Att3_SOW_Genetox ReCompete_Final.pdf

ATTACHMENT 3

Statement of Work

“Genetic Toxicology Support for the National Toxicology Program (NTP) and the National Institute of Environmental Health Sciences (NIEHS)”

September 4, 2019

The National Institute of Environmental Health Sciences (NIEHS), located in Research Triangle Park, North Carolina, is one of 27 research institutes and centers of the National Institutes of Health. NIEHS is a multidisciplinary research institution, with the primary mission of conducting research to discover how the environment influences the development and progression of human disease in order to promote healthier lives.

1.0 GENERAL

1.1 Background and Significance

An assessment of genotoxicity potential is a critical component of the comprehensive toxicological characterization a substance, due in large part to the mechanistic linkage between genetic damage and a number of defined adverse health outcomes including cancer, neurodegenerative disease, birth defects, and somatic mutational load. In addition, knowledge of the genotoxic potential of a substance provides insight into mode of action and may increase confidence in predictive toxicology models and assessments. Thus, the objective of this contract is to continue the long-term effort to provide the NTP with the capability to characterize the genetic toxicity potential of substances (e.g., individual chemicals, chemical mixtures, physical agents) of interest to the Program using a variety of in vitro and in vivo methods. The testing approaches will include a mix of traditional, well-characterized assays such as the bacterial mutation assay (Ames assay) and the in vivo peripheral blood rodent micronucleus (MN) assay, as well as new molecular approaches (for example, the MultiFlow® DNA Damage assay) that provide enhanced understanding of mechanism of action.

1.2 General Objectives and Requirements

Independently and not as an agent of the Government, the Contractor shall furnish services, qualified personnel, material, equipment, and facilities, not otherwise provided by the government under the terms of this contract as needed to perform the work set forth below.

The Contractor shall provide services and support to examine a variable number of chemicals annually, depending on the needs of the government, for induction of genetic changes (e.g., mutations, chromosomal changes, DNA damage, base sequence changes, differential gene expression profiles) in cells obtained from exposed animals, generally laboratory rats and mice, and/or humans. A variable number and mix of studies designed to evaluate these types of endpoints may be conducted annually.

As an example, studies may include comet assays to assess DNA damage in multiple tissues of rats and mice, and peripheral blood micronucleus assays to measure the frequency of red blood cells with evidence of chromosomal damage. The Contractor shall also provide services and support to examine chemicals for ability to induce these same kinds of genetic changes in cultured human and animal cells.

In addition to the in vitro and in vivo animal test systems, the contract shall provide the capability to test chemicals for induction of gene mutations in bacterial tester strains. It is anticipated that approximately 20 chemicals (or chemical mixtures) may be evaluated in one or multiple genotoxicity assays annually, although this number may fluctuate based upon the needs of the government. Because technologies applied to the investigation of exposure-induced genetic toxicities are in a state of rapid evolution and expansion, the contract will include efforts directed toward refining existing techniques and integrating new technologies into the NTP testing program to maintain a high level of scientific capability and relevance.

1.3 Period of Performance and Options

The Period of Performance shall be for one (1) Base Period of 12-months and nine (9) 12-month Option Periods. At the end of the contract period, the Government may also exercise an option per FAR 52.217-8 for an additional six (6) months of performance.

During the period of performance of the contract, the Government may, depending on the program needs and availability of funds, exercise an option to increase the level of effort performed under the contract. This option may be exercised multiple times a year up to a level of effort and cost that does not exceed 30% of the base amount for that year. The contractor shall have the capability and capacity to perform this additional level of effort if necessary.

1.4 Information Technology

The contractor shall follow all IT Security guidelines for NIEHS, NIH, and HHS, as specified in Section H of the contract, and any updates thereof.

