Attachment I NSA Blanket SOW Amended.pdf

STATEMENT OF WORK

NIEHS DIVISION OF THE NATIONAL TOXICOLOGY PROGRAM

HUMAN NEUROSPHERE ASSAY SERVICES

1.0. BACKGROUND: The National Institute of Environmental Health Sciences (NIEHS), located in the Research Triangle Park, North Carolina, is one of the 27 Institutes and Centers composing the National Institutes of Health. The NIEHS is home to the Division of the National Toxicology Program (DNTP), a Health & Human Services (HHS) interagency program dedicated to testing and evaluating substances in our environment whose mission is to evaluate agents of public health concern by developing and applying tools of modern toxicology and molecular biology. The program maintains an objective, science-based approach in dealing with critical issues in toxicology and is committed to using the best science available to prioritize, design, conduct, and interpret its studies. To that end, NTP is continually evolving to remain at the cutting edge of scientific research and to develop, validate and apply new technologies

The DNTP is exploring effects of toxicants during neurodevelopmental stages that may be uniquely sensitive to environmental insults. This potential window of sensitivity is due in part to the enormous changes in key neurodevelopmental processes of proliferation, migration, apoptosis, and neural network maturation. As a consequence, the DNTP has a requirement to investigate the sensitivity to environmental chemicals in a battery of assays that cover key neurodevelopmental events during embryonic and neonatal development. The human neurosphere assay (NSA) is one component of the battery used by the DNTP; the NSA allows for the assessment of multiple neurodevelopmental endpoints in a multiplexed format. The NSA captures proliferation, apoptosis, migration, differentiation, and neurite outgrowth in human NPCs. Examination of these processes in the 3D neurospheres will allow for complex interactions of multiple cell types (e.g. neurons, astrocytes, oligodendrocytes, oligodendrocyte progenitors and radial glia) not captured in other 2D assays that are involved in these key neurodevelopmental processes. DNTP requires a high throughput NSA for evaluation of developmental neurotoxicity to allow for the batch screening of compounds evaluated that might be used to prioritize compounds for targeted in vitro and in vivo DNT testing.

2.0. SCOPE: This Statement of Work (SOW) will be used to execute testing effects of compounds in the NSA testing services under the Indefinite Delivery/Indefinite Quantity (IDIQ) contract. During the contract the Government will identify tasks required to complete this testing effort. Task orders with specific details will be placed as needed by the DNTP. Specific performance dates and quantities will be specified on each individual task order.

3.0. OBJECTIVES: The purpose of this effort is to explore effects of environmental compounds with unknown developmental neurotoxicity potential in the NSA.

4.0. TASKS: The contractor shall evaluate the neurodevelopmental effects of environmental compounds using nine (9) neurodevelopmental endpoints in the NSA: 1) hNPC proliferation; 2) Viability (proliferating and differentiating hNPC); 3) Cytotoxicity (proliferating and differentiating hNPC); 4) Radial glia migration;

5) Neuronal differentiation; 6) Neuronal migration; 7) Neurite morphology; 8) Oligodendrocyte differentiation; and 9) Oligodendrocyte migration. Evaluation of the effects of environmental compounds in the NSA shall be conducted as two tasks. In Task 1 the Contractor shall run the NSA and collect data.

In Task 2 the Contractor shall analyze and report the data generated from Task 1.

4.1. Chemicals: All test compounds and dimethylsulfoxide (DMSO) will be supplied by the NIEHS/DNTP blinded in a one-time shipment. All other assay controls shall be supplied by the contractor. The Contractor shall be responsible for supplying all other reagents, equipment and facilities needed to conduct the specific assays

4.2. Task 1 (NSA data collection): The contractor shall employ a multiplexed approach in conducting the following assays: primary hNPC proliferation assay (NPC1), primary hNPC migration assay (NPC2a-c), primary hNPC neuronal differentiation assay (NPC3), primary hNPC neuronal morphology assay (NPC4), and primary hNPC oligodendrocyte differentiation assay (NPC5).

4.3. Task 2 (NSA data analysis and reporting): All assays shall be conducted in a semi-automated experimental workflow using an automated liquid handling system (MICROLABSTAR M; Hamilston), plate reader and high content imaging (Cellomics ArrayScan VTI; ThermoFisher) readouts, a bioinformatic workflow utilizing artificial intelligence, Ominsphero Software and a database-based biostatistics pipeline for unbiased sample evaluation and generation of concentration-response curves and respective benchmark concentrations (BMC).

5.0. DATA RIGHTS: The Government has unlimited rights to all documents/material produced under this contract to the extent permitted by the data rights clauses. The parties mutually acknowledge their understanding that this is the government’s intent. These documents and materials may not be used or sold by the contractor without written permission from the contracting officer. All materials supplied to the Government will be the sole property of the government and may not be used for any other purpose. This right does not abrogate any other government rights.

