Tice BCG; OncoTICE; Bacillus Calmette Guerin, live
Status: approved; marketed
Organizations involved:
Schering-Plough Corp. – Manuf.; Tech.; World mark.
Merck & Co., Inc. – Parent
Organon Teknika Corp. – R&D; Tech.; Former
Organon, Inc. – Former
Akzo-Nobel N.V. – Parent; Former
Pasteur Institute – R&D; Tech.; Former
University of Illinois – R&D; Tech.; Former
Cross ref: See the BCG Vaccine Products entry above, the other BCG Live product entries, and the entry for a similar product, BCG Vaccine, also from Akzo, used for prevention of tuberculosis.
Description: BCG Live or Tice BCG is a formulation of lyophilized (freeze-dried) live attenuated Mycobacterium bovis (Bacille Calmette Guerin) Tice strain bacterium. The source Tice strain was originally developed at the University of Illinois, derived from the original Bacillus of Calmette and Guerin strain obtained from the Pasteur Institute. Tice BCG/OncoTICE has been used since 1976 for the treatment of superficial bladder cancer.
TICE BCG is supplied as a freeze-dried powder in a box containing one vial. Each 2 mL vial contains 1 to 8 x 108 colony forming units (CFU) of bacteria, which is essentially equivalent to 50 mg (wet weight). The medium in which the BCG is cultured for the preparation of the freeze-dried cake is composed of the following: glycerin, asparagine, citric acid, potassium phosphate, ammonium citrate. The final preparation, prior to freeze drying, also contains added magnesium sulfate, and iron lactose. No preservatives are added. The vaccine is supplied in 2 mL ampules, providing one dose after reconstitution of the powder with sterile saline for administration by instillation into the patient’s bladder. The product is stored at 2-8˚C (refrigerated).
History: TICE BCG was originally developed in the mid-1930s at the University of Illinois (for tuberculosis prophylaxis) from a strain maintained by University of Montreal (which was derived from the original Bacillus of Calmette and Guerin strain from the Pasteur Institute) grown on Suuton (potato and glycerin-based) medium. The first major clinical studies for cancer bladder treatment were in the early 1980s.
Nomenclature: BCG Live/Schering-Plough [BIO]; Tice BCG [TR in U.S.; Tice reg. to the Univ. of Illinois]; OncoTICE [TR outside U.S.]; BCG Live [FDA]; Bacillus of Calmette and Guerin, live [SY]; Mycobacterium bovis Tice strain, live [SY]; Bacille Calmette Guerin (BCG), live [SY]; Bacillus Calmette Guerin (BCG), live [SY]; NDC 00052-0602-02 [NDC]
Companies.: BCG Live was originally developed by Organon, a subsidiary of Akzo-Nobel N.V.; manufactured at Organon Teknika Corp. (Durham, NC), CBER FDA est. no. 0956; marketed in the U.S. by Organon, Inc.; and marketed internationally by Akzo-Nobel affiliates. Organon was acquired acquired by and merged into Schering-Plough in March 2007.
In March 2009, Merck & Co. acquired Schering-Plough in a deal valued at over $41 billion..
FDA class: Biologic PLA
CBER class: Bacterial Antigens and Vaccines
Approvals: Date = 19890621, PLA; first approval according to CBER/FDA database
Date = 19900824; first approval according to ImmunoFacts
Date = 19940000; PLA/ELA supplements granted for changes in production facilities from Chicago, IL, to Durham, NC
Date = 19950110; first approval according to FDA vaccines approval list in the Jordan Report; and “Licensed Vaccines Currently Distributed in the United States,” Office of Vaccine Research and Review, CBER, FDA, July 29, 1999
Date = 19980821; PLA supplement (ref. no. 92-0308); Indication = intravesical instillation to include adjunct treatment of stage Ta or T1 papillary tumors of the bladder
Indications: [full text of "INDICATIONS AND USAGE” section of product insert/labeling]:
TICE BCG is indicated for the treatment and prophylaxis of carcinoma in situ (CIS) of the urinary bladder, and for the prophylaxis or primary or recurrent stage Ta and/or T1 papillary tumors following intraurethral resection (TUR). TICE BCG is not recommended for stage TaG1 papillary tumors, unless they are judged to be at high risk for recurrence.
