Biodosimetry_RFP-16-100-SOL-00010_6.7.2016_fbo.pdf

PAGES

15A. NAME

AND

ADDRESS

OF

OFFEROR

SEC. PAGE(S) SEC. PAGE(S)

(Date) (Hour)

CALENDAR DAYS

14. ACKNOWLEDGMENT OF AMENDMENTS

(The Offeror acknowledges receipt of amend-ments to the SOLICITATION for Offerors and related documents numbered and dated:

(Type or Print)

PAGES

(Date) (Hour)

SEC. PAGE(S) SEC. PAGE(S)

CALENDAR DAYS

14. ACKNOWLEDGMENT OF AMENDMENTS

(The Offeror acknowledges receipt of amend-ments to the SOLICITATION for Offerors and related documents numbered and dated:

15A. NAME

AND

ADDRESS

OF

OFFEROR

(Type or Print)

AUTHORIZED FOR LOCAL REPRODUCTION STANDARD FORM 33 (REV. 9-97)

PREVIOUS EDITION IS UNUSABLE Prescribed by GSA

SOLICITATION, OFFER AND AWARD 1. THIS CONTRACT IS A RATED ORDER

UNDER DPAS (15 CFR 700)

RATING

PAGE OF

1 150

2. CONTRACT NO.

N/A

3. SOLICITATION NO.

RFP-16-100-SOL-00010

4. TYPE OF SOLICITATION

SEALED BID (IFB)

X NEGOTIATED(RFP)

5. DATE ISSUED

06/07/2016

6. REQUISITION/PURCHASE

NO.

N/A

7. ISSUED BY CODE 8. ADDRESS OFFER TO (If other than Item 7)

HHS/OS/ASPR/AMCG

330 Independence Ave, SW, RM G-640 Washington, DC 20201

NOTE: In sealed bid solicitations “offer” and “Offeror” mean “bid” and “bidder.”

SOLICITATION

9. Sealed offers in original and 1 copies for furnishing the supplies or services in the Schedule will be received at the place specified in Item 8, or if handcarried, in the depository located in See Section L for Instructions until 12:00 PM local time 07/2216

CAUTION -- LATE Submissions, Modifications, and Withdrawals: See Section L, Provision No. 52.214-7 or 52.215-1.

All offers are subject to all terms and conditions contained in this solicitation.

10. FOR INFORMATION

CALL:

A. NAME

Amorette McKeithan

a. TELEPHONE (NO COLLECT CALLS)

(202) 692-4623

b. E-MAIL ADDRESS

Amorette.Mckeithan@hhs.gov

11. TABLE OF CONTENTS

((x) DESCRIPTION (x) DESCRIPTION

PART I – THE SCHEDULE PART II – CONTRACT CLAUSES

X A SOLICITATION/CONTRACT FORM 01 X I CONTRACT CLAUSES 64

X B SUPPLIES OR SERVICES AND PRICES/COSTS 03 PART III - LIST OF DOCUMENTS, EXHIBITS AND OTHER ATTACH.

X C DESCRIPTION/SPECS./WORK STATEMENT 12 X J LIST OF ATTACHMENTS 84

X D PACKAGING AND MARKING 21 PART IV – REPRESENTATIONS AND INSTRUCTIONS

X E INSPECTION AND ACCEPTANCE 22 REPRESENTATIONS, CERTIFICATIONS, AND

X F DELIVERIES OR PERFORMANCE 24 X OTHER STATEMENTS OF OFFERORS 85

X G CONTRACT ADMINISTRATION DATA 36 X L INSTRS., CONDS., AND NOTICES TO OFFERORS 98

X H SPECIAL CONTRACT REQUIREMENTS 41 X M EVALUATION FACTORS FOR AWARD 108

OFFER (Must be fully completed by Offeror) NOTE: Item 12 does not apply if the solicitation includes the provisions at 52.214-16, Minimum Bid Acceptance Period.

12. In compliance with the above, the undersigned agrees, if this offer is accepted within ___150___calendar days (60 calendar days unless a different period is inserted by the Offeror) from the date for receipt of offers specified above, to furnish any or all items upon which prices are offered at the price set opposite each item, delivered at the designated point(s), within the time specified in the schedule.

13. DISCOUNT FOR PROMPT PAYMENT

(See Section I, Clause No. 52-232-8)

10 CALENDAR DAYS

20 CALENDAR DAYS

30 CALENDAR DAYS

AMENDMENT NO. DATE AMENDMENT NO. DATE

CODE FACILITY 16. NAME AND ADDRESS OF PERSON AUTHORIZED TO SIGN OFFER

15B. TELEPHONE NO.

AREA CODE NUMBER EXT.

15C. CHECK IF REMITTANCE ADDRESS

IS DIFFERENT FROM ABOVE - ENTER

SUCH ADDRESS IN SCHEDULE.

17. SIGNATURE

18. OFFER DATE

AWARD (To be completed by Government)

19. ACCEPTED AS TO ITEMS NUMBERED 20. AMOUNT

22. AUTHORITY FOR USING OTHER THAN FULL AND OPEN COMPETITION:

21. ACCOUNTING AND APPROPRIATION

10 U.S.C. 2304(c)( ) 41 U.S.C. 253(c)( ) 23. SUBMIT INVOICES TO ADDRESS SHOWN IN (4 copies unless otherwise specified)

ITEM

24. ADMINISTERED BY (If other than Item 7) CODE 25. PAYMENT WILL BE MADE BY CODE

26. NAME OF CONTRACTING OFFICER (Type or print)

27. UNITED STATES OF AMERICA

(Signature of Contracting Officer)

28. AWARD DATE

IMPORTANT -- Award will be made on this form, or on Standard Form 26, or by other authorized official written notice.

