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Biologics CDMO

  • 180+ IND-Enabling Projects

  • 26 IND Filings Supported

By Mar.2023

Key technology driver
  • Host cell options:
    > CHOK1-GenS (in-licensed from ECACC)
    > Proprietary in-house developed CHOK1-ADCC+
  • CHO expression vectors:
    > Proprietary pGenHT 1.0-UP
  • Systems to support high-throughput clone selection:
    > VIPS™: single cell seeder
    > VIAFLO: channel handheld electronic pipettes
    > Cell Metric®: clone imager with assurance
bsAbs & protein cell line development experience
  • Extensive bsAbs cell line development experience in multiple formats, and reduce mismatches: bsAb with in vitro assembly, asymmetric bsAb, conjugated bsAb and other bispecific formats

    Case study: Reduce mismatches of bsAb

    Assembly of IgG-like bsAbs with correct polypeptide chains is one of the major challenges in their production. Random assembly of distinct heavy and light chains leads to non-functional or monospecific impurities. At ProBio, we test vector ratios to maximize the correct assembly during cell pool development stage to reduce mismatches and ensure production with high yield and purity

    • before：single-vector System

      before

    • Now：two-vector System

      now

    Fig. SEC-HPLC results shows that the ratio of mismatch of bsAb was reduced by 54%

  • Extensive protein cell line development experience for the production of hormone, enzyme, cytokines, blood coagulation factor, fc fusion protein and other functional proteins
  • Tool-box: solutions for improving titer and quality by optimizing the plasmid ratio and fermentation paramaters during process development
Service highlights
  • High-yield production records of various proteins:
    > Monoclonal antibody: average titer 5.4 g/L
    > Bispecific antibody: average titer 3.2 g/L
    > Protein: average titer 3.6 g/L

    Case study：Titer of mAb

    ProCLD shows up to 8.7g/L prior to cell culture

    Fed-batch培养第13天的产量（未经过优化）

    Fig. Titer at day 13 in Fed-batch culture using platform feeding strategy, without optimization

  • Production stability for top clones:
    > Consistent stability over 60 to 90 batches

    Case study : Stability of mAb

    ProCLD excellent stability in scale-up from 3L to 200L

    ProCLD细胞系开发克隆稳定性出色

    Fig. GenScript ProBio‘s cell line shows excellent scale-up stability from 3L to 200L

  • Meets quality regulatory compliance:
    > Full traceability of host cell and vectors
    > Full traceability of the cell line development process
    > Documented sequences of images to prove monoclonality
Cell Line Development Service Packages
PreCLD ProCLD ProCLD plus
Service package
  • Cell pool development
  • Developability assessment (optional)

    Case study：Developability assessment

    Cell pool and developability assessment help to identify the potential developability risk and help to select the CMC candidates

    Cell pool evaluation

    Candidates Cell pool Titer /mg/L
    A Middle
    B Middle 
    C High

    Developability: Candidate C was chosen and finally succeed in CMC.

    Stability  Analytical methods Changes from Tday0 and Tend
    Candidate A Candidate B Candidate C
    Free-thawn Appereance Remain the same Remain the same Remain the same
    Stressful (40℃ & 2 weeks) Appereance Remain the same Remain the same Remain the same
    CE-SDS-NR Decrease ca.10% Remain the same Remain the same
    SEC-HPLC Remain the same Remain the same Remain the same
    PTM by MS ~ 10% deamidation (not CDR) ~ 10% deamidation (not CDR) ~ 5% Oxidation (not CDR)
    cIEF Acidic and basic increased Main peak changed Acidic and basic increased
    Bioactivity Remain the same Remain the same Remain the same
    　Acidic condtion (pH3.5 & 25°C  & 4h)  Appereance Remain the same slight suspension slight suspension
    SEC-HPLC Decreased ca. 70% Decrease ca.40% Decrease ca.5%
    PTM by MS ~ 10% deamidation (not CDR) ~ 20% Oxidation (CDR) Remain the same
    cIEF Remain the same Main peak changed Remain the same
    Bioactivity Remain the same Decreased Remain the same
  • Cell line development
  • Top 6 clones
  • PCB & PCB stability
  • Cell line development
  • Feed & medium selection
  • Ambr15 bioreactor performance evaluation
Timeline 9 weeks 12 weeks (mAb, protein)
14 weeks (bsAb)		 16 weeks (mAb, protein)
18 weeks (bsAb)
Application scenario Late discovery stage, after humanized candidates Preclinical CMC development Preclinical CMC development
Transfection
High-titer Pool selection
Monoclonality assurance
Top 6 clones（PCB）
Top 1 clone

Bio-Rad for gene pulser xcell electroporator

  • The target vectors transfecte host cell lines with using electroporator

Solentim VIPS™ for single cell cloning

  • Evidence of successful single-cell seeding (Cell imaging of VIPS™ droplet in the plate)

Solentim cell metric®

  • Cell metric captures and records crucial evidence for monoclonality (4 photos/clone) , VIPS™ and cell metric® provide “double insurance”

Kuhner shaker for ISF1-Z incubator shaker/Infors HT for incubator shaker

  • Select top 6 clones by high throughput evaluation of cloning yield, cell growth and clonality

Ambr15 mini bioreactor

  • Clone evaluation & media & feed selection

Resources

  • Contact us
  • Phone: 1-877-436-7274 (Toll-Free); 1-732-885-9188
  • Fax: 1-732-210-0262