RFP-HHS-BARDA-08-09-final.pdf

DEPARTMENT OF HEALTH & HUMAN SERVICES Office of the Secretary

Assistant Secretary for Preparedness & Response Washington, D.C. 20201

Date: August 28, 2008

Re: Request for Proposal (RFP) Number RFP-HHS-BARDA-08-09 entitled “Building Domestic Cell-based Influenza Vaccine Manufacturing Facilities”

Dear Prospective Offeror:

This RFP represents HHS’s commitment to support the expansion of the domestic capacity to manufacture pandemic influenza vaccines. The successful Offeror(s) will be required to design, construct, validate and perform regulatory activities that will lead to FDA-licensure of new U.S.-based bulk influenza vaccine manufacturing facilities. The requirement will include pre-construction document development, construction, commissioning, validation and licensing.

This RFP is posted on the General Services Administration’s (GSA’s) Federal Business Opportunities Internet website known as FedBizOpps Electronic Posting System (www.FedBizOpps.gov). Any amendments to this RFP shall also be posted on the same internet website. No other notice shall be given to prospective Offerors and it is incumbent on Offerors to make periodic inquiries.

The RFP includes Mandatory Criteria for Eligibility, which are located in Section M.1.

Prospective Offerors are advised that HHS is operating under stringent security requirements applied to all incoming mail and packages. This includes all proposals submitted under HHS solicitations by regular mail, express mail delivery, or hand-delivered directly by an Offeror or by a courier service. Please note that personal identification of couriers or Offerors is required for delivery of proposals.

In accordance with the attached RFP, Offerors are required to submit their proposals to the Contracting Officer no later than September 29, 2008, at 3:00 PM local time.

Any questions concerning the RFP should be submitted in writing to Paquetta Myrick-Hancock, no later than September 08, 2008 at the address specified below or you may also email your questions to Paquetta.Hancock@hhs.gov. Questions should be marked “Questions Regarding RFP-HHS-BARDA-08- 09”. Any questions and answers will be made available via the FedBizOpps website.

Letters of Intent to submit a proposal must be received by September 22, 2008. Section J of the RFP contains a copy of the Proposal Intent Response Sheet. Please note that your expression of intent is not binding but will greatly assist us in planning for the proposal evaluation process.

Sincerely yours, \signed\

Paquetta N. Myrick-Hancock Contracting Officer Biomedical Advanced Research and Development Authority http://www.fedbizopps.gov/

PAGES

15A. NAME

AND

ADDRESS

OF

OFFEROR

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

(Date)(Hour)

CALENDAR DAYS

14. ACKNOWLEDGMENT OF AMENDMENTS

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

(Type or Print)

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

UNDER DPAS (15 CFR 700)

RATING

PAGE OF

1 107

2. CONTRACT NO.

3. SOLICITATION NO.

HHS-BARDA-08-09

4. TYPE OF SOLICITATION

SEALED BID (IFB)

X NEGOTIATED (RFP)

5. DATE ISSUED

08/28/2008

6. REQUISITION/PURCHASE NO.

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

OS/ASPR/BARDA

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

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

SOLICITATION

9. Sealed offers in original and 11 copies for furnishing the supplies or services in the Schedule will be received at the place specified in ARTICLE 8 , or if handcarried, in the depository located in Block 7 until 3:00pm local time 09/29/2008

10. FOR INFORMATION

CALL:

A. NAME

Paquetta N. Myrick-Hancock

B. TELEPHONE (NO COLLECT CALLS)

AREA CODE NUMBER: EXT:

(202) 260-0534

C. E-MAIL ADDRESS

Paquetta.Hancock@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 27-40

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 5-12 X J LIST OF ATTACHMENTS 41-72

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 12-17 X K OTHER STATEMENTS OF OFFERORS 73-76

X G CONTRACT ADMINISTRATION DATA 17-18 X L INSTRS., CONDS., AND NOTICES TO 76-92

X H SPECIAL CONTRACT REQUIREMENTS 18-27 X M EVALUATION FACTORS FOR AWARD 92-107

OFFER (Must be fully completed by offeror) NOTE: ARTICLE 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 120 calendar days (60 calendar days unless a different period is inserted by the offeror) from the date for receipt of offers specified above, to furnish any or all ARTICLEs upon which prices are offered at the price set opposite each ARTICLE, 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

17. SIGNATURE

18. OFFER DATE

AWARD (To be completed by Government)

19. ACCEPTED AS TO ARTICLES 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)

ARTICLE

K

24. ADMINISTERED BY (If other than 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)

31 U.S.C. 3322; 31 CFR 210

RFP-HHS-BARDA-08-09

SECTION B--SUPPLIES OR SERVICES AND PRICES/COSTS

B.1. Brief Description of Supplies or Services

The Department of Health and Human Services (HHS), Office of the Assistant Secretary for Preparedness and Response (ASPR), Biomedical Advanced Research and Development Authority (BARDA) requires the services of a contractor(s) to design, construct, validate and perform regulatory activities that will lead to FDA-licensure of new U.S.-based bulk influenza vaccine manufacturing facilities. The requirements will include pre-construction document development, land use and zoning, construction, commissioning, validation and licensing of the facility, and the regulatory licensure, manufacture and release of at least one

(1) lot of pandemic and/or pre-pandemic vaccine product. The number of doses that represents a manufactured batch (1 lot) is defined by the contractor, but shall in any event be at least 200,000 doses.

