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WuXia™ Cell Line Development

Proven, High-Yielding Cell Line Development Platform Accepted by Regulatory Agencies Worldwide

 

The WuXi Biologics Cell Line Development (CLD) Platform WuXia(TM) Logo

WuXi Biologics offers comprehensive mammalian cell line development (CLD) capabilities for various biotherapeutics as a standalone service as well as part of our integrated CMC (Chemistry, Manufacturing and Controls) biologics development platforms. Starting from client-provided DNA or amino acid sequences, we utilize our WuXia™ cell line development platform, that includes our highly optimized host cell line and proprietary vectors to provide a high quality and high yielding (up to 11 g/L in fed-batch mode) stable cell line for subsequent process development and GMP production activities. To date, we have constructed more than 800 stable cell lines for clinical and commercial production using our highly-vetted CLD technologies and process.

 

WuXia™ CLD Platform Performance Overview

Our flexible and robust CLD platform is capable of producing a wide array of biologics.

The Ideal Solution from cDNA to GMP Production

 

Our WuXia™ Cell Line Development system leverages our proprietary CHO-K1 cell line which has been shown to generate titers equal to or better than industry standards at accelerated timelines. All of our CLD services are supported by our cell culture process development and analytical development teams, and high-throughput automated systems to facilitate the delivery of high-yielding, well-characterized, stable single clones. In addition to our CHO-K1 cell line, HEK293, WuXiaADCC PLUS™ and GS CHO hosts are available for CLD if required.

The Chinese word “WuXia” translates to “flawless or ideal” in English.

Hence, this is why we chose to name our

cell line development (CLD) platform – “WuXia.”

The fast CLD timelines as shown below, coupled with the high titer, high quality, and excellent stability of the WuXia™ platform empowers our partners to rapidly move towards IND filing.
 
The WuXi Biologics Cell Line Development (CLD) Platform WuXia(TM) LogoCLD Platform: Flexible Timeline Options
 
The typical workflow of our CLD platform is as follows (a more detailed process description can be found here):

 


Key Features:

Watch the video and read below about the critical features of our WuXi CLD platform to understand what makes our system “ideal” for biologics development and eventual GMP production.

 

Video information updated till the end of 2022

Our Host Cell Toolbox Enables Fit-for-Purpose Development

 

In addition to our CHO-K1, HEK293, WuXiaADCC PLUS™ and CHO-K1 GSKO host cell lines, we provide gene editing services using our in-house CRISPR- guided RNA design tool and highly optimized and engineered host cell genome to further improve performance.

 

Learn more at the following links:

 

Proprietary In-Silico Toolbox  – Metadata Codon Optimization

 

We offer a collection of in silico protein molecule assessment, design and optimization tools, which include sequence liability and signal peptide analysis, and post-translational modification, immunogenicity and aggregation prediction.

 

Learn more at the following links:

 

Rapid Bulk Pool Enables Fast Material Generation for Development and Toxicology and Clinical studies.

 

Post transfection into our host cell line, we rapidly generate bulk pools for initial screening prior to single cell clone selection. Our Rapid Bulk Pool process is also used to quickly produce high quantity and high quality product for development and toxicology studies.

Lab Digitalization and Automation Ensure Development Quality

 

The WuXi Biologics CLD team utilizes multiple high-throughput automated equipment and systems throughout the cell line development process. Lab digitalization systems (e.g., LDMS) and automation helps ensure cell line and product quality through robust and reproducible sample handling and processing.

Exceptional Stability

 

Our WuXia™ CHO-K1 platform provides highly stable clones for large scale commercial manufacturing. The proof of the robustness of our host cell line comes from cell line and product stability studies conducted on over 300+ producer cell lines generated for clinical and commercial production.

Stable Expression of Afucosylated Antibodies

 

Increasing the antibody-dependent cell-mediated cytotoxicity (ADCC) response is a crucial mechanism researchers work to achieve when utilizing targeted antibody-based immunotherapy approaches. The development of novel cancer therapies entails designing and engineering antibodies with increased ability to heighten the ADCC response, which is known to improve therapeutic efficacy and patient outcomes.

 

Removal of fucose on the N-glycosylation site is an efficient and cost-effective way to enhance ADCC activity and increase the potency of antibody-based immunotherapies. To meet growing global demand for the production of afucosylated antibodies, the WuXiaADCC PLUS™ cell line was developed to address this need. WuXiaADCC PLUS™ was derived from the WuXi Biologics’ highly-vetted WuXia™ CHO-K1 cell line, and as such, the WuXiaADCC PLUS™ cell line exhibits comparable robust growth and metabolic profile to the WuXia CHO-K1 parental cell line.

 

Figure 1: Demonstration that an afucosylated antibody produced from the WuXiaADCC PLUS™ cell line exhibits significantly enhanced ADCC activity

 

WuXiaADCC PLUS™ provides an average mAb clone titer of 6 g/L and is compatible with the WuXia cell culture platform process which enables the stable production of afucosylated antibodies at various scales for clinical and commercial manufacturing.

