RFP-BARDA-09-32 Final 07-10-09.pdf

PAGES

RFP No. HHS-BARDA-09-32

15A. NAME

AND

ADDRESS

OF

CONTRACT

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

(Date)(Hour)

CALENDAR DAYS

14. ACKNOWLEDGMENT OF AMENDMENTS

(The Contractor acknowledges receipt of amend-ments to the SOLICITATION for Contractors

(Type or Print)

`SOLICITATION, OFFER AND

AWARD

1. THIS CONTRACT IS A RATED ORDER

UNDER DPAS (15 CFR 700)

RATING

PAGE OF

1 81

2. CONTRACT NO.

3. SOLICITATION NO.

HHS-BARDA-09-32

4. TYPE OF SOLICITATION

SEALED BID (IFB)

X NEGOTIATED (RFP)

5. DATE ISSUED

07/10/2009

6. REQUISITION/PURCHASE

NO.

7. ISSUED BY CODE 8. ADDRESS OFFER TO (If other than Item 7) Department of Health and Human Services

OS/ASPR/BARDA

330 Independence Ave. SW, Room G640 Washington, DC 20201

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

SOLICITATION

9. Sealed offers in original and 5 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 Block 7 until 1:00PM local time 08/26/2009

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

Kim L. Hall

B. TELEPHONE (NO COLLECT CALLS)

AREA CODE NUMBER: EXT:

(202) 205-1587

C. E-MAIL ADDRESS

Kim.Hall@hhs.gov

11. TABLE OF CONTENTS

(x) DESCRIPTION (x) DESCRIPTION

PART I – THE SCHEDULE PART II – CONTRACT CLAUSES

X A SOLICITATION/CONTRACT FORM 1 X I CONTRACT CLAUSES 24-30

X B SUPPLIES OR SERVICES AND PRICES/COSTS 2-4 PART III - LIST OF DOCUMENTS, EXHIBITS AND OTHER ATTACH.

X C DESCRIPTION/SPECS./WORK STATEMENT 4-12 X J LIST OF ATTACHMENTS 31

X D PACKAGING AND MARKING 12 PART IV – REPRESENTATIONS AND INSTRUCTIONS

X E INSPECTION AND ACCEPTANCE 12 REPRESENTATIONS, CERTIFICATIONS, AND

X F DELIVERIES OR PERFORMANCE 12-15 X K OTHER STATEMENTS OF CONTRACTORS 32-38

X G CONTRACT ADMINISTRATION DATA 15-17 X L INSTRS., CONDS., AND NOTICES TO 39-61

X H SPECIAL CONTRACT REQUIREMENTS 17-23 X M EVALUATION FACTORS FOR AWARD 62-69

OFFER (Must be fully completed by Contractor) 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 180 calendar days (60 calendar days unless a different period is inserted by the Contractor) 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

K

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.

AUTHORIZED FOR LOCAL REPRODUCTION / PREVIOUS EDITION IS UNUSABLE STANDARD FORM 33 (REV. 9-97) / Prescribed by GSA / FAR (48 CFR) 53.214(c) mailto:Kim.Hall@hhs.gov

ADVANCED DEVELOPMENT OF RECOMBINANT INFLUENZA VACCINE PRODUCTS AND

MANUFACTURING CAPABILITIES FOR PANDEMIC PREPAREDNESS

SECTION B--SUPPLIES OR SERVICES AND PRICES/COSTS

For the purposes of this solicitation, the U.S. is defined as the fifty states, the District of Columbia, Puerto Rico and all U.S. territories.

The terms “Government” and “USG” are collectively defined to mean the Federal Government of the U.S.

ARTICLE B.1. BRIEF DESCRIPTION OF SUPPLIES OR SERVICES

This project from the Department of Health and Human Services (HHS) through the Biomedical Advanced Research and Development Authority (BARDA) within the Office of the Assistant Secretary for Preparedness and Response (ASPR), focuses on the advanced development of recombinant seasonal and pandemic-like influenza vaccines utilizing hemagglutinin genes or proteins (plasmid DNA, virus-vectors, peptides, subunit proteins and virus-like particles) towards U.S.-licensure in exchange for a commitment to establish a rapid surge capacity for pandemic vaccine.

ARTICLE B.2. CONTRACT LINE ITEMS NUMBERS (CLINs)

(a) Contract Type

This is a cost reimbursement type contract with option periods. This contract shall contain a Base Period, an Option Period One and an Optional CLIN. The exercise of an option shall be in accordance with FAR 52.217-9, Option to Extend the Term of the Contract (March 2000).

(b) Consideration and Payment (CPFF)

This is a cost plus fixed fee (CPFF) contract. In consideration for completion of the work, described under the Base Period (CLINs 0001 through 0010) and in accordance with the Statement of Work (Section C), the Contractor shall be paid an amount not to exceed $__________ of which $__________ represents the estimated reimbursable costs and $_________ represents the fixed fee.

The amount currently allotted for the Base Period shall cover a 12 month performance period.

