36C24620Q0376-001.docx

Department of Veterans Affairs Office of Research & Development SAMVAMC Research and Development Service Rederivation of Transgenic Rat Models Performance Work Statement (PWS) (Not Final)

A. GENERAL INFORMATION

1. Title of Project: Rederivation of Transgenic Rat Models. Novel Complement-targeted treatment strategies in Renal Disease.

2. Background: Complement (C) is a system of interacting proteins that provides host defense by destroying microbes and strengthening immunity. However, abnormal regulation or pathologic activation of these proteins can destroy host cells and organs. A number of diseases can be caused by such dysregulation and include kidney diseases that can evolve to an irreversible stage referred to as Chronic Kidney Injury (CKD). CKD kills more Veterans than cancers of breast and prostate cancer combined. These dismal observations point to a critical need for innovation to prevent and treat CKD. This basic Research Proposal aims to find ways of minimizing C-mediated kidney injury by boosting a physiologic inhibitor of C activation known as Decay-Accelerating Factor (OAF). Efficacy of proposed strategies will be tested in kidney cells and a rat model of C-mediated kidney injury described below.

The recent identification and cloning of rodent analogues of DAF provide an opportunity to assess therapeutic potential of this complement regulator in pre-clinical studies. Rat DAF is similar in molecular mass (70kDa) and tissue distribution to human DAF. Importantly, DAF expression in the rat kidney is restricted in podocytes. This justifies and facilitates use of rat modes of C-mediated podocyte injury to assess efficacy of strategies aiming to upregulate DAF expression in order to preserve podocyte structural/functional integrity. The following groups (Sprague-Dawley rats, 150-180g, n=6-8 in each experimental and control group) will receive a heterologous (sheep) antibody (Ab) against a rat renal tubular brush border antigenic complex, known as Fx1A, and present in cell membrane of renal glomerular epithelial cells (GEC): 1) Wild-Type (WT) rats, 2) Rats with GEC-targeted HO-1 overexpression (GECHO-1), 3) Rats with decay-accelerating factor (DAF) deficiency (DAF1-/-), and 4) Rats with GEC-targeted Heme Oxygenase (HO)-1 overexpression that are DAF deficient (GECHO-1 / DAF1-/-).

The compounds/drugs to be tested in the rat model have either been approved by the FDA or have undergone clinical trials. Therefore, side effects are expected to be minimal or none. Test compounds will be given via the intravenous (tail vein-single injections) or the intraperitoneal rout (single injections). Therefore, pain/distress is expected to be minimal.

3. Scope of Work: This contract request is for the rederivation of transgenic rat models that will be used as founder pairs for the breeding needed to accomplish the goals of the VA Merit as it was funded.

4. Period of Performance: The period of performance (POP) shall be 3 months. The POP will begin with the date of Office of Management and Budget (OMB) approval.

5. Type of Contract: A Firm Fixed Price

6. Place of Performance: The Contractor shall support this effort at approved Contractor facilities as directed by the Contracting Officer’s Representative (COR) and mutually agreed to by the Contractor.

B. GENERAL REQUIREMENTS

1. The contractor will present a plan for project organization and staffing that demonstrates a knowledge of effective organizational structure, management, and how best to utilize key and other personnel. The contractor will have the personnel, equipment, material, supplies, forms, and systems of computer programs to manage this study and process the data collected for this study, unless otherwise stated in a specific contract.

C. SPECIFIC MANDATORY TASKS AND ASSOCIATED DELIVERABLES

Task 1: Select Personnel The contractor will designate personnel considered essential to the work being performed under this contract. If any essential personnel are to be removed from the contract, whether planned or unplanned, the contractor will notify the VA COR and submit written justification, including the names and vitae of proposed substitutions, in sufficient detail. This will occur within 30 days before departure of the personnel or as soon as possible, if, for example, it is a result of the personnel ending employment with the contractor. The VA COR must concur with the diversion of personnel and approve the replacement. Also, the VA may modify the contract to add or delete key personnel at the request of the contractor. The contractor will designate a main contact for prompt administration during this contract.

