W81XWH16T01950002.pdf

0010820002

AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT

Except as provided herein, all terms and conditions of the document referenced in Item 9A or 10A, as heretofore changed, remains unchanged and in full force and effect.

15A. NAME AND TITLE OF SIGNER (Type or print)

30-105-04EXCEPTION TO SF 30

APPROVED BY OIRM 11-84

STANDARD FORM 30 (Rev. 10-83) Prescribed by GSA

FAR (48 CFR) 53.243

The purpose of this amendment is to add Questions and Answ ers

1. CONTRACT ID CODE PAGE OF PAGES

J 1 7

16A. NAME AND TITLE OF CONTRACTING OFFICER (Type or print)

16C. DATE SIGNED

BY 14-Jul-2016

16B. UNITED STATES OF AMERICA15C. DATE SIGNED15B. CONTRACTOR/OFFEROR

(Signature of Contracting Officer)(Signature of person authorized to sign)

8. NAME AND ADDRESS OF CONTRACTOR (No., Street, County, State and Zip Code) X W81XWH-16-T-0195

X 9B. DATED (SEE ITEM 11)

08-Jun-2016

10B. DATED (SEE ITEM 13)

9A. AMENDMENT OF SOLICITATION NO.

11. THIS ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS

X The above numbered solicitation is amended as set forth in Item 14. The hour and date specified for receipt of Offer is extended, X is not extended.

Offer must acknowledge receipt of this amendment prior to the hour and date specified in the solicitation or as amended by one of the following methods:

(a) By completing Items 8 and 15, and returning 1 copies of the amendment; (b) By acknowledging receipt of this amendment on each copy of the offer submitted;

or (c) By separate letter or telegram which includes a reference to the solicitation and amendment numbers. FAILURE OF YOUR ACKNOWLEDGMENT TO BE RECEIVED AT THE PLACE DESIGNATED FOR THE RECEIPT OF OFFERS PRIOR TO THE HOUR AND DATE SPECIFIED MAY RESULT IN

REJECTION OF YOUR OFFER. If by virtue of this amendment you desire to change an offer already submitted, such change may be made by telegram or letter, provided each telegram or letter makes reference to the solicitation and this amendment, and is received prior to the opening hour and date specified.

12. ACCOUNTING AND APPROPRIATION DATA (If required)

13. THIS ITEM APPLIES ONLY TO MODIFICATIONS OF CONTRACTS/ORDERS.

IT MODIFIES THE CONTRACT/ORDER NO. AS DESCRIBED IN ITEM 14.

A. THIS CHANGE ORDER IS ISSUED PURSUANT TO: (Specify authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE

CONTRACT ORDER NO. IN ITEM 10A.

B. THE ABOVE NUMBERED CONTRACT/ORDER IS MODIFIED TO REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying office, appropriation date, etc.) SET FORTH IN ITEM 14, PURSUANT TO THE AUTHORITY OF FAR 43.103(B).

C. THIS SUPPLEMENTAL AGREEMENT IS ENTERED INTO PURSUANT TO AUTHORITY OF:

D. OTHER (Specify type of modification and authority)

E. IMPORTANT: Contractor is not, is required to sign this document and return copies to the issuing office.

14. DESCRIPTION OF AMENDMENT/MODIFICATION (Organized by UCF section headings, including solicitation/contract subject matter where feasible.)

10A. MOD. OF CONTRACT/ORDER NO.

2. AMENDMENT/MODIFICATION NO. 5. PROJECT NO.(If applicable)

6. ISSUED BY

3. EFFECTIVE DATE

14-Jul-2016

CODE

USA MED RESEARCH ACQ ACTIVITY

820 CHANDLER ST

FORT DETRICK MD 21702-5014

W81XWH 7. ADMINISTERED BY (If other than item 6)

4. REQUISITION/PURCHASE REQ. NO.

CODE

See Item 6

FACILITY CODECODE

EMAIL:TEL:

W81XWH-16-T-0195

SECTION SF 30 BLOCK 14 CONTINUATION PAGE

SUMMARY OF CHANGES

SECTION SF 1449 - CONTINUATION SHEET

SUPPLIES OR SERVICES AND PRICES

CLIN 0001

The unit of issue has changed from Each to Job.

