Our goal during cell culture process development is to develop high titer, scalable production processes that will express our customer’s target molecules efficiently with long term commercial production in sight. Our experience includes working with a wide array of expression systems including CHO, HEK, Vero, MDCK, EB66 and insect cells. We tailor our programs to meet the needs to each program, and especially for difficult to express and/or manufacture molecules.
We have modern facilities with access to state-of-the art equipment. With over 50 bioreactors (3-200L), as well as ambr™ systems (24x 250ml and 48x 15ml), FUJIFILM’s scientists develop and optimize batch and fed batch processes for mammalian and insect cell-based production. Our experience expands to working with Hollow Fiber and Stack Cell Culture Systems.
The Process Development team can generate and qualify scale down-models and fully characterize process parameters in support of process validation. Extensive use is made of DOE approaches, with the support of in-house statisticians.
UPSTREAM PROCESS DEVELOPMENT ACTIVITIES INCLUDE:
- Process Transfer-in and Development
- Process monitoring
- Supply & Toxicology Study Supply Batches
DOWNSTREAM DEVELOPMENT ACTIVITIES INCLUDE:
- Resin screening
- Intermediate stability
- UF/DF development
- Virus clearance studies support
- Pegylation, hapten conjugation, enzymatic cleavage
- Set processing targets
- Process characterization
- Scale down models
CHO Process Development
As compared to microbial expression systems, which usually do not have proper post-translational modifications (e.g. glycosylation) on recombinant proteins, CHO is able to produce humanized recombinant proteins with similar post-translational modifications. The production of these proteins is one of the main reasons that CHO has been popular in biotherapeutics manufacturing.
Other reasons include good and robust cell growth, high protein productivity, and relatively easy process operation make CHO more desirable as compared to other mammalian expression systems.
As long as recombinant protein needs proper post-translational modifications that cannot be achieved in microbial, it’s desired to express proteins in CHO including mAb, and non-mAb.
What are particular challenges of working with CHO?
High yield is no longer the big challenge with CHO as it used to be. Particular challenges include desired product quality attributes, reliable process scaling (up/down), robust upstream process (which is the purpose for QbD). Others related, including harvest challenges with high density process, high yield challenges to downstream, etc.
What do we bring to your CHO program?
Through many CHO programs, we have achieved significant experience/knowledge on diverse CHO cells/processes (e.g. media toolbox) which helps us to stand out. We bring our customer programs years of single-use experience which is becoming a significant manufacturing platform in the cell culture space as well as traditional stainless steel production. We have worked with an extensive number of molecules expressed in CHO, including monoclonal antibodies, bispecifics, mAb-like and Ig-fusion molecules among others.
Insect Cell Process Development
Insect cell Expression Vector systems are capable of producing proteins that are very large in size. These systems are also capable of producing multiprotein subunit complexes such as Virus Like Particles (VLPs) which are known to induce broad and strong immune responses, making them ideal in vaccine production. Other advantages of using a insect cell systems is that they can modify proteins post translationally, e.g., phosphorylation and glycosylation.
It is important to note that the post translational modifications are usually not to the the same extent as higher eukaryotes such as CHO. Insect cells can produce product intracellularly or extracellularly-excreted.
What are particular challenges of working with Insect Cells?
There are a few challenges when working with BEVS that should be kept in mind. BEVS are not able to fully glycosylate proteins so they are not a suitable system for the expression of antibodies.
From an Upstream Development perspective, media selection is an area that must be carefully considered as in our experience chemically defined medias do not work well in Insect Cell cultures. Purification can be a challenge mainly due to the low expression levels achieved by BEVS, especially when there is a capture step in the purification scheme. Purification of BEVS can go through very drastic scale changes, starting as very large processes going to become very low volume within a few units of operations. Having a solid and experience Downstream Development team is very important when working with BEVS.
The use of BEVS as an expression systems is still mainly academic. This may make Process Development a little more of an adventure as production optimization information in a large scale and/or cGMP setting is usually minimal.
What do we bring to your Insect Cell expressed program?
We bring over 15 years of hand-on insect cell development experience to your program. We have deep understanding of the challenges that will make an insect cell program successful, not only in development but taking all to the way to cGMP production, executing validation campaign(s) and supporting BLA and subsequent commercialization.
We are a licensed manufacturer of a commercially approved baculovirus expressed product.