6.4947338_SOW_Malaria.pdf

STATEMENT OF WORK

July 2, 2018

GENERAL INFORMATION

Title of Project:

Malaria Culture Service

Statement of Need and Purpose:

The scope of this work is to provide a 24 month malaria culture service that will provide asexual blood stage cultures and medium on a monthly basis, and enriched late stage gametocyte cultures, blood, and medium on a quarterly basis.

Malaria affects an estimated 250 million people worldwide, particularly in the tropical regions of Sub-Saharan Africa and approximately 650,000 patients die each year. Even while on current therapies, patients remain infectious for a period of time, allowing further mosquito-borne transmission to others.

Control of parasite transmission is critical for elimination and eradication of malaria. However, most antimalarial drugs are not active against sexual stage P. falciparum parasites — called gametocytes — which are responsible for the spread of malaria from person to person via mosquitoes. Torin2 was identified as a lead molecule in a new class of gametocytocidal antimalarial drugs.

As part of a lead optimization program, researchers in the TRND Program (Therapeutics for Rare and Neglected Diseases) at NCATS (the National Center for Advancing Translational Sciences) are using a gametocyte viability assay, as well as an asexual stage parasite assay to optimize the Torin2 series and advance a drug candidate through pre-clinical development and early clinical development.

Background Information and Objective:

Monthly asexual stage parasites and quarterly provision of Plasmodium falciparum enriched gametocytes for use in viability assays:

1. Plasmodium falciparum asexual parasites (20 mL), with ring stages >90%.

2. Complete medium (100mL) for asexual parasites.

3. Plasmodium falciparum enriched gametocytes (5 mL), stage IV-V >70%. 4-5X10^7 gametocytes/ml

4. 50% Blood (1-5 mL).

5. Complete medium (100mL) for enriched gametocytes.

Period of Performance:

POP is 24 months TBD after receipt of award

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:

Malaria Culture Service

Specific Requirements:

• Monthly, 20 ml asexual parasites at 1% parasitemia and 4% hematocrit are needed to this project. Ring stages must be >90%. The culture has to be maintained at 37 degree under hypoxia conditions (90% N2, 5% CO2, and 5% O2) all the time during the shipment. Additionally, 100 ml complete medium are needed for assay dilution.

• Quarterly, 5 ml enriched and purified gametocytes at 4-5X10^7 gametocytes/ml are needed for this project. In gametocyte culture, the percentage of the stage IV-V gametocytes needs to be >70% and asexual parasites and stage I-II needs to be minimal < 10%. The cultures will be used in house for viability assays for 72 hour drug sensitivity tests. TRND has developed alarmablue assay and ATP lite assay for the drug viability test. TRND prefer to < 10% or less red blood cells in the gametocyte culture in order to use the robust and sensitive ATP lite assay. However, If the red blood cells in the gametocyte culture is high than 10%, TRND will use alarmablue assay. Additional 1-5 ml of 50% blood and 100 ml complete medium are required for assay dilution. The culture has to be maintained at 37 degree under hypoxia conditions (90% N2, 5% CO2, 5% O2) all the time during the shipment. Delivery is on Tuesday.

• TRND will do the gametocyte QC each time when perform the assay. The viability data of gametocyte at 0h, 24h, 48h and 72h will be collected and the ratio of the luminescence of the gametocyte and medium alone at the indicated time will be used to evaluate the quality of the gametocyte. TRND and the Contractor will work together to reach a reasonable value for gametocyte QC according to the data collected in the future.

• If a gametocyte assay fail because of unhealthy gametocytes (eg, gametocyte or RBCs lysis), the Contractor will provide another 5 ml enriched gametocytes in the following month until the drug efficacy assays work. Any additional gametocytes will be provided at no additional cost. If the drug efficacy assays fail because of TRND biology related issues, the Contractor will not provide additional enriched gametocytes. TRND has an option to order four (4) additional supply of 5mL of the enriched late stage gametocyte cultures, blood and medium due to project needs. The contract will be two years. TRND will order asexual parasites monthly and gametocytes quarterly. TRND may terminate the contract at any time.

