ATTACHMENTS RFP 75N96025R00004 less Attach 11 Excel File.pdf

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RFP 75N96025R00004 NAMS Attachment 1

ATTACHMENT 2, RFP 75N96025R00004

STATEMENT OF WORK (SOW)

Support for Evaluating and Conducting Computational and

Alternative Toxicological Methods for the National Institute of Environmental Health Sciences

June 23, 2025

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 all services and supplies necessary to conduct research using computational and alternative toxicological approaches in support of the National Institute of Environmental Health Sciences (NIEHS), Division of Translational Toxicology (DTT).

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 as needed to assist the Government in accomplishing the objectives below. In general, studies shall be conducted according to the requirements described in a research outline (Source Selection Plan, Attachment B).

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.

New approach methodologies (NAMs) broadly refer to any in silico, in chemico, in vitro, and ex vivo technology, methodology, approach, and/or combination thereof, that can provide information on chemical and non-chemical hazard and risk assessment while supporting the 3Rs (replacement, reduction, and refinement of animal studies). Top areas of research focus in the evolving NIEHS Strategic Plan include “Developing and building confidence in human-based new approach methods”. Related efforts in implementing suitable computational and alternative methods for toxicological research have been carried out by DTT/NIEHS scientists in support of developing and applying innovative approaches to predict human-relevant health effects. The areas of focus for contract research include but are not limited to population variability, susceptibility, developmental neurotoxicity, carcinogenicity, ecotoxicity, acute toxicity and other areas related to environmental health.

To advance the development, evaluation, validation, qualification and application of alternatives for laboratory animal use, DTT/NIEHS is an active partner with the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM)1, the interagency Tox21 Program2, and more.

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 support for NAMs activities within DTT/NIEHS to develop, evaluate, validate, and utilize a variety of NAMs to predict human health effects more accurately while also replacing, reducing, or refining the use of animals in toxicity testing.

It is also anticipated that this contract will provide support for internal and external trainings on NAMs approaches and ensure the recognition and transferability of the alternative methods.

1.4 Overview of Required Capabilities

The Contractor shall provide scientific and administrative support for the activities of DTT/NIEHS to conduct research studies in the following Capability Areas:

Research, Development, and Validation of Computational Toxicological Approaches Research, Development, and Validation of Alternative Test Methods Meeting Support and Event Hosting Communication Management o Website maintenance o Database and information support o Training support

1.5 Policies and Procedures

The Contractor and applicable subcontractor facilities shall comply with the below regulations and specifications:

a. A Strategic Roadmap for Establishing New Approaches to Evaluate the Safety of Chemicals and Medical Products in the United States3 is a resource to guide U.S. federal agencies and stakeholders seeking to adopt new approaches to safety and risk assessment of chemicals and medical products that improve human relevance and replace or reduce the use of animals.

b. Validation, Qualification, and Regulatory Acceptance of New Approach Methodologies: a report of the ad hoc lnteragency Coordinating Committee on the Validation of Alternative Methods Validation Workgroup64 describes the ICCVAM validation and acceptance criteria for implementing NAMs, as well as for completeness and adherence to the most current version of the ICCVAM Guidelines for the Nomination and

Submission of New, Revised, and Alternative Test Methods5 (NIH Publication No. 03- 4508).

c. Selected studies may be conducted in accordance with OECD Test Guidelines Programme6 and OECD Overview of Concepts and Available Guidance related to Integrated Approaches to Testing and Assessment7 (IATA).

1.6 Reports and Deliverables

The Contractor shall ensure that the reporting timeframes for each milestone are met. All deliverables shall be electronic and PC and MAC compatible unless otherwise specified by the Contracting Officer’s Representative (COR). Each final report shall be submitted to the COR for review electronically in MS Word and/or PDF formats. Unless otherwise directed, all submitted final deliverables shall be Section 508-compliant (see section 1.6.4 in this SOW). Unless otherwise instructed, all reports submitted under this contract shall reference the contract number, the title and types of report, and the submission date on the first page of the report.

