RFP 2008-N-10242 IRR.doc

SOLICITATION, OFFER AND AWARD

1. THIS CONTRACT IS A RATED ORDER

UNDER DPAS (15 CFR 700)

RATING

PAGE OF

2. CONTRACT NO.

3. SOLICITATION NO.

2008-N-10242

4. TYPE OF SOLICITATION

X

NEGOTIATED (RFP)

5. DATE ISSUED

06/20/2008

6. REQUISITION/PURCHASE NO.

Centers for Disease Control and Prevention (CDC)

Procurement and Grants Office (PGO)

Acquisition & Assistance, Branch II, Team I

2920 Brandywine Road

Atlanta, GA 30341-5539

Approved as to Form and Legality: _____________________________

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

SOLICITATION

9. Sealed offers in original and 2 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 address in block 7., mailroom 1110 until

3:30PM

local time July 21, 2008 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

Jeff Miller

B. TELEPHONE (NO COLLECT CALLS)

AREA CODE NUMBER: EXT:

(770) 488-2651

C. E-MAIL ADDRESS

afx2@cdc.gov

11. TABLE OF CONTENTS

(x)

DESCRIPTION

(x)

DESCRIPTION

X

REPRESENTATIONS, CERTIFICATIONS, AND

OFFER (Must be fully completed by offeror)

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

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

13. DISCOUNT FOR PROMPT PAYMENT

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

10 CALENDAR DAYS

20 CALENDAR DAYS

30 CALENDAR DAYS

CODE

FACILITY

16. NAME AND ADDRESS OF PERSON AUTHORIZED TO SIGN OFFER

15B. TELEPHONE NO.

AREA CODE NUMBER EXT.

15C. CHECK IF REMITTANCE ADDRESS

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

23. SUBMIT INVOICES TO ADDRESS SHOWN IN

(4 copies unless otherwise specified)

ITEM

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

STANDARD FORM 33 (REV. 9-97)

PREVIOUS EDITION IS UNUSABLE

Prescribed by GSA

FAR (48 CFR) 53.214©

Section A – Solicitation/Contract Form (Continued)

EXECUTIVE SUMMARY

1. Description of the Item(s)/Service(s) being procured:

The Statement of Work (SOW) establishes the requirements for Contractor provided services to include the necessary management and personnel required to provide influenza reagent resource (IRR) services in accordance with the terms, conditions, clauses, provisions, attachments, and specifications included in this solicitation and subsequent contract.

2. Type of Contract:

Cost-reimbursement service contract that is the best value to the Government. Cost-reimbursement type contracts provide for payment of allowable incurred costs, to the extent prescribed in the contract. This contract will establish an estimate of total cost for the purpose of obligating funds and establishing a ceiling that the contractor may not exceed (except at its own risk) without the approval of the Contracting Officer.

3. Format of the Contract:

An initial one (1) year contract with nine (9), one (1) year options

4. The North American Industry Classification System (NAICS):

The NAICS code for this acquisition is 621511. The small business size standard is $5.0 million.

5. Unusual/Specific Aspects of the Acquisition:

Intellectual Property Rights

a. Intellectual property rights to all processes, procedures, protocols, patents, copyrights, etc., developed under this contract shall become and remain the property of the US Government (USG).

Government Ownership of Materials

b. All materials acquired and/or developed under this contract shall become and remain the property of the Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Immunization Division (CDC/NCIRD/ID) unless specifically authorized by the USG Contracting Officer and Project Officer.

Review of Data

c. The CDC Contracting Officer and Project Officer must review any materials or data generated under this contract prior to dissemination, release or publication by the Contractor. Review and approval shall be performed in accordance with the current CDC policies and procedures.

Dissemination of Information

d. No information related to data obtained or collected under this contract shall be released or published (including all publications) without the prior written consent of the CDC Contracting Officer and Project Officer and also reviewed and approved by the CDC Office of Communication prior to publication.

6. Contract Administration:

Please submit any and all questions in writing to afx2@cdc.gov. See Section L, clause L.12.

7. Additional information

a) See Section L for important information as to what is required to be submitted in response to this request for proposal and also that all questions must be submitted no later than June 30, 2008.

b) Biosafety and Security Requirements: Prior to commencement of work, the Contractor will submit in writing its plan for complying with the safety and health provisions of this contract and shall meet with the Contracting Officer or his/her designee to discuss and provide the safety plan. If live viruses or inactivated materials will be used the Contractor must comply with all applicable HHS and USDA safety and security requirements and must show evidence of appropriate biosafety containment and Select Agent Program compliance if applicable. (Additional information will be provided).

c) To be considered for award of this contract, the technical proposal submission must demonstrate that the offeror is USDA-approved BSL3 Enhanced; or, USDA-approved BSL3 Enhanced Laboratory, for purposes of this acquisition. In addition, Select Agent registration is required.

d) Government-Furnished and/or Contractor Acquired Property Within 30 days of Project Officer approval of contractor Standard Operating Procedures for handling and storage of viruses and reference reagents, the government will provide 75* different contemporary human influenza viruses; 42* highly pathogenic avian influenza viruses and other non-contemporary human influenza viruses; and, 40* non-influenza viruses, antiviral resistant influenza viruses and bacterial respiratory pathogens; under the provisions of a Materials Transfer Agreement to be signed at the time of contract award. On average, 20* additional influenza virus strains and a maximum of 5* additional non-influenza pathogens will be submitted each year to update the composition of the panels. The government will also provide the contractor with sequence information and PCR protocols necessary for molecular analysis of certain strains to be included in the repository.

