Attachment H - Statement of Work Template (see Section 11).docx

Attachment H – Statement of Work Template (SOW)

Statement of Work (SOW) for Battlefield Wound Infection Prevention and Treatment (BWI P&T) Barrier Combination (BC)

1.0 PURPOSE

The purpose of this requirement is for the development of a Barrier Combination product in support of the Battlefield Wound Infection Prevention and Treatment (BWI P&T) program. The Barrier Combination product is defined as being composed of both a physical barrier to protect a wound and an antibacterial and/or antifungal activity released from the barrier to prevent the spread of organisms and avoid systemic infections. This requirement aims to advance the development of novel medical countermeasures for the treatment of battlefield wounds. Technologies starting at a Technology Readiness Level (TRL) 5 or higher are preferred to achieve this goal.

Work under this requirement is intended to result in one award (i.e. Other Transaction Agreement (OTA)) for a prototype for a Barrier Combination product, which shall include Food & Drug Administration (FDA) regulatory communications, Chemistry, Manufacturing, and Controls (CMC) of Drug Substance and Drug Products, and clinical trials.

Upon prototype completion of Objective 3, the Government intends to assess whether this prototype is successful for a separate follow-on production acquisition between the Government and the Performer. Success is established when the Performer: (1) met the “key technical goals” of the prototype project, (2) satisfied “success metrics” incorporated into the pOTA and/or (3) accomplished a particularly favorable or unexpected result that justifies the transition to production.

All data is anticipated to support a future New Drug Application (NDA), Premarket Approval Application (PMA) and anticipated FDA approval and/or clearance.

It is the government preference that the Prime Performer serve as the Regulatory Sponsor.

2.0 BACKGROUND

The BWI P&T program is focused on identifying potential medical products for maturation that can prevent and treat infections in wounds sustained in combat. Current battlefield wound management care is governed based on the possibility of timely evacuation of wounded Service Members to a higher echelon of care. However, it is anticipated that future combat operations will require prolonged casualty care rather than immediate evacuation. Organisms commonly cultured from BWI include both bacterial and fungal species, and some are difficult to treat with currently available therapies. In addition, current fielded products require increased treatment frequency, target a limited number of organisms, are not effective against common drug-resistant pathogens, and have limited suitability throughout the entire continuum of care. The identification of novel solutions to address the needs of the Joint Force to prevent and treat BWI, especially as it pertains to counteracting emergent and/or drug-resistant organisms, would significantly enhance the preparedness of the warfighter for future combat operations.

3.0 SCOPE OF EFFORT

The scope of this effort includes all activities required to develop the Battlefield Wound Infection Prevention and Treatment (BWI P&T) Barrier Combination (BC) prototype product and achieve FDA approval (or clearance). That is, FDA approval/clearance may not be achieved during the period of performance, but MUST be submitted prior to end of PoP. The final product MUST a combination wound treatment that includes a barrier component that is either infused or impregnated with antimicrobial properties have U.S. Food Drug Administration (FDA) approval (or clearance). BWI P&T BC MUST meet a TRL 7 at time of submission to FDA; TRL 8 will be achieved once the prototype achieves FDA approval (or clearance).

It is the government’s expectation that the final FDA approved/cleared product be available for purchase via Defense Logistics Agency (DLA) e-catalog website (reference: https://www.dla.mil/Troop-Support/Medical/ECAT/).

4.0 OBJECTIVES

The primary objective of this effort is to develop a safe, effective, and commercially viable Barrier Combination product that meets the needs of the BWI P&T program. Specific tasks include:

