Clarity in cell line development

Postcard from BPI Europe in Vienna – Highlights of the Cell Line Development Stream

This annual meeting in early Spring is always a good forum for major new product and technology announcements. In previous years, discussions often mainly centred around assurance of clonality and the requirements of the FDA – still a key consideration for cell line development. Recently, however, the market has expanded from a focus on monoclonal antibodies towards biosimilars, bispecifics and different modalities and this was reflected at this year’s conference too.

Conspicuous by their absence were any major new product launches. Instead, there was a focus on validation of technologies and the practicalities of implementation for different platforms purchased within the last 12 months.

New platforms shaping the industry

Practical implementation of new cloning platforms featured in many presentations, including talks by Angela Tuckowski from Janssen speaking on Solentim’s VIPS system (see video interview), Kerensa Klottrup-Rees from Medimmune discussing single cell printing, and Christine Demaria from Sanofi US and Chris Tan from Amgen on the Beacon system from Berkeley Lights.

At times, it felt like technology ping-pong, as different presenters outlined their experiences with the alternative platforms.

Christine from Sanofi was very candid in reporting their struggles to export “clumpy” cells from the Beacon pens, necessitating the use of an additive (TrypLE) to reduce clumps. Moreover, a resultant clone survival rate of only 50% was achieved, with no improvement in identifying any higher producing clones over that achieved via a standard cell line development approach. Seemingly, for Sanofi and Amgen, gaining assurance of clonality using the Beacon still seems to require export of cells to a 96-well plate and validation via the Cell Metric whole well imaging system.

Shifting Host Cell Lines and the potential of Re-Engineering

Because of the issues mentioned above, Sanofi reported that they are considering changing its host cell – a decision that inevitably will have knock-on effects and necessitate substantial amounts of new validation.

Sanofi were not the only company considering swapping host cell lines, or even re-engineering cell lines to suit their needs.  During Medimmune’s talk, Kerensa Klottrup-Rees explained how the Company had needed to develop a new host cell line better suited to single cell printing. In doing so, Medimmune achieved a four-fold improvement in outgrowth. One point made by Kerensa that resonated with many was likening cell line development process to a jigsaw puzzle – changing a single instrument with the process can have massive implications for the whole cell line development workflow.

Thomas Jostock and Holger Laux from Novartis explained how they had elegantly engineered their in-house CHO host cell line (CHO-3). By engineering five genes on the telomeric region of chromosome 8 they were able to reduce process time for ‘transfection to the end of ambr’ from 14-18 weeks down to just 8 weeks.

Mario Pereira from Horizon similarly spoke of how they had used CRISPR screening to improve their commercial CHO cell host.

Stability Studies

Another major theme throughout the presentations was stability. Martin Allen from Pfizer discussed how, by using their Site-Specific Integration, the Company could move stability studies off the critical path. This provides massive potential time savings of 10 weeks in the overall workflow.

Anton Bauer from The Antibody Lab also talked about work done using BAC to create hotspots for targeted integration. Using this approach, he claimed stable clones can be generated within 3 weeks of transfection.

Growth and Quantitation

Hannah Byrne from ValitaCell presented on a number of kits the Company is developing and launching for clone attributes, including higher titers (TITER PLUS), media lot testing (ValitaQC) and chemical stress (ValitaProliferate). These particular assays use Fluorescence Polarisation for detection.

It will be interesting to see how detection and kits develop as the industry progresses, and how they differ from those for standard mAbs. For example, we will need kits which can detect and resolve bispecific heterodimers from homodimers.


The event this year saw very little in the way of presentations on supplements for better outgrowth of cells in the cloning process. At Solentim, we see ready-made supplements as a key area where life can be made easier for scientists. We will be sure to bring this to the floor during BPI’s next meeting in San Francisco in June.

We look forward to seeing many of you there.

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