NIHAO2009029 - Final RFP.pdf

Solicitation# DHHS-NIH-NIAID-AO-2009029

NOTICE TO OFFERORS

1. Proposal Submission

a. Please submit the Proposal Intent Sheet (Attachment 1) to the Contract Specialist by 4pm on May 3, 2010.

b. The Offeror must complete the appropriate areas of the SF1449 (Page 2), and return a signed copy with the Offeror’s Proposal

c. Please note that page limit restrictions have been placed on technical proposals. See the

RFP for details. Any pages included within the technical proposal that exceed the page limit will not be evaluated.

d. The Contracting Office is located within a security access facility. Proposals must be received by the Government by the date and time specified on Page 2. PLEASE ALLOW

ADEQUATE TIME TO FOR YOUR PACKAGE TO CLEAR THE SECURITY

CHECKPOINT AND TO REACH THE CONTRACT SPECIALIST OR DESIGNEE

BEFORE THE TIME SPECIFIED BY THE DUE DATE ON PAGE 2.

2. Questions

a. All questions pertaining to this solicitation must be submitted by email to the Contract Specialist, LaDonna Stewart at lstewart@niaid.nih.gov.

b. Offerors shall be advised that the Contracting Office will make every attempt to provide a timely response to any questions submitted by the due dated noted for receipt of questions. Questions or documents submitted by phone or facsimile will not be considered.

c. Questions submitted after the due date for receipt of questions may not receive a response by the solicitation closing date.

mailto:lstewart@niaid.nih.gov�

AUTHORIZED FOR LOCAL REPRODUCTION STANDARD FORM 1449 (REV. 3/2005)

PREVIOUS EDITION IS NOT USABLE Prescribed by GSA - FAR (48 CFR) 53.212

SOLICITATION/CONTRACT/ORDER FOR COMMERCIAL ITEMS 1. REQUISITION NUMBER PAGE 2 OF 66

Offeror to complete blocks 12, 17, 23, 24, & 30

2. CONTRACT NO. 3. AWARD/EFFECTIVE DATE 4. ORDER NUMBER 5. SOLICITATION NUMBER 6. SOLICITATION ISSUE DATE

DHHS-NIH-NIAID-AO-

2009029

04/15/2010

7. FOR SOLICITATION

A. NAME B. TELEPHONE (No Collect Calls) 8. OFFER DUE DATE/

LOCAL TIME

INFORMATION CALL LaDonna Stewart, Contract Specialist 301-451-8117 05/06/2010 10:00am

9. ISSUED BY CODE 10. THIS ACQUISITION IS 11. DELIVERY FOR FOB

DESTINATION UNLESS

12. DISCOUNT TERMS

UNRESTRICTED BLOCK IS MARKED

SEE SCHEDULE

NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES SET-ASIDE: 100% FOR 13a. THIS CONTRACT IS A RATED ORDER ACQUISITIONS MANAGEMENT AND OPERATIONS BRANCH SMALL BUSINESS UNDER DPAS (15 CFR 700)

10401 FERNWOOD ROAD, MSC 4813 SMALL DISADV. BUSINSESS 13b. RATING

SUITE 2NE-70 8(A)

BETHESDA, MD 20817-4813 NAICS: 325414 14. METHOD OF SOLICITATION

SIZE STANDARD: 500 Employees RFQ IFB RFP

15. DELIVER TO: CODE 16. ADMINSTERED BY CODE

SEE BLOCK 9 SEE BLOCK 9

17a. CONTRACTOR/OFFEROR CODE FACILITY 18a. PAYMENT WILL BE MADE BY CODE

SEE BLOCK 9

TO BE COMPLETED BY OFFEROR

EFT: T

TELEPHONE: 18b. SUBMIT INVOICES TO ADDRESS SHOWN IN BLOCK 18a UNLESS BLOCK BELOW IS CHECKED:

17b. CHECK IF REMITTANCE IS DIFFERENT AND PUT SUCH ADDRESS IN OFFER SEE ADDENDUM

19.

ITEM NO,

20.

SCHEDULE OF SUPPLIES/SERVICES

21.

QUANTITY

22.

UNIT

23.

UNIT PRICE

24.

AMOUNT

TITLE: Manufacture and Safety Test Experimental Virus Vaccines See Attachment 2

PERIOD OF PERFORMANCE: August 1, 2010 – July 31, 2011 (Plus Four

One -Year Options)

TYPE: Indefinite Delivery, Indefinite Quantity IDIQ with Fixed Price Task

Orders

(Attach Continuation Sheet as Necessary)

25. ACCOUNTING AND APPROPRIATION DATA 26. TOTAL AWARD AMOUNT (For Govt. Use Only)

27a. SOLICITATIONS INCORPORATE BY REFERENCE FAR 52.212-1, 52.212-2, 52.212-3. FAR 52.212-4 AND 52.212-5 ARE ATTACHED. ADDENDA ARE ARE NOT ATTACHED.

27b. CONTRACTS/PURCHASE ORDERS INCORPORATE BY REFERENCE FAR 52.212-4. FAR 52.212-5 IS ATTACHED. ADDENDA ARE ARE NOT ATTACHED.

28.

CONTRACTOR IS REQUIRED TO SIGN THIS DOCUMENT AND RETURN __3____ COPIES TO ISSUING OFFICE.

CONTRACTOR AGREES TO FURNISH AND DELIVER ALL ITEMS SET FORTH OR OTHERWISE IDENTIFIED ABOVE AND ON ANY ADDITIONAL SHEETS SUBJECT TO THE TERMS AND CONDITIONS SPECIFIED HEREIN.

29.

