The U.S. Food and Drug Administration (FDA), Office of Acquisitions and Grants Services (OAGS) is conducting market research to support the Center for Tobacco Products (CTP) to obtain services to support the implementation of the Tobacco Control Act through in vivo and in vitro toxicological analyses of tobacco and related products.

This is a Sources Sought notice to determine the availability of small businesses capable of supplying the required services. This notice is for planning purposes only, and does not constitute an invitation for Bids, Request for Proposal or Request for Quotation or an indication the Government to award a contract, nor does the Government intend to pay for any information submitted as a result of this notice. Your responses to the information requested will assist the Government in determining the appropriate acquisition method, including whether a set-aside is possible.

Scope of Work:

Respondents to this notice shall have the capabilities to furnish the necessary personnel, materials, services, equipment, facilities, and otherwise do all things necessary for the performance of the work described below.

The in vivo activities under the anticipated requirement shall include, but are not limited to, assessing systemic, genetic, respiratory or cardiovascular toxicology of tobacco products in in vivo nonclinical studies utilizing the inhalation route or exposure systems to assess systemic toxicological effects. The studies shall include pharmacokinetic analyses (PK) by varying routes, in addition to inhalation. The Contractor shall evaluate the pharmacokinetics of the test products following inhalation exposure for up to 48 hours (which may vary based on the half-life of the selected compound) and additional routes of administration, including oral, intravenous or intraperitoneal, for comparative pharmacokinetics. The Contractor shall conduct acute, sub-acute, and chronic inhalation (3-day to 180-day) toxicology studies on smoke or aerosols, aerosolized components such as chemicals on the FDA's harmful and potentially harmful constituent (HPHC) list, other potentially toxic compounds, additives or other ingredients, such as flavors, humectants, structural materials, and e-liquids from traditional tobacco products (cigarettes, cigars, cigarillos, etc.), waterpipe, electronic cigarettes, and other electronic nicotine delivery systems (ENDS) using an appropriate animal model. The Contractor shall evaluate tissue histopathological analyses of target organs exposed to aerosol or ingredients and metabolites produced from tobacco products in in vivo toxicology studies.

In vitro activities under the anticipated requirement shall include, but are not limited to, assessing the toxicity profile of tobacco products using genotoxicity (e.g., mutagenicity), cytotoxicity (e.g., neutral red assay) and other in vitro toxicology assays (e.g., metabolism, receptor assays) relevant to understanding hazard, harm, and risks of regulated tobacco products. The test materials will include, but are not limited to, tobacco products regulated by the FDA (e.g., combustible tobacco products, smokeless tobacco, waterpipe, e-cigarettes, other electronic nicotine delivery systems), their components (e.g., additives, flavors, humectants, structural materials, e-liquids) and aerosolized constituents (e.g., HPHCs). The Contractor shall conduct in vitro studies using an exposure system and cell lines appropriate to the tobacco product. For example, an air-liquid interface exposure system (or an aerosol delivery system) and human or animal respiratory cells (for example, Chinese hamster ovary and V79 cells) shall be used to measure toxicity of smoke/aerosol emitted from conventional cigarettes and ENDS products. The contractor shall expose the cells directly (in liquid) or via smoke/aerosol generated from tobacco products under intense and non-intense smoking regimens.

Specifically, the following task areas are anticipated:

In vivo studies:
• Development and discussion with FDA research methodologies specific scientific protocols and execute the protocols and methods.
• Selection research facilities.
• Development of documentation for FDA Animal Care and Use Committee (ACUC) and CTP Internal Animal Welfare Committee approval and provide animal subjects protection.
• Ordering, housing, handling, and maintaining animals.
• Conducting validation of inhalation systems prior to executing short- and long-term toxicology studies for each chemical and/or mixture to confirm uniform distribution in an inhalation chamber and/or stability of an administered dose.
• Administering test articles [smoke/aerosol generated from tobacco products, tobacco constituents (e.g., HPHCs), additives, e-liquids or other ingredients (e.g., flavors, humectants, structural materials)] generated from traditional tobacco products (cigarettes, cigars, cigarillos, etc.), waterpipe, electronic cigarettes, and other nicotine delivery systems to laboratory animals (e.g., rats) by inhalation or other routes of administration (e.g., oral and intravenous).
• Collecting toxicological and pharmacokinetic data and performing data analyses in SAS transport (. xpt) and Microsoft Excel (.xlsx) formt, including verification and chemical analysis of concentration/dose levels of tobacco products and tobacco product constituents, such as particle size. For example, the Contractor may conduct pharmacokinetic analyses, including pharmacokinetics using the tobacco specific nitrosamine, N-nitrosonornicotine (NNN), following inhalation exposure to tobacco constituents, by pharmacokinetically comparing various exposure routes, in addition to inhalation.
• Conducting subchronic (i.e., 90-day studies) or chronic (e.g., 180-day studies) on single chemicals or mixtures from traditional tobacco products, electronic cigarettes, electronic cigarette solutions, and other nicotine delivery systems.
• Writing scientific reports on data and findings, including periodic progress reports, interim and final data analysis, and scientific manuscripts for peer-review journals.
• Conducting scientific literature reviews.
• Providing comprehensive written minutes of all meetings and conference calls.
• Performing quality assurance assessments.
• Complying with Good Laboratory Practices (GLP)