Objective 1: The Performer shall ensure Objective 1 demonstrates the prototypes ability to provide a physical barrier to wound treatment and establish prototype antimicrobial activity against relevant pathogens. The Performer shall coordinate a kick-off meeting with Government and produce meeting minutes (Deliverable 1), provide spend plan (Deliverable 2) and other program specific documentation (Deliverables 3-6). Participate in monthly status meetings (Deliverable 7). Complete Monthly reports, including updates to the Project Management Plan (PMP) with Integrated Master Schedule (IMS) (i.e., including Risk Management Plan, Staffing Plan, and Integrated Master Schedule (IMS)) (Deliverable 8 & 9). Complete all necessary preclinical testing to support an Investigational New Drug (IND) or Investigational Device Exemption (IDE) application. (see Section 9.0 Constraints). Prior to use of human and animal blood samples in assay development and testing, the Performer shall obtain approval of assay development protocol from an Institutional Animal Care & Use Committee (IACUC) and U.S. Army Medical Research and Development Command’s (USAMRDC) Office of Human and Animal Research Oversight (OHARO) (Deliverable 10). The final product of Objective 1 is a working prototype of a barrier combination solution to prevent and/or treat wound infections ready to proceed into clinical study evaluations.

Objective 2: Execute clinical studies/trials to demonstrate the product's safety and efficacy in humans for an adult indication (see Section 8.0 Constraints). The Performer shall be required to prepare human use protocols and submit to relevant human use regulatory agencies including local Institutional Review Boards (IRB) and the U.S. Army Medical Research and Development Command’s (USAMRDC) Office of Human and Animal Research Oversight (OHARO) (Deliverable 10). Develop, maintain, and manage all regulatory submissions to the FDA and provide to the Government for review and comment (Deliverable 14). Develop and execute a regulatory strategy for the wound infection barrier combination as described in the Performer’s regulatory strategy to FDA approval/clearance for an adult indication. The regulatory strategy shall include a Target Product Profile (TPP) using the FDA TPP guidelines (Deliverable 3). This also includes establishing Chemistry, Manufacturing, and Controls (CMC) of Drug Substance and Drug Products and quality management processes to support the required clinical studies for FDA approval/clearance for an adult indication, quality release, stability testing, and other testing requirement for human use in compliance with applicable Title 21 Code of Federal Regulations or other activities required for FDA approval/clearance. Complete necessary optimization and processing development, manufacturing validation, manufacturing stability test for commercial availably (Deliverable 11). The final product of objective 2 must include, but is not limited to: a) completion of clinical studies and final technical report (Deliverable 13), b) preparation of and submitting FDA package for approval/clearance (Deliverable 14 & 15), and c) delivery of up to fifty (50) final design prototypes for operational test and evaluation, including instructions for use (Deliverable 12).

Objective 3: Delivering notice of FDA clearance or approval (Deliverable 14 & 15).

At the conclusion of this requirement, the below attributes are REQUIRED TO BE ACCOMPLISHED/COMPLETED for the BWI P&T BC final product:

NOTE: TRL 8 will be achieved upon FDA approval/clearance.

At the conclusion of this requirement, the below attributes are RECOMMENDED TO BE ACCOMPLISHED/COMPLETED for the BWI P&T BC final product:

5.0 PERIOD OF PERFORMANCE (PoP)

The period of performance is estimated to be 48 months. The PoP will begin upon award. Estimated time periods are:

Objective 1: 24 months Objective 2: 24 months Objective 3: 6 months

NOTE: The government anticipates that objectives 1 & 2 may be conducted simultaneously or overlapping for a period of several months but not to exceed 48 months. The remaining six (6) months are to account for pending FDA review and approval (or clearance) (Objective 3).

6.0 LOCATION

All work shall be performed at the Performer’s facilities and various clinical trial sites within the United States.

7.0 TRAVEL

Travel may be required for meetings with the Government program office, scientific conferences, and for the monitoring of clinical trial sites.

The Performer shall be authorized travel expenses consistent with the substantive provisions of the applicable travel regulations and the limitation of funds specified in the Agreement. Please refer Attachment E – OTA Agreement, Article 4 “Agreement Administration” for details.

All travel and transportation shall utilize commercial sources and carriers provided the method used for the appropriate geographical area results in reasonable charges to the Government. The Government will NOT reimburse the Performer for business class, first-class travel or for SUV/Trucks or luxury rental cars. Costs for transportation may be based on mileage rates, actual costs incurred, or on a combination thereof, provided the method used results in a reasonable charge. Receipts will be required to support incurred travel expenses.

