RFP_Attachment_3_SOW.pdf

Attachment #3

Support Contract for the National Toxicology Program Interagency Center for the

Evaluation of Alternative Toxicological Methods

September 2014

STATEMENT OF WORK

1 PURPOSE

The objective of this Research and Development (R&D) contract is to provide scientific and administrative support for the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM). NICEATM research supports activities of the NTP in general, and specifically the Biomolecular Screening Branch (BSB), the Tox21 consortium, and the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM).

2 BACKGROUND

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 NTP was organized to address increasing scientific, regulatory, and Congressional concerns about the human health effects of chemical agents in our environment. NICEATM contributes to the mission of NIEHS and the NTP by evaluating, developing, validating, and promoting the acceptance and utilization of improved safety assessment tools to protect, promote, and advance the health of people, animals, and the environment. The NICEATM Office is located at NIEHS in Research Triangle Park, NC and consists of two government professional staff augmented with off-site contract support (this solicitation).

In addition to supporting NIEHS and NTP, NICEATM is also responsible for ensuring compliance with the duties and provisions of the ICCVAM Authorization Act of 2000 (42 U.S.C. 285l-3)1. The overall goal of ICCVAM is 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. ICCVAM is a statutorily mandated interagency committee established under NICEATM. NICEATM carries out its mission by performing independent R&D activities as identified in Section 3.1, reviewing proposed test methods, organizing workshops, and facilitating peer reviews.

Proposed test methods include those submitted to ICCVAM by developers that include a complete submission package as well as those nominated by the general public or the Member Agencies making up ICCVAM that require additional validation studies, also supported through this contract.

Toxicology is shifting toward toxicity-pathway assays and targeted testing as described in the 2007 National Research Council report Toxicity Testing in the 21st Century: A Vision and a Strategy.2 This report emphasizes the use of human-derived cells, cell lines, and cell-component testing platforms in toxicity testing. NICEATM, with support from its contract, will develop and validate a variety of in vitro and computational approaches that can be used to more accurately predict human health effects while also replacing or reducing the use of animals in toxicity testing. No animal studies will be conducted under this contract.

3 TECHNICAL REQUIREMENTS

3.1 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 chemical prioritization, hazard identification, 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;

• Physiologically based pharmacokinetic/pharmacodynamic modeling;

• Reverse toxicokinetic modeling;

• Quantitative Structure-Activity Relationship modeling and comparisons;

• Analysis of quantitative high throughput screening and high content data; and

• Development of novel Integrated Testing and Decision Strategies (ITDS) and/or Integrated Approaches to Testing and Assessment (IATA) using in vivo, in vitro and/or in silico data sets.

The Contractor shall utilize new information from diverse data streams and multiple databases (e.g., ToxRef DB, ToxCastDB, ExpoCastDB, DSSTox, CEBS, etc.) to assist the Government in developing, evaluating, and/or comparing the approaches listed above. In addition, as directed by the Contract Officer’s Representative (COR), the Contractor shall develop Adverse Outcome Pathways (AOPs), in accordance with guidelines proposed by the Organization for Economic Co-operation and Development (OECD)3, for novel AOPs of interest to Federal agencies. As directed by the COR, the Contractor shall routinely analyze the performance characteristics of proposed AOPs in the context of emerging scientific literature and novel computational approaches.

To explore utility of alternative methods, the Contractor shall always be in search of identifying, retrieving , and comparing data generated from novel methods with extant data from traditional methods found in the published literature. Using public and proprietary databases, the Contractor shall gather all relevant production, use, exposure, and toxicological information on selected chemicals and mixtures currently included in or under consideration for inclusion in Tox21-related efforts or of interest to the Government. The Contractor shall routinely review, evaluateand integrate the data and information gathered in these literature searches into new and existing databases maintained within the Government’s network, with the goal of reducing the uncertainty of the data used in the validation of alternative test methods. Information maintained within the databases will be used to make recommendations regarding the content of the reports written and/or approved by the Government. Upon request, the Contractor shall prepare comprehensive reports in various forms and formats to be used as supporting documentation for NTP (Government) required reports. Based on the immediate needs, the COR will provide guidance on the content and format of the requested information. The COR and the Contractor shall agree on the timeline for each request.

3.2 Research, Development, and Validation of Alternative Test Methods

In order to promote the research, development, validation, acceptance, and use of new and alternative testing methods and strategies, the Contractor, in support of the Government, shall coordinate the evaluation of submitted and nominated test methods from various sources. For clarification:

• Test methods with adequate validation studies to characterize their usefulness and limitations are considered “submissions.” Tasks related to submissions include:

o Draft Pre-Screen Evaluation (Section 3.2.1);

o Test Method Technical Review Document (Section 3.2.4);

o Peer Review Meeting (Section 3.3.2); and o Test Method Evaluation Report (Section 3.2.5).