In vitro studies:
• Developing and discussing with FDA research methodologies and specific scientific protocols and execute the protocols.
• Ordering, housing, handling, and maintaining cell lines.
• Selection of research facilities.
• Ordering and preparing test materials, (e.g., tobacco products, product components, constituents, chemical mixtures).
• Collecting toxicological data and perform data analyses in SAS transport (.xpt) and Microsoft Excel (.xlsx) format, including verification and chemical analysis of concentration/dose levels of tobacco, tobacco product constituents, and other test materials.
• Writing detailed scientific reports on methods, data and findings, including periodic progress reports, interim and final data analysis, and scientific manuscripts for peer-review journals. All technical reports and data collected in the execution of the study must be reported in a database compatible format.
• Providing comprehensive written minutes of all meetings and recurring meetings via teleconference with the Contractor's key personnel to review overall progress, including progress made since the previous reporting period, anticipated activities accomplishments for the next reporting period, identification of any risks and discussion of mitigation strategies, and financial status.
• Conducting scientific literature reviews as needed, complete with a search strategy that includes search terms, databases (information resources), eligibility criteria, and data collection process.
• Performing quality assurance assessments.
• Complying with Good Laboratory Practices (GLP).

Capabilities Required:

Interested potential sources shall have the following capabilities to be determined as capable:
1. All work performed under this action will performed off-site at contractor facilities. Capable offerors shall conduct animal testing in facilities that are appropriately certified by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC).
In addition, in accordance with the Code of Federal Regulations (CFR) Title 21, Part 58, Good Laboratory Practice for Nonclinical Laboratory Studies (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?cfrpart=58), at all times during the life of the contract, the capable sources must be able to provide to the FDA Contracting Officer's Representative (COR) at their request a self-certifying statement concerning their GLP showing their facilities and operations meet all of the GLP requirements pursuant to Title 21, Part 58.
2. The contractor shall have the capability to provide staffing under the following labor categories to perform the work as described above, the labor categories of interest to the Government under this notice as follows:
a. Project Director: The Project Director shall plan, conduct, and manage task orders utilizing integrated business information technology services. The Project Director shall have advanced knowledge of the relevant science and the ability to apply new and unique methods and procedures to meet the FDA's requirements. Preferably, the Project Director shall have at least about six years of recent and relevant toxicology experience.
b. Senior Scientist: The Senior Scientist shall serve as a principal investigator and lead person for protocol development and order completion. The Senior Scientist shall provide technical and subject matter expertise on an order. Preferably, the Senior Scientist shall have at least about five years of toxicology experience and have a PhD in Toxicology.
c. Subject Matter Expert: The Subject Matter Expert shall provide technical knowledge, analysis, and advice on exceptionally complex problems that need extensive knowledge of the subject matter for effective implementation. The Subject Matter Expert shall develop innovative and creative technical solutions to problems, questions, and issues, using or extending state-of-the-art methods and technology. Preferably, the Subject Matter Expert shall have at least about six years of toxicology experience and a PhD in Toxicology.
d. Statistician: The Statistician shall analyze data and compile reports, charts, and tables based on established statistical methods. The Statistician shall perform empirical quantitative analysis and develop empirical tests including, but not limited to, goodness of fit, inferences of central tendency or dispersion, general distribution, association analysis, and randomness or trend. The Statistician shall support experimental project design, perform hypothesis testing, and provide analysis of experimental results. Preferably, the Statistician shall have at least about five years of toxicology experience and have at least a Bachelor's Degree in Statistics.
e. Data Manager: The Data Manager shall manage all aspects of data collection, including establishing and maintaining policies and procedures for gathering, coding, analyzing, and reporting data. Preferably, the Data Manager shall have at least about one year experience performing these data management activities.
f. Research Assistant: The Research Assistant shall execute research tasks under supervisory direction, such as collecting quantitative data, supporting protocol development, producing routine reports, and assisting with administrative tasks. Preferably, the Research Assistant shall have at least about two years of experience performing these Research Assistant type tasks.
g. Laboratory Technician: The Laboratory Technician shall provide administrative, clerical, and laboratory support. The Laboratory Technician shall execute routine tasks, such as maintaining files and ordering and managing supplies. The Laboratory Technician shall execute research tasks under the direction of senior scientific staff. Preferably, the Laboratory Technician shall have at least about one year of experience performing these Laboratory Technician type tasks.
h. Writer/Editor: The Writer/Editor shall support the collection and organization of information required for analyses, studies, guides, reports, training materials, and other documents. The Writer/Editor shall draft text based on source material or input from professional staff and provides conceptual and editorial review services to senior staff, including suggested revisions to improve clarity and editing and formatting documents to ensure readability and conformance with applicable standards. Preferably, the Writer/Editor shall have at least about two years of experience performing these Writer/Editor type tasks.