Section B - Supplies Or Services And Prices/Costs

B.1 Description of Services

The Contractor will propagate, characterize, store and distribute (as approved) CDC-furnished viruses and bacterial pathogens, including human influenza, low and highly pathogenic avian influenza viruses and their derivatives, and other viral and microbial respiratory pathogens associated with influenza-like illness in accordance with all terms, conditions, clauses, provisions, attachments, and specifications included in this solicitation and subsequent contract.

B.2 HHSAR 352.232-74 Estimated Cost and Fixed Fee -- Incrementally Funded

Contract (Apr 1984)

(a) It is estimated that the total cost to the Government for full performance of this contract will be $______________, of which the sum of $_______________ represents the estimated reimbursable costs and $________________ represents the fixed-fee.

(b) Total funds currently available for payment and allotted to this contract are $_______________, of which $_________________ represents the estimated reimbursable costs and $______________ represents the fixed-fee. For further provisions on funding, see the Limitation of Funds clause.

(c) It is estimated that the amount currently allotted will cover performance through (date) ________________.

(d) The Contracting Officer may allot additional funds to the contract without the concurrence of the Contractor.

B.3 Contract Line Item Numbers (CLINS)

BASE YEAR (YEAR I OF THE CONTRACT) 9-15-2008 THROUGH 9-14-2009

TOTAL PRICE – BASE YEAR $_______________

OPTION YEAR I (YEAR II OF THE CONTRACT) 9-15-2009 THROUGH 9-14-2010

TOTAL PRICE – OPTION YEAR I $_______________

OPTION YEAR II (YEAR III OF THE CONTRACT) 9-15-2010 THROUGH 9-14-2011

TOTAL PRICE – OPTION YEAR II $_______________

OPTION YEAR III (YEAR IV OF THE CONTRACT) 9-15-2011 THROUGH 9-14-2012

TOTAL PRICE – OPTION YEAR III $_______________

OPTION YEAR IV (YEAR V OF THE CONTRACT) 9-15-2012 THROUGH 9-14-2013

TOTAL PRICE – OPTION YEAR IV $_______________

OPTION YEAR V (YEAR VI OF THE CONTRACT) 9-15-2013 THROUGH 9-14-2014

TOTAL PRICE – OPTION YEAR V $_______________

OPTION YEAR VI (YEAR VII OF THE CONTRACT) 9-15-2014 THROUGH 9-14-2015

TOTAL PRICE – OPTION YEAR VI $_______________

OPTION YEAR VII (YEAR VIII OF THE CONTRACT) 9-15-2015 THROUGH 9-14-2016

TOTAL PRICE – OPTION YEAR VII $_______________

OPTION YEAR VIII (YEAR IX OF THE CONTRACT) 9-15-2016 THROUGH 9-14-2017

TOTAL PRICE – OPTION YEAR VIII $_______________

OPTION YEAR IX (YEAR X OF THE CONTRACT) 9-15-2017 THROUGH 9-14-2018

TOTAL PRICE – OPTION YEAR IX $_________________

TOTAL AGGREGATE COST (BASE AND ALL OPTION YEARS) $________________

Section C - Description/Specification/Work Statement

I.

Background and Need The National Strategy for Pandemic Influenza, issued by President Bush on November 1, 2005, guides our nation's preparedness and response to an influenza pandemic, with the intent of (1) stopping, slowing or otherwise limiting the spread of a pandemic to the United States; (2) limiting the domestic spread of a pandemic, and mitigating disease, suffering and death; and (3) sustaining infrastructure and mitigating impact to the economy and the functioning of society.

The Implementation Plan for the National Strategy, released by the President on May 3, 2006, translates the Strategy into more than 300 actions for Federal departments and agencies and sets clear expectations for State and Local governments and other non-Federal entities. It also provides guidance for all Federal departments and agencies on the development of their own plans.

The Strategy charges the U.S. Department of Health and Human Services (DHHS) with leading the federal pandemic preparedness. Within the DHHS, the Centers for Disease Control and Prevention (CDC), is responsible for detecting the onset of outbreaks with influenza pandemic potential; assisting the containment of such outbreaks; delaying the introduction and transmission of pandemic viruses in the United States; and, assisting State, Local and Territorial (SLTT) health authorities in the management of an influenza pandemic event.

