NICEATM_DRAFT-SOW_NIEHS_2023.pdf

Statement of Work for

Support for Evaluating and Conducting Computational and Alternative Toxicological Methods for the National Institute of Environmental

Health Sciences

Revised, May 2023

Table of Contents

SECTION 1: INTRODUCTION AND SCOPE OF WORK

SECTION 2: TECHNICAL REQUIREMENTS

2.1. RESEARCH, DEVELOPMENT, AND VALIDATION OF COMPUTATIONAL TOXICOLOGICAL APPROACHES

2.2. RESEARCH, DEVELOPMENT, AND VALIDATION OF ALTERNATIVE TEST METHODS

2.3. MEETING SUPPORT AND EVENT HOSTING

2.4. COMMUNICATION MANAGEMENT

2.4.1. Website maintenance

2.4.2. Database and information support

2.4.3. Training support

SECTION 3: PROGRAM AND PROJECT MANAGEMENT

3.1. PROGRAM MANAGEMENT

3.2. CONTRACTOR RESPONSIBILITY

3.3. CONTRACTOR PERSONNEL

3.4. PROJECT MANAGEMENT, PROJECT OUTLINES, AND WORK PLANS

3.5. SUBCONTRACTORS & CONSULTANTS

3.6. DELIVERABLES AND REPORTING REQUIREMENTS

3.6.1. Progress report

3.6.2. Publications and scientific reports

3.6.3. Supporting materials for coordinating and participating meetings

3.6.4. Databases and coding packages

3.6.5. Supporting materials for the NICEATM and ICCVAM websites

3.6.6. 508-compliance

3.7. TRAVEL REQUIREMENTS

SECTION 4. FACILITY, SECURITY, EQUIPMENT AND OTHER REQUIREMENTS

4.1. FACILITY

4.2. SECURITY AND DATA MANAGEMENT

4.3. EQUIPMENT

SECTION 4: APPENDIX

APPENDIX A. REFERENCE LINK

APPENDIX B. ACRONYMS AND ABBREVIATION

APPENDIX C. LIST OF SPECIFIC PROJECT TASKS

1. Validation of Alternative Test Methods

2. Supporting NICEATM and ICCVAM meetings

3. ICCVAM Peer Review/Expert Panel Meetings

4. NICEATM/ICCVAM Workshops, Symposia and Seminars

APPENDIX D. LIST OF DELIVERABLES

SECTION 1: INTRODUCTION AND SCOPE OF WORK

The mission of the National Institute of Environmental Health Sciences (NIEHS) is to discover how the environment affects people in order to promote healthier lives. The Division of Translational Toxicology (DTT) is an intramural division at NIEHS. 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 effort includes the development, validation, and application of alternatives for toxicity testing in partnership via the interagency Tox21 Program1 and/or the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM)2. ICCVAM is a permanent committee of NIEHS under the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)3. ICCVAM was formally established in 2000 by the ICCVAM Authorization Act (42 U.S.C. 285l- 3)4 to promote the research, development, validation, evaluation, acceptance, and use of new and alternative testing methods and strategies that are more predictive of human health and ecological effects than currently available methods and strategies. Such efforts are further refined in U.S. Strategic Roadmap document5. NICEATM is an office within DTT focused on the development and evaluation of alternatives to animal use for chemical safety testing. In addition to performing independent research and development (R&D) activities to provide bioinformatics and computational toxicology support for DTT/NIEHS research, NICEATM also carries out ICCVAM’s mission by providing technical and scientific support for ICCVAM and ICCVAM workgroup activities, reviewing proposed test methods, organizing workshops, etc.