• Test methods lacking sufficient validation information are submitted to the Government as “nominations.” Tasks related to nominations include:

o Draft Pre-Screen Evaluation (Section 3.2.1);

o Coordination of Validation Study (Section 3.2.2);

o Background Review Document (Section 3.2.3);

o Test Method Technical Review Document (Section 3.2.4);

o Peer Review Meeting (Section 3.3.2); and o Test Method Evaluation Report (Section 3.2.5).

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 or complete submitted and nominated methods, as well as to assure that the reference information used in the reports/packages can be substantiated and are in accordance with applicable guidelines (cited in 3.2.1 below) provided by the Government for this effort. The Contractor shall make recommendations relevant to the adequacy of the available information. Recommendations shall be provided in the form of draft documents for the Government’s consideration in preparing NTP-required reports or review processes. This process utilizes the data development, analysis, evaluation, and validation of novel computational approaches mentioned in Section 3.1 above. The information included in this Statement of Work represents the current process workflow;

it is subject to change, at the direction of the COR, over the period of performance of the contract.

3.2.1 Test Method Pre-Screen Evaluations and Pre-Screen Evaluation Report

The COR will provide Test Method Submission/Nomination Packages to the Contractor for evaluation. The Contractor shall review the information provided in the Test Method Submission/Nomination for completeness with regard to each of the ICCVAM validation and acceptance criteria as published in the most current version of Validation and Regulatory Acceptance of Toxicological Test Methods: a report of the ad hoc Interagency Coordinating Committee on the Validation of Alternative Methods4, 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.

The Contractor shall develop a Draft Pre-Screen Evaluation Report for Test Method Submission/Nomination Packages as directed by the COR. The Draft Pre-Screen Evaluation Report shall include details on the extent to which the Test Method Submission/Nomination Package meets the current ICCVAM validation and acceptance criteria4 and submission guidelines.5 The Contractor shall summarize the available information for each criterion, review statistical methods, comment on the appropriateness of the methods used and if methods were applied and interpreted appropriately. In addition, the Contractor shall include a current literature review for each proposed Test Method, including their search strategy, and their professional scientific interpretation of the adequacy of the extant literature. The Contractor shall make recommendations concerning additional steps needed to meet validation and acceptance criteria and submission guidelines.

The Contractor shall submit the Draft Pre-Screen Evaluation Report for review, comment, and/or approval by the COR within the timelines agreed upon by the COR and Contractor. The Contractor shall integrate COR-generated comments into the Draft Pre-Screen Evaluation Report and re-submit the Draft Pre-Screen Evaluation Report to the COR for approval.

The COR will forward the approved Draft Prescreen Evaluation Report to ICCVAM and appropriate ICCVAM Working Groups for review and comments. As directed by the COR, the Contractor shall address ICCVAM requests for clarification and additional information as well as incorporate recommended changes into the Draft Final Prescreen Evaluation Report and shall submit the Report to the COR for final review within the agreed upon timeline. Upon approval by the COR, this document becomes Final.

3.2.2 Coordination of Validation Studies

Occasionally, additional validation studies of Test Method Submissions/Nominations will be necessary. The purpose of a validation study is to evaluate a Test Method for its predictive performance (i.e., accuracy in prediction of the target endpoint) and reliability. As directed by the COR, the Contractor shall support tasks involved with the coordination of validation studies including, but not limited to:

• 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;

• Providing scientific and technical support necessary to implement and conduct an interlaboratory validation study with participating laboratories;

• Documenting study progress;

• Providing scientific and technical support necessary to resolve technical and procedural problems encountered during studies;

• Maintaining records documenting the activities and data generated during the validation study;

• Coordinating data analysis and final study report preparation; and

• Compilation of reference data necessary for evaluating test method performance.

Any necessary ICCVAM-identified validation work is usually conducted through collaborations with domestic and international partners; however, if additional validation efforts cannot be accomplished through such in-kind donations, the Contractor shall propose to the COR qualified laboratories to conduct validation testing under subcontract. On-site qualification of the subcontract laboratories by the Contractor may be required, as directed and approved by the COR. Therefore, practical laboratory experience shall reside within the Contract organization. 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 either at the Contractor’s facility or through subcontract organizations; any cells used for the conduct of validation studies shall be obtained from commercial sources.