FAR (48 CFR) 53.214©

K

Biodosimetry High-Throughput Tests

NOTE TO OFFERORS

The information in SECTION A - Solicitation/Contract Form, contains important information for any Offeror interested in responding to this solicitation. Any contract resulting from this solicitation will include in its SECTION A - Solicitation/ Contract Form, accounting, appropriation and general information applicable to the contract award.

The contract schedule, set forth in SECTIONS B through H, contains contractual information pertinent to this solicitation. It is not an exact representation of the contract document that will be awarded as a result of this solicitation. The contract cost or price and other contractual provisions unique to the Offeror's proposal may be included in the resultant contract.

The contract schedule is intended to provide the Offeror with information to aid in understanding the likely terms and conditions of any resultant contract.

SECTION B – SUPPLIES OR SERVICES AND PRICES / COSTS

B.1. BRIEF DESCRIPTION OF SUPPLIES OR SERVICES

This Request for Proposal (RFP) solicits proposals for contract(s) involving an initial phase for test validation and FDA approval using a cost reimbursement structure and subsequent phases to stock and replenish a stockpile using firm fixed pricing for the acquisition of Biodosimetry High- Throughput Diagnostic Tests.

The Biomedical Advanced Research and Development Authority (BARDA) within the Office of the Assistant Secretary for Preparedness and Response (ASPR) at the U.S. Department of Health and Human Services (HHS), seeks to establish preparedness via advanced development and procurement of Biodosimetry High-Throughput Diagnostic Tests that will determine absorbed doses of ionizing radiation and inform the use of Medical Countermeasures (MCMs) and administer medical care following a radiation or nuclear incident.

The Biodosimetry High-Throughput Diagnostic Test is designed to be run in a clinical laboratory that produces a quantitative estimate of the actual absorbed dose a person received from 0 to 10 Gray (Gy). The result will be used in conjunction with signs, symptoms, and hematology to give the health care provider additional information to allow the correct level of care to be administered to each patient.

The Pandemic and All Hazards Preparedness Act (PAHPA) of 2006 established the Biomedical Advanced Research and Development Authority (BARDA) and was reauthorized under the PAHPA of 2013 to support development and acquisition of medical countermeasures (MCMs) to prevent or treat the medical consequences of chemical, biological, radiological, and nuclear (CBRN) threats, pandemic influenza (PI), and emerging infectious diseases (EID). These MCMs include vaccines, therapeutics, diagnostics, and medical devices. Additionally, BARDA is entrusted to foster innovation of technologies that enable better manufacturing, testing, and utilization of these medical countermeasures.

BARDA intends to fund the advanced development and procurement of quantitative diagnostic radiation biodosimetry tests that will determine absorbed doses of ionizing radiation.

In an attempt to become fully prepared to medically manage hundreds of thousands of people with radiation injuries, some combined with mechanical trauma or thermal burns, and to distribute medical countermeasures effectively following a radiological or nuclear incident, the development and acquisition of radiation biodosimetry tests is necessary.

Under the Project BioShield (PBS) Act (2004) and the Pandemic and All-Hazards Preparedness Reauthorization Act of 2013, BARDA was charged with developing medical countermeasures (MCMs) to address radiological and nuclear threats to the United States as determined by the Department of Homeland Security as Material Threats. In the aftermath of an improvised nuclear device (IND) detonation or a nuclear accident, having rapid and accurate measurements of internal radiation absorption in exposed persons can inform life-saving medical decisions. The high-throughput biodosimetry test is a dose-dependent measurement of the biological changes caused by ionizing radiation that result in internal body damage. The test results will determine the level, duration, and combination of medical care administered to an individual. BARDA anticipates that contract(s) awarded from this RFP will serve to facilitate the test validation, EUA and FDA diagnostic filings, and the initial stockpiling of biodosimetry tests for use in a nuclear incident.

Upon development completion, the high-throughput laboratory-based assay(s) will produce an estimate of the ionizing radiation dose a person absorbed from 0 to 10 Gy. The result will be used in conjunction with clinical signs, symptoms and hematology, to give the health care provider additional information to allow an appropriate level of care to be administered to each patient in light of resource availability. This will greatly enhance the present health care capabilities for nuclear incident victims.

B.2. SPECIFIC REQUIREMENTS

For the high-throughput biodosimetry assay, BARDA is seeking a test that meets or exceeds the following criteria:

• Produces an estimate of the individual absorbed ionizing radiation dose over the 0 to 10 Gy from 24 hours to at least 7 days post-irradiation

• Is semi-quantitative or quantitative with an accuracy throughout the 2 to 6 Gy range of +/- 1.2 Gy (+/- 0.5 Gy preferred) from 24 hours to at least 7 days post-irradiation

• Can be used as an additional tool in the radiation evaluation arsenal in conjunction with signs, symptoms, and hematology to guide the medical treatment of affected individuals

• Is highly automated and can be used in a clinical laboratory setting by trained individuals

• Can be run on a system of no more than 150 commercially placed in clinical reference, hospital, or public health care laboratories, to potentially generate a daily result output capability of more than 60,000 test results over at least 7 days post-incident.

