UGA Biopharma offers stable mammalian cell line development for high-titer and scalable manufacturing of various molecules (e.g., IgG1, IgG2, IgG4 and non-antibody proteins). We have optional access to different CHO cell lines and optimized vector systems for transfection. Depending on the customer┬┤s requirements, cell lines are chosen to provide the cell line that is best suited for the subsequent workflow. The selection of the best suited CHO host/vector system is absolutely critical for the success of the project and significantly impacts all downstream workflow steps, as well as the quality of the manufactured research cell bank.
UGA Biopharma┬┤s contract development of product-expressing CHO cell lines -- used for the manufacture of biosimilars -- is a full service that starts with the acquisition of the originator molecule and analytical characterization and continues through final release QC:
Start with acquisition and analytical characterization of the reference drug (originator) to ensure highest biosimilarities in subsequent cell line development
Determine amino acid sequence to ensure sequence identity between biosmilar and reference drug
Construct synthetic gene
The originator molecule is also used as reference for method development in DSP and analytics.
Cell Line Development
With our optimized workflow, the entire cell-line-development service can be executed within 7 months. A full UGA project consists of the following:
Cloning of gene of interest into optimized vector systems
Transfection of selected CHO host cell line(s) using stable transfection protocols; the number of host cell lines determined by the project budget
Transient-expression evaluation at pool level and selection of most suitable host cell line
Pool generation with the most suitable host cell line
Single-cell cloning and selection of high-titer and high-similarity clones
Characterization within various fed-batch processes (e.g., media and feed screening)
Generation of a tested research cell bank (RCB)
Our workflow ensures fully traceable origin and history of clones generation and documents.
Upstream Process Development
To generate quality profiles that are highly similar to the originator drug, we fine-tune similarity and enhance cell productivity by developing extended upstream processing (USP). This processing includes the following:
Culture-process optimization at lab scale (250 ml)
Scale-up of optimized culture process to 5 liters
Proof of consistency confirmed with two identical runs at the 5-liter scale
In addition, top clones are selected based on behavior under stirred-tank reactor conditions. This work strategy ensures the successful generation of high-quality biosimilar-producing research cell banks.
Downstream Process Development
UGA`s downstream processing (DSP) department develops efficient strategies for the purification and recovery of biopharmaceuticals from cell-culture supernatants for the assessment of quantity, purity, potency and biosimilarity. Host-cell protein, leached protein A, residual cell DNA and protein aggregates must be removed. The purified protein should have physicochemical properties that are similar to the originator molecule. Developed purification protocols can be transferred to the customer.
Development of DSP purification procedure (for analytics) in parallel to cell line development
Optimization of a capture step followed by polishing steps
Adjustment of charge-variants profile
Extended fine-tuning of biosimilarity, depending on project budget
Analytical Method Development
UGA┬┤s analytical department develops methods to estimate product titer and to characterize the product┬┤s physicochemical properties. The role of analytics is crucial, as the results of sample analysis will aid cell line development and upstream and downstream processing to select a CHO host/vector system. Analytics also optimizes cell-culture-medium components and identifies optimal conditions for bioreactor and purification runs.
Development of standard analytical methods, e.g.:
||Protein A HPLC for titer estimation of IgGs
||N-glycans and sialic acid profiling
Further methods available through external partners
DELIVERABLES AND FINAL RELEASE OF RESEARCH CELL BANKS
After selection of a suitable biosimilar-expressing single clone and stability study, the final release includes analytical characterization, sterility and microbial load testing. Final vials containing the selected cell line as well as the development report are shipped to the customer.