B.2. Contract Line Item Numbers (CLINs):

(a) Cost Sharing – CLINS (Base Period)

In consideration for the completion of the work to be performed under the Contract Line Item Numbers (CLINs) shown below, and in accordance with the Statement of Work (see Section C), the Contractor shall be paid in accordance with the schedule shown below. In no event shall the Government’s share of the cost exceed 40% of the total cost for these line items:

Item Supplies / Services Qty / Unit Government Share of Cost

Offeror Share of

Cost

Total Cost

0001 Overall Project Plan (Milestone 1) 1 Job $ $ $

0002 Regulatory and Clinical Bridging Study Plan (Milestone 2) 1 Job $ $ $

0003 Facility Operation Feasibility Plan (Milestone 3) 1 Job $ $ $

0004 Detailed Manufacturing Facility Plan (Milestone 4) 1 Job $ $ $

0005 Contactor Defined Milestones (Milestone 5)

1 Job per Program

0005A Seasonal Influenza Vaccine Program (Milestone 5a) 1 Job $ $ $

0005B Pandemic Influenza Vaccine Program (Milestone 5b) 1 Job $ $ $

0006 Final Technical Closeout Report (Milestone 6) 1 Report $ $ $

Technical Progress Report and

Executive Summary (12 of each per year)

60 Reports $ $ $

TOTAL Cost (Items 0001 – 0007): $ $ $

(b) Cost Plus Fixed Fee (CPFF) CLINS (Base Period)

Upon licensure of the candidate vaccine within the new domestic manufacturing facility, the Contractor shall be paid in accordance with the schedule shown below to produce one (1) lot of pre-pandemic influenza vaccine each year for three (3) years. Strain selection will be at the discretion of the USG:

Item Supplies / Services Qty / Unit Est. Cost Fixed Fee Total Est.

CPFF

0008 Pre-pandemic Influenza Vaccine Production (Milestone 7)

1 Lot per Year

0008A 1st Pre-pandemic Influenza Vaccine Production 1 Lot $ $ $

0008B 2nd Pre-pandemic Influenza Vaccine Production 1 Lot $ $ $

0008C 3rd Pre-pandemic Influenza Vaccine Production 1 Lot $ $ $

TOTAL Cost Plus Fixed Fee (Items 0008A – 0008C): $ $ $

(c) Cost Plus Fixed Fee (CPFF) CLINS (Option Periods)

Should the Government decide to exercise an option(s) upon completion of Milestone 6 [Final Technical Closeout Report], the Contractor shall be paid in accordance with the schedule shown below. These estimates shall be revised to reflect the actual cost to manufacture influenza vaccine product and adjuvant (if applicable) as determined in Milestone 6. The actual cost of each option shall not exceed the estimated cost plus fixed fee for each line item:

Item Supplies / Services Qty / Unit Est. Cost Fixed Fee Total Est.

CPFF

0009 Pre-pandemic Influenza Vaccine Production (Milestone 6)

1 Lot per Year

0009A 1st Pre-pandemic Influenza Vaccine Production 1 Lot $ $ $

0009B 2nd Pre-pandemic Influenza Vaccine Production 1 Lot $ $ $

0009C 3rd Pre-pandemic Influenza Vaccine Production 1 Lot $ $ $

0009D 4th Pre-pandemic Influenza Vaccine Production 1 Lot $ $ $

0009E 5th Pre-pandemic Influenza Vaccine Production 1 Lot $ $ $

0009F 6th Pre-pandemic Influenza Vaccine Production 1 Lot $ $ $

0009G 7th Pre-pandemic Influenza Vaccine Production 1 Lot $ $ $

0009H 8th Pre-pandemic Influenza Vaccine Production 1 Lot $ $ $

0009I 9th Pre-pandemic Influenza Vaccine Production 1 Lot $ $ $

0009J 10th Pre-pandemic Influenza Vaccine Production 1 Lot $ $ $

0009K 11th Pre-pandemic Influenza Vaccine Production 1 Lot $ $ $

0009L 12th Pre-pandemic Influenza Vaccine Production 1 Lot $ $ $

0009M 13th Pre-pandemic Influenza Vaccine Production 1 Lot $ $ $

0009N 14th Pre-pandemic Influenza Vaccine Production 1 Lot $ $ $

0009O 15th Pre-pandemic Influenza Vaccine Production 1 Lot $ $ $

0009P 16th Pre-pandemic Influenza Vaccine Production 1 Lot $ $ $

0009Q 17thPre-pandemic Influenza Vaccine Production 1 Lot $ $ $

TOTAL Cost Plus Fixed Fee (Items 0009A – 0009Q): $ $ $

B.3 Contract Ceiling Amount

(a) The total estimated cost of performing the work under this contract is $________________________ (CLINs 0001 – 0008). Of this amount, the Government’s share of the cost of performance is $_______________________ and the Contractor’s share of the cost of performance is $_______________________. [To be completed at contract award]

(b) The Government’s share of the cost shall be increased to include the total estimated cost-plus-fixed fee of each option (CLINs 0009A – 0009Q) as it is exercised. The exercise of an option shall be in accordance with FAR 52.217-09 – Option to Extend the Term of the Contract (Mar 2000). In no event, however, shall the Government’s obligation under this contract exceed the amount stipulated as the Government’s share of the cost of performance. Costs incurred in the performance of the work under this contract are subject to FAR 52.232-20 – Limitation of Cost (Apr 1984).

