Cell line development

Reducing timelines in generating clonal cell lines for therapeutic protein production

Introduction

In the biopharmaceutical industry, many biological drugs are produced in mammalian cells. Cell line development (CLD) is used to determine which cell lines have the highest recombinant protein production and are also stable during large-scale manufacturing.

In the CLD workflow, cell lines undergo incremental scaling of culture from static to shaker flask expansion and further scaling up in bioreactors. Cell culture in early CLD is currently limited to static format as the size of the well plates and number of cells limit the ability to agitate the culture.

Introduction

In the biopharmaceutical industry, many biological drugs are produced in mammalian cells. Cell line development (CLD) is used to determine which cell lines have the highest recombinant protein production and are also stable during large-scale manufacturing.

In the CLD workflow, cell lines undergo incremental scaling of culture from static to shaker flask expansion and further scaling up in bioreactors. Cell culture in early CLD is currently limited to static format as the size of the well plates and number of cells limit the ability to agitate the culture.

Dynamic High-throuput screening in early stage

Traditional workflow

Traditionally, CLD starts from single cell isolation in post-transfection pools. After clones selection, the outstanding cells are transferred to larger and larger scale of cultivation system, and it almost takes several weeks.

cytena workflow

To improve and accelerate the cell line development, we offer the comprehensive product portfolio for significantly increasing the speed, quality, and efficiency of your cell line development workflows.

01

Comparability with
Shaker-flask

We cultured CHO cell lines that produce monoclonal antibodies with and without the c.bird system and compared cell profiles generated with that of cells cultured in a shaker-flask culture environment.
 
The results show that the c.bird improved live/total cell growth and cell viability and had superior comparability with those of large-scale shaker-flask cultures. In addition, it significantly improved cell doubling time and relative protein yields with no statistical difference when compared to shaker-flask cultures.

CHO-KI

CHO-S

C.BIRD enables early transition to suspension cell culture with higher cell growth rate in standard 96-well plates, potentially providing better translation to large-scale shaker-flask/bioreactor conditions for later CLD processes.

C.BIRD method on 24-well plates finalizes the workflow of CLD and offers a more amenable culture environment for suspension cell lines.

02

High-yield protein production

The high consistency of cell growth and protein yield profiles enables better predictability of biological profiles of the clones at early CLD stages. It also avoids additional time and costs spent on picking undesirable clones.

CHO-KI

CHO-S

96-well format

24-well format

CHO-KI
96-well format

CHO-S
96-well format

CHO-KI
24-well format

CHO-S
96-well format

Conclusion

Our results showed that the C.BIRD system with suspension culture exhibited superior performance compared to static culture, and exhibited comparable cell line profiles to shaker flask culture. Importantly, the C.BIRD suspension culture growth profile closely mimicked a late-stage shaker flask culture profile, an important feature for early cell clone selection and predictability.

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