BAA-Final-2-27.pdf

BAA-BARDA-09-36

UUU...SSS... DDDeeepppaaarrrtttmmmeeennnttt ooofff HHHeeeaaalllttthhh aaannnddd HHHuuummmaaannn SSSeeerrrvvviiiccceeesss Office of the Assistant Secretary for Preparedness and Response (ASPR)

Biomedical Advanced Research and Development Authority (BARDA)

BAA-BARDA-09-36

POINT OF CARE OR HIGH-THROUGHPUT BIOLOGICAL ASSAYS FOR DETERMINING ABSORBED IONIZING

RADIATION DOSE (BIODOSIMETRY) AFTER RADIOLOGIC AND NUCLEAR EVENTS

1. OFFERORS ARE RESPONSIBLE FOR ROUTINELY CHECKING THE FOLLOWING WEBSITE FOR ANY

BAA AMENDMENTS. NO ADDITIONAL NOTIFICATION OF ANY AMENDMENTS WILL BE PROVIDED BY

THIS OFFICE. http://www.fedbizopps.gov/

2. BAA/CONTRACT FORM – PURCHASE AUTHORITY: FAR 1.602-1

NOTE: The issuance of this BAA does not commit the USG to an award.

3. Issue Date:

February 27, 2009

4. Due Date: April 17, 2009

Time: 4:30 p.m., EST

5. Small Bus. Set-Aside: [ ]Yes [X] No

8(a) Set-Aside: [ ]Yes [X] No

NAICS #: 541711

6. Reserved

7. Number of Awards:

[ ] Only 1 Award [X] Multiple Awards

8. Technical Proposal Page Limits:

Number of Copies: See Attachment 1 (Packaging and Delivery of Proposals) Page Limits: 100 pages All appendices, Curriculum Vitaes (CV’s), attachments associated with the technical proposal may not exceed an additional 100 pages.

10. [X] BARDA reserves the right to make awards without discussions.

9. Issued By:

Carl A. Newman, Contract Specialist Biomedical Advanced Research and Development Authority (BARDA) 330 Independence Ave., SW, Room G640 Washington, D.C. 20201

11. Options:

[ ] No [ X ] Yes

12. Period of Performance:

Up to five (5) years beginning on or about September 16, 2009.

13. Primary Point of Contact:

14. Name: Carl A. Newman Phone: 202-205-1156 Fax: 202-205-4520 E-Mail: carl.newman@hhs.gov

15. Secondary Point of Contact:

Name: Glynis Fisher Phone: 202-260-1880 E-Mail: glynis.fisher@hhs.gov

16. Protest Officer:

Cynthia Montgomery

E-mail: cynthia.montgomery@hhs.gov Address: See Block 9

17. COLLECT CALLS WILL NOT BE ACCEPTED. FACSIMILE SUBMISSIONS ARE NOT ACCEPTABLE.

18. Offers will be valid for 120 days unless a different period is specified by the Offeror.

DELIVERY ADDRESS INFORMATION

19. Hand Delivery or Overnight Service:

Hand delivery is discouraged due to the difficulty in unloading vehicles near the building entrance. However if the proposals will be hand delivered, please contact the Contract Specialist 24 hours prior to the delivery of proposals.

20. U.S. Postal Service or an Express Delivery Service Biomedical Advanced Research and Development Authority Assistant Secretary for Preparedness and Response U.S. Department of Health & Human Services 330 Independence Ave. S.W., Room G640 Washington, D. C. 20201

21. Official Point of Receipt For the purpose of determining timely delivery, the address is provided in Block 19, above.

The original paper copy with original signatures is the official copy for recording timely receipt. If the original paper copy of the proposal is not received by the Contracting Officer or Designee at the place and time specified, then it will be considered late and handled in accordance with HHSAR 352.215-70 entitled "Late Proposals and Revisions" located in this BAA.

TABLE OF CONTENTS

A. INTRODUCTION 3

B. BACKGROUND 3

C. SCOPE 5

D. RESEARCH AND TECHNICAL OBJECTIVES 6

E. REPORTING REQUIREMENTS AND DELIVERABLES 12

F. EVALUATION FACTORS FOR AWARD 15

G. GENERAL INFORMATION FOR OFFERORS 25

H. LIST OF ATTACHMENTS 54

A. INTRODUCTION

This Broad Agency Announcement (BAA) is issued under the guidance of Federal Acquisition Regulations (FAR) 6.102(d)(2) and 35.016. Proposals submitted in response to this BAA and selected for award are considered to be the result of full and open competition and in full compliance with the provision of Public Law 98-369, “The Competition in Contracting Act of 1984” and subsequent amendments.

Offerors are invited to submit a proposal in accordance with the requirements of this BAA (BAA-BARDA- 09-36) entitled POINT OF CARE OR HIGH-THROUGHPUT BIOLOGICAL ASSAYS FOR DETERMINING

ABSORBED IONIZING RADIATION DOSE (BIODOSIMETRY) AFTER RADIOLOGIC AND NUCLEAR

EVENTS. A BAA identifies a United States Government (USG) agency’s specific research and development interest. The intent of this BAA is to encourage the submission of creative and innovative approaches to specific research and development areas identified herein.