B.4. Advanced Understandings

(a) Priority Rating

HHS intends to assign a priority rating to any contract awarded under this RFP. The Contracting Officer may unilaterally modify the contract to add FAR Clause 52.211-15, Defense Priority and Allocation Requirements (Sep 1990) AND ASSIGN A DO PRIORITY RATING UNDER 15

CFR 700.

(b) Costs

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

SECTION C - DESCRIPTION/SPECIFICATIONS

C.1. STATEMENT OF WORK

“Building Domestic Cell-based Influenza Vaccine Manufacturing Facilities”

Independently and not as an agent of the U.S. Government (USG), the Contractor shall furnish all the necessary services, qualified personnel, materials, equipment, and facilities not otherwise provided by the USG 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 the CWP, and the Gantt Chart referenced in Section J and attached to this contract.1

C.2. MILESTONES (also see Section F.3)

The following Milestone Plans are required to describe the activities that the Offeror will perform to successfully meet the objectives of the contract. The Contracting Officer may modify this contract, as described in Milestone 5a and Milestone 5b, to incorporate the Contractor- Defined Milestones, Work Breakdown Structures (WBS) and Gantt Charts provided in Milestone 1, Milestone 2, Milestone 3, and Milestone 4. For purposes of this statement of work, pre-pandemic vaccine is defined as an influenza vaccine with a pre-pandemic indication that is intended for immunization of persons against influenza virus subtypes of pandemic potential during the period when these subtypes have not yet evolved the capacity for sustained and efficient human-to-human transmission. These vaccines will ideally stimulate sustained immunological memory to enable boosting, resulting in an adequate immune response at a much later time point.

Milestone 1: Within three (3) months of contract award, the Contractor shall submit to HHS for review and acceptance, an Overall Project Plan. The Overall Project Plan shall present a preliminary Work Breakdown Structure (WBS) and Gantt Chart that includes all key regulatory and quality events, all contractual Milestone driven deliverables, and contractor-defined, project-specific elements in sufficient detail to outline the full scope of the effort.

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

1. 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 the Center for Biologics Evaluation and Research (CBER) in FDA. 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 (EUA) shall be included. Issues suitable for risk assessment include cell line qualification, assay development, process yields and facility management. Mitigation plans should include decision trees where applicable.

1 Will be submitted as a part of the Offeror’s proposal in response to solicitation and is subject to negotiation. Attachment will be provided at contract award.

2. A summary of pre-clinical studies including consultation(s) with the CBER should be incorporated as an appendix to the milestone report.

3. A detailed description of planned clinical bridging studies leading to licensure by the

CBER of the cell-based seasonal and pandemic influenza vaccine(s) produced in the new facility(s) should be presented. Clinical bridging studies of cell-based influenza vaccines manufactured and licensed at other sites, including abroad, is necessary to provide data in support of FDA licensure of this product in the newly created cell-based influenza vaccine manufacturing facility(s) located within the U.S.

4. A detailed description of clinical evaluation should be integrated with the manufacturing plans using the most current and available information including consultation with the CBER. A summary of clinical lot manufacturing results, provisional lot release specifications, and any additional stages of product development that have been completed should be incorporated as an appendix to the milestone report.

Many of the required elements of Milestone 2 may be satisfied by inclusion of the Contractor’s Investigational New Drug (IND) application and relevant supplements, if available.

Milestone 3: Within six (6) months of contract award, the Contractor shall provide HHS for review and acceptance a Facility Operation Feasibility Plan to manufacture, test, and release final container commercial biological products and vaccines for USG purchases during inter-pandemic and pandemic periods. In addition, the Facility Operation Feasibility Plan shall address, in specific terms, the schedule that satisfies release and delivery of 150 million finished doses of pandemic influenza vaccine with six (6) months of the declared pandemic. The purchase of any finished doses manufactured by the Contractor beyond the mandatory 150 million finished doses shall be negotiated at a later date, subject to funding and applicable appropriations rules and regulations. The Facility Operation Feasibility Plan should include the following elements:

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

2. An integration plan that outlines the addition of new facility(s) within the Contractor’s biological product franchise.

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

4. Proposed production schedules including detailed timelines for each production step from accessibility of pandemic influenza viral nucleotide sequence or receipt of pandemic influenza virus reference strain to release of initial lot(s) of 150 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 should be provided.

5. A detailed bulk upstream, bulk downstream, formulation, fill, and finish manufacturing capacity analysis for pandemic influenza vaccines.

6. An operational cost structure for pre-pandemic influenza vaccine lot production that includes the anticipated cost breakdown for a single dose of the vaccine.