BASE PERIOD (12 Months)

CLIN SUPPLIES / SERVICES QTY/UNIT EST. COST FIXED FEE TOTAL EST. CPFF

Product Development Plan (Milestone 1)

1 Job

Clinical Development and Regulatory Plan (Milestone 2)

Manufacturing Facility Plan (Milestone 3)

Feasibility Plan (Milestone 4)

0005A Contractor Defined Milestones - Recombinant Seasonal Influenza Vaccine Milestones (Milestone 5A)

1 Job $ $ $

0005B Contractor Defined Milestones – Recombinant Pandemic Influenza Vaccine Milestones (Milestone 5B)

0006 Draft Security Plan Not Separately Priced (NSP)

NSP NSP NSP

0007 Final Security Plan Not Separately Priced (NSP)

NSP NSP NSP

0008 Technical Progress Reports (Including EVM) and Executive Summary

12 reports of each

0009 Draft Final Report Not Separately Priced (NSP)

NSP NSP NSP

0010 Final Report

1 Report $ $ $

OPTION PERIOD ONE (48 Months)

Shall the Government decide to exercise an Option Period One upon completion of CLIN 0010, the Contractor shall provide the additional Contractor Defined Milestones for recombinant seasonal and pandemic influenza vaccines. In addition, the Contractor shall provide a separate timeline and milestone plan for the additional Contractor Defined Milestones.

Optional

CLIN

SUPPLIES / SERVICES QTY/UNIT EST. COST FIXED FEE TOTAL EST. CPFF

0011A Additional Contractor

Defined Milestones - Recombinant Seasonal Influenza Vaccine

0011B Additional Contractor Defined Milestones – Recombinant Pandemic

0012 Technical Progress Reports (Including EVM) and Executive Summary

48 reports of each

0013 Draft Final Report Not Separately Priced (NSP)

NSP NSP NSP

0014 Final Report

1 Report $ $ $

OPTIONAL CLIN 0015

Shall the Government decide to exercise Optional CLIN 0015 for drug substance manufacturing in response to a Public Health Emergency (for use under an Emergency Use Authorization (EUA)) and/or the Government foresees to have vaccines be placed in the Strategic National Stockpile (SNS), the Contractor shall manufacture a recombinant seasonal, pre-pandemic or pandemic influenza vaccine candidate.

Optional

CLIN

SUPPLIES /

SERVICES

QTY/UNIT UNIT PRICE EST. COST FIXED FEE TOTAL EST. CPFF

0015 The Contractor shall manufacture bulk Recombinant candidate*

150,000 / 15 mcg dose equivalents (Bulk)

* Strain selection to be supplied by HHS. (Note: The Contractor shall complete price per dose and propose their best estimate.) In the event of such an emergency, the Contracting Officer reserves the right to increase the quantity amount in order to meet the Governments’ needs.

ARTICLE B.3. PROVISIONS APPLICABLE TO DIRECT COSTS

Notwithstanding the clause, ALLOWABLE COST AND PAYMENT and FIXED FEE, incorporated in this contract, unless authorized in writing by the Contracting Officer, the costs of the following items or activities shall be unallowable as direct costs:

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

b) Special rearrangement or alteration of facilities;

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

(General purpose equipment is defined as any items of personal property which are usable for purposes other than research, such as office equipment and furnishings, pocket calculators, etc.);

d) Travel Costs;

e) Consultant Costs;

f) Subcontracts;

g) Patient Care Costs; and

h) Accountable Government Property (defined as both real and personal property with an acquisition cost of $1,000 or more and a life expectancy of more than two years) and “sensitive items” (defined and listed in the Contractor’s Guide of Government Property), regardless of acquisition value.

ARTICLE B.4. ADVANCE UNDERSTANDINGS

(a) Termination of Contract

If the Contractor fails to meet the milestones, within the specified time periods as stated in the statement of work, the Government has the right to terminate the contract for default, in accordance with FAR 52.249-6, Termination (Cost-Reimbursement) (May 2004).

(Note: Specific elements of cost, which normally require prior written approval of the Contracting Officer before incurrence of the cost (e.g., foreign travel, consultant fees, subcontracts) will be included in this Article if the Contracting Officer has granted his/her approval prior to contract award.)

SECTION C – DESCRIPTION/SPECIFICATIONS/WORK STATEMENT

DEFINITIONS – For the purpose of this Section

“Freedom to Operate” – ensures that the commercial production, marketing and use of the Contractor’s new product, process and service do not infringe the intellectual property rights of others.

ARTICLE C.1. BACKGROUND / PURPOSE

A. BACKGROUND

The development and acquisition of vaccines for use during an influenza pandemic is a key objective of the Biomedical Advanced Research and Development Authority (BARDA) in the U.S. Department of Health and Human Services (HHS). An influenza pandemic has a great potential to cause large numbers of deaths and illnesses over a short time period. An influenza pandemic can occur when an influenza strain with a new HA subtype (with or without a new NA subtype) appears to which the human population which has little or no immunity and in which the virus can also spread efficiently. Three influenza pandemics occurred during the 20th century. The most severe pandemic began in 1918 and caused an estimated 500,000 deaths in the U.S. and more than 20 million deaths worldwide. Recent outbreaks of human disease caused by influenza virus strains (i.e., H5N1, H1N1, etc.)

continue to pose a public health threat. Estimates for the next pandemic, extrapolating from those of the 20th century, range from about 100,000 to over 2 million deaths in the U.S. alone.