 

WuXia RidGS™ is a technology platform for cell line development that builds on our established WuXia technology. Retaining the robust cell growth, metabolism, and expression profile of WuXia, WuXia RidGS™ also boasts high expression levels, exceeding 6 g/L for monoclonal antibodies (mAbs). WuXia RidGS™ incorporates advanced zinc-finger nuclease (ZFN) technology to knock out the glutamine synthetase (GS) gene in CHO cells, stabilizing cell lines for mAbs, bispecific antibodies (BsAbs), Fc-fusion proteins, recombinant proteins, and other therapeutic modalities.

 

The quality of protein products expressed by the WuXia RidGS™ technology platform showcases favorable glycosylation patterns while maintaining an exceptional purity profile. Because the technology platform eliminates the need for antibiotics, host and production cells consistently maintain stable productivity and uniform product quality throughout intensive, long-term studies of cell line stability.

 

 

 

Supporting Services

The following capabilities can be utilized as part of our integrated cell line development activities or as standalone service offerings. 

Reagent and Bioassay Cell Lines to support Analytical Programs

 

In addition to biotherapeutic production cell line development services, WuXi Biologics’ CLD team generates cell lines for protein reagent production and bioassay cell lines to support analytical programs throughout development and into GMP quality control testing.

For more information, click here.

Specialized NGS & Molecular Biology Services

WuXi Biologics offers a wide range of Next Generation Sequencing and other critical molecular biology methodologies for the evaluation of cell lines and the gene of interest either in support of an integrated CLD program or as a standalone service. For more information, click here

Comprehensive and wide-ranging analytical methods are available to assess the product during developability studies and cell line development activities. Examples of our analytical services that support CLD include:

 

  • Purity
  • Aggregates
  • Identity
  • Titer
  • Glycan Profile
  • Binding or Potency Assay
  • Charge Variance
  • Sequence Variance
  • Post-Translational Modifications 

Our in silico assessment toolbox was designed for clients evaluating multiple lead molecule candidates to make economical and efficient CMC product development decisions. This in silico analysis could predict and mitigate the risks of subsequent development issues due to manufacturability, stability, immunogenicity and other issues.  These in silico services can be integrated into a CLD program or provided to you as a customized standalone service.

 

Our in silico assessment contains three core-aspects:

 

  1. Sequence analysis
  2. Aggregation propensity
  3. Determination of immunogenicity

 

For sequence analysis, we first check the sequence elements and identify the unknown domain/motif. Then, we verify if there are any sequence areas (“hot spots”) that could potentially be  susceptible to chemical and enzymatic modifications.

 

For aggregation propensity, we calculate the aggregation probability based on the surface hydrophobicity, charge, and free-cysteine residues of the protein.

 

Lastly, we evaluate the immunogenicity risk of the molecule by computing the sequence binding possibility to MHC molecules, and also comparing the sequence similarity to the human BCR database.

 

Through in silico assessment, the molecule candidates with higher CMC risks could be eliminated from further development to save cost and ensure development timeline milestones are met. Below we provide typical data or analysis resulting from our in silico biomolecule assessment program.

One-stop Cell Bank Creation

 

WuXi Biologics provides comprehensive, one-stop, EMA, PMDA and NMPA certified cell banking services. Twenty-two cGMP cell bank suites are available, providing the capacity to produce over 440 Master Cell Banks (MCB), Working Cell Banks (WCB) and End of Production Cell (EOPC) banks annually.  Integrated with our in-house cell line development and cell line characterization and biosafety testing services, performed per global regulatory guidelines (e.g., ICH, U.S. FDA, EMA and NMPA), we provide streamlined, efficient, one-stop service from cell line engineering to release of GMP manufactured cell banks.

 

For more information – click here.

WuXi Biologics’ biosafety testing lab is the leading biosafety lab in the Asia Pacific (APAC) region. We provide comprehensive, validated methods that meet global regulatory guidelines (e.g, USP/EP/JP/ChP and ICH, U.S. FDA, EMA and NMPA). Services include:

 

  • Cell line characterization (PCB/MCB/WCB/EOPC )
  • Mycoplasma, general virus and adventitious virus assays for various biologics, and cell and gene therapies.
  • Viral clearance validation studies for IND and BLA.
  • Clinical and commercial Unprocessed Bulk (UPB) lot release services.

 

More information about Biosafety Testing Click here. 

The need to evaluate genetic stability of clonal cell lines with multiple chromosomal insertions of an expression construct and used for biologics production is dictated by the global regulatory agencies.  The recommendations could include verification of nucleotide sequence by directional sequencing of the mRNA or cDNA, Southern and/or northern blotting, and determination of copy number by qPCR or ddPCR amongst other possible criteria.

 

We provide a one-stop all-inclusive genetic stability evaluation of Master Cell Banks (MCBs), Working Cell Banks (WCBs) and End of Production Cells (EOPC) either integrated into a cell line development project or as a customized standalone service. Our molecular biology team has successfully completed genetic stability studies for our global clients in >140 IND applications and >40 BLA filings.