7. A description of ongoing and/or anticipated process optimization activities.

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

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

10. A pandemic facility management plan including change procedures from seasonal to pandemic operations under Emergency Use Authorization (EUA).

11. A change control plan in the event the bulk manufacturing facility would be required by the USG for emergency production of an emerging, non-influenza infectious disease vaccine candidate.

Milestone 4: Within eight (8) months of contract award, the Contractor shall provide HHS for review and acceptance a Detailed Manufacturing Facility Plan describing the design, permitting approval, construction, commissioning, qualification and validation of a U.S.-based facility to produce the Contractor’s seasonal and pandemic influenza vaccine. The Detailed Manufacturing Facility Plan shall contain appropriate information concerning the following elements:

1. Site selection criteria, including site user requirement specifications, descriptions of site utilities and infrastructure, descriptions of local, state and federal land use, zoning and permitting issues and timelines, and security planning considerations.

2. A facility regulatory compliance plan that addresses any and all applicable local zoning, land use and construction standards, cGMP standards, NIH, CDC, USDA and WHO bio-safety standards, USDA animal testing standards, National Fire Protection Agency standards, DHS security issues and OSHA and EPA compliance.

3. A subcontractor use plan that contains a thorough discussion of the use and qualifications of known subcontractors and equipment vendors used in this contract as well as the criteria to be used for the future selection of anticipated subcontractor activities.

4. Manufacturing processes that include detailed descriptions of upstream and downstream processing, formulation, filling and finishing/packaging unit operations, bulk and finished product acceptance specifications, overall capacity needed to meet contract requirements, manufacturing support operations such as adjuvant solution/ media preparation, storage and distribution, glassware/equipment 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.

5. Architectural/ structural plans that include 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.

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

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

8. A description of the manufacturing facility quality assurance and regulatory acceptance including quality systems, the validation master plan (VMP) and regulatory milestones.

9. A copy of referenced procedures that govern the creation of quality driven documents and decisions in support of the contract efforts.

10. The work to be performed under this contract will involve access to sensitive Biomedical Advanced Research and Development Authority [BARDA] program information. Upon contract award, the Program Protection Officer (PPO) will review the Draft Security Plan (submitted as part of the Contractor’s Technical Proposal) in detail and submit comments to the Contracting Officer (CO) to be forwarded to the Contractor. The Contractor shall review the Draft Security Plan comments, if required, and submit a Final Security Plan to the U.S. Government as part of this Milestone deliverable. The Final Security Plan shall include a timeline for compliance of all the required security measures. Upon completion of initiating all security measures, the Contractor shall supply to the U.S. Government’s Project Officer a letter certifying compliance to the elements outlined in the Final Security Plan. The execution of the work under this contract shall be in accordance with the approved Final Security Plan. As outlined above, the content of the Final Security Plan shall be a continuation of the Draft Security Plan submitted as part of the Contractor’s Technical Proposal. Therefore, at a minimum, the Final Security Plan shall address the following items:

a. Personnel Security Policies and Procedures including, but not limited to:

Recruitment of new employees; Interview process; Personnel background checks;

Suitability/ adjudication policy; Access determination; Rules of behavior/ conduct; Termination procedures; Non-disclosure agreements.

b. Physical Security Policies and Procedures including but not limited to: Internal/ external access control; Identification/ badge requirements; Facility visitor access;

Parking areas and access; Barriers/ perimeter fencing; Shipping, receiving and transport (on and off-site); Security lighting; Restricted areas; Signage; Intrusion detection systems; Closed circuit television; Other control measures.

c. General Information Security Policies and Procedures including but not limited to: Identification of sensitive information; Access control/ determination; Secured storage infrastructure; Document control; Retention/ destruction requirements.

d. Information Technology Security Policies and Procedures including but not limited to: Intrusion detection and prevention systems; Encryption systems;

Identification of sensitive information/ media; Passwords; Removable media;

Laptop policy; Media access control/ determination; Secure storage; System document control; System backup; System disaster recovery.

e. The following instruction/ intent shall be incorporated: Security Reporting

Requirement - Violations of established security protocols shall be reported to the Contracting Officer (CO) and Project Officer (PO) upon discovery. The Contractor will investigate violations to determine the cause, extent, loss or compromise of sensitive and/or program information, and corrective actions taken to prevent future violations. BARDA will determine if the severity of the violation requires further U.S. Government (USG) intervention.

The manufacturing facility and process shall be maintained in compliance with current Good Manufacturing Practices (cGMP), World Health Organization (WHO) guidelines for pandemic influenza vaccine manufacturing and current bio-safety guidelines from the CDC, NIH, and the USDA. Ability to meet standards for Bio-Safety Level (BSL) 2+ [enhanced] as described in relevant guidelines may be necessary, if the Contractor will be handling and testing pathogenic influenza viruses or derivatives to generate pandemic influenza vaccines.

