Research and Analses of Clinical Pharmacology of Tobacco Products

TITLE: Research and Analyses of Clinical Pharmacology of Tobacco Products OPDIV : FDA, Center for Tobacco Products (CTP) Background: This is a SOURCES SOUGHT NOTICE to determine the availability of potential small businesses (e.g., 8(a), service-disabled veteran owned small business, HUBZone small business, small disadvantaged business, veteran-owned small business, and women-owned small business) in accordance with FAR 7.104(d). The potential small business will need to demonstrate the capability to perform all facets of a clinical pharmacology study from initiation and conduct of the study through the data analyses phase and preparation of the final reports. History: The primary function of the Food and Drug Administration ("FDA" hereinafter) is to promote public health associated with the use of foods, dietary supplements, cosmetics, drugs tobacco, and other products under its jurisdiction. FDA's Center for Tobacco Products ("CTP" hereinafter), implements PL 111-31 and H.R. 1256, Family Smoking Prevention and Tobacco Control Act, which was signed into law on June 22, 2009. The Contractor will provide scientific support necessary to assist in the implementation of this law under the Federal Food, Drug, and Cosmetic Act. Specifically, the contractor will assist FDA by evaluating the pharmacologic properties and safety of tobacco products. The manufacturers of some of the emerging tobacco products (dissolvable tobacco products, e-cigarettes, little cigars, hookahs, etc.) have direct or implied claims that their health risks are less than those of traditional cigarettes. These potentially modified risk tobacco products (MRTPs) have been on the market for too short a time for assessment of the validity of these claims. Since the tobacco products are not regulated as drugs, their pharmacologic and harmful effects have not been evaluated by FDA. An in-house literature review of the clinical and clinical pharmacology information for a one of the new tobacco products (dissolvable in the mouth) revealed that this information is very sparse. In fact, none of the clinical studies of the pharmacokinetics and pharmacodynamics of the dissolvable tobacco products was prospectively designed (i.e. used an appropriate population of people; adequate sample size; assessed several meaningful biomarkers of exposure and response during the adequate length of time post-dose). There is no clear picture of the absorption, distribution and elimination of nicotine, its pharmacologically active derivatives after the administration of the dissolvable tobacco lozenges, pellets, and/or strips. Moreover, the pharmacokinetics and harmful effect of toxic compounds found in tobacco, such as nitrosamines, polyunsaturated and/or fluorinated hydrocarbons, heavy metals and volatile compounds in human biologic fluids, are not properly characterized for DTPs. The relationship between the biomarkers of exposure and response are not established for DTPs. The dissolvable tobacco lozenges are composed from the milled tobacco leafs and several ingredients with the functions of binding, protection of degradation, coating, taste making and flavoring. Together with the other flavors (cinnamon, vanilla, etc.) some products contain menthol as a direct addition as well as a part of the natural products (i.e. peppermint) extracts. Since it is well known that menthol in general influences the buccal absorption, it is important to evaluate the effect of menthol on absorption of nicotine and other components of the dissolvable tobacco products, including nitrosamines. The Office of Science Center for Tobacco Products (CTP), therefore, plans to initiate a series of clinical pharmacology studies of the tobacco products. The first pilot study will be performed with the dissolvable tobacco products (DTPs), followed by full size studies of DTPs, e-cigarettes, little cigars, and hookahs. The information acquired in these studies will fill the gap of knowledge of clinical pharmacology of these products. The primary objectives of this IDIQ contract are to evaluate the pharmacokinetics and pharmacodynamics of nicotine, its metabolites, as well as tobacco specific toxic compounds after the administration of the tobacco products (dissolvable tobacco products, e-cigarettes, little cigars, hookahs) and to compare the bioavailability of nicotine after administration of these tobacco products with the conventional cigarettes and to evaluate effect of menthol additive in some of these products on the nicotine pharmacokinetics. In order to fulfill these tasks, the Government is proposing to perform a series of clinical pharmacology studies. For each task, the constractor shall screen and select participants, administer the tobacco products, collect data and perform data analyses, which includes but is not limited to, subject evaluation, laboratory tests, computer-assisted-self-administered interviewing, specimen collection, assay of the specified compounds in human blood and urine, non-compartmental pharmacokinetic and pharmacodynamics data analyses. Data collected under this mechanism will inform FDA on the nature and the impact of the use of dissolvable tobacco products on the public health which will have an impact on policies and regulations with respect to the dissolvable tobacco products, as well as risk communications regarding the use of tobacco products. 