Capability Statements:

Responses to this sources sought shall unequivocally demonstrate the respondent's capabilities to provide the services/data above. At a minimum, responses shall include the following:

1. Cover Page: Business name and bio, DUNS number, business address, business website, business size status (i.e., SB, VOSB, SDVOSB, HUBZone SB, SDB, WOSB, LB), point of contact name, mailing address (if different from business address), phone number and email address. Provide this same information again if responding to provide a service offered by another firm.

2. Relevant Past Performance information inclusive of date of services, description, dollar value, client name, client address, client contact name, client point of contact mailing address (if different from that provided for client), client point of contact phone number, client point of contact email address, and name of company (to include DUNS number and size status) if not the respondent.

3. Descriptive literature, brochures, marketing material, etc. detailing the nature of services the responding firm is regularly engaged in providing. At a minimum, to be considered a potentially capable source this material should include information on the following:

Facility/Certification Capabilities:

a.) Respondents shall demonstrate through a copy of their current AAALAC certification, or description of their ability to obtain, adequate AAALAC certified facilities that meet the needs of this requirement throughout a five (5) year period.
b.) Respondents shall demonstrate through self-certification their facilities and operations meet all of the GLP requirements throughout a five (5) year period.

Technical Capabilities:
• (1) Capability to develop documentation for ACUC approval and provide animal subjects protection.
• (2) Capability to conduct inhalation toxicological studies with aerosolized tobacco product constituents ranging in duration from acute and pharmacokinetic studies to chronic (i.e. 90-day) studies.
• (3) Capability to validate stability and administration of dose by all routes delineated in Section 2.
• (4) Capability to measure toxicological endpoints using a variety of methods, including but not limited to pharmacokinetics, histopathology, plethysmography, exposure and respiratory biomarkers, genotoxicity assays (e.g., Comet and Micronucleus Assays), plasma and urinary biomarkers and DNA adduct formation in several organs.
• (5) Capability to administer test articles (tobacco products, their components and constituents) to laboratory animals (e.g., rats) by inhalation or other relevant administration routes such as oral and intravenous. The test articles will include, but not limited to, tobacco products (e.g., smoke or aerosol generated from traditional tobacco products or specifically constructed test cigarettes or reference cigarettes incorporating specific additives, e-cigarettes, other electronic nicotine delivery systems), their components (e.g., additives, flavors, humectants, structural materials, e-liquids) and constituents (Harmful and Potentially Harmful Constituents (HPHC)).
• (6) Capability to collect and analyze toxicological, pharmacokinetic, and chemical data to document exposure levels/concentrations.
(7) Capability to characterize chemical composition of tobacco smoke/aerosol and electronic cigarette solutions.

Staffing Capabilities:

Capability statements submitted in response to this notice shall detail the respondent's ability to have all necessary staff available to perform the work as described above.

4. If applicable, identification of the firm's GSA Schedule contract(s) by Schedule number and SINs that are applicable to this potential requirement are also requested. If a large business, provide if subcontracting opportunities exist for small business concerns. The Government is not responsible for locating or securing any information, not identified in the response.

Response Instructions:

Interested parties shall respond with capability statements; no larger than 20 pages (not inclusive of the cover letter) via e-mail in PDF or Word format before 1:00 PM Eastern Time on February 4th, 2019 to [email protected]; with a cc to [email protected].

In your response, please use "FDA-19-SS-1207956" followed by your organizations name as the subject line.

Disclaimer and Important Notes: This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization's qualifications to perform the work. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. After a review of the responses received, a pre‐solicitation synopsis and solicitation may be published in Federal Business Opportunities. However, responses to this notice will not be considered adequate responses to a solicitation.

Confidentiality: No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non‐proprietary technical information in any resultant solicitation(s).