Personnel working on this contract should have experience in areas including:

· Rederivation of CD55-m6 rat strain

· Rederivation of T2-HO1 rat strain

· Analysis of rat strains & Confirmation analysis.

Deliverable 1 – Notification to VA in details of essential personnel with justifications. Deliverable 2 – Designation of an administrative contact.

Task 2: Regular Communication/Meetings and Recording Decisions The contractor and the VA investigator will have an initial meeting within 2 weeks of the contract award to discuss and review the activities of the contract. Topics will include the overall project management plan and schedule. A draft agenda will be prepared by the contractor and approved by the VA investigator 3 days before the meeting.

The contractor must communicate every month with the VA investigator or designees within VA research team. The communications will take place over the telephone. The contractor will brief the COR and/or designees and survey research staff as to the status of the project, quality control findings, description of any problems anticipated or encountered and their resolution or non-resolution, and milestones obtained or missed. During active data collection, the contractor will report the number and percent of responses and compare the progress in the current survey cycle with that of the previous cycle.

The contractor will keep a log of decisions made during the course of the study and provide the VA COR with an updated log of any new decisions made following the weekly meeting within 7 business days following each meeting. After review of the decision log, the VA COR will provide any necessary corrections to the decision log, which then will be revised.

Deliverable 3 – Attend monthly meetings with the COR and VA study team and keep minutes of discussions. Deliverable 4 – Keep log of study-related decision.

Task 3: Project Plan and Procedures The contractor will provide the following according to the agreed upon timeline below.

List of items/services to be covered by this agreement:

Animal holding costs not to exceed

Serological testing

Genotyping

Shipping

TOTAL NOT TO EXCEED

Noncontract Charges: The contractor shall not perform any service that will result in additional charges without prior approval from the Contracting Officer.

Task 4: Quality Assurance The contractor will develop a quality control plan that covers all aspects of the work to be performed under this contract. The quality control plan will include the following:

· The contractor will have a management system that identifies potential problems early, ensures high-quality data and adherence to schedules, controls project costs, and maintains close communication with the VA. Project operations will include frequent conversations concerning progress and challenges, meetings to discuss and resolve problems, and regular reporting between the contractor and the VA.

· The contractor has provided or will provide training to supervisors, laboratory staff, and other staff necessary for the project. This training must include study procedures and problem identification. All contractor personnel will satisfy VA training requirements in privacy, information security, and any additional training related to research and information security as required.

· The contractor will conduct logic and range edit checks on all data and correct all errors that are resolvable using available information.

· The VA COR, together with other VA staff, will make announced and unannounced visits to monitor contractor operations on-site.

Deliverable 5 – Develop a quality control plan and update COR within 2 months of contract award.

Deliverable 6 – Develop a data management system to track progress of lab activity and reporting to VA Investigator.

Task 5: Submit a Confidentiality Plan and Data Security Procedures Storage and Access to Data Data will be entered into separate, dated electronic databases on a weekly basis and the VA COR should be notified when complete. The VA shall have electronic access to all databases. A cumulative file of all records should be created and maintained by the contractor.

Data Security The contractor will ensure the highest degree of security to protect data from intentional or unintentional release, loss, or destruction. Prior to receipt of any data files from the VA, the contractor will submit a confidentiality plan and data security procedures for approval by the VA COR and revise it per the VA COR instructions. Contractors, contractor personnel, subcontractors, and subcontractor personnel shall be subject to the same Federal laws, regulations, standards, and VA Directives and Handbooks as VA and VA personnel regarding information and information system security.

Data will be transferred, retained, utilized, and destroyed in accordance with VA and VHA policy including the following: VA Handbook 5011/5, Chapter 4 (Alternative Workplace Arrangements); VA Directive and Handbook 6500, Information Security Program; VA Directive and Handbook 6502, Privacy Program; and VHA Directive 1605, VHA Handbook 1605.1 and 1605.2.

