Attachments_package.pdf

RFP-75N94026R00002

PACKAGING AND DELIVERY OF PROPOSAL

March 12, 2018

ATTACHMENT

1 Page 1 of 2

Attachment 1 - Packaging and Delivery of Proposals for Use with the NIH electronic Contract Proposal Submission (eCPS) Website

I. PROPOSAL SUBMISSION

A. eCPS

1. Proposals must be submitted via the electronic Contract Proposal Submission (eCPS) website at https://ecps.nih.gov.

2. Proposals submitted by facsimile or e-mail will not be accepted.

3. Follow the “How to Submit an Electronic Proposal” instructions provided on the eCPS website at: https://ecps.nih.gov/home/howto. Please note that creating an account to submit may take up to three (3) business days. Please apply for a new account early to allow enough time for the registration process.

4. Offerors are solely responsible for submitting proposals and any modifications or revisions so as to reach the Government office designated above by the date and time specified in the solicitation. If your proposal is not received by the date and time specified in the solicitation, it will be considered a “late proposal,” in accordance with FAR Clause 52.215-1 Instructions to Offerors – Competitive Acquisition.

B. Creating and Naming Files:

1. Create one PDF file of your Technical Proposal, including all attachments. The Technical Proposal should be created in a PDF format that enables word searches to the maximum extent practicable. Forms and/or documents requiring signature(s) may be scanned, but must be merged into the Technical Proposal PDF file.

2. Create one PDF file of your Business Proposal, including all attachments:

The Business Proposal should be created in a PDF format that enables word searches to the maximum extent practicable. Forms and/or documents requiring signature(s) may be scanned, but must be merged into the Business Proposal PDF file. Additionally, the “Breakdown of Proposed Estimated Costs (plus Fee) with Excel Spreadsheet” (http://oamp.od.nih.gov/sites/default/files/DGS/contracting-forms/spshexcl_dec2012.xlsx) must be included in the Business Proposal.

In addition, the NIEHS Level of Effort Worksheet (Attachment E) should be created in a PDF format that enables word searches to the maximum extent practicable.

3. Create your Business Document Excel. The Excel file should be the “Breakdown of Proposed Estimated Costs (plus Fee) with Excel Spreadsheet” (http://oamp.od.nih.gov/sites/default/files/DGS/contracting-forms/spshexcl_dec2012.xlsx) included in the Business Proposal in its original Excel format, not PDF.

Multiple Excel files may be included, as necessary including the NIH Level of Effort Worksheets.

Attachment 1 https://ecps.nih.gov/ https://ecps.nih.gov/home/howto http://oamp.od.nih.gov/sites/default/files/DGS/contracting-forms/spshexcl_dec2012.xlsx http://oamp.od.nih.gov/sites/default/files/DGS/contracting-forms/spshexcl_dec2012.xlsx http://oamp.od.nih.gov/sites/default/files/DGS/contracting-forms/spshexcl_dec2012.xlsx http://oamp.od.nih.gov/sites/default/files/DGS/contracting-forms/spshexcl_dec2012.xlsx

RFP-75N94026R00004

PACKAGING AND DELIVERY OF PROPOSAL ATTACHMENT 1

March 12, 2018 Page 2 of 2

4. Each of the proposals, Technical and Business, must be separate and complete in itself.

Do not reference one proposal in another.

5. File naming convention: It is requested that the filenames for your Technical Proposal, Business Proposal, and Excel Workbook include the name of the offeror, the solicitation number and the type of proposal (i.e., Technical, Business, or Excel Workbook).

Examples:

Technical Proposal: XYZ Company_NIHAI2012001_Technical.pdf Business Proposal: XYZ Company_NIHAI2012001_Business.pdf Excel Workbook: XYZ Company_NIHAI2012001_Business.xlsx

II. FORMATTING AND PAGE LIMITATIONS:

A. Formatting for proposals

1. Proposal page layout shall be letter size 8.5” x 11" for all pages.

2. Proposals shall not include links to internet web site addresses (URLs) or otherwise direct readers to alternate sources of information.

3. Proposals shall not include audio or video files of any type.

4. Font size must be 10 to 12 points.

5. Spacing should be no more than 15 characters per inch. Within a vertical inch, there must be no more than six lines of text.

6. Margins must be at least one-inch on all sides.

7. Failure to adhere to the formatting requirements above may impact whether your proposal is reviewed in its entirety.

B. Page limitations:

See Attachment 24 for page limitations.

PROPOSAL INTENT RESPONSE SHEET

RFP No: 75N94026R00002

Title: Chemistry Research for the Division of Translational Toxicology (DTT)

Please review the Request for Proposals (RFP). Furnish the information requested below and return this page to the Contracting Officer at the email address below by July 24, 2026.

Your expression of intent is not binding but will greatly assist us in planning for proposal evaluation. Note: Proposals may NOT be submitted via e-mail, but rather through the NIH e-CPS and you will need to allow several days for the registration process.

Choose one of the following:

[ ] Do intend to submit a proposal

[ ] Do Not intend to submit a proposal.