BARDA, in the Office of the Assistant Secretary for Preparedness and Response (ASPR), US Department of Health and Human Services (HHS), will not issue paper copies of this announcement.

BARDA reserves the right to select for award and fund all, some, or none of the proposals received in response to this solicitation. No funding for direct reimbursement of proposal development costs will be allowed. Technical and cost proposals (or any other material) submitted in response to this BAA will not be returned. However, depending on the markings on the proposal, BARDA will adhere to FAR policy on handling source selection information and proprietary proposals. It is the policy of BARDA to treat all proposals as sensitive, competitive information and to disclose their contents only for the purposes of evaluation or as agreed in any resulting contract. Multiple awards are anticipated to be issued through this BAA and will be based on an assessment of the overall best value to the government. Awards will be made based upon the proposal evaluation, funds availability, and other programmatic considerations.

Awards will each include a base contract with options to be exercised at the discretion of the government after successful completion of phases or milestones. BARDA anticipates awarding 4-6 contracts for this BAA. Awards are expected to be made on or about September 16, 2009. BARDA estimates that the average annual total cost (direct and indirect cost combined) for these contracts will be $8 million per contract. However, it is anticipated that the total cost for each award may vary depending upon the scope of the project and the technical objectives of the award. Year 1 base contract budget ranges from $4,000,000 to $15,000,000 commensurate with the Statement of Work (SOW) five years with costs not to exceed $41,400,000, pending availability of funds. The length of time for which funding is requested should be consistent with the nature and complexity of the proposed research and development.

The maximum period of performance is five (5) years for this BAA for research and development of physical or biological assays for the accurate determination of an individual’s absorbed dose of ionizing radiation within the boundaries of 0.5 Gray (Gy; a unit of absorbed dose of ionizing radiation) to 10 Gy with a stated statistical certainty. The award document will be tailored in the final negotiations with the selected Offeror(s) and modified as appropriate for the type of Offeror organization, cost and/or fee arrangements, and other elements as negotiated prior to award.

B. BACKGROUND

On December 19, 2006, President George W. Bush signed into law the Pandemic and All-Hazards Preparedness Act (Public Law 109-417), referred to as PAHPA. Title IV of PAHPA established the Biomedical Advanced Research and Development Authority (BARDA) in the Office of the Assistant Secretary for Preparedness and Response (ASPR) in the U.S. Department of Health and Human Services (HHS) to facilitate the research, development, and acquisition of medical countermeasures for chemical, biological, radiological, and nuclear (CBRN) agents and emerging infectious diseases, including pandemic influenza, that threaten the U.S. civilian population. BARDA encourages and facilitates the development and acquisition of medical countermeasures such as vaccines, therapeutics and diagnostics, as well as innovative approaches to meet the threat of CBRN agents and emerging infectious diseases, including pandemic influenza, in support of the mission and priorities of the HHS Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) articulated in the PHEMCE Implementation Plan for CBRN

Threats (http://www.hhs.gov/aspr/barda/phemce/enterprise/strategy/index.html) and the HHS Pandemic Influenza Plan (http://www.hhs.gov/pandemicflu/plan/).

The 2007 HHS PHEMCE Implementation Plan for CBRN Threats identified the top priorities for CBRN medical countermeasure research, development, and acquisition programs that HHS has determined, in collaboration with interagency partners, to have the greatest potential to improve public health emergency preparedness. As stated in the Plan, HHS is seeking to acquire medical countermeasures that will support an effective public health emergency response to a radiological or nuclear event. HHS regards radiological and nuclear agents as a significant threat to national security and is committed to supporting the advanced development and procurement of safe and efficacious medical countermeasures for the treatment of large affected populations who are acutely exposed to ionizing radiation as a result of a nuclear detonation (i.e. IND, improvised nuclear device), radiological dispersive device (RDD; such as a “dirty bomb”), or other radiological mechanisms. A large-scale radiological incident would result in an immediate critical need to assess the radiation doses received by potentially hundreds of thousands of individuals to allow for prompt triage and appropriate medical treatment.

Biodosimetry and bioassay capabilities, including both rapid biodosimetry assays for on-scene triage and a laboratory system capacity, were therefore called out as high priorities in the PHEMCE Implementation Plan for CBRN Threats. A mass casualty event such as an IND may bring 500,000 – 1,000,000 people or more for evaluation for radiation exposure and/or contamination.

• Ionizing Radiation – Effects and Medical Management

The deadly effects of ionizing radiation (IR) are wide-ranging and encompass both systemic and organ-specific damage. Acute effects of high-dose ionizing radiation (> 2 Gy) include depletion of specific types of peripheral blood cells, immune suppression, mucosal damage, and potential injury to other sites such as bone and bone marrow niche cells, lung, kidney, and central nervous system. Even exposures to low or moderate doses (1-3 Gy) of ionizing radiation can result in increased mortality if accompanied by physical injuries, opportunistic infections, and/or hemorrhage. Long-term effects include dysfunction or fibrosis in a wide range of organs and tissues and, ultimately, a higher risk of cancer. In most cases, the deadly effects of high (> 2 Gy) radiation exposure can be mitigated by early appropriate triage and treatment decisions.

