Living the Biopharma Dream in Lincoln

Dr. Michael Meagher has been planning his dream home for nearly two decades. Only this home isn’t where he lives, but where he works—on the lower levels of Othmer Hall on the campus of the University of Nebraska-Lincoln, his employer since he left Hoffman-LaRoche in 1989.

Under Meagher’s direction, UNL has built one of the top biopharmaceutical research facilities in academia, the Biological Process Development Facility. The BPDF has had GMP capabilities in its past, but the latest incarnation, set for its ribbon-cutting this winter, is the culmination of his dream—a state-of-the-art pilot-scale plant with core competencies in the development of vaccines and therapies from recombinant yeast and bacteria.

Meagher will have what he calls “an academic CMO on steroids,” able to develop robust Phase I and II trial products and technology transfer. He has built it. Now, will they come?

The Tour Begins Here

The BPDF already has quite a reputation. It has worked with the Department of Defense for 14 years to develop processes to manufacture vaccines against bioterrorism agents.  For one of its other clients, the BPDF is producing a Phase I recombinant subunit injectable vaccine.

The BPDF has made a name for itself in fed-batch fermentation and downstream processing of recombinant proteins from the methylotrophic yeast, Pichia pastoris, a protein expression system that utilizes methanol as an inducible carbon source for recombinant protein production. While not as fast as E. coli, Pichia pastoris has proven to be an effective system for proteins that are often very difficult to express in E.coli. The BPDF has extensive experience working in both systems. 

The new facility is modest in dimension—24,000 square feet, with 12,000 square feet for process research and development, 5,400 square feet of new modular cleanroom processing space, 600 square feet for a modular cleanroom QC laboratory, and 6,000 square feet of GMP utility area.

Nevertheless, the facility includes:

• A 1,200-square-foot fermentation suite with a 200-L BioEngineering bioreactor. (The suite can handle a 1,000-L reactor should someone want it, Meagher says.) The suite features a methanol-handling fume hood because of the plant’s emphasis on methylotrophic yeast.  The fermentation suite will be able to harvest by either membrane filtration using two NCSRT Model 50 membrane filtration systems or an Alpha Laval LAPX 404 centrifuge. There is also the capability for cell disruption using either an APV Gaulin homogenizer or Microfluidizer.
• A class 10,000 purification suite of 900 square feet with a built-in, 100-square-foot class 10,000 cold room. The suite is equipped with an NCSRT 6 L/min chromatography skid and NCSRT Model 10 and Model 5 membrane filtration systems.
• An aseptic processing suite outfitted with a VHP-sterilizable Class 10 isolator system, designed by Containment Solutions, Inc. and built by ConeCraft, Inc. to handle Master Cell Banks and Working Cell Banks. The isolator system is a one-of-a-kind built specifically for the BPDF. Along with the main five-glove isolator are two four-foot “isolets” that are used as class 10,000 incubators and can connect with a control panel on the wall to maintain temperature and humidity within.
• The remaining key spaces include an airlock that exits the three suites, dirty and clean staging areas, and a buffer prep room with a 500-L tank.

Operator movement around the facility will require certain gowning considerations, and the dirty staging area will be accessed from outside the cleanroom space through the main building corridor—concessions to working with a small footprint. “We just didn’t have enough square footage to do exactly what we wanted to do,” Meagher says.

That’s not to say that, like any dream home, the BPDF doesn’t have its share of extravagances. (See below.) One is a curved bank of windows within the aseptic suite that faces an atrium area with its own windows to the outside world. “The person working in the isolator is literally three feet from the window,” Meagher says.

Meagher likes windows for transparency. He wants the general public to see what is happening inside. The purification suite has glass windows on two sides along the main corridor of the first floor of Othmer Hall and people walking outside the building can look through the same windows into the purification suite. There’s another bank of windows on the second floor where passers-by can see all of the process piping and ductwork for the HVAC system. “Just imagine a big engineering drawing on the wall in a nice frame, color-coded, and then the ductwork that you’ll be looking at will also be color-coded,” Meagher explains. “You can go in there and give a tour, and sit there and play the game of looking back and forth to see which duct goes where.”