If you are not responding to this RFP, please provide your reason(s):

Please provide the following contact information:

COMPANY/INSTITUTION NAME:

FULL ADDRESS:

POINT OF CONTACT and TELEPHONE NUMBER:

POC E-MAIL ADDRESS:

Please submit this Proposal Intent Response sheet to the email address below:

sarah.bank@nih.gov

ATTACHMENT 2

mailto:hanacekp@mail.nih.gov

STATEMENT OF WORK (SOW)

Chemistry Research for the Division of Translational

Toxicology (DTT)

1. General Information

1.1 General

This is a non-personal service(s) contract under which the personnel rendering the service(s) are not subject, either by the contract’s terms or by the manner of its administration, to the supervision and control usually prevailing in relationships between the Government and its employees. The purpose of this contract is to provide chemistry research for the National Institute of Environmental Health Sciences (NIEHS), Division of Translational Toxicology (DTT) research. The type and extent of chemistry research provided by this contract will be tailored to specific DTT research needs.

1.2 Description of Services

Independently, and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, procedures, materials, equipment, and facilities not otherwise provided by the Government to perform the objectives set forth below. In general, studies shall be conducted according to the requirements described in the Specifications for the Conduct of Chemistry Activities for Toxicology Research Performed by the Division of Translational Toxicology at the National Institute of Environmental Health Sciences (DTT Chemistry Specifications) (https://ntp.niehs.nih.gov/data/research/chemistry/rfp).

1.3 Background and Scope

The mission of NIEHS is to discover how the environment affects people to promote healthier lives. DTT is an intramural division at NIEHS, and DTT scientists use a variety of traditional and cutting-edge approaches to better understand how factors in our environment may impact our health. One of DTT's goals is to lead the transformation of toxicology through the development and application of innovative tools and strategies. This contract will provide required chemistry research at each step of the DTT toxicological evaluation process.

Performance of this contract will involve program management procedures and chemistry technical activities in up to 8 Functional Areas as given below. Functional Activities under Functional Areas may be performed individually or in one or more combinations (see Functional Area 5, Special Studies below). Detailed requirements for Functional Areas and corresponding Functional Activities are given in the DTT Chemistry Specifications.

Recognizing the evolution and integration of data science remains crucial to the study of environmental health, the scope of this Research and Development (R&D) contract aligns with the DTT research portfolio and NIEHS strategic plan. The objective of this R&D contract is to provide scientific, operational, and administrative chemistry research for DTT/NIEHS research.

Attachment 3-Statement of Work

1.4 Overview of Required Capabilities

The Contractor shall provide scientific and administrative research support to conduct chemistry activities in the following Functional Areas. Activities include, but are not limited to, the Functional Activities described in the DTT Chemistry Specifications and shall be performed in accordance with the requirements set forth there.

Functional Area 1: Logistics and Handling Logistics and Handling include all activities pertaining to procurement, handling, and shipment of test articles and samples produced for all DTT research.

Functional Area 2: Characterization Characterization includes all activities related to establishing the identity and determining the purity of test articles, including developing methods needed to perform the analysis.

Functional Area 3: Formulation Formulation includes all activities related to preparation, mixing, and analysis of dose formulations containing one or more test articles in a vehicle (e.g., corn oil, water, feed).

Functional Area 4: Biosample Analysis Biosample analysis includes all activities related to determination of the concentration of an analyte (e.g., test article, a metabolite of the test article, DNA adduct, endogenous analyte) in a variety of matrices (e.g., blood, plasma, tissue).

Functional Area 5: Special Studies Special studies include activities that are part of the overall scope of the contract but may or may not be contained within a single functional activity or represent only a portion of a functional activity.

Functional Area 6: Animal Studies Animal studies include all activities related to determining absorption, distribution, metabolism, and excretion (ADME) parameters and toxicokinetic (TK) parameters of a test article administered to animals, typically rodents, via a route or routes of interest (e.g., oral gavage, drinking water, feed, and/or intravenous). Animal studies will use either non-labelled (e.g., TK studies) or radiolabelled (e.g., ADME studies) test articles.

Functional Area 7: Omics Omics activities typically include exposomics, proteomics, and metabolomics analyses, using state-of-the-art techniques, in biological matrices (e.g., cell lysates, urine, plasma) and/or environmental samples (e.g., water).

Functional Area 8: In Vitro Assays In vitro assays include all activities related to determining ADME of test article(s) typically in in vitro rodent and human models.

1.5 Policies and Procedures

The Contractor and applicable subcontractor facilities shall comply with the below regulations and specifications. Refer to DTT Chemistry Specifications Chapters 2 Facilities), 3, (Health and Safety) and 4 (Animal Care and Use) for details.

• All work performed under this contract by the Contractor or any Subcontractor for any assignment that directly supports a DTT GLP study (e.g., toxicology study) shall comply with Food and Drug Administration Good Laboratory Practices for Nonclinical Laboratory Studies (FDA GLP Regulations; Federal Register, 12/22/78, Part II et seq. (CFR Code of Federal Regulations Title 21) unless specifically authorized by the contracting officer’s representative (COR) or specifically excluded in the DTT Chemistry Specifications.

