Bacillus Calmette-Guérin Retains Clinically Relevant Viability for up to 72 Hours After Reconstitution: Potential Implications for Clinical Practice in Times of Shortage

Abstract

There have been repeated supply shortages of bacillus Calmette-Guérin (BCG), the gold-standard immunotherapy for patients with high-grade non-muscle-invasive bladder cancer (NMIBC). Organizations have issued guidance on coping with this shortage, including administering split-dose BCG such that one vial may treat up to three patients. However, logistical implementation of this strategy in a real-world setting is hampered by the recommendation to use BCG within 2 h of reconstitution. We assessed BCG viability in terms of colony-forming units (CFUs) and demonstrated that viability remained constant for at least 8 h after reconstitution (decline at 8 h of 9.1% for lot 1 [p = 0.3] and 4.8% for lot 2 [p = 0.2]). While the viability at 24 h was lower, it did not drop to a level below that of reducing the BCG dose to one-third (67% for lot 1 and 60% for lot 2) and remained close to 50% for at least 72 h. An in vitro model using co-culture of BCG and leukocytes with a BCG-sensitive cell line (RT4-V6) demonstrated no decrease in the cytotoxic potential of BCG at 72 h. In times of shortage, BCG vials may be split and administered for up to at least 8 h (or even 72 h) after reconstitution, allowing more patients to benefit from BCG while placing less strain on the logistics of clinical practice. PATIENT SUMMARY: The current supply of and increased demand for bacillus Calmette-Guérin (BCG), used in the treatment of bladder cancer, have led to repeated BCG shortages. One way to address this is to provide a reduced BCG dose to allow more patients to be treated. In this study we found that BCG viability remains clinically relevant up to 72 h after reconstitution, thus allowing for more patients to be treated from a single vial.

Keywords: BCG shortage; Bacillus Calmette-Guérin; Bladder cancer; Microbial viability.