Deliverable 8 – Submit a Data Security Procedure Plan

D. SCHEDULE OF DELIVERABLES

See Attachment A/ Task 3

E. INSPECTION AND ACCEPTANCE CRITERIA

Final inspection and acceptance of all work performed, reports and deliverables will occur at the place of delivery designated by the COR. Final approval and acceptance of documentation required herein shall be by letter of approval and acceptance by COR. The Contractor shall not construe any letter of acknowledgment of receipt of material as a waiver of review, or as an acknowledgment that the material is in conformance with this PWS.

F. CHANGES TO STATEMENT OF WORK

Any changes to this PWS shall be authorized and approved only through written correspondence from the CO. A copy of each change will be kept in a project folder along with all other products of the project. Costs incurred by the contractor through the actions of parties other than the CO shall be borne by the contractor.

G. GOVERNMENT RESPONSIBILITIES

The government shall assure that the contractor has access to VA toll-free telephone numbers for Veterans as appropriate.

H. KEY PERSONNEL

The Contractor shall be responsible for managing and overseeing the activities of all Contractor personnel, as well as subcontractor efforts used in performance of this effort. The Contractor's management responsibilities shall include all activities necessary to ensure the accomplishment of timely and effective support, performed in accordance with the requirements contained in the statement of work.

The Contracting Officer may notify the Contractor and request immediate removal of any personnel assigned to the task order by the Contractor that are deemed to have a conflict of interest with the government or if the performance is deemed to be unsatisfactory. The reason for removal will be documented and replacement personnel shall be identified within three business days of the notification. Employment and staffing difficulties shall not be justification for failure to meet established schedules.

The VA PI will provide oversight of the entire program, including the development and implementation of all policies and procedures. In these roles, the PI will be responsible for the implementation of the proposed experiments. He will run the animal components of the proposal and assure compliance with all institutional animal research policies. The VA will hold primary responsibility for characterization of injury and neurobehavioral characteristics.

1. Key Personnel: Certain skilled experienced professional and/or technical personnel are essential for accomplishing the work to be performed. These individuals are defined as "Key Personnel" and are those persons whose resumes were submitted and marked by the vendor as "Key Personnel". Substitutions shall only be accepted if in compliance with “Substitution of Key Personnel" provision identified below.

Substitution of Key Personnel: TBD

I. PERSONNEL QUALIFICATIONS:

a. Successful contractor shall have personnel with a proven track record of providing medical monitoring programs for high risk occupational groups, as well as designing and providing web and other communications activities.

b. Personnel must be experienced in enrollment of workers, performance of work history interviews and review of exam reports and Results Letters.

c. The Contractor shall document that the qualifications of the professional, technical and administrative staff proposed are adequate for full performance of tasks. Curriculum Vitae (CVs) or detailed bios are provided for each proposed staff member.

d. The Contractor shall identify the key roles and specific responsibilities for each key role of the professional, technical and administrative staff proposed.

e. The Contractor shall demonstrate the appropriate mix and balance of education, academic excellence, training and experience of proposed team members.

f. The Contractor shall ensure that proposed program managers and senior level professionals are qualified, and available for consultation with VA from 8 am EST to 6 pm PST.

J. SECURITY

Information System Security The contractor shall ensure adequate LAN/Internet, data, information, and system security in accordance with VA standard operating procedures and standard contract language, conditions laws, and regulations. The contractor’s firewall and web server shall meet or exceed the government minimum requirements for security. All government data shall be protected behind an approved firewall. Any security violations or attempted violations shall be reported to the VA project manager and the VHA Headquarters Information Security Officer as soon as possible. The contractor shall follow all applicable VA policies and procedures governing information security, especially those that pertain to certification accreditation.

Security Training All contractor employees and subcontractors under this contract or order are required to complete the VA's on-line Security Awareness Training Course and the Privacy Awareness Training Course annually. Contractors must provide signed certifications of completion to the CO during each year of the contract. This requirement is in addition to any other training that may be required of the contractor and subcontractor(s).

M. SECTION 508

The contractor shall comply with Section 508 of the Rehabilitation Act (29 U.S.C. § 794d), as amended by the Workforce Investment Act of 1998 (P.L. 105-220), August 7, 1998.