CLIN 0002 is added as follows:

ITEM NO SUPPLIES/SERVICES QUANTITY UNIT UNIT PRICE AMOUNT

0002 1 Each Contractor Manpower Reporting

FFP

The contractor shall report ALL contractor labor hours (including subcontractor labor hours) required for performance of services provided under this contract for the US Army Institute of Surgical Research via a secure data collection site. The contractor is required to completely fill in all required data fields using the following web address: http://www.ecmra.mil/. Reporting inputs will be for the labor executed during the period of performance during each Government fiscal year (FY), which runs October 1 through September 30. While inputs may be reported any time during the FY, all data shall be reported no later than October 31 of each calendar year, beginning with 2016. Contractors may direct questions to the help desk at help desk at: http://www.ecmra.mil FOB: Destination

NET AMT

INSPECTION AND ACCEPTANCE

The following Acceptance/Inspection Schedule was added for CLIN 0002:

INSPECT AT INSPECT BY ACCEPT AT ACCEPT BY

N/A N/A N/A Government

The following have been added by full text:

QUESTIONS AND ANSWERS

Questions and Answers to W81XWH-16-T-0195

1) Can you please provide any clinical or non‐clinical benchmarks or clinical descriptions of the extent of burn induction that is intended? This would include burn location, severity, depth, and/or size. Is the induced full thickness burn intended to reach muscle or bone or penetrate the sinus or oral cavity?

Answer: At present, we are looking at both deep partial‐ and full‐thickness burn wounds.

These should be all facial burns. The size of the burn should not be less than 3 cm in diameter if the burn is circular and 3 × 3 cm if the burn is rectangular. The full‐thickness burn should not be extended beyond the upper layers of the muscle and gotten into bones.

2) Typical induction of thermal burn wounds is approached by heating of a metal device and placement against skin for a consistent pressure and time duration. Can you confirm that this is this a satisfactory approach for inducement of the intended maxillofacial burns? Please describe the depth of burn that is intended to be induced and whether muscle or bone are intended to be burned during the would induction.

Answer: The use of a metal device (with consistent pressure and temperature) to create burns is an acceptable approach. See above for the answers of the remaining question.

3) Given the emphasis on imaging modalities for monitoring wound healing, can you please provide more information on the following:

a. Laser Speckle flowmetry and ultrasound are mentioned specifically – are alternative imaging modalities options for consideration. For example:

i. Is Laser Doppler Imaging (LDI) a suitable replacement over Laser Speckle flowmetry for measurements of wound area vascular profusion?

Answer: Yes.

ii. In addition to ultrasound based measurements for wound depth, elastic properties and scar formation; however, for characterization of deep burn wounds would MRI be of consideration for characterization over the course of healing?

Answer: Yes if it can provide similar information as the ultrasound measurement of these parameters. Please note that the purpose of this RFP is to establish a porcine facial burn model for the laboratories in the current Federal facilities to assess treatment efficacies of experimental therapeutics developed within the institute. At present, the institute does not have the MRI in the animal facilities.

b. Is sequential histologic evaluation via biopsy an intended endpoint for characterization of the wound repair process and correlation with information gained through imaging modalities?

Answer: Yes, histological evaluation is a key to the confirmation of information gained through imaging modalities.

c. Can you provide additional clarity on the “Elastic Properties” endpoint in section 2.2.3 (b)? Specifically, approaches for assessment of Elastic Properties by imaging techniques?

As a general assessment for collagen and wound quality would an evaluation based on mechanical tension or resilience be considered?

Answer: Overall, we are seeking non‐invasive means to access the burn tissue and the repair process. Some preliminary data indicated that ultrasound measurement of the healing wound could provide some information on the elastic properties of the wound.

An evaluation based on mechanical tension or resilience can be considered.

4) Model design frequently must take into consideration the nature of the therapeutics or clinical approaches that will subsequently be assessed by the model. We have experience with a variety of therapeutic approaches including cell based therapies, large molecule, small molecule, and skin grafts. If available, please provide the nature of therapeutics that will be explored in future work involving the burn induction model?

Answer: Topical therapeutics is being developed to treat deep partial‐thickness burn wounds.

For full‐thickness burn wounds, the therapeutic approaches would include mostly grafts (e.g., cellular and/or acellular matrix)

5) Are any specific standards of care either required or contraindicated for the model during wound recovery? Inclusive of debridement for full thickness wounds, and any pharmaceutical therapies for infection or pain management?