In addition to the reports mentioned herein, any incidence or unforeseeable occurrence not listed here, including physical modifications to the laboratory facilities and personnel changes which may impact study conduct, shall be immediately reported to the Government.

DELIVERABLE REFERENCE DUE/FREQUENCY SUBMIT TO

Quality Management Plan

Section 1.6.1.1

Revise as needed or when major changes occur

COR, CO, and CS

Monthly Status Reports

Section 1.6.1.2

Monthly status reports shall be due on the 15th day of each month or the closest workday

COR, CO, and CS

Monthly Budget Summary Report

Section 1.6.1.3

Monthly budget summary reports shall be due on the 15th day of each month or the closest workday

COR, CO, and CS

Draft Annual Report Section 1.6.1.4

Draft annual report shall be submitted 4 weeks in advance of the Final Annual Report.

COR, CO, and CS

Final Annual Report Section 1.6.1.4

Final annual report shall be submitted within 12 months from the effective date of the contract, and annually, thereafter.

COR, CO, and CS

Research plan Section 3.1 For each new project, a work plan shall be submitted to the COR for approval. Draft work plans shall be due within 2 working days of receipt of a research outline from the COR and final work plans shall be due within 2 working days of receipt of comments from the COR.

COR

Abstract, posters and presentations

Section 1.6.2.1

In accordance with the approved timeline within the detailed work plan

COR

Manuscripts Section 1.6.2.1

In accordance with the approved timeline within the detailed work plan

COR

Alternative testing study report

Section 1.6.2.2

In accordance with the approved timeline within the detailed work plan

COR

Supporting materials for coordinating and participating in meetings – Roster, Federal Register Notices, invitations, transcription, etc.

Section 1.6.2.3

In accordance with the approved timeline within the detailed work plan

COR, Alt-COR and prospective meeting participants and registrants

Database and coding packages

Section 1.6.2.4

In accordance with the approved timeline within the detailed work plan

NA

Supporting materials for websites

Section 1.6.2.5

In accordance with the approved timeline within the detailed work plan

NA

1.6.1 Periodic Reports

1.6.1.1 Quality Management Plan

A Quality Management Plan (QMP) shall be submitted before performance of work under the contract and updated versions submitted at regular intervals (e.g., biannually).

1.6.1.2 Monthly Status Report

Monthly Status Reports shall be submitted to the COR on the 15th day of each month or the closest workday and provide details on the status of all active projects, monthly web access statistics, any problems encountered, and remedial actions taken to resolve those problems.

Any deviations from the SOW should be noted. Summary information describing the work performed by any subcontractor and/or ad hoc consultant, including their activities, deliverables, etc., should be included in the Monthly Status Reports. The Contractor shall include a description of how the subcontractor/consultant work aided the Contractor in completing or nearing completion of a specific project within the Monthly Status Report.

Monthly Status Reports shall also include all requests from the public, date of receipt, date of response, and response.

1.6.1.3 Monthly Budget Summary Report

For each activity separately undertaken, and for the contract, submit a monthly Budget Summary Report. The report must include amounts of a budget for each project activity, total expenditures on the activity for the month, summaries of current contract year and cumulative expenditures, and projected expenses to complete each activity. Hours spent and cost by any subcontractor and/or ad hoc consultant should also be included in Budget Summary Report.

Budget Summary Reports shall be submitted monthly to the COR as MS Excel spreadsheets (or using another agreed upon spreadsheet software) and shall be sortable as required by COR.

Budget Summary Reports must be included as an attachment with the monthly invoices.

Monthly Budget Reports are due by the 15th of each month.

1.6.1.4 Annual Report

An Annual Report shall detail all significant outcomes resulting from the requirements as described within the SOW and Contract, including a detailed breakdown of costs by project activity incurred to date, any problems encountered and remedial actions taken to resolve the problem, as well as any deviations from the SOW and/or Contract. The draft Annual Report is due to the COR, alternate COR, and the Contracting Officer (CO) within 4 weeks from the last day of each contract year. The final report shall be submitted to the CORs and the CO within 2 weeks of receiving comments from the CORs.

