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We share our insights and information about biologic drug development, including: innovative technologies that save time and create efficiencies with a goal of getting novel drugs to patients FASTER.

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Cell Line Development: It’s More Complicated Than You Think

Dec 4, 2019 2:25:58 AM

Just as it is well understood that silicon chips must be made in sophisticated factories with the appropriate engineering, materials handling and precision fabrication capabilities, so must biologic therapeutics with sophisticated factories that have the appropriate engineering, materials handling and precision fabrication capabilities. Only in this case, the factories are living cells. Therefore, choosing the right cellular factory for biologics manufacturing is just as critical for managing timelines, quality and ROI, as it is choosing the right semiconductor plant for chip production. Today the mammalian cellular factories of choice for most biologics are Chinese hamster ovary cells (CHO). Even the most sophisticated contract development manufacturing organizations (CDMO) cannot solve production issues if the productivity of the manufacturing cell line is substandard.

Even the most sophisticated CDMO organization cannot solve production issues if the productivity of the manufacturing cell line is substandard.

Within CDMOs, there are competing philosophies. One class of #CDMOs views cell line development as the first of many steps and tends to approach production challenges during the upstream and downstream processing phases. We call this process innovation. Another class of CDMOs views cell line development as the critical first step, and thus they innovate around the cell line technology platforms to improve the quantity and quality of expressed proteins, even before manufacturing optimization. We call this technology innovation.

CDMOs with technology-innovative cell line developers have been able to keep their #CHO cellular “factories” current as they:

  1. tackle next-generation protein therapeutics (i.e., bi-specifics, multi-specifics, fusion proteins, antibody fragments, non-natural scaffolds, etc.)
  2. maintain flexibility
  3. establish themselves as knowledge leaders and trendsetters

The most successful organizations engaged in cell line development innovate technology beyond simply boosting the transcription levels of therapeutic protein. They holistically approach cell line development by addressing the range of transcriptional, translational and secretory requirements of any given therapeutic so that it can be manufactured at clinically and commercially viable levels.

Cell lines determine the performance of bioprocesses and the quality of the biologic drug substances they produce. Our CEO contributed to a recent article in BioPharm International, "Best Practices for Selecting a Top-Quality Cell Line." READ MORE

To achieve that breadth of understanding of the cells, there needs to be an in-depth understanding of their cell line’s genome and transcriptome and development of technology modules that can be applied to address a myriad of production bottlenecks. For example, a major biopharmaceutical company determined that deletion of a telomeric region on chromosome 8 correlates with higher productivity and stability of CHO cell lines. Researchers there also were able to identify a protease that was affecting product quality and were able to knock it out.  Here at Selexis, based on the genome and transcriptome of our manufacturing cell line, we have built libraries of gene families to help productivity issues sometimes experienced with certain proteins. In some cases, use of these libraries rescued projects that companies were at risk of having to abandon to productivity issues.

Therefore, choosing the right cellular factory for biologics manufacturing is just as critical for managing timelines, quality and ROI, as it is choosing the right semiconductor plant for chip production.

Even the most sophisticated CDMO organization cannot solve production issues if the productivity of the manufacturing cell line is substandard. It is best to start with cell production clones that are stable, high-producing and offer high-viability.

I’d be happy to discuss Selexis technology innovations with anyone who is interested in learning more about Selexis as well as to provide insight and questions to consider when planning for manufacturing cell line development. 

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