AWARD OF CONTRACT: REFERENCE OFFER DATED . YOUR OFFER

ON SOLICITATION (BLOCK 5), INCLUDING ANY ADDITIONS OR CHANGES WHICH ARE SET

FORTH HEREIN, IS ACCEPTED AS TO ITEMS:

30a. SIGNATURE OF OFFEROR/CONTRACTOR 31a. UNITED STATES OF AMERICA (SIGNATURE OF CONTRACTING OFFICER)

30b. NAME AND TITLE OF SIGNER (TYPE OR PRINT) 30c. DATE SIGNED 31b. NAME OF CONTRACTING OFFICER 31c. DATE SIGNED

32a. QUANTITY IN COLUMN 20 HAS BEEN 33. SHIP NUMBER 34. DO VOUCHER NUMBER 35. AMOUNT VERIFIED CORRECT

FOR

RECEIVED INSPECTED ACCEPTED, AND CONFORMS TO THE PARTIAL FINAL

CONTRACT, EXCEPT AS NOTED 36, PAYMENT

37. CHECK NUMBER

32b. SIGNATURE OF AUTHORIZED GOVT. REPRESENTATIVE 32c. DATE COMPLETE PARTIAL FINAL

38. S/R ACCOUNT NUMBER 39. S/R VOUCHER NUMBER 40. PAID BY

42a. RECEIVED BY (Print) 41a. I CERTIFY THIS ACCOUNT IS CORRECT AND PROPER FOR PAYMENT

41b. SIGNATURE AND TITLE OF CERTIFYING OFFICER 41c. DATE 42b. RECEIVED AT (Location)

42c. DATE REC’D (YY/MM/DD) 42d. TOTAL CONTAINERS

3 Solicitation# DHHS-NIH-NIAID-AO-2009029

Section SF 1449 - CONTINUATION SHEET

Section B: Supplies /Services

1. Price

The Price Schedule located at Attachment 2 of this solicitation shall contain prices for all products or services required under this contract. The Contractor shall fill in the Price columns for all line items to establish the offered prices. Any documentation (information other than cost or pricing data) required to support the Contractor’s prices shall be included within the Contractor’s business proposal submission only.

The proposed prices shall be reviewed for reasonableness and negotiated between the Contractor and the Government. A final Price Schedule shall be incorporated into any award resulting from this solicitation.

2. Performance Period

a. The Period of Performance for this contract shall be from:

August 1, 2010 through July 31, 2011

b. Option(s)

If the Government exercises its option pursuant to the Option Provision incorporated into this Contract, the contract performance period shall be extended as follows:

Option Option Period

I August 1, 2011 – July 31, 2012

II August 1, 2012 – July 31, 2013

III August 1, 2013 – July 31, 2014

IV August 1, 2014 – July 31, 2015

SECTION C

CI.1. STATEMENT OF WORK

Independently and not as an agent of the Government, the Contractor shall furnish all the necessary supplies/services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government, and as needed, to perform the work requirements as indicated below.

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I. Background:

The National Institute of Allergy and Infectious Diseases (NIAID) is dedicated to improving global human health through the rigorous pursuit of effective vaccines for human diseases. One of the key components of the NIAID mission involves the rapid advancement of promising vaccine candidates from the laboratory to the clinic.

The purpose of this contract is to enlist the services of a Contractor to effectively produce, fill, and qualify suspensions of both Influenza and Non-Influenza viruses which have been shown by evaluation in vitro and in vivo to be promising candidates for use in immunoprophylaxis of human diseases. Additionally, the Contractor may be required to qualify other vaccine components, such as vaccine diluents; or to prepare and qualify cell lines for use in the production of such viruses, or for other uses as directed by the Government.

The Government shall establish an Indefinite Quantity, Indefinite Delivery (IDIQ), Task Order type contract for the production of virus vaccine suspensions or cell lines as needed. The Government may also require the contractor to provide additional services for the ongoing post-production support (e.g., cryo preservation, product retrieval, and shipping) of vaccine suspensions and cell banks over the course of contract performance.

II. General Requirements:

A. The Contractor shall be required to prepare, at the request of the Government

Contracting Officer or Designee(s), any suspensions of viruses that are needed for evaluation of effectiveness of immunoprophylaxis or pathogenesis studies.

During the performance of a contract year, the Government shall request a minimum of two (2) and a maximum of six (6) virus suspensions to be grown in Vero cells or eggs.

The Government may also require up to one cell line to be produced and delivered annually.

The virus suspensions that will be made are predominantly for Phase I and II clinical studies, therefore, the traditional method of preparing Master and Working Virus Seed Banks will not be followed. Nevertheless, the cell lines and virus suspensions, which are intended for evaluation in human volunteers by the NIAID, shall be prepared using methods and facilities which meet all FDA and cGMP standards for preparation of live virus vaccine candidates as described in the most current Code of Federal Regulations;

specifically 21CFR58; 21CFR210; 21CFR211; 21CFR600, and 21CFR610 (See http://www.gpoaccess.gov/cfr/index.html). When applicable, animal-derived raw materials and virus suspensions shall be tested for bovine and porcine viruses as described in 9CFR113.46, 9CFR113.47, and 9CFR113.53. Further, these virus suspensions and cell lines shall be safety-tested to determine freedom from adventitious agents by procedures acceptable to the Center for Biologics Evaluation and Research (CBER), FDA, using the CFR sections indicated above and http://www.fda.gov/cber/guidelines.htm as guidelines.

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The Contractor shall be familiar with the following sources of information and how they pertain to the cGMP production of vaccine lots for use in Phase I and II clinical studies in humans:

• Points to Consider in the Characterization of Cell Lines Used to Produce

Biologicals, CBER (7/93), http://www.fda.gov/cber/gdlns/ptccell.pdf

• ICH Harmonized Tripartite Guideline Q5A: Viral Safety Evaluation of

Biotechnology Products Derived from Cell Lines of Human or Animal Origin.