1.5 Applicable Documents/Links

• Chemical Effects in Biological Specimens (CEBS) (https://tools.niehs.nih.gov/cebs3/ui/), (Ref

SOW 3)

• Provantis (http://www.instem.com/solutions/provantis/), (Ref SOW 3)

• NTP Specifications (https://ntp.niehs.nih.gov/ntp/test_info/finalntp_toxcarspecsjan2011.pdf)

2.0 SPECIFIC REQUIREMENTS

2.1 Activities

For the activities included in this Section 2.1, the number and mix of assays that are conducted annually may vary from year to year depending on the needs of the government. All activities related to testing shall be conducted in accordance with Good Laboratory Practice (GLP) regulations unless specifically exempted in writing by the Contracting Officer’s Representative (COR).

https://tools.niehs.nih.gov/cebs3/ui/ http://www.instem.com/solutions/provantis/ https://ntp.niehs.nih.gov/ntp/test_info/finalntp_toxcarspecsjan2011.pdf

The Contractor shall provide services and support for the following activities to be performed under the contract:

2.1.1 Activity 1 – In vivo micronucleus assays conducted with samples sent to the Contract Laboratory from another site: Determination of the frequencies of micronucleated immature and mature erythrocytes, and/or lymphocytes in bone marrow or whole blood samples obtained from animals, typically mice, rats, or occasionally humans exposed to a chemical(s) in a remote laboratory or site. Typically, these animal exposures will be conducted at an NTP contract laboratory that conducts studies in rodents. Samples from humans will be obtained at a collaborating clinic or hospital. Samples obtained at remote laboratories will be shipped under appropriate conditions to the Contract Laboratory for processing and evaluation. The number of samples shipped to the Contract Laboratory from remote sites is dependent on the number and type of animal studies initiated by the NTP. One such study would typically consist of a control group and up to five (5) treatment groups per sex, and such studies often include both male and female animals. Protocols for this assay will typically be consistent with OECD Test Guideline 474, and shall use flow cytometric methods for data collection.

2.1.2 Activity 2 – In vivo micronucleus assays conducted at the Contract Laboratory: Measurement of micronucleated erythrocyte and/or reticulocyte frequencies in bone marrow or whole blood samples obtained from animals, typically mice and/or rats, exposed to a chemical(s) on site at the Contract Laboratory. Blood samples will be collected, processed, and evaluated at the Contract Laboratory. In vivo micronucleus assays conducted in the Contract Laboratory will be short-term (i.e., no 2-year or 90-day studies), with a typical duration of 4 days or less. It is anticipated that approximately three in vivo micronucleus studies may be conducted at the Contract Laboratory annually. Protocols for this assay will typically be consistent with OECD Test Guideline 474, and shall use flow cytometric methods for data collection.

2.1.3 Activity 3 – In vivo comet assay: Quantification of DNA damage (e.g., single and double strand DNA breaks, oxidative damage, DNA-DNA crosslinks) using the single cell gel electrophoresis (comet assay) method in any tissue of interest in animals, typically mice and rats, or occasionally humans (in this case, blood cells only) exposed to a chemical(s) in an alternate laboratory or site, or for nonhuman animals only, in the Contract Laboratory. Examples of tissues or cells that may be examined for exposure-induced DNA damage include blood leukocytes, liver, kidney, stomach, ileum, colon, and brain. In addition, there is a requirement for the Contractor to prepare samples for histopathology assessment of cytotoxicity measures for the same tissues selected for DNA damage assessment. Protocols for this assay will typically be consistent with OECD Test Guideline 489, and shall use automated image analysis software specifically designed for evaluation of comet images for data collection.

2.1.4 Activity 4 – In vivo Pig-a (phosphatidylinositol N-acetylglucosaminyltransferase subunit A) gene mutation assays: Measurement of Pig-a mutant frequencies in erythrocytes and reticulocytes in peripheral blood samples obtained from animals, typically mice and rats, exposed to a chemical(s) either at an alternate laboratory or, infrequently, at the Contractor’s site. Basic Pig-a assay principles are the subject of numerous publications (for example, Gollapudi et al., 2015; Olsen et al., 2017; Avlasevich et al., 2019; Shemansky et al., 2019). Flow cytometric methods shall be used for data collection.