• With pre-event verification, could immediately be effectively and accurately run in a CLIA compliant health care or public health laboratory that have the instrument installed and in use for other clinical assays

• Has an analytical performance demonstrating the comparability of results between in vivo irradiated human and non-human primate samples, to support entering into design validation per requirements in the U.S. FDA Quality Systems Regulations (21 CFR Part

820) and pre-market clearance within approximately one year of contract award.

• The instrument and assay reliability yield a reportable result greater than 95% of the time.

• Uses commercially available instruments with sufficient pre-placements in CLIA compliant laboratories to perform the required number of tests in the United States. These instruments may require improvements to be installed on the instrument base to perform this test.

B.3. PRICES / COSTS

The final contract(s) will contain the price/cost provisions agreed upon by the Government and the Offeror.

The final contract(s) is expected to have a base and several options, dependent on the shelf-life of the reagent and assay kits) option periods, and an optional test update period running concurrent with another option period for a total maximum contract length of 10 years.

The Contractor shall maintain records of all contract costs and such records shall be subject to FAR 52.215-2 (Oct 2010), Audit and Records-Negotiation, and Health and Human Services Acquisition Regulation (HHSAR) 352.242-74, Final Decisions on Audit Findings, incorporated by reference into this Contract in SECTION I.

B.3.1. Base Period

The notional Base Period of Performance is September 30, 2016 through September 29, 2018.

An offeror may adjust this period of performance to align with their proposed project timeline.

CLIN Description Estimated Period of Performance

Estimated Cost

Fixed Fee

Cost Plus Fixed Fee

Advanced development of the Biodosimetry

High-Throughput Diagnostic tests in which will contribute to FDA filing and approval

9/30/2016 - 9/29/2018

* Business proposals shall include labor rate costs, facility costs, and all other costs necessary to complete test validation, filing pre- EUA and FDA approval documents, completing test definition software package, and initial manufacturing of the first portion (40,000 tests) of the radiation biodosimetry reagents and assay kits.

† The government will not be responsible for any Contractor-incurred costs that exceed this amount unless a modification to the contract is signed by the Contracting Officer (CO) which expressly increases this amount.

‡The government shall withhold the payment of a portion of the fee to protect the government’s interest as set forth in Federal Acquisition Regulation (FAR) 52.216-8, Fixed Fee (June 2011). The government shall withhold 15 percent of the total fixed fee or $100,000, whichever is less, until after government review and acceptance of the Final Technical Progress Report.

§Initial manufacturing upon the test receiving EUA status.

B.3.2. Option Periods

Pursuant to FAR 52.217-9, Option to Extend the Term of the Contract (Mar 2000), set forth in full in ARTICLE I.3 of this Contract, the government may, by unilateral contract modification, require the Contractor to perform discrete portions of additional work as specified in the Statement of Work.

Unless the Government exercises its option pursuant to the option clause referenced in SECTION I, Contract Clauses, this contract consists only of the base period. Below are the notional options that will be dependent on the shelf-life of the kits being produced.

The final contract(s) will contain Option CLINs with unit prices agreed upon by the Government and the Offeror. The Offeror can propose Option periods based on the shelf-life of their test and reagent kits not to exceed September 2026 in 1 year increments. The Options may be exercised after FDA approval is given for the test. The Government reserves the right to exercise or not exercise any options. A sample of subsequent Option timing is below:

* Business proposals shall include test stockpiling and replenishment, inventory management, distribution and services.

† The above-referenced time periods are based upon BARDA’s minimum requirements for a 2 year kit and reagent shelf-life. BARDA would prefer a longer shelf-life and offerors are encourages to propose longer shelf-lives that exceed BARDA’s minimum requirements. )

Firm Fixed Price CLINs CLIN Description Period of

Performance Units Quantity Price

Per Unit

Extended Price*

0002 Option One: Complete 1st stockpile fulfillment. Fulfillment Period – Manufacture and the delivery of biodosimetry tests, reagents and instrument test definition software

9/30/2018 - 9/29/2019†

Each 360,000

0003 Option Two: Test Replenishment;

Replenishment Period 1 – Planning for replenishment stocks of biodosimetry tests and reagents, and the manufacture of the first replenishment stocks

9/30/2019 - 9/29/2021†

Each 400,000

0004 Option Three: Test Replenishment;

Replenishment Period 2 - Manufacture of the replenishment stocks for biodosimetry tests and reagents

9/30/2021 - 9/29/2023†

Each 400,000

0005 Option Four: Test Replenishment;

Replenishment Period 3 - Manufacture of the replenishment stocks for biodosimetry tests and reagents

9/30/2023 - 9/29/2025†

Each 400,000

0006 Option Five: - Test Replenishment;

Replenishment Period 4 Manufacture of the replenishment stocks for biodosimetry tests and reagents

9/30/2025 - 9/29/2026†

Each 400,000

* A test upgrade could substantially increase the result output, significantly lower the cost of testing, or change amount of effort needed to produce an accurate result. Upgrades that change the intended use or pose new device or assay questions regarding safety or effectiveness will not be funded via this RFP.

B.3.2.1. Option Six

The USG may exercise Option Six (CLIN 0007) to fund a test upgrade that could substantially increase the result output, significantly lower the cost of testing, or change the amount of effort needed to produce an accurate result. The Contractor must provide evidence of the capability to achieve such an upgrade and propose the necessary activities, which may include:

Note: Upgrades that change the intended use or pose new device or assay questions regarding safety or effectiveness will not be funded via this RFP.