NICEATM, on behalf of ICCVAM, receives proposed test method nominations or submissions and communicates with the submitting organization or individual. Typically, the ICCVAM evaluation process involves an initial assessment by NICEATM of the adequacy and completeness of the proposed test method nomination or submission, and a determination by ICCVAM of the priority that the proposed test method will have for technical evaluation. Once a proposed test method has been accepted for evaluation, ICCVAM assembles an interagency working group of government scientists with scientific and regulatory expertise in the appropriate scientific disciplines to collaborate with NICEATM on the evaluation process. Depending on the validation status of the proposed test method, ICCVAM, in conjunction with NICEATM, develops recommendations and priorities for further efforts. Such efforts might include an expert workshop, an expert panel meeting, a peer review meeting, a peer review process, or a validation study. The areas of focus for the research include but are not limited to population variability, susceptibility, developmental neurotoxicity, carcinogenicity, ecotoxicity, acute toxicity, etc.

New approach methodologies (NAMs) broadly refer to any technology, methodology, approach, and/or combination of the three that can provide information on chemical hazard and risk assessment without the use of animals, such as in silico, in chemico, in vitro, and ex vivo approaches. The objective of this R&D contract is to provide scientific and administrative support for the activities of DTT/NIEHS and ICCVAM to develop, 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 transferability of the alternative methods.

SECTION 2: TECHNICAL REQUIREMENTS

2.1. 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 the toxicological studies including but not limited to chemical prioritization, hazard identification, read-across prediction, and risk assessment in the context of human health. 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: Exposure assessment and modeling; Adverse Outcome Pathways (AOPs); Physiologically based pharmacokinetic/pharmacodynamic modeling; In vitro-to-in vivo extrapolation (IVIVE) modeling; Quantitative Structure-Activity Relationship modeling (QSAR) and comparisons; Analysis of quantitative high throughput screening and high content data; Development of novel Integrated Approaches to Testing and Assessment (IATA)6 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., Integrated Chemical Environment [ICE]7, ToxRefDB, ToxCast, ExpoCast, DSSTox, CEBS, etc.) to assist the Government in developing, evaluating, and/or comparing the approaches listed above.

The Contractor shall routinely review, evaluate, and integrate the data and information gathered in these literature searches into new and existing databases maintained within the Government's network (e.g., ICE), with the goal of reducing the uncertainty of the data used in the validation of alternative test methods.

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

a) Develop novel Adverse Outcome Pathways (AOPs) and/or analyze the performance characteristics of proposed AOPs in the context of emerging scientific literature and novel computational approaches.

b) Perform analysis of quantitative high-throughput screening (qHTS) and high-content (HC) data to provide models for initial hit selection and follow up.

c) Provide robust and flexible computational toxicology solutions for risk characterization based on data from in vitro, in vivo, and in silico systems.

d) Apply and enhance new and established computational approaches including data mining, data analysis, large scale Structure-Activity Relationship (SAR) visualization, statistical and heuristic modeling, as well as the ability to extend or develop new techniques.

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

f) 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.).

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

2.2. Research, Development, and Validation of Alternative Test Methods The Contractor shall be familiar with the OECD Test Guidelines Programme8 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 in accordance with ICCVAM Guidelines for the Nomination and Submission of New, Revised, and Alternative Test Methods (NIH Publication No. 03- 4508)9 and Validation and Regulatory Acceptance o/Toxicological Test Methods: a report of the ad hoc Interagency Coordinating (NIH Publication No. 97-3981)10. The projects related to develop, evaluate, and utilize alternative methods in toxicological studies may include but not limited to cross validations on protocols, interlaboratory data, bioactivity indication, bioreactivity screening, database searching, exposure assessment, in silico modeling of physiochemical structure and hazard, in vitro high-throughput screening, dose-response assessment, transcriptomic signatures, analysis of cell-based biological processes and/or toxicity pathways, kinetics and dose extrapolation, etc. Specific project tasks for validation studies as directed by the COR can be found in Appendix C1.

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 that the most current and well-defined 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 (e.g., ICCVAM Guideline9). 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 2.1 above.

The Contractor shall assemble a summary report for each project, including for test method Submissions/Nominations progressing or for forwarding with ICCVAM recommendations to regulatory agencies. The report shall include all the available information submitted, obtained, and/or analyzed.

