Evaluation of Biopharmaceutics Classification System Class 3 Drugs for Possible Biowaivers

This is a SOURCES SOUGHT NOTICE to determine the availability and capability of small businesses (including certified 8(a), Small Disadvantaged, and HUBZone firms; veteran and service-disabled veteran-owned small businesses, and women-owned small businesses) to provide the Food and Drug Administration (FDA) with the Biopharmaceutics Classification System (BCS) characterizing drug substances based on their aqueous solubility and intestinal permeability. These properties, in addition to dissolution, control the rate and extent of drug absorption from immediate release, solid oral dosage forms. According to BCS, drug substances may be categorized as follows: Highly soluble, highly permeable (Class 1); poorly soluble, highly permeable (Class 2); highly soluble, poorly permeable (Class 3); and poorly soluble, poorly permeable (Class 4). Currently, an FDA guidance published in August, 2000 (BCS guidance), provides for waiver of in vivo bioequivalence studies for drugs determined to have BCS Class 1 properties, provided they are rapidly dissolving and not NTI drugs. This approach has allowed the approval of numerous new and generic drugs based on in vitro data alone, with tremendous savings in resources and reduction in unnecessary human testing. It is believed, with the appropriate testing, that biowaivers may be extended to drugs belonging to BCS Class 3. Such biowaivers could also result in significant savings to the drug industry and the American health care consumer. This contract shall evaluate a number of commonly used excipients for possible impact on the permeability and absorption of several BCS Class 3 drugs. In vitro as well as confirmatory in vivo studies shall be conducted. The results could support extending biowaivers to drug products in this class. Two or more candidate drugs belonging to BCS Class 3 will be selected. Test products of each drug will be prepared using different excipients, and different amounts of the same excipient. In vitro dissolution profiles will obtained for each test product using USP Apparatus I at 100 rpm, or Apparatus II at 50 rpm, in 900 mL in each of the following media: 0.1 N HCl or simulated gastric fluid USP without enzymes; a pH 4.5 buffer; and a pH 6.8 buffer (as described in the BCS guidance). In vivo bioequivalence studies are then conducted using crossover design, with appropriate power, to evaluate the impact of different excipients, and different amounts of excipients, on the permeability and bioavailability of the test products. The BE studies will involve drug administration to healthy subjects in a clinical setting, and collecting blood samples at timed intervals. Plasma levels of the test drugs will be measured using validated bioanalytical methodologies. Pharmacokinetic parameters will be obtained using plasma levels, and statistical analyses will be conducted to evaluate bioavailability and bioequivalence. References Guidance for Industry: Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. August 2000. Guidance for Industry: Bioavailability and Bioequivalence Studies for Orally Administered Drug Products'General Considerations, March 2003. Wu C-Y and Benet LZ. Predicting drug disposition via application of BCS: Transport/ absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm Res. 22: 11-23 (2005). Amidon GL, Lennernas H, Shah V and Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 12: 413-420 (1995). A cost type contract is expected for a one year period of performance. The NAICS code for this effort is 541712 with a size standard of 500 employees. RESPONSE INFORMATION: Interested contractors must submit a capability statement (five page limitation) describing their company's experience and ability to perform this effort which includes the following: (1) company's name, mailing address, e-mail address, telephone and fax numbers, website address, and point of contact (2) a summary list of similar work previously performed or being performed; (3) the professional qualifications and specific experience of staff who may be assigned to the requirement; resumes for proposed key personnel should be included; (4) qualifications of the Principal Investigator which reflect education, publications, and previous research projects relevant to this project (5) information on the quality of facilities required including laboratory space and analytical instrumentation (6) demonstrated ability to meet the requirements of the statement of work (7) if qualified as an 8(a) firm (must be certified by SBA), Small Disadvantaged Business (must be certified by SBA), Woman-Owned Small Business, HUBZone firm (must be certified by SBA), and/or Service-Disabled Veteran-Owned Small Business (must be listed in the VetBiz Vendor Information Pages) (submit copies of any documentation such as letters or certificates to indicate the firm's status); (8) DUNS number, CAGE Code, Tax Identification Number, and company structure (Corporation, LLC, partnership, joint venture, etc.). (9) Companies must be registered in the Central Contractor Registry (CCR at www.ccr.gov) to be considered as a potential source; (10) identification of the firm's GSA Schedule contract(s) by Schedule number and contract number and SINs that are applicable to this potential requirement are requested and (11) if the company has a government approved accounting system, identify the agency that approved the system. This notice is for planning purposes only, and does not constitute an Invitation for Bids, a Request for Proposals, a Solicitation, a Request for Quotes, or indication the Government will contract for the work contained in this announcement. No reimbursement will be made for any costs associated with providing information in response to this announcement and any follow-up information requests. Responses to this announcement will not be returned, nor will there be any discussions or debriefings of any responses. This announcement is Government market research, and may result in revisions in both its requirements and its acquisition strategy based on industry responses. Responses must be sent to this notice no later than 4:00 p.m. eastern standard time on May 23, 2008 submitted by email to the attention of Megan Gnall, Contracting Officer at the above stated address.