Note: When practical and desirable, assessment of micronucleus frequencies, Pig-a mutation frequencies, and/or DNA damage in multiple tissues may be conducted in an integrated fashion using samples from the same animal. These samples may be generated through in vivo tests conducted at the Contract Laboratory or they may be obtained at a remote laboratory and shipped to the Contract Laboratory for processing and analysis.

2.1.5 Activity 5 – In vitro micronucleus assays: The ability of a chemical(s) to induce micronuclei in cultured cells shall be examined in the Contract Laboratory as an alternative to evaluation of the endpoint in vivo. Cell type will be specified by the COR, but will typically be commercially available human TK6 lymphoblastoid cells, Chinese hamster ovary (CHO) cells, or human hepatocytes (HepG2, HepaRG, and primary hepatocytes). These exposures will be conducted with and without exogenous metabolic activation when the selected cell line is not metabolically competent.

Protocols for this assay will typically be consistent with OECD Test Guideline 487. Flow cytometric methods shall be used for data collection.

2.1.6 Activity 6 – In vitro Comet assays: The Contractor shall have the ability to evaluate the potential for a chemical(s) to induce DNA damage in cultured cells as an alternative to evaluation of the endpoint in vivo. Cell type will be specified by the COR, but will typically be commercially available human TK6 lymphoblastoid cells or human hepatocytes (HepG2, HepaRG, and primary hepatocytes). These exposures shall be conducted with and without exogenous metabolic activation when the selected cell line is not metabolically competent and may follow a standard slide-based protocol or employ high throughput (e.g., CometChip®) methodologies when appropriate to the study design. Automated image analysis software specifically designed for evaluation of comet images shall be used for data collection. Enzyme modified comet assay protocols to allow detection of oxidized bases may also be conducted from time to time (Collins, 2014).

2.1.7 Activity 7 – MultiFlow® DNA Damage Assay: Either as a prescreen for other genetic toxicity assays or as a follow-up assay to provide mechanistic insight into compound mode of action, the Contractor shall evaluate compounds using the MultiFlow DNA Damage Assay instrumentation that measures compound activity against specific relevant molecular targets (Bryce et al., 2017;

Bryce et al., 2018). A high throughput flow cytometer with capability to sample 96-well plates shall be used for data acquisition and the MultiFlow (p53, γH2AX, H3, PARP) kit from Litron Laboratories.

2.1.8 Activity 8 – Bacterial gene mutation assays: Gene mutation frequencies will be measured in several tester strains of Salmonella typhimurium and/or Escherichia coli following chemical exposures, with and without exogenous metabolic activation. For this activity, chemicals will typically be provided by the NTP, although on occasion, the Contractor may be directed to procure them from a commercial source. Protocols for this assay will typically be consistent with OECD Test Guideline 471. An automated colony counter shall be used for data collection.

2.1.9 Activity 9 – Toxicogenomics capabilities: On occasion, RNAseq for measuring differential gene expression profiles following chemical exposures shall be conducted generally using stored cell samples obtained from animals or from cell cultures (Sá et al., 2018; Costa-Silva et al., 2017).

Additional nucleic acid (e.g. DNA or RNA) isolations from cells, tissues, or biofluids may be required from time to time. Such nucleic acid isolates would be submitted for molecular analysis to NTP-identified laboratories or investigators. These analyses might include sequencing of circulating cell-free DNA, measuring changes in DNA methylation status related to gene expression, or whole exome sequencing to determine base pair changes related to chemical exposures. Such molecular investigations may be done by a subcontractor or other provider as approved by the COR.

2.1.10 Activity 10 – Assay development and refinement, and adoption of New Alternative Methods (NAMs): Efforts are anticipated for assay development and refinement, and integration of New Alternative Methods (NAMs) into the laboratory testing capabilities to allow the NTP to remain flexible and current as technology improvements and innovations occur over the course of this contract. Periodic staff training in new technologies may be required to meet these efforts.