• Health and Safety

a. The Contractor shall establish procedures to protect the health and safety of contract personnel performing work under this contract and provide staff with on-going training to ensure that they are aware of any potential hazards.

b. The Contractor’s Health and Safety Program shall:

i. Provide a qualified Health and Safety Officer.

ii. Obtain and maintain full Drug Enforcement Agency (DEA) licensing (Schedules 1-5) that provides for procurement, receipt, storage, and shipment of Schedule 1-5 substances.

iii. Develop and implement a detailed health and safety plan (HASP) that demonstrates compliance with the Occupational Safety and Health Act (Public Law 91-596 84 STAT 1590 1970, amended 2004) and applicable state and local safety and health codes, standards, and regulations. A DTT approved HASP is required prior to any work commencing under the contract and a copy of the proposed HASP shall be included in the contract proposal.

iv. Include safely dispose of hazardous wastes.

v. The Contractor shall comply with all federal, state, and local regulations for receipt, storage, handling, and shipping of hazardous chemicals, and with the National Cancer Institute (NCI) Safety Standards for Research Involving Chemical Carcinogens, DHEW Publication no. (NIH) 77-900 (1975), and subsequent revisions; and the NIH Guidelines for the Laboratory Use of Chemical Carcinogens, NIH Publication no 81-2385 (May 1981), and subsequent revisions.

vi. All shipments must comply with Department of Transportation (DOT) regulations and the DTT Specifications requirements for chemical shipments. International shipments must comply with all applicable regulations for the recipient’s location

• Animal Care and Use

a. Contractor shall comply with requirements in Chapter 4 of the DTT Chemistry Specifications and Chapter 6 of the Specifications for the Conduct of Toxicity Studies by the Division of Translational Toxicology at NIEHS

(https://ntp.niehs.nih.gov/data/research/toxicology).

i. For required animal record information, the contractor shall comply with the requirements in Chapter11, Appendix A, Section 3, unless otherwise specified.

b. The contract shall be conducted in compliance with the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals, the Animal Welfare Act Regulations, the current edition of the Guide for the Care and Use of Laboratory Animals (the Guide), and all local, state or federal regulations and policies.

c. Animal experimental protocols, approved by the contractor's IACUC, shall be deliverables to the COR prior to the commencement of work. These contractor-approved protocols shall also be available to the NIEHS ACUC.

d. The Contractor shall utilize a qualified Laboratory Animal Veterinarian to supervise the care and health of the animals.

1.6 Reporting Requirements

1.6.1. Reports and Deliverables

• The contractor shall comply with the requirements in DTT Chemistry Specifications

Chapter 7. A summary of required reports is given in Table 1.

Table 1. Summary of Required Reports

Report Type Report Due Submit to Contract Management Reports

Quality Management Plan

(QMP)

Within 60 days of the award of the contract

COR, CO, CS

Health and Safety Plan

(HASP)

Within 60 days of the award of the contract

COR, CO, CS

IT Security Plan Within 60 days of the award of the contract

COR, CO, CS

Standard Operating Procedures

Within 6-months of the award of the contract

COR

Chemical Inventory On the 15th day of each month of this contract, beginning with the second month after award

COR

Annual Water Analysis Report

Within 30 days of the start of the contract and annually thereafter

COR

Monthly Status Report On the 15th day of the second month after the start of the contract, and each month thereafter

COR, CO, CS

Monthly Level of Effort Spreadsheet

Before the 15th day of the following month

COR

Annual Report Within 60 calendar days of the end of each year of the contract

COR, CO, CS

Final Report On or before the expiration of the contract

COR, CO, CS

Functional Activity Reports

Interim Data Within one week of data generation

COR

Draft Final Report1 From 8 weeks to 12 weeks of laboratory work completion. Period varies depending on the Functional Activity

COR

Final Report Within 2 weeks of COR approval

COR

Letter reports Within 8 weeks of laboratory work completion

COR

Study Files (hard copies and pdfs)

Within 60 calendar days of the end of each year of the contract

COR

1Includes any applicable data summaries and data files

• All reports submitted under this contract shall reference the contract number, the title and type of report, any applicable DTT assignment number, and the represented period on the first page of the report.

• Posting Electronic Reports

a. Electronic copies of all final chemistry reports shall be submitted to the DTT information management system (DTT PMS, currently Microsoft Dynamics 365 Program Operations) drop box at a URL specified by the COR.

b. Electronic copies of contract management and status reports shall be submitted to the DTT PMS.

c. Electronic copies of financial reports shall be emailed to the Contracting Officer. The Contracting Officer will provide the email address to the Contractor.

• If paper copies of fiscal, status, and technical reports are required, they shall be delivered to the COR or the CO as directed.

• When reporting subcontracted work, the Contractor shall summarize the work in a report to the DTT and attach as an appendix the original report submitted to the Contractor by the Subcontractor.

1.7. Post Award Conference/Periodic Progress Meetings

The Contractor shall attend any post award conference convened by the contracting activity or contract administration office in accordance with FAR Subpart 42.5. The CO, COR, and other Government personnel, as appropriate, may meet periodically with the Contractor to review the Contractor's performance. At these meetings the CO will apprise the Contractor of how the Government views the Contractor's performance and the Contractor shall apprise the Government of problems, if any, being experienced. Appropriate action shall be taken to resolve outstanding issues. These meetings shall be at no additional cost to the Government.

