SOURCES SOUGHT:  OPERATION OF A VIRUS VACCINE PRODUCTION FACILITY 

Release Date:  April 26, 2002
NOTICE: NOT-AI-02-021

National Institute of Allergy and Infectious Diseases (NIAID)
 (http://www.niaid.nih.gov)

Receipt Date:  June 14, 2002

DESCRIPTION

The Laboratory of Infectious Diseases, Division of Intramural Research, 
National Institute of Allergy and Infectious Diseases, seeks Capability 
Statements from qualified sources to provide the necessary services, 
qualified personnel, material, equipment, and facilities, not otherwise 
provided by the Government as needed to prepare, with the approval of the 
Project Officer, suspensions of viruses which have been shown by evaluation 
in vitro and in vivo to be promising candidates for use in immunoprophylaxis 
of human diseases.  Also prepare suspensions of wild type viruses, which are 
needed for evaluation of effectiveness of immunoprophylaxis.  These virus 
suspensions, which are chosen for evaluation in volunteers by the Project 
Officer, shall be prepared using methods and in facilities which meet FDA 
standards for preparation of licensed live virus vaccines as described in the 
most current Code of Federal Regulations; specifically 21 CFR 58; 21 CFR 210; 
21 CFR 211; 21 CFR 600, and 21 CFR 610.  When applicable, animal derived raw 
materials and virus suspensions shall be tested for bovine and porcine 
viruses as described in 9 CFR 113.47 and 9 CFR 113.53. Virus suspensions 
shall be prepared by methods required by FDA for production of licensed live 
virus vaccines as described in the above referenced CFR.  Further, these 
suspensions shall be safety-tested for absence of adventitious agents by 
procedures required for live virus vaccines licensed by the Center for 
Biologics Evaluation and Research (CBER), FDA, using the CFR sections 
indicated above as guidelines.  In addition, the following guidelines should 
also be followed in the preparation of the live or the non-living viral 
vaccines or wild type viruses as needed: 

A.  Points to Consider in the Characterization of Cell Lines to Produce 
Biologicals, CBER (7/93), at: http://www.fda.gov/cber/gdlns/ptccell.pdf 
B.  ICH Harmonised 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). 
C.  ICH Guideline Q5D: Derivation and Characterization of Cell Substrates 
Used for the Production of Biotechnological/Biological Products at 
http://www.ifpma.org/pdfifpma/q5d.pdf
D.  FDA Guidance Document Concerning Use of Pilot Manufacturing Facilities 
for the Development and Manufacture of Biological Products; Federal Register; 
Vol 60 No.132;35750-35753 or http://www.fda.gov/cber/gdlns/pilot.txt
E.  Guidance for Industry: Content and Format of Chemistry, Manufacturing 
and Controls Information and Establishment Description for a Vaccine or 
Related Product at http://www.fda.gov/cber/gdlns/cmcvacc.pdf
F.  Guidance for Industry: Good Manufacturing Practice Guidance Q7A: Good 
Manufacturing Guidance for Active Pharmaceutical Ingredients at 
http://www.fda.gov/cber/gdlns/ichactive.pdf
G.  Guidance for Industry: Manufacturing, Processing or Holding Active 
Pharmaceutical Ingredients http://www.fda.gov/cber/gdlns/active.pdf
H.  Guidance for Industry for the Submission of Chemistry, Manufacturing, 
and Controls Information for a Therapeutic Recombinant Derived Product or a 
Monoclonal Antibody for in vivo use; http://www.fda.gov/cber/gdlns/cmcdna.pdf
I. ICH Guideline Q5B (Genetic Stability): Quality of Biotechnology 
Products: Analysis of the Expression Construct in Cells used for the 
Production of r-DNA Derived Protein Products, at 
http://www.ifpma.org/pdfifpma/q5b.pdf
J. ICH Final Guidelines on Stability Testing of Biotechnology/Biological 
Products, Federal Register, Vol. 61, No. 133 36466-36469, (7/10/1996).
K. ICH Guideline Q6B: Test Procedures and Acceptance Criteria for 
Biotechnological/Biological Products, Federal Register, Vol 63, No. 110 
31056-31513 (6/9/1998).
L. ICH Guideline Q2A: Text on Validation of Analytical Procedures 
http://www.ifpma.org/pdfifpma/q2a.pdf
M. ICH Guideline q2B: Validation of Analytical Procedures: Methodology, 
http://www.ifpma.org/pdfifpma/q2b.pdf
N. Guidance for Industry: The Sourcing and Processing of Gelatin to Reduce 
the Potential Risk Posed by Bovine Spongiform Encephalopathy (BSE) in FDA-
Regulated Products for Human Use at 
http://www.fda.gov/opacom/morechoices/industry/guidance/gelguide.htm
 