Central to the National Strategy for Pandemic Influenza for domestic pandemic preparedness is the goal to provide pandemic influenza vaccine to all U.S. citizens, that is, 600 million doses within six (6) months of the issuance of an influenza pandemic declaration. The timeline for the availability of egg- and cell-based inactivated, monovalent, pandemic influenza vaccines in the U.S. is estimated at 20-23 weeks post-pandemic onset, which may be towards the end of a first pandemic wave. Recombinant influenza vaccines, on the other hand, may benefit from manufacturing efficiencies, may not be dependent on pandemic influenza virus reference strain availability and/or the production and calibration of potency assay reagents needed for inactivated influenza vaccines. As a result, recombinant influenza vaccines may be available in a shorter time frame of 8 to 12 weeks post-pandemic onset. The development and commercialization of recombinant influenza vaccine products lag behind that of conventional inactivated influenza vaccines. In order to decrease the cycle-time of vaccine production and increase manufacturing surge capacity during a pandemic, HHS wishes to encourage and facilitate the advanced development and U.S.-licensure of recombinant seasonal and pandemic-like influenza vaccines. The combined effects of using pre-pandemic, recombinant pandemic, and conventional inactivated, pandemic influenza vaccines, with influenza antivirals and community mitigation measures are expected to delay the peak incidence of pandemic influenza infection and disease and to reduce the morality and morbidity in a severe pandemic.

This Request for Proposal (RFP) solicits proposals for awarding contracts that focus on the advanced development of recombinant seasonal and pandemic-like influenza vaccines utilizing hemagglutinin genes or proteins (plasmid DNA, virus-vectors, peptides, subunit proteins, and virus-like particles) towards U.S.-licensure in exchange for a commitment to establish a rapid surge capacity for pandemic vaccine.

B. PURPOSE

The purpose of this solicitation is to support (1) industrial, advanced-stage development of recombinant seasonal and pandemic influenza vaccines leading towards U.S. licensure, (2) expansion of domestic influenza vaccine manufacturing surge capacity, and

(3) to reduce the timeline for manufacturing and release of influenza vaccines during a pandemic. The proposed recombinant influenza vaccines shall be produced at commercial-scale levels as licensable products in U.S.-based manufacturing facilities and shall provide sufficient surge capacity to contribute substantially to U.S. and, ideally, global vaccine needs during an influenza pandemic.

Activities that may be supported by this solicitation shall include: (1) clinical lot manufacturing including consistency lots of recombinant seasonal and pandemic-like influenza vaccine, (2) clinical evaluation studies of the recombinant vaccine strategy for safety and immunogenicity including clinical assay development, (3) process and manufacturing scale-up development, (4) product lot release assay development and process validation, (5) product-dedicated manufacturing equipment, facility concept design and facility validation. U.S. Government support shall not be provided for building a manufacturing facility or purchasing an existing facility. Finally, development of recombinant pandemic influenza virus vaccine shall occur in parallel with the Contractor’s own advanced product development, towards licensure, of a recombinant seasonal influenza vaccine.

ARTICLE C.2. OBJECTIVES

Using intellectual property to which the Contractor has unencumbered and documented access including “freedom to operate”, the Contractor shall accomplish the following objectives associated with advanced development of recombinant seasonal and pandemic influenza vaccines within a 60 month performance period from the time of contract award:

A. Develop (i) recombinant seasonal and pandemic-like influenza vaccines, such as influenza virus strains to be designated by HHS (i.e., H5N1, H1N1, etc.) that are well-tolerated, immunogenic, and potentially cross-reactive against antigenically drifted strains, (ii) manufacturing processes that may be scaled for commercial-scale production and (iii) associated lot release product assays and specifications.

B. Validate manufacturing process, product lot release assays, and equipment used for product manufacturing.

C. Manufacture consistency lots of recombinant seasonal and pandemic-like influenza vaccine candidates for clinical evaluation. Clinical investigational lots of recombinant influenza vaccines may be manufactured by the Contractor or subcontractor in compliance with current Good Manufacturing Practices (cGMP), World Health Organization (WHO) guidelines for pandemic influenza vaccine manufacturing and current biosafety/research guidelines from the Centers for Disease Control (CDC), National Institutes of Health (NIH) and the United States Department of Agriculture (USDA).

D. Conduct pivotal clinical studies in adult, elderly, and pediatric groups to assess the safety, immunogenicity, and cross-reactivity of recombinant influenza vaccines. Clinical study protocols and clinical endpoints shall be compatible with FDA guidelines for production and clinical evaluation of seasonal and pandemic influenza vaccines. Clinical assays to assess human specimens generated from study protocols shall be appropriately qualified and/or validated

E. Develop a plan to manufacture the recombinant pandemic influenza vaccine in a manufacturing facility located in the U.S.

for lot release within 12 weeks of pandemic onset and surge capacity of 50 million doses within 6 months of pandemic onset.

Additional Information

In addition, it is critical that the Contractor understand the following:

This advanced development contract is milestone-driven and funding may occur in phases following periodic assessments of progress by HHS. Continuation of effort on initial and subsequent milestones and associated funding will be based on Contractor performance, timeliness, quality of deliverables, availability of other vaccine manufacturing strategies and products deemed more advantageous to the U.S. Government, and consultations between the Contractor and HHS.