In December 2000, the Architectural and Transportation Barriers Compliance Board (Access Board), pursuant to Section 508(2) (A) of the Rehabilitation Act Amendments of 1998, established Information Technology accessibility standards for the Federal Government. Section 508(a)(1) requires that when Federal departments or agencies develop, procure, maintain, or use Electronic and Information Technology (EIT), they shall ensure that the EIT allows Federal employees with disabilities to have access to and use of information and data that is comparable to the access to and use of information and data by other Federal employees. The Section 508 requirement also applies to members of the public seeking information or services from a Federal department or agency.

Section 508 text is available at:

http://www.opm.gov/HTML/508-textOfLaw.htm http://www.section508.gov/index.cfm?FuseAction=Content&ID=14

N. CONFIDENTIALITY AND NONDISCLOSURE

It is agreed that:

1. The preliminary and final deliverables and all associated working papers, application source code, and other materials deemed relevant by the VA which have been generated by the contractor in the performance of this task order are the exclusive property of the U.S. Government and shall be submitted to the CO at the conclusion of the task order.

2. The CO will be the sole authorized official to release verbally or in writing, any data, the draft deliverables, the final deliverables, or any other written or printed materials pertaining to this task order. No information shall be released by the contractor. Any request for information relating to this task order presented to the contractor shall be submitted in writing to the CO for response.

3. Press releases, marketing material or any other printed or electronic documentation related to this project, shall not be publicized without the written approval of the CO.

4. The Contractor will sign a National Business Associate Agreement with the VA, in accordance with the mandated guidelines.

O. RIGHTS IN DATA

Performance of this effort may require the contractor to access and use data and information proprietary to a Government agency or Government contractor which is of such a nature that its dissemination or use, other than in performance of this effort, would be adverse to the interests of the Government and/or others.

Contractor and/or contractor personnel shall not divulge, or release data or information developed or obtained in performance of this effort, until made public by the Government, except to authorize Government personnel or upon written approval of the Contracting Officer (CO). The contractor shall not use, disclose, or reproduce proprietary data that bears a restrictive legend, other than as required in the performance of this effort. Nothing herein shall preclude the use of any data independently acquired by the contractor without such limitations or prohibit an agreement at no cost to the Government between the contractor and the data owner which provides for greater rights to the contractor.

The Department of Veterans Affairs shall have unlimited rights to and ownership of all deliverables provided under this effort, including reports, recommendations, briefings, work plans and all other deliverables. This includes the deliverables provided under the basic award as well as and any optional task deliverables that are exercised by the Contracting Officer. The definition of “unlimited rights” is contained in Federal Acquisition Regulation (FAR) 27.401, Definitions.

P. TASK ORDER TERMINATION

VA has the right to terminate (in whole or in part) this task order at any time in accordance with the termination clauses of the governing GSA Schedule Contract. The Contractor will be paid only for the services rendered up to the point of receiving the termination notice, and then only to the extent that those services meet the requirements of this PWS.

Q. CONTRACT ADMINISTRATION:

Notwithstanding the Contractor's responsibility for total management during the performance of this contract, the administration of the contract will require maximum coordination between the Government and the Contractor. The following individuals will be the Government's points of contact during the performance of this contract:

1. Contracting Officer: Rodney Wilson Contract Specialist: TBD Contracting Officer Representative (COR): TBD

2. Contracting Officer’s Technical Representative (COR): To be designated at time of contract award.

The COR shall be designated on the authority of the Contracting Officer at the time of contract award to monitor all technical aspects of the contract. In no event is the COR empowered to change any of the terms and conditions of the contract. Changes in any section of this contract shall be made only by the Contracting Officer pursuant to a properly executed modification. The types of actions within the purview of the COR’s authority are to ensure that the Contractor performs the technical requirements of the contract, and to notify both the Contractor and the Contracting Officer of any deficiencies observed. A memorandum of designation shall be issued to the COR and a copy shall be sent to the Contractor at the time of contract award setting forth in full the responsibilities and limitations of the COR

Attachment A

Note that the Deliverable Table is directly related to the tasks and deliverables in Section C above.

Schedule of Deliverables

of contract award

of contract award