RE-ESTABLISH THE MANUFACTURE OF ADENOVIRUS VACCINES, TYPES 4 AND 7

Notice Date

January 5, 2001

Contracting Office

Director, USAMRAA, 820 Chandler St, Fort Detrick, MD 21702-5014

ZIP Code

21702-5014

Description

A -- Reestablishment of Production Capability for Manufacture of Adenovirus Vaccines, Types 4 and 7 in Support of the U.S. Army Medical Materiel Development Activity (USAMMDA), Fort Detrick, Maryland 21702; Michael A. Younkins, Contracting Officer, telephone (301)619-2503; Sherry D. Regalado, Contract Specialist, telephone (301)619-2376 SPECIAL NOTICE -- REQUEST FOR INFORMATION -- DRAFT STATEMENT OF WORK FOR INDUSTRY COMMENT. This is not a Solicitation or Request for Proposals. No proposals are sought. Any responses to this Request for Information (RFI) should be submitted by 26 Jan 01. The U.S. Army Medical Research Acquisition Activity (USAMRAA) is seeking potential sources and industry comments on a draft statement of work for the manufacture of Adenovirus Vaccines. This effort is based upon the need to re-establish the manufacturing of Adenovirus Vaccines, Types 4 and 7. Through this effort, the government intends to re-establish the production capability of adenovirus vaccines (Types 4 and 7) and to procure these vaccines on a competitive basis using a cost-reimbursement (cost-plus-fixed-fee) contract with both cost reimbursement and firm-fixed price elements. The thrust of the statement of work is for a contractor to furnish all necessary personnel, expertise, materials, supplies, facilities, equipment, transportation and travel required to (1) re-establish a manufacturing line for the production of adenovirus vaccines (types 4 and 7); (2) prove operational capability of the new line by manufacturing at least three pilot lots each of candidate adenovirus vaccines under good manufacturing processes; and (3) validate the safety and immunogenicity of the pilot lots in accordance with the FDA regulations. At the government's option, the contractor shall furnish the necessary personnel, expertise, materials, supplies, facilities, equipment, transportation, and travel required to validate the effectiveness of the adenovirus vaccines (types 4 and 7) and to obtain FDA licensure. Also, at the government's option, the contactor shall produce, store, and deliver doses of the vaccines in the quantities and schedules stated in Section B of the RFP. Contract Performance Period: Significant schedule uncertainty is associated with the re-establishment of production capability of adenovirus vaccines. An estimate of two to three years will be required to complete the base period. An additional two to three years will be required to complete the first option period. Five optional 12-month periods will be required for procurement of produced vaccines. STATEMENT OF WORK FOR INDUSTRY COMMENT: It is the Government's intent to allow the Offeror to propose a CLIN structure (starting with CLIN 0001) which allows the Offeror to best execute its proposed program. The guidelines below apply to the development and format of the CLINs. The contract types listed below are preferred by the Government; however, other structures and types may be proposed and will be taken into consideration as part of the best value evaluation and will be negotiated. The Offeror shall develop CLINS for all efforts necessary to submit Investigational New Drug (IND) applications to the U.S. Food and Drug Administration (FDA) for adenovirus vaccines Types 4 and 7 as well as the conduct of Phase I safety and immunogenicity trials (CPFF). The Offeror shall develop an OPTION for all remaining developmental efforts necessary to obtain approval of Biologic License Applications (BLAs) from the FDA for the manufacture and production of Adenovirus Vaccine, both Type 4 and Type 7 (CPFF). The Offeror shall develop five annual OPTIONS for the production and delivery of 150,000-300,000 doses each of adenovirus vaccines types 4 and 7 (FFP). SECTION C WORK STATEMENT C.1 BACKGROUND Prior to widespread immunization against adenoviruses, acute respiratory disease was the leading cause of morbidity and hospitalization in US military trainees during initial entry training. Adenoviruses infected 10%-20% of all initial entry trainees and were associated with up to 90% of all cases of pneumonia among trainees. Compared with their civilian peers, young adults undergoing initial entry training in the US military are at increased risk of respiratory infections due to crowding in living quarters and due to increased stress levels during initial entry training. Outbreaks incapacitated many training commands and occasionally halted the flow of new trainees out of these commands and into combat units. This had tremendous impact on military readiness and compelled military policy makers to establish adenovirus vaccine development programs. Several adenovirus vaccines were evaluated during the 1950s and 1960s. An effective live-virus vaccine against serotype 4 became available by the late 1960s and a similar vaccine against serotype 7 became available a few years later. By 1971 the combined use of serotype 4 and 7 vaccines was routine policy for new trainees; and for the next 28 years, this vaccination policy greatly reduced hospitalizations due to acute respiratory disease among trainees. In July 1980, Wyeth Labs received a license from the Food and Drug Administration (FDA) to manufacture adenovirus vaccines (both types 4 and 7), and Wyeth Labs became the sole manufacturer of adenovirus vaccines. These vaccines were live virus vaccines, delivered orally in enterically-coated tablets. Although vaccination with the Wyeth Labs vaccines resulted in fecal shedding in greater than 88 percent