For selected project, if development and/or validation 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 to the CO and COR for approval (Section 3.5). The Contractor shall be responsible for assuring that the validation 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 COI issues exist for the coordination and/or selection of the laboratories participating in the validation studies. No whole animal studies will be conducted under this contract, including by subcontractor.

2.3. Meeting Support and Event Hosting

As directed by the COR, the Contractor shall provide support for all meetings deemed necessary to carry out the goals and objectives of this contract in in-person, virtual, or a combination of in-person and virtual environments. These meetings include but are not limited to ICCVAM monthly meetings, ICCVAM Public Forums, ICCVAM workgroup meetings, workshops, webinars, the International Cooperation on Alternative Test Methods (ICATM) meetings, 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, NICEATM and/or ICCVAM-related meetings including workshops to provide on-site support as directed by the COR. For the ones 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 of the virtual component of the meeting.

The Contractor shall provide administrative, technical, and logistical support for the planning and execution of these meetings. Specific project tasks for supporting various type of meetings are provided in Appendix C2-C4. As requested, the Contractor shall assist NIEHS/DTT in obtaining information from participants for conflict-of-interest 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.

In addition to the ICCVAM monthly conference, as directed by the COR and approved by the CO, Contract staff may participate in ICATM and ICATM-partner (European Union Reference Laboratory for Alternative to Animal Testing, Japanese Center for the Validation of Alternative Methods, Korean Center for the Validation of Alternative Methods, and/or other international member organizations) meetings (e.g. Validation Management Team [VMT] meetings) depending on the project needs. The Contractor shall review and provide comments on any relevant draft documents produced by the ICATM-partner agencies.

The Contractor shall also provide meeting support to facilitate attendance of the ICATM partners at annual Scientific Advisory Committee on Alternative Toxicological Methods Meetings (SACATM)meetings. SACATM is a federally chartered external advisory group of scientists from the public and private sectors who provide input to ICCVAM, NICEATM, and NIEHS on programmatic activities and issues. The Contractor shall assist DTT Office of Policy, Review, and Outreach (OPRO) staff in arranging lodging, transportation, and travel and providing scientific and communication support as requested.

ICCVAM subcommittees are periodically established and charged with developing high-level guidance documents such as strategic plans, implementation plans, and progress reports. The Contractor shall coordinate subcommittee meetings and interagency working groups and assist the subcommittees in the preparation of draft and final documents, as directed by the COR. Subcommittee meetings may be accomplished via teleconference (TC) calls. The number of subcommittee members and frequency of meetings will vary depending on the task at hand.

2.4. Communication Management

2.4.1. Website maintenance

DTT/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 NICEATM/ICCVAM websites, registration sites for public meetings and public comments, etc. The Contractor shall work with NTP website contractors to establish new websites, review substantive edits and/or retire the pages that are no longer needed. The Contractor shall be responsible for updates of time-sensitive pages and minor edits independently, as directed by the COR, and 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 certain software; for example, updating web pages may require the contractor use a particular Content Management System.

The Contractor shall update and modify the websites with relevant information listed in Section 3.6.5 as directed by the COR.

2.4.2. Database and information support

DTT/NIEHS has established several databases and model tools, carrying high-quality curated toxicological data to support development and evaluation of new, revised, and alternative methods, such as ICE7 and OPERA11. The Contractor shall support the maintenance of existing and/or the development of new databases and tools by incorporating supporting dataset, identifying changes in data and endpoint level, data curation, updating database and associated websites, organizing, and providing training event on the use of tools, etc.

The Contractor shall assist the Government in preparing updates to support documentation for use in the NICEATM/ICCVAM section of the Environmental Factor, NTP Update, NTP Annual Report, ALTEX News, the ICCVAM Biennial Report, General Strategic Plan, and/or other planning and procedural documents necessary to complete the mission of NIEHS and/or ICCVAM, including social media streams, and other news outlets. The Contractor shall also maintain a current database of test method submissions and their review status, including a chronological record of all related transactions (meetings, correspondence, etc.) and respond to routine inquiries regarding ICCVAM and NICEATM activities.