1.6.2 Research Products

1.6.2.1 Manuscripts, abstracts, and presentations

Upon developing computational methods and/or validating alternative approaches in selected projects, the Contractor shall publish results in peer-reviewed journals as directed by the COR and register the publication in the DTT Research Data Catalog (https://cebs.niehs.nih.gov/datasets/). In some cases, the Contractor shall assist and coordinate the preparation of panel reports and manuscripts related to the findings of the panels, as directed by the COR. The format of manuscripts shall adhere to specific requirements of journals, and NIEHS internal review and/or DTT quality assessment review for the manuscript is required prior to submission. The Contractor shall interface with the NIEHS arts/graphics contractor as instructed by the COR.

The Contract staff with appropriate expertise on the topic may present data at national and/or international scientific conference(s) to support the NIEHS mission in accordance with the approved work plans. Responsible Contract staff shall develop and submit abstracts for DTT/NIEHS review and approval by the COR prior to submitting to the conference. Once selected by the conference, presentations (e.g., oral and/or poster format, tools and/or database demo, etc.) shall be prepared by the Contractor and approved by DTT/NIEHS.

1.6.2.2 Alternative test method study reports

In general, for alternative testing studies, the Contractor shall submit study reports to the COR for review and approval. This report may include but not be limited to a complete protocol, a summary of methods for the individual assays conducted as part of the testing, a summary of all experimental findings, the discussion and/or conclusions as appropriate and a subcontractor report if applicable. It shall also include difficulties encountered and remedial actions taken, including any deviations from the study protocol. An export of the data shall be organized in the format compatible with storage in CEBS (https://cebs.niehs.nih.gov/cebs/), as directed by COR.

The requirements for data management are stated in Section 3.2.

1.6.2.3 Supporting materials for coordinating and participating meetings As directed by the COR, the Contractor shall provide support for all meetings deemed necessary to carry out the Computational and NAMs goals and objectives of NIEHS and its stakeholders.

For NIEHS/NIH-sponsored meetings, and others as required, the Contractor shall prepare the supporting materials (e.g., Federal Register Notices, agendas, registration materials, mailing announcements, flyers, brochures, etc.) before, during, and after the meeting as stated in Section 2.4. The Contractor shall coordinate with NIEHS/NTP website contractors to make this information available on the corresponding public websites.

1.6.2.4 Databases and coding packages

The Contractor may develop new databases and/or coding packages and shall maintain existing ones relevant to the analysis and evaluation of alternative toxicological methods (e.g., reference chemicals, retrospective compilation of testing results from the literature, high throughput screening [HTS] data, etc.).

To the extent feasible, all data made available to NIEHS stakeholders and the public shall be compliant with FAIR data principles of findability, accessibility, interoperability, and reusability

(FAIR).

The DTT/NIEHS develops databases to provide high-quality curated data and tools to support development of new approaches for chemical safety testing. The Contractor shall support the maintenance and management of the database and website to keep the system components up to date with the latest releases and updates for each technology. All data derived or collected by Contractor shall reside at NIEHS in a format interoperable with other DTT databases.

Code delivered to the Government shall be written in such a way as to run on Government servers, adhere to Government security and other standards such as compliance with Section 508 of the Rehabilitation Act, as directed by the COR. The Contractor shall provide updates to software to address evolving security policies and other standards as directed by the COR. The

Contractor shall supply support to ensure that the code can transfer smoothly to the Government network and perform according to needs of the Government.

1.6.2.5 Supporting materials for the websites

At the direction of the COR, the Contractor shall work with NIEHS and NTP website contractors and coordinate maintenance of, and updates to websites as required, and shall adhere to U.S Department of Health and Human Services (HHS) and DTT standards for Section 508 compliance. The Contractor shall coordinate with DTT/NIEHS employees, other federal employees, and third-party contractor personnel as necessary to perform these duties.