1.8. Progress Meetings

The Contractor shall attend, participate in, and furnish input to scheduled and unscheduled meetings, conferences, and briefings that relate to the functions and services herein as required by the Government to provide effective communication and impart necessary information. The Principal Investigator and/or Deputy Principal Investigator shall attend meetings as requested by the Government. Meeting attendees shall at times include Contractor managerial, supervisory, and other personnel knowledgeable of the subject matter. Meetings may start or end outside of regular duty hours.

1.9. Personnel

The Contractor shall ensure that all Contractor personnel are adequately trained, possess the required credentials, and are fully qualified and skilled to perform the activities outlined in this SOW. The Contractor shall be responsible for all costs associated with technical training and necessary travel to ensure that staff maintain required certifications and proficiency to perform assigned duties. Refer to DTT Chemistry Specifications Chapter 1 for details.

In accordance with HHSAR 352.237-75, the following personnel are considered key personnel by the Government.

Contractor shall identify a Principal Investigator who shall be responsible for the performance of the work and provide the name of this person and that of a Deputy Principal Investigator, who shall act for the Contractor when the Principal Investigator is absent. The Principal Investigator and Deputy Principal Investigator shall have full authority on all contract matters relating to daily operation of this contract.

Each Functional Area Leads (e.g. Logistics and Handling, Characterization, Formulation, Biosample analysis, Animal Studies, Omics, and in Vitro Assays) shall be designated Key Personnel. For ADME and TK studies that Contractor shall have a subject matter expert (SME) on staff with relevant ADME and TK experience.

For activities involving animals, the Contractor shall employ a Lab Animal Veterinarian to monitor the study.

Key Personnel, along with the Health and Safety and Quality Assurance Officers and the Lab Animal Veterinarian shall be employees of the contractor (i.e., not consultants or subcontractors). Acceptance of the CV by the CO is required before these individuals are permitted to perform any task on this contract.

All subcontracted work (e.g., DNA barcoding of botanical materials for authentication; imaging mass spectrometry to determine xenobiotic distribution in tissues) must have a responsible staff member employed by the prime contractor who will oversee activities at the subcontractor. Subcontractors shall designate a project manager (PM) or SME with experience relevant to the subcontracted activities to oversee the work and serve as the point of contact for the prime contractor’s staff. When subcontracted work constitutes a significant fraction of an activity, the subcontractor must designate a QA SME to monitor the subcontracted work.

Any change in personnel that might have an impact on the conduct and results of studies shall be reported immediately to the DTT.

1.10. Data Rights, Patents, and Copyrights

The Government has unlimited rights to all documents and materials produced under this contract. All documents and materials produced under this contract shall be Government-owned and are the property of the Government with all rights and privileges of ownership and copyright belonging exclusively to the Government. These documents and materials may not be used or sold by the Contractor without written permission from the CO. All materials supplied to the Government shall be the sole property of the Government and may not be used for any other purpose. This right does not abrogate any other Government rights.

1.11. Source Documentation

All original source documentation is the property of NIEHS. Data summaries and other relevant information generated during the performance of this contract shall be submitted to the COR in the form of status reports and project specific reports as specified under the Deliverables in the DTT Chemistry Specifications. In addition, annual reports shall be submitted as described in DTT Chemistry Specifications. To the extent possible, the Government will retain unlimited access and rights to all materials, data, and technical information generated under the contract. The Contractor shall arrange for delivery of all raw data and study files for archival annually as directed by the COR.

1.12. Non-Disclosure Requirements

Performance under this contract may require the Contractor to access data and information proprietary to a Government agency, another Government Contractor, or of such nature that its dissemination or use other than as specified in this work statement would be adverse to the interests of the Government or others. The Contractor and Contractor’s employees shall not divulge, or release data or information developed, or obtained under performance of this contract, except to authorized Government personnel or upon written approval of the CO. The Contractor shall not use, disclose, or reproduce proprietary data, which bears a restrictive legend, other than as specified in this contract. All documentation showing individual names or other personal information shall be controlled and protected under the provisions of the Privacy Act of 1974, Public Law 93-579, 5 United States Code (U.S.C.) Section 552a.

1.13. Replication, Dissemination, or Use of the Results

It is anticipated that the results of the research conducted under the Contract shall be published in the open, peer-reviewed scientific literature and/or in a NTP or NIEHS technical report series. Specific details concerning authorship and technical issues surrounding the publication of the research shall be discussed and agreed upon by the PI and the DTT COR on a case-by-case basis.

Because premature release of information developed under the contract could be harmful to the public, the Contractor and the Government agree that it is important to consider issues related to the timing of the release of research results when submitting information for publication. With regard to public disclosures of the research to be carried out pursuant to this contract, the Contractor agrees to submit all proposed articles to the COR at least thirty (30) days in advance of submission for publication. Within this thirty-day period the COR shall inform the Contractor if there are serious concerns raised by the timing of said publication.

