IRR-SOW-2-26-28.doc

RFC – Attachment 1 STATEMENT OF WORK – 2/26/2008 (Draft) “CDC Influenza Reagent Resource (CDC-IRR)” 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 (Quantity “A”); and for selected products, in the event of an influenza pandemic (Quantity “B” – Option); see Appendix A.

2.

to improve availability of these materials to qualified public health professionals, clinicians and developers of influenza vaccines, antiviral drugs and influenza virus diagnostic products, through an electronic storefront (website); and,

3. 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.

Special note: This is a new CDC requirement. All quantities presented with asterisk notation (1*, 2*, 3*, etc.) in this Statement of Work reflect the government’s best estimates of anticipated need during performance of the contract. 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 annually, 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.

III. Scope of Work

The contractor will propagate, characterize and 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 (see Appendix A) 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.

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. Specificity Panels;

d. Independent Evaluation Panels;

e. Proficiency Panels;

f. Antiviral-Resistance 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 diagnostic testing for other respiratory viral and bacterial agents; See Appendix B

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 C

e. monoclonal and polyclonal antibodies to influenza viral antigens;

f. Animal antisera against influenza viruses (rabbit, ferret, sheep, etc.);

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 (see Appendix D; and,

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

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 dated ____________, to address proper contractor handling and storage 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 handling and storage 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.

2.

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.

3.

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 Appendix A, B, D, and E (instruction manual). 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.

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 Appendix A and F (instruction manual).

3.

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 Appendix A and G (instruction manual).

4.

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 viruses 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 Appendix A and G (instruction manual).

5.

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 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. These kits do not have to be manufactured at GMP or GMP-like quality processes; see Section IV.E.6 of the Statement of Work. See Appendix A and H (instruction manual).

6.

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.

7.

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 I (instruction manual).

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, 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. Panels may contain live or inactivated viruses and bacteria that are characterized quantitatively; see Section IV.B.3 of the Statement of Work.

8.

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.

2.

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, and immunoblotting, 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.

3.

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.

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.

5.

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.

6.

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.

7.

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.

8.

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

9. 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.

10. 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.

11. 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.

12. 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 Project Officer.

13.

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.

14.

The contractor shall provide protective garments, equipment and sufficient training and monitoring to assure safe handling of biohazard materials. Specifically, the contractor shall comply with all applicable health and safety regulations (http://www.cdc.gov/od/ohs/biosfty/biosfty.htm) while conducting the work set forth herein and follow the standards listed in the Statement of Work and attachments or amendments. See Appendix J.

H.

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; some shipments will require execution of an MTA; 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 safeguards and desired temperature levels for specific products in transit, depending on the mode of transportation employed.

9.

The contractor shall develop data sheets containing technical information to be packaged with viruses and reference reagents provided to recipients. Data sheets will be reviewed and approved by the Project Officer prior to distribution.

10.

The contractor shall establish specific safety standards for the safe handling and use of specific viruses and reference reagents, in compliance with all federal, state and local laws and regulations. Applicable safety standards will be documented and packaged with viruses and reference reagents provided to recipients. Safety Standards will be reviewed and approved by the Project Officer prior to distribution.

11.

The contractor shall utilize a secure package tracking and delivery system; and, written verification of receipt at destination shall be obtained, to document that approved shipments are made to intended recipients in a timely manner. Deliveries shall be guaranteed within 96 hours of shipment; and, will be scheduled for delivery on Mondays through Thursdays only.

Note: Certain materials may require special packaging and/or expedited shipment to ensure the integrity of materials being shipped.

12.

The contractor shall obtain appropriate licenses and permits required by federal, state and local United States and/or foreign government authorities for the safe import, storage, distribution and import/export of viruses and reference reagents. In addition, the contractor shall obtain all appropriate interstate, intrastate and/or foreign import/export shipping licenses and permits for transporting biohazardous materials. If shipments to overseas requestors are authorized, the contractor shall be also be responsible for obtaining appropriate Export Permits for H5N1 or equivalent materials from the U.S. Department of Commerce.

13.

The contractor shall coordinate all shipments to ensure that viability, biological activity or chemical integrity of viruses and reference reagents will not be adversely affected. Written notification of shipment scheduling and acceptance by recipient shall be documented to ensure that shipping and receiving of frozen and refrigerated viruses and reference reagents is fully coordinated.