3.2.3 Test Method Background Review Documents (BRDs)

As directed by the COR, the Contractor shall develop Background Review Documents (BRDs), in Draft and Final Draft versions, according to the timeframe established for BRD preparation, incorporating all data and reports resulting from additional Validation Studies. The Contractor shall organize the comprehensive BRDs in accordance with the most current version of the ICCVAM Test Methods Submission Guidelines.5 The Contractor shall recommend, with appropriate justification, a list of reference chemicals/substances for use in validating test methods. The Contractor shall structure each BRD in a monograph format, shall provide to the COR the document in an electronic camera-ready format as appropriate for NIH publications, and coordinate the printing and distribution of those documents designated by the COR as NIH publications.

3.2.4 Test Method Technical Review Document

For Test Method Submissions/Nominations recommended for Peer Review, and as directed by the COR, the Contractor shall assemble a Test Method Technical Review Document. Each Test Method Technical Review Document shall include all available information submitted, obtained, and/or analyzed during the pre-screen process, including the Pre-Screen Evaluation Report and/or the Background Review Document, as appropriate. Unless otherwise directed by the COR, the Contractor shall adhere to the most current version of the ICCVAM Test Method Submission Guidelines5 for guidance on document organization and content.

3.2.5 Test Method Evaluation Report (TMER)

As directed by the COR, the Contractor shall assemble a Test Method Evaluation Report (TMER) for all Test Method Submissions/Nominations progressing through peer reviews. The Contractor shall include all of the available information submitted, obtained, and/or analyzed during the pre-screen process as a Test Method Technical Review Document. The organization and information provided in the TMER will adhere to that listed in the most current version of the ICCVAM Test Method Submission Guidelines5, or as otherwise directed by the COR. This task involves the review and technical evaluation of Test Method Pre-Screen Evaluation Report and/or a Background Review Documents, as appropriate. The Contractor shall structure each TMER in a monograph format, shall provide to the COR the document in an electronic camera-ready format as appropriate for NIH publications, and coordinate the printing and distribution of those documents designated by the COR as NIH publications. The Peer Review Report (see Meeting Support, below) is included as an appendix to the TMER.

3.2.6 Review of Validation Studies and Test Guidelines

In accordance with the ICCVAM Authorization Act, the Contractor shall support the review of validation studies conducted through third party organizations and/or Test Method Guidelines to determine their relevance to the ICCVAM member agencies. In support of this effort, the Contractor shall anticipate that Contract staff members may participate on appropriate working groups or teams and report to NICEATM and/or ICCVAM, when and as appropriate. As directed by the COR, the Contractor shall prepare comments on the adequacy and limitations of specific validation studies/test method guidelines in the context of U.S. regulatory testing requirements (Validation Study/Test Method Guideline Relevance Report). ICCVAM will review and comment on the Relevance Report; appropriate comments will be forwarded through appropriate channels to the originators of the validation studies/test method guidelines. Upon review, validation studies/test method guidelines may be recommended for a formalized Peer Review.

3.3 Meeting Support

3.3.1 General Meeting Support for NICEATM- and ICCVAM-related Meetings [including ICATM (International Cooperation on Alternative Test Methods) and ICATM-Partner Agency 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, including but not limited to:

a) Providing recommendations for subject matter experts and participants for each specific meeting, either within or outside Federal Government;

b) Evaluating recommended subject matter experts for potential conflict of interest issues;

c) Planning and coordination of ICCVAM-related peer reviews/expert panels, workshops/symposia, and/or seminars, or other relevant meetings as directed by the COR;

d) Provide administrative and logistical support associated with planning and execution of meeting events, including, but not limited to, identification of meeting venue (including arrangements for hotel blocks of rooms), ensuring the functionality of audio/visual equipment, taking meeting minutes, organizing presentations;

e) Preparation, duplication, and distribution of pre-meeting, meeting, and post-meeting materials;

f) Preparation of invitations and associated correspondence for prospective participants;

g) Preparation and completion of travel arrangements, reimbursements, and honoraria, as appropriate, for invited non-Federal Government participants and Contract staff;

h) Preparation of all electronic presentations for meetings, as needed;

i) Provide oral technical presentations reflecting R&D activities conducted by NICEATM or other third party organization;

j) Meeting support for both on-site and off-site participants, including support for off-site participants via a COR-approved web-based conferencing service;

k) Posting of meeting materials to the NICEATM/ICCVAM website (public and/or restricted domains, as appropriate) in a timely fashion both advance of and at the completion of all meetings ;

l) Transcription of proceedings of all public meetings;

m) Preparation of a summary of all public meetings;

n) Preparation and revision of draft and final reports of all public or other meetings as directed by the COR;

o) For peer review/expert panel meetings, provide assistance to the Panel in formatting the Peer Panel

Report;

p) Participate in meetings external to, but focused on, ICCVAM and ICATM-relevant topics, with the purpose of sharing information with the COR and ICCVAM, as appropriate.

