables. Profiles will then be compared to: those observed from specific subjects who had desired clinical outcomes and those observed from a typical young male normal subject. Rank the 5 dose selection proposals based on the degree of similarities to the standard concentration-time profiles. Form general statistics and a recommendation on future general dosage adjustment strategy. Period of Performance: One year from date of award. The following FAR Clauses shall apply to this solicitation: 52.212-1 Instructions to Offerors-Commercial; 52.212-4 Contract Terms and Conditions-Commercial Items; and 52.232-33 Electronic Funds Transfers. All responsible sources that can provide and meet the above requirements shall submit written quotations by the due date referenced above. The award will be issued to the contractor offering the best value to the government. FAR provisions can be found at the following website: http://www/arnet.gov.