of immunized individuals, vaccination did not result in virus excretion as detected in throat secretions. Preferential viral infection in the gastrointestinal tract rather than in the upper respiratory tract resulted in the development of neutralizing antibody responses in 85% percent of immunized individuals. Vaccine induced immune responses resulted in protection against future viral infection and disease. In May 1994, the manufacturer informed the DoD that it would no longer produce the vaccines in the existing facility due to changes in Good Manufacturing Practice (GMP) standards and Occupational Safety and Health Agency (OSHA) regulations. The last lot of adenovirus vaccine was produced in 1995 and delivered to the DoD in 1996. Afterward the manufacturer dismantled the production facility. Shelf-life extensions and rationing allowed continued use of adenovirus 4 vaccine until 1998 and adenovirus 7 vaccine until 1999. Since the end of the vaccination program, numerous adenovirus outbreaks have been reported at Army (Fort Jackson, SC and Fort Leonard Wood, MO), Navy (Naval Training Center, Great Lakes, IL), Air Force (Lackland Air Force Base, Texas), and Marine Corps (Marine Corps Recruit Depot, San Diego, CA) initial training centers. To prevent future adenovirus outbreaks at training centers, the DoD has a requirement for safe and effective adenovirus vaccines (types 4 and 7) at the earliest possible date. C.2 STATEMENT OF WORK The contractor shall furnish the necessary personnel, expertise, materials, supplies, facilities, equipment, transportation, and travel required to: 1) Manufacture at least three pilot lots each of candidate adenovirus vaccines (Types 4 and 7) for evaluation 2) Prepare protocols for evaluating the safety of the candidate vaccines 3) Submit INDs to the FDA, and 4) Conduct clinical trials to demonstrate candidate vaccines safety and immunogenicity individually and in combination. At the Government's option, the contractor shall also furnish the necessary personnel, expertise, materials, supplies, facilities, equipment, transportation, and travel required to complete the development of the adenovirus vaccines (Types 4 and 7), obtain FDA licensure, and produce, store, and deliver doses of vaccine in the quantities and schedules stated in Section B. C.3 Adenovirus Vaccine Minimum Requirements. The minimum requirements for the newly produced adenovirus types 4 and 7 vaccines shall be similar in potency as the original vaccine produce by Wyeth Labs. Past experience indicates that 85% percent of susceptible individuals (serum neutralizing (SN) titers < 1:4) develop neutralizing antibody and excrete virus in the feces when given the minimum or greater required vaccine dose of 104.5 tissue culture infectious dose 50. Following immunization with this dose a 90% or greater reduction in acute febrile respiratory disease (ARD) to adenovirus types 4 and/or 7 occurs during outbreaks of ARD. The vaccine viruses were not detected in throat secretions. C.4 POTENTIAL DEPARTMENT OF DEFENSE SUPPORT Department of Defense organizations possess expertise in infectious diseases, epidemiology and laboratory diagnosis. Support from these organizations may be provided for controlled clinical studies and large field studies on request from the vaccine manufacturer. This support will be negotiated. On request, Department of Defense organizations conducting respiratory disease surveillance programs will provide data and information needed to design and conduct field trials for safety, immunogenicity and efficacy leading to licensure. C.5 DOCUMENTS AND TECHNOLOGIES AVAILABLE FROM WYETH LABS The documents/technologies listed below are available from Wyeth Labs, the previous manufacturer of the Adenovirus Vaccines. Wyeth Labs has indicated to the Government their willingness to transfer these documents/technologies to the selected Offeror after negotiation. Standard Operating Procedures (SOPs) for cell culture and virus production, equipment set up for previously used equipment, lyophilization of intermediates, compounding, inspection of filled drug product, raw materials and intermediate testing, and final product testing. Sample batch records for previously manufactured vaccines. Frozen seed stocks of both Type 4 and Type 7 Adenovirus, and associated passage histories. List of Raw Materials used in the manufacture of the drug substance and drug product. Formulas for manufacturing solutions used in the manufacture of the drug substance and drug product. Results of safety testing of the virus seeds that were used to support product approval. HOW TO RESPOND TO THIS NOTICE: Please submit your information and comments to Ms. Sherry Regalado, Contract Specialist at the above address by the requested date. Please submit replies in hard copy. You may also submit your responses via electronic mail to: sherry.regalado@amedd.army.mil. The use of information received in response to this notice may be used by USAMRAA for acquisition planning and solicitation preparation activities. Any subsequent solicitation will be synopsized prior to release. Eligibility in participating in a future acquisition does not depend upon a response to this notice. USAMRAA will not critique the responses to this notice and the notice should not be used by offerors to market their products/services. USAMRAA does not intend to pay for the information solicited and will not recognize any cost associated with responding to the RFI. Proprietary information is neither sought or desired. If such information is submitted, it must clearly be marked "proprietary" on every sheet containing such information.

Record

Loren Data Corp. 20010109/SPMSC001.HTM (W-005 SN50A2H2)