RFP 09-100-SOL-00005 ARS.pdf

OMB No. 0990-0115

09-100-SOL-00005

SOLICITATION, OFFER AND AWARD

4. TYPE OF SOLICITATION2. CONTRACT NUMBER 3. SOLICITATION NUMBER

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

ORDER UNDER DPAS (15 CFR 700)

6. REQUISITION/PURCHASE NUMBER

NOTE: In sealed bid solicitations "offer" and "offeror" mean "bid" and "bidder".

NEGOTIATED (RFP)

SEALED BID (IFB)

5. DATE ISSUED

1. THIS CONTRACT IS A RATED RATING PAGE OF PAGES

1 58

C. E-MAIL ADDRESS

EXT.NUMBERAREA CODE

B. TELEPHONE (NO COLLECT CALLS)A. NAME

10. FOR

INFORMATION

CALL:

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.

(Date)(Hour) local timeuntildepository located in copies for furnishing the supplies or services in the Schedule will be received at the place specified in Item 8, or if hand carried, in the

SOLICITATION

9. Sealed offers in original and

PART IV - REPRESENTATIONS AND INSTRUCTIONS

OTHER STATEMENTS OF OFFERORS

EVALUATION FACTORS FOR AWARD

INSTRS., CONDS., AND NOTICES TO OFFERORS

REPRESENTATIONS, CERTIFICATIONS AND

LIST OF ATTACHMENTS

CONTRACT CLAUSES

PART III - LIST OF DOCUMENTS, EXHIBITS AND OTHER ATTACH.

I

J

K

L

M SPECIAL CONTRACT REQUIREMENTS

CONTRACT ADMINISTRATION DATA

DELIVERIES OR PERFORMANCE

INSPECTION AND ACCEPTANCE

PACKAGING AND MARKING

DESCRIPTION/SPECS./WORK STATEMENT

SUPPLIES OR SERVICES AND PRICES/COSTS

SOLICITATION/CONTRACT FORM

PART II - CONTRACT CLAUSESPART I - THE SCHEDULE

H

G

F

E

D

C

B

A

SEC. DESCRIPTION PAGE(S) (X) DESCRIPTION SEC. (X)

11. TABLE OF CONTENTS

18. OFFER DATE17. SIGNATURE

SUCH ADDRESS IN SCHEDULE.

IS DIFFERENT FROM ABOVE - ENTER

15C. CHECK IF REMITTANCE ADDRESS

EXT.NUMBERAREA CODE

15B. TELEPHONE NUMBER

(Type or print)AND

ADDRESS

OF

OFFEROR

CODE FACILITY

16. NAME AND TITLE OF PERSON AUTHORIZED TO SIGN OFFER15A. NAME

DATEAMENDMENT NO.DATEAMENDMENT NO.

and related documents numbered and dated):

amendments to the SOLICITATION for offerors

(The offeror acknowledges receipt of

14. ACKNOWLEDGEMENT OF AMENDMENTS

CALENDAR DAYS (%)30 CALENDAR DAYS (%)20 CALENDAR DAYS (%)10 CALENDAR DAYS (%)

(See Section I, Clause No. 52.232.8)

13. DISCOUNT FOR PROMPT PAYMENT

designated point(s), within the time specified in the schedule.

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

12. In compliance with the above, the undersigned agrees, if this offer is accepted within ______________ calendar days (60 calendar days unless a different period is inserted

NOTE: Item 12 does not apply if the solicitation includes the provisions at 52.214-16, Minimum Bid Acceptance Period.

OFFER (Must be fully completed by offeror)

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

28. AWARD DATE

(Signature of Contracting Officer)

27. UNITED STATES OF AMERICA

25. PAYMENT WILL BE MADE BY

26. NAME OF CONTRACTING OFFICER (Type or print)

CODE 24. ADMINISTERED BY (If other than Item 7)

ITEM

(4 copies unless otherwise specified)

23. SUBMIT INVOICES TO ADDRESS SHOWN IN

41 U.S.C. 253 (c) ( 10 U.S.C. 2304 (c) (

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

21. ACCOUNTING AND APPROPRIATION20. AMOUNT19. ACCEPTED AS TO ITEMS NUMBERED

AWARD (To be completed by government)

CODE

03/13/2009 X

HHS/OS/ASPR/BARDA

HHS/OS/ASPR/BARDA

330 Independence Ave, SW Washington DC 20201

05/07/2009

ANTHONY KRAM

ANTHONY.KRAM@HHS.GOV

X

X

X

X

X

X

X

X

X

X

X

X

X

PAGE(S)

LINDA D. LUCZAK

AUTHORIZED FOR LOCAL REPRODUCTION

Previous edition is unusable

STANDARD FORM 33 (Rev. 9-97)

Prescribed by GSA - FAR (48 CFR) 53.214(c)

Anthony.Kram Text Box See Sec L

Anthony.Kram Text Box See Para F.2 (bldg access delays are possible) 2:00 pm

Anthony.Kram Text Box 202 205-4709

ITEM NO. SUPPLIES/SERVICES QUANTITY UNIT UNIT PRICE AMOUNT

NAME OF OFFEROR OR CONTRACTOR

2 58

CONTINUATION SHEET

REFERENCE NO. OF DOCUMENT BEING CONTINUED PAGE OF

09-100-SOL-00005

(A) (B) (C) (D) (E) (F)

FOB: Destination

1 BASE:

CPFF

Advanced Development of Therapeutics for Treating

Neutropenia Resulting from Acute Exposure to Ionizing Radiation.