The exact period of performance is likely to begin after FDA approval is given to the initial High-throughput Biodosimetry Test.

B.4. ADVANCE UNDERSTANDINGS

B.4.1. Funding

This solicitation is subject to the availability of funds.

B.4.2. Cost Unallowable Unless Authorized by the Contracting Officer

This solicitation and subsequent contract(s) prohibits or restricts the use of contract funds for the following, unless otherwise approved in advance by the Contracting Officer:

a) Acquisition, by purchase or lease, of any interest in real property;

b) Rearrangement or alteration of facilities;

c) Purchase or lease of any item of general purpose office furniture or office equipment regardless of dollar value;

d) Accountable Government Property;

e) Overtime

f) Travel to attend general scientific meetings/conferences;

g) Foreign Travel Costs;

h) Costs incurred in the performance of any cost-reimbursement type subcontract(s) (including consulting agreements);

i) Costs to be paid for the performance of a fixed-price subcontract(s) that exceeds

$150,000.00 or 10 % of the total estimated cost of the Contract, whichever value is greater.

CLIN Description Period of Performance Estimated Cost

Fixed Fee

Cost Plus Fixed Fee

0007 Biodosimetry High- Throughput Test Upgrade*

Flexible

B.4.3. Invoices - Cost and Personnel Reporting, and Variances from the Negotiated Budget

For contract work performed on a cost reimbursement basis, the Contractor agrees to provide a detailed breakdown on invoices of the below cost categories as applicable. A sample invoice form is provided as Attachment #2.

1. Direct Labor - Include salaries and wages paid (or accrued) for direct performance of the contract. List individuals by name, title/position, hourly/annual rate, level of effort (actual hours or % of effort), breakdown by task performed by personnel, and amount claimed.

2. Fringe Benefits - Cite rate and amount

3. Overhead - Cite rate and amount

4. Materials & Supplies - Include detailed breakdown when unit price is over $1,000.

5. Travel - Identify travelers, dates, destination, purpose of trip, and amount. Cite COA, if appropriate. List separately, domestic travel, general scientific meeting travel, and foreign travel.

6. Consultant Fees - Identify individuals and amounts.

7. Subcontracts - Attach subcontractor invoice(s).

8. Equipment - Cite authorization and amount.

9. G&A - Cite rate and amount.

10. Total Cost

11. Fixed Fee

12. Total Cost Plus Fixed Fee (Total CPFF)

For contract work performed on a cost reimbursement basis, monthly invoices must include the cumulative total expenses to date, adjusted (as applicable) to show any amounts suspended by the Government. Also note the Contracting Officer may require the Contractor to submit detailed support for costs claimed on payment requests. All claimed costs must be allocable, reasonable, and allowable per FAR Part 31. BARDA reserves the right to disallow any costs that are not allocable, reasonable or allowable per FAR Part 31. Offerors are encouraged to review FAR Part 31 to assure that their estimated costs will meet the standards under FAR Part 31 and that their billing structure and accounting system will enable them to account for costs that meet those standards. Invoice submission information is provided in SECTION G.6.

This invoicing structure is not applicable to fixed price options. Please see Attachment #3 for fixed price invoicing instructions.

B 4.4 Travel Costs

1. Total expenditures for all travel (transportation, lodging, subsistence, and incidental expenses) incurred by the Contractor in direct performance of this Contract during the base period shall not exceed $ 25,500 without the prior written approval of the Contracting Officer.

Cost must be consistent with FAR 52.247-63 – Preference for U.S. - Flag Air Carriers.

2. The Contactor shall invoice and be reimbursed for all travel costs in accordance with FAR 31.205-46, Travel Costs and GSA Per Diem Rates (www.gsa.gov/perdiem).

3. Requests for foreign travel must be submitted at least four weeks in advance and shall http://www.gsa.gov/perdiem contain the following:

• Meeting(s) and place(s) to be visited, with costs and dates;

• Names(s) and title(s) of Contractor personnel to travel and their functions in the contract project;

• Contract purpose to be served by the travel;

• How travel of Contractor personnel will benefit and contribute to accomplishing the contract project, or will otherwise justify the expenditure of AMCG Contract funds;

• How such advantages justify the costs for travel and absence from the project of more than one person if such are suggested; and

• What additional functions may be performed by the travelers to accomplish other purposes of the contract and thus further benefit the project?

B 4.5 Subcontracts

Prior written consent from the Contracting Officer in the form of a Contracting Officer Authorization (COA) is required for any subcontract that:

Is of the cost-reimbursement type or Time-and-Materials (T&M);

Is Fixed-Price and exceeds $150,000 or 10% of the total estimated cost of the Contract, whichever value is greater.

The Contracting Officer shall request appropriate supporting documentation in order to review and determine authorization, pursuant with FAR Clause 52.244-2, Subcontracts (Alternate I).

After receiving written consent of the subcontract by the Contracting Officer, a copy of the signed, executed subcontract and consulting agreement shall be provided to the Contracting Officer within ten (10) calendar days.

Note: Consulting services are treated as subcontracts and subject to the ‘consent to subcontract’ provisions set forth in this Article.

B.4.6 Confidential Treatment of Sensitive Information

The Contractor shall, to the extent permitted by law, guarantee strict confidentiality of sensitive/confidential information/test results that is provided by the USG during the performance of the contract. The USG has determined that certain information/test results that the Contractor will be provided during the performance of the contract are of a sensitive nature.

