Upstream Processing Archives - BioProcess InternationalBioProcess International

Accelerating Cell Line Development with an Efficient, Combined Platform Approach

The determination of product critical quality attributes (CQAs), key process parameters and indicators (KPPs and KPIs respectively) is a critical step for process efficiency during cell line development. Thousands of clones are typically screened with the goal of finding those that are stable, produce high yields of the bioproduct and exhibit desired CQAs. Screening and process optimization activities are typically carried out at the small scale in bioreactor cultures and are aimed at ensuring that results translate to larger bioreactor…

Kuhner TOM For Off-Gas Analysis in Shake Flasks

by BPI Contributor

To facilitate and speed up process- and media development, online measurement techniques for shake flasks accompany manual sampling for maximum information output per cultivation. Off-gas analysis gives oxygen transfer rate (OTR), carbon dioxide transfer rate (CTR) and respiratory quotient (RQ) as quantitative measures of the physiological state of the culture. On shake flask scale, multiple cultivations are usually run in parallel. Off-gas analysis should therefore be cost effective, easy to handle and versatile to match various applications. Therefore, we developed…

Automated Cell Line Development With Greater Than 99% Monoclonality On the Beacon® Platform

by BPI Contributor

For all cell lines used in production for commercial therapeutics, FDA guidelines require assurance of monoclonality. This standard means that typical cell line development (CLD) campaigns often require multiple rounds of cloning easily spanning several weeks to months. However, Berkeley Lights, Inc. (BLI) has developed the ability to save time and money spent on CLD processes via automation. The uniquely powerful Beacon® optofluidic platform performs single-cell cloning, growth and titer measurements, and recovery of top clones with unrivaled (>99%) monoclonality…

Long-Term Reliability of an Aseptic On-line Glucose Monitoring and Control System for Perfusion CHO Cell Culture

by Konstantin Konstantinov, Yeong-shou Tsai, Donald Moles, Ricardedo Matanguihan and William Miller

Among the variables that are appropriate for direct feedback control of the perfusion rate in mammalian cell cultures, high priority should be given to the glucose concentration. Here we describe the application of a closed-loop control scheme for the long-term cultivation of CHO cells in a high cell density (35 – 40 million cells/ml) perfusion process. The monitoring and control system worked successfully for 2.5 months without any signs of performance degradation. In targeting industrial applications, issues such as reliability,…

Novel Single-Use Systems Allow Faster Powder Transfer and Higher Recovery Rates (Poster)

by Ronald Szewczyk, Douglas Durney and William Ayrey

Single use powder containment practices are still in their infancy but keeping your product from cross contamination and reducing airborne particulates is important. Understanding how more modern bag designs can increase safety and speed is a concern to the industry. We looked at the ease of fill along with dispensing times and product loss. ILC Dover’s EZ-Biopac shows a 71% decrease in filling times when measured against an industry standard 2D bag. Due to the non-static film we saw an…

Immuno-Oncology Therapies: In Vitro Functional Assays for Drug Selection and Development

by Felicity Rudge, Maryam Ahmadi, Rebecca Klippstein, Mark Fogg, Anaïs Manin, Gary Bembridge and Campbell Bunce

The immune system is at the center of a new era in effective strategies to treat cancer leading to significant growth in the immunooncology sector, and the development of competing technologies to further improve patient survival rates. Essential to the successful development of cancer immunotherapeutics are ex vivo and in vitro assays to: Confirm mode of action Compare activity with competitors Identify lead candidates Evaluate and select combinations At Abzena, we have developed a suite of assays to confirm and…

Comparison of the Finesse SmartGlass™ and SmartVessel™ 3L Bioreactors: Engineering Data and Cell Cultivation Results

by Stephan C. Kaiser, Phillip Meier, Valentin Jossen and Dieter Eibl, PhD

Finesse Solutions Inc. recently introduced the single-use benchtop scale SmartVessel 3L bioreactor, which was developed based on its re-usable counterpart, the SmartGlass bioreactor. With identical main geometrical parameters, the plastic bioreactor mimics the glass vessel with minor modifications for manufacturability. The following study focuses on the engineering data of both vessels, which have been determined with special focus on animal cell culture applications. Furthermore, data from material tests on leachables and extractables as well as results from cell cultivations using…

An Introduction to the FUTURA pico for Mini-bioreactors

by John Carvell and Aditya Bhat

Small bioreactors are gaining share in process development laboratories. It is vital that these bioreactors are realistic scale down models of larger systems and it is equally important that online sensors for measuring live biomass can also be used in these vessels. ABER, known and trusted for its sensors that measure live cell concentrations using capacitance technology and adopted in the world’s leading bio pharmaceutical companies from R&D through to cGMP processes brings you the new FUTURA PICO. Our Conventional…

A Systematic Development Approach to Optimize and Control Biopharmaceutical Product Quality

by Min Zhang, Leisha Youngblood, Carrie Weymer, Gian Arias and Timothy Hill

The complexity of recombinant protein manufacturing processes, including expression systems, cell culture process conditions, and choice of media and feeds, present signifi-cant challenges to achieve desired product quality of bio-pharmaceuticals. To address these challenges, Fujifilm Diosynth Biotechnologies (FDB) has developed a unique systematic approach of combining “Media Toolbox” methodology, key chemical components, and cell culture bioprocess “know-how” to optimize and control manufacturing condi-tions that promote the desired product quality profiles of recombinant proteins. Case studies are presented to highlight the…

Targeting Desired N-Linked Glycosylation Profiles Through The Use Of Glycosylation Enhancing Feeds And High Throughput And High Resolution N-Glycan Analysis By Multi Capillary Electrophoresis

by Ryan Boniface, Bharti Solanki, Jaime Goldfuss, Johnie Young, Shaheer Khan, Shawn Barrett, Mark Stramaglia, Jenkuei Liu, Baburaj Kunnummal and Steve Gorfien

Glycosylation is a key product quality attribute for many biotherapeutic proteins expressed in CHO cells. N-linked glycans may display macro- and micro-heterogeneity; the degree of this variation can depend on several factors, including cell line, media/feeds, and process. As a consequence, it has often been challenging to achieve and maintain preferred glycosylation profiles from cell culture development through bioreactor scale-up. In order to address these challenges, we have developed a new feed technology in conjunction with a unique fed-batch process…