Biomedical Engineering and Bioengineering Commons^™

Protein Refinery Operations Lab (Pro Lab): A Sandbox For Continuous Protein Production & Advanced Process Control, Mark Brower, David Pollard, Finn Hung

Integrated Continuous Biomanufacturing II

Significant strides towards implementation of continuous bioprocessing are being made at an ever increasing rate. Advances in technology for traditional unit operations such as cell-retention devices in perfusion cell culture, continuous multi-column chromatography (CMCC) and single-pass tangential flow filtration have led to demonstrations of both semi-continuous and fully-continuous protein production processes operating at periodic steady states at the pilot-scale. Previous proof of concept work at Merck & Co., Inc. has shown an automated (DeltaV) and single-use monoclonal antibody (mAb) purification scheme through Protein A CMCC and pH viral inactivation with minimal human interaction for 30 days fed from a perfusion …

Small-Scale Platform For Rapid On-Demand Manufacturing Of Recombinant Proteins, J. Christopher Love

Integrated Continuous Biomanufacturing II

The current timeline for manufacturing high-quality recombinant proteins used for therapeutics and vaccines, and delivering them to patients, typically requires many months. There are many circumstances, however, where the rapid production, release, and delivery of these biologics could address unmet medical needs, including shortages, emergency situations, and pandemics. This talk will present a new platform developed to produce biologic medicines on demand called Integrated and Scalable Cyto-Technology (InSCyT). This platform comprises an integrated, subliter-scale portable system for the (semi)continuous operation of fermentation, filtration of cell debris from secreted product, innovative affinity-based purification, polishing, and finishing. This program also emphasizes integrated …

Exploring Continuous And Integrated Strategies For The Up- And Downstream Processing Of Human Mesenchymal Stem Cells, Barbara Cunha, Tiago Aguiar, Ricardo Silva, Cristina Peixoto, Manuel Carrondo, Margarida Serra, Paula Alves

Integrated Continuous Biomanufacturing II

The integration of up- and downstream unit operations can result in the elimination of hold steps, thus decreasing the footprint, and ultimately can create robust closed system operations. This type of design is desirable for the bioprocess of human mesenchymal stem cells (hMSC), where high numbers of pure cells, at low volumes, need to be delivered for therapy applications. The aim of this work is to perform a proof of concept of the integration of a continuous perfusion culture in bioreactors with a tangential flow filtration (TFF) system for the concentration and washing of hMSC. In particular, we have evaluated …

From Fed-Batch To Perfusion: Productivity And Quality Considerations For A Late-Stage Program, Sen Xu, Hao Chen

Integrated Continuous Biomanufacturing II

In this poster, we will present the rapid development of a perfusion process with high productivity for late-stage manufacturing. The process uses a Chinese Hamster Ovary (CHO) cell line for monoclonal antibody production. Prior to the development, the clinical supply was manufactured by a fed-batch process with the same cell line.

To achieve desired productivity and comparable quality attributes, we developed a repeated batch shake flask model to rapidly screen media and process conditions. Shake flasks were inoculated at 10 × 10⁶ cells/mL and maintained in a CO₂ incubator with medium exchange for every 48 hours, repeated for …

Designing A Microbial Cultivation Platform For Continuous Biopharmaceutical Production, Nicholas Mozdzierz, Kerry Love, Alan Stockdale, John Clark, Noelle Colant, Christopher Love

Integrated Continuous Biomanufacturing II

The existing biopharmaceutical manufacturing paradigm is poorly suited to produce biologic drugs on demand at a point-of-care. Generally, commercial-scale (~2,000 - 10,000 L) manufacturing using fed-batch cultivation and fixed stainless-steel infrastructure is concentrated in developed nations and results in process cycle times on the order of weeks to months.^1,2 Coupled with the complex logistical challenges associated with continuous “plant-to-patient” cold-chains, the geographically biased nature of therapeutic protein production today can limit access to biologic drugs in developing areas of the world.³ There is an opportunity to create technologies capable of rapidly generating biopharmaceuticals in situ in emergency situations, …

Integrated Solutions For Continuous Processing In Mobius® Bioreactor Systems, Andrew Clutterbuck

Integrated Continuous Biomanufacturing II

Throughout the bioprocess industry, the use of disposable systems such as bioreactors is playing an increasingly significant role. Manufactures are recognising the strategic benefits of single use systems in both reducing production costs and increasing overall manufacturing throughput.

Over the past few years there has been increasing demand for larger scale disposable bioreactor systems, to satisfy the manufacturing demands and an emphasis on suppliers such as Merck Millipore to demonstrate robust and reproducible scale-up within these systems.

This presentation will explore the design philosophies behind the Mobius^® bioreactors and will also give an overview of the novel SensorReady external …

Pilot Scale Hybrid Fed Batch And Continuous Processing Of Biologics, Dave Sullivan, Michael O'Connor, Samir Gondalia, Matt Gagnon

Integrated Continuous Biomanufacturing II

Pfizer Bioprocessing R&D is focused on developing enabling technologies that will reduce capital and operational expenses, decrease equipment scale, increase automation and utilize fewer FTEs. To realize this vision, our Pilot Facility has partnered with our cell culture process development colleagues to adapt a fed batch platform 150L stainless steel bioreactor to run in hybrid perfusion, standard perfusion, low volume cell controlled perfusion, and continuous stirred tank modes. Through adjustments to impeller configuration, sparging strategy, and addition ports the bioreactor was able to deliver multiple batches that produced ~3X gains in cell density and volumetric productivity versus conventional fed batch …