Host Cell Switching and Re-Cloning
Switching Host Cells
An important decision in the development of biosimilars is the choice of cell line. Changing from the originator cell line can lead to changes in post-translational modification, which can affect the characteristics of the product. The largest variations can occur in glycosylation patterns which have a significant effect on antibody-dependent cell cytotoxicity (ADCC), half-life, stability and immunogenicity.
Despite these potential pitfalls, there are sometimes clear benefits to host cell switching which include:
- Recreation of an existing production cell line
- To evaluate an alternative route for biosimilar production and improve productivity
- Avoid issues arising from cell line licences or improve regulatory acceptability and provenance
GreenLight’s CLD technology can be used to switch host cell platform from older originator cell lines (e.g. NS0 and Sp2/0) to Composite CHO™ . The product expressed by the new Composite CHO™ manufacturing cell line is fully screened for Critical Quality Attributes, including binding specificity and mode of action of the innovator molecule, leveraging GreenLight’s extensive in-house bioanalytical and bioassay capabilities.
The regulators’ evolving guidance on the stringency of evidence required to demonstrate assurance and probability of clonality for a mAB or biosimilar, means that clonality is currently a “hot topic”. GreenLight’s validated CLD expertise can be used to re-clone an existing production cell line, providing extensive documentary and statistical evidence of monoclonality in alignment with current FDA expectations. Re-cloning can also be used to improve the antibody production of older cell lines where production has decreased over time.
GreenLight’s re-cloning includes:
- Expression screening and colony selection or ELISA based screening
- PQA and Bioanalytics at multiple stages
- Limiting dilution cloning for a high statistical probability of monoclonality
- High definition imaging (Solentim CellMetric) to trace colony back to a single cell at point of plating
- Lead selection and generation of GMP ready RCB suitable for MCB generation
- Extensive validation and documentation for each stage of the process
- Alignment to the current FDA guidance
Working with GreenLight
GreenLight’s cell line development services are tailored for each project to ensure that the objectives are met or exceeded. Experienced project teams are assigned to each study focusing on progressing projects through to results in the minimum amount of time. Our clients widely regard us as professional and attentive partners who deliver quality results.
To get more information, a quote or to schedule a teleconference please contact us.