Upon receipt of a notification that the Government objects to the publication of said information the Contractor agrees to withhold submission of said publication while the author and the COR discuss the issues of concern. The Contractor agrees to give good faith consideration to all such issues and further agrees that it will not knowingly submit for publication any article, abstract or other item that would be harmful to the public welfare. The final decision on whether to submit an article for publication shall rest with the DTT COR after the procedures set forth above are followed. Similar procedures shall apply for scientific presentations and meeting abstracts.

1.14. Protection of Government and Contract Information

The Contractor shall not cite any information (e.g., contract information, pictures, locations, etc.) obtained through this contract on any hard copy or digital marketing tools to include on its company website.

1.15. Non-Disclosure Statements

The Contractor shall provide signed non-disclosure agreements to the Government no later than five (5) days prior to commencement of work under the contract. Disclosure of information by Contractor personnel may result in removal of Contractor personnel from performance under this contract.

2. Required Capability Areas

2.1. General Requirements

The Contractor shall provide services, qualified personnel, materials, equipment, and facilities needed to conduct chemistry services in Functional Areas given below. Detailed requirements for Functional Areas and Functional Activities are given in DTT Chemistry Specifications Chapter 6.

2.2. Required Capabilities

2.2.1. Functional Area 1: Logistics and Handling

Logistics and Handling include all activities pertaining to procurement, handling, and shipment of test articles and samples produced for all DTT research. Activities in this area include, but are not limited to, the Functional Activities described in Chapter 6.2 of the DTT Chemistry Specifications and shall be performed in accordance with the requirements set forth there.

Logistics and Handling typically involve performing any or all of the following activities:

• Procure and/or receive test articles, analytical standards, or samples (e.g., rodent plasma) from commercial and/or non-commercial sources.

• Handle test articles to include, but are not limited to repackage, mill blend, prepare solutions, aliquot, homogenize, or photograph of procured material.

• Store materials (e.g., test articles, formulations, biological matrices).

• Maintain test article inventories.

• Ship and/or arranging for shipment of analytical standards, test articles, or samples to

DTT-designated research laboratories.

• Develop protocols for test article, handling and reanalysis, and dose formulation and analysis.

2.2.2. Functional Area 2: Characterization

Characterization includes all activities related to establishing the identity and determining the purity of test articles, including developing methods needed to perform the analysis. Activities in this area include, but are not limited to, the Functional Activities described in Chapter 6.3 of the DTT Chemistry Specifications and shall be performed in accordance with the requirements set forth there.

Characterization typically involves performing any or all of the following activities:

• Determine physical properties (e.g., melting point, color, optical rotation)

• Establish identity and/or structure.

• Establish purity.

• Determine long-term storage stability.

2.2.3. Functional Area 3: Formulation

Formulation includes all activities related to preparation, mixing, and analysis of dose formulations containing one or more test articles in a vehicle (e.g., corn oil, water, feed).

Activities in this area include, but are not limited to, the Functional Activities described in Chapter 6.4 of the DTT Chemistry Specifications and shall be performed in accordance with the requirements set forth there.

Formulation typically involves performing any or all of the following activities

• Determine solubility, suspendability, and/or syringeability of a test article in a vehicle or vehicles designated by the COR.

• Develop methods for the formulation of a test article in a vehicle. For similar test articles (e.g., a chemical class), a common preparation method shall be considered.

• Develop, qualify, and/or validate methods needed to perform an analysis of a formulation for test article concentration. For similar test articles (e.g., a chemical class), a common analysis method shall be considered.

• Evaluate physical and chemical properties of a formulation, e.g., pH, suspendability.

• Evaluate the homogeneity of formulations that are not solutions.

• Evaluate the stability of a formulation under several storage regimes, e.g., ambient temperature, refrigerator, and/or freezer conditions.

• Evaluate the stability of a formulation under conditions of dosing.

• Prepare and/or analyze formulations using qualified and/or validated analytical methods. Formulations to be analyzed may be prepared by the Contractor or supplied to the Contractor from a DTT-designated laboratory. Ship formulations to a DTT-designated laboratory as directed.

• Analyze vehicles used in formulations for conformance to DTT, US Pharmacopeia (USP), or other specified requirements.

2.2.4. Functional Area 4: Biosample Analysis

Biosample analysis includes all activities related to determination of the concentration of an analyte (e.g., test article, a metabolite of the test article, DNA adduct, endogenous analyte) in a variety of matrices (e.g., blood, plasma, tissue). Activities in this area include, but are not limited to, the Functional Activities described in Chapter 6.5 of the DTT Chemistry Specifications and shall be performed in accordance with the requirements set forth there.

Biosample analysis typically involves performing any or all of the following activities:

• Develop, qualify, and/or validate methods needed to quantitate analytes.

• Evaluate the stability of the analyte in one or more matrices during storage.

• Determine the concentration of an analyte in one or more matrices.

2.2.5. Functional Area 5: Special Studies

Special studies include activities that are part of the overall scope of the contract but may or may not be contained within a single functional activity or represent only a portion of a functional activity. Activities in this category include, but are not limited to, the Functional Activities described in Chapter 6.6 of the DTT Chemistry Specifications and shall be performed in accordance with the requirements set forth there.