All final documents and reports shall be essentially error free; manuscripts received from Contractor shall be ready to send directly to NIEHS internal review with minimal additional editing by the COR.

The Contractor shall anticipate Contract Staff travel (local, domestic, and/or foreign) to support NICEATM and/or ICCVAM-related meetings and/or activities and to present ICCVAM and NICEATM data at professional meetings. For the purposes of this contract, a professional meeting is one that planned or sponsored by a professional society and requires registration. The Contractor shall anticipate that Contract staff may be required to attend the World Congress on Alternatives and Animal use in Life Sciences (not to exceed 4 Contract Staff) and the annual Society of Toxicology Meeting (not to exceed 3 Contract Staff). The 9th World Congress was in Prague, Czech Republic in 2014. On-site qualification of the subcontract laboratories by the Contractor may be required. All requests for travel must comply with current Government processes; all travel other than local must be submitted to the COR and CO for approval PRIOR to traveling. Sponsored travel (travel that is financed by a non-Federal agency) may be accepted in limited situations, with PRIOR APPROVAL by the COR and CO. The acceptance of this type of travel must not create an actual or apparent conflict of interest. Contract staff shall adhere to NIH travel policies as detailed at:

http://oma1.od.nih.gov/manualchapters/management/1500/.

ICCVAM meets approximately four times per year for a one-day meeting usually held on the NIH campus in Bethesda, MD. It is estimated that one Contract staff member may be required to attend ICCVAM meetings in order to provide on-site support.

The Contractor shall provide administrative and logistical travel assistance as described above for all invited members of ICATM and necessary Contract staff, as identified by the COR, for ICCVAM-related meetings and domestically held ICATM meetings. Contract staff will be reimbursed at the Federal government per diem rate for the city/state of the venue. The Contractor shall anticipate that Contract staff may be required to perform international travel. As directed by the COR, Contract staff shall participate in ICATM and ICATM-partner (European Union Reference Laboratory for Alternative to Animal Testing, Japanese Center for the Validation http://oma1.od.nih.gov/manualchapters/management/1500/ of Alternative Methods, Korean Center for the Validation of Alternative Methods, and/or other international member organizations) meetings, to include, but not limited to Validation Management Team (VMT) meetings.

The Contractor shall review and provide comments to the COR on any relevant draft documents produced by the ICATM-partner agencies. The COR will transmit comments to ICCVAM and/or ICATM partner through the appropriate channels of communication.

The Contractor shall provide meeting support as described above to facilitate attendance of the ICATM partners at the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM). SACATM meets up to twice a year at NIEHS in Research Triangle Park, NC.

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 shall be accomplished via teleconference (TC) calls. The number of subcommittee members and frequency of meetings will vary depending on the task at hand.

3.3.2 NICEATM Peer Review/Expert Panel Meetings

When adequate validation studies are available for new Test Methods, peer review/expert panels composed of subject matter experts from industry, academia, and government, and including the international community, are convened and charged with developing a scientific consensus on the validation status of the proposed test method, including its usefulness and limitations for generating information for specific human health and/or ecological risk assessment purposes. NTP’s Office of Liaison, Policy and Review (OLPR) organizes the review of data reported in the NICEATM-prepared Test Method Technical Review Document. Reviews are most often conducted in a meeting environment; occasionally, mail reviews may be more appropriate. As directed by the COR, the Contractor shall provide organizational and administrative assistance to NTP’s OLPR to facilitate Peer Review/Expert Panel Meetings. In addition to being responsible for all general meeting support as described in 3.3.1, the Contractor shall prepare a Test Method Technical Review Documents (see section 3.2.4 above), as directed by the COR.

The Contractor shall ensure that each Peer Review/Expert Panel report is structured in a monograph format, shall provide the document to the COR substantially error free, in an electronic camera-ready format as appropriate for NIH publications, and coordinate the printing and distribution of those documents designated by the COR as NIH publications.

Published reports of panel evaluations and ICCVAM recommendations regarding the scientific validity and potential acceptability of test methods are forwarded to ICCVAM member agencies for their consideration.

Each Federal Agency then determines the regulatory acceptability of a method according to its statutory mandates and in accordance with P.L. 106-545.

3.3.3 NICEATM and ICCVAM Workshops/Symposia and Seminars

When adequate validation studies have not yet been conducted for a test method(s), workshops are convened as needed to:

• Evaluate the adequacy of current methods for assessing specific toxicities;

• Identify areas in need of improvement or new methods;

• Assess the current validation status of available methods; and

• Recommend additional research, development, and validation activities.