Because the Government cannot anticipate the types of changes that may occur, we expect varying levels of these efforts over the course of the contract to appropriately support the needs of the NTP. Additional efforts will be devoted to customizing specific testing strategies in cases where the nature of the exposure requires a modified approach to the Standard Operating Procedure to identify and evaluate induced genetic changes. As interest grows in examining exposure-associated changes in gene sequence or expression patterns directly in humans rather than measuring such events in surrogate animals alone, refinement and adoption of NAMs to allow for such translational studies to monitor these molecular changes in humans has heightened significance.

2.1.11 Activity 11 – Study support activities may be required from time to time, such as focused literature searches, manuscript drafting, poster preparations for professional meetings reporting NTP study results, and other activities in support of the NTP genetic toxicology testing efforts.

2.2 Additional Requirements:

2.2.1 Chemicals tested under this Contract shall be supplied by the COR through the NTP Chemistry Group or will be identified by the COR for purchase by the Contractor. The Contractor will be notified by the COR in writing of the anticipated shipment of a chemical supplied by the NTP. For all chemicals, the COR will identify, in writing, the specific assay(s) to be conducted.

2.2.2 Standard laboratory protocols for each assay type, as described in Section 2.1 above, shall be established by the Contractor and be approved by the COR within 30 days after the Award is made.

2.2.3 The Contractor shall follow procedures in accordance with current FDA Good Laboratory Practice Regulations (originally published in Federal Register, 1978, pp. (21 CFR Section 58)). All animal testing shall be conducted in AALAC-certified facilities in strict accordance with the NIH Care and Use of Animals guidelines and the IACUC regulations of the Contract laboratory. The Contractor shall perform all work in a manner compatible with the NTP Health and Safety Minimum Requirements (https://ntp.niehs.nih.gov/ntp/test_info/finalntp_toxcarspecsjan2011.pdf).

2.2.4 For each test conducted by the Contractor, the specific, tailored protocols will be prepared by the Contractor and be approved in writing by the COR in advance of sample preparation and the initiation of testing; any required modifications to standard assay procedures will be discussed and agreed to prior to implementation. Once a protocol has been approved by the COR, the Contractor shall not alter the protocol without a formal amendment to the protocol and written approval from the COR.

2.2.5 Any coded human blood samples that may be evaluated for biomarkers of genotoxicity will be provided from a collaborating laboratory, within or outside the NIH; no personal identifying information will accompany these human samples. All laboratory personnel working with human blood samples shall have documentation of training in safe handling of infectious agents.

2.2.6 Tissue and blood samples collected for analysis will either be analyzed immediately (in vivo comet assay or Pig-a gene mutation assay) or stored frozen in a minus 80°C freezer for future analysis (for example, in vivo micronucleus assay). For the comet assay, the Contractor shall have the capability to provide histopathological assessment of tissues collected in the comet assay to evaluate chemical-related cytotoxicity (for example, apoptosis or necrosis). The Contractor shall have the ability to store biological samples in a minus 80°C freezer at the Contract Laboratory for up to 3 years or until the COR provides notification that samples are no longer needed, whichever comes first. In no case, however, shall samples be disposed of without consent from the COR.

Samples shall be disposed of according to approved hazardous biological waste policies.

2.2.7 The Principal Investigator and other key personnel shall visit the NIEHS to consult with the COR and other NIEHS staff, as directed by the COR. In addition, the Principal Investigator, or a designee, shall attend at least one scientific meeting and/or conference annually to present data and discuss results of genetic toxicity tests performed under the contract, as directed by the COR.

2.2.8 As directed by the COR, the Contractor shall occasionally be required to ship animal tissues, slides, or other biological material or information including (but not limited to) protocols and data to the NIEHS or to another location in the U.S. Some of the shipments may require dry ice or shipment on wet ice or cold packs.

2.2.9 The Government shall provide B6C3F1/N mice or arrange for receipt of tissues or cell samples from remote laboratories for the studies described in this SOW. On occasion and at the direction of the COR, the Contractor shall be required to procure animals (for example, rats or other strains of mice) from outside sources to be used in studies conducted at the Contract Laboratory.