Potential offerors shall be able to prepare the following virus suspensions 
and associated services as requested by the project Officer: 

1. Paramyxoviruses.   Prepare 1-2 liters of four (4) suspensions of wild type 
or attenuated parainfluenza or respiratory syncytial virus per year in (i) 
human or simian diploid cells such as FRhL cells or (ii) heteroploid cells 
such as Vero cells that have been qualified for use in the production of a 
live virus vaccine for administration to humans as currently recommended by 
the FDA.  These viruses shall include human wild type, temperature sensitive 
(ts) and cold adapted (ca) viruses, and viruses derived using recombinant DNA 
technology.  Produce and test these viruses as described above and ensure 
that they have an infectivity of 106 or greater for parainfluenza viruses and 
105 or greater for respiratory syncytial virus. Vaccine candidates for the 
recently described human metapneumoviruses might also need to be made.
2. Rotavirus.  Prepare 2-3 liters of three (3) rotavirus suspensions 
each year in cell cultures of primary or secondary African green monkey 
kidney (demonstrated previously to be free of simian adventitious agents) or 
in human or simian cells suitable for production of vaccines intended for use 
in humans.  Aliquot virus suspensions which (a) have acceptable infectivity, 
i.e., 106 pfu per ml titered in MA104 cells or other suitable infectivity 
titers as determined by the Project Officer and (b) retain the identity of 
the rotavirus supplied by the Project Officer.
3. Hepatitis.  Each year, distribute up to two (2) different suspensions 
of non-living hepatitis virus vaccine (eg., inactivated whole virus vaccine 
or virus like particles prepared by recombinant DNA technology) into vials 
and perform final container safety test for sterility and general animal 
safety.  In addition, prepare 2-3 liters of two (2) virus suspensions of 
candidate live attenuated hepatitis virus vaccines per year.  It may be 
necessary to clone and characterize selected tissue culture cells for their 
usefulness as substrates for hepatitis virus vaccine production.
4. Vaccinia Viruses.  Prepare about 500 ml of 2 preparations per year of 
recombinant vaccinia virus, primarily a derivative of MVA (Modified Vaccinia 
Ankara), bearing an insert of a gene of interest to NIAID scientists (e.g., 
the G and F glycoproteins of respiratory syncytial virus or the E protein of 
dengue virus) for studies in humans.  Produce such candidate virus vaccines 
in cells derived from avian species suitable for use in preparation of 
viruses destined for use in humans.  Ensure that each preparation has a virus 
titer of approximately 108.5-9.0 pfu/ml.
5. Dengue viruses.  Prepare 2-3 liters of three (3) wild type or live 
attenuated dengue virus per year in Vero or other cells qualified for use in 
preparing vaccines for administration to humans.  Viruses will be supplied by 
the Project Officer in the form of DNA-derived viruses recovered from 
transfected C6/36 mosquito cells or Vero cells.  The viruses will be 
amplified and cloned in Vero or another cell line qualified for use in the 
preparation of viruses to be given to humans.  Ensure that the viral 
preparations have an infectivity of 105.0-6.0 or greater.  The viruses are to be 
administered parenterally and should contain no serum or antibiotics.  The 
amount and size of cell DNA that contaminates the vaccine should meet FDA 
requirements for parenterally administered vaccine preparations prepared in 
cell lines such as Vero cells.
6. Caliciviruses.  Prepare two (2) suspensions of recombinant virus-like 
particles (VLPs) per year for calicivirus reference strains of interest.  The 
VLPs will be purified from the culture fluids of insect cells infected with 
recombinant baculoviruses expressing the capsid protein of human calicivirus 
strains such as the Hawaii, Toronto, and Desert Shield viruses.  
