Biopharma and biosimilar companies are increasingly considering final production costs during early-stage process development rather than blindly racing to the clinic with an inferior process that must undergo redesign during subsequent clinical stages. Furthermore, the most advanced companies have a laser-like focus on product quality and consider this early on in development. This ensures that they progress the best product candidate into the clinic and avoid costly failures.
Just-Evotec Biologics is helping partners with antibody product candidates achieve the highest product quality with Cost of Goods Manufactured (COGM) below $50/g by combining our new J.CHO™ High Expression System (J.CHO™) with our unique continuous manufacturing platform. This extraordinary productivity represents a 75% reduction in industry standard COGM and is driven by the exceptionally high titers exceeding 4g/L/day in perfusion achieved utilizing J.CHO™. This performance is equivalent to a titer of approximately 30 g/L in fed-batch mode.
The J.CHO™ High Expression System comprises:
- Engineered GS knockout CHO-K1 host cell lines capable of delivering specific productivities more than 50 pg/cell/day and growing at target densities of 60-100 million cells/mL
- Transposon-based expression vectors with strong promoter sequences allowing stable integration and high expression of genes-of-interest (GOI)
- Proprietary chemically defined, protein-free and dual sourced perfusion cell culture media designed with cost-efficiency in mind
Just-Evotec Biologics developed product sales royalty-free cell lines to work perfectly with our upstream perfusion platform process and to scale seamlessly from 3L to 500L or 1000L bioreactors for clinical or commercial production.
Figure 1: Comparison of antibody yields in a 20-day continuous perfusion culture using an industrystandard CHO (Chinese Hamster Ovary) cell line
Seamlessly Integrating Product and Cell Line Development
Just-Evotec Biologics can leverage its unique J.MD™ Molecule Design suite of services to create multiple variants of an antibody candidate with improved developability characteristics. Our innovative high-throughput cell line development workflows allow us to produce up to 96 stable transfectant pools of variants and screen for productivity and product quality in parallel. Expression in stable pools produces more representative material for testing than from transients and by combining candidate development with cell line development we can save partners up to two months from your timelines. Most importantly, we identify antibody candidate variants with excellent manufacturability properties that have been shown to increase expression titer by 3-fold compared to parental sequences. We are delivering elevated levels of productivity for monospecific, bispecific- and multi-specific antibodies, Fc-fusion proteins, and single-chain Fv-antibody fusion proteins.
Perfusion Delivers Superior Product Quality
Just - Evotec Biologics has demonstrated that our perfusion platform delivers superior antibody product quality compared to fed-batch systems. Perfusion cultures give healthier cells with more complete glycosylation patterns while shorter product residence times in the bioreactor result in lower levels of oxidation and deamidation. We modulate media and bioreactor conditions to meet our partners’ product quality requirements.
Our J.CHO™ High Expression System provides partners with opportunities to refine the product quality attributes of their candidate. Partners may choose to do this for a variety of reasons, for example, we collaborate with companies developing biosimilar products that must match the product quality profile of innovator molecules and innovator companies developing novel biologics with unique features. Our additional capabilities within the J.CHO™ High Expression System service offering includes:
- FUT8 Knock Out Cell Line enabling afucosylated antibodies for enhanced ADCC and improved efficacy.
- Inducible Cell Lines for the controlled protein expression of cyto-toxic products used in next-generation therapies.
- Additional advanced glycoengineered cell lines capable of delivering a range of glycan modifications on biosimilar candidates that match those of innovator products.
Our cell line development process can take as little as 14-weeks and uses the latest high-throughput cell culture methods and analytics to maximize efficiency.
Figure 2: Typical cell line development program at Just-Evotec Biologics to select clones with optimum performance in continuous perfusion culture; DWP = deep-well plates, tfxn = transfection
Highest Titers and Best Product Quality
In conclusion, in an increasingly mature and competitive market, biopharma companies are finding ways to differentiate themselves based on product quality attributes and on cost. Just-Evotec Biologics is supporting partners with its new J.CHO™ High Expression System that integrates with its continuous manufacturing platform for antibodies and delivers the highest titers in the industry and the product quality our partners demand.