Supporting materials for the websites may include but are not limited to:

a. Posting of meeting dates to the NIEHS calendar, DTT intranet calendar, as well as to appropriate web pages as a calendar of events.

b. Posting of meeting-related materials, such as agendas, reference materials, minutes, proceedings, draft and final meeting reports, for all specific scientific meetings, workshops, symposia, seminars, webinar and conference calls (telephonic or web-based) as appropriate.

c. Committee rosters.

d. Posters and abstracts for presenting at professional meetings such as the Society of

Toxicology, World Congress on Alternatives to Animal Use, etc.

e. Test method reports and related documents.

f. Federal Register notices with links.

g. Updating approved federal and international testing guidelines and regulations.

h. Listings or hyperlink access to all currently approved national (e.g., FDA, EPA, OSHA, CPSC, DOT) and international (e.g., ISO, OECD, ICH, UN GHS) toxicity testing guidelines and requirements, as well as methods currently in development or validation and other relevant websites.

1.6.3 IT Security Plan and Other IT Deliverables

Refer to Appendix A specific requirements related to IT Security.

1.6.4 508 Compliance The Contractor shall comply with Section 508 of the Rehabilitation Act of 1973 (29 U.S.C. 794d) which requires Federal agencies to purchase Electronic and Information Technologies (EIT) that meet specific accessibility standards. In order to conform to the Section 508 EIT Accessibility Standards, the Contractor shall perform all work required under this contract in compliance with the provisions delineated in the Code of Federal Regulations (CFR) Title 36 (36 CFR Part 1194) and outlined below.

All electronic deliverables including reports, data entry, web pages, web applications, audio and video shall be Section 508-compliant; drafts do not need to be compliant. Detailed data that are meant to be processed by a program and not meant to be read by people do not need to be

Section 508-compliant. The following Section 508 accessibility technical standards apply to this

SOW:

E205.1 General Electronic content shall comply with E205.

The Contractor shall submit an annual Section 508 report in accordance with the schedule set forth in the ELECTRONIC AND INFORMATION TECHNOLOGY ACCESSIBILITY Article in SECTION H of the contract. Additional information about testing documents for Section 508 compliance, including guidance and specific checklists, by application, can be found at:

https://www.hhs.gov/web/section-508/index.html and at:

https://www.section508.gov/create/documents , "Create Accessible Documents."

Remediation of any materials that do not comply with the applicable provisions of 36 CFR Part 1194 as set forth in the SOW, shall be the responsibility of the Contractor.

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.

1.7.1 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 Program Manager 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.

1.8 Contracting Officer’s Representative

As determined by the CO, a COR will be appointed and identified by letter of designation, a copy of which will be provided to the Contractor by the CO. The designation letter states the responsibilities and limitations of the COR. The COR has the responsibility and authority to monitor all aspects of the day-to-day administration of the contract. Responsibilities include ensuring the timeliness and delivery of quality products and services to meet requirements of the contract.

1.9 Personnel

This contract requires a high degree of collaboration between Contractor staff, especially among the Principal Investigator (PI)/Program Manager (PM), toxicologists, computational toxicologists, toxicology data analysts, and chem/bio-informaticists. Each requirement described in this SOW shall be performed by an appropriate mix of professional, technical, and clerical staff. Contract personnel shall have the expertise to contribute to problem formulation and study design as required. Personnel assigned to this contract, including subcontractors and/or consultants, shall demonstrate to the COR that there are no conflicts of interest relative to the work to be performed prior to conducting work under the contract. Personnel assigned to this contract with access to federal IT resources may be required to pass a security investigation (Section 4).

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.

1.9.1 Professional Personnel

The Key Personnel (Principal Investigator and Program Manager) must be approved by the CO and shall be employees of the prime Contract organization and members of the professional staff. The Principal Investigator and Program Manager shall be responsible for the daily management of the contract and serve as points of contact for communication with Government officials. Collectively, the Principal Investigator and Program Manager are expected to be knowledgeable and involved in all aspects of the contract, including project status, record keeping, reporting, and detailed analysis of budget for all contract functions.

The Principal and Senior Toxicologists shall have the expertise in the following areas, including but not limited to computational toxicology; developmental/reproductive toxicology; endocrine disruption; carcinogenicity; inhalation toxicology; acute/chronic systemic toxicity testing; ocular and dermal toxicity testing; chem/bio-informatics; data management; regulatory testing methods and health hazard and safety assessment; and the development and/or validation of modern new approach methodologies, particularly Defined Approaches (DA) and Integrated Approaches to Testing and Assessment (IATA).