Approximately 50 mg of purified VLP protein for each virus strain will be 
needed for use in diagnostic assays.  Safety testing of these diagnostic 
reagents will not be required.  In addition, VLPs will be purified for 
evaluation as vaccine candidates. Approximately two (2) preparations of 10-30 
mg of VLP for administration to humans will be made per year.  Prepare one 
(1) challenge virus suspension per year derived from a stool filtrate 
according to tests required by FDA for biological materials suitable for 
administration to humans.
7. Influenza Viruses.  Prepare (2) virus suspension of 2-3 liters of 
influenza virus in embryonated chicken eggs obtained from specific pathogen 
free flocks and safety test these suspensions during each contract year.  
These viruses include wild type and attenuated influenza virus of H1N1 and 
H3N2 subtypes or other subtypes as they appear in nature.  Seed virus will be 
provided by the Project Officer.  The suspensions shall be grown in SPAFAS 
avian leucosis virus-free embryonated eggs.  The final product shall be 
tested for freedom from avian leucosis virus and other adventitious microbial 
agents.  The viral suspensions shall (a) have requisite infectivity, i.e., 
107.5 to 108.0 plaque forming units (pfu) per ml measured on MDCK cell culture 
monolayers in the presence of ~1 µg of trypsin per ml and (b) 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).
8. Provide documentation for all animal derived raw materials used in the 
manufacture of these virus suspensions including country of origin and 
certificates of analysis documenting the quality control tests performed by 
the vendor.
9. Store the virus suspensions at -70° C or below and distribute aliquots 
to laboratory of clinical investigators at the direction of the Project 
Officer.
10. Provide detailed protocols for those virus suspensions  which meet FDA 
requirements for preparation of seed virus, for growth of virus suspension, 
and for demonstration of freedom of the virus suspension from adventitious 
agents.  These preparations will include, but not be limited to, the 
following viruses.  The ability to prepare viruses using BSL3 conditions 
might be needed in rare situations.
11. Deliver the materials, i.e., viruses and appropriate Clinical Lot 
Release Protocols within five (5) months of the date of availability of seed 
viruses in order to accomplish the goals of this contract.
12. Provide a repository for the long-term storage of government-owned 
viruses at –75°C for viruses and and cells banks –150°C for the cell lines.  
13. Produce and qualify cell lines as directed by the Project Officer for 
use by LID and by the contractor in the production of viruses to be 
administered to humans or for other uses as directed by the Project Officer.  
Cell lines produced and qualified for use under this contract will be 
considered government-owned materials. 

Any potential offeror must be able to document the experience and 
capabilities of professional and technical personnel assigned to this 
project. The professional and technical personnel shall have extensive 
experience in the preparation of suspension of viruses, including wild type 
viruses.  In addition, the offeror must possess the necessary facilities to 
accomplish this work, or must demonstrate the ability to obtain these.  
Capability statements may be submitted to the following address:

Contracting Officer
Acquisition Management and Operations Branch
National Institutes of Allergy and Infectious Diseases
National Institutes of Health 
6700-B Rockledge Drive
Room 1127, MSC 7605 
Bethesda, MD, 20892-7605

Point of Contact: 
Ivan Hernandez, Contract Specialist, Phone 301-496-3878
John Foley, Contracting Officer, Phone 301-496-3878 

This announcement does not commit the Government to award a contract. No 
collect calls will be accepted.


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