This RFP contains Mandatory Criteria for Eligibility; see Section M for specific information.

ARTICLE C.3. STATEMENT OF WORK

STATEMENT OF WORK

Independently and not as an agent of the government, the Contractor shall furnish all the necessary services, qualified personnel, materials, equipment, and facilities not otherwise provided by the government as needed to perform the work described below.

The Contractor shall perform the work in accordance with the Contractor’s Work Plan (CWP) (or Summary of CWP) and the Contractor’s Gantt chart (Gantt chart will be referenced in Section J and attached to this contract at time of award.) The contract schedule milestones takes precedence over discrepancy with the attachments.

The following Milestone Plans are required to describe the activities that the Contractor will perform to successfully meet the objectives of the contract. The Contractor shall demonstrate their full understanding of the key elements essential to complete the requirements, including how each milestone plan is organized, staffed and managed. The completeness and quality of the Contractor’s milestone plans and supporting data will be evaluated in terms of relative risk and the likelihood of successful completion of the project. The level of detail contained in the milestone plans shall be sufficient to facilitate management of and execution of the contract by the Contractor. Acceptable milestone plans are a requirement of this contract. The Contracting Officer may modify this contract, as described in Milestones 5a and 5b, to incorporate the Contractor Defined Milestones, work breakdown structures and Gantt charts provided and accepted in Milestones 1-4.

Milestones

I. Milestone 1: Within three (3) months of contract award, the Contractor shall provide to HHS for review and acceptance a comprehensive milestone-driven Product Development Plan for recombinant seasonal and pandemic influenza vaccines.

The Plan shall be inclusive of pre-clinical and clinical activities performed and completed prior to a contract award and those clinical and manufacturing activities to be performed post-contract award. The Plan shall be a high-level overview and include the following elements:

A. Gantt chart timeline or equivalent.

B. Description of the process development and scale-up of recombinant vaccine manufacturing.

C. Description of clinical and consistency lot manufacturing to support process validation, clinical evaluation and FDA

Center for Biologics Evaluation and Research (CBER) product licensure.

D. Description of the general clinical development plan including development and validation of clinical sample assays.

E. Description of product lot release assay development including assay specifications and validation.

F. Regulatory master plan that focuses on the critical pathway to product licensure.

G. Cost-accounting system based on the original budget estimates (that includes earned value management) to monitor all costs related to the contract award for both prime and sub-Contractors on a real time basis.

II. Milestone 2: Within three (3) months of contract award, the Contractor shall submit to HHS for review and acceptance, a comprehensive, integrated Clinical Development and Regulatory Plan. The following issues shall be addressed in the Plan:

A. A summary of pre-clinical studies including consultation(s) with the FDA Center for Biologics Evaluation and

Research (CBER) incorporated as an appendix to the milestone report.

B. A detailed description of clinical evaluation shall be integrated with the manufacturing plans using the most current and available information including consultation with CBER. Clinical trials performed as a result of this solicitation shall include any Phase 1, Phase 2, and Phase 3 trials needed to achieve U.S. licensure. Trials shall include children, adults, and the elderly, as needed, to support licensure for both low and high-risk populations. Given the duration, cost, and importance of clinical trials, the plan for each clinical trial shall clearly indicate key outcomes, populations, study sites and collaborators, analytic strategy, sample size, timelines, and other key components. Studies related to pandemic –like vaccine shall be done using recombinant influenza vaccine to a relevant influenza virus strain to be designated by HHS (i.e., H5N1, H1N1, etc.) A summary of available clinical lot manufacturing results, provisional lot release specifications, completed Phase 1 trials and any additional stages of product development that have been completed shall be incorporated as an appendix to the milestone report.

C. A detailed description of regulatory activities shall be integrated with all products, clinical testing and manufacturing activities using the most current and available information, including consultation with CBER. A risk assessment and mitigation plan addressing potential manufacturing, clinical and regulatory obstacles that might prevent or delay licensure as well as a plan for the production and distribution of vaccine in the case of emergency use authorization shall be included. Issues suitable for risk assessment include recombinant DNA constructs, cell lines, assay development, process yields and facility management. Mitigation plans shall include decision trees where applicable.

Many of the required elements may be satisfied by inclusion of the Contractor’s Investigational New Drug (IND) application and relevant supplements.

III. Milestone 3: Within nine (9) months of contract award, the Contractor shall provide HHS for review and acceptance a

Manufacturing Facility Plan describing the design, construction, commissioning, qualification and validation of a U.S.-based facility to produce the Contractor’s recombinant seasonal and pandemic-like influenza vaccines. The Plan shall contain appropriate information concerning the following elements:

A. Site selection criteria, including site user requirement specifications, descriptions of site utilities and infrastructure, descriptions of local, state and federal permitting issues and security planning considerations.

B. A facility regulatory compliance plan that addresses cGMP standards, NIH, CDC, USDA and WHO biosafety standards, USDA animal testing standards, National Fire Protection Agency standards, DHS security issues and OSHA compliance.

C. Manufacturing processes that includes descriptions of upstream and downstream processing, formulation, filling and finishing unit operations, bulk and finished product acceptance specifications, overall capacity needed to meet contract requirements, manufacturing support operations such as solution preparation, storage and distribution, glassware washing and sterilization, clean-in-place and steam-in-place operations, a risk management plan at each stage of production, process flow diagrams, equipment capacity calculations, an automation plan and an equipment list detailing sizing capacity criteria, utility requirements, dimensions, clearances weights, mounting and purchasing lead times.