Answer: One of the goals to establish a porcine facial burn model is to recapitulate the facial burn injury and healing process occurring in wounded warriors. The response of the injury to the standard of care treatment modalities is one of the keys to define the validity of the model developed. Normal healthy animals should be used in the model development. Duroc pigs might be considered in the model development because they typically produce a more well‐ defined hypertrophic scarring as a result of deep partial‐thickness burns.

6) Regarding the 10 pigs that are specified; must a successful measurable model be demonstrated in 10 pigs, or is a total of 10 pigs to be involved in the model development effort? Is it the interest that this PWS only involves a total of 10 animals?

Answer: The 10 pigs are used in the model development effort and to demonstrate a successful measurable model—not all 10 pigs are required to demonstrate a successful measurable model. If needed, upon negotiation, more pigs could be involved in the developmental process.

7) What duration of wound assessment that is targeted for investigation? Presumably this would extend to an objective endpoint such as 100% reepithelization or scar formation. Any follow up beyond full scaring that is intended to be an aspect of the model?

Answer: Ideally, we would be interested in seeing both endpoints, i.e., re‐epithelialization and scar formation. The duration of wound assessment might need to be extended up to 60‐90 days in order to determine scar formation while re‐epithelialization could occur within 3‐4 weeks.

8) Considering this is a firm fixed bid contract, please confirm that a reporting of all contractor and subcontractor labor hours is required.

Answer: Regardless of contract type, Contractor Manpowr Reporting is required as indicated in the PWS at Section 2.8. See the following website for additional information:

https://cmra.army.mil/Help/CMRA_FAQ_NEW.pdf

9) In addition to reading through and signing this document are there other documents we must submit along with this? For instance, are we expected to submit another proposal along with this and if so where do I find more information to ensure I do not miss out on important pieces.

Answer: This information is listed on page 8.

10) Does the Combined Synopsis/Solicitation under solicitation number W81XWH16T0195 contain requirements similar to a current contract? If possible, please provide the current contract number. Or, is this a new requirement for the government?

Answer: This is a new requirement and is not a follow‐on to an existing contract.

The following have been modified:

PERFORMANCE WORK STATEMENT

PERFORMANCE WORK STATEMENT (PWS)

PORCINE PRE-CLINICAL MAXILLO-FACIAL BURN MODEL

Vision Statement (United States Army Institute of Surgical Research) (USAISR) The USAISR Dental and Trauma Research Detachment's mission is to provide militarily relevant research and solutions for the prevention and rehabilitation of craniofacial trauma and infections dental diseases.

1.0. Introduction

The U.S. Army Institute of Surgical Research (USAISR) Dental and Trauma Research Detachment (DTRD) has a plan to develop a pre-clinical porcine model mimicking maxillofacial burn trauma seen clinically.

1.2. Background

The Problem: Burn injuries (Bl) are common to all military conflicts and historically constitute approximately 5 to 10% of all military casualties. The most severe maxillofacial BI characterized by contaminated lacerations and open fractures are occasionally further complicated by composite tissue avulsions and burns (77% of evacuated burn casualties involve the face). The mission of the Institute of Surgical Research (ISR) and Dental and Trauma Research Directorate (DTRD) is to optimize combat casualty care. Currently, there are very few therapeutic options for scar management as the result of burn injury. As such, we are interested in obtaining the preclinical data through the use of a clinically relevant animal model for studying the disease process and scar formation of facial burns.

Knowledge gained will be used for clinical translation to improve quality of healed wounds for the wounded warrior.

The Solution: The US Army ISR and DTRD has a requirement to develop a pre-clinical porcine model for maxillofacial burn trauma that can be studied non-invasively using different imaging modalities that monitor blood flow (laser speckle flowmetry), wound depth, elastic properties and scar formation (ultrasound based). Such a pre-clinical model shall be suitable for testing various treatment strategies aimed at improving the wound outcomes.

1.3. Scope

1.3.1. This PWS contains no services that are inherently governmental functions, as defined in FAR Part

1.3.2. The Government shall neither supervise contractor employees nor control the method by which the contractor performs the required tasks. Under no circumstances shall the Government assign tasks to, or prepare work schedules for, individual contractor employees. It shall be the responsibility of the contractor to manage its employees and to guard against any actions that are of the nature of personal services, or give the perception of personal services. If the contractor believes that any actions constitute personal services, it shall be the contractor's responsibility to notify the Contracting Officer (KO) immediately.

