Attachment 1 -Statement of Work -NIMH-20-003939.pdf

Version 11-30-2016-1 FAR Part 11—Describing Agency Needs

STATEMENT OF WORK (SERVICES)

(SOW)

GENERAL INFORMATION

Title of Project:

Expansion, Differentiation, and Validation of Neural Progenitor Cells (NPCs) from Human Induced Pluripotent Stem Cells (iPSCs) Derived from Psychiatrically Revelent Subjects.

Statement of Need and Purpose:

The expansion, differentiation, and validation of NPC cells from subject iPSC samples is time consuming, labor-intensive, and expensive, both in labor hours and reagent costs before experiments can begin.

Outsourcing this process as a service to a large, established iPSC laboratory that is equipped and staffed to provide these services will dramatically reduce costs through economies of scale and free up valuable staff time for carrying out the actual experiments in-house.

Background Information and Objective:

Over the past 10 years, investigators within the National Institute Mental Health (NIMH), Intramural Research Program (IRP) have accumulated a large collection of fibroblasts, lymphocytes, and other live cells obtained from participants in various studies that ascertained individuals on the basis of bipolar disorder, adult and childhood-onset schizophrenia, neurodevelopmental disorders, or known sex chromosomal aneuploidy (SCA). These samples contain rare chromosomal structural variants (SVs). Some of these cells have been reprogrammed into iPSCs and a few have been differentiated into NPCs, neurons, or glial cells.

In addition to these cells offering a powerful model system for the functional and experimental study of alleles that confer risk of neuropsychiatric disorders, they also provide a flexible experimental platform upon which the transcriptomic impact of gene dosage changes can be measured and compared, using powerful techniques such as RNA sequencing, high-content imaging, and multi-electrode arrays.

If successful, this project will provide a living catalog of some of the most important, psychiatrically-relevant SVs that will form the basis for a broad range of studies. By selecting SVs that range across psychiatric diagnoses and chromosomal locations, we will be able to carry out cross-diagnostic and cross-SV experiments that could provide the first insights into pathophysiologic mechanisms that are common to several neuropsychiatrically-relevant SVs.

Such common mechanisms should be the most promising targets for novel therapeutics.

Period of Performance:

One (1) 12-month base period.

SCOPE OF WORK

General Requirements:

Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government as needed to perform the Statement of Work below:

Specific Requirements:

• Contractor shall first expand and perform quality control and characterization analyses on 36 iPSC lines. Each line may be represented by 1-2 separate clones. Quality control and characterization analyses for each clone shall include sterility, mycoplasma, karyotyping, identity testing, pluripotency expression profiling, and differentiation capacity.

• iPSC clones that pass all quality control and characterization analyses will be differentiated into neural progenitor cells.

• Six master bank vials of each expanded iPSC clone will be shipped to Principal Investigator.

Differentiated NPCs will be tested using standard immunofluorescence methods for presence of cell-type markers including, but not limited to, MAP2 and nestin.

• Contractor shall ship multiple vials of each NPC clone (totaling approximately 10 million cells) to Principal Investigator.

LEVEL OF EFFORT:

For each period of performance, one or more experienced biological laboratory technicians as well as one or more senior scientific researchers will be required.

The estimated number of labor hours for iPSC clone expansion as well as performing quality control and characterization analyses is 60 labor hours per clone. The timeline is 5-7 months for iPSC expansion, quality control, and characterization.

The estimated number of labor hours for differentiation to NPCs as well as performing quality control analyses is 40 labor hours per clone. The timeline is 2-3 months for differentiation of iPSCs to NPCs.

GOVERNMENT RESPONSIBILITIES

The government will send the contractor frozen vials containing iPSC clones, as well as associated coded IDs. No personally identifiable information (PII) will be available to the contractor. All work will be performed at the contractor’s facility.

The government shall be responsible for reviewing and approving quality control and characterization reports as well as the final products (expanded iPSCs and NPCs) generated under the contract.

DELIVERY OR DELIVERABLES

1. For each clone submitted to Contractor, Contractor shall generate quality control data as specified under specific requirements and provide a written/electronic report to the Principal Investigator within 7 months of sample receipt.

