SAFC has recently launched the CHOZN Platform, a CHO (Chinese Hamster Ovary) cell expression system. This new system enables biopharmaceutical producers to create and scale up high-producing clones for the production of recombinant protein drugs. Director of Cell Sciences and Development, Kevin Kayser, talks about the platform and what this launch means for the biotech industry
The CHOZN Platform couples the CHOZN GS-/- CHO cell line with a cGMP-produced, chemically defined (CD) medium and feed that are optimized for the cell line to maximize production of r-proteins. Powered by the CompoZr Zinc Finger Nuclease (ZFN) technology, it is the first commercially available glutamine synthetase (GS) knockout CHO line proven to shorten bioproduction time lines in early development. It is designed and validated to perform from initial cell line engineering and stable cell line selection, through large-scale growth and production. Ultimately, it provides an off-the-shelf production solution to biopharmaceutical developers who do not currently have a cell line platform. CHOZN allows developers to create and select a stable cell line to maximize production of recombinant proteins quickly and effectively, increasing speed to market and reducing development costs.
Origins of CHOZN
Platform cell line systems are quickly becoming highly sought after fundamental in the biopharmaceutical producers’ bag of tricks. Not only does a platform system allow for quick evaluation of newly discovered molecules, but it also provides process development scientists with historical information on how the cell line has behaved in the past, allowing for quicker process optimization and subsequent scale up.
Many smaller biopharma organizations do not have the resources required to create a cell line platform in house. With the onset of biosimilars and increased competition in the industry, there is a significant advantage in being the first to market. This is where a cell line platform is particularly valuable.
SAFC went about developing the line with the ultimate goal of developing a robust, reproducible process that could be completed by one FTE (full time equivalent). One factor that remained critical to the design criteria was creating a system capable of preserving the integrity of production characteristics important to the biopharm industry. These characteristics include growth, productivity, and stability. The resulting specifications were entered into the ISO 9001:2008 design control process to initiate development of the CHOZN Platform.
The parental host cell line was a CHO-K1 that had been adapted to CD, suspension growth, by SAFC scientists. Multiple cell line characteristics were evaluated during the development, including metabolic selection systems (GS and DHFR), cell culture performance (titer, growth, longevity, transfection efficiency, stability), and product quality and efficacy (glycosylation patterns). When SAFC’s research team extensively vetted these modifications, the CHOZN GS-/- cell line consistently proved to be the highest producing host cell line that also maintained favorable growth characteristics.
Moving ahead
SAFC applied 25 years of media design experience to create the CHOZN platform of cell line, medium and feed. The CHOZN GS knockout CHO cell line was chosen as the base of the design, as developers considered it to be the strongest system and the system with the highest potential for growth in the future. Additionally, all of the components were designed together to ensure harmony between the cell line, medium, feed and procedures to optimize the process.
Once the CHOZN GS-/- cell line was selected as a lead candidate, it was put through media screening and optimization workflow. In order to maintain consistency with industry trends concerning raw material safety, the CHOZN medium and feed are chemically defined.
Accessing CHOZN
CHOZN Platform licensees have access to an extensive traceability package that is provided to support them in their filing processes. This package contains a detailed history of the CHOZN cell line development, as well as the final cGMP banking and testing documentation. It also provides users with full traceability of all raw materials (including all lot numbers) used throughout the development, along with quality control documentation.
SAFC structured the research and commercial licensing terms for the CHOZN Platform with multiple options available to accomodate biopharma producers of all sizes. There are no royalties associated with the use of the CHOZN Platform for production of commercial drug products, which was an important consideration in making this product available to customers of all sizes. Leveraging Sigma Aldrich’s extensive distribution network, SAFC is able to deliver the CHOZN GS cell line and accompanying reagents to customers on a global basis.
The future of CHOZN
In the immediate future, Kayser says he expects that the CHOZN system will enable smaller organizations to manufacture with the same efficiency as large companies without investing a lot of time and money. The team plans to trait-stack on top of the existing platform cell line to make further improvements to cell culture performance; this will also improve efficacy with a view to create a cell line with the GS, GGTA1 and CMAH genes all knocked out.
Additionally, SAFC will incorporate advancements in the nutritional biochemistry knowledge of CHO into the media and feeds as they arise. It’s an ongoing process that is expected to create a platform that increasingly enhances productivity and efficiency for customers.
And finally, updates to the CHOZN Platform are provided to current licensees at no additional cost. As SAFC makes enhancements to their system, their customers will be able to reap the benefits of accessing the most optimized system available.