Period of Performance: 09/30/2009 to 09/29/2010

The contractor shall provide all personnel, supplies, equipment and other items and services (not specifically identified herein to be Government-furnished), necessary to meet the performance tasks and objectives in accordance with the Statement of

Work and this Contract.

2 OPTION 1:

CPFF

Advanced Development of Therapeutics for Treating

Neutropenia Resulting from Acute Exposure to Ionizing Radiation.

(Option Line Item)

Period of Performance: 09/30/2010 to 09/29/2011

3 OPTION 2:

CPFF

Advanced Development of Therapeutics for Treating

Neutropenia Resulting from Acute Exposure to Ionizing Radiation.

(Option Line Item)

Period of Performance: 09/30/2011 to 09/29/2012

4 OPTION 3:

CPFF

Advanced Development of Therapeutics for Treating

Neutropenia Resulting from Acute Exposure to Ionizing Radiation.

(Option Line Item)

Period of Performance: 09/30/2012 to 09/29/2013

5 OPTION 4:

CPFF

Advanced Development of Therapeutics for Treating

Neutropenia Resulting from Acute Exposure to Ionizing Radiation.

(Option Line Item)

Period of Performance: 09/30/2013 to 09/29/2014

OPTIONAL FORM 336 (4-86)

Sponsored by GSA

FAR (48 CFR) 53.110

NSN 7540-01-152-8067

09-100-SOL-00005 3

SECTION B – SUPPLIES OR SERVICES AND PRICES/COSTS

B.1. BRIEF DESCRIPTION OF SUPPLIES OR SERVICES

Independently, and not as an agent of the USG, the Contractor shall furnish all the necessary services, qualified personnel, materials, supplies, equipment, facilities, transportation and travel not otherwise provided by the USG as required to plan, develop and conduct studies that support licensure/approval for the treatment of neutropenia resulting from Acute Radiation Syndrome for a medical countermeasure, as defined under the following Statement of Work (SOW), Section C.

B.2 CONTRACT FUNDING

The amount allotted by the Government to this contract for payment of cost, exclusive of fee, is $_________. This allotment covers the period from ___________ to _____________.

An additional amount of $______________ is obligated under this contract for payment of fixed fee.

Total Funded: $____________.

B.3 CONTRACT LINE ITEM NUMBERS (CLINS)

ESTIMATED TOTAL ESTIMATED

CLIN COST FIXED FEE COST + FIXED FEE

0001 Base $____________ $____________ $____________

0002 Option 1 $____________ $____________ $____________

0003 Option 2 $____________ $____________ $____________

0004 Option 3 $____________ $____________ $____________

0005 Option 4 $____________ $____________ $____________

TOTAL $____________ $____________ $____________

09-100-SOL-00005 4

SECTION C – DESCRIPTION/SPECIFICATIONS/STATEMENT OF WORK

C.1 INTRODUCTION/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.

C.2 SCOPE OF WORK

BARDA plans to support advanced research and development of medical countermeasures that can specifically treat the neutropenia component of Acute Radiation Syndrome (ARS) and have demonstrated efficacy when administered 24 hours or more following lethal ionizing radiation exposure and are the type of agent that is within the regulatory purview of the CDER or CBER, FDA.

This solicitation does not acquire product for delivery to the Strategic National Stockpile. Ultimately, under a separate acquisition, it is the goal of BARDA to acquire a Final Drug Product that is licensed for the ARS indication. The Final Drug Product may be used for therapy of neutropenia associated with acute exposure to ionizing radiation measured in the 2-8 Gray (Gy) range which corresponds approximately to the LD10/60 – LD90/60. This effort supports advanced research and development of products on the path to FDA approval/licensure for the ARS indication. ARS product development activities on the path to obtaining a New Drug Application (NDA) or a Biologic License Application (BLA) that can be supported include:

• Clinical Development and Regulatory Management.

• Project Plan and Management.

• Product Stability.

• Manufacturing (including Facilities).

• Security

C.3 DESCRIPTION OF TASKS/TECHNICAL REQUIREMENTS:

Task 1: Clinical Development and Regulatory Management (a): Contractors shall develop, maintain, and implement fully integrated clinical, non-clinical, and regulatory management plans that will support initiation and/or continuation of an IND for the ARS indication (without any clinical holds) and subsequent accrual of data that supports eventual FDA approval/licensure for an ARS indication.

09-100-SOL-00005 5

(b): Contractors shall maintain a relationship with the FDA and be on alert for updated broad area and product specific regulatory information. The regulatory requirements for FDA approval/licensure are likely to be defined in an iterative decision-making process with the appropriate CDER/CBER authorities, based upon the ongoing review of the product during the advanced development process and as specific product-related data emerge. The Contractors shall consult with the FDA on the appropriate development path for eventual product approval and licensure for an ARS indication for treatment of neutropenia. The Contractors shall obtain information from the FDA regarding data needed to support the use of the Contractor’s product prior to licensure under a declared emergency.

