Pfizer Case Study: Single-use Conversion
The challenge
Pfizer was looking to accelerate the development of 2 biosimilar monoclonal antibodies (mAbs) to achieve regulatory approval. Their goal is to be first to market in China. In order to meet their aggressive timelines, they needed to implement single-use technologies in place of stainless steel in under 6 months.
The solution Summary
GE’s Fast Trak scientists took a hands-on collaborative approach, working side by side with Pfizer scientists and engineers. Together they aimed to implement the changeover from stainless steel to single-use and prepare materials for analytical comparability testing.
The project began with proof-of-concept 10 L runs of the 2 mAbs using GE single-use bioreactors—WAVE bioreactors and Xcellerex bioreactor systems. Other GE single-use technologies were utilized for both upstream and downstream processes.
After demonstrating analytical comparability to the originator molecules, they scaled up to 200 L runs of each molecule. The 200 L runs were successful for both mAbs.
200 L process workflow
Details – Upstream
The teams identified critical process parameters (CPP) for upstream unit operations. They scaled down Pfizer`s 12 000 L stainless steel process and adapted it to GE’s single-use bioreactors at a 10 L scale. Then, they scaled the process up to 200 L. The cell densities and product titers were determined.
Details – Downstream
The teams identified CPP for downstream process transfer to single-use. They scaled down Pfizer’s stainless steel downstream process and adapted it to GE’s single-use TFF systems, depth filtration systems, chromatography columns, buffer systems, bags, tubing sets, and sensors.
The results Summary
- Comparability: All outputs from the new process achieved Pfizer’s expectations for cell growth, titers, and analytical comparability.
- Speed: Migration to single-use and scale up from 10 L to 200 L was finished in 5 months, 1 month quicker than target.
- Process transfer: More than 50 process documents and 4 complete bills of material were generated.
- Time savings: By outsourcing this activity 6 to 12 months of time were saved versus Pfizer’s internal timelines.
Details – Upstream
GE determined the cell densities and product titers; the maximum value of each was normalized to data from Pfizer’s 12 000 L (12K) stainless steel process. Pfizer performed the analytical comparability testing after purifying the mAbs using their standard process.
The upstream process results met Pfizer`s expectations for cell density, product titer, and analytical comparability.
Details – Downstream
GE calculated the recovery at each step and the total process recovery. Pfizer performed analytical comparability testing.
The downstream process met Pfizer`s expectations for recovery and analytical comparability.
The secret to success
Close collaboration between GE and Pfizer staff was crucial to the project. Mixed teams drawing knowledge from both businesses worked side by side, on site and in plant. This approach led to trust and strong working relationships, paving the way for future collaboration.
“Working closely with GE Healthcare, a small cross-company team of scientists and engineers worked with lightning speed to transfer two processes to the GE Marlborough facility for proof of concept runs, first at 10 L scale and then at 200 L. The data produced help forge an informed decision to proceed with a single-use biologics facility in China.”
– John Coyne, Pfizer Bioprocess R&D, Sr. Manager Pilot Plant, Andover, MA
What’s next for GE and Pfizer?
Pfizer invested in a GE single-use KUBio facility for its manufacturing site in Hangzhou, China. KUBio is a cGMP-compliant single-use biomanufacturing facility that incorporates the FlexFactory platform. KUBio can be installed within 18–24 months.
While the new facility is under construction, GE will provide bridge manufacturing services to keep clinical timelines for both mAbs on target. Then, GE will tech transfer the materials and processes to Pfizer teams with full training to get them up and running in their new KUBio plant.