Production of Antibodies and Hormones

Monoclonal antibody production

Rising time and cost pressures make the development and manufacturing of therapeutic proteins challenging. Antibodies dominate the biopharmaceutical market and their production is widely established. Alternative technologies like the recombinant production of antibody fragments and nanobodies, however, keep the research field exciting. Improved cultivation techniques such as perfusion and new possibilities in process analytics and automation offer companies the chance to set themselves apart from the competition.

Flexible solutions for all stages of development

Since the 1980s, production of monoclonal antibodies (mAbs) using hybridoma cells has been accepted as an effective technology for cancer treatment. Meanwhile, mAbs make more than half of the total biopharmaceutical market. In antibody production, many factors have to be taken into account before entering the manufacturing stage.

Eppendorf bioprocess solutions support the upstream bioprocessing cycle from early development to scale-up to pilot-scale production. Powerful hardware and software tools help to build process understanding, implement control strategies, and streamline process scale-up.

 

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Infographic of Antibody Production Workflow

Process development in cell culture

The production of complex biomedical proteins represents one of the primary applications in animal cell culture. During process development, research scientists need to find the optimum settings for critical process parameters, like temperature, pH, gassing rates as well as nutrient compositions, as they influence cell growth, product titers, and product quality.

Eppendorf offers parallel bioprocess systems at small and bench scale. They allow multiple experimental parameters to be tested simultaneously in one run, which ensures maximum comparability between runs and saves time and resources.

Scientists at CEVEC Pharmaceuticals® performed a successful scale-down of their established process to 170 mL working volume using a DASbox® Mini Bioreactor System with BioBLU® 0.3c Single-Use Vessels.

 

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The Morbidelli group at ETH Zurich uses a DASGIP® Parallel Bioreactor System for process optimization in various projects, from scale-up studies and development of a perfusion process to the cultivation of stem cells.

Vania Bertrand, PhD candidate at the ETH Zurich, was interviewed about her work in the Morbelli group and her private life.

 

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Technology transfer and scale-up

Scaling up cell culture processes is key to the success of biopharmaceutical production. Scale-up based on maintaining constant tip speed is one of the common strategies, especially for cultures sensitive to shear force damage. This strategy maintains a relatively constant shear force level. Other important parameters for scale-up are mixing times, oxygen transfer, and power numbers.

The pH of the culture medium is a critical process parameter in mammalian and microbial bioprocesses.

Scientists at Roche® Pharma Technical Development, Penzberg, Germany present a simple and non-invasive method to apply CO2 exhaust levels to indirectly monitor and control pH in cell free systems, using a DASGIP GA4 exhaust analyzer. 

 

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Perfusion

Increasing the efficiency of production processes is one of the major tasks biopharmaceutical manufacturers are facing nowadays. Continuous processing and perfusion cultivation are techniques to increase cell density and product titers while leading to smaller production volumes.

Eppendorf offers Fibra-Cel® Disks, a three-dimensional growth matrix to support perfusion without the need for cell filtration. Alternatively, the integration of cell retention devices with Eppendorf bioprocess systems facilitates perfusion based on tangential flow filtration.

> Download publication: Culture methods in mAb production

> Download application: Perfusion in CHO cell culture

Process automation and data analysis

The integration of external analysis data into running production processes has attained major importance over the past few years, pushed by the FDA’s process analytical technology (PAT) initiative. In addition, Multivariate Data Analysis (MVA) and Design of Experiments (DoE) are advanced techniques which enable bioprocess laboratories to improve their data and ultimately accelerate biopharmaceutical development, reduce costs and shorten the time to market. 

> Watch webinar: Automated bioreactor sampling and glucose control

> Download eBook: QbD and PAT in biopharmaceutical development

The Applied Process Company (APC) integrated external PAT and an APC-developed controller with an Eppendorf DASGIP Parallel Bioreactor System. Online PAT measurement and control of critical process parameters led to greater understanding and the streamlined optimization of the bioprocess. 

“The ability of the DASGIP system to integrate both the external PAT and in-house developed controllers was vital to the success of our application.”, comments Dr. Stephen Craven, Life Science Team Leader at APC.

> Download publication: A QbD approach to bioprocess intensification

> Download interview with Jessica Whelan

Process automation and data analysis

At the University of Delaware, Babatunde A. Ogunnaike and his team have established the foundation for effective real-time online control of glycosylation patterns on monoclonal antibodies produced with Chinese Hamster Ovary (CHO) cells. For establishing base regulatory control of key process variables known to effect glycosylation, they set up a bioprocess with nutrient control and cellular metabolite monitoring through integration of an external analyzer.

 

Download application note (PDF)

 

A selection of our customers