However, because current and foreseeable medical countermeasures for radiation injuries are often expensive, labor-intensive and time-consuming to administer (and monitor), limited in availability, and occasionally associated with serious toxicities, they should only be administered to persons who will likely benefit from their use. Fast, accurate radiation dose assessment could greatly facilitate identification of exposed people who could benefit from early medical intervention.

Unfortunately, no rapid point-of-care single-time-point diagnostic that can reliably discriminate levels of IR exposure currently exists. The complete blood count, particularly the lymphocyte count, is useful, but optimally requires at least two samples spaced hours to days apart to estimate dose. The diagnostic “Gold Standard” in the field of radiation biodosimetry, the dicentric chromosome assay, is labor-intensive and slow, and its use in mass casualty situations would be problematic.

BARDA seeks to support development of dose assessment tools, devices, biomarkers, and bioassays1 that contain both diverse and integrated elements, each of which possesses a sensitivity and specificity appropriate for the diagnostic issue presented. Such tools will (1) identify patients requiring urgent medical assessment (the target population for therapies); (2) provide assurance to anxious individuals who received radiation doses below the threshold for immediate concern; (3) improve risk

1 The term “bioassay”, for purposes of this Broad Agency Announcement, refers to the analysis of any biologic material for the purpose of determination of absorbed doses of ionizing radiation. This is distinct from the use of the term by both the Radiological Emergency Medical Management (REMM; www.remm.nlm.gov) system and CDC to mean specifically “a measurement of radioactive materials present inside a person’s body through analysis of the person’s blood, urine, feces, or sweat”.

assessment for the delayed or late effects of radiation exposure; (4) improve patient tracking efficiency for repeated observation or therapeutic administration; and, (5) potentially, have a role in the monitoring of therapy and long term follow-up (for example, biomarkers of damage and recovery to assess pharmacologic effect and potential long term cancer risk). Collectively, these benefits will enhance the medical and operational responses to radiation incidents of all types.

C. SCOPE

BARDA is specifically seeking medical countermeasures that will serve as diagnostics which will be clinically useful in a civilian medical emergency situation that results from or involves exposure of a large population to the effects of a nuclear detonation, a radiologic dispersion device (RDD), or exposure to ionizing radiation/ radioactive material with or without combined injury or trauma. The purpose of this BAA, entitled “POINT OF CARE OR HIGH-THROUGHPUT BIOLOGICAL ASSAYS FOR DETERMINING

ABSORBED IONIZING RADIATION DOSE (BIODOSIMETRY) AFTER RADIOLOGIC AND NUCLEAR

EVENTS”, is to solicit proposals for research and development programs that focus on: physical or biological tools, devices, biomarkers and bioassays for the accurate determination of an individual’s absorbed dose of ionizing radiation within the boundaries of 0.5 Gy to 10 Gy with a stated statistical certainty. At the conclusion of the base period plus option periods, if exercised, BARDA will receive study reports to independently assess the state of the technology and possibly obtain prototype models for more mature technologies.

After a radiation incident, dosimetry assessment tools for rapid determination of an individual’s exposure to ionizing radiation, i.e. absorbed dose, would be immensely helpful in screening, triage, and the management of clinical facilities in a mass casualty incident. Persons having an exposure to ionizing radiation exceeding 2 Gy determined using an initial Point of Care (POC) device may be advised to seek medical attention immediately as they are likely to need medical intervention to avoid acute radiation syndromes, specifically hematopoietic syndromes such as neutropenia. There is likely to be a great need for rapid, High-Throughput (HT) devices and bioassays that will define, with high statistical certainty, an individual’s absorbed ionizing radiation dose from 0.5 Gy to 10 Gy.

For purposes of this BAA, a promising dosimetry assessment tool, device, biomarker, or bioassay provides either a Point of Care (POC) diagnosis or is part of a High-Throughput (HT) system which may be confirmatory of a POC assessment but allows for a significantly greater number of assays per unit time.

The POC and HT tools and devices that employ biomarkers and bioassays are defined as diagnostics that meet the following characteristics:

• Point of Care (POC) bioassay devices shall provide accurate and reproducible measure of an absorbed ionizing radiation dose which is >2 Gy with high degree of certainty over days following a radiologic or nuclear event.

• HT biodosimetry devices shall provide quantitative, accurate, and reproducible radiation-responsive dose response measurements from 0.5 Gy to 10 Gy with a high degree of certainly for total body absorbed doses of ionizing radiation.

• It is desirable that the biodosimetry device use a well qualified biomarker for absorbed radiation and the device output can be readily interpretable and obtainable, i.e. retain its information, in the subsequent weeks to months following a radiological or nuclear event.

• The system (tool, device, biomarker, or bioassay) shall be reviewed within the regulatory processes of the Food and Drug Administration’s (FDA) Center for Devices and Radiologic Health (CDRH) and, any required animal studies could have added regulatory overview under either the FDA’s Centers for Drug Evaluation and Research (CDER) or the Centers for Biologics Evaluation and Research (CBER).