Disclosure of confidential/sensitive information/test results, in whole or in part, by the Contractor can only be made after the Contractor receives prior written approval from the Contracting Officer. Whenever the Contractor is uncertain with regard to the proper handling of information/ test results under the contract, the Contractor shall obtain a written determination from the Contracting Officer.

Notwithstanding the foregoing, such information/test results shall not be deemed of a sensitive or confidential nature with respect to the Contractor for purposes of this Contract if such information/test results: (a) was already known to the Contractor other than by prior disclosure by the USG or discovered through work under a prior USG contract; (b) was generally available or known, or was otherwise part of the public domain, at the time of its disclosure to the Contractor;

(c) became generally available or known, or otherwise became part of the public domain, after its disclosure to, or, with respect to the information/test results by, the Contractor through no fault of the Contractor; (d) was disclosed to the Contractor, other than under an obligation of confidentiality or non-use, by a third party who had no obligation to the USG that controls such information/test results not to disclose such information/test results to others; or (e) was independently discovered or developed by the Contractor, as evidenced by its written records, without the use of information/test results belonging to the USG.

The Contractor may disclose information/test results of a sensitive nature provided by the USG to the extent that such disclosure is: (a) made in response to a valid order of a court of competent jurisdiction (b) otherwise required by law or regulation, or (c) made by the Contractor to the Regulatory Authorities as required in connection with any filing, application or request for Regulatory Approval; provided, however, that reasonable measures shall be taken to assure confidential treatment of such information/test results.

B 4.7 Sharing of contract deliverables within United States Government (USG)

In an effort to build a robust medical countermeasure pipeline through increased collaboration, the Government may share technical deliverables with USG entities responsible for Medical Countermeasure Development. In accordance with recommendations from the Public Health Emergency Medical Countermeasure Enterprise Review, agreements established in the Integrated Portfolio Advisory Committee (PAC) Charter, and agreements between BARDA and the Department of Defense, the National Institutes of Health, the Centers for Disease Control, and the Food and Drug Administration, BARDA may share technical deliverables and test results created in the performance of this Contract with colleagues within the Integrated Portfolio. This advance understanding does not authorize the Government to share financial information outside of the United States Government. The USG will retain Contractors’ proprietary rights notices and restrictive legends on all copies of deliverables and will disclose them outside the USG only to parties that have a need to know and are subject to non-disclosure obligations at least as restrictive as those set forth in Section B.4.9. The Contractor is advised to review the terms of FAR 52.227-14, Rights in Data – General, regarding the government’s rights to deliverables submitted during performance as well as the government’s rights to data contained within those deliverables.

B. 4.8 Approval of Human and Animal Protocols

The Contractor shall submit all human and animal protocols and human informed consent documents as referenced under this Contract to the COR for review and approval prior to seeking other approvals (Institutional Review Board, Human Use Committee, Institutional Animal Care and Use Committee). The Government requires no fewer than eight (8) business days to perform a review. The Contractor shall take this review time into account and submit protocols as early as possible to avoid delays. The Government’s comments and feedback shall be addressed prior to approval. The COR will review and provide approval of protocols. Human informed consents shall also be submitted and reviewed with any human protocol.

B.4.9 Rights in Data

The contract will incorporate the Alternate II to FAR Clause 52.227-14, Rights in Data—general, pursuant to FAR Clause 52.227-14 (g)(3). The Contractor is advised to review the terms of FAR 52.227-14, Rights in Data, regarding the government’s rights to deliverables submitted during performance as well as the government’s rights to data contained within those deliverables.

ELEMENT OF COST AS INDENTIFIED SECTION C –

DESCRIPTION/SPECIFICATIONS/STATEMENT OF OBJECTIVES (SOO)

C.1. INTRODUCTION/BACKGROUND

Within the Federal government, the Department of Health and Human Services (HHS) is tasked with protecting the civilian population by providing leadership in research, development, acquisition, deployment, and use of effective medical countermeasures for the adverse health effects resulting from intentional exposure to CBRN threat agents, pandemics and emerging infectious disease threats.

Under the Project BioShield (PBS) Act (2004) and the Pandemic and All-Hazards Preparedness Reauthorization Act of 2013, BARDA was charged with developing medical countermeasures (MCMs) to address radiological and nuclear threats to the United States as determined by the Department of Homeland Security as Material Threats Assessments. In the aftermath of an improvised nuclear device (IND) detonation or a nuclear accident, having rapid and accurate measurements of internal radiation absorption in exposed persons can inform life-saving medical decisions. The high-throughput biodosimetry test is a dose-dependent measurement of the biological changes caused by ionizing radiation that result in internal body damage. The test results will assist in determining the level, duration, and combination of medical care administered to an individual. The Government anticipates that contract(s) awarded from this RFP will serve to facilitate the test validation, pre-EUA and FDA diagnostic filings, the initial stockpiling of biodosimetry tests, and stockpile replenishments to substantially improve our national preparedness for a nuclear incident.

The Product Specific Requirements document approved in 2009 and the 2015 Scenario Based Analysis on Improvised Nuclear Detonation approved by the Public Health Emergency Medical Countermeasures Enterprise (PHEMCE), which includes members from the DOD, FDA, NIH, NCI, CDC, DHS, and BARDA, called for biodosimetry assays to be used in laboratory settings to meet the large diagnostics surge demand after a nuclear incident. These documents called for develop of rapid, accurate FDA-cleared biodosimetry diagnostic assays/systems to inform patient management, improve health and psychosocial outcomes, and save lives. The completion of the activities proposed in these award(s) produce and stockpile FDA-cleared biodosimetry diagnostic assays/systems to inform patient management, improve health and psychosocial outcomes, and save lives.