Federal Register, Vol 63; No.185 51074-51084 (9/24/1998) or http://www.fda.gov/cber/gdlns/virsafe.pdf

• ICH Guideline Q5D: Derivation and Characterization of Cell Substrates Used for the Production of Biotechnological/Biological Products. Federal Register, Vol 63;

No.182 50244-50249 (9/21/1998) or http://www.fda.gov/cber/gdlns/qualbiot.pdf

• Guidance for Industry: Content and Format of Chemistry, Manufacturing and Controls Information and Establishment Description for a Vaccine or Related Product. http://www.fda.gov/cber/gdlns/cmcvacc.pdf

• ICH Final Guidelines on Stability Testing of Biotechnology/Biological Products, Federal Register, Vol. 61, No. 133 36466-36469, (7/10/1996) or http://www.fda.gov/cber/gdlns/ichq5c071096.pdf

• ICH Guideline Q6B: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products, Federal Register, Vol 63, No. 110 31056- 31513 (6/9/1998) or http://www.fda.gov/cder/guidance/Q6Bfnl.pdf

• Guidance for Industry: Revised Preventive Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) and Variant Creutzfeldt-Jakob Disease (vCJD) by Blood and Blood Products. 2002.

http://www.fda.gov/cber/gdlns/cjdvcjd.pdf

• Guidance for Industry: Characterization and Qualification of Cell Substrates and Other Biological Materials Used in the Production of Viral Vaccines for Infectious Disease Indications. CBER/FDA. 2010.

http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInfor mation/Guidances/Vaccines/default.htm

Note: All policies and guidelines for products used in human Phase I and II clinical studies are subject to periodic review by the FDA, and may change over the course of contract performance. Additionally, the Government may require additional testing to be performed to ensure that virus suspensions and cell lines meet all sterility and efficacy standards in accordance with NIH protocol and FDA guidance. The Contractor shall be required to produce all virus suspensions and cell lines in accordance with the most current standards as required by the Government.

B. The Contracting Officer Technical Representative (COTR) will provide the Contractor with sufficient seed virus to inoculate the substrate (e.g., Vero cells or SPF eggs) used for virus lot production. The Contractor shall confirm microbial sterility of material provided by the COTR before initiating virus production. The virus suspension (candidate vaccine lot) will be produced, processed, filled, and qualified by the Contractor as directed by the COTR. As required by the Contractor, the COTR will supply sufficient quantities of antiserum directed against the virus for use in the in vitro

6 Solicitation# DHHS-NIH-NIAID-AO-2009029 and in vivo tests performed to detect the presence of adventitious viral agents in the virus suspension.

III. Specific Requirements

A. Production of Virus Suspensions in Vero Cells

1. Virus Preparations

The preparation of the virus suspensions will be performed at Biosafety Level 2 by the Contractor.

The Contractor shall prepare virus suspensions that meet current FDA requirements of Good Manufacturing Practices. All steps of the manufacturing process will be performed according to a fully executed and approved batch production record.

Notwithstanding any additional instructions noted for any specific virus type, virus preparations shall be filled into suitable screw-cap vials containing 0.6 - 1.0 mL of virus suspension. Filled vials are multi-dose and are intended for dilution at the clinical site prior to administration. The Contractor shall prepare 1-2 liters (approximately 2500 vials) for each of the lots made in Vero cells. Vials shall be filled, flash frozen, and handled in a manner that maintains even and consistent potency throughout the entire fill process.

The Government will supply the Contractor with qualified Vero cells from their Working Cell Bank for production of the virus suspensions. The suspensions are produced and processed as directed by the COTR with harvest and filling performed on the same day, if possible.

The virus suspensions shall be prepared without serum or antibiotics. Additionally, the Contractor shall take every possible precaution to avoid the use of animal derived materials.

Virus suspensions are conditionally acceptable based on sterility, virus titer, and nucleotide sequence. The Contractor will provide sample vials to the NIAID who will perform virus titer, nucleotide sequence analysis, and testing to determine if the candidate vaccines retain the laboratory markers of attenuation. The lots that meet titer, sequence, and sterility requirements are then subjected to the complete series of lot release and safety testing.

Preparations will include, but are not be limited to the following viruses (the most frequently manufactured preparations are listed first):

i. Paramyxoviruses

These viruses include respiratory syncytial virus (RSV) subgroups A and B, parainfluenza viruses (PIV) types 1, 2, and 3, human metapneumovirus (hMPV), and avian parainfluenza viruses such as Newcastle disease virus (NDV).

7 Solicitation# DHHS-NIH-NIAID-AO-2009029

Viruses shall include human wild type (wt), temperature sensitive (ts), cold-adapted

(ca) viruses, and viruses derived using recombinant DNA technology. Vaccine candidates for the recently described human metapneumoviruses and for avian parainfluenza vectors, such as Newcastle disease virus bearing foreign viral protective antigens, may also need to be prepared.

Seed viruses will be supplied by the COTR in the form of DNA-derived viruses recovered from Vero cells qualified for use in the preparation of viruses to be given to humans.

The Contractor shall prepare wild type or attenuated parainfluenza or respiratory syncytial virus in Vero cells. In some cases, infected cell cultures will require the addition of trypsin to maintain virus infectivity.