BARDA recognizes that the regulatory path to a diagnostic’s FDA Pre-market Approval (PMA) or

510(k) clearance may not be well defined and it is not the purpose of this BAA to obtain PMA or 510(k) approvals. The regulatory requirements are likely to be defined in an iterative decision-making process with the CDRH, CBER, and CDER authorities, based upon ongoing review of the product during the advanced development process and as specific product-related data emerge. Despite the uncertainty of the development process, the Offeror(s) shall provide a Statement of Work that would ultimately lead to a prototype guided by approval or clearance based regulatory pathways and discussions with the appropriate FDA Division recognizing risks and areas of significant uncertainty. Thus, it is requested that part of the Offeror’s proposal must include strategies for device development risk mitigation.

BARDA is aware that no single Offeror or institution may have the expertise and facilities required to perform all parts of their SOW. Therefore, it may be necessary for the Offeror to subcontract a portion of the work. The Offeror shall be responsible for all work performed under this contract including that performed by any subcontractor(s).

D. RESEARCH AND TECHNICAL OBJECTIVES

The experimental objectives, approaches, methodology, possible outcomes and alternatives, as well as the personnel, percent of effort, specific duties, work location, supervision, lines of authority, and available equipment, facilities, and other resources should be described by the Offeror for their proposed research and development area. When preparing proposals in response to this BAA, the Offeror must follow the format described in “Technical Proposal Instructions.”

The Offeror shall furnish all the necessary services, qualified personnel, materials, equipment, and facilities, not otherwise provided by the USG under the terms of this contract, as needed to provide the services delineated in the negotiated SOW. The specific components of the SOW and the scope of the product development activities to be undertaken will depend on the status of the individual diagnostic product as part of an overall Strategic Staged Product Development Plan (SSPDP), as well as regulatory requirements. The Offeror shall carry out activities within the contract SOW only as requested and approved by the Project Officer through the authority of the Contracting Officer. Approval to carry out specific activities will be linked to the Project Officer’s approval of the Strategic Staged Product Development Plan (SSPDP) and the Comprehensive Staged Product Development Plan (CSPDP) following contract award, approval of monthly and quarterly Progress Reports, review and approval of Clinical Trial Protocol(s) and supporting materials (see reporting requirements for a description of these reports).

Offerors shall provide the following information for each proposal:

• The Comprehensive Staged Product Development Plan (CSPDP): The CSPDP shall include scientific, technical and administrative processes to achieve the goals of the contract. The CSPDP shall include Gantt charts (WBS) with milestones based upon metrics for the research and development program, and shall include risk identification and mitigation. The CSPDP shall also include plans to meet industry standards for QMS (Quality Management System; e.g., quality control and quality assurance), data management and IT security for the conduct of proposed activities. For all proposed studies, the experimental designs shall be sufficiently detailed with rationale and experimental approaches, including descriptions of alternative approaches, if these methods do not achieve the defined goals, is required. The feasibility of the technical methods proposed in the CSPDP (e.g. animal models, non-clinical studies, manufacturing, and assay development) shall be outlined with milestones that are supported by an FDA-driven regulatory plan. Milestones, and the expected timelines for achieving each milestone, will be used to assess progress in the product development of the ionizing radiation dosimetry tool, device, biomarker, or bioassay for human exposure triage or dose confirmation. The first year CSPDP shall be in sufficient detail to allow for monitoring the success of the research and development project over that interim. Out years to year five may be less specific. Program Meetings (see below for description of Program Meetings) shall be incorporated into the CSPDP. An update to the CSPDP is required quarterly and will be part of the Quarterly Reports and the Annual Report (See “Technical Proposal Instructions”).

• The Strategic Staged Product Development Plan (SSPDP): The Offeror shall prepare and implement a SSPDP to advance the diagnostic product for a five year period. The SSPDP defines the overall market strategy for the tool, device, biomarker or bioassay. The plan includes flexibility of the Offeror’s program to modify the CSPDP and market position of the product based upon adverse experimental or production results, new scientific findings, FDA communications and reviews, or changes authorized by the Contract Officer.

Within fourteen (14) days of the effective date of the contract award, the Offeror shall submit an updated CSPDP and SSPDP. The plans shall be approved by the Project Officer and the Contracting Officer prior to initiation of any activities related to their implementation. The plans shall contain:

a) Sufficient detail, documentation and analysis to support successful completion of the stage as a milestone according to the Offeror’s predetermined qualitative and quantitative criteria that have been established for Go/No Go decisions

b) Cost estimates which will be incurred to complete the stage(s) (base and options) within negotiated amounts

c) A description of the negotiated product development plan to be initiated, as a revised CSPDP, if necessary, an updated budget, and a request for approval to proceed to the next stage of product development.

• Regulatory Compliance As required for the implementation of the CSPDP and SSPDP, the Offeror shall:

a) Be responsible for the regulatory aspects of the development and implementation of data management and quality control systems/procedures, including the transmission, storage, confidentiality, and retrieval of all study data.

b) Provide for the statistical design and analysis of data resulting from the research undertaken.

c) Provide raw data or specific analyses of data generated with contract funding to the Project Officer.

d) Ensure strict adherence to FDA regulations and guidance, including requirements for the conduct of device qualification, animal studies and assays under GLP, the manufacturing of the radiation dose assessment tool, device, or reagents for the proposed assays under cGMP, and the conduct of animal studies under GCP standards. The Offeror shall maintain quality assurance documentation to support adherence in these areas.

e) Arrange for independent audits, as needed or as requested by the Project Officer and as concurred by the Contracting Officer. Audits may be requested to assure that Offeror and/or sub-Offeror facilities and all planned procedures comply with the FDA regulations and guidance that are required to meet GLP, cGMP and GCP standards. In addition, the Offeror shall ensure that all Offeror and/or sub-Offeror records and staff are available for site visits or audits. The Offeror shall provide interim and final audit reports to the Project Officer and the Contracting Officer within thirty

(30) calendar days of the completion of the audit. BARDA reserves the right to conduct independent audits of the Offeror and its sub-Offerors as needed to evaluate compliance with the FDA regulations and guidance, including those required to meet GLP, cGMP or GCP standards.