Foreign Travel. Foreign travel under this requirement is defined as any travel outside of the continental United States and its territories and possessions. The cost of foreign travel is allowable only when specific written approval of the Agreements Officer (AO) is obtained 90 days prior to the commencement of the foreign travel. In order to obtain AO approval PRIOR to foreign travel, the Performer shall:

Allow 90 calendar days for completion for AO approval. Consult the DoD Foreign Clearance Guide at https://apacs.milcloud.mil/fcg2/prelogin for travel requirements. Costs incurred by Performer on official company business, whether foreign travel and/or domestic/local travel, are allowable subject to the limitations set forth in the Agreement’s terms and conditions.

8.0 GOVERNMENT FURNISHED PROPERTY

This requirement will not use Government Furnished Property.

9.0 CONSTRAINTS

a. Animal Care and Use Review Office (ACURO) approval.

Research under this requirement involving the use of animals SHALL NOT begin until the U.S. Army Medical Research and Development Command (USAMRDC) ACURO provides authorization that the research may proceed. Written approval to begin research shall be issued from the USAMRDC ACURO, under separate notification to the recipient. Written approval from the USAMRDC ACURO is also required for any sub-awardee that shall use funds from this award to conduct research involving animals. See Agreement Terms & Conditions, Article 14 General Provisions for submission requirements.

b. Office of Research and Regulatory Compliance (ORRC).

Research under this award involving the use of human subjects, to include the use of human anatomical substances or identifiable private information, SHALL NOT begin until ORRC provides authorization that the research may proceed. Written approval to begin research shall be issued from the ORRC, under separate notification to the recipient. Written approval from ORRC is also required for any sub-awardee that will be using funds from this award to conduct research involving human subjects or human anatomical substances. See Agreement Terms & Conditions, Article 14 General Provisions for submission requirements.

Per FDA guidelines, the Performer shall ensure that Good Laboratory Practice (GLP) recommendations are followed for pivotal animal studies. The studies and product development must be compliant with 21 CFR Part 58 and Part 11 and follow FDA’s various guides for industry, as applicable.

10.0 DELIVERABLES:

NOTE: For this requirement “deliver” means that the AOR is in receipt of the deliverable.

Deliverable 1:

Joint Government/Performer Kick-Off Meeting & Minutes Section: 4.0 Objective 1

Agreements Officer Representative (AOR) & Agreement Specialist (AS)

Minutes due NLT 7 days after the meeting occurs

N/A

Deliverable 2:

Spend Plan Section: 4.0 Objectives 1-3

Deliverable 3: Regulatory Strategy/Development Plan

Reference: CDRL A001, DID no. DI-TCSP-82040 Section: 4.0 Objectives 1-3

Deliverable 4: Quality Management Plan

Reference: CDRL A001, DID no. DI-TCSP-82040 Section 4.0 Objectives 1-3

Objectives 1-3

Objectives 1-3

Deliverable 7:

Monthly Meeting & Minutes Section: 4.0 Objective 1-3

Objective 1-3

Deliverable 9:

Project Management Plan with Integrated Master Schedule (IMS) detailing developmental effort (including Risk Management Plan, Staffing Plan, Integrated Master Schedule, Subcontractor Management Plan (if applicable), and Work Breakdown Structure) Section: 4.0 Objective 1-3

Deliverable 10:

USAMRDC’s Office of Human and Animal Research Oversight (OHARO) approvals.

AOR shall be included on all OHARO communications, submissions & approvals, study protocols, & study reports.

Reference: CDRL A001, DID no. DI-TCSP-82040 Section 4.0 Objective 1 & 2

Deliverable 11: Chemistry, Manufacturing, and Controls (CMC) Development Plan, Protocols & Reports (i.e. including production capability data)

Reference: CDRL A001, DID no. DI-TCSP-82040 Section 4.0 Objective 2

Deliverables 12:

Delivery of fifty (50) BWI P&T BC prototype(s) with instructions for use.

