Uncover Hidden Capacity
“Scheduling issues during scale-up are not usually associated with main process directly,” points out Charles Siletti, director of planning and scheduling application at engineering and simulation software firm Intelligen. “They most often arise with support systems like buffer preparation downstream and media prep during cell culture expansion.” Preparing, cleaning, filling, and dispensing tanks are operations processors often take for granted, “until you try to fit them into a plant at large scale.” Bioprocessors have a good feel for these operations at small-scale where everything is done by hand, but this changes at large scale, particularly as resources are shared.
For example, processors assume that if a piece of equipment is utilized 25% of the time at small scale, its potential utilization at large scale should be 60 or 70%. But due to scheduling conflicts 70% may not be feasible, particularly when several processes or operations share one piece of equipment.
Siletti suggests paying attention, not only to major process operations, but to support systems as well, including details as to when every prep and holding tank needs to be turned around, cleaned, and used.
Intelligen’s SchedulePro scheduling software can help smooth out the kinks in equipment utilization scheduling, Siletti reports. The software, which uses an interface language familiar to bioprocessors, checks for equipment conflicts and overbooking, and allows users to create what-if scenarios to optimize processes.
Companies looking for bench-to-feasibility scale-up services up to early-stage clinical manufacturing have a number of choices including larger contract manufacturers.
An increasingly attractive option is a university-based manufacturing organization like Florida Biologix, which is affiliated with the University of Florida. The nonprofit company, with 35 employees, boasts 16,000 square feet of validated, cGMP, multiproduct manufacturing and testing space, and a 5,000 square foot development laboratory next door. Florida Biologix customers include large biotechs with exploratory projects, to virtual and startup companies. According to director of scientific operations Robert Zwerner, Ph.D., “no students work here.”
Many Florida Biologix clients are new to clinical development, and most have non-GMP processes. The company tries to give them a complete package, which they can transfer to a larger contract manufacturer as their molecules progress, Dr. Zwerner reports. That includes batch records, regulatory support, cell banking, cloning, serum-free adaptations, and upstream/downstream unit operation development. The company also performs extensive downstream process optimization and scale-up, particularly for chromatographic separations.
One current customer taking advantage of the Florida Biologix services had developed its own cell line but found after Phase I that those cells would not serve them through commercialization due to low expression yields.
With the primary scale-up focus on equipment and machinery, media companies will point out the importance of ingredients in the scale-up process.