The deliberations of panels and workshops are conducted in public sessions, and opportunities for public comment are provided before and during meetings. NICEATM conducts national and international workshops, symposia, and seminars on alternative toxicological methods and approaches to reduce, refine, and replace animal used in testing of interest to ICCVAM and NTP. The Contractor shall provide meeting-associated administrative and logistical support as detailed in 3.3.1. The Contractor is responsible for the development of a report for each Workshop/Symposium; each Workshop/Symposium Report shall be structured as a monograph and shall be provides to the COR in an electronic camera-ready format as appropriate for NIH publications. The Contractor shall coordinate the printing and distribution of those documents designated by the COR as NIH publications.

3.4 Maintenance of the NICEATM/ICCVAM Web Site and Webinar Hosting

NICEATM uses public and restricted access websites (see http://ntp.niehs.nih.gov/go/niceatm and http://ntp.niehs.nih.gov/go/iccvam) to communicate with the public and stakeholders. The Contractor shall ensure the timely and accurate posting of materials and information on the ICCVAM and NICEATM websites, as directed by the COR. All final documents posted to the website shall be Section 508 compliant. In addition, the Contractor shall have the capacity to organize, initiate, and participate on Webinars on topics of interest to NICEATM and/or ICCVAM, and provide technical support for remote viewers.

3.5 Ad Hoc Expertise

While the Government composes its list of Contract Staff specifications based on past experience and anticipated future needs, they cannot predict the specific types of subject matter expertise required to evaluate new emerging technologies or novel test methods. The types of ad hoc expertise that could be anticipated include, but are not limited to: toxicologists with expertise in drug metabolism, drug absorption, chemical assessment, pharmacokinetics, or other specialized area; informaticists with biological and/or chemical specialization; specialized computer code developers; statisticians; technical writers, including writing for the web and translating scientific concepts for lay audiences; etc.

If specific expertise outside of the Contractor’s staffing capabilities is needed requiring a consultant to prepare work or documents for test methods or technologies under review, the Contractor shall provide a detailed written project plan to the CO and COR for approval. The project plan shall include the area of expertise and http://ntp.niehs.nih.gov/go/niceatm http://ntp.niehs.nih.gov/go/iccvam 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. The CO and the COR must approve this plan before any contract is signed with the consultant. Once the specific task is completed, no further work shall be given to the consultant until a new detailed project plan is presented to, and approved by, the CO and COR. The Contractor shall ensure that no COI issues exist for the any proposed ad hoc consultant and the assigned task.

3.6 Other NICEATM Support

The Contractor shall assist the Government in preparing updates to support documentation for use in the NICEATM/ICCVAM section of the NTP Annual Report, the ICCVAM Biennial Report, General Strategic Plan, and/or other planning and procedural documents necessary to complete the mission of ICCVAM.

Other related assistance shall include, but is not restricted to:

a) Maintaining current status reports on the activities of NICEATM, ICCVAM (Government), test method submissions, peer review panels;

b) Updating the website with current information on ICCVAM activities and maintaining current listing of, or access to, approved federal and international testing guidelines and regulations;

c) Preparing summaries of new or revised regulations to update the website;

d) Assist in preparing support documents and correspondence associated with ICCVAM and NICEATM activities as directed;

e) Maintaining a current database of test method submissions and their review status, including a chronological record of all related transactions (meetings, correspondence, etc.);

f) Responding to routine inquiries regarding ICCVAM and NICEATM activities;

g) Assist the COR with archiving documents in accordance with the ICCVAM File Management Plan

(Appendix C).

After the Government has approved the final editing of documents, the Contractor shall distribute the published reports and proceedings within five (5) working days of receipt of such requests in a format approved by the

COR.

4 DELIVERABLES AND REPORTING REQUIREMENTS

4.1 Introduction

A deliverable is the product of work done on this contract; the finished result of a step of work; or any unique and verifiable product, result, or capability to perform a service that must be produced to complete a process, phase, or project under this contract. Required Reports (below) for all contract activities shall comply with requirements in respect to submission milestones, report formats and content, and reporting timeframe. All submitted electronic copies of final deliverables shall be Section 508-compliant as detailed below. Any document, including presentations, posted to a website shall be 508 compliant. Additional details regarding 508-compliance of electronic documents are found at http://www.hhs.gov/web/508/index.html. A complete list of Deliverables is detailed in Attachment #3.