(c): Based on guidance received from the FDA, the Contractor shall conduct studies to support licensure/approval of their product for the proposed indication. Studies shall include but are not limited to the following list and any deletion or addition of studies shall be approved by the Contracting Officer:

Non-Clinical:

1. Non-Human Primate (NHP) LD50/60

2. NHP Pharmacokinetics and Pharmacodynamics (PK/PD) Pilot single dose plus arm for +/-

Irradiation (IR) at-6 Gy

3. NHP PK/PD – pilot repeated dose plus arm for +/- IR at 6 Gy

4. NHP PK - Pivotal – clinical dose +/- IR (LD30, LD50, LD70)

5. NHP Efficacy – dose ranging

6. NHP Efficacy – Pivotal

7. NHP – toxicology- cardiovascular

8. NHP - 14 day rep dose + IR 6 Gy

9. NHP toxicology - Drug-Drug (D-D) interaction (several drugs vs "Offeror Product”, as determined by discussions with FDA)

10. NHP-cynomologus primate- reproductive toxicology - Segment II

11. Second Animal Species (SAS) - IR LD50

12. SAS - Pilot PK

13. SAS - Pivotal PK

14. SAS - Efficacy dose ranging

15. SAS - Pivotal efficacy

16. SAS -Cardiovascular

17. SAS -D-D Interaction (several drugs verses "Offeror Product")

18. NHP Neutrophil function

Clinical:

1. Clinical Phase 1 – safety and PK

2. Clinical Phase 1B – safety and PK

3. Clinical Phase 2A – safety

4. Clinical Phase 3 – safety

5. Clinical – Pediatric safety and PK

6. Clinical – Geriatric safety and PK

All Pivotal studies, as defined by the FDA, shall utilize FDP from a validated manufacturing process and shall be initiated only upon the acceptance of plans and protocols by the FDA and the BARDA Contracting Officer. Clinical studies shall enlist both genders within the age range of 18 to 64 years.

Non-clinical studies for efficacy shall be designed so as to match the clinical age-sex weighted equivalents of the clinical setting. Continuation of effort on initial and subsequent studies and associated funding will be based on contractor performance, timeliness and quality of deliverables, and consultations between the Contractor and HHS.

(d) The Contractor shall be the product sponsor and shall be responsible for: (a) preparing materials for and requesting, scheduling and participating in all meetings with the CBER or CDER (FDA), including meetings to review IND, NDA and BLA packages (as needed); (b) submitting all

09-100-SOL-00005 6

documentation to the FDA in a timely manner, consistent with timelines set out in the contract and by the FDA; (c) including BARDA staff, as designated by the Contracting Officer’s Technical Representative (COTR), in meetings and teleconferences with the FDA; and (d) providing copies of all FDA correspondence and meeting minutes that are relevant to the therapeutic candidate/product to the COTR.

(e) Audits may be requested to ensure that Contractor and/or subcontractor facilities and all planned procedures meet the FDA regulations and guidance that are required to meet GLP, GMP and GCP standards. In addition, the Contractor shall ensure that all Contractor and/or subcontractor records and staff are available for site visits or audits.

Task 2: Project Plan and Management (a): The Contractor shall develop, maintain, and support a Project Management Program that meets all HHS reporting requirements described in this statement of work and resultant contract.

(b): The Contractor shall implement an Earned Value Management System (EVMS) in the management of this contract that is consistent with ANSI/EIA-STD-748 guidelines.

(c): The Contractor shall provide all expertise needed for Project management and implementation to be performed under this contract including: research, manufacturing, regulatory, clinical, statistical, managerial and administrative activities. The Contractor’s team shall include strong scientific leadership, as well as significant experience and expertise in the management, design and execution of an advanced research and development program focused on product development, manufacturing, and testing in humans and in vertebrate animals, and subsequently eventual FDA approval/licensure.

The Project Leader (PL) shall be responsible for all aspects of project performance and communication with the BARDA COTR and Contracting Officer. In addition, the Contractor shall provide Project Manager(s) who are responsible for the day-to-day monitoring and tracking of progress and timelines, the coordination of project activities, and costs incurred.

(d): The Contractor shall use subcontractors at their discretion for activities involved in research and product development. Contractors are responsible for identifying capable and compliant subcontractors. Contractors shall establish Quality Agreements between themselves and subcontractors. Contractors, as IND sponsors, are responsible for all activities performed under this contract including those activities performed by sub-contractors.

Task 3: Product Suitability (a): The Contractor shall submit data and evidence to demonstrate suitability of the proposed product for potential use in a declared emergency in treating neutropenia resulting from ARS. Human safety and immunogenicity data shall be provided.

(b): Contractor shall perform stability assessments to support the proposed dating period of the bulk drug substance (BDS) and the FDP, and conduct ongoing stability assessments to support extension of the product expiration1 (ICH Q1A), if feasible. Elements of this Task include:

1. Assay Validation - Contractor shall validate assays used for BDS and FDP release and stability testing.

2. Stability Studies - Contractor shall conduct stability studies, including tests for identity, strength, quality and purity on the FDP throughout the contract lifetime. The FDP shall undergo stability testing in accordance with ICH Q1A, and Q6A (drugs)2 or Q6B (biologics)3. Contractor shall perform product shipping and handling stability studies indicative of expected life cycle product transfer requirements.

1 ICH Q1A, www.fda.gov/OHRMS/DOCKETS/98fr/110701a.htm 2 ICH Q6A www.fda.gov/cber/gdlns/frich122900.pdf 3 ICH Q6B www.fda.gov/cber/gdlns/ichtest.pdf

09-100-SOL-00005 7

3. Expiration Dating - Stability test results shall support an FDP dating period of at least three years. In addition, Contractor shall, within six months of the contract initiation, create a program to pursue at least a five year expiry.

Task 4: Manufacturing (a): The Contractor shall develop, maintain, and support a robust Manufacturing process for both BDS and FDP demonstrated by a plan, fully mapped using a Work Breakdown Structure (WBS) to the task level.