Within the CDC, the Influenza Division is responsible for providing laboratory support to the public health and medical sectors to minimize the impact of an influenza pandemic on the health of Americans.

This contract is a critical component of CDC’s extramural efforts to ensure the availability of influenza viruses and diagnostic reagents for public health responses; and, the ability to provide enhanced technical assistance and materials to state and local public health laboratories and commercial developers of vaccines, antiviral drugs and diagnostic tests, in support of our common goal to minimize the impact of an influenza pandemic on the health of Americans.

II.

Project Objectives

The objectives of this contract are:

1.

To ensure that adequate stocks of influenza viruses and reference reagents are available to the CDC on a routine basis (see Appendix A - Quantity “A”); and, for selected products, in the event of an influenza pandemic (see Appendix A - Quantity “B” - Option);

2.

To implement a Proficiency Testing (PT) program, to routinely verify that public health and selected other laboratories are able to adequately characterize circulating seasonal and other non-circulating or novel influenza viruses; and, 3.

To improve access to these materials to qualified public health professionals, clinicians, researchers and developers of influenza vaccines, antiviral drugs, and influenza virus diagnostic products.

Special note: This is a new CDC requirement. All quantities presented with asterisk notation (1*, 2*, 3*, etc.) in this Statement of Work (including Appendices) reflect the government’s best estimates of anticipated need during each year of contract performance. Estimates are based on annual usage projections and include a minimum inventory quantity which the government considers necessary and appropriate for each item; they are being provided to assist potential offerors in formulating estimated costs of performance; and, are not intended to restrict in any way the government’s ability to request more or less than stated quantities of viruses, reagents, kits, etc., during actual performance of the contract.

This is a cost reimbursement requirements type contract with options, which will be funded to meet anticipated routine (Quantity “A”) needs of the government. In the event of an influenza pandemic, additional funding would be made available to meet anticipated surge (Quantity “B” – Option) requirements of the contract.

Special Notes:

Quantity A Items: Contractor inventories shall be fully stocked by the end of Year 1, and maintained thereafter in accordance with current government priorities. The contractor’s acquisition, production and manufacturing plans shall be reviewed by the government on at least an annual basis; and, approved in writing by the Project Officer prior to implementation. This is intended to ensure that contractor inventory levels are reviewed on a routine basis, and adjusted as may be required to meet the changing needs of the program (see Appendix A).

Quantity B Items: In the event that Quantity B (Option) quantities are authorized for performance, it shall be understood that contractor delivery of selected items will be required as soon as possible to meet an imminent threat to the nation’s public health. The contractor shall establish, plan, routinely test and update emergency acquisition, production and manufacturing plans to respond to such an event (see Appendices A and B).

III. Scope of Work

The contractor will propagate, characterize, store and distribute (as approved) CDC-furnished viruses and bacterial pathogens, including human influenza, low and highly pathogenic avian influenza viruses and their derivatives, and other viral and microbial respiratory pathogens associated with influenza-like illness.

In addition, the contractor will produce or otherwise acquire, characterize, store and distribute (as approved) the below listed reagents, which include human sera, animal sera, animal anti-sera, DNA plasmids, RNA standards, antigens, antibodies, nucleic acids and lyophilized primers and probes.

Viruses and reagents will be available to qualified recipients, both individually and as parts of standardized panels and kits, to aid in the development, evaluation, validation and testing of influenza diagnostic products; to support vaccine development; and, to assist in characterization of viruses as part of influenza surveillance activities.

With the exceptions of WHO Influenza Reference Reagent Kits (Item 7 below), and Animal Antisera Against Influenza Viruses (Item 15 below), all viruses and reagents will be manufactured (to the maximum extent practicable) in accordance with Good Manufacturing Practices (GMP) or GMP-like processes, in a Good Laboratory Practices (GLP) laboratory environment; see Section IV.E.6 of the Statement of Work (SOW).

The CDC Influenza Reagent Resource inventory of viruses and reagents will be regularly updated during contract performance, to ensure that current panels for development, validation and proficiency testing are on-hand and available for distribution (see Appendix A).

1. Human Influenza Virus Real-Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) Detection and Characterization Kits;

2. Hemaggluttinin Inhibition Assay kits for detection of hemagglutinating antibodies in human sera against seasonal and animal influenza viruses, including avian;

3. Virus Microneutralization Assay kits for detection of neutralizing antibodies in human sera against seasonal and animal influenza viruses, including avian;

4. live seasonal and live and beta-propiolactone (BPL)-killed animal influenza viruses for use in Virus Microneutralization and Hemaggluttinin Inhibition Assay kits;

5. WHO Influenza reference reagent kits for identification of seasonal and animal influenza isolates, including avian, from human cases. These reagents are for use at National Influenza Centers (NIC) and Global Influenza Surveilance Network (GISN) and U.S. Public Health Laboratories;

6. live influenza seed stocks;

7. purified influenza virus stocks;