Milestone 5a and 5b: Contactor Defined Milestones. Within nine (9) months of contract award, the Contractor shall propose milestones, at which time data will be presented, summarizing results of prior activities and new plans/protocols that will be submitted for review and approval in order to guide all subsequent activities. Milestones for seasonal (5a) and pandemic (5b) influenza vaccine programs shall be provided to track program progress and cost reimbursements. The proposed milestone list must include details and timing for the following:

• Manufacturing of an investigational lot of vaccine in the new facility(s), and

• Submission of biologics license application (BLA). Within one (1) week of submission to CBER, the Contractor shall provide a copy of the BLA to the Contracting Officer.*

* Note, this contract will not fund costs associated with the Prescription Drug User Fee Act (PDUFA) for submittal of the BLA to CBER

Potential milestones may include the following:

• Architectural and Engineering (A&E) activity [e.g. 60% Design, 90% Design, 100% Design/Build],

• Facility permitting and construction,

• Validation of facilities, systems and equipment,

• Validation of Quality Control product lot release methods,

• Completion of appropriate clinical trials,

• Validation of manufacturing processes,

• Stability study programs,

• Engineering lot manufacturing, and

• Validation/Consistency lot manufacturing.

Following the Project Officer’s acceptance of the Contractor Defined Milestones, the Contracting Officer may modify this contract to incorporate the Contractor Defined Milestones along with a current version of the Work Breakdown Structure (WBS) and Gantt Chart.

Reporting of these activities will be required on a monthly basis as a part of the contractor’s monthly technical report.

Milestone 6: Within two (2) months of completion of last acceptable consistency/ validation lot in the new bulk facility, the Contractor shall submit to HHS for review and acceptance, a comprehensive, integrated Final Technical Closeout Report. The following items shall be addressed, in detail, via this report:

1. Equipment qualification/validation summary with supporting documentation (this includes, but is not limited to, stand alone/ off-the-shelf equipment, custom built process skids, qualified utility/HVAC systems, validated automation systems).

2. Process qualification/validation summary with supporting documentation referring to the manufacture of both engineering/demonstration lots and consistency/validation lots.

3. Proposed process schedule for the sequential manufacture of four (4) seasonal bulk vaccine lots. The schedule shall include a table that specifies all the raw materials necessary to manufacture the bulk, perform the necessary release testing, formulate the bulk, and complete all filling and packaging activities.

4. Accelerated proposed process schedule for the sequential manufacture of four (4) pandemic bulk vaccine lots to include change-over from seasonal manufacturing.

Schedule shall include all steps required to reach final filled product.

5. Detailed production schedule for master and working viral seed production (seasonal and pandemic).

6. A table outlining the cost of all raw materials (including disposables), labor, overhead and depreciation for a bulk lot of vaccine.

7. A table outlining the cost of raw materials (including disposables), labor, overhead and depreciation for the formulation and filling for a finished lot of vaccine [adjusted for 15µg/dose].

8. A table outlining the cost of raw materials (including disposables), labor, overhead and depreciation for a bulk lot of adjuvant (if applicable).

9. A table outlining the cost of raw materials (including disposables), labor, overhead and depreciation for the formulation and filling for a finished lot of adjuvant (if applicable).

10. Maintaining Facility Operation Plan: This plan shall demonstrate a commitment from the Contractor to manufacture and release at least one (1) lot of vaccine product per year post-licensure of the facility in order to maintain cGMP compliance and licensure to produce sufficient doses of the vaccine depending on Federal regulatory guidelines. Any pandemic and/or pre-pandemic vaccines, as defined by the U.S. Government (USG), that result from potential future contracted production activities shall be delivered to a USG-designated site. The Contractor shall incorporate this requirement into their work plan and timeline and include an updated cost breakdown per dose.

Milestone 7: Upon licensure of the candidate vaccine within the new domestic manufacturing facility, the Contractor shall produce one (1) lot of pre-pandemic influenza vaccine each year for three (3) years. Strain selection will be at the discretion of the USG and will be communicated to the Contractor at a suitable, negotiated time to ensure that the Contractor can schedule manufacture of the annual lot and satisfy the terms of the contract.

Pandemic Preparedness

Upon declaration of a pandemic by the Secretary of HHS or the President, the Contractor shall provide to the U.S. Government 150 million finished doses of the targeted pandemic vaccine strain within six (6) months. The pricing of those doses will be negotiated based upon, and will not exceed, the unit price calculated from the cost plus fixed fee of doses under the last executed Base or Option Period. Any pandemic vaccine doses manufactured in excess of the original 150 million doses shall be offered to the U.S. Government for purchased based on the same or lower pricing. The U.S. Government reserves the right to direct the disposition of those doses if they are not purchased directly by the U.S. Government. These rights remain in effect throughout the duration of a declared influenza pandemic event and only the Secretary of HHS or the President has the authority to declare or suspend a pandemic influenza event in the United States.

Emerging Infectious Diseases

In the event that the Secretary determines, pursuant to 47 U.S.C. 247d, that: (1) a disease or disorder presents a public health emergency or (2) a public health emergency, including significant outbreaks of infectious diseases or bioterrorist attacks otherwise exists, the USG reserves the right to direct the Contractor to manufacture a vaccine candidate for an emerging infectious disease to address such public health emergency. If modification of the facility to manufacture the new vaccine is required, then the cost sharing of that modification will be negotiated with the Contractor.