2.4.3. Training support

DTT/NIEHS aims to promote the development 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 directly by the COR, the Contractor shall support education and training opportunities to scientists on computational and alternative approaches by developing educational and training materials, coordinating training and/or demo sessions, etc.

SECTION 3: PROGRAM AND PROJECT MANAGEMENT

3.1. Program Management

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

a) Ensuring that the timeframes for each milestone are met

b) Submitting deliverables in a timely manner

c) Providing accurate invoices on time

d) Managing personnel and staffing

e) Providing project management and tracking

f) Maintaining the transparency in operations

g) Providing timely communication with the COR.

3.2. Contractor Responsibility

The Contractor shall support work involved with the coordination of studies using computational and alternative approaches as well as other requirements listed in Section 2, including, but not limited to:

a) Providing scientific and technical support during the planning and finalization of the study design including preparation of documentation necessary to reach decisions on standardized test method protocols and chemical selection

b) Providing scientific and technical support necessary to implement and conduct the study

c) Documenting study progress

d) Providing scientific and technical support necessary to resolve technical and procedural, problems encountered during the study

e) Maintaining records documenting the activities and data generated during the study duration

f) Coordinating data analysis and final study report preparation

g) Compiling reference data necessary for the study.

The Contractor shall identify sources and furnish information necessary to fulfill this contract, such as source data and all necessary specifications for databases covered for the project as well as the necessary information pertaining to the web site maintenance.

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 and literature-based analysis activities shall be approved by the CORs.

The Contractor shall ensure that all activities conducted, and all deliverables are adhered to COR-approved instructions or specifications for content and format where applicable (e.g., ICCVAM guidelines).

The Contractor shall maintain records on all activities of DTT/NIEHS and ICCVAM activities. 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 CORs.

Some work from this contract support will require attending meetings at NIEHS or NIH in the Washington, DC area. The NIEHS main campus is located at 111 T.W. Alexander Drive, Research Triangle Park, NC 27709 and the NIEHS satellite campus is located at 530 Davis Drive, Morrisville, NC 27650.

3.3. Contractor 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 assigned work outlined in this SOW. The Contractor shall be responsible for all costs associated with training and necessary travel to ensure that staff maintain required certifications and proficiency to perform assigned duties. Contract personnel shall have the expertise to contribute to problem formulation and study design as required.

The Key Personnel (Principal Investigator and Program Manager) must be approved by the CO and shall be employees of the 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 the 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 Contractor shall employ and/or have access to staff with expertise in at least one of the following areas: acute/chronic systemic toxicity testing; ocular and dermal toxicity testing;

reproductive toxicology; computational toxicology; and modern new approach methodologies (NAMs), to include but not be limited to the assessment of endocrine active substances and/or development and validation of alternative toxicological methods.

This Contract requires a high degree of collaboration between Contract staff, especially between 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. Personnel assigned to this contract, including subcontractors and/or consultants, shall demonstrate that there are no conflicts of interest relative to NICEATM and/or ICCVAM 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).

3.4. Project Management, Project Outlines, and Work Plans

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 project outline will be initiated and issued by the COR for each project to be conducted under the Contract. Each project 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 work plan 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 plans.

Submission of project outlines by the Government, and technical work plans and budget information prepared by the Contractor shall be transmitted through a Government furnished program and project management (PPM) software (i.e., ORBIT and/or JIRA). All substantive communication and decisions throughout the performance of work on a study shall be documented within the software.

3.5. Subcontractors & 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 Contracting Officer (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 validation 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 task within the monthly progress report. Once the specified task 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

3.6. Deliverables and Reporting Requirements

The Contractor shall ensure that the reporting timeframes for each milestone are met. In general, specific formatting requirements will be provided by the COR. All electronic deliverables must be PC and MAC compatible unless otherwise specified by the COR. Each final document/report shall be submitted to the COR for review electronically in Microsoft Word and/or PDF formats and approval. Unless otherwise directed, all submitted electronic copies of final deliverables shall be Section 508-compliant (see section 3.6.7 in this SOW). Unless otherwise instructed, all reports submitted under this Contract shall reference the contract number, the title and type(s) of report, and the represented period on the first page of the report. Electronic copies of the Monthly Status Report, Invoices/Financial Reports, and other reports as directed shall be emailed to the CO. Summary of deliverables requirements can be found in Appendix D.

