0141_J A.doc

Control No. JA16373

JUSTIFICATION AND APPROVAL FOR

OTHER THAN FULL AND OPEN COMPETITION

Interagency Agreement between the National Institutes of Health and the Department of Defense

1. Contracting Activity:

The contracting activity for this action is the U.S. Army Medical Research Acquisition Activity (USAMRAA), Fort Detrick, MD, in support of the U.S. Army Medical Research Institute of Chemical Defense (USAMRICD) at Aberdeen Proving Ground-Edgewood Area, MD.

2. Description of Action:

This approval is being requested for the issuance of a Research & Development (R&D) to Carnegie Mellon University. The award is in support of the National Institutes of Health (NIH) Interagency Agreement (IAA) titled “Generation of a bioengineered posterior cornea construct for use in evaluating mechanisms of ocular vesicant injury.” A firm fixed-price award will be issued to the Carnegie Mellon Univerisity using Fiscal Year 2016 Public Health funding that is being transferred to USAMRICD.

3. Description of Supplies/Services:

USAMRICD has a requirement to issue an R&D contract as part of a Memorandum of Agreement (MOA) and related IAA with the NIH. Carnegie Mellon University possesses unique, propriety, personnel, and equipment for Descemet’s membrane (DM) simulant production and evaluation as defined in the accompanying Statement of Work. The contractor shall perform to the standards in this contract. Total estimated value for this R&D effort is $81,000. Year 1 estimated value is $46,000 and Year 2 estimated value is $35,000.

4. Authority Cited:

The statutory authority permitting other than full and open competition is 10 U.S.C. 2304(c)(1) as implemented by FAR 6.302-1, “Only one responsible source and no other supplies or services will satisfy agency requirements. The MOA is authorized under the Economy Act U.S.C. §1535.

5. Reason for Authority Cited:

The NIH CounterACT program has established the IAA in which directed research projects were submitted, evaluated and selected to sponsor a network of collaboration amongst researchers. As established by the MOA and NIH, only certain universities or institutions have been selected to conduct specific portions of the research proposals. The research will be carried out in accordance with the MOA. It is neither cost effective nor realistic to expect another contractor to perform the requirements of the collaboration established.

Preventable costs to the Government include start-up costs, human resources and relocation, and duplication of peer and outside reviewer time. The MOA and NIH funding structure allows for research objectives to be met on a long term basis without the administrative costs associated with short term contracting arrangements. Failure to comply with the MOA and NIH arrangement will result in the failure of USAMRICD’s mission to carry out research for the Army and its supported agencies. Research hindrance or disestablishment of research programs could occur if these research contracts are not issued.

Vesicating chemical warfare agents (CWAs) have been in use since World War I, and continue to represent a major instrument of coersion and fear utilized by modern terrorists. Today, the potential use of CWAs also represents a severe threat to the Homeland, in both humanitarian and economic terms. The vesicating agent sulfur mustard (SM) elicits life-threatening injury to the lungs, skin, eyes and bone marrow. The cornea is the first tissue to display signs of exposure to the vesicant sulfur mustard (SM). Symptoms initially include irritation, photophobia, inflammation, corneal erosion and conjunctivitis. At low exposure doses, these symptoms will eventually subside. In victims exposed to higher doses however, this initial stage is followed by more severe pathology, characterized by recurring erosions, corneal scarring and abnormal vascularization. Recurring SM-induced ocular pathology will eventually lead to blindness. To date, pharmacological intervention has proven inadequate in the treatment of SM complications, establishing an unusual and compelling urgency for the Government to develop a therapeutic that effectively addressess SM injury for victims of domestic terrorism and for the Warfighter.

The execution of previous and currently funded projects has allowed our laboratory to gain extensive experience in the isolation and propagation of two corneal cell types: (1) corneal endothelial cells (CECs) and (2) corneal fibroblasts (keratocytes). USAMRICD intends to incorporate these two cell types within a single bioengineered tissue construct to produce a functional representation of the posterior cornea. The construct will initially be employed in profiling the molecular and cellular aspects of vesicant injury progression. Importantly, this work will serve as the basis for developing a transplantable tissue product that definitively resolves vesicant-induced corneal injury.

Rapid design and production of a functional corneal construct requires that USAMRICD seek highly specific extra-governmental expertise to generate a biomimetic DM. An effective artificial DM must promote adhesion of the CEC monolayer to stromal tissue and maintain native CEC phenotype and functionality. Carnegie Mellon University (CMU) maintains comprehensive and highly unique capabilities in the manufacturing and evaluation of substrates that represent biomimetic DM candidates. CMU has developed a unique technology to directly engineer a biomimetic DM using a process termed surface-initiated assembly (SIA). CMU owns the intellectual property covering SIA technology. Laboratories at CMU have already validated through rigorous experimental studies that the biomimetic DM can be seeded with human CECs to engineer a functional human corneal endothelium. It is neither cost effective nor realistic to expect that a contractor other than CMU will provide the expertise required for execution of this contract.

The potential for SM utilization as a CWA threatens the Homeland and our deployed Warfighters, creating an unusual and compelling urgency to develop effective medical countermeasures for the treatment of SM injury. Funding for immediate research has become available through the NIH-USAMRICD IAA.