The Contractor shall produce and test these viruses as described in the work statement and ensure that they have a consistent final vial potency of greater than

106.5 PFU/mL for parainfluenza viruses and greater than 106 PFU/mL for respiratory syncytial virus.

Note: Programmatic or situational requirements may require larger lots of up to four liters (4 L) to be produced. The Contractor must have the ability to meet the additional capacity requirements and produce larger production lots as needed, and as specified by the COTR.

ii. Dengue viruses

Seed viruses will be supplied by the COTR in the form of DNA-derived viruses recovered from transfected C6/36 mosquito cells or Vero cells qualified for use in the preparation of viruses to be given to humans.

The Contractor shall prepare 1 - 2 liters of attenuated dengue virus that have been processed and concentrated from 5 - 6 liters of culture fluid.

The Contractor shall produce and test these viruses as described above and ensure that they have a consistent final vial potency of greater than 106 PFU/mL.

These viruses are to be administered parenterally in clinical studies conducted by the NIAID, therefore the Contractor shall be required to institute procedures required to reduce the amount and size of contaminating Vero cell DNA. To accomplish this, the Contractor may treat crude virus harvests with Benzonase endonuclease. The size and amount of Vero cell DNA that contaminates the final virus suspension shall meet FDA requirements for parenterally administered vaccine products prepared in cell lines such as Vero. Benzonase should not be detectable in the vaccine preparation administered to humans.

8 Solicitation# DHHS-NIH-NIAID-AO-2009029

iii. Chimeric flaviviruses

These chimeric virus vaccine candidates consist of dengue virus type 4 in which the prM and E structural proteins have been replaced with those derived from such viruses as West Nile virus, St. Louis encephalitis virus, tick-borne encephalitis virus or Japanese encephalitis virus. Seed viruses will be supplied by the COTR in the form of DNA-derived viruses recovered from transfected C6/36 mosquito cells or Vero cells qualified for use in the preparation of viruses to be given to humans.

Chimeric flaviviruses will have been approved for work at Biosafety Level 2 by the NIH Biosafety Committee prior to being transferred to the Contractor.

The Contractor shall prepare 1 - 2 liters of attenuated chimeric flavivirus that have been processed and concentrated from 5 - 6 liters of culture fluid.

The Contractor shall produce and test these viruses as described and ensure that they have a consistent final vial potency of greater than 106 PFU/mL.

These viruses are to be administered parenterally in clinical studies conducted by the NIAID, therefore the Contractor shall be required to institute procedures required to reduce the amount and size of contaminating Vero cell DNA. To accomplish this, the Contractor may treat crude virus harvests with Benzonase endonuclease. The size and amount of Vero cell DNA that contaminates the final virus suspension shall meet FDA requirements for parenterally administered vaccine products prepared in cell lines such as Vero. Benzonase should not be detectable in the vaccine preparation administered to humans.

iv. Influenza viruses

These viruses include influenza A viruses belonging to hemagglutinin subtypes H1 to H15 and neuraminidase subtypes N1-N9 or to other subtypes as they appear in nature. Influenza viruses will be grown in qualified Vero cells when such viruses replicate poorly in eggs or when Vero cell production is preferred.

Seed virus will be provided by the COTR.

The viruses will have been approved for work at Biosafety Level 2 by the NIH Biosafety Committee prior to transfer to the Contractor.

The Contractor shall produce and test these viruses as described above and ensure that they have a consistent final vial potency of greater than 107 to TCID50/mL measured on MDCK cell culture monolayers in the presence of ~1 µg of trypsin per mL.

2. Lot Release / Safety Test procedures

The Contractor will perform lot release/safety test procedures as specified in the approved batch production record for in-process samples and final vials.

9 Solicitation# DHHS-NIH-NIAID-AO-2009029

All testing shall be conducted in compliance with Good Laboratory Practice regulations (21CFR58) using validated procedures.

Required testing may include any of the following: Microbial sterility test (21CFR610.12) with Bacteriostasis and Fungistasis determination; Mycoplasma sterility (cultivatable and non-cultivatable) (21CFR610.30); Spiroplasma sterility;

Mycobacterium ssp. sterility; tissue culture safety test; Detection of adventitious viruses by inoculation into guinea pigs, mice, and embryonated chicken eggs (In vivo safety test); General safety test (21CFR610.11); Assay to detect viral reverse transcriptases (PCR based); Endotoxin determination (Limulus ameobocyte lysate assay); Concentration of residual DNA determination; Size of residual DNA determination; Concentration of residual endonuclease (Benzonase) determination;

Residual intact cell assay; pH determination; Sucrose concentration.

The type, quantity, and sequence of required testing is not limited to the above referenced. Additional testing, as determined by either the COTR and/or the Contractor, may be required for specific virus products.

Potency testing (virus titer), virus identity, genome sequence, and toxicology testing will be performed by the NIAID.

3. Storage and Shipping

Virus suspensions are to be stored by the Contractor at -80 ± 10°C in a monitored freezer according to cGMP guidelines. It is anticipated that the virus will maintain its titer during this storage period. Upon release, virus suspensions will be transferred by the Contractor to a long-term cGMP storage facility designated by the COTR.

B. Production of Influenza A Virus Suspensions in the Allantoic Cavity of Embryonated Eggs

1. Preparation

These viruses include attenuated influenza A viruses belonging to hemagglutinin subtypes H1 to H15 and neuraminidase subtypes N1-N9 or to other subtypes as they appear in nature.

Seed virus will be provided by the COTR.

The Contractor shall prepare virus suspensions that meet current FDA requirements of Good Manufacturing Practices. All steps of the manufacturing process will be performed according to a fully executed and approved batch production record.

The preparation of the virus suspensions will be performed at Biosafety Level 2 by the Contractor and all viruses will have been approved for work at Biosafety Level 2 by the NIH Biosafety Committee prior to transfer to the Contractor.

