Capabilities and Services
scalable processes for “difficult-to-refold” products
rapid biomass production cycle times, scalable to 300L-2,000L scale
Biologics manufacturing by high-density microbial fermentation has advantages of development speed, low cost and scalability. KBI’s approach is the best fit when selecting E. coli as the preferred host for expression of non-glycosylated proteins, including both soluble and insoluble product accumulation including downstream capture, host-cell impurity clearance and, where necessary, controlled and scalable refolding. KBI is also experienced with various non-E. coli bacterial hosts such as Pseudomonas-based and third-party proprietary expression systems. In cases of insoluble protein accumulation in inclusion bodies (IBs), KBI develops high-yielding recovery processes with analytical characterization of conversion to active product by solubilization and refolding techniques. KBI’s unique expertise in this area has enabled the use of microbial hosts for the expression of several known “difficult-to-refold” products at favorable scale and cost.
KBI applies proven, well-characterized microbial recombinant protein expression systems to provide state-of-the-art, early stage/preclinical through cGMP services including:
Off-the-shelf and engineered E. coli strain evaluations:
- Arabinose, rhamnose, phosphate depletion, and IPTG-inducible gene promoters
- Removable leader sequences for localizing proteins, increasing expression or editing the amino-terminus
- Soluble protein accumulation
- Insoluble protein / inclusion bodies (IB) accumulation
- Periplasmic protein accumulation
- Gene and codon optimization of the expression plasmids
- High throughput cell line selection based on fermentation performance, product yield and product quality
- Options to integrate early analytical characterization into the clone selection process, e.g. state-of-the-art mass spectrometry
- Understanding of business and science driven objectives related to the expression platform choice, e.g. product quality, IP status and licensing terms
- Implementing ICH Q5D and ICH Q5B guidelines
- Preclinical programs designed to meet the client’s timeline and budgetary objectives
- Cell line development activities can be performed as stand-alone services, or are integrated into larger-scope POC or scalable process development programs
- Selected cell line(s) are used to generate Research Cell Banks (RCBs) that are the foundation for further development and scale up.
- Master Cell Bank (MCB) generation, testing and characterization is outsourced to established, qualified and quality-audited third party vendors.
- High-throughput high-density fermentation optimization
- Scalable harvest and recovery process optimization
- Downstream chromatography screening and optimization of orthogonal purification strategies
- Pilot scale confirmation and GLP-enabling material generation
- 300L single use fermentation and 2000L stainless steel fermentation scale options.
- Existing open capacity with US-based expansion planned for near future
- Full PPQ expertise to prepare your product for a successful commercial launch
- Facility with existing commercially licensed products with favorable inspection outcomes
- Fully staffed quality and regulatory departments providing inspection-ready status at any time
- Access to real-time data trends and highly qualified Manufacturing Sciences staff to ensure process runs smoothly while in the plant
- May provide a PiP (person in plant) during at-scale production