Adenovirus Vaccine, Live, Oral, Type 4 and Type 7
Status: used by U.S. military
Organizations involved:
Teva Pharmaceutical Industries Ltd. – R&D; Tech.;Parent
Barr Labs. – Former
BioReliance Corp. – Manuf.
U.S. Army Medical Research Acquisition Activity (USAMRAA) – USA mark.
Dept. of Defense – Parent
Description:
Adenovirus Vaccine, Live, Oral, Type 4 and Type 7 is a live orally administered lyophilized (freeze-dried) vaccine consisting of two enteric-coated tablets containing a viable selected strain of either type 4 or type 7 adenovirus cultured in WI-38 human diploid fibroblast cells. The viruses have not been attenuated, i.e., they are potentially pathogenic if taken up by the respiratory system. The viruses are separately culture in Dulbecco's Modified Eagle's Medium (MEM), fetal bovine serum and sodium bicarbonate. The virus is harvested, cellular material is removed by filtration and it is formulated and dried by lyophilization. The dried virus material contains monosodium glutamate, sucrose, D-mannose, D-fructose, dextrose, human serum albumn (HSA), potassium phosphate and plasdone C.
The live viruses are formulated in enteric-coated tablets designed to pass through the stomach and release their contents in the intestines. Each tablet contained 4.5 log10 TCID50 (32,000 TCID50) of lyophilized (freeze-dried) live infectious virus in lactose powder. Tablets also contain excipients – monosodium glutamate, lactose, sucrose, d-mannose, d-fructose, dextrose, human serum albumin [Albumin ( Human)], potassium phosphate, and plasdone C. Tablets contain residual components from the growth media for virus and host cells, certain materials used in processing. The inner core tablet contains anhydrous lactose, microcrystalline cellulose, prolacrlin phosphate, magnesium stearate, and live virus. The outer portion contains microcrystalline cellulose, magnesium stearate and anhydrous lactose, with an outer enteric coating of cellulose acetate phthalate, ethyl alcohol, acetone, castor oil and FD&C Yellow #6 aluminum lake dye.
The vaccine is officially defined as the separate Type 4 and 7 tablets (unlike the prior vaccine with its 2 separate approvals).
Adenovirus Vaccine, Live, Oral, Type 4 and Type 7 contains human plasma-derived Albumin at concentrations <0.3 mg/tablet.
The dating period is 24 months from the date of manufacture when stored at 2-8°C (35°-46° F).. The date of manufacture is defined as the date that the drug substance (Adenovirus Type 4 lyophilized intermediate or Adenovirus Type 7 lyophilized intermediate) is blended with the inner core excipients (anhydrous lactose, microcrystalline cellulose, polacrilin potassium and magnesium stearate) prior to inner core compression. The expiration date for the packaged product, Adenovirus Type 4 and Type 7 Vaccine, Live, Oral, is the expiration of whichever vaccine component has the earliest date of manufacture.
Nomenclature: Adenovirus Vaccine [BIO];
Adenovirus Type 4 and Type 7 Vaccine, Live, Oral [FDA];
Adenovirus Type 4 and Type 7 Vaccine, Live, Oral [FDA used in product insert but apparently not the primary CBER-assigned name];
NDC 51285-174-02 [NDCi for type 4 tablet];
NDC 51285-175-02 [NDCi for type 7 tablet];
Companies: In Sept. 2001, Duramed Pharmaceuticals, Inc., a subsidiary of Barr Labs., the largest generic drug company in the U.S., received a $35.4 million six-year contract from the U.S. Department of Defense (DOD) for the clinical development and production of Adenovirus Vaccine Types 4 and 7 tablets (comparable to the original Wyeth products). Under terms of the contract with the DOD, the government provided Barr with ~$17.4 million to support Phase I clinical development of the vaccines, and $18 million to support Phase II and Phase III clinical studies and BLA filing.
As part of the agreement, Barr was required to construct a dedicated facility to support the production of supplies through FDA approval, after which Barr will manufacture the vaccines under DOD contract for dispensing to U.S. armed forces. The contract included the construction of a new freestanding, dedicated manufacturing facility near Barr Labs’ existing building on Perrowville Road in Forest, VA. In July 2003, Barr opened its manufacturing and packaging facility, a 20,000 square foot building, designed specifically to produce these vaccines. Barr had originally indicated that FDA approval of its adenovirus vaccines could come as early as 2007.