(b): The Contractor shall manufacture in accordance with GMP per FDA requirements during the performance period.

(c): The Contractor shall facilitate GMP site visits and inspections, as determined by BARDA and/or the FDA. The Contractor shall provide all information requested by the Contract Officer and the FDA in order to facilitate an inspection or site visit.

(d): The Contractor shall develop, maintain, and support a QA/QC program.

Task 5: Security (a): The Contractor shall maintain appropriate security in accordance with Attachment 5, Security, unless otherwise approved by the BARDA Security Officer.

(b): The Contractor shall submit and comply with a BARDA approved Security Plan.

(c): Security Reporting Requirement - Violations of established security protocols shall be reported to the BARDA COTR upon discovery. The Contractor shall investigate violations to determine the cause, extent, loss or compromise of sensitive program information, and corrective actions taken to prevent future violations. BARDA will determine if the severity of the violation requires further government intervention.

C.4 PLANNED PRESENTATIONS AND MEETINGS

The Contractor shall participate in regular onsite meetings and teleconferences to coordinate and oversee the performance of the contract as requested by the COTR. Such meetings may include, but are not limited to, meetings to discuss clinical study designs, site visits to the Contractor’s facilities, and meetings to discuss the technical, regulatory, and ethical aspects of the program. The Contractor shall provide data, reports, and presentations to groups of outside experts and USG personnel as required by the COTR in order to facilitate review of contract activities. The Contractor shall plan to have meetings with HHS in Washington, D.C. with the appropriate number of staff required to address the meeting objectives as defined by the Contracting Officer’s Technical Representative (COTR) and approved by the Contracting Officer. Meetings are subject to change throughout the course of performance.

C.5 GOVERNMENT FURNISHED PROPERTY

None

C.6 CONTRACTOR FURNISHED SERVICES

The Contractor shall furnish all the necessary services, qualified personnel, materials, supplies, equipment, facilities, transportation and travel not otherwise provided by the USG as required to develop, manufacture and acquire data to support licensure for an ARS indication for the medical countermeasure, as defined in this Statement of Work (SOW) and the awarded contract.

09-100-SOL-00005 8

SECTION D - PACKAGING, MARKING AND SHIPPING

D.1. PACKAGING, HANDLING and TRANSPORTATION

All deliverables required under this contract shall be packaged, marked and shipped in accordance with Government specifications as described in Section F. All deliverables shall be marked with the contract number and Contractor name. The Contractor shall guarantee that all required materials shall be delivered in immediate usable and acceptable condition to the specified Government Representative per this contract.

D.2. SHIPPING

Shipment of deliverables to the Contracting Officer and COTR shall be performed in accordance with Section F.

09-100-SOL-00005 9

SECTION E - INSPECTION AND ACCEPTANCE TERMS

E.1 CLAUSES INCORPORATED BY REFERENCE

FAR CLAUSE TITLE and DATE 52.246-5 Inspection of Services—Cost-Reimbursement (APR 1984) 52.246-9 Inspection of Research and Development (Short Form) – Cost Reimbursement (APR

1984)

E.2 INSPECTION AND ACCEPTANCE TERMS

Unless otherwise stated in paragraph F.6, the “Deliverable Schedule” of this contract, the COTR is the authorized Government representative for inspection and acceptance of deliverables.

09-100-SOL-00005 10

SECTION F – DELIVERIES OR PERFORMANCE

F.1 CLAUSES INCORPORATED BY REFERENCE

FAR CLAUSE TITLE and DATE 52.242-15 Stop Work Order Alternate I (APR 1984) 52.247-34 F.O.B. Destination (NOV 1991)

F.2 DELIVERY ADDRESS

Ms. Linda D. Luczak, Contracting Officer

HHS/OS/ASPR/BARDA

330 Independence Avenue, S.W.

Room G640 Washington, DC 20201 Email: Linda.Luczak@hhs.gov

Mary Homer, Ph.D., Contracting Officer Technical Representative (COTR)

HHS/OS/ASPR/BARDA

330 Independence Avenue, S.W.

Room G644 Washington, DC 20201 Email: Mary.Homer@hhs.gov

F.3 PERIOD OF PERFORMANCE

The period of performance of this contract is anticipated to be a maximum of 60 months after date of award in accordance with FAR 52.232-22 Limitation of Funds (APR 1984).

F.4 PLACE OF PERFORMANCE

The place of performance shall be at the Contractor’s facilities, Subcontractor’s facilities and/or other sites as specified in the successful offeror’s proposal.

F.5 DELIVERABLES

1. Initial Baseline Financial Management Report: The Contractor shall prepare a time-phased baseline initial financial management report, detailing by month how the Contractor plans to incur costs for the total 60-month contract period, utilizing the form format in Attachment 1. The report shall be prepared and submitted in accordance with instructions set forth on the reverse side of the form.

The initial baseline financial management report shall be submitted to the CO within 30 business days after the contract effective date.

The total estimated cost and direct labor hours reflected in the baseline report must equal the contract values for the total contract period. The report shall be updated, as required, during the contract performance by submission of revised pages for approval by the Contracting Officer. The baseline financial report shall be revised each time a contract modification is executed which increases or decreases the contract estimated cost, for a reason other than an overrun. The report shall not be revised to include overrun costs.

