Development and Evaluation of a Cryopreserved Platelet (CPP) Product for the U.S. Military

Purpose

This solicitation, issued by MTEC, represents a Request for Project Proposals (RPP) for MTEC support of the U.S. Army Medical Materiel Development Activity (USAMMDA) technology objectives. Military relevance is a critical component of Solution Brief submission. Strategic and tactical oversight for the award(s) supported by this RPP will be provided by a combination of the Pharmaceutical Systems (PS) Program Management Office (PMO) at USAMMDA and the Integrated Program Team (IPT) or working group (WG).

Program Objective

The awardee(s) of this RPP is expected to perform all manner of research and development activities, as necessary, to achieve a U.S. Food and Drug Administration (FDA)-licensed dimethyl sulfoxide (DMSO) cryopreserved platelet (CPP) product that meets or exceeds U.S. Military requirements (see Table 1 in the RPP) and is commercially sustainable, thus mitigating the risk of exhausted supply in mass casualty situations.

Problem Definition

Management of severe hemorrhage due to trauma and/or surgical repair of damaged organs and tissues requires the contemporaneous replacement of large volumes of blood products, including platelets. Platelets are a normal component of blood and a key initiating factor in hemostasis (blood clotting). Current standard of care in both civilian and military settings consists of walking donor, room-temperature stored, apheresis platelets (i.e., liquid stored platelets), which only have a shelf life of 5-7 days with decreasing efficacy during this period of storage. Platelet supply in an unsettled military theater of operations is inherently limited due to the inability to store current platelet products for more than 5-7 days. In the event of in-theater mass casualty situations, the supply of walking donor apheresis platelets will not meet demand, thus compromising the ability (and capacity) of U.S. Army field medical teams to curtail bleeding and stabilize patients.

Limitations of Current Standard of Care

The current standard of care involves utilizing liquid stored platelets (LSP), currently licensed for storage for up to 5 days at room temperature (20 - 24°C) under gentle agitation. The storage requirements impose inherent constraints and compromise availability of the platelets, especially in the theater of operations. Additionally, LSP are available only via walking donor; i.e., they cannot be shipped due to their brief shelf life.

Leading Technology

The leading candidate for a long-term stored platelet product, by virtue of technological maturity and risk, is DMSO CPP. DMSO CPP is a frozen platelet product (regulated as a biologic by the FDA) composed of γ-irradiated (2500 centigray (cGy))-leukocyte-reduced apheresis platelets stored in plasma and anticoagulant citrate dextrose solution A (for up to 57 hours after apheresis), concentrated, and frozen in approximately 6% DMSO at -80°C and stored at ≤ -65°C. Hence forward, this candidate will be referred to as CPP. Development of CPP is in direct support of the USAMMDA’s line of effort to enhance battlefield management of severe hemorrhage due to combat trauma.

The objective of this program is to achieve an FDA-licensed, commercially-viable CPP product. As such, Offerors are expected to conduct all manner of development, test, and evaluation activities (as necessary) to achieve an FDA-licensed CPP product that is suitable for use by the U.S. Military. Anticipated activities include (but are not limited to):

1. Design and development of a CPP manufacturing process that is compliant with FDA regulations and applicable guidance for current good manufacturing practices (cGMP).
2. Design, development, and validation of processes (inclusive of any necessary materials, equipment, and tests/assays) to enable storage and shipment of CPP for U.S. Military use.
3. Performance of all necessary non-clinical (in-vitro) studies and clinical trials.
4. Execution of all activities commensurate with serving as the Investigational New Drug (IND) holder and regulatory sponsor in accordance with 21 Code of Federal Regulations (CFR) 312 subpart D, including all regulatory submissions and regulatory sponsorship.
5. Development and maintenance of various management, risk, project, and quality plans/reports (as necessary) to provide documented evidence that the development effort is being effectively managed in accordance with the risk profile.

Note: Government experience thus far has shown that the CPP product will be regulated by the FDA as a Biologic product.

Scope of Work

Statement of Work (SOW)

The SOW developed by the Lead MTEC member organization is intended to be incorporated into a binding agreement if the Solutions Brief is selected for award. If no SOW is submitted, there will be no award. The proposed SOW shall contain a summary description of the technical methodology as well as the task description, but not in so much detail as to make the contract inflexible. Do not include any proprietary information or company-sensitive information in the SOW text. The following is the required format for the SOW:

Statement of Work

Submitted under Request for Project Proposal (Insert current Request No.)

(Proposed Project Title)

Introduction/Background (To be provided initially by the Offeror at the time of submission. Submitted information is subject to change through negotiation if the Government selects for funding.)

Scope/Project Objective (To be provided initially by the Offeror at the time of submission. Submitted information is subject to change through negotiation if the Government selects for funding.)

This section includes a statement of what the project covers. This should include the technology area to be investigated, the objectives/goals, and major milestones for the effort.

Requirements (To be provided initially by the Offeror at the time of submission to be finalized by the Government based on negotiation of Scope/Project Objective.)

State the technology objective in the first paragraph and follow with delineated tasks required to meet the overall project goals. The work effort should be segregated into major phases, then tasks, and identified in separately-numbered paragraphs (similar to the numbered breakdown of these paragraphs). Early phases in which the performance definition is known shall be detailed by subtask with defined work to be performed. Planned incrementally-funded phases will require broader, more flexible tasks that are priced up front, and adjusted as required during execution and/or requested by the Government to obtain a technical solution. Tasks will need to track with established adjustable cost or fixed price milestones for payment schedule. Each major task included in the SOW should be priced separately in the Cost Proposal. Subtasks need not be priced separately in the Cost Proposal.

Deliverables (To be provided initially by the Offeror at the time of submission. Submitted information is subject to change through negotiation if the Government selects for funding.)

Results of the technical effort are contractually binding and shall be identified herein. Offerors are advised to read the Base Agreement carefully. Any and all hardware/software to be provided to the Government as a result of this project shall be identified. Deliverables should be submitted in PDF or MS Office format. It must be clear what information will be included in a deliverable either through a descriptive title or elaborating text.

Milestone Payment Schedule (To be provided initially by the Offeror at the time of submission. Submitted information is subject to change through negotiation if the Government selects for funding. The milestone schedule included should be in editable format (i.e., not a picture).)

The Milestone Payment Schedule should include all milestone deliverables that are intended to be delivered as part of the project, a planned submission date, the monetary value for that deliverable, and any cost share, if applicable. For fixed-price agreements, when each milestone is submitted, the MTEC member will submit an invoice for the exact amount listed on the milestone payment schedule. For cost-reimbursable agreements, the MTEC member is required to assign a monetary value to each milestone. In this case, however, invoice totals are based on cost incurred and will not have to match exactly to the amounts listed on the milestone payment schedule.

The milestones and associated deliverables proposed should, in general:

• be commensurate in number to the size and duration of the project (i.e., a $5M multiyear project may have 20, while a $700K shorter term project may have only six);
• not be structured such that multiple deliverables that might be submitted separately are included under a single milestone;
• be of sufficient monetary value to warrant generation of a deliverable and any associated invoices;
• include at a minimum Quarterly Reports which include both Technical Status and Business Status Reports (due the 20th of March, June, September, December), Annual Technical Report, Final Technical Report, and Final Business Status Report. Reports shall have no funding associated with them.

Points of Contact

For inquiries, please direct your correspondence to Biomedical Research Associate Chuck Hutti, Ph.D. at Chuck.Hutti@ati.org.