Surveillance and Monitoring / Maintain Manufacturing Standards: The USG reserves the right to inspect the Offeror’s facilities for cGMP compliance. HHS will audit manufacturing, testing and other relevant activities and sites as part of the overall surveillance and monitoring of contractor progress. 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, a time-plan for remediation must be in place and remediation shall be complete within twelve (12) months of award unless otherwise extended in the sole discretion of the Contracting Officer. These on-site audits will supplement the HHS detailed review of technical progress reports and milestone deliverables to monitor progress against the contract and overall contractor performance.

Furthermore, any official notices or reports that reference or result from a Federal, State, or local agency inspection or audit of the Contractor’s facility(s) shall be provided to the Contracting Officer within two (2) business days of receipt by the Contractor.

Meetings and Conferences: The Contractor shall participate in regular meetings to coordinate and oversee the contract effort as directed by the Project Officer. Such meetings may include, but are not limited to, meetings of all contractors/ subcontractors to discuss progress of the program, 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 between the Contractor/ key subcontractors and HHS officials shall be held at times and dates to be determined to review technical progress, except during engineering and validation lot manufacturing when meetings shall be held on a weekly basis.

SECTION D--PACKAGING, MARKING AND SHIPPING

D.1. SHIPPING

I. Method of Delivery

Unless otherwise specified by the Contracting Officer or the Contracting Officer’s representative, delivery of items, to be furnished to the Government under this contract (including invoices), shall be made by the United States Postal Service mail delivery, overnight mail delivery or courier service.

For delivery of the vaccine lots under Milestone 6, Milestone 7, and Optional CLIN 0009, the Contracting Officer or the Contracting Officer’s Technical Representative (COTR) will provide delivery instructions prior to the delivery date.

II. Addressees – For all contract deliverables.

[To be completed at contract award]

SECTION E--INSPECTION AND ACCEPTANCE

The Contracting Officer or a duly authorized representative (who for purposes of this contract will be the Project Officer) will inspect and accept materials and services to be delivered under the contract.

FAR 52.252-2 CONTRACT CLAUSES INCORPORATED BY REFERENCE (Feb 1998)

This contract incorporates one or more solicitation clauses by reference, with the same force and effect as if they were given in full text. Upon request, the Contracting Officer will make their full text available. Also, the full text of a clause may be accessed electronically at this/these address(es):

http:// www.acquisition.gov or http://www.hhs.gov/oamp/policies/ or http://www.gpoaccess.gov/cfr/index.html

FAR CLAUSE TITLE DATE

52.246-03 Inspection of Supplies – Cost Reimbursement MAY 2001 52.246-12 Inspection of Construction AUG 1996 52.246-15 Certificate of Conformance APR 1984

SECTION F--DELIVERIES OR PERFORMANCE

F.1. PERIOD OF PERFORMANCE

The period of performance for contract line item numbers (CLINs) 0001 through 0008 of this contract is from the date of contract award to ninety-six (96) months after contract award. Each http://www.arnet.gov/ http://www.dhhs.gov/oamp/dap/hhsar.html/ option, if exercised will extend the contract for an additional 12 month period. Each option will be exercised in accordance with FAR Clause 52.217-09 entitled “Option to Extend the Term of the Contract (MAR 2000). “

ITEM

No. PERIOD PERFORMANCE PERIOD

0009A Option Year1 Ninety-six (96) months and one day after the effective date of contract through one-hundred eight (108) months after the effective date of contract.

0009B Option Year 2 One-hundred eight (108) months and one day after the effective date of contract through one-hundred twenty (120) months after the effective date of contract.

0009C Option Year 3 One-hundred twenty (120) months and one day after the effective date of contract through one-hundred thirty-two (132) months after the effective date of contract.

0009D Option Year 4 One-hundred thirty-two (132) months and one day after the effective date of contract through one-hundred forty-four (144) months after the effective date of contract.

0009E Option Year 5 One-hundred forty-four (144) months and one day after the effective date of contract through one-hundred fifty-six (156) months after the effective date of contract.

0009F Option Year 6 One-hundred fifty-six (156) months and one day after the effective date of contract through one-hundred sixty-eight (168) months after the effective date of contract.

0009G Option Year 7 One-hundred sixty-eight (168) months and one day after the effective date of contract through one-hundred eighty (180) months after the effective date of contract.

0009H Option Year 8 One-hundred eighty (180) months and one day after the effective date of contract through one-hundred ninety-two (192) months after the effective date of contract.

0009I Option Year 9 One-hundred ninety-two (192) months and one day after the effective date of contract through two-hundred four (204) months after the effective date of contract.

0009J Option Year 10 Two-hundred four (204) months and one day after the effective date of contract through two-hundred sixteen (216) months after the effective date of contract.

0009K Option Year 11 Two-hundred sixteen (216) months and one day after the effective date of contract through two-hundred twenty-eight (228) months after the effective date of contract.

0009L Option Year 12 Two-hundred twenty-eight (228) months and one day after the effective date of contract through two-hundred forty (240) months after the effective date of contract.

0009M Option Year 13 Two-hundred forty (240) months and one day after the effective date of contract through two-hundred fifty-two (252) months after the effective date of contract.

0009N Option Year 14 Two-hundred fifty-two (252) months and one day after the effective date of contract through two-hundred sixty-four (264) months after the effective date of contract.

