Michael G. Hanna

Time-Dependent Aggregation of Reconstituted BCG Vaccine

The procedures for the reconstitution, dilution and storage of BCG for intravesical use in superficial bladder cancer have not been previously analyzed. Package inserts in the FDA-approved BCG vaccines suggest instillation immediately after reconstitution but allow storage of diluted vaccines for as long as 2 hours prior to treatment. In this report, we examined the effect of storage of diluted BCG vaccines on the quality and antitumor activity of various BCG vaccine preparations. The data show a time-dependent aggregation of BCG after reconstitution. All vaccine preparations tested, including Connaught, Institute Armand Frappier, Japanese, Pasteur, RIVM, and Tice, aggregated after reconstitution and dilution. Visible aggregation was reduced by elimination of the liquid/gas interface. Aggregation appeared to have no effect on colony forming unit counts but adversely affected antitumor activity. We conclude that for optimal results, BCG vaccines should be reconstituted and diluted immediately prior to instillation.