6. Efforts to Obtain Competition:

No effort was taken to obtain competition by the contracting agency because the competitive proposal submission and selection was performed by the NIH. Under the agreement, sixteen proposals were initially selected for funding by NIH, with only six proposals making the final funding approval. The collaborative research was approved in accordance with the MOA and this action is one of the six approved. .

7. Actions to Increase Competition:

It is the policy of USAMRAA to promote the use of competitive procedures whenever and wherever possible. The NIH maintains the following website that addresses the IAA and research categories for considereation with USAMRICD. See the section on Contracts, Inter-Agency Agreements, and Other Resources at:

http://www.ninds.nih.gov/research/counterterrorism/counterACT_researchers _projects.htm

8. Market Research:

Development of effective medical countermeasures for SM exposure has proven difficult. In spite of nearly 100 years of research, there are no candidate SM therapeutics ready for FDA submission. This lack of progress is likely due in part to the fact that SM does not occur in nature. Addressing the unique mechanism of action involved in SM-induced tissue damage is heightened by the absence of data from any comparable disease or injury.

The following facts are derived from literature searches performed 25 AUG 2016 and prior, using PubMed, Athens, and EduServe databases:

No examples of efforts to develop biomimetic DM for the treatment of SM-induced injury are found.

No examples of clinical research using biomimetic DM for the treatment of any injury are found.

Muhammad et al. have evaluated patterned polystyrene tissue culture plastic to support human CEC growth and maintainence of phenotype. Although results were positive, the substrate is not a transplantable material (it is not biodegradable or bioabsorbable). Reference: Acta Biomater. 2015 Jun;19:138-48.

Koizumi et al. cultured primate CECs on collagen I carriers and transplanted them to the anterior chambers of primate subjects in which the endothelial layer had been denuded. CECs grafted sucessfully. Although promising, the results of this study are based on a highly limited number of subjects (4 experimental and 1 control subject). Reference: Cornea. 2008 Sep;27 Suppl 1:S48-55.

Palchesko et al. demonstrated that a bioengineered polydimethylsiloxane surface with elastic modulus of 50 kPa and collagen IV coating recapitulated DM chemo-mechanical properties. CECs grown on this substrate achieved an impressive 3000-fold expansion. High density monolayers showed native polygonal morphology and cell type-specific marker expression (ZO-1) localized to cell-cell junctions. Control cells on polystyrene lost these phenotypic markers and increased pathological smooth muscle actin expression and fibronectin fibril assembly. Reference: Sci Rep. 2015 Jan 22;5:7955. Polydimethylsiloxane-collagen IV coating of a wide range of carrier scaffolds is a readily applicable strategy for the generation of the desired posterior corneal construct. No examples of other efforts on the effectiveness of various anticonvulsant treatments, either benzodiazepines or other drugs used clinically to stop SE, in pediatric models of NA and OP-induced SE are found.

For future consortium projects, Market Research will be accomplish through posting a Sources Sought notice in FedBizOps in order to obtain additional sources who can meet the requirements that will be identified through a Broad Agency Announcement.

9. Interested Sources: A sources sought notice with the NIH IAA information and a notice of intent to issue a sole source award for this reqquirement was posted to the FedBizOpps.gov website in September 2016. The notices provide another Government Point of Entry for interested sources to become familiar with the CounterACT program and compete with collaborators for future NIH IAA research funding cycles.

10. Other Facts: Work statements suitable for full and open competition are not available for this acquisition. Universities were required to submit proposals thru USAMRICD to NIH. As part of the proposal submission process, USAMRICD and the university collaborators were required to submit budget forecasts and justification to assist the NIH review process. As a result, final selection of projects was completed for all proposals that have been identified.

NIH is the primary Institute at the NIH for research on infectious, immunologic, and allergic diseases, including research on emerging and re-emerging infectious diseases, HIV/AIDS, and potential agents of bioterror. The project is known as Interagency Agreement with an official title of “Generation of a bioengineered posterior cornea construct for use in evaluating mechanisms of ocular vesicant injury”. Carnegie Mellon University has been identified by NIH and USAMRICD as the only source for Descemet’s membrane (DM) simulant production and evaluation as defined in the accompanying Statement of Work..

a. Procurement History – N/A

b. Acquisition Data Availability - A statement of work suitable for full and open competition can be developed for this procurement. It is not being competed becayse there is anticipation that no sources will respond to the Notice of Intent to Sole Source via FedBizOpps for 30 days. Carnegie Mellon University is the only source who can accomplish the requirement.

c. Unusual and compelling urgency – Not Applicable. FAR 6.302-2 is not being cited.

d. Subcontracting Competition – Carnegie Mellon University has not established subcontracting opportunities. If they shall, they must indicate whether or not they will go through Small Business Subcontractors as identified in the FAR.

11. Technical and Requirements Certification: I certify that the supporting data under my cognizance, which are included in the justification, are accurate and complete to the best of my knowledge and belief.

12. Fair and Reasonable Cost Determination: I hereby determine that the anticipated cost for this contract extension action will be fair and reasonable. Fair and reasonable pricing will be assured through price analysis to include comparison with historical costs for services performed, an Independent Government Cost Estimate, and negotiation with the universities. Cost and pricing data is not required per the exception at FAR 15.403-1.

13. Contracting Officer Certification: I certify that this justification is accurate and complete to the best of my knowledge and belief.