The Role of Fermentation in BCG Manufacture: Challenges and Ways Forward

AbstractThe BCG vaccine has been in existence for a century and has been instrumental in the control of tuberculosis. The method for producing the vaccine has not changed in a very long time and consists of pellicle growth followed by ball-milling, which is a lengthy and variable approach. There has been increasing interest in the possibility of producing the BCG vaccine by growing it in bioreactors, which could address some of the issues around variation between batches, increase yield, and circumvent the challenges associated with supply and demand. There is evidence that fermentation would be a quicker, more reproducible method of production, and would deliver BCG to a higher yield in a form that would be easier to characterise. However, a change to the manufacturing process may require new evidence of bioequivalence and may attract a requirement for preclinical studies as well as clinical trials from Phase I, through to efficacy studies. This chapter describes the history of the BCG vaccine and the issues of the current production method. We discuss the potential benefits of BCG fermentation and the regulatory steps required for such a method of production to be implemented.