0009O Option Year 15 Two-hundred sixty-four (264) months and one day after the effective date of contract through two-hundred seventy-six (276) months after the effective date of contract.

0009P Option Year 16 Two-hundred seventy-six (276) months and one day after the effective date of contract through two-hundred eighty-eight (288) months after the effective date of contract.

0009Q Option Year 17 Two-hundred eighty-eight (288) months and one day after the effective date of contract through three-hundred (300) months after the effective date of contract.

F.2. TECHNICAL REPORT DISTRIBUTION

CLIN Deliverable Quantity Due Date

Final Technical Closeout

Report (Milestone 6)

Original – C.O.

2 Copies – P.O.

1 Electronic Copy – Sent to C.O. and P.O.

Within two (2) months of completion of last acceptable consistency/ validation lot in the new bulk facility.

0007 Technical Progress Report (12 of each per year)

1 Electronic Copy – Sent to C.O. and P.O.

The initial Technical Progress Report due on/before ________; thereafter, due on/before the 15th of the month or milestone following each reporting period. NOTE: A Technical Progress Report is not due when the Final

Technical Closeout Report is due.

Executive Summary (12 of each per year)

1 Electronic Copy – Sent to C.O. and P.O.

The initial Executive Summary due on/before ________; thereafter, due on/before the 15th of the month or milestone following each reporting period. NOTE: An Executive Summary is not due when the Final Technical Closeout Report is due.

0008A Manufacturing Summary

Report – Year 6 (Base Period)

Original – C.O.

Copy – P.O.

1 Electronic Copy – Sent to C.O. and P.O.

Within six (6) weeks of completion of the manufacture of the lot for HHS, a written report summarizing the campaign, cost of goods, and release documents must be submitted.

0008B Manufacturing Summary

Report – Year 7 (Base Period)

Original – C.O.

Copy – P.O.

1 Electronic Copy – Sent to C.O. and P.O.

Within six (6) weeks of completion of the manufacture of the lot for HHS, a written report summarizing the campaign, cost of goods, and release documents must be submitted.

0008C Manufacturing Summary

Report – Year 8 (Base Period)

Original – C.O.

Copy – P.O.

1 Electronic Copy – Sent to C.O. and P.O.

Within six (6) weeks of completion of the manufacture of the lot for HHS, a written report summarizing the campaign, cost of goods, and release documents must be submitted.

0009A Manufacturing Summary

Report - Option Year 1

Original – C.O.

Copy – P.O.

1 Electronic Copy – Sent to C.O. and P.O.

Within six (6) weeks of completion of the manufacture of the lot for HHS, a written report summarizing the campaign, cost of goods, and release documents must be submitted.

0009B

Report - Option Year 2

1 Electronic Copy – Sent to C.O. and P.O.

Within six (6) weeks of completion of the manufacture of the lot for HHS, a written report summarizing the campaign, cost of goods, and release documents must be submitted.

0009C

Report - Option Year 3

1 Electronic Copy – Sent to C.O. and P.O.

Within six (6) weeks of completion of the manufacture of the lot for HHS, a written report summarizing the campaign, cost of goods, and release documents must be submitted.

0009D

Report - Option Year 4

1 Electronic Copy – Sent to C.O. and P.O.

Within six (6) weeks of completion of the manufacture of the lot for HHS, a written report summarizing the campaign, cost of goods, and release documents must be submitted.

0009E

Report - Option Year 5

1 Electronic Copy – Sent to C.O. and P.O.

Within six (6) weeks of completion of the manufacture of the lot for HHS, a written report summarizing the campaign, cost of goods, and release documents must be submitted.

0009F

Report - Option Year 6

1 Electronic Copy – Sent to C.O. and P.O.

Within six (6) weeks of completion of the manufacture of the lot for HHS, a written report summarizing the campaign, cost of goods, and release documents must be submitted.

0009G

Report - Option Year 7

1 Electronic Copy – Sent to C.O. and P.O.

Within six (6) weeks of completion of the manufacture of the lot for HHS, a written report summarizing the campaign, cost of goods, and release documents must be submitted.

0009H

Report - Option Year 8

1 Electronic Copy – Sent to C.O. and P.O.

Within six (6) weeks of completion of the manufacture of the lot for HHS, a written report summarizing the campaign, cost of goods, and release documents must be submitted.

0009I

Report - Option Year 9

1 Electronic Copy – Sent to C.O. and P.O.

Within six (6) weeks of completion of the manufacture of the lot for HHS, a written report summarizing the campaign, cost of goods, and release documents must be submitted.

0009J

Report - Option Year 10

1 Electronic Copy – Sent to

Within six (6) weeks of completion of the manufacture of the lot for HHS, a written report summarizing the campaign, cost of goods, and

C.O. and P.O. release documents must be submitted.

0009K Manufacturing Summary Report - Option Year 11

Original – C.O.

Copy – P.O.

1 Electronic Copy – Sent to C.O. and P.O.

Within six (6) weeks of completion of the manufacture of the lot for HHS, a written report summarizing the campaign, cost of goods, and release documents must be submitted.