Such audits may also be conducted prior to contract award as a part of the technical evaluation of the Offerors’ Technical Proposal.

f) Comply with FDA regulations and guidance for preparation, format, and submission of all regulatory documents to the FDA.

g) Provide data-extractable electronic media copies of all contract-generated regulatory documents to

BARDA.

• Radiation Controls and Safety The Offeror must describe the conditions of use and disposal of radioactive materials anticipated to be used in any of the BAA funded activities as well as operational safety, controls and standardization of devices used for radiation measurement and exposure. The Offeror shall provide evidence of Federal, State and Local health and safety regulatory compliance as well as evidence of holding appropriate institutional license(s) from regulatory authorities and documentation of oversight from a Radiation Safety Committee. This shall also be required of all subcontracted work.

• Animal Model Studies The rationale for proposed animal model studies and a detailed description of their relevance to human radiation injury shall be provided. Offerors proposing an animal model shall comply with all required guidelines for animal welfare. BARDA currently uses the guidelines employed at NIH as found in: http://grants1.nih.gov/grants/olaw/olaw.htm. An approved Plan for animal care and use is required of all Offerors and each must provide evidence of an ongoing and active Institutional Animal Care and Use Committee (IACUC) with USDA oversight of the facilities. AAALAC certification is a plus.

a) Care of Vertebrate Animals If awarded a contract, the Offeror, and all subcontractors under this contract, must annotate and comply with all veterinary care, husbandry, welfare and use of vertebrate animals in accordance with the following, if applicable to any negotiated statements of work:

i. Before undertaking performance of any contract involving research on live, vertebrate animals, the Contractor shall register with the Secretary of Agriculture of the United States in accordance with 7 U.S.C. 2316 and 9 CFR Section 2.30. The Contractor shall furnish evidence of such registration to the Contracting Officer.

ii. The Contractor shall acquire vertebrate animals used in the research endeavors contracted with BARDA from a dealer licensed by the Secretary of Agriculture under 7. U.S.C. 2131- 2157 and 9 CFR Sections 2.1-2.11, or from a source that is exempt from licensing under those sections.

iii. The Contractor agrees that all research involving live, vertebrate animals shall be conducted in accordance with applicable local, state, federal (including 21 CFR 58), or other regulations and policy on humane care and use of laboratory animals.

iv. If at any time during performance of the contract, the Contracting Officer determines that the

Contractor is not in compliance with any of the requirements and/or standards stated in paragraphs (a) through (c) above, the Contracting Officer may immediately suspend, in whole or in part, work and further payments under this contract until the Contractor corrects the noncompliance. Notice of the suspension may be communicated by telephone and confirmed in writing. If the Contractor fails to complete corrective action within the period of time designated in the Contracting Officer’s written notice of suspension, the Contracting Officer may terminate this contract in whole or in part.

• Clinical Studies and Associated Clinical Trials: Clinical studies are not anticipated in this BAA.

However, collection of ex-vivo samples may be necessary and all patient privacy and HIPPA compliance is mandated under the following:

a) Human Subjects Research involving human subjects shall not be conducted under this contract until the protocol has been approved by DHHS, written notice of such approval has been provided by the Contracting Officer, and the Contractor has provided to the Contracting Officer a properly completed “Protection of Human Subjects Assurance Identification/IRB Certification/Declaration of Exemption”, Form OMB No. 0990-0263 (formerly Optional Form 310) certifying IRB review and approval of the protocol. The human subject certification can be met by submission of the Contractor’s self designated form, provided that it contains the information required by the “Protection of Human Subjects Assurance Identification/IRB Certification/Declaration of Exemption”, Form OMB No. 0990-0263 (formerly Optional Form 310).

When research involving Human Subjects will take place at collaborating sites or other performance sites, the Contractor shall obtain, and keep on file, a properly completed “Protection of Human

Subjects Assurance Identification/IRB Certification/Declaration of Exemption”, Form OMB No.

0990-0263 (formerly Optional Form 310) certifying IRB review and approval of the research.

b) Protection of Human Subjects

i. No contract involving human subjects research shall be awarded until acceptable assurance has been given that the project or activity will be subject to initial and continuing review by an appropriate institutional review committee(s) as described in 45 CFR Part 46. Contracts involving human subjects will not be awarded to an individual unless the individual is affiliated with or sponsored by an institution that has an Office for Human Research Protections (OHRP) approved assurance of compliance in place and will assume responsibility for safeguarding the human subjects involved. The OHRP web site is: http://www.hhs.gov/ohrp. The Offeror further agrees to provide certification at least annually that the institutional review board (IRB) has reviewed and approved the procedures which involve human subjects in accordance with 45 CFR Part 46 and the Assurance of Compliance.

ii. The Offeror shall bear full responsibility for the performance of all work and services involving the use of human subjects under this contract in a proper manner and as safely as is feasible.