D. Architectural/structural plans that includes concept functional designs, descriptions, and diagrams of space requirements, adjacency plans, floor plans, equipment layouts, material, product and personnel flows, solid, liquid contaminated and other waste flows, and an air balance description or diagram detailing zoning, pressurization, air flows and air quality classification.

E. Process and building/ mechanical engineering including energy balances, utility flow diagrams, automation plan, equipment lists and a preliminary layout.

F. A proposed construction schedule including installation, commissioning and installation/operational/performance qualification and a risk mitigation analysis.

G. A description of the manufacturing facility quality assurance and regulatory acceptance including quality systems, the validation master plan and regulatory milestones.

The manufacturing facility and process shall be maintained in compliance with current Good Manufacturing Practices, World Health Organization guidelines for pandemic influenza vaccine manufacturing and current biosafety/research guidelines from the CDC, NIH, and the USDA. Ability to meet standards for Biosafety Level (BSL) 2 + and 3 as described in relevant guidelines may be necessary, if the Contractor will be handling and testing highly pathogenic avian influenza viruses or derivatives to generate recombinant pandemic-like influenza vaccines.

IV. Milestone 4: Within twelve (12) months of contract award, the Contractor shall provide HHS for review and acceptance a Feasibility Plan to manufacture, test, and release final container product containing recombinant pandemic-like influenza vaccine within 12 weeks of a pandemic declaration with a surge capacity of 50 million doses within six (6) months. The Plan shall include the following elements:

A. A process description, including a summary of process data that describes the yield and purification efficiencies of key process steps.

B. A comparison of process data that describes the significance of process scale-up and strain variability on production capacity.

C. Proposed production schedules including detailed timelines for each production step from accessibility of pandemic influenza viral nucleotide sequences or receipt of pandemic influenza virus reference strain to release of initial lot(s) of 50 million doses of final container vaccine product during a pandemic. Additionally, a description of material management and the number of doses of vaccine released each week after pandemic declaration shall be provided.

D. A bulk and fill-finish manufacturing capacity analysis for pandemic influenza vaccines.

E. A description of process optimization activities.

F. Dose calculations and contingency plans to address the need for higher dosages of the active product ingredient.

G. A pre-pandemic facility management plan including a pandemic preparedness plan.

H. A pandemic facility management plan including change procedures for pandemic operations and operation under

Emergency Use Authorization (EUA).

V. Milestone 5a and 5b: Contactor Defined Milestones. The Contractor shall provide a work breakdown structure including comprehensive and integrated timelines (Gantt chart or equivalent) and major milestones to complete the remaining scope of work as relevant given the stage of vaccine development and evaluation toward product licensure. The Contractor shall propose milestones, at which time data will be presented, summarizing results of prior activities and new plans and protocols that will be submitted for review and approval in order to guide all subsequent activities. Milestones for recombinant seasonal (5a) and pandemic-like (5b) influenza vaccines shall be provided to track program progress and cost reimbursements. Potential milestones may include manufacturing of an investigational lot of vaccine, validation of facilities, systems and equipment, validation of Quality Control product lot release methods, validation of manufacturing processes, stability study programs, consistency lot manufacturing, completion of a clinical trial and progress to a new phase of vaccine evaluation, submission of a license application, etc. Following the Project Officer/Contracting Officer’s Technical Representative (COTR) acceptance of the Contractor Defined Milestones, the Contracting Officer may modify this contract to incorporate the Contractor Defined Milestones, work breakdown structure and Gantt chart.

VI. Manufacturing Standards: The USG reserves the right to inspect the Contractor’s facilities for cGMP compliance. HHS will audit manufacturing, testing and other relevant sites. Focus areas will include manufacturing, quality systems and regulatory affairs relative to the contract milestone activities within six (6) months of contract award. Any deficiencies observed in the audit will require remediation. Within three (3) months after receiving the audit report, a time-plan for remediation must be in place and remediation shall be complete within the Base Period of the contract.

[END OF STATEMENT OF WORK]

Meetings and Conferences:

The Contractor shall participate in regular meetings to coordinate and oversee the contract effort as directed by the Project Officer/COTR. Such meetings may include, but are not limited to, meetings of all Contractors and subcontractors to discuss clinical manufacturing progress, product development, product assay development, scale up manufacturing development, clinical sample assays development, clinical study designs and regulatory issues, meetings with individual Contractors and other HHS officials to discuss the technical, regulatory, and ethical aspects of the program; and meetings with technical consultants to discuss technical data provided by the Contractor. Monthly teleconferences with the Contractor and subcontractors with HHS officials will be held at times and dates to be determined to review technical and product development progress, except during clinical lot manufacturing when meetings shall be held on a weekly basis. In addition, the Project Officer/COTR may schedule progress reviews, including quarterly progress reviews, on-site at the Contractor’s facilities and other locations.