1.9.2 Technical Personnel

Technical Personnel shall work with the Principal and Senior Toxicologist to support the program depending upon the job functions, such as bioinformatician, computational chemists, data analyst, project coordinator, etc.

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, to include the source codes of software, 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.

1.10.1 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 in the Deliverables section above. In addition, annual reports shall be submitted for all activities as specified in the Deliverables section above. To the extent possible, the Government will retain unlimited access and rights to all materials, data, and technical information generated under the contract.

1.11 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 (including Subcontractors), 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.

1.12 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.

1.13 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.

1.14 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.

1.15 Safety Laws and Regulations

The Contractor shall comply with FAR 52.236-13, Accident Prevention (November 1991), In addition to other requirements for accident prevention specified in this contract, the Contractor shall comply with all Federal and State requirements governing safety and health protection.

The Contractor shall indicate its plan for compliance considering conditions of the work described by the design, technical proposal, operational activities of the Government or others in the area of the work, identification of the coordinator, and implementation of all other accident prevention provisions of this contract.

The Contractor shall complete and provide safety notifications as required by national, state, and local regulatory bodies, and will provide documented proof to the CO via the COR, no later than 10 days that such notifications were made.

2 Required Capability Areas

2.1 General Requirements

The Contractor shall provide services, qualified personnel, materials, equipment, and facilities needed to establish and/or utilize NAMs approaches, as well as to coordinate validation studies.

2.2 Research, Development and Validation of Computational Toxicological Approaches The Contractor shall assist the Government in acquiring and applying new and existing scientific knowledge to develop, evaluate, and validate novel computational approaches that can be used for human health safety and risk assessments, including but not limited to chemical screening and prioritization, hazard identification, classification and labeling, mechanisms of toxicity, organ-specific toxicities, identification of sensitive populations, windows of susceptibility, routes of exposure, read-across prediction, and quantitative risk assessment.

Data development, analysis, and evaluation represent a large portion of the daily work conducted under this requirement. These approaches include, but are not limited to:

computational systems biology/toxicology modeling; internal and external route-specific exposure assessment, modeling, and prediction; automated/assisted development of quantitative adverse outcome pathways (qAOPs); physiologically-based pharmacokinetic/pharmacodynamic (PBPK/PBPD) modeling; reverse toxicokinetic (RTK)/in vitro-to-in vivo extrapolation (IVIVE) modeling to correlate in vitro and in vivo bioactivity;

quantitative structure-activity relationship modeling (QSAR) and comparisons; application of Bayesian approaches to aid in the development of predictive models for risk assessment, QSARs, PB/PK, RTK, and qAOPs; application of artificial intelligence (AI) to structured and unstructured data to build predictive models, including but not limited to machine learning (ML), expert systems, and computer vision; knowledge graph capabilities to hypothesize causal relationships between chemical exposures and biological effects; analysis of quantitative high throughput screening (qHTS) and high content data; development of novel DA and IATA using in vivo, in vitro, and/or in silico data sets; etc.

The Contractor shall utilize information from diverse data streams and multiple databases (e.g., ICE, ToxRefDB, ToxCast, ExpoCast, DSSTox, CEBS, PDB, ECHA, EFSA/OpenFoodTox, IUCLID, PubChem, MassIVE, TCGA, NIH Data Commons, NCI Proteomic Data Commons, etc.) to assist the Government in developing, evaluating, and/or comparing the approaches listed above. The Contractor shall track data provenance, version of data and any limitations on publication of results.

The Contractor shall routinely review, evaluate, curate and integrate the data and information gathered in literature searches into new and existing databases maintained within the Government's network, with the goal of expediting the adoption and increasing the confidence in these methods by reducing the uncertainty and ensuring the quality of the data used in the validation of alternative test methods.

