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Innovation Center

Located in Shanghai Zhangjiang Science City, Chime Biologics Innovation Center, covering an area of over 1500 square meters, focuses on highly efficient cell line development and the state-of-art development of early-stage projects.

It is dedicated to becoming a leading international biopharmaceutical R&D center, complementary to Chime Biologics Wuhan manufacturing facility with its successful experience in multi-country clinical trial applications and new drug launches. Chime Biologics Innovation Center currently provides the services of cell line development, early-stage drug candidate preparation, drug developability studies as well as process development, with the initial capacity to undertake more than 20 biologics projects per year.

Drug Developability Studies

Simultaneously develop stable cell pools for multiple candidate molecules at the early-stage of customer projects. Generate high-productivity and high-quality stable cell pools required for early-stage development, from which the candidate protein is produced. Once the drug candidate is determined by the customer, the stable cell pool can be used immediately for single-cell cloning, reducing the time required for IND project development. The expression level of stable cell pools can be achieved over 5g/L.

By using transient expression based on the CHO cell platform, gram quantities of monoclonal antibody can be generated within 4 weeks with an expression level of more than 1 g/L.

Perform in silico analysis to predict molecular characteristics and potential PTM (post-translational modification) sites.

After replacing the candidate molecule in the preliminary formulation condition, and adjusting the concentration to the target level. Conduct physicochemical analysis and characterization of the molecule, including physicochemical properties, structural characterization, and functional characterization.

Perform high-throughput conformational stability and colloidal stability analysis with a protein stability analyzer (NT PR Panta), including Tonset, Tm, Tagg, Tsize and kD, to determine the stability of the molecule. Evaluate the developability of the molecule for liquid or lyophilization formulation.

Conduct forced degradation stability study, including thermal stress, agitation, freeze-thaw, photostability, and acid-base conditions, to do the further developability assessment.

Cell line Development

We have a highly productive, rapid, and stable cell line development platform to select the optimal stable expression clones based on expression titer and quality. Our cell line development is based on our proprietary and highly expressed CHO system. Our CHO-K1-derived cell lines have a clear history of use and are tested and qualified. We use advanced single-cell printers and high-resolution imaging systems to ensure cell line monoclonality and shorten the screening time. Cell line generation and monoclonality are fully documented and traceable according to regulatory requirements. The yield achieved more than 10 g/L.

  • High-productive, fast, and stable cell line development platform
  • High-yield CHO expression system with IP rights, titer can exceed 10g/L for Monoclonal antibody

Stable Cell Line Construction: Service Features

Chime Biologics can provide the development services for stable cell line, which is suitable for large-scale manufacturing. Our CHO-K1 cell lines have a clear history of use and high productivity, and can be sublicensed globally.

  • Host cell CHO-K1 has clear history, well documented, officially licensed
  • Independently developed and synthesized expression vectors
  • High-throughput cell screening system: Solentim Cell Metric, Octet Qke
  • Cell line construction process control
  • Traceable records
  • Monoclonal imaging systems for verification
  • Multiple screening systems based on plate reactors, tube reactors, shake flasks, fermenters, etc.
  • Select GS High Expression Screening System, offering a wide selection of commercially licensed host cells
  • We were able to establish a highly productive stable cell pool for protein production and single-cell cloning within 4-6 weeks
  • The process of constructing a stable cell line from the target gene to RCB can be completed in 3.5 months

Stable Cell Line Construction Flow Chart

Estimated timeline is around 3.5-4 months

Cell Culture Process Development

Based on our understanding on Chime Biologics’ self-developed cell line, we utilize shake flask and 3L bioreactor platform to develop the robust cell culture process. First, several platform medium and feed will be screened in shake flask reactors; then the cell culture process parameters, such as pH, temperature, DO, pCO2 etc. will be studied in 3L bioreactors. The process scalability is considered during the early process development stage. Good process scalability (scale-up to 50L or 500L) can support fast-track IND-enabling program.

Protein Purification Process Development

As guided by quality-by-design (QbD) principles, platform experience gained from different biologics entities is adopted to develop a robust purification process for IND projects. Firstly, the downstream process unit operations which could potentially impact product quality are identified by prior knowledge and risk assessment tools; then, both DOE and OFAT are used to scout the potential design space of process parameters based on the interaction of process inputs; finally, the purification process is confirmed at small scale. During the early stage of process development, the process scalability from benchtop to pilot scale and then commercial scale is taken into consideration.

Analytical Method Development

Chime Biologics Innovation Center provides the services of analytical method development, and testing of early development samples, cell line development and process development samples.

  • Physiochemical analysis: SEC-HPLC, IEC-HPLC, icIEF, CE-SDS (reduced/non-reduced), peptide mapping, glycan profile, sialic acid, etc.
  • Impurity analysis: residual host cell protein (HCP), residual DNA, residual Protein A, endotoxin etc.
  • Bioactivity analysis: Elisa binding activity

Our Equipment

  • Applikon My Control

  • Cytiva AKTA Pure

  • Fortebio Octet Qke

  • Merck Milli-Q IQ7000

  • Molecular Devices SpectraMax i3x

  • Solentim Single-Cell Imaging System