The parties hereto agree that the Offeror retains the right to control and direct the performance of all work under this contract. Nothing in this contract shall be deemed to constitute the Offeror or any subcontractor, agent or employee of the Offeror, or any other person, organization, institution, or group of any kind whatsoever, as the agent or employee of the Government. The Offeror agrees that it has entered into this contract and will discharge its obligations, duties, and undertakings and the work pursuant thereto, whether requiring professional judgment or otherwise, as an independent Offeror without imputing liability on the part of the Government for the acts of the Offeror or its employees.

iii. If at any time during performance of this contract, the Contracting Officer determines, in consultation with the OHRP, that the Offeror is not in compliance with any of the requirements and/or standards stated in paragraphs (a) and (b) above, the Contracting Officer may immediately suspend, in whole or in part, work and further payments under this contract until the Offeror corrects such noncompliance. Notice of the suspension may be communicated by telephone and confirmed in writing.

iv. If the Offeror fails to complete corrective action within the period of time designated in the Contracting Officer’s written notice of suspension, the Contracting Officer may, in consultation with OHRP, terminate this contract in whole or in part, and the Offeror’s name may be removed from the list of those Offerors with approved Health and Human Services Human Subject Assurances.

• Data Management. Data created from this contract shall be stored and managed at the Offerors’ site in a Laboratory Management System controlled and maintained by the Offeror, in consultation with the Project Officer. The Database Management System (DMS) shall be commercially available, documented, and supported by a relational database management system.

• Other Points of Consideration but not part of the Technical Evaluation:

a) Security Systems and Security Plan – contract generated data and IT systems. The Offeror shall provide, under the guidance and auspices of BARDA Security advisors, security systems, firewalls, and computer virus detection systems to be used to ensure database integrity and security. The local database at each Offeror site will contain, at a minimum: a) raw data and original results, and,

b) detailed experimental protocols. To ensure database integrity and interoperability, the Offeror shall include bioinformatics experts, in consultation with and approved by the Project Officer, in the research and development team. Key bioinformatics team members shall participate in the annual meetings (described below) in special sessions to define and execute standard operating procedures (SOPs) for data management and analysis. Additionally, during the life of the contract, the Offeror may be required to submit data to a centralized database developed and maintained by

BARDA information technology personnel. After contract award, the Project Officer and a BARDA- IT representative will work with the successful Offeror(s) to develop a process for data submission to the BARDA-IT maintained database.

b) Post-award Offeror Requirements:

i. Comply with all Federal and BARDA/NIH Clinical Terms of Award (http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf).

Submit to the BARDA Project Officer, all study protocols and supporting documentation (e.g., IACUC approvals, site quality management plan, data management plan, safety oversight plan, and local Institutional Review Board committee approvals or exemptions for human samples prior to study initiation) and amendments to the Project Officer for review and approval by the appropriate BARDA review committee. Preliminary data in appropriate animal models using ionizing radiation may support applicability of the animal model. In summary, the indication being sought drives the study design. The desired outcomes of the study (i.e., absorbed dose radiation-responsive biodosimetry tools, devices, biomarkers, and bioassays) should be determined early and carefully factored into the study design to ensure that the study meets both scientific and regulatory objectives (and is subject to approval by the Project Officer).

ii. Obtain final approval of all anticipated in vivo animal study protocols from the Project Officer prior to FDA submission for review of the proposed tools, devices, biomarkers or bioassays.

iii. Serve as the Product Sponsor with responsibility for:

a. Submitting all documentation to the FDA in a timely manner, consistent with timelines set out in the contract and by the FDA.

b. Including BARDA staff, as designated by the Project Officer, in meetings and teleconferences with the FDA.

c. Providing copies of all FDA correspondence and meeting minutes that are relevant to the therapeutic product to the BARDA Project Officer.

Although clinical trials (per se) will not be funded under this program for investigation of tools, devices, biomarkers, or bioassays, IRB-approved protocol(s) for any proposed human in vivo, ex vivo, or in vitro studies to support these techniques or devices, shall be included with the proposal as part of the human subjects section. Drafts of proposed informed consent form(s) for samples, if available at the time of the proposal submission, should be included as examples.

Prior to award, the Offeror shall provide to BARDA a “Memorandum of Understanding” signed by the Offeror, an appropriate representative of the applicant institution, the principal investigator of the parent(s), and an appropriate representative of the Offeror attending to the parent. The Memorandum shall outline the specifics of the agreement between the parties with respect to the following areas:

• Nature of all the biological specimens and the access controls;

• Timing and manner of access to data produced by the parent or core site(s) that will be used in the proposed studies;

• Ownership, analysis, and release of data resulting from the proposed studies;

• Documentation of quality assurance procedures for the proposed studies;

• Documentation of data and safety monitoring procedures for the studies;

• Ownership of intellectual property developed during the proposed studies; and,

• Publication of the results of the proposed studies.

c) Human Materials. Descriptions of any human tissue and/or clinical samples or data to be used in the proposed studies, including how human subjects shall be protected from research risks and justification for the ethnic, gender, and age compositions of the human populations chosen for analysis, is required. BARDA is utilizing and requiring compliance with all NIH guidelines for human subjects research as found in: http://www.hhs.gov/ohrp. Descriptions of human use shall be sufficiently detailed to allow the Technical Evaluation Panel (TEP) to determine the feasibility and appropriateness of the proposed experimental approaches.