Minimum reporting categories shall include:

a. Direct Labor Hours

b. Direct Labor Dollars

c. Overhead(s)

d. Subcontract

e. Material

f. Other Direct Cost

g. General and Administrative (G&A)

h. Total Estimated Cost

09-100-SOL-00005 11

i. Fixed Fee

j. Total Estimated Cost and Fee

2. Monthly Financial Management Report (FMR)-- The contractor shall submit a Monthly Financial Management Report in the format in Attachment 2. The FMR shall also serve as the Contractor’s invoice. The form shall be prepared and submitted in accordance with the instructions set forth on the reverse side of the form and as further definitized below:

a. Due not later than the 10th working day following the close of the Contractor's accounting period being reported.

b. Columns 8.a and b shall be completed using estimates (forecasts) for the succeeding two months.

c. The reporting categories shall be the same as those specified for the Initial Baseline Financial Management Report.

The FMR shall include a narrative explanation for variances exceeding +-5 percent between estimated dollars shown in the prior month and actual dollars shown in the current month at the contract level. (For example, the estimated dollars shown for June in column 8a. in the May report and the actual June dollars shown in column 7a. in the June report) Accuracy of financial reporting will be evaluated as part of the annual performance evaluation.

3. Final Security Plan – This report shall include the negotiated changes developed from the Draft Security Plan. Upon Government approval and completion of the Final Security audits, the Contractor shall submit to the Contracting Officer a letter certifying compliance. Performance of the work under this contract shall be in accordance with this approved Final Security Plan.

4. Technical Progress Reports (TPR) – The Contractor shall submit technical progress reports monthly. The contractor shall submit the progress reports via e-mail of less than 20 pages in length.

Reports shall be in narrative form, informal, and may include additional graphics if needed. The TPR shall contain brief descriptions of what was accomplished since the last reporting, what is planned for the next month, and what are the current or anticipated impediments, technical or otherwise, to accomplishing the planned activities. The TPR is not required in months that an Annual Technical Progress Report or Final Report are required. The general format shall be:

a. A title page containing the heading “Technical Progress Report” that lists the contract number, title, the period of performance being reported, the Contractor's name, address, and other contact information, the author(s), and the date of submission. Include:

b. A brief introduction covering the purpose and scope of the contract effort.

c. A brief description of the progress including work performed, test results, and milestones achieved during the period covered.

d. A brief description of the work proposed for the next reporting period including a summary table of activities or tasks to be accomplished by a certain date and by whom.

e. A brief description of any outstanding problems and issues with options and recommendations for resolution. An explanation of any difference between planned progress and actual progress, causes of the differences and, if project activity is delinquent, then what corrective actions were completed, planned or in progress.

f. Manufacturing updates of progress in relation to the Manufacturing plan including attainment of milestones, updates to the product development timeline, lot manufacturing schedules and release dates, and anticipated regulatory inspections and preparation

g. FDA inspections and consultation results.

h. Updated timelines that reflect accurate progress on the schedule/critical path

i. A summary of the meetings, conference calls, workshops that have taken place during the reporting period

09-100-SOL-00005 12

j. Distribution List – A list of persons receiving the Technical Progress Report

k. Attachments – Results or protocols developed on the project must be provided as attachments, preprints/reprints of papers and abstracts.

5. Annual Technical Progress Report (ATPR) – The Contractor shall submit an Annual Technical Progress Report in lieu of a TPR following each anniversary month from the contract effective date.

The ATPR shall summarize all of the work completed during the previous year and be suitable for publication. The ATPR shall follow the same format as the TPR with the inclusion of an Executive Summary. An ATPR is not required for the period when the Final Report is required.

6. Study Protocols – The Contractor shall develop a protocol for each clinical trial as listed in Task #1 paragraph C.3 and submit all protocols and protocol amendments for approval by the COTR prior to submission to the FDA.

7. Final Study Reports – Final Study Reports shall be submitted for non-clinical and clinical studies.

The clinical trial reports shall follow the format of International Conference on Harmonization document ICH E3 “Guidelines on Structure and Content of Clinical Study Reports” http://www.fda.gov/CDER/GUIDANCE/iche3.pdf. Draft Final Reports will be submitted to the COTR and CO for review and comment within 30 days of completion of the analysis of the study data. The Contracting Officer shall provide written comments within 30 days after the submission of the Draft Final Report. The comprehensive Final Report will be submitted to the CO and the COTR within 30 days after receiving comments on the Draft Final Report from the CO.

8. FDA Communications and Submissions – Within thirty (30) days of receiving correspondence or meeting with the FDA, submit appropriately formatted electronic copies of the correspondence or meeting minutes/summaries to the COTR.

Within thirty (30) days of an audit related to conformance to FDA regulations and guidance, including adherence to GLP, GMP, or GCP guidelines, the Contractor shall provide copies of the audit 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.

9. Subcontracting Reports (Ref FAR 52.219-9 APR 2008) - Submit Standard Form 294, Subcontracting Report for Individual Contracts, and Standard Form 295, Summary Subcontractor Report using the Electronic Subcontract Reporting System (eSRS ). Access to eSRS can be found at:

http://www.esrs.gov/

10. Federal Contractor Veterans Employment Report -- In compliance with Clause 52.222-37 (SEP 2006), Employment Reports on Special Disabled Veterans, Veterans of the Vietnam Era, and Other Eligible Veterans, the Contractor shall submit the Federal Contractor Veterans Employment Reports (VETS-100) as required by this clause.

