Biotech Manufacturing
Bioreactors
I began working with bioreactors in the 1990s at Genentech, focusing on their 60L, 400L, 2K, and 12L analog fixed-tank systems. My work included mastering Clean-in-Place (CIP) and Steam-in-Place (SIP) processes. After gaining experience with these systems, I contributed to Genentech’s transition to automated, fixed-tank, stainless steel bioreactors as part of their new manufacturing capabilities.
Later, I assisted in designing custom-built 2500L fixed-tank stainless steel bioreactors for a new manufacturing suite utilizing a chemostat process. This involved close collaboration with engineers and programmers to optimize ergonomics and automation for user-friendly operation.
At Baxter, I was part of the team that developed the first-ever Single-Use Stirred Tank Bioreactor (SUB) with our Process Development group. I was among the first to operate these systems, identifying and resolving early design flaws to achieve the desired performance. This culminated in the first successful GMP run using the SUB. The reactor became a showcase for visiting biotech companies and has since become a standard in the industry.
Over my career, I’ve operated a wide range of bioreactors, from 500mL to 20,000L, encompassing off-the-shelf, custom, glass, stainless steel, and single-use systems.
Filtration
I have extensive experience with various filtration types and methods, including TFF, Reverse Osmosis, Depth Filtration, Ultrafiltration, Nanofiltration, and Clarification.
One particularly memorable experience occurred after the company I worked for acquired a new site. The site had a process requiring a Tangential Flow Filtration (TFF) harvest for Whooping Cough vaccine production. This process was infrequently run, and no one on-site was familiar with the outdated, custom-built TFF equipment. Additionally, there was no existing Standard Operating Procedure (SOP).
I was tasked with troubleshooting and learning how to operate the equipment, training the staff, and authoring a comprehensive SOP. Through careful analysis and hands-on work, I successfully revived the process, ensured proper staff training, and documented the procedure for future operations.
Columns
I have a wide range of experience with purification columns, spanning various sizes and chromatography methods. This includes operating bench-top columns for small-scale development and optimization, as well as managing larger production-scale columns, including those up to 200L in size.
I have utilized multiple chromatography techniques such as affinity, ion-exchange (both cation and anion), hydrophobic interaction, and size-exclusion chromatography, customizing each method to meet specific process requirements. My hands-on responsibilities have included column packing, qualification, and performance testing to ensure reproducibility and consistency. I am adept at troubleshooting challenges such as resin fouling, channeling, and improper packing to maintain process efficiency and product quality.
Additionally, I have worked with automated column systems integrated into large-scale manufacturing processes, collaborating closely with process engineers to refine operational parameters and maximize yields. My experience also includes supporting process scale-up, transferring methods from development to GMP production, and ensuring compliance with stringent regulatory standards.
While at Genentech, I served as the first “Skid Owner” and Subject Matter Expert (SME) for the 55L Protein A stainless steel column used in the Herceptin process. My role involved optimizing the process, authoring SOPs, training staff, and serving as the primary contact during audits. This work was instrumental as Herceptin transitioned from clinical manufacturing to an FDA-approved commercial product.