3.6.1. Progress report

Periodic status reports, including Monthly Status Reports, shall be submitted to the COR due on the 15th day of each month or the closest workday and provide details on the status of all active assignments, monthly web access statistics, current costs for active assignments, cumulative costs for the contract, including direct and administrative costs, and 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 deliverables, hours spent, cost, 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 task within the monthly status report. Monthly status reports shall also include all requests from the public, date of receipt, date of response, and response.

An Annual Report detailing all significant outcomes resulting from the requirements as described within the SOW and Contract, including a detailed breakdown of costs 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 is due to the COR, alternate COR, and the CO within 12 months from the effective date of the Contract and annually thereafter. Four weeks in advance of the Annual Report, the Contractor shall submit a draft Annual Report to the COR and alternate COR.

3.6.2. Publications and scientific reports

3.6.2.1. 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. 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 follow specific requirements of journals, NIEHS internal review and/or DTT quality assessment review for the manuscript is required prior to submission. The Contractor, as required by the COR, shall provide support in obtaining document covers and related graphics. The Contractor shall interface with the NIEHS arts/graphics contractor for their preparation as instructed by the COR.

The Contract staff who is the scientific expert leading the project 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 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.

3.6.2.2. 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.

Types of deliverable reports as results of validating alternative test method nominated through ICCVAM (Section 2.2) can be referenced to NICEAM report website12 and shall meet the ICCVAM validation and acceptance criteria10 and submission guidelines9.

3.6.3. 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 goals and objectives of NICEATM and ICCVAM. For NICEATM and ICCVAM-related meetings, the Contractor shall prepare the supporting materials (e.g., Federal Register Notices, agendas, registration materials, mailing announcements, flyers, brochures, meeting notebooks, etc.) before, during, and after the meeting as stated in Section 2.3. The Contractor shall also make this information available on the ICCVAM restricted website.

3.6.4. 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, HTS data, etc.).

The Integrated Chemical Environment (ICE)7, developed by NICEATM/DTT, provides 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 ICE database and website to keep the system components up to date with the latest releases and updates for each technology.

The contractor shall provide DTT/NIEHS a copy of the tool including binaries, documentation, and software generated. DTT/NIEHS shall have unrestricted rights to the tool for its own purposes including rights to use the software and modify the software and its documentation for DTT purposes. The Government shall own and have rights to modify, distribute, and share contractor source code and data unless stated otherwise by the COR.

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. Contractor shall provide updates to software to address evolving security policies and other standards as directed by the COR. Contractor shall supply support to ensure that the code can transfer smoothly to the government network and run as expected.

3.6.5. Supporting materials for the NICEATM and ICCVAM websites At the direction of the COR, the Contractor shall work with NTP website contractors and coordinate maintenance of, and updates to, the public and restricted Internet website for NICEATM and ICCVAM and shall adhere to HHS and NTP standards in compliance with Section 508. Password-accessible restricted websites for ICCVAM, its working groups, peer review panel sites, as well as additional sites as needed shall be established as directed by the COR. 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 NICEATM and ICCVAM websites may include but not limited to:

a) Posting of meeting dates to 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 NICEATM/ICCVAM meetings, workshops, symposia, seminars, and conference calls (telephonic or web-based) to public and restricted ICCVAM and ICCVAM workgroup sites, as appropriate.

c) Committee rosters.

d) Posters and abstracts for large professional meetings such as the Society of Toxicology, World Congress, etc.

e) Test method evaluation reports and related documents.

f) ICCVAM Biennial Progress Report (e.g., https://ntp.niehs.nih.gov/go/2021iccvamreport)

g) Federal Register notices with links.

h) NICEATM/ICCVAM reports such as the Biennial progress reports and other strategic planning documents.

i) Updating approved federal and international testing guidelines and regulations.

j) Listings or hyperlink access to all currently approved National (FDA, EPA, OSHA, CPSC, DOT) and international (ISO, OECD, ICH, UN Transport Committee) toxicity testing guidelines and requirements, as well as methods currently in development or validation (including EURL/ECVAM, JaCVAM, KoCVAM, Health Canada) and other relevant Internet sites.