Activities utilizing computational approaches as directed by the COR include, but are not limited to:

a. Develop novel AOPs, including qAOPs and/or analyze the performance characteristics of proposed AOPs in the context of emerging scientific literature and novel computational approaches.

b. Perform curation and analysis of qHTS and develop predictive models of hazard, toxicity, and disease.

c. Perform curation and analysis of high content data (e.g., cell painting, metabolomics, proteomics, transcriptomics, whole genome sequencing) of toxicity or disease using internal and external resources for analysis as needed.

d. Provide robust and flexible computational toxicology solutions for hazard characterization and risk assessment based on information in scientific literature and data from in vitro, in vivo, and in silico systems.

e. Apply and enhance new and established computational approaches including data mining, data analysis, AI and ML, large scale SAR visualization, knowledge graphs, statistical and heuristic modeling, as well as the ability to extend or develop new techniques.

f. Develop chem/bioinformatics-based models of in vivo toxicity that rely on concomitant exploration of chemical descriptors, qHTS data, high content data, and population-based screening data.

g. Develop and maintain databases relevant to the analysis and evaluation of alternative toxicological methods (e.g., reference chemicals, retrospective compilation of testing results from the literature, HTS data, etc.).

h. Provide written reports and/or manuscripts based on the review and evaluation of comprehensive literature searches on selected topics.

Specific activities for developing computational approaches as directed by the COR can be found in Section 8.2.1.

2.3 Research, Development, and Validation of Alternative Test Methods The Contractor shall be familiar with testing and data requirements of federal regulatory agencies and the OECD Test Guidelines Programme6 necessary for conducting and publishing analyses and/or evaluations of data from alternative testing approaches as directed by the COR.

Additionally, the Contractor shall assist the Government in generating and/or using toxicity testing data to evaluate new, revised, and alternative test methods with regulatory applicability, and providing recommendations on their use to federal agencies. The work related to developing, evaluating, establishing confidence, and utilizing alternative methods in toxicological studies may include wet lab procedures, and includes, but is not limited to, cross qualification on protocols via interlaboratory studies, collecting, generating, and/or evaluating various data types such as bioactivity indication, bioreactivity screening, database searching, exposure assessment, in silico modeling of physiochemical structure and hazard, in vitro high-throughput screening, in vitro immuno-screening, microphysiological system testing, dose-response assessment, transcriptomic signatures, analysis of cell-based biological processes and/or toxicity pathways, kinetics and dose extrapolation, error-corrected next-generation sequencing, etc. Specific activities for qualification testing studies as directed by the COR can be found in Section 8.2.2. An export of the data shall be organized in the format compatible with storage in CEBS, as directed by COR.

For selected projects, if development and/or qualification efforts cannot be accomplished through the primary Contractor, the Contractor shall propose to the COR qualified laboratories to conduct validation testing under a subcontract mechanism and present them to the CO and COR for approval (Section 3.3). The Contractor shall be responsible for ensuring that the qualification study facilities and equipment meet all qualification requirements, including adherence to identified protocols, and that appropriate laboratory experience is available at the facility. The Contractor shall ensure that no institutional or individual conflict of interest (COI) issues exist for the coordination and/or selection of the laboratories participating in the qualification studies. No whole mammal or avian studies will be conducted under this contract, including by subcontractor.

Related to the work described above, the Contractor shall assist the Government in this area by identifying appropriate data, databases, and/or peer reviewed literature to assure the most current and accurate information available is being used to evaluate, as well as to assure that the reference information used in the reports can be substantiated and are in accordance with applicable guidelines. As needed for individual projects, Contract personnel shall have the expertise to contribute to problem formulation and study design as required. The Contractor shall make recommendations relevant to the adequacy of the available information for the Government's consideration in preparing NIEHS-required reports or review processes. This process may utilize the data development, analysis, evaluation, and validation of novel computational approaches mentioned in Section 2.2.