0009L Manufacturing Summary Report - Option Year 12

Original – C.O.

Copy – P.O.

1 Electronic Copy – Sent to C.O. and P.O.

Within six (6) weeks of completion of the manufacture of the lot for HHS, a written report summarizing the campaign, cost of goods, and release documents must be submitted.

0009M Manufacturing Summary Report - Option Year 13

Original – C.O.

Copy – P.O.

1 Electronic Copy – Sent to C.O. and P.O.

Within six (6) weeks of completion of the manufacture of the lot for HHS, a written report summarizing the campaign, cost of goods, and release documents must be submitted.

0009N Manufacturing Summary Report - Option Year 14

Original – C.O.

Copy – P.O.

1 Electronic Copy – Sent to C.O. and P.O.

Within six (6) weeks of completion of the manufacture of the lot for HHS, a written report summarizing the campaign, cost of goods, and release documents must be submitted.

0009O Manufacturing Summary Report - Option Year 15

Original – C.O.

Copy – P.O.

1 Electronic Copy – Sent to C.O. and P.O.

Within six (6) weeks of completion of the manufacture of the lot for HHS, a written report summarizing the campaign, cost of goods, and release documents must be submitted.

0009P Manufacturing Summary Report - Option Year 16

Original – C.O.

Copy – P.O.

1 Electronic Copy – Sent to C.O. and P.O.

Within six (6) weeks of completion of the manufacture of the lot for HHS, a written report summarizing the campaign, cost of goods, and release documents must be submitted.

0009Q Manufacturing Summary Report - Option Year 17

Original – C.O.

Copy – P.O.

1 Electronic Copy – Sent to C.O. and P.O.

Within six (6) weeks of completion of the manufacture of the lot for HHS, a written report summarizing the campaign, cost of goods, and release documents must be submitted.

F.3. OTHER CONTRACT DELIVERABLES:

CLIN Deliverable Quantity Due Date

0001 Overall Project Plan

(Milestone 1)

Original – C.O.

2 Copies – P.O.

1 Electronic Copy – Sent to C.O .and P.O.

Within three (3) months after contract award.

0002 Regulatory and Clinical Bridging

Study Plan

(Milestone 2)

Original – C.O.

2 Copies – P.O.

1 Electronic Copy – Sent to C.O. and P.O.

Within three (3) months after contract award.

0003 Facility Operation

Feasibility Plan

Original – C.O.

2 Copies – P.O.

1 Electronic Copy – Sent to

Within six (6) months after contract award.

(Milestone 3) C.O. and P.O.

0004 Detailed Manufacturing

Facility Plan

(Milestone 4)

Original – C.O.

2 Copies – P.O.

1 Electronic Copy – Sent to C.O. and P.O.

Within eight (8) months after contract award.

0005a Contactor Defined Milestones

(Milestone 5a – Seasonal Influenza Vaccine Program)

Original – C.O.

2 Copies – P.O.

1 Electronic Copy – Sent to C.O. and P.O.

Within nine (9) months after contract award.

0005b Contactor Defined Milestones

(Milestone 5b – Pandemic Influenza Vaccine Program)

Original – C.O.

2 Copies – P.O.

1 Electronic Copy – Sent to C.O. and P.O.

Within nine (9) months after contract award.

F.4 PLACE AND METHOD OF DELIVERY

(a) Delivery of contract deliverables specified in F.2 and F.3 above shall be F.O.B. destination, within consignee’s premises.

(b) Unless otherwise specified, deliveries shall be Monday through Friday (excluding Federal Holidays) between the hours of 8:30 a.m. and 5:00 p.m. EST only. Contract deliverables scheduled for delivery on a Federal holiday shall be made the following business day.

(c) Deliveries shall be made to the address specified in Section D.1.II.

F.5 FAR 52.252-2 CONTRACT CLAUSES INCORPORATED BY REFERENCE (Feb 1998)

This contract incorporates one or more solicitation clauses by reference, with the same force and effect as if they were given in full text. Upon request, the Contracting Officer will make their http://www.arnet.gov/

FAR CLAUSE TITLE DATE

52.242-15 Stop Work Order AUG 1989 52.242-15 Stop Work Order Alternate I AUG 1984 52.247-35 F.O.B. Destination, Within Consignee’s Premises APR 1984

SECTION G.--CONTRACT ADMINISTRATION DATA

G.1. CONTRACTING OFFICER

1) The Contracting Officer is the only individual who can legally commit the Government to the expenditure of public funds. No person other than the Contracting Officer can make any changes to the terms, conditions, general provisions or other stipulations of this contract.

2) 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.

3) No information, other than that which may be contained in an authorized modification to this contract, duly issued by the Contracting Officer, which may be received from any person employed by the United States Government, or otherwise, shall be considered grounds for deviation from any stipulation of this contract.

G.2. PROJECT OFFICER

The Government's Project Officer(s) will be:

[To be completed at contract award]

The Project Officer is responsible for: (1) monitoring the Contractor's technical progress, including the surveillance and assessment of performance and recommending to the Contracting Officer changes in requirements; (2) interpreting the statement of work and any other technical performance requirements; (3) performing technical evaluation as required; (4) performing technical inspections and acceptances…