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White Paper –
Streamlining the Biological Factory: Making a Better CHO Cell for Biopharma Production

Developing the CHOZN Platform
What the Technology Implies

View the PDF

SAFC’s CHOZN® Platform has been developed as a ‘plug and play’ manufacturing system for the creation of biopharmaceutical producing cell lines. The design criteria were initially focused on the production of therapeutic monoclonal antibodies, but it can also be used for other recombinant biologics, such as different types of proteins and vaccines. From the introduction of DNA into the CHO (Chinese hamster ovary) cell, all the way through to the process development stages, SAFC has developed a system that includes not only the cell line, but all the media, feed media and optimized procedures required for the fast selection of high producing cell lines for a therapeutic monoclonal antibody. In this white paper, SAFC discusses the development of this cell platform and how it affects the market.

Developing the CHOZN Platform

During development of the CHOZN Platform, there was a focus on creating cells that gave high production titers and improved growth characteristics to produce high-quality proteins. The system can be used to express any antibody using the same parental cell line and the same media and feed formulations. All that is changed is the DNA that is introduced into the CHO cell, which creates the desired product in the cell culture.

The system was deliberately built to be regulatoryfriendly. The cell banks are manufactured and tested under cGMP conditions, and thus full documentation and traceability of the cell line’s development process are also available. Similarly, the media and feed are serum-free, animal component-free, chemically defined and also manufactured under cGMP conditions. All of this is designed to enable the user to move through the drug development process faster, and be fully prepared to support their regulatory filings at the various stages along the drug development pathway.

When biopharma companies purchase this cell line they can be confident that the system is safe for their drug development purposes, as a full suite of viral safety tests has been performed. Similarly, the media and feed raw materials are sourced from approved primary and secondary vendors SAFC has established relationships with, allowing for a more in-depth, regulatory friendly product history package.

The CHOZN Platform itself was designed using quality by design principles and using ISO9001:2008 product development guidelines. In 2007, SAFC scientists asked industry experts and key leaders what they believed would make an optimal manufacturing process for antibodies. Using this information, design features such as robust cell growth, high transfection efficiency, and ability to produce r-proteins at high levels, were incorporated into the specifications before we started developing the parental cell line.

We started our cell line engineering process using the CHO-K1 cell line, which is well known and characterized, and has been used by many biopharma companies to develop their in-house cell lines. Initial efforts were used to develop a CHO-K1 sibling cell line that had been adapted to suspension culture within a chemically defined media, which would grow to high cell densities in bioreactors, and be easily transfected with exogenously supplied DNA.

This suspension adapted CHO-K1 line was then used as a template to create mutations within the glutamine synthetase (GS) gene using CompoZr® zinc finger nuclease (ZFN) technology. This game-changing technique allows precise genome editing to be carried out with no known off-target effects. Knocking out the GS gene and subsequent enzymatic activity has been shown to be effective in cell line development manufacturing processes, reducing the overall development time, and removing the need for the MSX (L-methionine sulphoximine) inhibitor altogether for selection of production clones. Importantly, the cells lead to cell lines that give a long-term stable expression of the desired r-protein, and will grow in fed–batch processes that are typically used to make monoclonal antibodies.

What the Technology Implies

Customers have the option to purchase the CHOZN cell lines as a separate catalog item, complete with all regulatory and quality documentation. While many large biopharma companies have over the years developed their own in house proprietary cell lines, it is a very different picture for start-up biosimilar and smaller biopharmaceutical manufacturing firms, which have limited resources and capability to invest in developing their own platform cell line. These smaller biopharma organizations are anticipated to find the CHOZN Platform a more favorable solution, as it allows users an off the shelf platform cell line solution that has already been optimized with appropriate media and feeds for use in fed-batch bioreactor systems.

The use of SAFC’s CHOZN Platform offers a streamlined process from initial production cell line development to large scale manufacturing with everything needed in between.

More information about CHOZN Platform

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