2.2.10 Cell lines and bacterial strains to be used in the in vitro tests shall be obtained by the Contractor, at the direction of the COR.

2.2.11 The Contractor shall comply with ''Humane Care of Rodents in NTP Studies" as follows:

a. The testing laboratory shall comply with the NTP Specifications, the specific regulations listed below, and other applicable Federal, state, and local laws, regulations and policies.

• U.S. Government Principles

• PHS Policy on Humane Care and Use of Laboratory Animals

• Animal Welfare Act Regulations – Title 9: Code of Federal Regulations, Chapter 1, SubChapter

A: Animal Welfare

• Animal Welfare Act

• Guide for the Care and Use of Laboratory Animals, 8th Edition http://grants.nih.gov/grants/olaw/references/phspol.htm#USGovPrinciples https://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf http://www.ecfr.gov/cgi-bin/text-idx?SID=891e14e1125910a4ff614b3997fbfbda&c=ecfr&tpl=/ecfrbrowse/Title09/9cfrv1_02.tpl http://www.ecfr.gov/cgi-bin/text-idx?SID=891e14e1125910a4ff614b3997fbfbda&c=ecfr&tpl=/ecfrbrowse/Title09/9cfrv1_02.tpl https://www.aphis.usda.gov/animal_welfare/downloads/awa/awa.pdf http://grants.nih.gov/grants/olaw/Guide-for-the-Care-and-Use-of-Laboratory-Animals.pdf

b. The testing laboratory shall have a PHS Assurance from the NIH Office of Laboratory Animal Welfare (OLAW), and shall be accredited by AAALAC International.

c. The testing laboratory shall have a qualified Laboratory Animal Veterinarian(s) to supervise the care and health of the animals.

2.3 Oversight of animal experiments

The Contractor shall have a functional and experienced institutional animal care and use committee (IACUC) for approval of in vivo animal experiments in addition to showing strict adherence to NIH guidelines for animal care and use. For all in-life animal studies conducted at the Contract Laboratory as described in this SOW, euthanasia will be accomplished by CO2 inhalation followed by exsanguination to ensure death prior to sample collection.

2.4 Personnel Needs To Be Met By The Contractor

The Contractor shall be responsible for providing trained, experienced staff for performing the requirements of this contract, and for continuously monitoring, managing and controlling the work. The Contractor shall make its best efforts to retain staff members with experience and to minimize staff turnover.

The Contractor shall provide qualified personnel for the positions listed below which represent the minimum requirements necessary to meet needs of the Government. Additional personnel/positions not listed may also be required if determined necessary to meet contract requirements.

2.4.1 Principle investigator (Ph.D., M.D., and/or D.V.M.) – Key Personnel

2.4.2 Laboratory director (Ph.D., M.D., and/or D.V.M.) – Key Personnel

2.4.3 Flow Cytometry Technician - Experienced and highly proficient for analysis of blood samples to evaluate micronucleus and Pig-a gene mutation frequencies – Key Personnel

2.4.4 Experienced technicians for sample acquisition and preparation for in vivo Pig-a, micronucleus, and comet assays

2.4.5 Experienced, highly proficient comet assay technician and scorer (automated image analysis and scoring software)

2.4.6 In Vitro Assay Specialist - Experienced for in vitro micronucleus and comet assays – Key Personnel

2.4.7 Experienced Ames assay technician(s)

2.4.8 Experienced personnel for conducting MultiFlow™ DNA Damage analyses

2.4.9 Experienced dose formulation scientist

2.4.10 Experienced, appropriately trained, and certified animal care personnel

2.4.11 Certified laboratory animal veterinarian (DVM) (may be a consultant)

2.4.12 Experienced prosectors for sample acquisition for in-house animal studies

2.4.13 Quality Control and Quality Assurance personnel trained in Good Laboratory Practices for review of study protocols, data presentations, and study reports

3.0 TECHNICAL REPORTING REQUIREMENTS AND DELIVERABLES SCHEDULE

Deliverables for this contract include data for all activities supported by the Contract, all specimens collected under this Contract, all data analyses performed under this Contract, and documentation. The delivery of the data and any required data analyses will be as directed by the COR and NIH Principal Investigator (PI). Specimens shall be delivered to the appropriate processing or storage facilities as directed by the COR. The COR shall be immediately notified of any problem associated with the collection or delivery of data or materials.