Section 4.0 Objective 2

Deliverable 13:

Final Technical Report

Reference: CDRL A001, DID no. DI-TCSP-82040 Section 4.0 Objective 2

Deliverable 14:

FDA Interactions & Submission Packages (i.e. phone calls, meetings, communications, submission packages, inspections/enforcements, Registration & Listing, post-marketing commitments, and clinical Lab improvement amendments/waivers/supporting docs).

Government shall be included on all FDA correspondences and any phone calls with the FDA.

Reference: CDRL A001, DID no. DI-TCSP-82040 Section 4.0 Objective 2

Deliverable 15:

Notice of FDA Approval/Clearance (i.e. responses, approval/clearance, refusal) Section 4.0 Objective 3

10.1 Deliverable Descriptions.

Deliverable 1: Joint Government/ Performer Kick-Off Meeting & Minutes. The Performer shall organize a kick-off meeting with designated AOR and Government representatives. The kick-off meeting will occur virtually. For the kick-off meeting, the Performer shall be prepared to provide an overview of the proposed product/system, information regarding the company and hold discussions with the AOR and Government representatives regarding the award and deliverables. The kick-off meeting duration is anticipated to be approximately 1 hour in length and occur only once.

Deliverable 2: Spend Plan. Spend Plan. The Performer shall provide a Spend Plan in accordance with IMS activities, which details how the Performer expects to incur and invoice on a monthly basis for costs against the Agreement. Actual cost reporting in accordance with IMS activities: The IMS shall inform the Spend Plan reporting structure. Actual incurred costs, per IMS activity should be reported as well as planned spending across the remaining Period of Performance. The Spend Plan total shall match with the total costs proposed for the entire effort. The Spend Plan shall be updated and submitted on a quarterly basis in Excel format.

Deliverable 3: Regulatory Strategy/Development Plan. Describe and outline the critical regulatory pathways and objectives to ensure adequate planning to bring a new product to market as well as the overall sustainability and the product end of life. Please refer to the Contract Data Requirements List (CDRL) A001 and Data Item Description (DID) No. DI-TCSP-82040. The DID can also be access at: https://quicksearch.dla.mil/qsSearch.aspx. Enter the DID No. under “Document ID.”

Deliverable 4: Quality Management Plan. Define the criteria and processes that will ensure and verify that data meets specific data-quality objectives throughout the Data lifecycle of clinical studies and meet U.S. FDA requirements to support FDA approval/clearance submission. Please refer to the Contract Data Requirements List (CDRL) A001 and Data Item Description (DID) No. DI-TCSP-82040. The DID can also be access at: https://quicksearch.dla.mil/qsSearch.aspx. Enter the DID No. under “Document ID.”

Deliverable 5: Business Plan. Outline the company’s current business status and describe the company’s growth plan for the next 5 years, outlining business goals and strategies for reaching them as it relates to the development of the candidate product. It should also include market research to support the company’s business plan.

Deliverable 6: Commercialization Plan. Describes the company’s strategy to generate revenue and business opportunities, outlines a strategy to move candidate product(s) into the Market, and describes current and anticipated market landscape and resources required to address the opportunity of the candidate product.

Deliverable 7: Monthly Meeting & Technical Updates. The Performer MUST organize and establish reoccurring monthly meetings with the AOR throughout PoP. The meetings MUST be used as a means for both the Performer and Government to exchange status updates and discuss any other planning considerations or relevant information. The monthly meetings between Performer and Government may be conducted virtually and are anticipated to last approximately 30 minutes to 1 hour in length. Performer MUST submit meeting minutes.

Deliverable 8: Monthly Report. The Performer MUST organize and provide a monthly technical report/summary demonstrating progress towards prototype development and milestone completion, addressing development risks, and identifying issues/delays. The monthly report from the Performer can be provided electronically to the Government no later than 15 days after the 1st of the following month (i.e. June report would be due no later than July 15).