10 Solicitation# DHHS-NIH-NIAID-AO-2009029

The Contractor will prepare virus suspensions of 2-3 liters (2000 - 3000 vials) of influenza virus in embryonated chicken eggs obtained from specific-pathogen-free (SPF) flocks and safety test these suspensions. Vials shall be filled, flash frozen, and handled in a manner that maintains even and consistent potency throughout the entire fill process.

The suspensions shall be grown in SPF avian leucosis virus-free embryonated eggs.

The final virus suspension shall be tested for freedom from avian leucosis virus and other adventitious microbial agents.

The viral suspensions shall have a consistent final vial potency of 107.3 to 108.0 TCID50/mL measured on MDCK cell culture monolayers in the presence of ~1 µg of trypsin per mL. In addition, viral suspensions shall retain the laboratory markers of the attenuated seed virus such as high efficiency of plaque formation at low temperature (ca phenotype) or decreased efficiency of plaque formation at high temperature (ts phenotype). These tests will be performed by NIAID scientists.

Virus suspensions are conditionally acceptable based on sterility, virus titer, and nucleotide sequence. The Contractor will provide sample vials to the NIAID who will perform virus titer, nucleotide sequence analysis and testing to determine if the candidate vaccines retain the laboratory markers of attenuation. The lots that meet titer, sequence, and sterility requirements are then subjected to the complete series of lot release and safety testing.

Note: Laboratory workers who handle these viruses should be immunized with currently licensed influenza A virus vaccines.

2. Lot Release and Safety Test Procedures

The Contractor will perform lot release/safety test procedures as specified in the approved batch production record for in-process samples and final vials.

All testing shall be conducted in compliance with Good Laboratory Practice regulations (21CFR58) using validated procedures.

Required testing may include any of the following: Microbial sterility test (21CFR610.12) with Bacteriostasis and Fungistasis determination; Mycoplasma sterility (cultivatable and non-cultivatable) (21CFR610.30); Mycobacterium ssp.

sterility; In vivo tissue culture safety test; Detection of adventitious viruses by inoculation into guinea pigs, mice, and embryonated chicken eggs (In vivo safety test); General safety test (21CFR610.11); Avian leucosis virus assay; Assay to detect viral reverse transcriptases (PCR based).

The type, quantity, and sequence of required testing is not limited to the above referenced. Additional testing, as determined by either the COTR and/or the Contractor, may be required for specific virus products.

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Potency testing (virus titer), virus identity, genome sequence, and toxicology testing will be performed by the NIAID.

Virus suspensions are to be stored by the Contractor at -80 ± 10°C in a monitored freezer according to cGMP guidelines. It is anticipated that the virus will maintain its titer during this storage period. Upon release, virus suspensions will be transferred by the Contractor to a long-term cGMP storage facility designated by the COTR.

C. Production of Qualified Cell Lines

1. Preparation

The Contractor may be required to produce and qualify up to one (1) cell line per year for use by the NIAID and by the Contractor in the production of viruses to be administered to humans or for other uses as directed by the COTR.

Qualified cell lines may include the production of Master Cell Banks (200 vials, >107 viable cells/mL), Working Cell Banks (200 vials, >107 viable cells/mL), and End of Production Cell Banks (usually 10 passages beyond Working Cell Bank passage level). End of Production Cell Banks are for testing purposes only.

2. Lot Release and Safety Test Procedures

The Contractor will perform Lot Release / Safety Test procedures as appropriate for specific cell lines and as directed by the COTR. All testing shall be conducted in compliance with Good Laboratory Practice regulations (21CFR58) using validated procedures. Required testing may include any of the testing described in Lot Release and Safety Test Procedures for other Influenza and Non-Influenza vaccine productions, as well as, any of the following: Karyotype and Isoenzyme analysis;

Ultrastructural evaluation and virus particle detection by electron microscopy; PCR detection of specific retroviruses and virus families; Detection of bovine adventitious viral agents (9CFR113); Detection of porcine adventitious viral agents;

Determination of tumorigenicity in athymic nude mice.

Cell lines are to be stored in a monitored vapor phase liquid nitrogen freezer in accordance with cGMP guidelines. Upon release, cell lines will be transferred to a long-term cGMP storage facility designated by the COTR.

D. Process Development.

During the course of contract performance, the Contractor may be asked to assist with basic process development as directed by the COTR.

12 Solicitation# DHHS-NIH-NIAID-AO-2009029

These requirements may include the development of improved manufacturing methods designed to: (a) increase vaccine potency (titer); (b) determine optimal day of virus harvest, (c) improve vaccine stability; and (d) increase vaccine purity by the reduction of undesirable contaminants such as cellular DNA, serum, and animal derived proteins.

E. Qualification of other vaccine components.

As directed by the COTR, the Contractor may be asked to safety test materials intended for use as vaccine components. Such materials may include vaccine excipients, diluents, and placebo fluids. In general, these filled materials are purchased by the COTR from commercial sources and qualified for human use by additional safety testing, which can include: Microbial sterility test (21CFR610.12) with Bacteriostasis and Fungistasis determination; Mycoplasma sterility (cultivatable and non-cultivatable) (21CFR610.30); General safety test (21CFR610.11); pH determination; Assay for amino acid composition.

IV. Deliverables and Reporting Requirements:

All virus suspensions and reports produced by the Contractor and all cell lines produced and qualified for use under this contract will be considered government-owned materials.

In order to accomplish the goals of this contract, The Contractor is required to provide delivery of virus suspensions within six months of the date that a suitable seed virus is made available to the Contractor.

For all contract facilities located outside of the United States of America, the Contractor will be responsible for ensuring the timely import and export of virus seed lots and all deliverables.