6.0. DELIVERABLES AND REPORTING REQUIREMENTS: 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 final deliverables received from the Contractor shall be essentially error free. All submitted electronic copies of final deliverables shall be Section 508-compliant as detailed in section 7.2 (below). Additional details regarding 508-compliance of electronic documents are found at http://www.hhs.gov/web/508/index.html.

6.1. Required Reports: A draft and final report for this effort shall provide a summary of the methods used and the results obtained in sufficient detail and quality to meet the requirements for peer reviewed literature. The draft report shall be delivered in both hard and electronic formats (MS Word) for review and comment by the Contracting Officers Representative (COR); the final report shall be delivered in hard and electronic (PDF) formats. Some reporting of data may be required on an ad hoc basis, the need for any ad hoc reporting shall be determined from periodic status reports described in section 6.3. below.

All final electronic documents shall be section 508 compliant. All raw data shall be attached as an appendix to the report and submitted electronically to the COR as an Excel spreadsheet. The final report shall include but not be limited to:

6.1.1. A detailed description of all experimental procedures

6.1.2. A full set of all raw data, summarized/normalized data

6.1.3. Guidance on the interpretation of the DNT in vitro NSA testing results.

6.1.4. Concentration response curves for each compound and endpoint with a BMC value as point of departure and corresponding confidence intervals.

6.1.5. Identification of compounds as "specific DNT compounds," unspecific DNT compounds," or "negative compounds" using an NSA-specific classification model.

6.1.6. Prioritization of specific DNT compounds using the ToxPi tool and the BMC of most sensitive endpoints.

6.2. Contract Management Reports: These shall consist of Standard Operating Procedures (SOP) related to conduct of NPC1-5.

6.3. Periodic Status Reports: These shall detail the status of active assignments and any problems encountered and remedial actions taken to resolve those problems should be provided to the COR quarterly. Deviations from the SOW and/or protocols shall be noted.

6.4. Draft Final Report: This shall detail all significant outcomes resulting from the requirements as described within the SOW and contract, problems encountered and remedial actions taken to resolve the problem, as well as any deviation from the SOW and/or SOPs shall be submitted to the COR for review http://www.hhs.gov/web/508/index.html and comment within 15 working days of completion of the last of the studies; the Final Report responding to any comments shall be submitted to the COR and the contract officer (CO) within 15 working days of receipt of COR comments.

6.5. General Reporting Requirements: Final electronic deliverables shall be Section 508 compliant according to the checklists at http://www.hhs.gov/web/508/index.html under Helpful Resources.

The Contractor shall ensure that the reporting timeframes for each milestone are met. In general, specific formatting requirements will be provided by the COR. If changes are required by the COR, revised electronic version of the document shall be submitted. The COR will notify the principle investigator (PI) when original or revised reports are approved.

Unless otherwise instructed, all reports submitted under this contract shall reference the contract number, the title and types of report, and the represented period on the first page of the report.

6.6. Electronic Deliverables: Unless otherwise directed, electronic deliverables shall be submitted to the COR, Alternate COR, and CO. Electronic copies of the Contract Management Report and Monthly Status Reports shall be submitted to the COR and Alternate COR. The COR will designate a forum for these reports. Electronic copies of Monthly Status Report, Invoices/Financial Reports and other reports as directed shall be emailed to the CO. The CO will provide email addresses to the Contractor.

7.0. PLACE OF PERFORMANCE: The opportunities for sample degradation and compromising the quality of data are greater with the continued movement of samples to various sites for analysis, therefore; analysis shall take place at the contractor’s facility.

8.0 PERIOD OF PERFORMANCE: Five (5) year ordering period

9.0. Section 508 Requirements for Deliverables: All Final Reports and all documents shall be prepared, formatted, and checked for conformance with Section 508 standards, prior to delivery to NIEHS or posting to the websites, as appropriate. Draft reports need not be Section 508 compliant.

The Department of Health and Human Services has written procedures and checklists based on the US Access Board Standards (http://www.access-board.gov/about.htm) for preparing documents to meet all requirements of Section 508 standards, using either Microsoft Word or Adobe Professional, version 8.0 or higher. The Contractor shall refer to the checklists and standards found on HHS’s Section 508 website (http://www.hhs.gov/web/508/checklists/index.html) for further guidance. Submission of electronic documents which satisfy the appropriate HHS Checklists and Standards will be considered acceptable.

Should an accessibility problem be found in the documents, the Government will return them for remediation, with a timeframe to be negotiated at that time.

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” Section 508 compliance for PDF files: The NIH Section 508 Coordinator approved a Section 508 accommodation for certain DNTP reports. As the accommodation must be renewed annually, the COR will inform the Contractor about any changes. Currently, the accommodation applies to the posting of public comments.

10.0. CONTRACTOR FURNISHED MATERIALS: The Contractor is required to supply all equipment, property and services needed to fulfill the SOW.

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