3. SCOPE Contractor tasks shall include, but not be limited to: A. Establish and validate the assay methodology for the compounds of interest. B. Perform the series of studies to evaluate the pharmacokinetics and pharmacodynamics of nicotine and all compounds of interest after the administration of dissolvable tobacco products, e-cigarettes, little cigars, hookahs, etc. The measurements on nitrosamines in urine will be performed until their concentrations will reach a minimum detectable level. The contractor's activities shall include but not be limited to the following: - Recruit the candidates; assess their inclusion and exclusion criteria, evaluate the drop out rate in order to achieve sufficient number of evaluable subjects for the appropriate data analyses; - Select the clinical research facility to perform the study; - Provide physicians, laboratory technicians and other staff to perform the screening and laboratory tests, to collect specimen samples, to assay the biologic samples. - Perform assay validation for the compounds of interest in human blood, plasma and urine; - Take all necessary measures to ensure and maintain the confidentiality of data. - Analyze pharmacokinetic and pharmacodynamic data. - Provide the intermediate as well as final data reports. F. Upon request from the COR, the contractor shall deliver interim raw data as well as the results of the data analyses in SAS transport (.xpt) format and a written report to the Government by a specified date during the testing period. G. Provide other technical and research assistance as needed and specified by the Government, which may include but shall not be limited to the following: - Conduct literature reviews - Develop, design, and review research protocols, instruments, and questionnaires - Provide in-depth analysis of primary or secondary research data - Prepare Information Collection Requests (ICR) for OMB approval - Compose research reports and review manuscripts for peer-reviewed journals NAICS Code: 541990 Contractor Requirements: Contractors must respond to all of the following points, by indicating your experience and capability: 1. To perform the full scope of pharmacokinetic and pharmacodynamic data analyses. 2. To recruit and identify staff (key personnel) with the expertise to utilize the clinical study methodology, establishment and validation of assay of chemicals in the human biologic fluids and interpretation of results (e.g. clinicians, nurses, laboratory technicians, data managers, pharmacokineticists, statisticians). 3. Demonstrate experience in performing a clinical pharmacology study, including but not limited to recruitment of male and female candidates and assessment of their inclusion or exclusion in the study, selecting a clinical research facility which is equipped to perform the study, ensuring . 4. To identify and recruit physicians, nurses, laboratory technicians and other staff with the necessary capability and experience to perform the screening and laboratory tests, to collect specimen samples and to assay the biologic samples. Interested parties having the capabilities necessary to perform the stated requirements may submit capability statements via email to Ann Argaman, Contract Specialist ann.argaman@fda.hhs.gov. CAPABILITY STATEMENTS MUST DEMONSTRATE THE MINIMUM REQUIREMENTS OUTLINED ABOVE. Please address each in order listed above. Teaming Arrangements: All teaming arrangements shall include the above-cited information for each entity on the proposed team. Teaming arrangements are encouraged. Responses must be submitted not later than January 5, 2012. Capability statements will not be returned and will not be accepted after the due date. This is not an invitation for bid, request for proposal or other solicitation and in no way obligates FDA to award a contract. The sole intent of this Sources Sought Notice is to obtain capabilities for set-aside and procurement planning purposes. Please provide the follow Business information: 1. DUNS Number 2. Company Name 3. Company Address. 4. Company Point of Contact, phone number and email address 5. Type of company under NAICS, as validated via the Central Contractor Registration (CCR). Additional information on NAICS codes can be found at www.sba.gov. Any potential government contract must be registered on the CCR located at http://www.ccr.gov/index.asp. 6. Corporate structure (corporation, LLC, sole proprietorship, partnership, limited liability partnership, professional corporation, etc.); 7. Current GSA Schedules appropriate to this Sources Sought 8. Current Government Wide Agency Contracts (GWACs) 9. Point of Contact, phone number and email address of individuals who can verify the demonstrated capabilities identified in the responses. 10. Responders should also include a statement about whether or not they have an approved Federal audited accounting system. If the responder has an approved accounting system, please provide the certification in which the accounting system was deemed adequate (e.g. the name of the audit agency and audit number). You may submit as an attachment, which will not count towards the overall page limit. All capability statements can be submitted via e-mail, facsimile, or regular mail to the point of contact listed below. Responses shall be limited to 10 pages Responses must be submitted no later than January 5, 2012 Documentation should be sent to: US Food and Drug Administration Office of Acquisition and Grants Services 5630 Fishers Lane, Room 2118 Rockville, Maryland 20857 Attn: Ann Argaman Contract Specialist