An Integrated Approach to Buffer Dilution and Storage

Also, the type of flow control strategy implemented will impact the magnitude of a disturbance effect. In our studies, flow control by the positive displacement pump alone was not sufficient. Instead, we recommend controlling flow by an inline pneumatic or electric diaphragm valve or by simultaneous control of the pump and valve to control flow rate and backpressure, respectively. One other important aspect of our inline dilution system design was the use of a filter housing as the mixing chamber for the blended buffers. The housing was positioned upstream of the inline analytical instruments, such as pH and conductivity meters, and served a dual function of both mixing and filtering the buffers prior to delivery onto the chromatography column.

The capital savings from implementing inline dilution at our large-scale facility were tremendous. We were able to significantly reduce the size of buffer prep tanks, we replaced many buffer hold tanks with disposable bag containers, and also reduced the WFI and CIP chemical requirements for the facility. In the future, we could further increase the capacity of our facility by concentrating buffers greater than 10x⁸. We will also consider inline dilution applications for other unit operations such as media prep and tangential flow filtration (TFF). Inline dilution may provide additional benefits for renovation of our existing biomanufacturing facilities to increase capacity. Using bags together with inline dilution makes such renovation less complicated and more cost-effective.

About the Authors

Tim Matthews is a Senior Engineer and group leader in Process Development Engineering at Genentech. He has a B.S. in Chemical Engineering with a Minor in Environmental Engineering from Penn State University. Please address correspondence to matthews.tim@gene.com.

Bryan Bean is currently working in Manufacturing Sciences supporting commercial bacterial fermentation operations at Genentech. He has worked in the Process Development Engineering group at Genentech from 2004 to 2008 with a focus on testing and implementing novel bioprocessing technologies. Bryan has a B.S. in Chemical Engineering from the University of Washington.

Poonam Mulherkar is a Senior Engineer in Manufacturing Sciences, Vacaville. She has 12 years of experience in various aspects of Process Development, Technology Transfer and Facility Startup. She has an M.S. in Chemical Engineering from the University of Cincinnati.

Bradley Wolk is a Distinguished Engineer and Director of Pharmaceutical and Packaging Engineering at Genentech. He joined the company in 1991 and has been active in facility and equipment design, process and technology development, and technical collaborations in the areas of cell culture, purification, filling and material sciences. He has a B.S. in Chemical Engineering from U.C. Davis. 

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