NTP study results will be reported as indicated by this SOW and as required by Good Laboratory Practice procedures for studies that will be conducted under a GLP protocol. The Contractor shall enter study data as required by SOW Section 3.1 (below).

3.0.1 Study Protocols

The Contractor shall electronically submit for the COR’s review a written study protocol prior to the start of any study. All protocols shall be approved and signed by the COR prior to beginning the study. Any changes to the protocol that might be required during the conduct of the study will be detailed in a written amendment, approved and signed by the COR.

3.0.2 Study Reports

For each assay conducted with a test article for the NTP at the Contract Laboratory, a written study report shall be submitted, unless otherwise directed by the COR. An acceptable format will be agreed upon by the COR and the Contractor. Study Report requirements include the reporting of NTP data as indicated by this Statement of Work and as required by Good Laboratory Practice procedures, as applicable. Laboratory historical control data for the assay shall be included to assist in data interpretation. In addition, the study report shall include a summary description of the assay protocol, the rationale for conducting the study (e.g., the value in collecting data on the endpoint in question), a description of how the doses were determined, and a description of any unusual findings or problems encountered, and the resolution of those problems. The report may also contain the laboratory’s interpretation of the study results, although the formal data analysis for the comet, micronucleus, and bacterial mutation data will be conducted by the NTP. The Study Report shall also include name of the test article, CASRN, physical appearance, and storage conditions. For tests conducted on shipped samples received at the Contract Laboratory (i.e., testing was conducted at a remote laboratory), the Study Report shall include name of the test article, CASRN, condition of the samples upon receipt, and processing procedures at the Contract Laboratory.

3.0.3 Contract Annual and Final Reports

3.0.3.1 The Contractor shall submit Annual reports beginning twelve months after the date of contract award. One Annual report will be submitted for each one-year performance period. Each Annual report shall be due within 30-days following the anniversary date of the contract. Annual reports shall be submitted electronically and include a summary of results from each chemical/assay conducted, status of all chemicals tested, entered on test, or scheduled to be tested, problems encountered, problem resolution, and anticipated problems. The Annual reports shall not contain the assay data.

3.0.3.2. The Contractor shall electronically submit a draft final report to the COR 45 days prior to the completion of the date of the contract, with the approved final report submitted within 30 days after the expiration date of the contract. The Final report shall include a summary of all samples tested for the Government and the assay results.

The Contractor shall submit Annual and Final reports electronically to the COR in a current version of Microsoft® Word, unless otherwise directed by the COR. All electronically submitted reports must be 508 compliant. The Contractor shall not include detailed experiment data in the Annual or Final reports.

3.0.4 Summary of Salient Results

The Contractor shall be required to prepare and submit, with the final report, a summary (not to exceed 200 words) of salient results achieved during the performance of the contract. This report will be required at the same time as submission of the approved final report.

3.0.5 Invoicing

The Contractor shall submit detailed monthly invoices in accordance with the invoice instructions provided in Section G of the contract. In addition, the Contractor shall identify the name of each employee who charged hours to the Contract, the project or study on which the employee worked, and the activities or work category involved (e.g., flow cytometry, animal care, comet assay slide evaluation, laboratory direction, study director). Substantial expenditures should also be detailed (e.g., micronucleus assay kits, comet slides, liver microsome S9 mix for bacterial mutation studies).

3.1 Data Delivery

The Contractor shall enter data into one or more COR-specified electronic data systems. The Contractor shall not record data manually when an automated system is provided unless the electronic data system is unavailable.

Currently, a Laboratory Information Management System (LIMS), Provantis, is used to collect data for in-life studies. NTP Provantis is a web application and requires the Contractor to access the Internet from animal facilities.