2.0. Performance Requirements. DEVELOPMENT OF A PRE-CLINICAL PORCINE MODEL FOR

MAXILLO-FACIAL BURN TRAUMA

2.1 Outline a protocol to define the steps in the development of the porcine maxillofacial burn trauma model based on a sample size of 10 pigs.

2.1.1 Animal protocol will include a data management and statistical analysis plans for all study data

2.1.2 Obtain vendor IACUC approval of animal protocol and all appropriate and required documents.

2.1.3 Submission of all required documents including the vendor IACUC approved animal protocol to the Animal Care Use Research Office (ACURO) of the US Army Medical Research and Materiel Command (USAMRMC) for approval.

2.2 Provide project management support activities to include the following:

2.2.1 Develop Preliminary and Final Project Plan. This includes the establishment of Gantt Chart(s), or similar, listing all tasks and milestones detailing study dates and timelines assigned to each task. Provide the estimate dates of the initiation and completion for each task. As applicable, define what is needed to complete the study and identify tasks that could be dependent on the other tasks to complete the study.

2.2.2 Provide personall to coordinate contact specific research and provide finanical management and reporting on all research conducted by the Contractor.

2.2.3 Manage the technical, administrative, and operational activities required to conduct the study and track deliverables and reporting requirements.

2.2.4 Identify and resolve problems with contract performance.

2.2.5 Provide teleconferencing capabilities to support collaborations of the study and related activities.

Teleconference lines will enable up to 10 attendees to dial in to conference toll free.

2.2.6 Provide quarterly status reports (to include, at a minimum, total budget, total invoiced to date, total paid to date, schedule status, problems/issues that put timely completion at risk)

2. 3 Conduct and monitor the development of the porcine model for maxillofacial burn trauma. The deliverables shall include the following in the quarterly and final reports to USAISR Dental and Trauma Research Detachment:

a. Macroscopic images documenting the progression of the full -thickness burn injury and characterizing the burn wound-induced contracture of afflicted skin areas. The bur n injuries shall include the general facial area, facial epithelial-oral mucosal junctions, and facial epithelial-ocular junction areas.

b. Images of burn wounds during the entire course of injury and wound healing obtained by using different imaging modalities that characterized blood flow (laser speckle flowmetry), wound depth, elastic properties, and scar formation (ultrasound based).

c. Histological, histochemical, and immunohistological characterization of burn wounds throughout the course of wounding and healing to include determinations of burn wound depth, cellular infiltration, collagen deposition, and scar formation.

Deliverables:

Number Deliverable Title When Due

2.4 Period of Performance: From Date of Award for 12 months.

2.5 Location of Work: All work will be done at the Contractors facility.

2.6 The contractor shall submit invoicing through Wide Area Work Flow (WAWF).

2.7 Contract Administration

2.7.1 The KO will have overall responsibility for administering the contract. The KO is the only person authorized to obligate the Government and make changes to the contract. The KO will manage contract administration and quality assurance surveillance functions supported by contract administrators, COR, quality assurance personnel, property administrators, cost and price analysts, and legal personnel.

2.7.2 The COR will be appointed in writing and will be directly responsible to the KO. The COR serves as the Government ‘s-point of contract for contact-level coordination of administration and technical performance matters.

2.8 CONTRACTOR MANPOWER REPORTING

The contractor shall report ALL contractor labor hours (including subcontractor labor hours) required for performance of services provided under this contract for the US Army Institute of Surgical Research via a secure data collection site. The contractor is required to completely fill in all required data fields using the following web address: http://www.ecmra.mil/ Reporting inputs will be for the labor executed during the period of performance during each Government fiscal year (FY), which runs October 1 through September 30. While inputs may be reported any time during the FY, all data shall be reported no later than October 31 of each calendar year, beginning with 2016. Contractors may direct questions to the help desk at help desk at: http://www.ecmra.mil1.

(End of Summary of Changes)

1 Preliminary Project Plan 30 days after contract award date

2 Final Project Plan 60 days after contract award date

3 Develop animal protocol and all appropriate documents

90 days after contract award date for data management

4 Send copy of IACUC Approval 6 months after contract award

5 Approval from the ACURO of the

USAMRMC

9 months after contract award

6 Conduct and monitor animal study and Analyze Data

9 to 12 months after contract award

7 Quarterly Reports Quarterly after award date

8 Submit Final Contract and Reports 12 months after award date