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Confident clonality: How to make your IND approval a reality

One of the key approval steps on the path to commercialization of a new therapeutic is an FDA-accepted Investigational New Drug (IND) application. During preclinical development, the main goal is to determine if the product is safe for initial use in humans, and when this is established, the focus shifts to collecting data that ensures the drug is appropriate for large scale clinical studies. 

A clonally derived Master Cell Bank is seen as a critical component of a robust, consistent process that ensures drug product quality and safety, and insufficient evidence of clonality in an IND submission can lead to costly delays when trying to get to first-in-human trials. In short, monoclonality assurance can make or break your IND application.

A successful IND 

In January, at the 39th annual JP Morgan conference, our CEO Eric Hobbs, Ph.D., announced that the first IND application incorporating monoclonality assurance data from the Beacon® system was approved by the FDA. In Eric’s words, “This means that our highly replicable, standardized, automated CLD workflows, with associated data capture received approval for the creation of monoclonal cell lines. We believe that this will further shorten cycle times in the overall approval process.” 

The OptoCell Line Development workflow on the Beacon system has been demonstrated to provide >99% probability of clonality from a single automated round of cloning. So just how exactly do we achieve this level of clonal ity assurance? The Opto CLD workflow tackles it in 3 parts. 


In the first stage of the Opto CLD workflow, cells are loaded onto an OptoSelectchip and software identifies single cells that are then moved into NanoPenchambers. Imaging and automated cell counting means that cells can be visually tracked within the chambers to ensure only a single cell is loaded for culture. 


Once penned into the chambers, the OptoSelect chip is perfused with media, and cells are cultured on-chip over several days. As cells grow, fluorescence-based assays can be performed multiple times to find clones with desirable growth rates, antibody secretion, and relative cell productivity. If clones expand too quickly, overgrowth is removed through automated “pruning.”


After a few days of culture, OEPtechnology is used to move the clone out of the chamber and export it into a 96-well plate. The channel is flushed with media before and after each individual clone export, which means there’s no cross-contamination. This media is also collected in blank wells, which can be stained and imaged to ensure no contaminating cells were present in the channel during export as well.



>99% monoclonality in action

When it comes to IND-caliber monoclonality assurance, we have the data to back it up. During a month-long experiment, a total of 30 OptoSelectchips were loaded with CHO cells on two different Beacon systems from which 650 clonal populations were selectively unloaded. In total, only three contaminating colonies were identified across all blanks, which resulted in monoclonality of 99.88% — the equivalent to four rounds of limiting dilution. To get a closer look at all of the details, check out the application note.

The clonality assurance of the Opto CLD workflow has been independently validated as well. In a paper by Kim Le, et al., the Beacon system provided a stronger data package for single cell cloning, and improved efficiency over FACS and limiting dilution.

End-to-end assurance

Taking a potential drug target to commercialization is a rigorous, multi-step process that can take years to complete. The Opto CLD workflow on the Beacon system can help accelerate this process by providing superior end-to-end clonality assurance, which means a faster path to a confident IND application.

Want to learn more about how the Opto CLD workflow can set your IND up for success? Reach out to us and we’ll be in touch within 24 hours.


This story originally appeared in the Spring/Summer 2021 edition of BLI News. To read more, check out the latest edition.