In summer 2008, Teva Pharmaceutical Industries Ltd. acquired Barr Labs., making Teva the largest generic drug company.
In Jan. 2009, Duramed/Barr concluded a contract with BioReliance Corp. for supply of bulk Adenovirus Types 4 and 7 Live Oral Vaccines, i.e,. BioReliance cultures the viruses.
FDA class: Biologic BLA
CBER class: Viral And Rickettsial Vaccines
Approvals: Date = 20110316; BLA 125296/0 officially assigned to Teva Women’s Health, Inc., Horsham, PA
Indications: [Full text of the "INDICATIONS AND USAGE" section of product insert/labeling]:
Status:
In Dec. 2008, FDA accepted for filing Duramed's/Barr's BLA, with a PDUFA (target action) date of July 31, 2009. A Complete Response letter (CRL) was issued by FDA on July 16, 2009. Full BLA approval was granted on March 16, 2011.
The vaccine is subject to CBER lot release requirements.
Administration of the adenovirus vaccine to all basic trainees began again in mid to late 2011.
Medical: The tablets should be swallowed whole, without chewing, to avoid releasing live virus in the upper respiratory tract.
Live virus can be shed in stools and potentially cause disease. Vaccinees should exercise caution in their contacts with immune compromised persons for 28 days after vaccination.
Trials: Clinical trials supporting licensure were conducted jointly by the Walter Reed Army Institute of Research, and Navy, Naval Health Research Center, investigators at Fort Jackson, S.C., and Great Lakes Naval Training Center, Great Lakes, Ill. In a study of approximately 4,000 volunteers, the adenovirus vaccine provided 99.3% protection against febrile respiratory illnesses due to the adenovirus type 4 and stimulated protective levels of antibodies against the adenovirus type 7.
Market: The U.S. Dept. of Defense distributes the vaccine to new recruits entering boot camp.
Companies involvement:
Full monograph
403 Adenovirus Vaccine
Adenovirus Type 4 and Type 7 Vaccine, Live, Oral is a vaccine indicated for active immunization for the prevention of febrile acute respiratory disease caused by Adenovirus Type 4 and Type 7. AAdenovirus Type 4 and Type 7 Vaccine, Live, Oral is approved for use in military populations 17 through 50 years of age.
ears of age.
Nomenclature:
Adenovirus Vaccine [BIO]
Adenovirus Type 4 and Type 7 Vaccine, Live, Oral [FDA]
Adenovirus Type 4 and Type 7 Vaccine, Live, Oral [FDA used in product insert but apparently not the primary CBER-assigned name]
NDC 51285-174-02 [NDCi for type 4 tablet]
NDC 51285-175-02 [NDCi for type 7 tablet]
FDA Class: Biologic BLA
Year of approval (FDA) = 2011
Date of 1st FDA approval = 20110316
(in format YYYYMMDD)
Index Terms:
biopharmaceutical products
bovine serum, fetal (FBS)
enteric coating (tablets)
live microorganisms (as active agent)
lyophilized (freeze-dried)
nonoxynol 101 (Triton N101)
vaccines, live
vaccines, viral
adenovirus infection prophylaxis
cells, human
Dubos medium
Eagle's Minimum Essential Medium
fermenters, 1,000 liter
fibroblasts, WI-38 human diploid
mammalian cell culture
WI-38 human diploid fibroblasts
acetone
Albumin (Human)
castor oil
cells, human <!-- humancellculture -->
dextrose
ethanol
fatty-acid esters
fructose
fructose
human Rho(D) cells
lactose
magnesium stearate
mannose
microcarrier culture
monosodium glutamate
plasdone
plasdone
potassium phosphate
proinsulin-tryptophan synthetase fusion protein
sodium bicarbonate
sucrose
Complement-Fixation Test
EU000 Not yet/Never filed with EU
UM100 Controlled/Gov't Distribution in US
US200 Currently Approved in US
EM999 Not Available/Not Marketed in EU
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