I. Establish and Conduct a Proficiency Testing (PT) Program

Detection of novel influenza viruses is a critical component of pandemic preparedness and response. All public health interventions are dependent on initial recognition, characterization, and confirmation of these viruses. The majority of the diagnostic determination of novel strains of influenza occurs at public health laboratories and academic or reference laboratories in the United States and abroad. Many of these confirmatory tests, both in current use or under development, require a high level of laboratory expertise or may involve multiple steps in preparation and processing. Because mitigation efforts to control pandemic spread must be initiated rapidly, testing at these laboratories must be performed with the maximum of quality control to achieve accurate and timely results. To ensure that laboratories on the front lines of detection are adequate in their performance of these tests, routine evaluation to measure their proficiency is needed. A proficiency testing (PT) program is needed 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. Proficiency testing shall be performed at:

Laboratories participating in the Proficiency Testing Program a.

Laboratories participating in virologic surveillance through the CDC-sponsored World Health Organization (WHO) Collaborating Laboratories in the U.S.

Approximately 80 WHO collaborating laboratories located throughout the United States report the total number of respiratory specimens tested and the number positive for influenza types A and B each week. These include all state and some large local public health laboratories. Most of the U.S. WHO collaborating laboratories report the influenza A subtype (e.g., H1N1 or H3N2) of the viruses they have isolated and the ages of the persons from whom the specimens were collected. A subset of the influenza viruses collected by laboratories are sent to CDC for further characterization, including gene sequencing, antiviral resistance testing and antigenic determination. For the 2006-07 season, 6,102 of these were subtyped (e.g., H1 or H3).

Annual testing of WHO Collaborating Laboratories in the U.S. will serve to ensure that the U.S. is prepared to act confidently on results identifying novel or emerging pandemic strains of influenza. This confidence in distributed laboratories is necessary so that CDC confirmation of testing is not necessary for the rapidly increasing number of positive results during the early intervals of the pandemic.

Proficiency testing must be kept current as influenza viruses undergo antigenic changes each season. During a pandemic, any changes that are detected in the pandemic strain will need to be rapidly incorporated into the diagnostic tests used at the WHO Collaborating Laboratories and incorporated into the proficiency testing panels.

b.

Laboratories serving as National Influenza Centers in the WHO Global Influenza Surveillance Network

The WHO Global Influenza Surveillance Network (GISN) was established in 1952. The network comprises 4 WHO Collaborating Centers (England, Japan, Australia, and at CDC in the U.S.) and 118 institutions in 89 countries, which are recognized by WHO as WHO National Influenza Centers (NICs). These NICs collect specimens in their country and perform primary virus isolation and preliminary antigenic characterization. They ship newly isolated strains to WHO Collaborating Centers for high level antigenic and genetic analysis, the result of which forms the basis for WHO recommendations on the composition of influenza vaccine for the Northern and Southern Hemisphere each year.

Proficiency testing has been periodically performed, but no routine testing at all NICs has been conducted. Regular proficiency testing will demonstrate if NICs are adequately capable of detecting circulating and novel influenza viruses. This will facilitate rapid detection of strains with pandemic potential.

2.

Proficiency Testing Program a.

The contractor shall develop and distribute 200* blinded panels per year as described in IV.C.7.c. in accordance with CDC-furnished specifications as described herein.

b.

Panels will be nmailed to participants designated by the Project Officer within five (5) days of the Project Officer’s request.

c. Each panel will contain a CDC-supplied instructional and score sheet for return mailing to CDC upon completion (see Appendix I.

d. Collation and analysis will be conducted by CDC or its designee.

J.

Maintain Inventory and Distribution Database and Management System 1.

The contractor shall establish and maintain an on-going computerized inventory and distribution database and processing system on a personal computer (PC)-compatible system that will track and assist in the coordination of the activities under this contract. A separate database must be provided for BSL3++ agents regulated under the Select Agent Rules, in compliance with Federal Law including measures to ensure data security and sample history recording.

2.

The contractor shall maintain records for all viruses and reference reagents maintained in inventory, which shall include, but not necessarily be limited to the following information:

a.

the source/donor of the virus or reagent;

b.

a full description of the virus or reagent, including relevant epidemiologic information and identifiers to link to genetic sequence databases;

c.

category of virus or reagent (e.g., not of human origin, human-derived, biohazardous, radioactive, donor assigned category for commercial use);

d.

lot number and date of receipt;

e.

quality control information;

f.

storage conditions;

g.

solubility of the virus or reagent (when appropriate);

h.

storage location;

i.

restrictions, if any, on release, disposition and use;

j.

how and when dispensed; and, to whom;

k.

date and time shipped; and, to whom;

l.

by whom it was shipped;

m.

date and time received by intended recipient; and, documentation from the recipient that the virus or reagent was received;

n.

viral passage number indicating substrate (e.g., M2E1) and date passaged; and, o.

concentration of material or agent.

3.

The contractor shall establish and maintain an electronic sample tracking system capable of generating and reading bar-coded labels for virus and reagent vials in different formats including numeric, alpha numeric and colored bar codes. Material (software and hardware) for maintaining these records shall be provided by the contractor.