http://www.hhs.gov/web/508/index.html

The following shall apply to all work performed by the Contractor:

a) All documents received from the Contractor shall be prepared in accordance with NIH style manuals, specific requirements of journals, and in compliance with the Federal Plain Language Guidelines, March 2011.1

b) The Contractor shall follow the NIH Publication Standards for print materials. Materials produced by the Contractor shall not exceed the limitations imposed by the Government Printing and Binding Regulations2 published by the Joint Committee on Printing, Congress of the United States.

c) All final electronic deliverables received from the Contractor shall be Section 508 compliant as required by Section 508 of the Rehabilitation Act (29 U.S.C. 794d), as amended by the workforce Investment Act of 1998 (P.L. 105-220), August 7, 1998.3 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 site at http://www.access-board.gov. The second regulation issued to implement Section 508 is the Federal Acquisition Regulation (FAR). FAR Part 39.2 requires that agency acquisitions of Electronic and Information Technology (EIT) comply with the Access Board’s standards. The entire FAR is found at Chapter 1 of the Code of Federal Register (CFR) Title 48, located at http://www.acquisition.gov. The FAR rule implementing Section 508 can be found at http://www.section508.gov. The third applicable regulation, the HHS Acquisition Regulation (HHSAR), can be found at http://www.hhs.gov/policies/hhsar/.

d) The quantity and diversity of materials required for this contract (e.g., documents, publications, posters, and presentations) requires a flexible delivery schedule. Upon assignment of a specific task by the COR, the Contractor shall prepare and submit within two working days, written timelines, milestones, and deliverables for both draft and final materials for approval by the COR prior to project initiation.

e) The Contractor shall provide all deliverables to the COR in accordance with the timeline prepared by the Contractor and approved by the COR at the start of each activity.

f) All documents received by the COR shall be edited and substantially error free.

a. On a Contract Basis

a) For each new assignment, the Contractor shall submit for approval by the COR a detailed Draft Project plan, including timelines, milestones, and all deliverables (both draft and final draft) for the proposed project prior to project initiation.

b) The Contractor shall maintain a current database of Test Method Submissions/Nominations and the review status of each method, including a chronological record of all related transactions (meetings, http://www.access-board.gov/ http://www.acquisition.gov/ http://www.section508.gov/ http://www.hhs.gov/policies/hhsar/ correspondence, etc.). The Contractor shall make this information available on the ICCVAM (restricted) website.

c) The Contractor shall develop and maintain rosters for ICCVAM, ICCVAM working groups, subcommittees, peer/expert panel meetings, and workshops/symposia.

d) The Contractor shall maintain current status reports on all activities of NICEATM, ICCVAM, ICCVAM working groups, peer review/expert panels, workshops/symposia, and other activities. These status reports shall be available to the COR upon request.

b. Research, Development and Validation of Computational Toxicological Approaches

Deliverables for pre-validation screening will vary depending on the project, and will be specifically identified at the beginning of each new project. In general, the Contractor, as directed by the COR, shall:

a) Perform analysis of qHTS and HC data to provide models for initial hit selection and follow up;

b) Provide robust and flexible computational toxicology solutions for risk characterization based on data from in vitro (to include qHTS and HC data), in vivo, and in silico systems;

c) 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 in support of NICEATM research efforts;

d) 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;

e) Develop novel AOPs, in compliance with the guidelines proposed by the OECD4 for responses of interest to Federal agencies, or analyze the performance characteristics of AOPs proposed by OECD and other institutions;

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 solutions for incorporating data from the Big Data to Knowledge (BD2K) initiative (http://www.nih.gov/news/health/dec2012/od-07.htm) into NICEATM R&D efforts;

h) Submit comprehensive written reports based on the review and evaluation of comprehensive literature searches on topics identified by the COR.

i) Publish results in peer-reviewed journals in a timely manner.

c. Research, Development and Validation of Alternative Test Methods http://www.nih.gov/news/health/dec2012/od-07.htm

i. Test Method Prescreen Evaluation and Prescreen Evaluation Report

The Contractor shall be responsible for completing a Prescreen Evaluation for each Test Method Submission/Nomination Package as directed by the COR. The COR will provide the Contractor with Test Method Submission/Nomination Packages proposed for evaluation. For each Test Method Submission/Nomination package, the Contractor shall develop a Draft Pre-Screen Evaluation Report detailing the extent to which the Test Method Prescreen Evaluation package meets the ICCVAM validation and acceptance criteria5 and submission guidelines.6 The Test Method Prescreen Evaluation Report shall summarize the available information for each criterion, review statistical methods, comment on the appropriateness of the application and interpretation of methods used within each Nomination/Submission Package. In addition, the Contractor shall include as part of the Report a current literature review for each proposed Test Method, including the Contractor’s search strategy, and their professional scientific interpretation of the adequacy of the extant literature. The Contractor shall make recommendations concerning additional steps needed to meet validation and acceptance criteria and submission guidelines.