Contract deliverables include:

(a) Manufactured virus suspensions or cell lines;

(b) Technical reports

(c) Clinical Lot Release / Safety Test Reports;

(d) Summary of Manufacturing Process and Safety Test results

(d) Production and Manufacturing batch records, including all reports of environmental monitoring and deviations;

(e) Compilation of raw material including Certificates of Analysis and Certificates of

Origin (for animal-derived raw materials).

1. Reporting Requirements

In addition to the delivery of any other reports set forth elsewhere in this Schedule, the preparation and submission of regularly recurring Technical Progress Reports shall be required in any contract resulting from this solicitation.

For all progress reports, the Contractor shall be required to deliver one (1) electronic copy to the COTR and one (1) hard copy to the Contracting Officer or other designated Contracting Official.

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Brief and factual progress reports shall be submitted using the following format:

i. A cover page containing:

• Contract number and title

• Period of performance being reported

• Contractor’s name and address

• Author’s name

• Date of preparation

ii. SECTION I - An introduction covering the period and scope of the contract.

iii. SECTION II - Substantive performance: a description of current technical or substantive performance and any problems that may exist along with proposed corrective action.

a. Quarterly Reports: The Contractor shall submit copies of a quarterly report that summarizes all pending and completed task orders issued during the reporting period.

The first quarter reports shall include the first 120 days of the contract, and be due within 5 business days of the completed quarter.

The quarterly progress report shall contain all of the following:

i. A summary of the results for each task in progress and/or completed during the quarter;

ii. Identification of any problems incurred during the quarter and whether they have an impact on delivery or completion. If the problems are anticipated to impact delivery or completion, new delivery dates shall be noted;

iii. The percent of work completed for each task order on a quarterly basis.

b. Final Progress Report: the results of the contract performance period including all task orders issued therein. This final report shall be in sufficient detail to explain comprehensively the results achieved. This report shall be submitted at contract expiration

c. The Contractor shall submit reports to:

i. [COTR to be named at contract award]

ii. Contract Specialist

DHHS/NIH

National Institute of Allergy and Infectious Diseases Acquisition Management and Operations Branch 10401 Fernwood Road Room 2NE-70

14 Solicitation# DHHS-NIH-NIAID-AO-2009029

Bethesda, MD 20892-4813

2. Delivery Schedule

The Contractor shall adhere to the following delivery schedule:

Deliverable Deliverable Due Date Progress Reports Quarterly

Final Progress Report On date of contract expiration

Clinical Lot Release/Safety Test Reports Six months after receipt of suitable seed virus

Batch Records for Production/Manufacture Six months after receipt of suitable seed virus

Compilation of raw material Certificates of Analysis and Certificates of Origin (for animal-derived raw materials)

Six months after receipt of suitable seed virus

Summary of Manufacturing Process and Safety Testing results

As required & specified in Government requests

Other Deliverables (includes vaccine suspensions and other cell bank materials stored at the Contractor facilities

As required & specified in Government requests.

Revised Deliverables (includes all end-products and report deliverables requiring modification by the Contractor. Revised deliverables shall be completed by the Contractor at the Contractor’s expense unless otherwise indicated.

Within a mutually agreed upon period.

CI.2. COMMERCIAL ITEM CLAUSES INCORPORATED BY REFERENCE, FAR

52.252-2 (FEBRUARY 1998)

This contract incorporates the following clause(s) by reference, with the same force and effect as if it were given in full text. Upon request, the Contracting Officer will make its full text available. Also, the full text of a clause may be accessed electronically at this address: http://www.acquisition.gov/comp/far/index.html

a. FEDERAL ACQUISITION REGULATION (FAR) (48 CHAPTER 1) CLAUSES

52.212-1, Instructions to Offerors-Commercial Items (June 2008)

52.212-4, Contract Terms and Conditions-Commercial Items (October 2008)

CI.3. 52.212-1-Addendum

1. Customer Past Performance Questionnaires http://www.acquisition.gov/comp/far/index.html�

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a) The Contractor shall have references complete the attached Customer Past Performance Questionnaires attached to this RFP, and return the forms directly to the contracting office by the solicitation closing date. It is the Contractor’s responsibility to ensure that the references return the questionnaires to the Contracting Office by the proposal due date and time. (At least three surveys shall be received via e-mail directly from the offeror’s references).

b) References will be verified. The Government is not required to contact all references provided by the Offeror. Also, references other than those identified by the Offeror may be contacted by the Government to obtain additional information that will be used in the evaluation of the Offeror's past performance.

c) The Questionnaires will be used, in addition to any other past performance information evaluated by the Contracting Officer, to develop a performance risk rating

2. The Contractor is required to be registered in the Central Contractor Registry

(CCR) to be eligible for an award. (Visit www.ccr.gov to initiate registration and obtain additional information). Contractors are required to maintain CCR registration throughout contract performance and final payment of all invoices.

3. Any contract resulting from this solicitation may require the use of live vertebrate animals. As such, prior to the award of any contract, a potential awardee must have, or be able to obtain, an assurance from the NIH Office if Laboratory Animal Welfare, as well as, an accreditation from the Association for the Assessment and Accreditation of Laboratory Animal Care, or an equivalent agency.

4. The Offeror’s proposal must include a completed copy of the Representations and Certifications included in C.I.5.

5. The Contractor’s proposal shall be divided into two separate volumes and provided in the number of copies specified below.

Each hard-copy volume must be submitted in a separate three ring binder with the identification of the Offeror and Volume number on the spine of the binder. In-lieu of a 3-ring binder, a hard-copy of each volume may also be submitted unbound using a rubber-band or binder clip separation. Spiral binding is not acceptable.