2.4 Meeting Support and Event Hosting

As directed by the COR, the Contractor shall provide support for Computational and NAMs meetings deemed necessary to carry out the goals and objectives of NIEHS/DTT either in-person, virtually, or a combination of in-person and virtual environments. These meetings include but are not limited to specific scientific meetings, export group meetings, workshops, webinars, symposia, seminars, and national and/or international professional meetings (e.g., Society of Toxicology annual meeting and World Congress). Contract staff may be required to attend NIEHS/DTT-sponsored meetings including workshops to provide on-site support as directed by the COR. For meetings conducted in public sessions, opportunities for public comment shall be provided before and during meetings. The Contractor shall work with the NIEHS Office of Communications and Public Liaison to obtain technical support for running the virtual component of the meeting.

The Contractor shall provide administrative, technical, and logistical support for the planning and execution of these meetings. Specific activities for supporting various types of meetings are provided in Section 8.2. As requested, the Contractor shall assist NIEHS/DTT in obtaining information from participants for COI screening. The Contractor shall handle travel arrangements for participants, subject to applicable Government regulations. Prior to confirming any arrangements for meetings, the Contractor shall consult with and receive approval from the COR. The Contractor shall provide support for managing or preparing materials for the meeting and drafting any needed documents, minutes/reports, notes, or summaries of major points from reports, minutes, or public comments. The Contractor shall also provide support for preparing information for meeting website(s), distributing materials, and handling communications with targeted individuals.

2.5 Communication Management

2.5.1 Website maintenance

NIEHS uses various websites and may need to develop new ones to communicate with the public and stakeholders. These websites include public and restricted access research report, registration sites for public meetings and public comments, web-tool for analysis, etc. The Contractor shall work with NIEHS and NTP website contractors to establish new websites, review substantive edits, and/or archive the pages that are no longer needed. The Contractor shall also work with NIEHS and NTP website contractors to update and modify the public websites with relevant information and edits in a timely manner as directed by the COR. The Contractor shall ensure the timely and accurate posting of materials and information on these websites. All final documents posted to the website shall be Section 508 compliant. The Contractor shall prepare the web access statistics report for these websites to be included in the monthly report. The Government may direct the Contractor to use specific software; for example, updating web pages may require the contractor use a particular Content Management System (CMS; current CMS is Drupal).

2.5.2 Database and information support

NIEHS has established several databases and model tools, containing high-quality curated toxicological data to support development and evaluation of new, revised, and alternative methods. The Contractor shall support the maintenance of existing and/or the development of new databases and tools by ensuring data interoperability among databases, incorporating supporting datasets, curating new datasets from the literature or other sources, identifying changes in data and endpoint level, data curation, updating database and associated websites, recording help videos and writing user manuals, organizing, and providing training events on the use of tools, etc.

The Contractor shall assist the Government in preparing updates to support documentation for use in the Environmental Factor, NTP Update, ALTEX News, and/or other planning and procedural documents necessary to complete the mission of NIEHS, including social media streams, and other news outlets.

2.5.3 Training support

DTT/NIEHS aims to promote the development, validation, and application of novel computational tools and alternative approaches that help researchers, regulators, and the public better understand how environmental agents can affect human health. As directed by the COR, the Contractor shall support education and training opportunities for federal stakeholder and public-sector scientists on computational and alternative approaches that include but are not limited to developing educational and training materials, participating in organizing conferences, workshops, and continuing education courses, and coordinating training and/or demo sessions.

3 Operating Procedures

3.1 Project Management

The Contractor shall provide project management support for the contract to include but not limited to:

Ensuring that the timeframes for each milestone are met Submitting deliverables in a timely manner Providing accurate invoices on time Managing personnel and staffing Providing project management and tracking Maintaining the transparency in operations Providing timely communication with the COR

Although the Contract, as a whole, shall be for the ongoing and recurring support for NIEHS/DTT computational and alternative toxicological research and testing evaluations, a research outline will be initiated and issued by the COR for each project to be conducted under the Contract. Each research outline will include a detailed description of study objectives, the study(s) to be performed, expected deliverable(s), and anticipated timeline. In response, the Contractor shall submit a technical work plan and budget outlining the proposed technical approach including detailed workflow, staffing plan, data management, milestone schedule, list of deliverable(s), and estimated budget describing the proposed costs and level of effort. The technical work plan and budget for the proposed project shall be submitted for approval by the COR prior to project initiation. In general, a specific study shall begin after the Government has reviewed the technical work plan, and any questions have been discussed and resolved between the Government and Contractor. As needed based on specific changes in a particular project, revisions may be made to these documents after study initiation. If the revisions are significant, the COR may request updated technical work plan and budget for the revision.

