75N95023R00004_Att. 6_Sample TORFP Technical Area 3.pdf
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- Attached to
- Pharmacology Studies and Animal Model Development and Related Services for Drug Development
- Solicitation number
- 75N95023R00004
About this file
This document outlines the requirements for a task order to establish induced pluripotent stem cell lines from Alagille syndrome patients, generate differentiated liver cell types from those lines, and produce a three-dimensional organoid system for drug development studies. The task order is for 18 months under Solicitation Number 75N95023R00004 issued by the Department of Health and Human Services National Institutes of Health. The contractor will generate iPSC lines from patient fibroblasts and lymphoblasts, characterize the lines, differentiate them into hepatocytes, hepatic stellate cells, and cholangiocytes, and use those cells to produce 3D cholangiocyte organoids modeling various genetic backgrounds for efficacy testing. The contractor must submit monthly progress reports and final reports within two weeks of completing each task. The deliverables are to be provided electronically to the contracting officer's representative by the specified due dates.
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SAMPLE TASK ORDER REQUEST FOR PROPOSAL FOR TECHNICAL AREA 3
I. Task Order Information
A. Task Order Title: Generation and characterization of an ex vivo system to support drug development for Alagille Syndrome
B. Task Order Period of Performance: 18 months
C. Task Order Type: Cost plus Fixed Fee or Firm Fixed Price
D. Task Order Technical Area(s): Technical Area 3
II. Task Order Proposal Instructions
See Section L – Instructions to Offerors of Request for Proposals No. 75N95023R00004 for proposal instructions.
III. Task Order Technical Requirements
A. TASK DESCRIPTION: The following study involves work described in Technical Area 3 of the Statement of Work.
The Government seeks to identify and develop therapeutic candidates for Alagille Syndrome (ALGS), a rare autosomal dominant condition that manifests in malfunctions in multiple organ systems. Liver dysfunctions are common in ALGS patients, due to disruptions in bile duct development. The objectives of this SOW are to establish induced pluripotent stem cell (iPSC) lines; to generate differentiated liver cell types from the iPSCs; and to produce a physiologically relevant three-dimensional (3D) liver organoid system suitable for subsequent drug development studies.
Task 1. Establishment of ALGS patient-derived iPSCs for disease modeling
ALGS is driven by various gene mutations, most frequently in JAG1 and less frequently in NOTCH2. The Government, through its clinical collaborators, has access to cells derived from 10 ALGS patients. The Contractor is to generate and characterize 10 iPSC lines from these patient fibroblasts (7) and lymphoblasts (3), which will be used in subsequent studies to evaluate the efficacy of therapeutic candidates across a range of ALGS mutations. A normal control iPSC line shall be developed, derived from a commercially acquired fibroblast sample. The iPSC lines are to be characterized with respect to morphology, phenotype, genotype, identity, mutation status and differentiation potential.
The Government will supply the Contractor with the necessary patient-derived fibroblast and lymphoblast samples. The Contractor will be responsible for obtaining the normal control fibroblast cells from an appropriate commercial source.
Task 2. Generation of differentiated liver cell types
Cholangiocytes are the epithelial cells lining the bile duct. Hepatic stellate cells (HSCs) regulate the proliferation of hepatoblast progenitors and hepatocytes by producing key growth factors. The Contractor is to use the 10
RFP No. 75N95023R00004 Attachment 6 patient-derived and the normal control iPSC lines from Task 1 to generate differentiated hepatocytes, HSCs and cholangiocytes. These differentiated cell types will be used to generate three-dimensional liver organoids in subsequent studies. Cell types are to be characterized with respect to morphology, gene expression, presence of relevant protein markers, and cellular function.
Task 3. Production of a three-dimensional (3D) liver organoid system
The Contractor is to generate a three-dimensional (3D) organoid system to model the biliary duct in vitro. The Contractor will use the differentiated cell types produced in Task 2 to generate 3D cholangiocyte organoids representing the 10 patient-derived genetic backgrounds plus the normal control. The organoids are to be cultured in a format of not less than a 96-well plate. The Contractor will characterize the biliary epithelial function of the ALGS and normal control organoids, and will develop biomarkers that can be incorporated into efficacy assays.
Assumptions, Constraints, Clarifications and Qualifications
1. The Contractor is to assume that all patient-derived cells not commercially acquired from public repositories have been obtained through IRB approved protocols and have been properly consented for secondary research purposes, including all aspects of the work described in this task order.
B. TASK ORDER REPORT, DELIVERY SCHEDULE AND REPORTING REQUIREMENTS: Satisfactory performance of the task order shall be deemed to occur upon performance of the work described in the TO award, and upon completion, delivery, and acceptance by the Contracting Officer, or duly authorized representative, the below listed deliverables.
Technical Reports
1. Monthly Progress Report
This report shall include a description of the activities during the reporting period, and the activities planned for the ensuing reporting period. The first reporting period consists of the first full month of performance plus any fractional part of the initial month. Thereafter, the reporting period shall consist of each calendar month. Reporting shall be due on or before the 10th calendar day following each reporting period. A monthly report will not be required for the final month covered by the last Final Study Report.
2. Final Study Report
The Final Study Report shall accurately and completely describe the study design, procedures, and findings;
and present an analysis and summary of the data followed by the conclusions derived from the analyses.
The report shall also include: (i) a cover page that includes the task order title, contract and task order numbers, report authors, laboratory addresses, dates of study initiation and completion, and sponsor; (ii) an abstract at the beginning of the report; (iii) a summary that follows the abstract; (iv) the signature of the study director; (v) a table of contents; and (vi) a statement prepared and signed by the Quality Assurance Unit that refers to all phases of the study and to where the raw data, records, reports, and samples are stored.
Task Order Deliveries
Item Description Delivery Delivery Schedule
1 Monthly Progress Report Electronically to COR & CO
Due on the 10th calendar day following each reporting period.
2 Report of Completed Technical Requirements (Task 1)
Electronically to COR & CO
No later than (NLT) 2 weeks after the completion of Task 1
3 Report of Completed Technical Requirements (Task 2)
Electronically to COR & CO NLT 2 weeks after the completion of Task 2
4 Report of Completed Technical Requirements (Task 3)
Electronically to COR & CO NLT 2 weeks after the completion of Task 3
5 Final Study Report Electronically to COR & CO
Due on or before Task Order expiration date
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