Since 2009, BARDA has funded several contractors who found biomarkers associated with radiation injury, demonstrated feasibility of algorithms that combine the biomarkers, and tested the combinations using irradiated non-human primate and human samples. BARDA currently has contracts for high-throughput tests, originating from Advanced Research and Development Broad Agency Announcement for biodosimetry diagnostics that may lead to radiation biodosimetry products. These contracts have resulted in radiation biodosimetry tests that may meet the requirements for this follow-on acquisition(s), which when realized represent the PHEMCE’s first ever radiation biodosimetry products under Project Bioshield.

Upon development completion, the high-throughput laboratory-based assay(s) will report an estimate of the ionizing radiation dose a person absorbed from 0 to 10 Gy. The result will be used in conjunction with clinical signs, symptoms and hematology, to give the health care provider additional information to allow an appropriate level of care to be administered to each patient in light of resource availability. This will greatly enhance the present health care capabilities for nuclear incident victims.

Independently and not as an agent of the government, the Contractor shall furnish all the necessary services, qualified personnel, materials, equipment, project management, and facilities not otherwise provided by the government as needed to perform the work necessary to complete development, file for licensure, and fulfill the initial acquisition of a high-throughput radiation biodosimetry test that most closely approximates the key attributes listed below:

For the high-throughput biodosimetry assay, the Government is seeking a test that meets or exceeds the following criteria:

• Is semi-quantitative or quantitative with an accuracy throughout the 2 to 6 Gy range of +/- 1.2

Gy (+/- 0.5 Gy preferred) from 24 hours to at least 7 days post-irradiation

• Can be used as an additional tool in the radiation evaluation arsenal in conjunction with signs, symptoms, and hematology to guide the medical treatment of affected individuals

• Is highly automated and can be used in a clinical laboratory setting by trained individuals

• Can be run on a system of no more than 150 pre- placed instruments whose total daily output can deliver up to 400,000 test results within 7 days of radiological or nuclear incident

• With pre-event training in place, could immediately be effectively and accurately run in a

CLIA compliant health care or public health laboratory that has the instrument installed and in use for other clinical assays

• Has sufficient pre-verification test results, including in vivo irradiated human and non-human primate results, to support entering into design validation phases consistent with the United States Food and Drug Administration (FDA) quality systems regulations and pre-market clearance within one year of contract award.

• The assay system yields an accurate and reportable result greater than 95% of the time.

• Uses commercially available instruments with sufficient pre-placements in CLIA compliant laboratories to perform the required number of tests in the United States. These instruments may require improvements to be installed on the instrument base to perform this test.

The high-throughput laboratory-based assay(s) will produce a quantitative estimate of the ionizing radiation dose a person absorbed from 0 to 10 Gy. The result will be used in conjunction with clinical signs and, symptoms, and as well as hematology, to give the health care provider additional information to allow an appropriate level of care to be administered to each patient in light of resource availability. This will greatly enhance the present health care capabilities for nuclear incident victims.

In conjunction with the response to the objectives below, the contractor shall provide a summary of the patent protection and freedom to operate analyses associated with the proposed biodosimetry high-throughput assay.

The contractor shall provide details of the activities necessary to fully develop their proposed high-throughput radiation biodosimetry test candidate. The work plan outlined by the contractor for the project should not exceed ten years while achieving the following objectives:

C.2. General Objectives

C.2.1. Advanced development and clinical validation of a high-throughput radiation biodosimetry test candidate for U.S. Food and Drug Administration clearance as an in vitro diagnostic. Necessary activities should be proposed by the offeror, but at a minimum must include the following:

1. Non-human primate studies using a quality system under the principles of GLP The contractor will submit to the Contracting Officer for review and acceptance the proposed protocols, on-going status reports and final reports for:

a. A total body irradiation study to evaluate the accuracy of the proposed final test.

b. A fractionated irradiation study to compare TBI NHP and human fractionated results using the final test

c. An NHP study of filgrastim (10mg/kg/sc), Leukine (6.1 µg/kg/sc), and other agents held in the SNS plus irradiation compared to irradiation alone

d. Additional studies necessary for diagnostic test licensure

2. Human clinical studies using a quality system under the principles of GCP

The contractor will submit to the Contracting Officer for review and acceptance the proposed protocols, on-going status reports and final reports for:

a. Radiotherapy Patient study to demonstrate accuracy of the proposed radiation biodosimetry test and compared to the NHP results.

b. Normal and potential confounder population human study to demonstrate a sufficiently low false positive rate or inform the product insert.

c. Additional human studies necessary for product licensure

3. FDA Compliant Regulatory Activities

a. The contractor will submit to the Contracting Officer for review and acceptance, pre-submission documents and all proposed regulatory filing documents.

b. The contractor will generate the test results to initially support BARDA filing of a Pre- Emergency Use Authorization (Pre-EUA) package for use of the product during a declared emergency, declared potential emergency or identification of material threat under an Emergency Use Authorization (EUA).

c. The contractor will submit an FDA filing package, including a premarket notification (510k) or a PMA and support the filing via meetings and teleconferences or other regulatory filings/inspections that may be required.