Special studies include, but are not limited to, performing any or all of the following activities:

• Performance of a portion or subset of any functional activity. For example, only determining the stability of the formulation would be a special task, because the formulation development and validation activity requirement includes developing and validating a formulation development and analysis method, in addition to determining stability.

• Performance of a combination of several portions or subsets of two or more functional activities as a single activity. For example, determining the test article identity and purity and formulation preparation and analysis is a combination of parts of the characterization and formulation analysis activities.

• Performance of activities such as extraction and analysis of samples other than biological matrices (e.g., PM2.5 filters), nontargeted analysis of mixtures (e.g., botanical dietary supplements), identification of a metabolite of a test article in a biological matrix, partition coefficient determination of an analyte between two matrices, protein binding of an analyte, and inhalation feasibility studies conducted in a small chamber to determine the ability of a chemical or test article to be generated as a uniform atmosphere in an inhalation chamber.

• Performance of activities to determine enzyme activity using probe substrates (e.g., use of midazolam to determine CYP 3A4 activity) and enzyme inhibition or induction following exposure to a test article (e.g., induction of CYP 1A1 following exposure to benzo(a)pyrene).

• Development and application of prediction models such as Physiologically Based

Pharmacokinetic (PBPK) Models to predict disposition of chemicals in animal or human models.

• In vitro to in vivo extrapolation (IVIVE) of data to predict phenomena in vivo in biological systems.

• Performance of the annual water analysis required to confirm the acceptability of water supplied to animals under study in the Contractor’s animal facility.

• Preparation of products per DTT COR request (e.g., manuscripts for submittal to peer reviewed journals, meeting abstracts and presentations for scientific conferences).

2.2.6. Functional Area 6: Animal Studies

To support animal studies, some Functional Activities in Functional Areas 1-4 shall be conducted as appropriate including preparation and analysis of formulations for the study and analysis of study samples for analyte concentrations as described above or as directed by the

COR.

Animal studies include all activities related to determining absorption, distribution, metabolism, and excretion (ADME) parameters and toxicokinetic (TK) parameters of a test article administered to animals, typically rodents, via a route or routes of interest (e.g., oral gavage, drinking water, feed, and/or intravenous). Animal studies will use either non-labelled (e.g., TK) or radiolabelled (e.g., ADME) test articles. All animal studies require a signed study protocol, which has been reviewed and approved by the Contractor’s Institutional Animal Care and Use Committee (or equivalent) and the DTT COR. Animal studies include the Functional Areas described in Chapter 6.7 of the DTT Chemistry Specifications and shall be performed in accordance with the requirements set forth there.

Animal studies typically involve performing any or all of the following activities:

TK Studies

• The test article may be administered following single or repeated exposure via the route(s) of interest.

• Typically measure concentration of analyte(s) (e.g., test article, metabolites) in a matrix (e.g., plasma, serum, tissues) over time following administration of test article.

• Typically consist of studies with number of animals <100 per species.

• Studies typically obtain samples from multiple animals (e.g., 3) per time point.

Definitive studies typically utilize up to 3 doses, 2 species, and both sexes following single or repeated exposure via the route of interest.

• A preliminary study may be conducted using limited doses and number of animals per time points. Results of preliminary studies may be used to establish doses and time points for definitive studies, and, if needed, analyte concentration ranges to be validated in the biosample analysis method.

• Analysis of data and determination of TK parameters from analyte concentration versus time course data are described in the DTT Chemistry Specifications.

ADME Studies

• The test article may be administered following single or repeated exposure via the route(s) of interest.

• Typically consist of studies with numbers of animals <100 per species.

• Studies typically utilize up to 3 doses, 2 species, and both sexes and obtain samples from multiple animals (e.g., 3) per end point.

• Typically measure radiolabel equivalents (e.g., total, bound) in blood, excreta, and tissues, over the study duration.

• Qualitatively and/or quantitatively determine the test article-specific metabolites or products in blood, plasma, serum, tissues, or urine, as directed by the COR.

• ADME parameters determined are described in the DTT Chemistry Specifications

2.2.7. Functional Area 7: Omics

Omics activities typically include exposomics, proteomics, and metabolomics analyses, using state-of-the-art techniques, in biological matrices (e.g., cell lysates, urine, plasma) and/or environmental samples (e.g., water). Activities in this category include, but are not limited to, the Functional Activities described in Chapter 6.8 of the DTT Chemistry Specifications and shall be performed in accordance with the requirements set forth there.

Omics analyses typically involve performing any or all of the following activities:

• Utilizing state-of -the art analytical systems and nontargeted analysis approaches using state-of-the-art analytical systems (e.g., high resolution mass spectrometry, tandem mass spectrometry) to identify and/or quantify analytes (e.g. xenobiotics and/or their metabolites) in biological or environmental matrices (e.g., exposomics), as directed by the COR.

• Utilizing state-of-the-art analytical systems and nontargeted analysis approaches to identify and/or quantify perturbations in the endogenous metabolome (i.e., metabolomics) following an insult (e.g., exposure to a test article).

• Utlizing state-of-the-art analytical systems (e.g., high resolution mass spectrometry, tandem mass spectrometry) and approaches to identify and/or quantify changes of the proteome (e.g., proteins, protein adducts) following an insult (e.g., exposure to a test article).