TICE BCG is not indicated for papillary tumors of stages higher than T1.
Status: Previous FDA-approved Tice BCG vaccines were manufactured by: the Univ. of Illinois, approved in July 1950, revoked in May 1987; license assumed by (approval revoked and reissued to) Bionetics Research Inst. on May 1987, revoked in June 1989; by Connaught Labs. Ltd., approved in March 1967, revoked in Oct. 1998; and Glaxo Operations U.K. Ltd., approved January 1963, revoked July 1990.
No centralized EU approval granted, with approvals country-by-country.
Tech. transfer: Vaccinogen Inc. has exclusively licensed rights to TICE BCG and has a supply agreement with Organon for vaccine use in autologous carcinoma tumor cell vaccines.
Medical: A standard treatment schedule of TICE BCG consists of one intravesicular instillation per week for six weeks. The schedule may be repeated once if tumor remission has not been achieved. Thereafter, BCG administration may be continued at monthly intervals for 6-12 months.
Tice BCG should be administered 7-14 days after bladder biopsy. Patients should not drink fluids for four hours before treatment, and should empty their bladder prior to BCG administration. The reconstituted BCG is installed into the bladder by gravity flow using a catheter. TICE BCG should be retained in the bladder for two hours and then voided. While the BCG is retained in the bladder, the patient should be repositioned (from laying on front, side, back, etc.) every 15 minutes to maximize internal surface exposure.
The dose for the intravesical treatment of carcinoma-in-situ (CIS; bladder cancer) and for prophylaxis of recurrent papillary tumors consists of one vial of TICE BCG suspended in 50 mL of preservative-free saline. Since it is a live bacterium, all supplies and receptacles in contact with TICE BCG should be considered a biohazard. To prepare the BCG suspension, one mL of sterile-preservative free saline (0.9% sodium chloride USP) is drawn into a small syringe and then added to one vial of TICE BCG. After gentle mixing, the BCG suspension is dispensed from the syringe into either another syringe which contains 49 mL of saline diluent or into a 50 mL plastic i.v. saline bag. The suspended Tice BCG should be used immediately after preparation.
Market: The 2007 Average Wholesale Price (AWP) is not available (not in the 2007 Red Book). The 2005 AWP was $169.10/vial (no change from 2004).
Companies involvement:
Full monograph
410 BCG Live/Schering-Plough
Nomenclature:
BCG Live/Merck [BIO]
Tice BCG [TR in U.S.; Tice is the reg. trademark and is held by the Univ. of Illinois]
OncoTICE [TR all countries outside U.S.]
BCG Live [FDA]
Bacillus of Calmette and Guerin (BCG), live [SY]
Mycobacterium bovis (Bacillus of Calmette and Guerin strain), live [SY]
Mycobacterium bovis Tice strain, live [SY]
Bacille Calmette Guerin (BCG), live [SY]
Bacillus Calmette Guerin (BCG), live [SY]
NDC 00052-0602-02 [NDC]
FDA Class: Biologic PLA
Year of approval (FDA) = 1989
Date of 1st FDA approval = 19890621
(in format YYYYMMDD)
Index Terms:
biopharmaceutical products
live microorganisms (as active agent)
vaccines, bacterial
vaccines, live
asparagine
Bacille Calmette Guerin (BCG)
bacterial culture <!-- bacterialculture -->
citric acid
glycerin
iron ammonium citrate
magnesium sulfate
Mycobacterium bovis
potassium phosphate
lactose
approval dates uncertain (FDA reports erroneous, conflicting, or simply has lost the original approval dates) (FDAapproved)
approval dates uncertain (FDA reports erroneous, conflicting, or simply has lost the original approval dates) (FDAapproved)
EU200 Currently Approved in EU
UM001 Marketed Product in US
US200 Currently Approved in US
EM001 Marketed Product in EU
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