8. Specific panels of viruses and/or bacteria:

a. Seasonal Panels;

b. Development Panels;

c. Proficiency Panels;

d. Specificity Panels;

e. Antiviral-Resistance Panels;

f. Independent Evaluation Panels;

9. nucleic acids from influenza and other respiratory agents, to use as viral test standards;

10. Other kits as available;

11. Other reagents/kits: available individually or as kit/panel components:

a. lyophilized primers and probes for:

1) diagnostic testing for other respiratory viral and bacterial agents (see

Appendix C); and,

2) antiviral resistance testing of influenza viruses (see Appendix C).

b. plasmid DNA with relevant influenza gene sequences;

c. RNA Standards for controls for RNA based detection systems;

d. recombinant expressed influenza viral antigens (see Appendix D);

e. monoclonal and polyclonal antibodies to influenza viral antigens;

f. Animal antisera and hyperimmune antisera against influenza viruses (rabbit, ferret, sheep, etc.); see Appendix E.

g. normal human sera;

h. cell lines required for virus growth and antigenic determination of influenza viruses;

i. real-time one step RT-PCR reagent kits, Nucleic acid extraction kits and other reagents for use with influenza real time RT-PCR testing;

j. lyophilized or otherwise modified enzymes for diagnostic testing for influenza and other respiratory viral and bacterial agents; and,

k. Influenza Neuraminidase (NA) Inhibition Resistance detection kits (NA Star®) or other approved assay for the functional detection of NA inhibition.

Products in the Influenza Reagent Resource will be provided to qualified persons and institutions as determined by criteria provided by the project officer. Access to these resources will be made through an electronic “storefront” website as described in IV.J.1 below. In addition, the CDC Project Officer will periodically request transfer of selected products from the Influenza Reagent Resource to the National Institute of Allergy and Infectious Diseases (NIAID/NIH) for inclusion in the Biodefense and Emerging Infections Research Resources Repository (http://www.beiresources.org/).

IV. Detailed Technical Requirements

Independently and not as an agent of the government, the contractor shall provide all management, labor, facilities, materials, supplies and equipment necessary to establish, operate and maintain the “CDC Influenza Reagent Resource”, as set forth below.

More specifically, the contractor shall:

A.

Develop Standard Operating Procedures (SOPs)

Prior to performance of any task requirement of this contract, the contractor shall develop draft Standard Operating Procedures (SOPs), consistent with the methodology and approach reflected in the contractor’s technical proposal to address proper contractor receipt, handling, storage and shipment of viruses and reference reagents; and, contractor performance of all contract tasks. The contractor shall establish and validate the SOP for sterility and innocuity testing of inactivated H5N1 (or equivalent BSL3+ agents) virus panels or any other materials derived from infectious raw materials. Draft SOPs shall be provided to the Project Officer for review and comment, within 30 days of contract award. The Project Officer shall review draft SOPs and furnish written comments to the contractor within 30 days of receipt. The contractor shall address the Project Officer’s comments in writing; and, submit final Standard Operating Procedures to the Project Officer for review and approval within 75 days of contract award. The Project Officer shall review and approve final SOPs or furnish additional comments to the contractor within 15 days of receipt.

Project Officer approval of the SOP for any given task shall be obtained before the contractor shall be authorized to initiate any work under that task. SOPs shall be in full compliance with all international, federal, state and local laws and regulations; and, World Health Organization guidelines; especially in the areas of bio-safety and security. The contractor’s Institutional Biosafety Committee will be required to approve SOPs prior to release of such materials.

B. Establish a Virus Resource Program for Influenza and Related Reagents

By no later than 30 days after government approval of the contractor’s SOP for receipt, handling, storage and shipment of viruses and reference reagents; and, under the provisions of an MTA to be initiated as soon as practicable after contract award, the government will provide the contractor:

a. 75* different contemporary human influenza viruses;

b. 42* highly pathogenic avian influenza viruses and other non-contemporary human influenza viruses; and, c.

40* non-influenza viruses, antiviral-resistant influenza viruses and bacterial respiratory pathogens.

A list of viruses to be provided to the contractor can be found at Appendix A. Restricted viruses may require documentation in addition to an MTA to facilitate their transfer.

Propagate influenza viral strains in Madin-Darby canine kidney (MDCK) cell culture and/or embryonated eggs under conditions that maintain maximum infectivity and integrity while minimizing sequential passages to reduce genetic/antigenic change. Antiviral-resistant strains may require sequence analysis to confirm absence of reversion of the antiviral genotype.

Characterize influenza viral stocks by measuring the following parameters:

a.

Hemagglutinin titer by hemagglutination of chicken, turkey, guinea pig or other red blood cells, as appropriate.

b. Infectious influenza virus titer by endpoint dilution and inoculation into embryonated chicken eggs or MDCK cells, as appropriate, to establish the median tissue culture infectious dose (TCID50) or median egg infectious dose (EID50) of the materials.

c. Relative viral genomic RNA concentrations determined by real-time RT-PCR.