The Contractor shall submit the Draft Pre-Screen Evaluation Report for review, comment, and/or approval by the COR within the timelines agreed upon by the COR and Contractor. The Contractor shall integrate COR-generated comments into the Draft Pre-Screen Evaluation Report and re-submit the Draft Pre-Screen Evaluation Report to the COR for approval.

The COR will forward the approved Draft Prescreen Evaluation Report to ICCVAM and appropriate ICCVAM Working Groups for review and comments. As directed by the COR, the Offeror shall address ICCVAM requests for clarification and additional information as well as incorporate recommended changes into the Draft Final Prescreen Evaluation Report and shall submit the Report to the COR for final review within the agreed upon timeline. Upon approval by the COR, this document becomes Final.

ii. Coordination of Validation Studies

The Contractor shall support tasks involved with the coordination of validation studies including, but not limited to: 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; providing scientific and technical support necessary to implement and conduct an interlaboratory validation study with participating laboratories; documenting study progress;

providing scientific and technical support necessary to resolve technical and procedural problems encountered during studies; maintaining records documenting the activities and data generated during the validation study;

coordinating data analysis and final study report preparation; and compilation of reference data necessary for evaluating test method performance.

In the event that ICCVAM recommends additional validation studies that cannot be accomplished through collaborations with our domestic or international partners, the Contractor, as directed by the COR, shall identify and propose qualified laboratories to conduct the validation studies for targeted testing to fill essential data gaps.

Subcontract laboratories may be engaged to carry out laboratory studies, including analytical and computational studies. Prior to the award of any subcontract, the Contractor shall:

a) Provide a detailed project plan, including goals, costs, etc. to the COR.

b) The COR will provide the detailed Subcontract Project Plan to the Contract Officer (CO) for approval.

c) If deemed necessary, and approved by the COR, conduct an on-site qualification of proposed Subcontract laboratory.

Only upon approval of the CO shall work at the subcontract organization begin.

The Contractor shall summarize subcontractor Validation Study Reports and include the summary in the Contractor’s monthly progress report to the COR. Information included in this summary consists 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.

iii. Test Method Background Review Document (BRD)

Upon receipt of reports and data resulting from the conduct of approved Validation Studies for incomplete Test Method Submissions/Nominations, the Contractor shall prepare a comprehensive BRDs (sample BRD found at http://iccvam.niehs.nih.gov/methods/pyrogen/pyr_brd.htm), as directed by the COR. The Contractor shall:

a) Obtain and present in written form all information necessary to adhere to the most recent ICCVAM test method submission guidelines.5

b) Develop search strategies and perform literature searches on specified test methods or methodologies for specific endpoints in preparing the BRD, and prepare a summary describing the validation status of such methods including test method performance, data quality, evidence of interlaboratory reproducibility, and the chemical and/or product classes that have been evaluated and including relevant exposure data in the target species for evaluated chemicals. Upon request by the COR, the Contractor shall compile a reference list of chemicals/substances recommended for use in validating the test methods.

c) Provide all deliverables to the COR in Draft and Draft Final forms based on a timeline prepared by the Contractor and approved by the COR at the start of each activity.

The Contractor shall structure each BRD in a monograph format, shall provide to the COR the document substantially error free in an electronic camera-ready format as appropriate for NIH publications, and coordinate the printing and distribution of those documents designated by the COR as NIH publications.

http://iccvam.niehs.nih.gov/methods/pyrogen/pyr_brd.htm

iv. Test Method Technical Review Document

For Test Method Submissions/Nominations recommended for Peer Review, and as directed by the COR, the Contractor shall assemble a Test Method Technical Review Document. Each Test Method Technical Review Document shall include all available information submitted, obtained, and analyzed during the pre-screen process. Unless otherwise directed by the COR, the Contractor shall adhere to the most current version of the ICCVAM Test Method Submission Guidelines5 for guidance on document organization and content. The Contractor shall include the Test Method Pre-Screen Evaluation and/or Background Review Document, as appropriate, specific for the Test Method under review. The Contractor shall submit the Test Method Technical Review Document to the COR for review, comment, and/or approval in accordance with the timeline prepared by the Contractor and approved by the COR at the start of this activity. As directed by the COR, the Contractor shall provide the Test Method Technical Review Document to the Peer Review Panel in advance of Peer Review Meetings.

v. Test Method Evaluation Report (TMER)

For test methods proceeding through peer review, or for forwarding with ICCVAM recommendations to regulatory agencies, all of the available information submitted, obtained, and analyzed during the prescreen process (including the Test Method Prescreen Evaluation Report and/or BRD, as appropriate) shall be compiled by the Contractor as a TMER as directed by the COR. A sample TMER may be viewed at:

http://ntp.niehs.nih.gov/go/40419. The organization and information provided in the document shall adhere to that information listed in the most current version of the ICCVAM test method submission guidelines5 or as otherwise directed by the COR. The Contractor shall include the following in the TMER:

a) Pre-screen Evaluation Report and/or Background Review Document, as appropriate.

b) Peer Review Report, as an appendix.