3.6.6. 508-compliance Section 508 of the Rehabilitation Act of 1973, as amended, 29 U.S.C. 794d, requires federal agencies to ensure that people with disabilities can access to the Information and Communication Technology (ICT) which federal agencies develop, procure, maintain, or use. There are three regulations addressing the requirements detailed in Section 508. The Section 508 technical and functional standards are codified at 36 CFR Part 1194 and may be accessed through the Access Board's Web site13. The second regulation issued to implement Section 508 is the Federal Acquisition Regulation (FAR)14. FAR Part 39.2 requires that agency acquisitions of Electronic and Information Technology (EIT) comply with the Access Board's standards. The third applicable regulation is the HHS Acquisition Regulation (HHSAR)15.

Unless an agency exception to this requirement exists, the Contractor must conform to applicable Section 508 standards and must apply best practices associated with Section 508 compliance during the application design, development, and testing phases. The Contractor shall refer to standards found on HHS's Section 508 website16 for further guidance. Submission of electronic documents which satisfy the appropriate HHS Checklists and Standards will be considered acceptable. All electronic deliverables including Final Reports and all documents posted to the NICEATM/ICCVAM web pages shall be prepared, formatted, and checked for conformance with Section 508 standards, prior to delivery to NIEHS or posting to the websites, as appropriate.

https://ntp.niehs.nih.gov/go/2021iccvamreport

The following Section 508 accessibility standards apply to the content or material identified in this SOW:

36 CFR Part 1194.22 "Web-based Intranet and Internet Information and Applications" 36 CFR part 1194.41 "Information, Documentation, and Support"

3.7. Travel Requirements

The Contract staff shall anticipate attending meetings (via remote or in-person options; local, domestic, and/or foreign) to support NICEATM and/or ICCVAM-related activities, and to present scientific results at professional meetings as determined by the Contractor’s Principal Investigator and CORs. For the purposes of this Contract, a professional meeting is one that is planned or sponsored by a professional society and requires registration. On-site qualification of the subcontract laboratories by the Contractor may be required. Sponsored travel (travel that is financed by a non-Federal agency) may be accepted with prior approval by the COR and CO. All requests for travel must comply with current Government processes; all travel must be submitted to the COR and CO for approval prior to traveling.

Contract staff will be reimbursed at the Federal Government per diem rate for the city/state of the venue. Sponsored travel shall not be reimbursed as no travel costs are incurred. However, level of effort may be reimbursed if pre-approved by the COR and CO.

SECTION 4. FACILITY, SECURITY, EQUIPMENT AND OTHER

REQUIREMENTS

4.1. Facility

The Contractor shall provide space and facilities necessary to perform the work described in this SOW.

The conference room shall be equipped with a computer compatible projector and projection screen for seminars as well as with the capability to conduct virtual meetings via various platforms (e.g., Zoom, Microsoft Teams, etc.). It is anticipated that the maximum capacity of the conference room shall accommodate 20 persons.

4.2. Security and Data Management

Contract staff shall obtain appropriate security clearances (e.g., Homeland Security Presidential Directive 12, [HSPD-12])17 and onboarding trainings18 prior to accessing Federal Government IT resources. The Contract staff who require access shall obtain NIEHS security badges, NIH account, and comply with US Department of Health and Human Services Office of the Chief Information Officer (HHS OCIO) policy19 for connecting to the NIEHS information technology resources. Contract staff shall also complete all annual refresher training associated with the use of an NIH account in a timely manner.

The Government shall provide the Contractor access to the NIEHS and NIH electronic resources including but not limited to Citrix and Virtual Private Network (VPN) client software to access the NIH and NIEHS networks, NIEHS library, Content Management Software necessary to maintain NIEHS-hosted websites, Webtrends, or equivalent software to report on NIEHS-hosted websites, etc.

