A CMO's Approach

Industry leading biologics contract manufacturer Fujifilm Diosynth Biotechnologies located in Research Triangle Park, NC (formerly Diosynth Biotechnology) and in Billingham, UK (formerly Avecia Biologics) provides third-party contract development and manufacturing services to the biopharmaceutical industry.

Fujifilm Diosynth Biotechnologies has supplied clinical and commercial recombinant proteins produced in cell culture for more than 14 years. We have extensive experience in microbial development and manufacturing and equal experience in the cell culture space. Our development experience includes over 30 cell culture processes, of which two-thirds were CHO derived, and over 20 monoclonal antibody programs. In addition, Fujifilm Diosynth has executed four baculovirus programs with scale-up to 1,500-L for the first time in the industry for human use. To date, Fujifilm Diosynth has produced over 100 cell culture GMP batches, primarily using CHO cell and baculovirus technologies and manufactures one cell culture commercial product.

Fujifilm Diosynth cell culture offering consists of cell line development; upstream, downstream and analytical development; GMP manufacturing and process validation; single-use development and 200-L to 1,000-L manufacturing capacity in addition to our existing 2,000-L stainless-steel cell culture train; and proven biosimilar development package.

Cell Line Development

Our proprietary DHFR expression system and CHO-DXB11 ACF suspension adapted cell line is the foundation of Fujifilm Diosynth cell line development capability. Using Genetix Clonepixtm technology to screen thousands of colonies, we can pick out the most favorable clones and quickly determine the lead candidates for clone selection. Identification of the lead candidate is based on several factors such as productivity per cell, growth rate, and product quality. Combined with our approach to clone selection, compatibility with the Fujifilm Diosynth platform fed-batch process can lead to significant time savings in the gene to GMP trajectory. Complementing the Clonepix, Genetix Clone Select Imaging technology offers absolute assurance of clonality of your cell line by tracing a colony back to its origin.

Development Approach

Fed-batch development at Fujifilm Diosynth starts with commercial and in-house basal and feed media with studies in shake flasks and 2-L or 10-L bioreactors to identify the best media and feed combinations. Fujifilm Diosynth has platform feed formulations that have increased productivity fourfold in some cases. Media and/or feed development can be enhanced by spent media analysis to develop a feed specifically tailored for your cell line. Fujifilm Diosynth platform conditions for mixing and mass transfer minimize the number of parameters studied in development and ensure manufacturing fit and right-first-time manufacture. The recovery and purification approaches use broad platform processes for monoclonal antibodies that consider the properties of the molecule. For non-antibodies, recovery still starts with a platform approach, while purification development or transfer must be tailored to the molecule.

Biosimilars

The Fujifilm Diosynth biosimilars development program incorporates the cell line development and process development activities listed above with addition of a full analytical arsenal. Characterization of multiple lots of the originator molecule identifies the historical analytical “bandwidth” targets for the process development teams. This approach to biosimilar development can be applied to client programs to provide a rapid path to clinical manufacture.

Single-Use Expansion

Currently, we are increasing manufacturing capacity by adding single-use bioreactor capabilities. Fujifilm Diosynth has evaluated the available single-use reactors over the past three years through university collaborations and the operation of our Xcellerex 200-L reactor in our PD labs. The expertise gained in this area has been applied to design a 200-L to 1,000-L single-use manufacturing expansion that includes complementary single-use seed train and harvest technologies. In Q1 2012, we will offer our clients the benefits of single-use upstream manufacturing in a proven organization with commercial cGMP compliance standards.

About the Author

Author Details
Adrian Knight is staff scientist of expression and cell sciences at Fujifilm Diosynth Biotechnologies, Billingham, UK. Stewart McNaull, Philip Ropp, and Gregory Adams are section leaders of biotech development, and George Koch is director of process development at Fujifilm Diosynth Biotechnologies, 3000 Weston Parkway, Cary, NC 27513; 1-919-388-5700; ([email protected]).