4. Validation of the instrument, algorithms and test definition files for the new intended use.

C.2.2 Development of comprehensive milestone-driven test and reagent manufacturing and procurement plans and their execution. At minimum the plans and subsequent activities must include:

• Provide a plan to produce sufficient GMP compliant pilot lots of reagents and assay kits for the stability studies, and validation activities planned to support the FDA submission

• Activities necessary to establish and extend the maximum shelf-life of reagents and assay kits

• Demonstrated capability and capacity to manufacture the reagent and assay kits (400,000 tests) over a nine month time frame, in preparation for stockpiling and deployment.

• Investigate the feasibility and opportunity cost to manufacture and supply these kits under a vendor managed inventory (VMI) system and provide written assessment of the analysis.

• Completion of qualification procedures to ensure the newly manufactured kits perform equivalently or better to than the pilot kits and are fully validated, including design, process, lot to lot validation and acceptance procedures.

• Manufacturing of initial kits with multi-ply labeling to ensure usability under a EUA and after full approval.

• Manufacturing and acceptance testing of additional kits or assays kits, if the initial stock expires prior to FDA approval of the test or the initial stock is a fraction of the amount needed to fulfill the desired level of preparedness.

• Manufacturing and acceptance testing of additional reagent kits or assays kits to replenish the stockpiled supplies as they expire.

• Activities necessary to monitor the shelf-life of reagents and assay kits through the end of the contracting period.

• Documented ability to manage and rotate inventory in accordance with a Quality Assurance Agreement.

• Provide a production plan and timeline that describe the facilities, processes, resources and capabilities necessary to manufacture product under normal market conditions and a risk assessment of the industrial base.

• Provide a Surge Capacity production plan and timeline that describe the processes, resources and capabilities necessary to support a rapid ramp up of product manufacturing capacity during public health emergencies. Include a risk assessment of the industrial base during a public health emergency.

• A GMP compliant storage and stability plan that describes the methodology for long term storage, shelf- life extensions, labeling and re-labeling requirements, inventory management and processes that minimize or eliminate loss due to expiry. Product may be stored at the Offeror’s site, a CDC designated location or with a third party (for example, under a vendor managed /distributor managed arrangement). In any case, the Offeror will be responsible to ensure compliance of any asset under non-USG storage.

• If the Offeror plans to store product at a site being used for other products, indicate how the storage and shipment of BARDA product will be separated, secured and protected.

The contractor and its subcontractors shall agree to allow a BARDA personnel or designee(s) to be present at a manufacturing or contract manufacturing site (CMO) in order to observe operations, review records, or provide quality assessments.

C.2.3. Provide specimen collection tube capabilities (if applicable), which may include additional production of a commercially available/manufactured tube or specialized production of custom collection devices depending on the assay. At minimum the plans and subsequent activities must include:

• Provide a plan for GMP compliant pilot manufacturing of the initial lots of specialized specimen collection tubes (if needed for the test) or additional volume for commercially available tubes for pre-submission activities.

• Provide a plan to manufacture sufficient GMP compliant pilot lots of specimen collection tubes for the stability and validation activities planned prior to the FDA submission

• Manufacture GMP compliant specialized collection tubes or arrange additional volume production of commercialized tubes to prepare the nation (i.e. produce 400,000 tests for a quantitative test within 7 days). Specific attention should be paid to the opportunity to develop these tubes under a contractor managed inventory (CMI) system or a distributor managed inventory (DMI) system.

• Complete the qualification procedures to ensure the newly manufactured tubes perform equivalently to or better than any pilot tubes and ship them to the designated location(s).

• Perform a second manufacture of collection tubes, if the initial stock expires prior to FDA approval/clearance of the test, qualify the newly manufactured tubes and ship them to the designated location(s).

• Manage and perform subsequent manufacture of collection tubes as specified in the contract, qualify the newly manufactured tubes and ship them to the designated location(s).

C.2.4. Establish and maintain Quality, Risk, Security, and Earned Value Management Systems.

Necessary activities should be proposed by the contractor, but may include the following:

1. Quality Management System

a. Establishment and maintenance of a medical device quality system for the proposed biodosimetry device with sufficient content to include but not limited to the elements contained in the Code of Federal Regulations Title 21 Part 820 (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=8

b. Establish routine internal reviews of the medical device quality system documentation and evidence of the ability to maintain, and adhere to the Code of Federal Regulations Title 21 Part 820 (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=8 20) http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=82 http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=82

c. Contract for an independent audit of the medical device quality system adherence, resolve any issues noted by the auditor, and provide the audit findings and resolutions to BARDA.

2. Risk Management System

a. Establishment and maintenance of an active, enterprise-wide risk management system as well as a specific risk management plan for the proposed project that includes the SOPS governing risk management, a description of the risk management activities required to oversee the project from research to commercialization, and the processes for reviewing completed risk mitigations.

b. Completion of the necessary risk management documentation for the program to date, including, but not limited to:

• Preliminary hazard analyses as necessary for each product component

• Design, user, and process FMEA plans (or reports if completed)

• Risk control plans to verify the proposed mitigations

c. Participate in regular meetings to coordinate and oversee the contracting effort.

d. Provide a list of individuals to serve as primary and secondary points of contact who will be available 24 hours a day, seven days a week, to be notified in case of a public health emergency.