Over the course of a given project, the Government anticipates that the processes used to develop documents and research products and carry out related activities may change as program-related changes are implemented. Additionally, updates to the instructions for a specific activity may be made by the COR due to changing Government requirements or for particular cases due to the unique or complex nature of a particular assignment. Any updates to processes or instructions would be communicated in writing by the COR to the Contractor.

The Contractor shall use a DTT program and project management (PPM) software (i.e., Microsoft Dynamics 365 Project Service Automation)) specified by the Government to document and update research activities, including, but not limited to, research outlines submitted by the Government, technical work plans and budget information, milestone schedule, work status, interim data (in the form of tables, graphs, spreadsheets, and/or other documents), and deliverables. All substantive communication and decisions throughout the performance of work on an activity shall be documented within the software.

The Contractor shall ensure that all activities conducted, and all deliverables adhere to COR-approved instructions or specifications for content and format where applicable.

The Contractor shall maintain records on all activities of DTT/NIEHS. These records shall be available to the COR upon request.

Any incident or unforeseeable occurrence not listed in this document, or any change in personnel that might have an impact on fulfilling the requirements as described in the SOW shall be reported immediately to the COR.

Some activities performed under this Contract will require attending meetings at NIEHS or other government facilities. The NIEHS main campus is located at 111 T.W. Alexander Drive, Research Triangle Park, NC 27709 and the current NIEHS satellite campus is located at 530 Davis Drive, Morrisville, NC 27650.

3.2 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. This data management plan shall adhere to HHS Office of the Chief Information Officer (OCIO) policy8 and be approved by the COR. The Contractor shall keep all data and documents used or prepared confidential until Government publication. 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. Contractor shall use IDs and metadata interoperable with those used in the NIEHS/DTT data ecosystem for interoperability, accuracy and reliability across the NIEHS/DTT data ecosystem. Metadata shall meet DTT standards for discoverability and re-use. Sensitive data shall be stored securely in accordance with patient agreements. Code shall be stored in Government repositories such as but not limited to BitBucket or in GitHub as directed by COR. All research data products shall be registered in the DTT Research Data Catalog with metadata to facilitate discoverability.

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.

3.3 Subcontractors and Consultants

The Contractor, as directed by the COR, shall identify, and propose qualified laboratories and/or organizations to conduct the work as subcontractor(s) and present to the CO and the COR for approval. A detailed written subcontract plan shall be provided to the CO and COR. The subcontract plan shall include the area of expertise and related peer-reviewed journal articles authored by the proposed consultant relevant to the request, as well as cost and a detailed timeline of accomplishing this project. Only upon approval by the CO shall work at the subcontract organization begin. The Contractor shall ensure that no institutional or individual COI issues exist for the coordination and/or selection of the laboratories participating in the qualification testing studies.

The Contractor shall summarize subcontractor performance and include the summary in the Contractor’s monthly progress report to the COR. Information included in this summary shall consist of work performed by the subcontractor including deliverables, level of effort, and costs expended during the past month, etc. In addition, the Contractor shall provide a description of how the subcontract aided the Contractor in completing or nearing completion of a specific project within the monthly progress report. Once the specified project is completed, no further work shall be given to the subcontractor until a new detailed project plan is presented to the

COR.

The Contractor shall ensure that the employees of the prime contract and any subcontractors work together as a unified team. It should be transparent to the Government whether a contract employee works for the prime or a subcontractor. The Contractor and any subcontractors shall conduct or provide to their employees detailed instruction on government statutes, regulations, policies, and guidelines in areas such as employee conduct, ethics, safety, security, health, fire prevention, and the environment as they pertain to this contract.

3.4 Contractor Travel

The Contract staff shall anticipate attending meetings (via remote or in-person options; local, domestic, and/or foreign) to support DTT/NIEHS activities, and…