The biotherapeutics industry, particularly the development of monoclonal antibodies and recombinant proteins, is witnessing a significant transformation driven by advancements in automation technologies. Key issues within cell line development (CLD), such as genetic instability and unwanted post-translational modifications, pose challenges that can dramatically impact the production process. These issues often become apparent only after considerable time and resources have been invested, which can lead to costly setbacks.
One of the persistent challenges in CLD is the trade-off between productivity and stability during cell line selection. Typically, scientists favour high-yielding clones; however, these selections often struggle to perform consistently under large-scale manufacturing conditions due to various environmental stresses. The integration of automated screening and predictive capabilities is emerging as a critical strategy to address these concerns throughout the CLD workflow.
Automation, while not set to replace human roles entirely, is progressively streamlining processes that have traditionally relied on manual interventions. Many companies in the biologics development arena are introducing innovative products aimed at minimising waste, controlling costs, and equipping researchers with data analysis tools to make informed decisions in real-time regarding productivity and stability.
A noteworthy development in this space is the application of gene editing techniques alongside next-generation sequencing (NGS) to enhance the generation and characterization of clones on a large scale. Automation facilitates the editing, isolation, and screening of thousands of clones, using methods such as CRISPR-Cas9 and transposase systems to ensure the selection of optimal clones for further development. Additionally, scientists now have access to automated tools that quickly assess the genetic stability of clones, confirming integration sites and identifying any off-target effects.
To expand on the evolving role of automation in CLD, GEN engaged with industry professionals, including Michael Lutz, PhD, CEO of iotaSciences. Lutz stated, “Automation is facilitating any gene editing techniques for clone generation. According to a recent internal survey about CRISPR-Cas9, single-cell cloning poses the biggest challenge of such workflow. Automation helps to overcome this by performing all tedious liquid handling steps, while reliably assuring monoclonality and high cloning efficiency."
Adam Causer, PhD, global product manager for the Solentim portfolio at Advanced Instruments, highlighted the transformative nature of automation in cell screening. He noted, “Automation has fundamentally transformed cell screening in CLD by incorporating sophisticated imaging technologies and artificial intelligence, allowing for the high-throughput analysis of cellular images and enabling the detection of subtle phenotypic differences for selecting the most promising clones." Furthermore, he remarked on how automated platforms enhance the accuracy and efficiency of outcomes, significantly reducing development timelines and costs.
The shift towards integrated automation presents a holistic approach to CLD workflows. As per Lutz, while automation can provide solid end-to-end solutions, some manual tasks remain, particularly between the identification of monoclonal cultures and subsequent operational steps. Nevertheless, the continuous evolution of equipment and processes aims to address these operational bottlenecks.
Causer added that while automation has drastically improved the CLD workflow by connecting isolated stages—ranging from single-cell seeding through to productivity analysis—the challenge of seamless data integration remains. Laboratories often experience issues with data silos created by disparate systems, which leads to cumbersome manual data consolidation processes. However, advancements in fully integrated systems are poised to reduce these issues significantly, enabling real-time monitoring and predictive analytics while also facilitating regulatory compliance through the generation of comprehensive, audit-ready datasets.
Moreover, the ability of automated technologies to adapt CLD to different therapeutic modalities, such as vectors for vaccines or gene therapies, is further reinforcing their pivotal role in biomanufacturing. Lutz explained that the adaptability of automation varies with the CLD platform, emphasizing the relationship between cell robustness and overall viability for these diverse applications. Causer also noted that one of the critical benefits of automation is its flexibility, enabling consistent performance across various therapeutic modalities, thereby supporting scalability from research to production.
The growing automation landscape in CLD not only promises to enhance efficiency and reliability but also aligns with the increasing demand for precision in biotherapeutic development. The transition towards these advanced methodologies represents a significant step forward in addressing the complex challenges of biomanufacturing in an ever-evolving industry.
Source: Noah Wire Services