3. Security and Surveillance System

• Establish and maintain a comprehensive security program, compliant with BARDA requirements, that provides a security plan for the overall protection of personnel, information, test results, and facilities associated with fulfilling the BARDA requirements.

• Submit and implement a security plan which establishes security practices and procedures that demonstrate how the Contractor will meet and adhere to the security requirements outlined in the BARDA table below by within 30 days of contract award.

• Ensure that other entities (sub-contractors, consultants, etc.) performing work on behalf of the offeror, establish and manage a security program that complies with BARDA security requirements. (See SECTION J, Attachment 12).

4. Earned Value Management System Subject to the requirements under FAR Clause52.234-4 , the Contractor shall use principles of Earned Value Management System (EVMS) in the management of any work ordered under a cost reimbursement contract that exceeds the cost thresholds set forth in HHSAR334.201(c ) and (d). The Seven Principles of EVMS are:

• Plan all work scope for the program to completion.

• Break down the program work scope into finite pieces that can be assigned to a responsible person or organization for control of technical, schedule, and cost objectives.

• Integrate program work scope, schedule, and cost objectives into a performance measurement baseline plan against which accomplishments may be measured.

Control Changes to the baseline.

• Use actual cost incurred and recorded in accomplishing the work performed.

• Objectively assess accomplishments at the work performance level.

• Analyze significant variances from the plan, forecast impacts, and prepare an estimate at completion based on performance to date and work to be performed.

• Use Earned Value information in the company’s management processes.

The contractor shall ensure the:

• Development of an Earned Value management System (EVMS) to integrate

EVMS consistent with ANSI/EIA standard-748 into the monthly progress reports.

• Assignment of personnel to ensure that EVMS goals, function and maintenance are accomplished.

• Participation in an initial Integrated Baseline Review and conduct annual validation and surveillance reviews throughout the life of the contract.

C.2.5. If applicable, development of a comprehensive milestone-driven instrument upgrade plan

The Contractor is advised to review the terms of FAR 52.227-14, Rights in Data – General, regarding the government’s rights to deliverables submitted during performance as well as the government’s rights to data contained within those deliverables. The Contractor is advised to review the terms of FAR 52.227-14, Rights in Data – General, regarding the government’s rights to deliverables submitted during performance as well as the government’s rights to data contained within those deliverables. Provide a detailed plan of how a combination of new, existing, and/or improved instruments can be used to produce the needed results, including manufacturing capacity, and field support plan.

• If applicable, provide a detailed plan of how the fielded instruments will be transitioned from their current state to the needed state and how the Contractor will verify the equivalency of the improved instrument to new production GMP instruments.

The Contractor shall provide an explanation of the scope, cost, and magnitude of effort required to implement the improvement plans on the number of instruments needed to evaluate up to 400,000 clinical samples in 7 days.

C.2.6. Development of items for Sustainability of Preparedness

• Provide appropriate training material, such as a manual, quick start guide, or video

(depending on the complexity of the test) to ensure the ability of the USG to train a core group of individuals on the biodosimetry assay.

• Provide an operationalization plan describing a feasible scenario for laboratories that could be contracted to run the assays at the volume needed for a nuclear detonation response. Alternatively, the Contractor shall provide a marketing plan [or “commercialization plan”] to demonstrate that within a year of launching the biodosimetry test, clinical testing laboratories will have the capability to deliver results for all assays within the required time frame (7 days post-incident).

• Identify a series of CAP-certified, CLIA-regulated laboratories that have the capability to run and report the test results on up to 400,000 clinical samples in 7 days.

C.2.7. Project Management, Reporting, Meetings/Site Visits

The Contractor shall submit monthly and quarterly progress reports, conduct quarterly reviews with subcontractors, meet at least annually with the Government staff, participate in bi-monthly teleconferences and manage contract efforts.

• Monthly and Quarterly Reports - The Contractor shall meet the monthly and quarterly reporting requirements

• Annual Reviews - The Contractor shall meet the annual review reporting requirements of the contract

• Final Report - The Contractor shall write a final technical, non-clinical, and clinical report.

• Program Management -The Contractor shall manage subcontractors’ efforts, task integration, program security, and regulatory compliance.

The Contractor shall participate in regular meetings to coordinate and oversee the contracting effort as requested by the Contracting Officer (CO)/Contracting Officer’s Representative (COR).

Such meetings may include, but are not limited to, a kickoff meeting to be held at a location determined by the COR, status update meeting or teleconferences, site visits to the Contractor’s and/or subcontractor’s facilities, and meetings with individual Contractors and other HHS officials to discuss the technical, regulatory, and ethical aspects of the program. The Contractor shall provide test results, reports, and presentations to groups of outside experts and USG personnel and USG-contracted subject matter experts as required by the CO/COR facilitating review of activities.

• The kickoff meeting will be to orient the Contractor to HHS/ASPR/BARDA and review contract requirements. This meeting usually occurs within a month after contract award.

• Expect Bi-weekly or monthly status update meetings/teleconferences. The schedule for these meetings will be established by the CO and COR.

• Periodic site visits will occur on an ad hoc basis (At least twice a year)

FDA Audits Within thirty (30) calendar days of an FDA audit of Contractor or subcontractor facilities, the Contractor shall provide copies of the audit findings, final report, and a plan for addressing areas of nonconformance to FDA regulations and guidance for GLP, GMP or GCP guidelines as identified in the final audit report.

Other U.S. Government Audits The United States Government (USG) reserves the right to conduct an audit of the Contractor with 48 hours advance notice.