Deliverable 9: Project Management Plan with Integrated Master Schedule (IMS). The Performer MUST provide a detailed IMS specifying developmental plans to the proposed device/system. The IMS shall address what the anticipated steps are and overall timelines in order for all components of the Performer’s proposed prototype. Throughout each tasks period of performance, the Performer MUST update the IMS monthly with any changes. Additionally, the PMP shall include Risk Management Plan, Staffing Plan, Subcontractor Management Plan (if applicable), and Work Breakdown Structure.

Deliverable 10: OHARO communications, submissions & approvals, study protocols, & study reports. Conduct all development activities in compliance with US FDA (to include both human subject protection and animal care and use regulations), ICH, local, regional, and other applicable regulations; as necessary in order to achieve Government requirements. The Contractor shall comply fully with 32 CFR Part 219 and DoD Directive 3216.02, applicable DoD component policies, 10 U.S.C. 980, and, when applicable, FDA policies and regulations. The Contractor shall not commence performance of research involving human subjects that is covered under 32 CFR Part 219 or that meets exemption criteria under 32 CFR 219.101(b), or expend funding on such effort, until and unless the conditions of either the following paragraph (1) or (2) have been met: Include AOR on all OHARA communications & submissions. Deliver approvals, study protocols and study reports. Please refer to the Contract Data Requirements List (CDRL) A001 and Data Item Description (DID) No. DI-TCSP-82040. The DID can also be access at: https://quicksearch.dla.mil/qsSearch.aspx. Enter the DID No. under “Document ID.”

Deliverable 11: Chemistry, Manufacturing, and Controls (CMC) Development Plan, Protocols & Reports. Define production capacity and ability to produce products within specifications. Provide cGMP manufacturing documentation for all product materials. Provide all manufacturing process protocols and reports. Please refer to the Contract Data Requirements List (CDRL) A001 and Data Item Description (DID) No. DI-TCSP-82040. The DID can also be access at: https://quicksearch.dla.mil/qsSearch.aspx. Enter the DID No. under “Document ID.”

Deliverable 12: Delivery of fifty (50) BWI P&T BC prototype(s) with instructions for use.

Deliverable 13: Final Technical Report. Deliver final technical report summarizing development efforts and outcomes. Please refer to the Contract Data Requirements List (CDRL) A001 and Data Item Description (DID) No. DI-TCSP-82040. The DID can also be access at: https://quicksearch.dla.mil/qsSearch.aspx. Enter the DID No. under “Document ID.”

Deliverable 14: FDA interactions & Submission Packages. Include Government on all FDA interactions throughout performance period. FDA interactions include, but are not limited to phone calls, meetings, communications, submission packages, inspections/enforcements, Registration & Listing, post-marketing commitments, and clinical Lab improvement amendments/waivers/supporting documents. The AOR MUST be copied on all correspondence with the FDA, included at meetings and phone calls that occur at any time throughout the POP. Please refer to the Contract Data Requirements List (CDRL) A001 and Data Item Description (DID) No. DI-TCSP-82040. The DID can also be access at: https://quicksearch.dla.mil/qsSearch.aspx. Enter the DID No. under “Document ID.”

Deliverable 15: Notice of FDA Approval/Clearance. Inform the Government of all FDA responses to include but are not limited to: 1) submission responses, 2) notifications of FDA approval/clearance, and 3) Submission package refusal.

11.0 Tasks

Tasks for Objective 1:

11.1 11.2

Tasks for Objective 2:

11.3 11.4

Tasks for Objective 3:

11.5 11.6

12.0 Milestones

Cost/ Price

See Attachment G1 – Cost or G2 FFP Template, tab “Milestones”

See Attachment G1 – Cost or G2 FFP Template, tab “Milestones”

See Attachment G1 – Cost or G2 FFP Template, tab “Milestones”

See Attachment G1 – Cost or G2 FFP Template, tab “Milestones”

13.0 ABBREVIATIONS

(End of Attachment H - Statement of Work template)