2.2.8. Functional Area 8: In Vitro Assays

In vitro assays include all activities related to determining in vitro ADME of a test article typically in rodent and human models, as directed by the COR. Activities in this category include, but are not limited to, the Functional Activities described in Chapter 6.9 of the DTT Chemistry Specifications and shall be performed in accordance with the requirements set forth there. Examples of activities that fall under this Functional Area include, but not limited to:

• Performance of assay(s) using suitable model(s) to determine absorption of a test article (e.g., Caco-2 monolayer model to determine intestinal absorption).

• Performance of assay(s) using suitable model(s) to identify transporters responsible for ADME of a test article (e.g., Pgp GloTM assay to determine Pgp substrates).

• Performance of assay(s) using suitable model(s) to determine clearance and metabolism of a test article (e.g., HepaRG cells, 3D liver organoids, or primary hepatocytes to determine hepatic clearance and metabolism).

• Performance of assay(s) using suitable model(s) to determine bioaccumulation of a test article following repeated exposure (e.g., HepatoPac® or plateable hepatocyte model to determine bioaccumulation).

• Performance of assays using suitable model(s) to determine in vitro percutaneous absorption of a test article (e.g., Franz diffusion cells, Flow Through Diffusion Cells).

3. Operating Procedures

3.1. Project Management

The Contractor shall comply with the Project Management requirements described below and in Chapters 2-5 of the DTT Chemistry Specifications during performance of all work under this contract and apply appropriate staff expertise and facilities to ensure that assigned work is completed in a timely and cost-effective manner.

3.1.1. Contract Servicing

• To ensure timely start-up of contract work, the Contractor shall:

I. Ensure that all proposed staff are in place within 60 days after contract award.

II. Ensure that all the proposed management documents are in place, including but not limited to, the IT Security Plan, the Health and Safety Plan (HASP) and the Quality Management Plan (QMP) within 60 days after award. All management documents shall conform to the requirements, including delivery requirements, set forth in the DTT Chemistry Specifications.

III. Ensure that facilities are as proposed and in good working order within 15 calendar days after contract award.

• Coordination and Continuity of Services I. The Contractor shall provide for effective and efficient coordination of contract performance with DTT personnel and other DTT-designated contractors.

3.1.2. Scheduling and Information Management

• The Contractor’s work in this area shall comply with the requirements described in the DTT Chemistry Specifications.

• The Contractor shall use a DTT program management system (PMS) specified by the Government to document assignments, including, but not limited to, assignment descriptions and activities under the contract; and to communicate with the COR regarding the status of ongoing assignments. DTT will provide access to this system.

The Contractor shall provide the computer hardware, appropriate software (e.g., browser, MS365, MS D365), and a high-speed internet connection to access these systems.

• The Contractor shall employ an internal information management system (IMS) to track the work performed under the contract. This system shall:

I. Monitor the status of all on-going work, including schedule, hours, and costs.

II. Serve as a Master Schedule for all assignments performed under U.S. Food and

Drug Administration (FDA) Good Laboratory Practice (GLP) compliance requirements.

• The Contractor shall provide schedules and assignment cost estimates that accurately reflect the work to be performed for all assigned work. The Contractor shall update the estimated assignment costs and schedules in their internal IMS and the DTT PMS when there are changes to cost and/or schedule (e.g., assignments that do not proceed as planned or assignment priorities change).

• The Contractor shall develop and implement an IT security plan that demonstrates compliance of their data management systems and practices with the Federal Information Security Management Act of 2002 (FISMA) and the Federal Information Technology Acquisition Reform Act of 2014 (FITARA). A DTT approved IT Security Plan is required prior to any work commencing under the contract and a copy of the proposed IT Security Plan shall be included in the contract proposal.

• The Contractor shall comply with all applicable NIEHS/DTT Data Management Plans when submitting data to or holding/archiving data for the Government

3.1.3. Quality Program

• The Contractor shall establish an effective Quality Program, which addresses the requirements described below for any assignment that directly supports a DTT GLP study, including for work performed by any Subcontractor.

• The Contractor’s quality program shall:

o Conform to the requirements set forth in the DTT Chemistry Specifications.

o Implement a comprehensive quality management plan (QMP), which addresses the requirements of the DTT Chemistry Specifications (see Chapter 5). A DTT approved QMP is required prior to commencement of any work under the contract and a copy of the proposed QMP must be included in the contract proposal.

o Establish an effective quality control (QC) program to ensure that data obtained under this contract is of high quality.

o Establish an independent Quality Assurance Unit (QAU) headed by a qualified Quality Assurance Officer (QAO).

o Establish Standard Operating Protocols (SOPs) for all activities performed under this contract, as required by the DTT Chemistry Specifications.

o Provide appropriate, ongoing staff training to ensure that all work conforms to contract requirements, DTT Chemistry Specifications, and where appropriate, to FDA GLP requirements.

3.2. Technical Activities

3.2.1. General Requirements

• Independently, and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, procedures, materials, equipment, and facilities not otherwise provided by the Government, as needed to perform the work set forth below.

o The Contractor shall have a fully functional facility adequate to conduct the work described herein. An on-site evaluation of facilities and equipment may be made prior to award.

