Tuesday, September 17, 2013

Biologics Process Development is NOT Biologics Manufacturing Sciences

I often run into folks who think that Process Development duties are the same as or similar to Manufacturing Sciences... that you can port the skills and knowledge of late-stage process development straight over to manufacturing support.

Other than the Manufacturing Sciences lab looking like a PD lab, not much else is the same.
miniferms on benchtop But let's think about this.

Historically, success was achieved when PD defines a process that yields high titers and stable quality characteristics with very little focus on manufacturability.

There's actually a lot wrong with this. Firstly, titer ought not be the optimized parameter; the correct KPI to measure cell culture productivity is volumetric productivity. Secondly, a process is defined by identifying critical process parameters and proving the limits of their ranges. I've seen cases CPPs were defined so narrow that it is impossible to operate within the defined ranges. I've also seen cases where CPPs were not defined at all. When million-dollar batches get rejected over brief excursions outside of the process limits, people start rethinking their strategy.

Over time, some PD groups began listening to manufacturing (sciences) and began understanding that when 100% gains in volumetric productivity can be erased if the process could be successfully executed half the time. They began focusing on fully exploring the parameter space and locking down wide limits for higher process capability.

Some overachieving PD groups even studied excursions and intentionally perturbed cultures to prove that brief excursions outside of the operating limits did not impact product quality. When MSAT campaign monitoring groups had these types of processes, life was heaven.

A Manufacturing Sciences team's job is scientific support of the commercial biologics process.
  • The process is already defined (by PD).
  • Critical process parameters are already known (by PD).
  • The proven acceptable range already specified (by PD).
The goal now is to characterize variability at large-scale, understand how KPIs respond to the measurable main effects and interactions and find the "sweet spot" that produces the most product in the least amount of time.   Oh, and when SHTF, be available to harness your formidable process experience and act to save the campaign from failing the campaign goals.

Most of this can happen with statistical analysis and SPC... bunch of chemical engineers with "fun" software programs.  Sometimes you need lab support to test your hypothesis. Sometimes the motions in this lab look the same as that of a PD lab, but the superficial similarity is about all the overlap there is.

Overall, the day-to-day tasks executed by folks in PD are (and should be) drastically different than the tasks executed by Manufacturing Sciences.


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