11. Audit Reports - The Contractor shall provide interim and final audit reports to the COTR 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 Contractor and its subcontractors as needed to evaluate compliance with the FDA regulations and guidance, including those required to meet GLP, GMP or GCP standards

12. Plan Updates: Any updates or revisions of the plans required by this contract shall be a required deliverable. Plans include but are not limited to the Clinical Development and Regulatory plan, Project and Management plan, Disposition plan, Assay Validation plan, Stability Study plan, Expiration Dating plan, Labeling Plan, Manufacturing plan and Security plan.

13. EVMS Reports: As part of the EVMS implementation process the Contractor shall deliver EVMS

09-100-SOL-00005 13

reports:

13(a). Integrated Baseline Review (IBR) – The Contractor shall conduct an Integrate Baseline Review (IBR) in coordination with the CO. In the IBR the Contractor and Government shall review the Contractor's planned baselines. The IBR is designed to achieve confidence that the baselines accurately capture the entire technical scope of work, are consistent with contract schedule requirements, are reasonably and logically planned, and have adequate resources assigned.

13(b) Earned Value Contract Performance Report – The Contractor shall deliver an Earned Value

Contract Performance Report (EV-CPR) on a monthly basis. Department of Defense DI-MGMT- 81466A 881A is recommended as guidance in the creation of the EV-CPR. The Contractor shall only provide Format 1, Format 3, and Format 5. Format 1 will be reported at the WBS level agreed to by the Government and the Contractor. The Contractor shall write a narrative description for WBS legs that exceed a variance of +/- 10% from planned values explaining the reason for the variance.

14. Final Report – The contractor shall summarize all of the work done under this contract into a final report suitable for publication as an HHS Contractor Report. The final report may include proprietary information but it must be documented in either a separate Appendix to the final report (which can stand on it’s own without the Appendix) or as a completely separate document. The final report should include tables, graphs, diagrams, curves, sketches, photographs, and drawings in sufficient detail to explain comprehensively the results achieved under the contract. The report shall contain but not be limited to:

a. Executive summary

b. Details of each of the tasks, clinical trials and studies with figures

c. A summary of the progress toward the goals established in the proposal and as modified by the work completed

d. A prioritized suite of enabling technologies with descriptions and roadmaps of the steps needed to achieve the goals of the program

e. The Final Drug (FDP) or Biologic Product’s (FBP) manufacturing history (if applicable) over the life of the contract, compliance requirements (federal, state, and local) and final product specifications including rejection criteria and history

f. Conclusions

g. Any additional research or follow-on activates that may further the science

09-100-SOL-00005 14

F.6 DELIVERABLE SCHEDULE

PARA

F.5

REF

DELIVERABLE FORMAT DISTRIBUTION DELIVERY DATE

1 Initial Baseline Financial Management Report Excel or PDF A-1, B-1, C-1 30 Days After Award

2 Financial Management Report Excel or PDF A-1, B-1, C-1

10th Working Day following close of Contractor’s accounting period.

3 Final Security Plan MS Office Suite or PDF A-1, B-1 30 Days after Award

4 Technical Progress Reports (TPR)

MS Office Suite or PDF A-1, B-1, C-1, D-1 10th Day of each month

5 Annual Technical Progress Reports (ATPR)

MS Office Suite or PDF A-1, B-1, C-1, D-1 15th Day after anniversary of contract effective date

6 Study Protocols MS Office Suite or PDF A-1, B-1, C-1, D-1 Prior to Trial(s) Beginning

7 Final Study Reports (Draft)

MS Office Suite or PDF A-1, B-1, C-1, D-1 30 Days after completion of analysis of study data

FDA communications and submissions

MS Office Suite or

PDF A-1, B-1, C-1, D-1

30 Days after communications and/or submissions

9 Subcontracting Reports SF 294/295 http://www.esrs.gov . A-1, B-1, K -Apr 30 Annually

-Oct 30 Annually

Federal Contractor Veterans Employment Report

VETS-100 K Sep 30 Annually

11 Audit Reports MS Office Suite or PDF A-1, B-1, C-1 30 Days after Audit

12 Plan Updates MS Office Suite or PDF A-1, B-1, C-1 30 Days after Update

13 EVMS Reports MS Office Suite or PDF A-1, B-1 Dates TBD

14 Final Report MS Office Suite or PDF A-1, B-1, C-1, D-1 30 Days Prior to the Last

Day of the Contract.

F.7 DOCUMENT DISTRIBUTION REQUIREMENTS

1. Unless specified elsewhere in this contract, reports and other deliverables shall be submitted electronically in the prescribed format, Times New Roman or Arial font pitch 10 or larger, F.O.B.

destination as specified below in paragraph F.2.

2. The following letter codes designate the recipients of reports and other documentation which are required to be delivered to BARDA by the Contractor.

A--Contracting Officer: Linda Luczak: Linda.Luczak@hhs.gov B--Contract Specialist: Anthony Kram: Anthony.Kram@hhs.gov C--Contracting Officer’s Technical Representative: Mary Homer, PhD: Mary.Homer@hhs.gov D--Alternate Contracting Officer’s Technical Representative: Ronald Manning, PhD:

Ronald.Manning@hhs.gov K--According to instructions on form

3. The numeral following the letter code specifies the number of copies to be provided.

09-100-SOL-00005 15

SECTION G - CONTRACT ADMINISTRATION DATA

G.1. GENERAL

The Contracting Officer is the only person with authority to act as agent of the Government under this contract. Only the Contracting Officer has authority to: (1) direct or negotiate any changes in the statement of work; (2) modify or extend the period of performance; (3) change the delivery schedule;

(4) authorize reimbursement to the Contractor for any costs incurred during the performance of this contract; or (5) otherwise change any terms and conditions of this contract. The Contractor performs at risk if accepting direction from any person other than the Contracting Officer.

