(594f) From Grams of Drug Substance to Commercial Scale Clinical Supply Manufacture in Less Than a Year

The combination of continuous manufacturing (CM) and small scale development characterization has enabled rapid development timelines and allowed for delayed determinations of clinical quantity needs. In less than one year, a pre-FHD compound at Eli Lilly advanced from gram quantities of development API to commercial scale tablets for Phase I Clinical Trials. The initial gram quantities of API, of varying particle size distributions, were evaluated and compared in formulated tablets formed on a single station press. Results were used to determine particle size targets for increasing the scale of API manufacture. With low kilogram quantities of scaled-up API available, small demonstration drug product batches using a CM direct compression platform on a rotary press were successfully completed, and tablets were then coated for development stability. The demonstrated development process was transferred to a GMP facility and CT batches were manufactured at commercial scale, occurring within a year of the initial gram scale development assessments.