Antibody Drug IND

皓阳生物抗体药物CMC 开发时间进度表2-3.png

From DNA to IND: Total 15 months

Stable cell line construction


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  • From transfection to screening to complete high expression of monoclonal cell lines and provide a preliminary Fed-batch process, the shortest time is only 11 weeks.
  • Using a commercialized, chemically-defined medium, the expression of conventional antibodies can reach 4-7 g/L in a 14-day Fed-batch process, up to 8 g or more.
  • Use the method of limiting dilution and automatic microphotographing to effectively prove the monoclonality.
  • Project status: Phase I

Upstream process development


  • 12 sets of 3L reactors, 4 sets of 10L reactors
  • Increase in expression (evaluation data for expression of 106 items)
  • Regulation of glycosylation (glycosylation data of 106 items)
  • CEX adjustment (cief data of 106 items)
  • ADCC improvement (transient 048 data)

Downstream process development

It has a mature protein purification preparation process platform, equipped with intelligent protein chromatography purification system such as AKTA Pure and Avant, and a pilot purification system compatible with 200L cell culture scale. It has process development for protein drugs such as monoclonal antibodies and fusion proteins. Experienced. According to customer needs, we can develop protein purification preparation processes that meet the requirements of relevant Chinese and international regulations to ensure that the process meets the needs of industrialization amplification.

  • Chromatography process development and optimization (filler screening, buffer system screening, dynamic capacity screening, etc.)
  • Microfiltration, ultrafiltration and other process development
  • In addition to virus process development (low pH incubation, S/D treatment, nanofiltration)
  • Pilot level purification process amplification and confirmation

Analytical method development

Analytical development and detection platform with advanced instruments such as Waters H-Class UPLC, Waters ARC UHPLC, Agilent 1290 Infinity, Agilent 1260 Infinity, Protein Simple Maurice, Tecan INFINITE 200 PRO, Biorad realtime PCR, etc. , fusion proteins, etc. for the development, validation and validation of analytical methods, as well as the provision of quality testing for clinical trials for pilot production.

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Formulation method development

Using platform technology, based on the protein characteristics of different projects, quickly and efficiently screening appropriate formulation prescriptions, preliminary evaluation of product stability.

  • DSF high-throughput screening buffer system and pH range
  • Combination formula to investigate the effects of excipients and excipients
  • Influencing factors test preliminary investigation of product formulation stability
  • Choice of packaging materials
  • Confirmation of filling process

Pilot production

Using platform technology, based on the protein characteristics of different projects, quickly and efficiently screening appropriate formulation prescriptions, preliminary evaluation of product stability.

Case Study

CHO DG44 Project cho dg44 CHO-K1 Project Cho-K1
Project Overview
  • Format: mAb
  • Timeline from transfection to top clones: 18 weeks
  • Top Pool: 0.5 g/L, Top Clone in Spin Tune: 3.8 g/L, Top Clone in Bioreactor: 4.6 g/L
  • Project status: Phase I
Clonality
Top Clones

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Process Optimization in Bioreactor: pH, temperature shift, seed density etc.
Project Overview
  • Format: Fc-Fusion
  • Timeline from transfection to top clones: 13 weeks
  • Top Pool: 1.9 g/L, Top Clone in Spin Tune: 3.4 g/L, Top Clone in Bioreactor: 7.5 g/L
  • Commercial CD Basal and Feed Medium
  • Project status: Scale –up & 3-batch Production
Cell Culture Process Optimization