G.2 INVOICE SUBMISSION/MONTHLY FINANCIAL MANAGEMENT REPORT

The Contractor shall follow the instructions found in Attachment 2 “Monthly Financial Management Report” and submit the invoice/report to the Contracting Officer as specified in paragraph F.6.

The Monthly Financial Management Report shall be transmitted as an attachment via e-mail to the Contracting Officer’s address listed in paragraph F.2 in MS Word, MS Excel, or Adobe Portable Document Format (PDF).

G.3 POST AWARD EVALUATION OF CONTRACTOR PERFORMANCE

1. Contractor Performance Evaluations

Interim and final evaluations of Contractor performance will be prepared on this contract in accordance with FAR 42.15. The final performance evaluation will be prepared at the time of completion of work. In addition to the final evaluation, interim evaluation(s) shall be submitted annually from the contract award date.

Interim and final evaluations will be provided to the Contractor as soon as practicable after completion of the evaluation. The Contractor will be permitted thirty days to review the document and to submit additional information or a rebutting statement. If agreement cannot be reached between the parties, the matter will be referred to an individual one level above the Contracting Officer, whose decision will be final.

Copies of the evaluations, Contractor responses, and review comments, if any, will be retained as part of the contract file, and may be used to support future award decisions.

2. Electronic Access to Contractor Performance Evaluations

Contractors that have Internet capability may access evaluations through a secure Web site for review and comment by completing the registration form that can be obtained at the following address:

http://oamp.od. NIH.gov/OD/CPS/cps.asp

The registration process requires the Contractor to identify an individual that will serve as a primary contact and who will be authorized access to the evaluation for review and comment. In addition, the Contractor will be required to identify an alternate contact that will be responsible for notifying the cognizant contracting official in the event the primary contact is unavailable to process the evaluation within the required 30-day time frame.

09-100-SOL-00005 16

SECTION H – SPECIAL CONTRACT REQUIREMENTS

H.1 CLAUSES INCORPORATED IN FULL TEXT

HHSAR 352.270-5 KEY PERSONNEL, (JAN 2006)

The key personnel specified in this contract are considered to be essential to work performance. At least 30 days prior to diverting any of the specified individuals to other programs or contracts (or as soon as possible, if an individual must be replaced, for example, as a result of leaving the employ of the Contractor), the Contractor shall notify the Contracting Officer and shall submit comprehensive justification for the diversion or replacement request (including proposed substitutions for key personnel) to permit evaluation by the Government of the impact on performance under this contract.

The Contractor shall not divert or otherwise replace any key personnel without the written consent of the Contracting Officer. The Government may modify the contract to add or delete key personnel at the request of the contractor or Government.

(End of clause)

The following individual(s) is/are considered to be essential to the work being performed hereunder:

Name Title

HHSAR 352.270-6 PUBLICATIONS AND PUBLICITY (JAN 2006)

(a) Unless otherwise specified in this contract and the Confidentiality of Information clause is included, the Contractor is encouraged to publish the results of its work under this contract. A copy of each article submitted by the Contractor for publication shall be promptly sent to the CO and COTR. The Contractor shall also inform the CO and COTR when the article or other publication is published, and furnish a copy of it as finally published.

(b) The Contractor shall include in any publication resulting from work performed under this contract a disclaimer reading as follows:

‘‘The views expressed in written conference materials or publications and by speakers and moderators at HHS-sponsored conferences, do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government.’’

(c) Unless authorized by the CO, the contractor shall not display the HHS logo on any conference materials or publications.

HHSAR 352.270-8 PROTECTION OF HUMAN SUBJECTS (JAN 2006)

(a) The Contractor agrees that the rights and welfare of human subjects involved in research under this contract shall be protected in accordance with 45 CFR Part 46 and with the Contractor’s current Assurance of Compliance on file with the Office for Human Research Protections (OHRP), Office of Public Health and Science (OPHS). The Contractor further agrees to provide certification at least annually that the Institutional Review Board has reviewed and approved the procedures, which involve human subjects in accordance with 45 CFR Part 46 and the Assurance of Compliance.

(b) The Contractor shall bear full responsibility for the performance of all work and services involving the use of human subjects under this contract and shall ensure that work is conducted in a proper manner and as safely as is feasible. The parties hereto agree that the Contractor 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 Contractor or any subcontractor, agent or employee of the Contractor, or any other person, organization, institution, or group of any kind whatsoever, as the agent or

09-100-SOL-00005 17

employee of the Government. The Contractor 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 contractor without imputing liability on the part of the Government for the acts of the Contractor or its employees.

(c) If at any time during the performance of this contract, the Contracting Officer determines, in consultation with the OHRP, OPHS, ASH, that the Contractor 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 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, in consultation with OHRP, OPHS, ASH, terminate this contract in a whole or in part, and the Contractor’s name may be removed form the list of those contractors with approved Health and Human Services Human Subject Assurances.

HHSAR 352.270-9 CARE OF LIVE VERTEBRATE ANIMALS (JAN 2006)

(a) Before undertaking performance of any contract involving animal related activities the Contractor shall register with the Secretary of Agriculture of the United States in accordance with 7 U.S.C. 2136 and 9 CFR sections 2.25 through 2.28. The Contractor shall furnish evidence of the registration to the Contracting Officer.

