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 (#407). See also the entry below for the other BCG Vaccine, and the entry (#410) for TICE BCG, essentially the same at this product but used for treatment of bladder cancer.

Description: BCG Vaccine is a formulation of lyophilized (freeze-dried) live attenuated Mycobacterium bovis (Bacille Calmette Guerin) Tice strain bacterium, used for prevention of tuberculosis. The source Tice strain was originally developed at the University of Illinois, and was derived from the original Bacillus of Calmette and Guerin strain obtained from the Pasteur Institute. The concentration of bacteria in the vaccine is 1 to 8 x 108 colony (100-800 million) forming units (CFU) per ampule. A similar product also from Akzo, Tice BCG (OncoTICE), has been used since 1976 for the treatment of superficial bladder cancer. The medium in which the BCG is grown for the preparation of the freeze-dried cake is composed of glycerin, asparagine, citric acid, potassium phosphate, and 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). 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, which is essentially equivalent to 50 mg (wet weight). Since it is a live bacterium, all supplies and receptacles in contact with BCG Vaccine should be considered a biohazard.

Nomenclature: BCG Vaccine/Akzo [BIO]; BCG Vaccine [FDA USAN]; BCG Vaccine for Percutaneous Use [FDA full]; BCG Vaccine USP [USP]; Bacillus Calmette Guerin, live [SY]; Bacille Calmette Guerin vaccine [SY]

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 Calmette Guerin strain from the Pasteur Institute) grown on Sauton (potato and glycerin-based) medium.

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; approval date according to the CBER/FDA database

Date = 19900824; first approval according to Immuno-Facts

Date = 19940000; PLA/ELA supplements granted for change in production facilities from Chicago, IL, to Durham, NC

Date = 19950110; first approval according to the 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

Status: This is the only prophylactic tuberculosis vaccine currently available in the U.S. The joint recommendations of the CDC’s Advisory Committee on Immunization Practices and the Advisory Committee on Elimination of Tuberculosis were published in the April 15, 1996, issue of Morbidity and Mortality Weekly Report (MMWR, 1996;45 [no. RR-4]:1-18).

No centralized EU approval granted, with approvals country-by-country.

Market: The 2007 Average Wholesale Price (AWP) is $169.10/vial (unchanged from 2004) (Red Book, 2007). As discussed in the BCG Vaccine Products entry (#407), prophylactic tuberculosis vaccines are rarely used in the U.S.