C.

Assemble Influenza and Other Reagent Panels and Kits

1.

Human Influenza Virus Five Target Real-Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR): The contractor shall develop or otherwise acquire, store, and distribute 1000* kits containing lyophilized polymerase chain reaction (PCR) primers, lyophilized dual-labeled fluorescent probes, and controls; Influenza primers and probes for up to 8 signatures manufactured using detailed sequence information and according to CDC specifications (see Appendices A and B). Each signature is comprised of 1 probe labeled with fluorophor and black hole quencher and 2 unlabeled primers. Lyophilized primer/probe signatures will be assembled and made available as 3 component kits and/or as separate signatures. The use of these reagents will be to provide epidemiologic information for surveillance for seasonal and novel influenza viruses.

2.

Commercial kits: Roche MagNA Pure Compact RNA Isolation Kit, Qiagen RNAeasy® Mini kit, Invitrogen SuperScript™ III Platinum® One-Step Quantitative kit, NA Star® Influenza Neuraminidase (NA) Inhibition Resistance detection kits or other kits as identified by the Project Officer.

3.

Hemaggluttinin Inhibition Kits: The contractor shall develop or otherwise acquire, store and distribute 150* kits containing negative human sera, positive control sera, and live or inactivated viruses to assess hemaggluttinating antibodies in human sera. Kits will be developed in three formats: (1) vaccine kits will include 3 live viruses which correspond to the current seasonal vaccine; (2) seasonal kits will include an average of 5* circulating strains; and (3) avian kits will include an average of 5* inactivated avian influenza viruses (see Appendices A and F).

4.

Virus Microneutralization (MN) Assay Reagent Kit: The contractor shall develop or otherwise acquire, store and distribute 150* kits containing Negative human sera, Anti-nucleoprotein (NP) monoclonal antibody, and Goat Anti-mouse IgG-horse-radish peroxidase (HRP) conjugate substrate for detection of neutralizing antibodies in human sera (see Appendices A and G).

5.

MN Assay Viral Kit: The contractor shall develop or otherwise acquire, store and distribute 150* MN Assay Viral Kits for detecting antibodies to seasonal vaccine influenza viruses (H3N2, H1N1, and B strain contained in the yearly seasonal vaccine). Kits will also include either three highly pathogenic avian wild type H5N1 influenza viruses for use in BSL3+ conditions; or, three reassortant avian influenza viruse strains representing different H5N1 clades and subclades for use in BSL2 conditions. The contractor will acquire virus specific animal antisera to be used as controls in the MN Assay Viral Kits (see Appendices A, E, H and I).

6.

WHO Influenza Reference Reagent Kits: The contractor shall prepare or otherwise acquire, assemble, store and distribute 400* kits containing reference reagents listed in Appendix E to National Influenza Centers (NIC), Global Influenza Surveilance Network (GISN) Laboratories, Public Health Laboratories, academics, and other recipients, as approved by the Project Officer. In addition, the contractor shall prepare, or otherwise acquire and store 200* individual kit components for distribution to laboratories, as approved by the Project Officer. With reference to Section IV.E.6 of the Statement of Work, these kits do not have to be manufactured at GMP or GMP-like quality processes (see Appendices A and H).

7.

Individual Viruses: The contractor shall prepare or otherwise acquire, aliquot and store 117* influenza viruses, to be made available to the CDC, public health partners, developers and researchers, as approved by the Project Officer. These viruses will be available for distribution in individual units in an “a la carte” fashion. This may include preparation of reference reagents to include live viruses and inactivated viruses including BioSafety Level (BSL) 2 and BSL3 enhanced (BSL3+) viruses in aliquots with a volume of at least 0.5 milliliter with virus concentrations ranging from 1 x 106-109 infectious particles per milliliter or the molecular equivalent as determined by a quantitative assay (unless otherwise specified by the Project Officer) or nucleic acids in 1-10 microgram aliquots with a volume of at least 10-100 microliliters. The contractor shall receive, propagate, aliquot, characterize and store 20* additional contemporary and non-contemporary human or animal influenza viruses per year and update the composition of the reagent matrices and panels to be distributed to represent the most relevant circulating strains (see Appendix A).

8.

Evaluation Panels: The panels will consist of viruses and bacterial agents and will require quarterly composition review and possible update to include the most recent relevant variant strains, as specified by the Project Officer.

a. Seasonal Panel: The contractor shall prepare, store and distribute 150* panels containing 9* influenza viruses in matrices, including vaccine strains from the current seasonal vaccine, to be specified by the Project Officer. This panel is intended to provide: 1) two strains of the most currently circulating H3N2 viruses, 2) two strains of the most currently circulating H1N1 viruses and 3) two strains of the most currently circulating B viruses. Reference reagents must be quantified to reflect relative viral infectivity (EID50 or TCID50) as well as protein and/or nucleic acid concentrations if needed. Relative viral genomic RNA concentrations will be determined by real-time RT-PCR.

b.