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 OCIO policy19 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 DTT research data management coordinator after acceptance by the COR. Contractor shall use IDs and metadata interoperable with those used in the DTT data ecosystem for interoperability, accuracy and reliability across the NIEHS data ecosystem. Metadata shall meet DTT standards for discoverability and re-use. Sensitive data shall be stored securely in accordance with patient agreements. All research data products shall be registered in the DTT Research Data Catalog with metadata to facilitate discoverability.

The Government will retain sole 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.

4.3. Equipment

The Contractor may request approval from the COR for computers, tools, software packages, or database products to be used by the Contractor to generate or analyze data and/or generate, maintain, or store information for Web pages. These tools and software package include but not limited to TIBCO Spotfire, Partek Genomics Suite, GastroPlus.

The Contractor is required to supply all equipment, property, and services needed to fulfill the SOW that are not explicitly specified as being provided by the Government. These materials include but are not limited to computers, printers, phones, Microsoft Office, Web-based conferencing software, and Adobe Acrobat Professional (for Section 508 compliance). Equipment such as computers and printers shall support Internet and Intranet connections, be compatible with NIH computer operating systems, and comply with NIH security policies.

The Contractor shall conform to security requirements or usability guidelines as appropriate. The Contractor shall maintain compatible versions of software applications and licensure and shall provide personnel properly trained with the latest releases and upgrades. Further, the Contractor shall provide a plan for maintaining computer skills as upgrades and computer program enhancements become available.

SECTION 4: APPENDIX

Appendix A. Reference Link

# Reference Link 1 Interagency Tox21

Program (Tox21) https://ntp.niehs.nih.gov/go/tox21

2 Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) https://ntp.niehs.nih.gov/go/iccvam

3 NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) https://ntp.niehs.nih.gov/go/niceatm https://ntp.niehs.nih.gov/go/tox21 https://ntp.niehs.nih.gov/go/iccvam https://ntp.niehs.nih.gov/go/niceatm

4 ICCVAM Authorization Act (42 U.S.C. 285l-3) https://ntp.niehs.nih.gov/iccvam/docs/about_docs/pl106545.pdf

5 A Strategic Roadmap for Establishing New Approaches to Evaluate the Safety of Chemicals and Medical Products in the United States https://ntp.niehs.nih.gov/go/natl-strategy

6 Integrated Approaches to Testing and Assessment

(IATA)

https://www.oecd.org/chemicalsafety/risk-assessment/iata/

7 Integrated Chemical Environment (ICE) https://ice.ntp.niehs.nih.gov/

8 OECD Test Guidelines Programme https://www.oecd.org/env/ehs/oecd-guidelines-testing-chemicals-related-documents.htm

9 ICCVAM Guidelines for the Nomination and Submission of New, Revised, and Alternative Test Methods (NIH Publication No. 03-4508) https://ntp.niehs.nih.gov/iccvam/suppdocs/subguidelines/sd_sub g034508.pdf

10 Validation and Regulatory Acceptance o/Toxicological Test Methods: a report of the ad hoc Interagency Coordinating Committee on the Validation of Alternative Methods (NIH Publication No. 97-3981) https://ntp.niehs.nih.gov/iccvam/docs/about_docs/validate.pdf