Currently, the Chemical Effects in Biological Systems (CEBS) is used to store data from non in-life studies (data from in vivo specimens received from NTP or from in vitro studies conducted by Contractor). The Contractor shall include the metadata and data in an Excel spreadsheet formatted to COR-specified standards. The Contractor shall deposit these assay data electronically into CEBS after the data have undergone Quality Assurance assessment by the Contractor and within 30 days of completing the assay.

The Government shall provide all necessary equipment, licensing, and training required for access to and use of NTP Provantis and CEBS. Over the course of the contract, the Government expects to transition to new electronic data systems or may improve current versions of existing electronic data systems. The Contractor shall be required to make any necessary changes or upgrades for a smooth transition to any new or upgraded system, and the Government shall provide all necessary equipment, licensing, and training required for such transition.

3.2 Deliverables Schedule

DELIVERABLE REFERENCE FREQUENCY FORMAT SUBMIT TO

Standard

Laboratory

Protocols

SOW 2.2.2 Submitted within

30 days of contract award

Electronic COR - witt@niehs.nih.gov

Study Data - CEBS SOW 3.1 Entered within 30 days of completion of testing

Data Entry Data Entry into CEBS

Study Protocols 3.0.1 Prior to the start of any study

Electronic COR - witt@niehs.nih.gov

Study Reports SOW 3.0.2 Submitted within

30 days of completion of testing

Electronic COR - witt@niehs.nih.gov

Annual Reports SOW 3.0.3 Annually, within 30 days following the anniversary date of contract award

Electronic COR - witt@niehs.nih.gov;

CO - julie.bardo@nih.gov

Draft Final Report SOW 3.0.3 45 days before contract end

Electronic COR - witt@niehs.nih.gov

Final Report SOW 3.0.3 30 days after contract end

Electronic COR - witt@niehs.nih.gov;

CO - julie.bardo@nih.gov

Summary of

Salient Results

SOW 3.0.4 30 days before contract end

Electronic COR - witt@niehs.nih.gov

IT Security Plan and other IT

Related

Deliverables

SOW

Section 7.0

See SOW Section

7.0

Electronic COR - witt@niehs.nih.gov;

CO - julie.bardo@nih.gov

Annual Section

508 Compliance

Report

SOW

Section 8.0

Due 30 days after

PoP end

Electronic COR - witt@niehs.nih.gov;

CO - julie.bardo@nih.gov

*NOTE - All electronically submitted reports must be 508 compliant.

mailto:witt@niehs.nih.gov mailto:witt@niehs.nih.gov mailto:witt@niehs.nih.gov mailto:witt@niehs.nih.gov mailto:witt@niehs.nih.gov mailto:witt@niehs.nih.gov

4.0 MEETINGS

The contractor agrees to attend any post award conference convened by the contracting activity or contract administration office in accordance with Federal Acquisition Regulation Subpart 42.5. The Contracting Officer, Contracting Officer’s Representative (COR), and other government personnel, as appropriate, may meet periodically (by telephone, teleconference or in person at the place of performance) with the Contractor to review the Contractor’s performance. These meetings will be at no additional cost to the government.

5.0 TRAVEL REQUIREMENTS

Travel for contract personnel is not likely to be required, except for specific instances as described in Section 2.2.7 herein. For any contract-supported travel, Government per diem rates shall apply. The Government will not provide travel funds or reimbursement associated with attendance at any professional meetings or training workshops for Contract employees without prior written approval from the CO. Contract staff who require Government PIV cards for accessing the NIEHS network for data deposition into CEBS or for use of the NTP Provantis system shall be provided contract-supported travel to a Government badging facility, if one is not located within a one hour drive from the Contractor site.

6.0 FACILITIES/EQUIPMENT/GOVERNMENT FURNISHED PROPERTY

6.1 Facilities/Equipment: The Contractor shall provide all facilities and equipment as outlined in this SOW and not otherwise provided by the Government.