2. Within 21 days of providing the expanded iPSC quality control report, Contractor shall ship at least 6 vials of each expanded iPSC clone. Clones will be frozen, packed on dry ice, and delivered safely to the Principal Investigator.

3. Principal Investigator shall review quality control report pertaining to characterization of iPSCs within 14 calendar days from date of receipt and notify Contractor which clones are authorized to be carried forward for NPC differentiation.

4. Within 2 months of this notification, Contractor shalll use published protocols to generate neural progenitor cells (NPCs) that display >80% positivity for both MAP2 and Nestin.

Contractor shall provide a report of the immunostaining results electronically when directed by the Principal Investigator.

5. Within 21 days of providing this report, Contractor shall ship multiple vials of each NPC clone (totaling approximately 10 million cells). Clones will be frozen, packed on dry ice, and delivered safely to the Principal Investigator.

6. Contractor shalll retain detailed records of all work for a period not less than 2 years after completion of the project and provide these reports to Principal Investigator upon request.

7. The data and deliverables may be staggered in time as contractor completes various stages of the project. Given the evolving COVID-19 situation, both government and contractor resources may need to be reviewed and revised to determine feasible delivery dates.

REPORTING REQUIREMENTS

The contractor is required to provide, minimally, monthly written progress reports. The reports will cover accomplishments, any problems encountered and/or resolved. The progress reports should be emailed to the Principal Investigator or designee.

END RESULTS/ DELIVERABLES

The following tables describes 1) the products and tangible end results that are expected from each task contained in the specific requirement, 2) the date each deliverable is due, and 3) the Government acceptance criteria. All days are business days unless otherwise specified.

End Result/Deliverable Due Date Acceptance Criteria Expanded iPSC Quality Control Report

Within 7 months of receiving a Clone sample.

Contractor shall generate quality control data as specified under specific requirements

Ship a minimum of 6 vials of each expanded iPSC Clone.

Within 21 days after the contractor delivers an iPSC Quality Control Report.

Contractor shall ship Clones frozen, packed on dry ice, and delivered within 2 days of shipment via a trackable shipment method, to the Principal Investigator (PI). Contractor shall notify PI in advance of sending shipments and provide tracking numbers.

Immunostaining Results Report.

When directed by the Principal Investigator

Contractor shall use previously agreed upon specific published protocols to generate neural progenitor cells (NPCs), verified by immunostaining that display >80% positivity for both MAP2 and Nestin

Ship multiple vials of each NPC clone (totaling approximately 10 million cells).

Within 21 days after the contractor delivers an Immunostaining Results Report.

Contractor shall ship Clones frozen, packed on dry ice, and delivered within 2 days of shipment via a trackable shipment method, to the Principal Investigator (PI). Contractor shall notify PI in advance of sending shipments and provide tracking numbers.

Monthly Progress Reports (MPR)

By 10th day of the following month.

The MPR is accurate, complete, submitted on time in and is prepared in accordance with the Reporting Requirements section. The Principal Investigator or designee will review and provide acceptance and/or feedback within 10 days of receipt.

OTHER CONSIDERATIONS

Travel:

Contractor travel will not be required.

Key Personnel:

Several experienced biological laboratory technicians as well as one or more senior scientific researchers will be essential to successful performance by the contractor.

Information System Security Plan:

The contractor is not required to develop, access, or host/maintain a federal information system.

Data Rights:

Quality control and characterization data and results are required from the contractor in meeting the requirements of the SOW. The government has unlimited rights regarding use, production, and disclosure of all data generated by the contractor under the scope of this SOW.

Section 508—Electronic and Information Technology Standards:

The contractor will use EIT in the performance of the SOW. The public will not have access to the EIT.

Publications and Publicity:

The contractor will not write and publish articles of data produced as a result of the requirements of the SOW.

Confidentiality of Information:

The government will not provide to the contractor any information or data of a personal nature about individual(s) or proprietary information or data pertaining to an institution or organization which is confidential. The contract is not expected to generate information or data which is confidential.