Development Panel: The contractor shall prepare, store and distribute 150* panels including all of the components of the “Seasonal Panel” plus three subtypes of human or avian H5N1 viruses. Panels will fall into one of four categories: BSL2 Live, BSL2 Inactivated, BSL3+ Live, and BSL3+ Inactivated. BSL2 Live panels will include H5N1 vaccine reassortant strains in place of the H5N1 wild type strain. BSL3+ Live panels will contain wild type live strains. BSL3+ Inactivated panels will contain inactivated wild type strains which the contractor must confirm innocuity of the strains and obtain approval from the Project Officer before distribution. Reference reagents must be quantified to reflect relative viral infectivity (EID50 or TCID50) as well as protein and/or nucleic acid concentrations if needed. Relative viral genomic RNA concentrations will be determined by real-time RT-PCR.

c.

Proficiency Panel: The contractor shall prepare, store and distribute 200* blinded panels containing 10* influenza viruses in a matrix, to be specified by the Project Officer. Reference reagents must be quantified to reflect relative viral infectivity (EID50 or TCID50) as well as protein and/or nucleic acid concentrations if needed. Relative viral genomic RNA concentrations will be determined by real-time RT-PCR. These panels will be blind-coded prior to distribution, as specified by the Project Officer. The contractor shall provide instructions for the recipient for safe handling of the panel and of reporting requirements and timelines (see Appendix J).

d.

Specificity Panel: The contractor shall develop or otherwise acquire, store and distribute 150* specificity panels containing, in part or whole, 40* different non-influenza human viral and bacterial pathogens associated with respiratory disease and influenza-like illness, as well as bacteria representative of the commensal flora of the respiratory tract and influenza strains as positive controls. Such panels will contain characterized microorganisms by positive identification tests to determine genus and species as well as the concentration of the infectious agent by endpoint dilution and evidence of growth following inoculation into appropriate indicator substrate systems. Inactivated materials will be quantified by validated molecular tests. The contractor shall receive, propagate, aliquot, characterize and store 5* additional non-influenza viral and bacterial respiratory pathogens per year to update the composition of the reagent matrices and panels to be distributed.

e.

Antiviral Resistance Panel: The contractor shall develop or otherwise acquire, store and distribute 150* panels containing 10* antiviral-resistant influenza viruses in varying concentrations, representing different genotypic and phenotypic variants, in a panel of antiviral-resistant and antiviral-sensitive influenza viruses. Such panels will contain characterized microorganisms by positive identification tests to determine subtype as well as the concentration of the infectious virus by endpoint dilution and evidence of growth following inoculation into appropriate indicator substrate systems. Inactivated materials will be quantified by validated molecular tests. Sequence analysis is required to confirm non-regression of antiviral resistant strain.

f.

Independent Evaluation Panel: The contractor shall assemble and distribute 150* Independent Evaluation panels containing 50* different microorganisms, including contemporary and non-contemporary human influenza viruses, highly pathogenic influenza viruses and other respiratory pathogens or commensals of human origin to be distributed as open or blinded panels for independent evaluation of diagnostic test prototypes. Panels will fall into one of four categories: BSL2 Live, BSL2 Inactivated, BSL3+ Live, or BSL3+ Inactivated. BSL2 Live panels will include H5N1 vaccine reassortant strains in place of the H5N1 wild type strain. BSL3+ Live panels will contain wild type live strains BSL3+ Inactivated panels will contain inactivated wild type strains which the contractor must confirm innocuity of the strains and obtain approval from the Project Officer before distribution. Panels may contain live or inactivated viruses and bacteria that are characterized quantitatively; see Section IV.B.3 of the Statement of Work.

9.

Additional kits. The CDC is sponsoring the development of additional reagents and kits (not currently listed in Appendix B) that will be appropriate for purchase and distribution under this contract, upon completion of validation and testing of these products. However, it would be extremely difficult for the government to describe this requirement in advance, at any level of precision; and, it would be equally difficult for potential offerors to accurately estimate costs of performing this requirement. To ensure that this essential capacity is built into the contract, while ensuring a level playing field for evaluation of competitive proposals, potential offerors are instructed to anticipate that such costs will not exceed $50,000 (total direct cost) per year.

D.

Establish, Operate and Maintain an Inventory of Influenza Reagents

The contractor shall produce reference reagents, as authorized by the Project Officer. Production of reference reagents shall include expansion of renewable reference reagents, e.g., includes cell lines, monoclonal and polyclonal antibodies, proteins, viral and expressed antigen, primers and probes and DNA clones. A list of reference reagents to be produced can be found at Appendix A; however, this list should be considered a work in progress, which the government may update from time to time during contract performance.

E.

Maintain Quality Control of Viruses and Reference Reagents

The contractor shall perform stability testing and determine shelf life of selected reagent panels, virus, viral RNA, cells and other reagents containing materials held under appropriate storage conditions to be shipped to requestors; and, clearly communicate the expiration date of all reference reagents stored under specified conditions to requestors. Prior to distribution of new lots of frozen reagents, the contractor shall perform stability testing. The contractor will provide the results of all stability testing prior to distribution.

