Statement of Work NIAID-NOI-22-2117352.pdf

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Statement of Work (SOW)

Good Manufacturing Practice (cGMP) Production of Trichuris trichiura

INTRODUCTION AND BACKGROUND

The National Institutes of Health (NIH) is one of the world's foremost biomedical research organizations. It is the principal Federal agency for the conduct and support of medical research in the United States. The National Institute of Allergy and Infectious Diseases (NIAID), Division of Intramural Research (DIR) was established to conduct and support research to better understand the causes of allergic, immunologic, and infectious diseases, and to develop better means of preventing, diagnosing, and treating illness.

Type-2 immunity induced by helminth infections may be therapeutically beneficial for improving symptoms of inflammatory bowel diseases and metabolic syndromes, but this may also benefit only specific subsets of individuals. The mechanisms underlying the heterogeneity of type-2 responses between individuals still remains poorly understood. We believe that characterizing these mechanisms will enable us to develop strategies to utilize helminth infections as treatment for specific inflammatory conditions (e.g., autoimmune diseases and metabolic conditions) for the right individuals, as well as designing better approaches toward limiting pathology that is caused by helminth infections.

This requirement is for the generation, inventory, and storage of two to six million Good Manufacturing Practice (cGMP) grade nematode parasite Trichuris trichiura isolated from a healthy human donor for use in a Controlled Human Trichuris Infection (CHTI) with fecal samples received by Georg Washington University (GWU). In addition, this Statement of Work (SOW) covers the Good Documentation Practices (GDP) required for cGMP as well as how to prepare an Investigation New Drug (IND) application for controlled Human Trichuris Infection with the U.S.

Food And Drug Administration (FDA). There will be no exchange of personally identifiable information (PII) between the NIAD and the contractor. This is not a Research and Development (R&D) requirement.

SCOPE

The scope of activities for this project will encompass all tasks and functions associated with the initiation, implementation, conduct, analysis, completion, and closeout of cGMP production of up to 6 million Trichuris trichiura inoculum to be used by the Laboratory of Parasitic Diseases (LPD) at the NIAID in the Trichuris Trichiura Production Unit (TTPU).

TECHNICAL 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 SOW as stated herein.

General and Task Area specific requirements as defined in the SOW are applicable.

TO Specific Requirements

The contractor shall be required to:

Study Conduct:

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a. Current cGMP production of up to six million of the nematode parasite Trichuris trichiura isolated from a healthy human donor for use in a CHTI in the TTPU.

b. Receive fecal samples from healthy human donor(s) infected with Trichuris trichiura, isolate T.

trichiura eggs, store eggs until maturation to the infective stage, and produce an inoculum of T. trichiura for controlled infection of human participants in the in the TTPU.

c. cGMP compliant manufacturing services include quantitative counts of T. trichiura eggs in fecal samples, isolation of eggs, and release (via test for viability and molecular speciation) in the TTPU. If necessary, T. trichiura eggs will be prepared for microbiological testing conforming to requirements of the US-FDA for an orally administered biological.

d. Maintain GDP for cGMP production of T. trichiura eggs to facilitate preparation for an IND application for administration of T. trichiura in human participants, which includes standard operating procedures (SOP), a quality management plan (QMP), and a documentation system.

e. Shipping services for fecal samples from healthy human donors infected with T. trichiura to the TTPU and subsequent shipping of inoculum to LPD, and (if necessary) shipping to a facility for bioburden testing.

f. Write and submit an IND to the US-FDA to infect healthy human participants with T. trichiura T in a controlled human infection model.

Technical Requirements:

a. Establish and maintain laboratory space at GWU for cGMP manufacture of up to six million of the Trichuris trichiura isolated from a healthy human donor for use in a CHTI in the TTPU.

b. Establish a dedicated effort of research associate to conduct cGMP manufacture of T.

trichiura eggs for use as an inoculum in CHTI in the TTPU.

c. Maintain regulatory component for the cGMP manufacture for conducting cGMP manufacture of T. trichiura, including project management; patient recruitment and clinical data collection and management; technical assistance, and training of local staff.

d. Document close communication and coordination of off-site NIAID scientists designing clinical studies through regular written and verbal communications.

e. Provide shipping services to support cGMP manufacture of T. trichiura eggs for CHTI, including shipping of fecal samples from infected donor from Denmark to US.

Administrative Oversight:

a. Oversee laboratory operations, including work conducted by research associates as needed in the TTPU.

b. Prepare, monitor, and track local budgets and expenditures for supplies and resources for TTPU.

c. Prepare and submit transport documentation between the clinical and testing sites, including any permit processing, as requested.

d. Prepare and submit the necessary documentation for cGMP production of T. trichiura, including SOPs, QMP, and IND application.

Manufacturing Oversight:

a. Conduct cGMP manufacture of T. trichiura as described above. Microbiology, PCR, and

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Flow cytometry assays as required by the clinical protocols outlined above.

b. Maintain production and release testing equipment to the cGMP standard.

c. Conduct quality control procedures on production and testing systems at of up to six million of the T. trichiura inoculum.

d. Report manufacturing and regulatory results to NIAID.

Site Oversight:

The manufacture of T. trichiura eggs is being done in the cGMP compliant TTPU. Biosafety Level 2 (BSL2) facility (Suite 511) in the Department of Microbiology, Immunology, and Tropical Medicine at the GWU.

Government Furnished

There will be no Government furnished supplies or materials.

OPTIONS

In addition to the services/quantities outlined above to be provided for the base requirement, Options(s) for additional services/quantities under the contract may be exercised at the discretion of the Government and are defined as follows:

Option 1 – 4: Extend the Period of Performance: The Government includes options to extend the period of the performance. Each option is for one additional year or less of performance. The total period of performance resulting from the base period plus all potential Term Options is five (5) years. If Option 1-4 are exercised, the services required will be the same as provided during the base year.

DELIVERABLES

a. Generation, inventory, and storage of up to six million of cGMP compliant Trichuris trichiura isolated from a healthy human donor for FDA compliance.

b. Shipment of batches of Trichuris trichiura to LPD upon request.

c. Report cGMP manufacturing and US-FDA regulatory results to NIAID.

REPORTING REQUIREMENTS

All written documents for this contract shall be submitted electronically in a format readable by standard word processing technology. All electronic files shall be submitted to the Task Leader, COR and Contracting Officer as designated.

In addition to any other required reporting set forth elsewhere by the Contract, submission of the following Technical Progress Reports shall also be required:

Quarterly Reports: The contractor shall submit two (2) copies of a quarterly summary report that documents and summarizes the results of each quarter of the contract reporting period.

Brief and factual progress reports will be submitted using the following format:

• A cover page containing:

• Contract number and title

• Period of performance being reported

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• Contractor’s name and address

• Author’s name(s)

• Date of preparation

SECTION I – An introduction covering the period and scope of the contract.

SECTION II – Number of shipments made, including quantities of items shipped during the quarter.

SECTION III – Substantive performance: a description of current technical or substantive performance and any problems that may exist along with proposed corrective action.

PERIOD OF PERFORMANCE

The period of performance for full performance will be a base year with four (4) one-year option periods.