Bacillus Calmette-Guérin (BCG) is an immunotherapy product derived from a live, weakened strain of Mycobacterium bovis. It has been a standard treatment for certain cancers and an established vaccine for decades. A significant and prolonged shortage of this drug has created a decade-long crisis for specific patient populations worldwide, causing substantial consequences for the medical community that relies on this unique biological agent.
The Dual Role of BCG
BCG has two primary medical applications, contributing to its global demand and supply complexity. Its original and most widespread use globally is as a vaccine to protect against Tuberculosis (TB). The vaccine is administered to billions of people, mainly in countries where TB is common, to prevent severe forms of the disease.
The second major use is as an immunotherapy for non-muscle-invasive bladder cancer (NMIBC). For this treatment, BCG is administered directly into the bladder, stimulating a local immune response against cancer cells. This treatment is highly effective at preventing cancer recurrence and progression, particularly for high-risk tumors like carcinoma in situ (CIS). The specific TICE strain manufactured by Merck is primarily used for bladder cancer treatment in the United States and many other regions.
Current Status of BCG Availability
The shortage of the TICE strain of BCG continues to be a major challenge for the bladder cancer community in 2024 and 2025. Global demand consistently outpaces the maximum manufacturing capacity of the sole U.S. supplier, Merck. Although the company has increased production by over 100% and is operating at full capacity, supply constraints persist due to rising worldwide need.
This ongoing supply issue necessitates conservation measures at many institutions. Merck allocates its limited supply to wholesalers and distributors based on historical purchasing patterns. The earliest projection for a substantial increase in supply is tied to the completion of a new manufacturing facility, expected to be fully operational by late 2026. This facility is intended to triple the current TICE BCG manufacturing capacity, which should meet anticipated global demand. Additionally, the U.S. Food and Drug Administration (FDA) authorized an expanded access program in early 2025 for an alternative BCG source from the Serum Institute of India, offering immediate relief.
Core Reasons for Supply Constraints
The prolonged BCG shortage is rooted in the complex nature of its production and reliance on a limited number of manufacturers. BCG is a live, attenuated bacterium, meaning its culture and quality control process are significantly more difficult than for standard chemical drugs. The cultivation process for a single batch of BCG is lengthy, taking more than three months to complete.
The global reliance on one major supplier, Merck, for the TICE strain in the U.S. and other areas is a major vulnerability. This single-source dependency became acute after Sanofi Pasteur ceased production of the rival Connaught strain in 2012 due to manufacturing and quality control issues. Facilities producing biological agents like BCG are subject to rigorous regulatory standards, and any contamination or quality lapse can lead to a complete production shutdown. This combination of a complex, time-consuming manufacturing process and limited global production sites creates a fragile supply chain easily overwhelmed by increased demand.
Clinical Strategies for Managing the Shortage
Persistent supply constraints have forced clinicians to adopt specific strategies to conserve BCG supply and prioritize its use. Current guidelines recommend that BCG not be used for patients with low-risk non-muscle-invasive bladder cancer (NMIBC). Instead, the limited supply is reserved for high-risk patients, such as those with carcinoma in situ (CIS) or high-grade T1 disease.
One common conservation method is dose reduction, where a single vial of BCG is split to provide one-half or one-third of the standard dose to multiple patients. This practice is based on clinical data suggesting that reduced-dose BCG can still be effective, especially for maintenance therapy. Maintenance therapy, which typically extends for one to three years, is often delayed or limited to one year to stretch the existing supply.
When BCG is unavailable, urologists use alternative treatments, primarily intravesical chemotherapy agents. Options like Mitomycin C, Gemcitabine, or Docetaxel are administered directly into the bladder. Newer therapies like nadofaragene firadenovec-vncg (Adstiladrin) and checkpoint inhibitors are also emerging as alternatives for patients whose disease is non-responsive to or who cannot receive BCG.