Lyophilization process engineering and thermostability of ID93 + GLA-SE, a single-vial adjuvanted subunit tuberculosis vaccine candidate for use in clinical studies

Abstract

Promising clinical efficacy results have generated considerable enthusiasm for the potential impact of adjuvant-containing subunit tuberculosis vaccines. The development of a thermostable tuberculosis vaccine formulation could have significant benefits on both the cost and feasibility of global vaccine distribution. The tuberculosis vaccine candidate ID93 + GLA-SE has reached Phase 2 clinical testing, demonstrating safety and immunogenicity as a two-vial point-of-care mixture. Earlier publications have detailed efforts to develop a lead candidate single-vial lyophilized thermostable ID93 + GLA-SE vaccine formulation. The present report describes the lyophilization process development and scale-up of the lead candidate thermostable ID93 + GLA-SE composition. The manufacture of three full-scale engineering batches was followed by one batch made and released under current Good Manufacturing Practices (cGMP). Up to 4.5 years of stability data were collected. The cGMP lyophilized ID93 + GLA-SE passed all manufacturing release test criteria and maintained stability for at least 3 months when stored at 37°C and up to 24 months when stored at 5°C. This work represents the first advancement of a thermostable adjuvant-containing subunit tuberculosis vaccine to clinical testing readiness.

Safety and immunogenicity of a thermostable ID93 + GLA-SE tuberculosis vaccine candidate in healthy adults

“…Notably, some liquid vaccine formulations with thermostable properties have progressed through clinical testing and even to licensure, with significant beneficial impact due to their thermostability profile demonstrated in field use 11 , 19 , 20 . Nevertheless, the stability of such vaccines outside of refrigerated temperatures is generally limited to days or a few weeks, whereas the thermostable single-vial presentation of ID93 + GLA-SE is stable for 3 months at 37 °C 12 , 13 .…”

“…Results from a previous trial informed dose selection (2 µg ID93 and 5 µg GLA-SE) and schedule for this trial 8 . The thermostable single-vial lyophilized presentation of ID93 + GLA-SE was developed and manufactured as described earlier, including optimization of excipient content, lyophilization process engineering, and comprehensive physicochemical and potency stability monitoring 12 , 13 . The thermostable single-vial lyophilized ID93 + GLA-SE was reconstituted with sterile water for injection (WFI) prior to administration.…”

“…However, maintaining the particulate structure inherent to the activity of many vaccine adjuvant formulations, including emulsions and aluminum salts, requires unique process development and characterization approaches. We previously described the formulation design, process development, and manufacture of a lyophilized formulation of the emulsion-adjuvanted subunit TB vaccine candidate ID93 + GLA-SE that maintained stability for 3 months when stored at 37 °C 12 , 13 .…”

Stressed stability and protective efficacy of lead lyophilized formulations of ID93+GLA-SE tuberculosis vaccine

“…Taken together, the combined data enabled selection of a lead candidate lyophilized formulation of ID93 + GLA-SE containing the disaccharide glass-forming excipient trehalose and Tris buffer. The lead formulation clearly demonstrated enhanced long-term thermostability compared to liquid formulation controls, including the current two-vial clinical presentation, and was considered suitable for future advanced development involving cGMP manufacturing and clinical testing [ 22 ].…”