4.

Unless prohibited by law, the contractor shall ensure protection against the loss of data by establishing a data mirror for files with storage outside of the main facility. The system in its entirety shall be completely documented and capable of being transferred to the Project Officer without interruption.

5.

The contractor shall ensure the security and safety of data of viruses and reference reagents; information related to the use of the viruses and reference reagents; and, results from design validation activities and independent evaluation. All information regarding the evaluation of viruses and reference reagents shall be considered “government property”; and, shall be maintained in accordance with applicable provisions of the contract. The Project Officer alone shall be responsible for determining the level of information concerning a particular virus or reagent that will be made available for dissemination and to whom the information will be made available.

6.

The contractor shall maintain detailed up-to-date inventories of all the biological materials collections, in electronic databases and on paper; shall report this information to the Project Officer on a monthly basis; and, shall be capable of providing special reports of this information within one day of a request from the Project Officer.

K.

Publicize Information Concerning Availability of Viruses and Reference reagents; and, Provide Ordering and Handling Support to Requestors 1.

The contractor shall establish, operate and maintain an electronic “storefront” (website), through which information concerning the “CDC Influenza Reagent Resource” will be publicized. The storefront shall serve as an online ordering portal for requestors needing influenza viruses, reagents and other resources outlined in Appendix A.

2.

The storefront will serve as an electronic bulletin board for this contract, through which the government will publicize the purpose and intent of the project, procedures for requesting viruses and reference reagents, turn-around times, etc. However, it will be the responsibility of the contractor to develop and update all materials to be published at the “storefront”, subject to approval of the Project Officer.

3.

The contractor will collaborate with the Project Officer to identify innovative ways to enhance dissemination of information relating to products and services available through the contract to intended audiences. This may involve selective publication in scientific journals, publications, newsletters, etc.; developing posters, staffing booths and making presentations at scientific conferences, meetings, workshops, etc.

4.

The contractor shall establish, staff and maintain a published “hotline” phone number, Monday through Friday during normal business hours, through which current and potential “users” can contact a live operator, to obtain information on available products and services; to document, discuss and resolve problems with current orders and deliveries; etc.

After hours callers will be greeted with a taped message, advising that they have reached the CDC Influenza Reagent Resource; and, they will be invited to please leave their name and phone number or call back during normal working hours. Phone messages will be returned by 12:00 noon, the following working day. CDC subject matter experts (SMEs) will be available to assist the contractor in responding to technical questions, as necessary.

L.

Provide for the Orderly Transition of Contract Services to Successor Contractor 1.

It is intended that the “CDC Influenza Reagent Resource” will continue in operation beyond the initial ten (10) year performance period of this contract.

2.

In the event that the incumbent contractor is not successful in the competition for award of the follow-on contract, the contractor will exert its best efforts to ensure a safe and orderly transition of services, with minimum impact to the public. Operational control of the CDC-IRR web site will be transferred; and, all stored viruses, biologics and reagent samples, data and government furnished property will be shipped to the successor contractor as soon as practicable after award of the new contract.

V.

Reporting Requirements The contractor shall prepare and submit the following reports to the Contracting Officer and the Project Officer, in the number of copies, and within the time frames specified below:

A.

Monthly Reports. By the fifteenth day of the month following the month covered by the report, the contractor shall submit three paper copies (one to the Contracting Officer and two to the Project Officer) and one electronic copy (to the Project Officer) of the contractor’s Monthly Report of work performed during the previous month. Each Monthly Report shall consist of the following:

1.

A cover page containing:

a.

Contract number and title;

b.

Period covered by the report;

c.

Contractor's name and address;

d.

Author(s); and e.

Date of submission.

A brief narrative summary of work performed during the reporting period to highlight major accomplishments during the reporting period, progress toward meeting established contract performance milestones, any problems experienced during the reporting period or anticipated during future reporting periods, contractor actions to remedy current problems, contractor suggestions to remedy anticipated problems, etc.

In addition, monthly reports shall contain, but not necessarily be limited to the following information:

a.

An inventory report of the quantity and types of viruses and reference reagents on hand as of the last day of each month;

b.

A list of viruses and reference reagents assayed during the month, type of assay and results of the assay;

c.

A list of all investigators and sites that have applied for certification as recipients of Category A, B & C CDC Select Agents (Appendix A to Part 72, CFR 42, http://www.cdc.gov/od/ohs/lrsat/p54605.pdf).

d.

A summary of viruses and reference reagents shipped, to include the following information for each virus and reagent:

(1) Quantity and characterization of the reagent;

(2) Date of shipment;

(3) Date of receipt of shipment;

(4) Name and address of the recipient; and

(5) Problems associated…