ARTICLE C.3.1. SECURITY OF CONTRACT OPERATIONS AND INFORMATION TECHNOLOGY

The work performed for development, manufacture, transport, storage and distribution will be performed under a detailed security plan that ensures against theft, tampering or destruction of the specific pertinent product-related material, equipment, documents, information, and data. The Contractor shall develop a written Draft Security Plan, for the protection of physical facilities, using, for example, fencing, controlled access, surveillance equipment, 2-person integrity rule, tamper evident packaging, and armed guards.

The Contractor shall submit the Draft Security Plan to the Contracting Officer and Project Officer/COTR within 30 days after the contract award. The Draft Security Plan shall describe the procedures to be utilized to manage and monitor the general internal operations of the firm and a description of the Contractor’s facility(ies) in which the work will be performed and related activity conducted, including work by any subcontractors and consultants. The Draft Security Plan shall also include the Contractor’s procedures for screening and background investigations of all employees, subcontractors and consultants who have access to the development, manufacturing, transport, storage, and distribution of the product. Such background inquiries and screening shall include, but not be limited to, education, previous employment, fingerprints and complete criminal history (FBI, state, and local), credit reports, civil actions, DMV, social security account number verification, drug testing, and references. Screening data shall include the employee’s full name, any aliases, date(s) of birth, and Social Security numbers and other identifying numbers as appropriate, e.g., Passport number. At time of award, the USG can audit and review at its discretion the Contractor’s personnel records in order to confirm compliance with personnel screening and background investigation requirements. Such access will also include interviews with relevant Contractor human resources supervisory and hiring personnel.

This plan shall ensure confidentiality, integrity of, and timely access by authorized individuals to data, information and information technology systems, consistent with OMB Circular A-130, Appendix III. This plan shall also address the Contractor’s security-related due diligence on public information, marketing, advertising, including use of web site(s) impacting product and supply chain security.

This plan shall also include the security measures to be used to protect the medical countermeasure to be stored at the Contractor’s facility (e.g., refrigeration/freezer alarm systems, backup electrical power generator systems, etc.), and the contingency plan to accommodate any manufacturing and storage problems caused by natural or man-made disasters, power loss, refrigerant loss, equipment failures, etc.

The Project Officer/COTR, Contracting Officer and the Information Protection and Systems Security (IPASS) Coordinator will review the plan and submit comments to the Contractor within 10 business days after receipt. The Contractor shall revise the Security Plan, if required, and submit a Final Security Plan to the Government within 30 days of notification. Upon completion of all the required security measures, the Contractor shall supply to the Project Officer/COTR a letter certifying compliance. Performance of work under this contract shall be in accordance with this written Security Plan.

ARTICLE C.4. EARNED VALUE MANAGEMENT (EVM)

FAR Clause 52.234-3, Notice of Earned Value Management System – Post Award IBR (July 2006) and FAR Clause 52.234-4, Earned Value Management System (July 2006) are incorporated herein by reference.

C.4.1 Managerial Approach

The Contractor shall deliver a Management Plan that explains how the Contractor shall provide for the effective and efficient management of the technical, administrative, logistical, and support functions described in this statement of work. This Earned Value Project Management System shall meet the Seven Principles of Program Performance Based Management. The Seven Principles are:

1. Plan all work scope for the program to completion.

2. 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.

3. 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.

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

5. Objectively assess accomplishments at the work performance level.

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

7. Use Performance Based information in the company's management processes.

C.4.2 Performance Measurement Baseline (PMB)

Contractor and BARDA shall mutually agree upon cost, schedule and technical plan baselines. These baselines shall be the basis for monitoring and reporting progress throughout the life of the contract.

C.4.3 Integrated Baseline Review (IBR)

The Contractor shall submit a plan for an Integrated Baseline Review to occur within 90 days of contract award. At the IBR, the Contractor and BARDA shall mutually agree upon cost, schedule and technical plan baseline (Performance Measurement Baseline).

This baseline shall be the basis for monitoring and reporting progress throughout the life of the contract. The IBR is conducted to provide a mutual understanding of the inherent risks in Contractor’s performance plans and the underlying management control systems, and it shall formulate a plan to handle these risks.

In the IBR, the Contractor shall:

• Demonstrate that there is a logical sequence of effort consistent with the contract schedule;

• Demonstrate the validity of the allocated cost accounts and budgets, both in terms of total resources and scheduling;

• Support BARDA’s technical assessment of the performance measurement methodologies and variance analysis reporting thresholds that the Contractor is using to measure progress;

• Support BARDA’s technical assessment of quality metrics;

• Verify that the cost, schedule, and technical plans are integrated. (The technical content of control accounts and work packages is consistent with the contract scope of work, the WBS and the WBS dictionary).

C.4.4 Contract Performance Report (CPR)

The Contractor shall deliver a Contract Performance Report on a monthly basis consistent with the instruction in Department of Defense Data Item Description (DID) DI-MGMT-81466A. Contractor shall provide Format 1, Format 3 and Format 5 only. Format 1 will be reported at the Work Breakdown Structure level agreed to by BARDA and the Contractor. Contractor shall provide preliminary CPR on the 15th day after end of Contractor reporting period and final CPR on the 20th day. EV Variance thresholds will be negotiated with the Contractor post-award but for planning purposes will likely be (+/- 10%).

C.4.5 Integrated Master Schedule

The Contractor shall deliver a program level Integrated Master Schedule (IMS) that rolls up all time-phased WBS elements down to the activity level. This IMS shall include the dependencies that exist between tasks.