• Ongoing, recurring chemistry services are assigned as required for DTT research activities.

The requirements described in the DTT Chemistry Specifications for each functional activity are typical of the work to be performed. The Contractor shall perform each assignment according to the requirements described at the time of assignment, and in compliance with the requirements of the DTT Chemistry Specifications for each Functional Activity.

3.2.2. Management of Technical Activities

• The day-to-day work performed under this contract will be managed as assignments, governed by assignment memos describing the work to be performed. Assignments shall be initiated by the COR to perform the Functional Activities described in the DTT Chemistry Specifications. The assignment description shall be provided by the COR to the Contractor, who shall document the assignment scope and description in the DTT PMS as described below. If a specific conflict arises between the SOW and the Chemistry Specifications, the Chemistry Specifications requirements shall take precedence.

I. The Contractor shall consult with the COR to develop a schedule for the proposed work that includes, at minimum, the following milestones.

The estimated start date of work for the assignment.

The estimated completion date of lab work for the assignment. If no lab work is involved, the estimated lab work completed date will reflect the date the data package will be completed and work on the draft report will begin.

The estimated date of issuance of the Draft Final report.

The Contractor shall enter the agreed milestones into the DTT PMS.

II. The Contractor shall provide an estimated cost and hours budget, based on the work to be performed and post the estimated hours and cost to the DTT PMS.

III. The Contractor may not proceed with work on an assignment until the COR has reviewed and approved the proposed schedule and estimated cost in the DTT

PMS.

• During performance of an assignment, the Contractor shall develop and follow assignment- or test article-specific SOPs for all work that employs validated analysis methods.

I. As work on an assignment proceeds, the Contractor shall update the DTT PMS with actual milestone dates as they are completed and revise estimated milestones when necessary. The Contractor’s intention to revise milestone dates must be communicated to the COR, who must approve any change to a milestone date.

II. As work on an assignment proceeds, the Contractor shall update the DTT PMS cost and hours budget on a regular basis and/or requested by the COR. The Contractor’s intention to revise the cost and hours budget for an assignment must be communicated to the COR.

III. The Contractor shall update the assignment workflow (e.g., status flag updated from ‘lab work in progress’ to ‘lab work complete’) in the DTT PMS when an assignment’s status changes. Specific status flags corresponding to assignment milestones will be established in the DTT PMS for all assignments.

IV. The Contractor shall provide to the COR updated information on progress and/or changes in approach during the performance of each assignment.

Updates shall be posted to the DTT PMS in the form of notes and threaded discussions as they occur, or at least weekly, whichever is more frequent.

Updates may also be required by the COR via other communication methods as needed (e.g., telephone). The Contractor shall summarize these communications in the DTT PMS.

Updates shall include data, when applicable, in the form of tables, graphs, spreadsheets, and/or other documents, as specified by the COR.

• The Contractor shall update the assignment workflow as work proceeds, compile all data supporting the assignment, and prepare and submit data and report per requirements set forth in the DTT Chemistry Specifications.

3.2.3. Ongoing Activities

The Contractor is expected to perform a combination of Functional Activities under any or all of the Functional Areas. Requirements for each Functional Area are described in detail in the DTT Chemistry Specifications.

• Required Base and Option Years

I. Ongoing activities for the base contract and option years (Option Years 1 through 9) may include any or all Functional Activities under the Functional Areas 1-8. Assignments may vary from year to year.

• Option 1 for additional work I. One Option 1 for additional work may be exercised per year.

II. If required, may include any Functional Activity or combination of Functional Activities under Functional Areas 1-8. The requirements for Option 1 will therefore vary each time Optional Item 1 is exercised.

• A 6-month extension of period of performance may be exercised after Option Year 9 I. Includes all of the chemistry services in Functional Areas 1-8 under the base contract.

3.3. Data Management

The Contractor shall provide a data management plan for the management, sharing, backup, storage, and security of all paper and electronic files and information collected and generated as part of completing the products outlined in this SOW.

All software and databases used or secured must be PC and MAC compatible unless approved by the COR.

All electronic deliverables must be PC and MAC compatible unless approved by the COR. Once projects are completed, all paper and electronic files will be transferred to the Government upon the COR’s request for long term storage.

All data derived or collected by Contractor shall reside in a data management system approved by the Government after acceptance by the COR.

The Government will have unlimited data rights ownership of all data and information generated during the Contract. The Government retains the right to access all information and data generated under this Contract at any time.

The Contractor shall plan for or acquire any subscriptions needed for accessing databases and/or information resources upon COR’s approval. All software and databases used to carry out the project objectives and requirements for scientific data management shall be approved by the CORs.

3.4. Contractor Travel

Under this contract, travel is authorized for activities pursuant to contract requirements, in accordance with the Office of Management and Budget (OMB) Memo, M-12-12. Travel is authorized, with prior approval of the COR, to professional meetings for the purpose of presenting work conducted under this contract, for meetings with DTT staff, or as specified by the COR.

Contract staff will be reimbursed at the Federal…