PROOF OF PRINCIPLE
To demonstrate proof of principle, processes were developed for two different mAbs from two different cell lines. One of the
processes was then scaled to the 100-L level using predetermined sizing and selection tools. These tools allowed process development
scientists to determine not only the membrane area or resin volume required for a particular bioreactor volume and titer,
but also the specific device and system size, and associated bag and mixer sizes.
The process delivered effective clearance of impurities in two different production runs for two different monoclonal antibodies;
impurity levels were below targeted levels at the end of the process.
We then scaled up the process in a 200-L bioreactor for one of the antibodies. Overall, yield at both scales was approximately
85% which is satisfactory for a clinical-scale process. Product quality attributes were also assessed. There were no differences
in the charge variant distribution pattern between scales or between unit operations. Distribution of change variants was
the same in final pool from both scales.
The overall process required less than 12 months from start to finish. Manufacturing clone selection required three months;
process development and fitting was completed in two months, during which all assays and a confirmatory run of the final process
at bench scale were completed. The preparation time for pilot scale required about one month and included a water run which
was found to be exceedingly helpful to confirm the workflow and ensure everything fit properly together before conducting
the three 200-L scale runs.
This project demonstrates the value of combining a process template with a preconfigured, single-use process train. Benefits
included reduced time and effort for process development as well as equipment specification and procurement. Most importantly,
this approach allowed both of these activities to be conducted in parallel, thus shortening the overall project timeline.
Single-use technology has come a long way in recent years. And while there is a need for standardization, there is also a
need for continued innovation in this area. If the industry tries to standardize too many things, too early, there is a risk
that it may actually end up limiting itself in terms of finding innovative approaches.
RICHARD PEARCE is director of strategy and business development, BioPharmaceutical Process Solutions, EMD Millipore, Bedford, MA, firstname.lastname@example.org