Volume Title Hard Copies

I Technical Original + 4 copies II Business Original + 2 copies

6. TECHNICAL PROPOSAL INSTRUCTIONS

http://www.ccr.gov/�

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Technical Proposals must not include cost or price information. Facsimile and e-mail copies of proposals will not be accepted.

a. TECHNICAL DISCUSSION

The discussion provided in the Contractor’s Technical Proposal should respond to the items set forth below:

1) Technical Approach

a) The Contractor’s technical approach should reflect a clear understanding of the nature of the work to be undertaken. Information should be provided relative to current or previous projects which demonstrate the Contractor’s expertise and understanding of this requirement, as well as the ability to provide the managerial oversight, security controls, facilities and resources, and qualified personnel necessary to meet the delivery requirements as outlined by the Statement of Work.

b) Subcontractors

If subcontractors are proposed, please include a commitment letter from the subcontractor detailing:

i. Willingness to perform as a subcontractor for specific duties (list duties).

ii. What priority the work will be given and how it will relate to other work.

iii. The amount of time and facilities available to this project.

iv. Information on their cognizant field audit offices.

v. How rights to publications and patents are to be handled.

vi. A complete cost proposal in the same format as the offeror's cost proposal.

Note: Organizations that plan to enter into a subcontract with an educational concern under a contract awarded under this RFP should refer to the following Web Site for a listing of clauses that are required to be incorporated in Research & Development (R&D) subcontracts with educational institutions:

http://ocm.od.nih.gov/contracts/rfps/FDP/FDPclausecover.htm

2) Staffing

a) Management and Oversight — The Contractor shall list the name and current title of the Principle Investigator (PI) or Project Manager (PM) who shall be responsible for the overall implementation of the contract. The PI or PM shall serve as the key contact for technical

17 Solicitation# DHHS-NIH-NIAID-AO-2009029 aspects of the project. The Contractor shall discuss the qualifications, experience, and accomplishments of the PI or PM. In addition, the Contractor shall state the estimated time to be spent on the project, list all proposed duties, and indicate the areas or phases for which he/she will be directly responsible.

b) Other Key Personnel

c) Resumes—Resumes of all proposed key personnel are required. At minimum, each must indicate educational background, recent experience, and specific or technical accomplishments.

3) Experience - Within the technical proposal, the Contractor shall submit a brief summary of General Experience, Organizational Experience related to this solicitation, Performance History, and any Pertinent Contracts of similar scope.

a) General Experience - General experience is defined as general background, experience and qualifications of the Offeror. A discussion of proposed facilities which can be devoted to the project may be appropriate.

b) Organizational Experience Related to the Statement of Work - Organizational experience is defined as the accomplishment of work, either past or on-going, which is comparable or related to the effort required by this RFP. This includes overall corporate experience, but not the experience and/or past performance of individuals who are personnel proposed to perform under any contract resulting from this

RFP.

c) Performance History - Performance history is defined as meeting contract objectives within delivery and cost schedules on efforts, either past or on-going, which is comparable or related to the effort required by this RFP.

d) Pertinent Contracts - Pertinent contracts are defined as a listing of each related contract completed within the last three years or currently in process. The listing should include: 1) the contract number; 2) contracting agency; 3) contract dollar value; 4) dates contract began and ended (or ends); 5) description of contract work; 6) explanation of relevance of work to this RFP; 7) actual delivery and cost performance versus delivery and cost agreed to in the contract(s). For award fee contracts, separately state in dollars the base fee and award fee available and the award fee actually received. The same type of organizational experience and past performance data should be submitted.

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7. Any contract resulting from this solicitation will be Indefinite Delivery, Indefinite Quantity with Firm Fixed Price Task Orders.

8. Where applicable, a subcontracting plan will be required by this solicitation.

9. Page Limitation – The Contractor’s technical proposal is limited to 50 pages.

Resumes for key personnel should be limited to five (5) pages, and will be included in the 50 page limit. The only exceptions to the page limit are: the proposal cover-page, the table of contents, and any section title page which does not include any other proposal information. Font size for the main text of the proposal shall be no smaller than 12 Point Times New Roman (smaller fonts are acceptable for graphics, figures, tables, footnotes and legends). The Offeror’s technical proposal shall be printed double-sided with each side counting individually towards the specified page limit.

10. Potential award without discussions. The Government reserves the right to make a/an award(s) without discussions if the Contracting Officer determines that the initial prices are fair and reasonable and that discussions are not necessary.

11. If award will be made without conducting discussions, an Offeror may be given the opportunity to clarify certain aspects of their proposal (e.g. the relevance of an Offeror's past performance information and adverse past performance information to which the Offeror has not previously had an opportunity to respond) or to resolve minor or clerical errors.

12. If the Government intends to conduct discussions prior to awarding a contract, communications will be held with offerors whose past performance information is the single determining factor preventing them from being placed within the competitive range. Such communications shall address adverse past performance information to which an Offeror has not had a prior opportunity to respond. Also, communications may be held with any other offerors whose exclusion from, or inclusion in, the competitive range is uncertain. Such communications shall not be used to cure proposal deficiencies or omissions that alter the technical or cost elements of the proposal, and/or otherwise revise the proposal, but may be considered in rating proposals for the purpose of establishing the competitive range.

13. The Contracting Officer will, in concert with the program staff, decide which proposals are in the competitive range. The competitive range will be comprised of all of the most highly rated proposals. Oral or written discussions will be conducted with all offerors in the competitive range.

14. While it is NIAID's policy to conduct discussions with all offerors in the competitive range, NIAID reserves the right, in special circumstances, to limit the number of proposals included in the competitive range to the greatest number that will permit an efficient competition.