(b) The Contractor shall acquire vertebrate animals used in research from a dealer licensed by the Secretary of Agriculture under 7 U.S.C. 2133 and 9 CFR Sections 2.1-2.11, or from a source that is exempt from licensing under those sections.

(c) The Contractor agrees that the care and use of any live vertebrate animals used or intended for use in the performance of this contract will conform with the PHS Policy on Humane Care of Use of Laboratory Animals, the current Animal Welfare Assurance, the Guide for the Care and Use of Laboratory Animals prepared by the Institute of Laboratory Animal Resources and the pertinent laws and regulations of the United States Department of Agriculture (see 7 U.S.C. 2131 et seq. and 9 CFR Subchapter A, Parts 1-4). In case of conflict between standards, the more stringent standard shall be used.

(d) If at any time during performance of this contract, the Contracting Officer determines, in consultation with the Office of Laboratory Animal Welfare (OLAW), National Institutes of Health (NIH), 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, in consultation with OLAW, NIH, terminate this contract in whole or in part, and the Contractor’s name may be removed from the list of those contractors with approved PHS Animal Welfare Assurances.

Note: The Contractor may request registration of its facility and a current listing of licensed dealers from the Regional Office of the Animal and Plant Health Inspection Service (APHIS), USDA, for the region in which its research facility is located. The location of the appropriate APHIS Regional Office, as well as information concerning this program may be obtained by contacting the Animal Care Staff, USDA/APHIS, 4700 River Road, Riverdale, Maryland 20737.

HHSAR 352.270-11 PRIVACY ACT (JANUARY 2006)

This contract requires the Contractor to perform one or more of the following: (a) Design; (b) develop; or (c) operate a Federal agency system of records to accomplish an agency function in

09-100-SOL-00005 18

accordance with the Privacy Act of 1974 (Act) (5 U.S.C. 552a(m)(1)) and applicable agency regulations. The term ‘‘system of records’’ means a group of any records under the control of any agency from which information is retrieved by the name of the individual or by some identifying number, symbol, or other identifying particular assigned to the individual. Violations of the Act by the Contractor and/or its employees may result in the imposition of criminal penalties (5 U.S.C. 552a(i)).

The Contractor shall ensure that each of its employees knows the prescribed rules of conduct and that each employee is aware that he/she is subject to criminal penalties for violation of the Act to the same extent as HHS employees. These provisions also apply to all subcontracts awarded under this contract which require the design, development or operation of the designated system(s) of records (5 U.S.C. 552a(m)(1)). The contract work statement: (a) identifies the system(s) of records and the design, development, or operation work to be performed by the Contractor; and (b) specifies the disposition to be made of such records upon completion of contract performance.

HHSAR 352.270-14 RESTRICTION ON USE OF HUMAN SUBJECTS (JAN 2006)

Pursuant to 45 CFR part 46, Protection of Human Research Subjects, the Contractor shall not expend funds under this award for research involving human subjects or engage in any human subjects research activity prior to the receipt by the Contracting Officer of a certification that the research has been reviewed and approved by the Institutional Review Board (IRB) designated under the Contractor’s Federal-wide assurance of compliance. This restriction applies to all collaborating sites, whether domestic or foreign, and subcontractors. The Contractor must ensure compliance by collaborators and subcontractors.

H.2 REGISTRATION OF CLINICAL TRIALS IN THE GOVERNMENT DATABASE (ClinicalTrials.gov) Pursuant to Public Law 110-85, Food and Drug Administration Amendments Act of 2007, Title VIII- Clinical Trial Databases, the Contractor shall register the clinical trial(s) performed under this contract in the Government database; ClinicalTrials.gov ( http://www.ClinicalTrials.gov ) by 21 days after the first patient is enrolled.

Additional information is available at: http://prsinfo.clinicaltrials.gov

H.3 REPORTING MATTERS INVOLVING FRAUD, WASTE AND ABUSE

Anyone who becomes aware of the existence or apparent existence of fraud, waste and abuse in OS/ASPR/BARDA funded programs is encouraged to report such matters to the HHS Inspector General's Office in writing or on the Inspector General's Hotline. The toll free number is 1-800-HHS- TIPS (1-800-447-8477). All telephone calls will be handled confidentially. The e-mail address is Htips@os.dhhs.gov and the mailing address is:

Office of Inspector General Department of Health and Human Services

TIPS HOTLINE

P.O. Box 23489 Washington, D.C. 20026

H.4 PROHIBITION ON CONTRACTOR INVOLVEMENT WITH TERRORIST ACTIVITIES

The Contractor is prohibited from engaging in transactions with, and providing resources and support to, individuals and organizations associated with terrorism. The Contractor is responsible to ensure compliance with E.O. 13224 and P.L. 107-56. This clause shall be included in all subcontracts issued under this contract.

H.5 MANUFACTURING STANDARDS

The Current Good Manufacturing Practice Regulations (GMP) (21 CFR Parts 210-211) and

09-100-SOL-00005 19

regulations pertaining to biological products (21 CFR Part 600) will be the standard to be applied for manufacturing, processing, packing, storage, and delivery of this product.

If at any time during the life of the contract, the Offeror fails to comply with GMP in the manufacturing, processing and packaging of this therapeutic product and such failure results in a material adverse effect on the safety, purity or potency of this therapeutic product (a material failure) as identified by CBER and CDER, the Offeror shall have thirty (30) calendar days from the time such material failure is identified to cure such…