It is understood that the acquisition and supply of all human specimen material (including fetal material) used under the resultant contract will be obtained by the Contractor in full compliance with applicable State and Local laws and the provisions of the Uniform Anatomical Gift Act in the United States and that no undue inducements, monetary or otherwise, will be offered to any person to influence their donation of human material.

• Facilities, Equipment and other Resources The Offeror shall provide the equipment, facilities, training and other resources required to implement the SOW and the Strategic Staged Product Development Plan in compliance with all Federal regulations. Depending on the stage of development of the absorbed radiation dose assessment technique or device, this may include:

a) The development of, testing in appropriate radiation injury models (i.e. GLP animal studies), establishment of performance standards, and qualification validations of tools, devices, biomarkers, or bioassay for assessment of an individual’s absorbed ionizing radiation dose.

b) Production, characterization and release testing of required reagents, biomarkers and bioassay associated configuration products (i.e. lateral flow systems) under cGMP conditions.

c) Performance of bioassays using human samples under GCP.

d) The humane care and use of vertebrate animals with IACUC and USDA oversight

e) The handling, storing and shipping of radioactive agents and radiologic devices. In terms of radiologic operations, BARDA expects operational standards for handling radioactive material, radiologic devices and radioactive waste to be managed under environmental health and safety practices that follow, for example, the guidance of the Department of Energy’s Lawrence Berkeley Laboratory Environmental Health and Safety Publication 3000 (http://www.lbl.gov/ehs/pub3000/CH21.html#_Toc407168416).

f) The handling and disposal of potentially dangerous biological and chemical agents. These activities shall require Biosafety practices and procedures as described in Biosafety in Microbiology and Biomedical Laboratories, 4th ed., which is available at:

http://www.cdc.gov/od/ohs/biosfty/bmbl4/bmbl4toc.htm. In addition, and if the Offerors propose using Select Agents as named by the Centers for Disease Control and Prevention (CDC) Select Agent Program, shall refer to: http://www.cdc.gov/od/sap.

The Offeror is required to undertake all studies with documentation of approvals from all Institutional Biosafety, radiologic and animal oversight committees. At the request of the Project Officer, the Offeror shall provide copies of all notes, letters and materials submitted to and from all such committee reviews. Documentation of all approvals of experiments, protocols and procedures shall be copied and forwarded to the Project Officer for retention in the Project File at BARDA.

• Possession, Use and Transfer of Select Agents or Toxins. The contractor will not conduct any work involving Select Agents or toxins under this contract until the contractor and any associated subcontractor(s) comply with the following requirements:

a) For prime or subcontract awards to US companies or institutions that will possess, use, and/or transfer Select Agents under this contract: The prime and/or subcontractor must comply with the provisions of 42 CFR Part 73, 7 CFR Part 331, and/or 9 CFR Part 121, as required, before using BARDA funds for any work involving Select Agents. BARDA funds can not be used for any work associated with Select Agents if the CDC or USDA denies the final registration certificate authorizing work with Select Agents or Toxins.

b) For prime or subcontract awards to foreign companies or institutions that will possess, use, and/or transfer Select Agents under this contract: Before using BARDA funds for any work directly involving the Select Agents or Toxins, the foreign company or institution must meet the safety, security, and training standards equivalent to those described in 42 CFR Part 73, 7 CFR Part 331, and/or 9 CFR Part 121. The contractor or and/or subcontractor must submit a written security plan that meets the requirements of 42 CFR Part 73, 7 CFR Part 331, and/or 9 CFR Part 121 and is sufficient in scope to safeguard Select Agents or Toxins against unauthorized access, theft, loss or release. The foreign company or institution will not use any Select Agents or Toxins associated with this contract until approved by BARDA. Prior to allowing a foreign company or institution to work with Select Agents or Toxins, BARDA must determine that appropriate security measures, as outlined the companies’ security plan, are in place. This determination will include an inspection of the foreign facility by a BARDA representative. During this inspection, the contractor must provide the following information: concise summaries of safety, security, and training plans; names of individuals who will have access to the Select Agents, and procedures for ensuring that only approved and appropriate individuals will have access to the Select Agents under the contract. The contractor will also provide copies of or links to any applicable laws, regulations, policies, and procedures applicable to the contactor that provide for the safe and secure possession, use, and/or transfer of Select Agents or Toxins. BARDA will coordinate with the CDC, the US Department of Justice, and/or other federal law enforcement or intelligence agencies prior making a final determination on allowing the contractor to possess, use, and/or transfer Select Agents or Toxins.