The Contractor shall provide all deliverables in Draft and Final Draft Versions to the COR based on a timeline prepared by the Contractor and approved by the COR at the start of each activity. The Contractor shall structure each TMER in a monograph format, shall provide to the COR the document in an electronic camera-ready format as appropriate for NIH publications, and coordinate the printing and distribution of those documents designated by the COR as NIH publications.

d. Meeting Support

i. General Meeting Support for NICEATM- and ICCVAM-related Meetings (including ICATM)

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. Contractor tasks shall include, but are not limited to, the following:

http://ntp.niehs.nih.gov/go/40419

a) Preparation of Draft and Final versions of Federal Register Notices for all meetings open to the public.

b) Creation and maintenance of a directory of subject matter experts and organizations, both within and outside Federal Government, who represent the many scientific disciplines in toxicology necessary to conduct a thorough and integrated assessment of all scientific data supporting the validity of new testing methods and strategies for risk assessment purposes.

c) Planning and coordinating of all ICCVAM-related peer review/expert panel, workshops/symposia, and/or seminar arrangements including, but not restricted to, procurement/rental of meeting rooms, lodging, local transportation, A/V equipment, copier and computer, etc.

d) Preparation, duplication, and distribution to meeting participants and registrants all pre-meeting, meeting, and post-meeting information and materials including, but not limited to, agendas, registration materials, mailing announcements, flyers, brochures, scientific materials, targeted mailing lists, meeting notebooks, and other communications media including press releases, ICCVAM-all communications, articles in government and non-government publications, etc.;

e) Preparation of invitations and associated correspondence and materials to forward to prospective participants for these meetings detailing logistics, travel regulations, and other pertinent information. The Contractor shall be responsible for extending invitations to those individuals selected to be active participants in workshops and other meetings.

f) Preparation and completion of travel arrangements, reimbursements, and honoraria, as appropriate, for invited non-Federal Government participants and Contract staff necessary for administrative support during the meetings (e.g., ensuring functionality of A/V equipment, taking meeting minutes, organizing presentations, etc.) including airline reservations, hotel reservations, arranging local transportation, etc. Each non-Federal Government participant and Contract staff shall be reimbursed at the Federal Government rate of per diem for the city/state of the venue.

g) Preparation of all electronic presentations needed at all meetings;

h) Prepare Abstracts and Posters for meetings, including but not restricted to, Society of Toxicology, World Congress, and other identified professional meetings, in Draft and Final versions;

i) Manuscript Preparation7 for all meeting presentations (poster or platform) for which a manuscript is required (e.g., Society of Toxicology, World Congress, etc.);

j) Meeting support for both on-site and off-site participants via an NIH-approved web-based service (e.g., Adobe Connect) and including live editing of web-shared documents;

k) Posting of meeting materials to the NICEATM/ICCVAM website (public and/or private domains, as appropriate) in a timely fashion both in advance of and at the completion of all meetings;

l) Transcription of all public meetings (peer review/expert panel and workshop/symposia meetings).

Draft transcripts of all public meetings shall be provided within 10 working days after meetings and final versions shall be made within 5 working days of receipt of edits and comments from the COR;

m) Preparation of a meeting summary for all public meetings (peer review, expert panel, and workshop meeting);

n) Preparation of Draft and Draft Final versions of meeting reports.

For peer review/expert panel meetings, the Contractor shall provide assistance in formatting and publication of the Panel-authored Report. The Contractor shall prepare Draft and Final versions of Transmittal Packages detailing the ICCVAM recommendations for all Peer Review/Expert Panel meetings and forward to the appropriate Agency heads. All tasks shall be completed according to the timeline prepared by the Contractor and approved by the COR.

ICCVAM meets approximately four times per year for a one-day meeting usually held on the NIH campus in Bethesda, MD. It is estimated that one Contract staff member may be required to attend all ICCVAM meetings in order to provide on-site support.

In regards to ICCVAM-related meetings involving ICATM members and ICATM Meetings:

a) When these events are held domestically, the Contractor shall provide assistance in arranging travel for all invited members of ICATM and Contract staff…