• All work must be conducted with strict compliance to vendor Standard Operating Procedures (SOP), with all excurisons from these SOP immediately reported to TRND and comprehensively noted in the final report.

DELIVERY OR DELIVERABLES

The following table contains a list of deliverables with notation of due dates. All days identified are intended to be normal business days unless otherwise specified. The Contractor may suggest an alternative due date for any or all deliverables in their offer. The final schedule will be agreed to by TRND based on the Contractor’s proposed cost and proposed delivery schedule.

Deliverable Summary and Due Dates

Deliverable Due Date

Status reports Monthly

Asexual parasites and medium Monthly

Gametocytes, blood and medium Quarterly

Deliverable Descriptions and Acceptance Criteria

Descriptions and Specific Acceptance Criteria

The following deliverables shall be developed in this project. The Offeror’s proposed Project Plan should clearly contain all tasks and milestones required to produce these deliverables.

All deliverables shall be developed according to constraints lists in the “Conformance and Compliance” section above where applicable.

Deliverable: Gametocytes.

Description and Acceptance Criteria: The culture must have purified and enriched gametocyte at 4-5X10^7 gametocytes/ml. > 70% gametocytes needs to be at stage IV- V. The percentage of asexual parasites need to be very minimum (< 10%). It has to be maintained at 37 degree under hypoxia conditions (90% N2, 5% CO2, 5% O2) all the time during the shipment.

Deliverable: Asexual stage parasites.

Description and Acceptance Criteria: The culture must be prepared at 1% parasitemia and 4% hematocrit. Ring stages must be >90%. It has to be maintained at 37 degree under hypoxia conditions (90% N2, 5% CO2, 5% O2) all the time during the shipment.

Ring stages has to be more than 90%.

Deliverable: complete medium.

Description and Acceptance Criteria: the same batch of complete medium used for parasite culture are required. At least 100 ml of complete medium is required for both asexual culture and gametocyte culture.

Deliverable: 50% human blood.

Description and Acceptance Criteria: 50% human blood is required for gametocyte cultures. The human blood must be able to maintain gametocyte culture. The human blood must be less than 3 weeks after withdrawing.

General Acceptance Criteria

• In addition to specific acceptance criteria listed above, general quality measures, as set forth below, will be applied to each deliverable received from the Contractor under this Statement of Work.

• Accuracy – Deliverables shall be accurate in presentation, technical content, and adherence to accepted elements of style.

• Clarity – Deliverables shall be clear and concise. Any/all diagrams shall be easy to understand and be relevant to the supporting narrative.

• Consistency to Requirements – All deliverables must satisfy the requirements of this Statement of Work.

• Timeliness – Deliverables shall be submitted on or before the due date specified in this Statement of Work or the PMP, or submitted in accordance with a later scheduled date determined by the Government.

REPORTING REQUIREMENTS

Monthly and Quarterly Analytical Report

The Contractor shall document the analyses for each monthly and quarterly delivery in a report due with each delivery. It is expected that this report will include, but not be limited to:

• Document the percentage of ring stages for asexual culture.

• Document the percentage of gametocytes for each stage (I-II, III, and IV-V).

• Document the age of the blood (time since the blood was drawn) and the time since the parasites were thawed.

Final Report

The Contractor shall submit a Final Report within 30 days of contract completion and shall include the following:

• Contractor Name and Address

• Name of Person Submitting the Report

• Contract Number

• Report Date

• Period Covered by the Report

• A comprehensive Summary of Work performed during reporting period

OTHER CONSIDERATIONS

Travel:

The majority of the work will be performed at the Contractor’s facilities; however, TRND may ask that specific tasks, such as testing and demonstrations, be performed at other locations.

Publications and Publicity:

Contractor does not have permission to publish NCATS data.