Scale-up of a low-temperature spray-drying process for a tuberculosis vaccine candidate using lab-scale equipment.

Laboratory-scale spray drying can be a useful tool in developing new dry powder formulations for the delivery of biologics such as therapeutic proteins or vaccines. Low-temperature drying is often used in these processes to prevent the exposure of biologics to harsh conditions that could potentially lead to degradation or instability of the final product. However, low-temperature drying on small-scale equipment can result in very low production rates that may not be practical for generating sufficient material for studies requiring larger sample quantities, such as key preclinical or toxicology studies. This study demonstrates a scale-up effort for a spray dried adjuvanted protein tuberculosis (TB) vaccine candidate using a custom lab-scale spray dryer. To achieve higher throughput without compromising the stability of the powder and biologic material, a process model for the spray dryer was used to determine optimal processing parameters and establish general vaccine powder manufacturing guidelines, such as minimizing exposure to high temperatures and relative humidity during drying. Maximizing dryer throughput and increasing overall feed concentration resulted in a tenfold increase in production rate using lab-scale equipment, such that 97.6 g of powder (the equivalent of about 5,000 human doses) could be produced using a lab-scale spray dryer in a single 6-hour spray drying run.