6.2 Equipment/Property supplied by the Contractor: In addition to Section 6.1 above, the Contractor shall provide all equipment required to conduct the assays described in the SOW, including, but not limited to the following:

6.2.1 Single-sample flow cytometer and high throughput flow cytometer for sampling 96-well plates

6.2.2 AAALAC-approved clean (microbe-free) animal housing/treatment rooms and necropsy rooms

6.2.3 Climate controlled, electronically monitored room for conducting the comet assay (humidity, temperature, light controls)

6.2.4 Automated image analysis and data analysis software for comet assay measurements

6.2.5 CometChip® platform, or equivalent, for high throughput comet assays

6.2.6 MultiFlow™ DNA Damage Assay instruments, including a high throughput flow cytometer for sampling 96-well plates

6.2.7 Automated colony counter for bacterial mutation assays

6.2.8 Several (>4) dedicated minus 80°C freezers (20 cu. ft minimum) for sample storage for periods of up to 3 years

6.2.9 High speed access to the Internet including from animal facilities

6.2.10 Other Software: Adobe Acrobat Pro and the Microsoft Office suite of software, most current and advanced versions. Note: The required software shall be upgraded as new versions become available.

6.3 Government Furnished Equipment and Property:

Government Furnished Equipment and Property is identified in the Attachment labeled “Government Furnished Equipment.”

7.0 IT SECURITY PLAN AND OTHER IT RELATED DELIVERABLES

Refer to Section C, Article C.2 of the contract for specific requirements related to IT Security.

8.0 SECTION 508 COMPLIANCE

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

All electronic deliverables including reports, data entry, web pages, web applications, audio and video shall be Section 508-compliant; drafts do not need to be compliant. Detailed data that is meant to be processed by a program and not meant to be read by people does not need to be Section 508 compliant. The following Section 508 accessibility technical standards apply to this SOW:

• 1194.41 Information, documentation, and support The Contractor shall submit an annual Section 508 report in accordance with the schedule set forth in the ELECTRONIC AND INFORMATION TECHNOLOGY ACCESSIBILITY Article in SECTION H of the contract.

The Section 508 Report Template and Instructions for completing the report are available at:

https://www.hhs.gov/web/508/contracting/technology/vendors.html under "Vendor Information and Documents."

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

9.0 REFERENCES CITED IN THIS SOW:

Avlasevich SL, Torous DK, Bemis JC, Bhalli JA, Tebbe CC, Noteboom J, Thomas D, Roberts DJ, Barragato M, Schneider B, Prattico J, Richardson M, Gollapudi BB, Dertinger SD. Suitability of Long-Term Frozen Rat Blood Samples for the Interrogation of Pig-a Gene Mutation by Flow Cytometry. Environ Mol Mutagen.

2019 Jan;60(1):47-55. doi: 10.1002/em.22249.

Bryce SM, Bernacki DT, Smith-Roe SL, Witt KL, Bemis JC, Dertinger SD. Investigating the Generalizability of the MultiFlow ® DNA Damage Assay and Several Companion Machine Learning Models With a Set of 103 Diverse Test Chemicals. Toxicol Sci. 2018 Mar 1;162(1):146-166. doi: 10.1093/toxsci/kfx235.

Bryce SM, Bernacki DT, Bemis JC, Spellman RA, Engel ME, Schuler M, Lorge E, Heikkinen PT, Hemmann U, Thybaud V, Wilde S, Queisser N, Sutter A, Zeller A, Guérard M, Kirkland D, Dertinger SD.

Interlaboratory evaluation of a multiplexed high information content in vitro genotoxicity assay. Environ Mol Mutagen. 2017 Apr;58(3):146-161. doi: 10.1002/em.22083.

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SOW – Appendix A

Flow chart showing typical activities and milestones in routine genotoxicity studies to be conducted at the Contract laboratory*

*Note: In vitro and in vivo studies may be initiated at the request of the COR on a specified chemical(s) or on biological samples received from a remote laboratory. From that point on, the process steps are the same, beginning with the development of the study protocol.