BCG, Live - PACIS; Bacillus Calmette Guerin (BCG), substrain Montreal
Status: approved; marketed
Organizations involved:
ID Biomedical Corp. – Manuf.; R&D; Tech.; Canada mark.
GlaxoSmithKline plc – Intl. mark.; Parent
UroCor, Inc. – USA mark.
Institut Armand Frappier – R&D; Tech.; Former
Shire Biologics, Inc.. – Former
Shire Pharmaceuticals Group plc – Parent; Former
BioChem Vaccines, Inc. – R&D; Tech.; Former
BioChem Pharma, Inc. – Parent co.; Former
Institute Pasteur – R&D; Tech.; Former
Cross ref: See the entry for BCG Vaccine Products and the entries for other BCG Live products.
Description: BCG, Live or PACIS is a lyophilized (freeze-dried) formulation of a live attenuated strain of the bacterium Mycobacterium bovis – Bacillus Calmette-Guerin (BCG), substrain Montreal, also known as the Armand-Frappier strain of BCG. This therapeutic vaccine is administered by intravesical instillation (placed into the bladder) for treatment of carcinoma-in-situ of the urinary bladder (superficial bladder tumors). Instillation of the live bacteria leads to local inflammatory reactions associated with the elimination or reduction of superficial cancerous lesions of the urinary bladder.
The Montreal/Armand-Frappier strain of BCG has more than 25 years of clinical experience, and is used in a number of countries worldwide. The Montreal strain has the longest therapeutic history for the treatment of bladder cancer of any BCG strain. The original Bacillus of Calmette and Guerin strain was developed by the Pasteur Institute. The Mon-treal substrain of BCG originates from a BCG culture given in 1937 to Dr. A. Frappier, Institut Armand Frappier (IAF; Mon-treal, Canada), by Dr. C. Guerin, Institute Pasteur. The Montreal substrain was maintained by passaging (repeated cy-cles of culturing; which may have contributed to variability of the bacterium over years) until 1973, when the current primary and secondary seed lots were developed (i.e., the cells were preserved by modern cryogenic storage).
PACIS is formulated to contain 120 mg of dry weight semi-solid containing 2.4 to 12 x 108 colony-forming units (CFU) of live BCG per ampoule. The product contains no preservatives. PACIS is reconstituted before use with sterile, preservative-free saline (0.9% Sodium Chloride Injection USP). The potency of PACIS is determined by colony counts derived from a serial passage assay using Dubos medium. The dating period is 12 months from the date of the last valid potency test when stored at 2-8˚C (refrigerated). PACIS contains live, attenuated mycobacteria, and because of the potential risk for transmission, it should be prepared, handled and disposed of as a biohazardous material.
Nomenclature: BCG Live/GSK [BIO]; PACIS [TR in U.S. and other countries]; BCG, Live [FDA]; Bacillus Calmette Guerin (BCG), substrain Montreal [SY]; Mycobacterium bovis, live [SY]; BCG, Armand-Frappier strain [SY]
Companies.: PACIS was commercially developed by Bio-Chem Vaccines, a subsidiary of BioChem Pharma, which became Shire Biologics, now ID Biomedical Corp., which was acquired by and became a subsidiary of GlaxoSmithKline plc (GSK) in late 2005. BioChem Pharma agreed to be acquired by Shire in Dec. 2000, and became Shire Biologics. In April 2004, ID Biomedical Corp. acquired Shire’s vaccine business and R&D and manufacturing facilities for $120 million.
PACIS is manufactured by Shire Biologics, Inc., CBER/FDA est. no. 1620, now ID Biomedical/GSK. PACIS is marketed in the U.S. by UroCor, Inc. GSK now, presumably, handles some or all international marketing.
Manufacture: BCG is cultured in glycerinized potato medium, followed by further passages in Souton medium. After harvesting of the cells by filtration, the bacteria are resuspended in a 15% (w/v) lactose solution, filled into ampules, and lyophilized.
FDA class: Biologic BLA
Approvals: Date = 20000329; first approval; BLA Ref. No. 95-0606 and 95-0628
Indications: [full text of the "Indications and Usage” section of product insert/labeling]:
PACIS is indicated for intravesical use in the treatment of carcinoma-in-situ (CIS) in the absence of associated invasive cancer of the bladder in the following situations: 1) primary treatment of CIS with or without papillary tumors after TUR, 2) secondary treatment of CIS in patients failing to respond or relapsing after intravesical therapy with other agents, 3) primary or secondary treatment of CIS for patients with medical contraindications: to radical surgery. PACIS is not indicated for the prevention of papillary tumors after TUR or for the treatment of papillary tumors occurring alone.
Status: No centralized EU approval granted, with approvals country-by-country.
Medical: The recommended course of treatment is a single dose (instillation or pumping of vaccine suspension into the bladder), once per week, for six weeks, usually administered in a urologist’s office. PACIS treatment should begin 7-14 days after biopsy or TUR (transurethral resection).
Market: The 2007 Average Wholesale Price (AWP) is not available (product not in 2007, 2005 or 2004 Red Book).
Companies involvement:
Full monograph
408 BCG Live/GSK
Nomenclature:
BCG Live/GSK [BIO]
PACIS [TR in U.S. and other countries; assigned to BioChem Pharma]
BCG Live [FDA]
Armand-Frappier strain of BCG [SY]
Bacillus Calmette-Guerin (BCG), substrain Montreal [SY]
Bacillus of Calmette and Guerin (BCG), live [SY]
Mycobacterium bovis (Bacillus of Calmette and Guerin strain), live [SY]
FDA Class: Biologic BLA
Year of approval (FDA) = 2000
Date of 1st FDA approval = 20000309
(in format YYYYMMDD)
Index Terms:
biopharmaceutical products
live microorganisms (as active agent)
vaccines, bacterial
vaccines, live
Bacille Calmette Guerin (BCG)
bacterial culture <!-- bacterialculture -->
Dubos medium
glycerinated-water-potato medium
Mycobacterium bovis
potato medium, glycerinized
Souton medium
lactose
lyophilized (freeze-dried)
sodium chloride
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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