The Contractor shall provide monthly delivery of the IMS status with performance data and shall include actual start/finish and projected start/finish dates. The status schedule shall be delivered 5 days after reporting month end.

C.4.6 Work Breakdown Structure

Work Breakdown Structures (WBS) shall be discernable and consistent. For example, BARDA may require a Contractor to furnish WBS data at the cost account level or at the work package level or at a lower level if there is significant complexity and risk associated with the task. Work Breakdown Structures shall be product and/or deliverable based where possible. BARDA encourages the use of MIL-HNDBK-881 as guidance.

The Contractor’s baseline schedule shall have each task (activity) aligned to its corresponding WBS identification. The WBS identification shall be visible in its own unique field in the project schedule.

C.4.7 Risk Management Plan

The Contractor shall develop a risk management plan highlighting potential problems and/or issues that may arise during the life of the contract, their impact on cost, performance and timelines, and appropriate remediation plans. This plan shall reference relevant WBS elements, where appropriate.

ARTICLE C.5. REPORTING REQUIREMENTS

In addition to those reports required by other terms of this contract, the Contractor(s) shall submit to the Contracting Officer and the Project Officer/COTR technical progress reports covering the work accomplished during each reporting period on a periodic basis as established by the Project Officer/COTR. These reports are subject to the technical inspection and requests for clarification by the Project Officer/COTR. These reports shall be brief and factual and prepared in accordance with the following format:

I. Technical Progress Reports: On the fifteenth of each month for the previous calendar month, the Contractor shall submit a report to the Project Officer/COTR and the Contracting Officer. The format and type of Technical Progress Report and Executive Summary will be provided by the Project Officer/COTR. Technical Progress Reports will include project timelines, milestones and summaries of product manufacturing, testing and clinical evaluation. A Technical Progress Report will not be required for the periods when a Final Report is due. The Contractor shall submit one copy of the Technical Progress Report electronically via e-mail. Any attachments to the e-mail report shall be submitted in Microsoft Word, Excel, PowerPoint, Microsoft Project and/or Adobe Acrobat PDF files. Such reports shall include the following specific information:

A. Title page containing Technical Progress Report, the contract number and title, the period of performance or milestone being reported, the Contractor's name, address, and other contact information, the author(s), and the date of submission;

B. Introduction/Background - An introduction covering the purpose and scope of the contract effort;

C. Progress - The report shall detail, document, and summarize the results of work performed, test results, and milestones achieved during the period covered. Also to be included is a summary of work planned for the next reporting period including overall progress towards obtaining FDA approvals and licensure on new influenza vaccine(s);

D. Issues - Issues resolved, new issues and outstanding issues are enumerated with options and recommendations for resolution. An explanation of any difference between planned progress and actual progress, why the differences have occurred, and, if project activity is delinquent, then what corrective steps are planned. Revised timelines are provided.

E. Invoices – Summary of any invoices submitted during the reporting period.

F. Action Items – Summary table of activities or tasks to be accomplished by a certain date and by whom.

G. Distribution List – A list of persons receiving the Technical Progress report

H. Attachments – Results on the project are provided as attachments

III. The Executive Summary, which shall accompany each Technical Progress Report, will be formatted in Microsoft Power Point presentations and include the following:

A. Title page containing Executive Title, the contract number and title, the period of performance or milestone being reported, the Contractor's name and the date of submission;

B. Project Progress presented as milestone events, test results, tasks and other activities achieved during the reporting period as talking point bullets;

C. Project Issues presented headings and each item as a talking point bullet.

IV. Final Reports – The Contractor shall submit a Draft Final Report for the Base Period and Option Period One to the Project Officer/COTR and Contracting Officer within 45 calendar days prior to the contract expiration date. The Project Officer/COTR will review the draft report and provide the Contracting Officer with comments within 15 calendar days after receipt. The Final Report shall be corrected by the Contractor, if necessary and the final version delivered by the expiration date of the contract.

The Contractor shall submit a comprehensive Final Report for the Base Period and Option Period One that shall detail, document and summarize the results of the entire contract work. The report shall explain comprehensively the results achieved.

SECTION D – PACKAGING, MARKING AND SHIPPING

ARTICLE D.1. SHIPPING

I. Method of Delivery

Unless otherwise specified by the Contracting Officer or the Project Officer/COTR, delivery of items, to be furnished to the Government under this contract (including invoices), shall be made by first class mail. All deliverables shall be marked with the contract number and Contractor name.

For delivery of the bulk vaccines under Optional CLIN 0015, the Contractor shall provide the Contracting Officer or the Project Officer/COTR with the estimated date of final QC release of the bulk vaccines. Within 30 days post-final release of the vaccine by the Contractor, the Contracting Officer or the Project Officer/COTR will provide delivery instructions to the Contractor.

II. Addressees – For all contract deliverables.

Project Officer/COTR Contracting Officer

HHS/OS/ASPR/BARDA HHS/OS/ASPR/BARDA

330 Independence Avenue , SW 330 Independence Avenue, SW Room G640 Room G640 Washington, D.C. 20201 Washington, D.C. 20201

SECTION E – INSPECTION AND ACCEPTANCE

The Contracting Officer or the duly authorized representative (who for the purposes of this contract will be the Project Officer/COTR) will perform inspection and acceptance of materials and services to be provided under the contract. The contract will identify who will perform inspections and where the inspections will be performed. Acceptance may be presumed unless otherwise indicated in writing by the Contracting Officer or the duly authorized representative within 30 days of receipt.