The contractor shall maintain quality control of viruses and reference reagents. Quality control includes assay and evaluation of reference reagents following established SOPs that incorporate quality control procedures as part of an overall quality assurance (QA) program. Quality control testing shall be performed to confirm consistency of reagent performance and integrity as defined by CDC standards.

Assays used for quality assurance shall include but are not limited to sterility, stability, solubility, neutralization, HPLC, restriction enzyme analysis, polymerase chain reactions, immunoblotting and IN SITU hybridizations. A minimum of two applicable assays for each reagent/kit/panel will need to be performed and approved by the Project Officer prior to contractor distribution. The contractor shall anticipate assays using antibodies and antisera, cell lines, primers and probes, lysates, nucleic acids, protein and peptide preparations; however, this list should be considered a work in progress, which the government may update from time to time during contract performance.

Quality Assurance supervision will be provided by an independently reporting unit within the organization or an independent consulting organization.

4.

QA and QC activities will ensure that the assay SOPs utilized by the laboratory are approved by the Project Officer, fully validated for uses and supported by published evidence of reliability with regards to key performance parameters.

5.

Quantification assays will be validated by including external and internal standards, and controls that meet a precision goal of no more than 5-10% coefficient of variation (CV) for intra- and inter-assay precision. The number and types of assays to be performed will require the prior approval by the Project Officer.

6.

With the exceptions of WHO Influenza Reference Reagent Kits (see Section III, Item 8 of the SOW), and Animal Antisera Against Influenza Viruses (Section III, Item 15 of the SOW), all viruses, reagents, panels and kits that are produced or otherwise acquired, stored and distributed under this contract shall be manufactured (to the maximum extent practicable) in compliance with Good Manufacturing Practices (GMP) or GMP-like processes, in a Good Laboratory Practices (GLP) laboratory environment; see: http://www.fda.gov/cdrh/devadvice/32.html.

The contractor shall obtain approval of the Project Officer prior to purchase or development of viruses, reagents, panels and/or kits that are not compliant with the processes described above.

F.

Facility Requirements

1.

The contractor shall provide facilities and equipment to receive, handle, propagate, aliquot, fully characterize, vial, weigh, store and ship potentially hazardous viruses and reference reagents while maintaining their activity and/or viability under BSL2 and BSL3+ containment conditions, as appropriate. BSL-4 facilities are not required under this contract. Information regarding requirements for these facilities can be found at http://bmbl.od.nih.gov/contents.htm; and http://www.cdc.gov.od.ohs.biosfty/bmbl4/bmbl4oc.htm

Handling open containers of live wild-type highly pathogenic influenza H5N1 viruses shall be conducted only in a USDA-approved BSL3+ containment facility. Information regarding BSL3 enhancements, USDA permits, and select agent needs for working with live virus are described at http://www.cdc.gov/flu/h2n2BSL3.htm.

2.

CDC and USDA approved laboratory facilities and SOPs for work with highly pathogenic influenza viruses and other respiratory pathogens of human and animal origin in BSL3+ conditions shall be available for inspection at the time of contract award.

3.

USDA Select Agent Program, with approved laboratory facilities, personnel and SOPs for work with highly pathogenic and exotic avian influenza viruses as well as other respiratory pathogens of human and animal origin shall be available for inspection at the time of award. (Examples of strains to be included in the virus panels can be found at Appendix A).

4.

The contractor shall have accredited BSL2 and BSL3+ animal facilities as governed by the Institutional Animal Care and Use Committee (IACUC) and Association for the Assessment and Accreditation of Laboratory Animal Care International (AAALAC).

5.

Facility design and SOP for storage conditions include validation procedures and all necessary evidence that the integrity of virus and bacterial stocks, proteins and nucleic acids will be maintained and the risk of accidents or contamination is minimized.

6.

Laboratory, storage and shipping facilities, and SOPs for BSL3+ highly pathogenic and exotic avian influenza viruses and other respiratory pathogens of human and animal origin, as well as BSL2 facilities for work with seasonal influenza A and B viruses and other respiratory pathogens are available for inspection no later than the time of award. USDA Select Agent program shall be in place by no later than the date of contract award.

7.

The contractor shall provide suitable air-conditioned floor space sufficient for the installation, storage and maintenance of equipment and all items necessary for the virus storage and distribution operation. Refrigeration and cryogenic equipment units will be housed in an air-conditioned facility with the capacity to maintain a room temperature of 66 to 72 °F, when all equipment is operational.

8.

The contractor shall provide, maintain and operate facilities for the storage of virus collections and derived reagent panels at 2 to 8°C., at -10 to -20 °C., at -70 to -90 °C, and liquid nitrogen conditions.

9.

The contractor shall provide uninterruptible power supply to accommodate the refrigerators/freezers and other critical security and surveillance equipment.