11 Open (Quantitative) Structure-activity/property Relationship App (OPERA) https://ntp.niehs.nih.gov/go/opera

12 NICEAM report website https://ntp.niehs.nih.gov/go/iccvam-rpts

13 Access Board's Web site http://www.access-board.gov

14 GSA Section 508 http://www.section508.gov

15 HHS Acquisition Regulation (HHSAR) http://www.hhs.gov/policies/hhsar/

16 HHS's Section 508 website https://www.hhs.gov/web/section-508/index.html

17 Homeland Security Presidential Directive 12 https://www.dhs.gov/homeland-security-presidential-directive-12

18 NIH onboarding website https://hr.nih.gov/working-nih/onboarding 19 US Department of Health and Human Services Office of the Chief Information Officer (HHS OCIO) policy https://www.hhs.gov/about/agencies/asa/ocio/cybersecurity/ind ex.html https://ntp.niehs.nih.gov/iccvam/docs/about_docs/pl106545.pdf https://ntp.niehs.nih.gov/go/natl-strategy https://www.oecd.org/chemicalsafety/risk-assessment/iata/ https://ice.ntp.niehs.nih.gov/ https://www.oecd.org/env/ehs/oecd-guidelines-testing-chemicals-related-documents.htm https://www.oecd.org/env/ehs/oecd-guidelines-testing-chemicals-related-documents.htm https://ntp.niehs.nih.gov/iccvam/suppdocs/subguidelines/sd_subg034508.pdf https://ntp.niehs.nih.gov/iccvam/suppdocs/subguidelines/sd_subg034508.pdf https://ntp.niehs.nih.gov/iccvam/docs/about_docs/validate.pdf https://ntp.niehs.nih.gov/go/opera https://ntp.niehs.nih.gov/go/iccvam-rpts http://www.access-board.gov/ http://www.section508.gov/ http://www.hhs.gov/policies/hhsar/ https://www.hhs.gov/web/section-508/index.html https://www.dhs.gov/homeland-security-presidential-directive-12 https://hr.nih.gov/working-nih/onboarding https://www.hhs.gov/about/agencies/asa/ocio/cybersecurity/index.html https://www.hhs.gov/about/agencies/asa/ocio/cybersecurity/index.html

20 Example of

NICEATM/ICCVAM

workshop report https://ntp.niehs.nih.gov/iccvam/docs/biologics-docs/bontwkshprept.pdf

Appendix B. Acronyms and Abbreviation

Abbreviation Full name CPSC U.S. Consumer Product Safety Commission DOT Department of Transportation ECVAM The European Centre for the Validation of Alternative Methods EPA U.S. Environmental Protection Agency EURL/ECVAM European Union Reference Laboratory for Alternative to Animal Testing FDA U.S. Food and Drug Administration ICATM International Cooperation on Alternative Test Methods ICCVAM The Interagency Coordinating Committee on the Validation of Alternative

Methods ICE Integrated Chemical Environment ICH International Council for Harmonisation of Technical Requirements for

Pharmaceuticals for Human Use ISO International Organization for Standardization JaCVAM The Japanese Centre for the Validation of Alternative Methods KoCVAM The Korean Centre for the Validation of Alternative Methods NICEATM NTP Interagency Center for the Evaluation of Alternative Toxicological Methods OECD Organisation for Economic Co-operation and Development OPERA Open (Quantitative) Structure-activity/property Relationship App ORBIT The Organizational Resource and Business Information Tool OSHA The Occupational Safety and Health Administration UN The United Nations VMT Validation Management Team

Appendix C. List of specific project tasks

1. Validation of Alternative Test Methods As directed by the COR, the Contractor shall support tasks involved with the coordination of validation studies including, but not limited to:

a) Providing scientific and technical support during the planning and finalization of the validation study design, including preparation of documentation necessary to reach decisions on standardized test method protocols and chemical selection.

b) Providing scientific and technical support necessary to implement and conduct an interlaboratory validation study with participating laboratories.

c) Providing scientific and technical support necessary to resolve technical and procedural problems encountered during studies.

d) Maintaining records documenting the activities and data generated during the validation study.

e) Coordinating data analysis and final study report preparation.

f) Compilation of reference data necessary for evaluating test method performance.

https://ntp.niehs.nih.gov/iccvam/docs/biologics-docs/bontwkshprept.pdf https://ntp.niehs.nih.gov/iccvam/docs/biologics-docs/bontwkshprept.pdf

2. Supporting NICEATM and ICCVAM meetings As directed by the COR, the Contractor shall provide administrative and technical support for NICEATM and ICCVAM meeting with work tasks including but not limited to:

a) Preparation of…