BARDA will make the approval decision and notify the Contracting Officer. The BARDA Contracting Officer will inform the prime contractor of the approval status of the foreign institution.

c) Listings of HHS select agents and toxins, and overlap select agents or toxins as well as information about the registration process for domestic institutions, are available on the Select Agent Program Web site at http://www.selectagents.gov/ . For foreign institutions, see the NIAID Select Agent Award information web site at: http://www.niaid.nih.gov/ncn/clinical/default_biodefense.htm.

• Intellectual Property Rights. For issued patents or published patent applications that will be used in the performance of the contract, provide the patent number or patent application publication number, a summary of the patent or invention title, and indicate whether the offeror is the patent or invention owner.

E. REPORTING REQUIREMENTS AND DELIVERABLES

Some reports and other deliverables are relevant to specific activities that may or may not be performed during the contract period of performance. The Contractor, the Project Officer and the Contracting Officer shall agree in the final contract negotiations on which reports and other deliverables are relevant and shall be required as deliverables in the negotiated Statement of Work (SOW).

As part of the work to be performed under this BAA, the Contractor shall prepare and deliver the following reports throughout the period of performance. For all reports the Contractor shall submit two (2) paper copies and one (1) electronic copy to the Project Officer and one (1) original paper copy and one (1) electronic copy to the Contracting Officer.

• Monthly, Quarterly and Annual Technical Progress Reports

The Contractor(s) shall provide written monthly, quarterly and annual reports of project activities, budget changes and projections of costs, personnel actions in the period of the report, and vendor/subcontractor activities that are conducted by way of the contract to the Contracting Officer and Project Officer.

The Contractor shall submit two (2) copies of the Monthly, Quarterly and Annual Technical Progress Reports on the 15th of the month following the end of each month, 3 months (90 calendar days), and 12 month performance period respectively. The original shall be submitted to the Contracting Officer with one (1) copy submitted to the Project Officer. Each Monthly, Quarterly and Annual Technical Progress Report shall include the following:

a). Face page, to include the contract number, contract title, performance period covered, Contractor’s name and address, telephone number, fax number, email address, the author(s) and any other contact information, and the submission date. In addition provide a brief introduction covering the purpose and scope of the contract effort.

b). Executive summary shall be formatted in Microsoft PowerPoint to include:

i. An overview of the status of the project, including adherence to timelines, since the previous reporting period and specific milestones achieved;

ii. An overview of the activities conducted during the current reporting period, including test results, tasks and other activities achieved, any problems that occurred (technical or financial) and justification for any failure to complete the intended work, as well as any work that was performed beyond that initially planned;

iii. The extent to which the goals and specific objectives set forth in the SOW were fulfilled

iv. The present project issues as headings with each item a talking point bullet c). Progress Report(s) to include a detailed description of the work performed during the reporting period and a brief description of the work proposed for the next reporting period toward the designated advanced research and development of physical or biological assays for the accurate determination of an individual’s absorbed dose of ionizing radiation within the boundary of 0.5 Gy to 20 Gy with a stated statistical certainty. The Progress Reports shall include:

i. A full disclosure of the results obtained and their relevance, explanations of any differences between planned and actual progress, and, if necessary, what corrective steps are planned or have been implemented to achieve the goals and objectives of the contract

ii. A regular update to the Project Plan. The Contractor shall update the milestones of the research program and time-line implementation of milestones for aim/goal/ data and their intermediates for the upcoming 2 quarters, highlighting (in color, bold, italic, etc.) any changes in the previously reported Plan. Alterations in the Plan shall be sufficiently outlined and justified;

iii. A summary of the meetings, conference calls, and workshops that have taken place during the reporting period. This report shall include the slide presentations and all other meeting materials as well as summaries of all discussions.

iv. Distribution List-A list of persons receiving the Technical Progress Reports;

v. Attachments – Results or protocols developed on the project shall be provided as attachments;

vi. Annual Technical Progress Report. In addition to the requirements above, the Annual

Technical Progress Report shall require the Contractor to update the Project Plan’s milestones of the research program and time-line implementation of milestones for aim/goal/ data and their intermediates for the upcoming 4 quarters, highlighting (in color, bold, italic, etc) any changes in the previously reported Plan. Alterations in the Plan shall be sufficiently outlined and justified. Additionally, the Contractor shall update any changes in milestones and plans for the remaining years of the project.

d). Copies of manuscripts (published or unpublished) derived from research performed under the contract and copies of all abstracts, manuscripts, preprints, and publications that resulted from work conducted, as well as any protocols and methods developed specifically under the contract during the performance period;

e). A full disclosure of intent to file patent applications or copyrights within or outside of the U.S. on procedures utilized, derived, or established by the work supported under the contract; and full disclosure of any patent applications or copyrights filed, as well as copies of patent or copyright applications;

f). An update of the status of the Intellectual Property Rights Plan shall be provided;

g). A Quarterly Technical Progress Report is not required for the period in which an Annual Technical

Progress Report or a Final Report is due;

h). A Monthly Technical Progress Report is not required for the period in which a Quarterly, Annual or a Final Technical Progress Report is due.

• Final Report of the Contract

The Contractor shall submit two (2) copies of the Final Report one week prior to the completion date of the contract. The original shall be submitted to the Contracting Officer, with one (1) copy submitted to the Project Officer. The Final Report shall include the following:

a). Face page, to include the contract number, contract title,…