10. The contractor shall ensure that refrigerators, freezers, and incubators are connected to a central alarm system that is monitored 24 hours per day. Emergency stand-by refrigerators and freezers shall be available in case of mechanical failure of storage space.

11. The contractor shall provide, maintain and operate surveillance systems to assure that the stored materials remain accessible only to authorized personnel. The contractor should utilize state-of-the-art electronic security system with fail secure locking hardware to ensure controlled access to all of the designated virus storage areas of the contractor’s facility. A minimum of two separate levels or layers of physical and electronic security shall be employed. These levels of security may be increased at any time during the life of the contract if the federal government's security guidelines for facilities are modified.

12. The contractor shall develop and implement procedures to track and catalog, at both prime and subcontractor locations, the handling and manipulation of the stores of infectious disease agents and materials related to these agents. All computer systems shall utilize state-of-the-art software firewalls, computer security systems and encryption approved by Department of Health and Human Services (DHHS) and other computer software to prevent unauthorized access to the computer system and to prevent ‘hacking’ by those outside the secure system. A separate electronic record-keeping system will be established for Select Agents.

13. The contractor shall establish an administrative audit and control

SOP to ensure that virus panels distributed to requestors have met all the requirements set forth by the provider of the virus specimens and the Project Officer.

14.

The contractor shall establish archival systems to ensure that all the transaction records, including Material Transfer Agreements are kept and accessible and electronic copies stored off-site.

15.

The contractor shall provide protective garments, equipment and sufficient training and monitoring to assure safe handling of biohazard materials. More specifically, the contractor shall comply with all applicable health and safety regulations and standards (http://www.cdc.gov/od/ohs/biosfty/biosfty.htm) while performing the requirements of this contract (see Appendix L).

G.

Process Requests for Viruses and Reference Reagents from Qualified Recipients, Subject to Project Officer Approval

1. The contractor shall develop an SOP to receive, acknowledge and process requests for viruses, panels and/or other reference reagents, from requestors, as set forth below; and, the SOP shall be approved in writing by the Project Officer prior to implementation.

All requests for viruses, panels and/or reference reagents shall be approved by the Project Officer for shipment and delivery to qualified recipients only.

The contractor shall process requests from qualified recipients within five (5) days of Project Officer approval. The contractor will retain the following written documentation in support of each request:

a. copy of the original request

b. copy of the Project Officer’s written approval or disapproval

c. record of shipment

d. written confirmation of receipt by intended recipient

e. copies of any required MTAs, supporting documentation, permits, etc.

f. record of any problems experienced, delays, etc..

In addition, a formal shipping/receipt log will be maintained to document the date that each of the above actions occurred.

Note: Some shipments will require execution of an MTA (see Appendix K); and, some shipments will require execution of an MTA plus additional documentation, permits, etc. In any case, the contractor will process requests from qualified recipients within five (5) days of Project Officer approval. Both the requestor and the Project Officer will be kept informed of any problems that might delay shipment, steps being taken to mitigate the extent of any delays, and the target date for shipment.

The contractor shall comply with all federal, state and local regulations governing access, distribution within a facility, shipment to other facilities, transport, and use of CDC and/or USDA Select Agents (http://www.bt.cdc.gov/Agent/Agentlist.asp).

4.

The contractor shall verify that transfer of virus panels to requestors are in compliance with the requirements of the Select Agents program and all international, federal, state and local biosafety regulations.

5.

The contractor shall distribute materials (e.g., live virus, inactivated virus, viral RNA) either individually or as panels in response to Project Officer approved requests from qualified recipients, in compliance with all international, federal, state and local laws and regulations. Specific materials will be transferred to requestors under the provisions of a Materials Transfer Agreement (MTA) that will specify the appropriate use of the viral strains, panels, and products (see Appendix K). In addition to other assurances, viruses and reference reagents shall be transferred in compliance with all relevant standards and regulations for safe handling, use and shipment of research reagents.

6.

The contractor shall obtain written agreements from recipient investigators and their institutions to indemnify and hold harmless the United States of America, the Department of Health and Human Services (DHHS), the Centers for Disease Control and Prevention (CDC), its contractor, their suppliers, and contributors of reference reagents from any claims, costs, damages, or expenses. The contractor shall secure and update/modify these agreements, as requested by the Project Officer.

7.

As requested by the Project Officer, the contractor shall develop and update form letters to be used for acceptance and refusal of requests for viruses and reference reagents.

8.

The contractor shall ensure that shipping is performed in compliance with all international, federal, state and local laws and regulations for distribution of infectious materials. The contractor shall utilize shipping containers for viruses and reference reagents that fully comply with current domestic and international transport regulations and pertinent (IATA) International Air Transport Association/International Civil Aviation Organization Dangerous Goods Regulations (http://www1.iata.org/cargo/dg/index).

Shipping containers must provide a sufficient margin of safety for maintaining appropriate environmental…