15. The NIAID reserves the right to make a single award, multiple awards, or no award at all in response to this solicitation. In addition, this RFP may be amended or

19 Solicitation# DHHS-NIH-NIAID-AO-2009029 canceled as necessary to meet NIAID's requirements. Synopses of awards exceeding $25,000 will be published in FedBizOpps website (www.fbo.gov).

16. By submission of a proposal, the Offeror understands that its facilities may be subject to inspection under the Federal Regulations of “Good Laboratory Practices” and “Good Manufacturing Practices”

17. Site Visit. After establishment of the competitive range, the Government reserves the right to conduct a site visit of the facilities of any Offeror within the competitive range. Information from the site visit will be considered along with any proposal revisions in the final technical review.

18. In order to ensure a timely response, all questions regarding this solicitation must be submitted in writing to LaDonna Stewart at lstewart@niaid.nih.gov by 10:00am EST on April 23, 2010.

19. METHOD OF ORDERING

Any contract awarded as a result of this solicitation will be an Indefinite Delivery Indefinite Quantity type.

a. A Task Order Number shall be issued at the time that any order is placed.

The Contractor is cautioned not to accept an order unless a task order is signed by the Contracting Officer. Work performed without a signed task order form will not be accepted by the Government.

b. The Contracting Officer shall sign all orders involving requests for supplies and/or services under this contract. Each delivery shall be accompanied by a packing slip or other evidence of delivery/performance.

20. TASK ORDER/DELIVERY ORDER CONTRACT OMBUDSMAN

In accordance with FAR 16.505(b)(5), the following individual has been designated as the NIH Ombudsman for task order and delivery order contracts.

For Non R&D Contracts:

Dr. Richard G. Wyatt NIH Competition Advocate

1 Center Drive, Room 160, MSC

Bethesda, MD 20892-0151 Phone: (301) 496-4920

FAX: (301) 402-4273

e-mail: WyattRG@mail.nih.gov http://www.fbo.gov/� mailto:lstewart@niaid.nih.gov�

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C.I.4. FAR 52.212-2 Evaluation – Evaluation -- Commercial Items (Jan 1999)

(a) The Government will award a contract resulting from this solicitation to the responsible Offeror whose offer conforming to the solicitation will be most advantageous to the Government, price and other factors considered.

1. GENERAL

Selection of an Offeror for contract award will be based on an evaluation of the Offeror’s proposal against four factors. The factors in order of importance are: technical factors (which encompass technical knowledge and approach including evaluation of resources, and personnel); past performance; Small Disadvantaged Business (SDB) participation; and price.

Although technical factors are of paramount consideration in the award of the contract, past performance, SDB participation, and price are also important to the overall contract award decision. In accordance with FAR 15.304, all evaluation factors other than price, when combined, are significantly more important than price.

2. EVALUATION FACTORS

The technical portion of the proposal will be the most important single consideration in the award of the contract, and should therefore, be as complete and specific as possible.

The evaluation will be based on the demonstrated capabilities of the Offeror in relation to the needs of the project as set forth in the Statement of Work. The merits of the Offeror’s proposal will be carefully evaluated in terms of the requirements, and in relation to the criteria established below. The Offeror must submit information sufficient to evaluate its proposal based on the technical criteria listed below. Failure to provide the information required to evaluate the proposal may result in rejection of that proposal without further consideration.

The criteria contained within this element will be used by the technical evaluation committee in reviewing the Offeror’s technical proposal. All technical criteria, including all sub-factors contained within each criterion, are of equal importance.

1) Technical Knowledge and Approach

The Offeror shall include a discussion of its manufacturing process activities including coordination/collaboration with internal, as well as, external sources. Evaluation shall be based upon the following:

a) Demonstration of the Offeror’s technical knowledge and understanding of the scope and purpose of the requirements as delineated by the Statement of Work (SOW).

b) Adequacy and realism of the Offeror’s proposed approach for preparing cell banks and virus vaccine suspensions of the type described by the SOW, including the Offeror’s timeline for generation of batch records, completion of all testing, and preparation of release/safety test reports.

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2) Adequacy of Resources

a) Adequacy of the Offeror’s proposed facilities which meet requirements listed in the Code of Federal Regulations (CFR 21) for an establishment engaged in the preparation of live virus vaccines approved for human use in Phase I and II clinical trials by the Center for Biologics Evaluation and Research (CBER).

b) Realism of the Offeror’s discussion of the types and quantities of internal, as well as, external resources and facilities necessary to accomplish the work delineated by the SOW, including discussion of problems likely to occur and how these problems would be handled in order to minimize the impact on the production process and the delivery timetable.

3) Personnel Qualification and Experience

a) Experience and proficiency of the proposed Project Manager, Project Director, and other support staff, in the growth of vaccine viruses and production of cell lines in accordance with the standards set forth in the Code of Federal Regulations.

b) Experience and proficiency of the proposed Project Manager, Project Director, and other support staff, in the release/safety testing of vaccine virus suspensions and cell lines by procedures required for live virus vaccines by the Food and Drug Administration using the Code of Federal Regulations as guidelines.

c) Experience of the proposed Project Manager, Project Director, and other support staff in preparing final reports suitable for submission to the CBER, FDA in support of Investigational New Drug applications.

4) Corporate Experience

a) Demonstrated experience and proficiency in the growth of vaccine viruses and production of cell lines in accordance with the standards set forth in the Code of Federal Regulations.

b) Demonstrated experience and proficiency of the proposed Organization/Corporation in the release/safety testing of vaccine virus suspensions and cell lines by procedures required for live virus vaccines by the Food and Drug Administration…