Should the Government exercise Optional CLIN 0015, pursuant to FAR 52.246-16, risk of loss or damage to materials under Optional CLIN 0015 of this contract, shall pass to the Government upon the Government’s acceptance of materials delivered to the destination provided by the Contracting Officer pursuant to D.1. of this contract. Government acceptance of materials under Optional CLIN 0015 shall occur after inspection pursuant to FAR 52.246-3 (except to the extent provided in FAR 52.246-16(c) regarding nonconforming materials), with written documentation for acceptance provided by the Contracting Officer to the Contractor as promptly as practicable after delivery but not later than 30 days of receipt.

The following clause is incorporated by reference with the same force and effect as if it were given in full text.

FAR Clause 52.246-3, Inspection of Supplies – Cost Reimbursement (May 2001)

FAR Clause 52.246-9, Inspection of Research and Development (Short Form) (April 1984)

SECTION F – DELIVERIES OR PERFORMANCE

ARTICLE F.1. PERIOD OF PERFORMANCE

The period of performance for the Base Period (CLINs 0001 through 0010) shall be twelve (12) months from the effective date of contract award. This contract contains option periods. Each option, if exercised, could potentially increase the period of performance an additional forty-eight (48) months. Each option will be exercised in accordance with FAR Clause 52.217-9, Option to Extend the Term of the Contract (March 2000).

PERIOD PERFORMANCE PERIOD

Option Period One Twelve (12) months after the effective date of the contract through sixty (60) months after the effective date of the contract.

Optional CLIN 0015 Performance period will be determined at the time Optional CLIN 0015 is exercised.

ARTICLE F.2. CONTRACT DELIVERABLES / TECHNICAL REPORT DISTRIBUTION

The items specified below as described in the Reporting Requirements in SECTION C and ARTICLE G.5. of this contract, will be required to be delivered F.O.B. Destination as set forth in FAR 52.247-35, F.O.B. Destination, Within Consignees Premises (April 1984) and in accordance with and by the dates specified below and any shipping specifications stated in SECTION D of this contract:

A. The following contract deliverables and technical reports are required for the Base Period of this contract.

CLIN Deliverable Quantity Due Date

0001 Product Development Plan (Milestone 1)

Original – C.O.

2 Copies – P.O.

1 Electronic Copy – P.O.

Within Three (3) months after contract award.

0002 Clinical Development and Regulatory Plan (Milestone 2)

Original – C.O.

Within Three (3) months

0003 Manufacturing Facility Plan (Milestone 3)

Original – C.O.

Within Nine (9) months after contract award.

0004 Feasibility Plan (Milestone 4)

Original – C.O.

Within Twelve (12) months

0005A Contractor Defined Milestones (Milestone 5A)

Original – C.O.

Within sixty (60) months

0005B Contractor Defined Milestones (Milestone 5B)

Original – C.O.

0006 Draft Security Plan Original – C.O.

Within thirty (30) days after contract award.

0007 Final Security Plan Original – C.O.

Within thirty (30) days after USG’s final comments.

0008 Technical Progress Reports (Including EVM) and Executive Summary

Original – C.O.

Due on/before the 15th of the month for the previous calendar month. See ARTICLE C.2. Not due when Final Report is due.

N/A Contract Financial Report Original – C.O.

Due on a quarterly basis on/before the 15th of the month. Not due when Final Report is due. See

ARTICLE G.5.

0009 Draft Final Report Original – C.O.

Due 45 days prior to the expiration date of the contract.

0010 Final Report Original – C.O.

Due on/before the expiration date of the contract.

B. The following contract deliverables and technical reports are required for Option Period One of this contract.

CLIN Deliverable Quantity

Due Date 0011A Remaining Contractor Defined Milestones -

Recombinant Seasonal Influenza Vaccine

0011B Remaining Contractor Defined Milestones - Recombinant Pandemic Influenza Vaccine

00012 Technical Progress Reports (Including EVM) and Executive Summary

Due on/before the 15th of the month for the previous calendar month. See ARTICLE C.2. Not due when Final Report is due.

N/A Contract Financial Report Original – C.O.

Due on a quarterly basis on/before the 15th of the month. Not due when Final Report is due. See

ARTICLE G.5.

0013 Draft Final Report Original – C.O.

Due 45 days prior to the expiration date of the contract.

0014 Final Report Original – C.O.

Due on/before the expiration date of the contract.

C. The following contract deliverables are required for Optional CLIN 0015 of this contract.

1. The funded quantity, based on the exercise of optional CLIN 0015, shall be delivered to a location(s) to be designated by USG. The funded quantity by the exercise of the optional CLIN 0015 must be delivered to a location(s) to be designated by USG within a timeframe not to exceed six (6) months after the optional CLIN is exercised.

2. A FDA approval/licensure letter for the recombinant seasonal and pandemic influenza vaccine or copies of the Emergency Use Authorizations (EUA).

3. Copies…