Transforming Analytics to Optimize Cell Line Development
For cell line development (CLD), much of a workflow’s success hinges on how much analytical data a team can get – and how quickly – to inform their process. The analytical methods supporting a CLD workflow are often complex, and many of the most crucial insights are gained from instruments that are often large capital expenses, too large to bring in-house, or too challenging for most CLD personnel to operate easily.
Achieving the analytical insights that enable decision-making is a key challenge for CLD laboratories. For many organizations, the technologies and expertise needed to drive these insights requires outsourcing a majority of their analytics to an external laboratory. While CLD labs can leverage certain analytics in-house to quickly measure immunoglobulin G (IgG) titer or count cells, these techniques are used for screening of cell lines. Other critical quality attributes (CQAs), such as product glycosylation or protein charge variants, typically require outsourcing. Once clones are identified, many of the outsourced analytics needed to determine the best clones can take days to return results, delaying insights and potentially impacting other steps in a process.
When it comes to achieving right-sized analytical methods for a CLD workflow, another core challenge relates to securing enough purified drug substance to perform necessary assays. Many of the most common assays performed in CLD, such as glycan analysis or charge variant analyses, are undertaken using liquid chromatography/mass spectrometry (LC/MS), which requires sample purification steps prior to testing. Volumes inevitably lost during purification and preparation mean operators must prioritize testing based on what insights are needed most critically at various points in a process.
Combining higher accuracy with greater flexibility for the assays needed in-house can reduce the hands-on time needed and increase lab capacity. For the Life Sciences companies of Danaher, these efforts are combined with a push to enable integration between analytical instruments and liquid handlers to establish more automated processes, connecting these, in turn, to digital solutions that can offer operators faster, more readily interpretable data.
Pursuing New Technologies for Accelerated Analytical Insights
The primary challenges that can preclude bringing many key analytics for a CLD workflow in-house frequently come down to the costs and resources involved. It is often difficult to find instruments for certain analytical methods that aren’t prohibitively expensive, that can fit into a lab’s existing footprint, or that don’t require a dedicated operator with specialized expertise. While most CLD labs choose to address this by outsourcing these analytics to dedicated third-party laboratories, this practice can create new challenges by delaying time-to-data, often by days. While the turnaround times associated with this outsourcing are less than ideal, the data generated by these instruments is too valuable when compared to more accessible – but less sensitive – equipment that may fit better into a lab or budget.
One of the most common assays that CLD labs relegate to outsourced testing for these reasons is IgG titer quantification. This is because the instruments best suited to performing these assays are HPLC systems, which have an associated footprint, cost, and complexity that makes them inviable for most CLD labs. Other, simpler methods, such as ELISA, may be more easily integrated into a laboratory but lack the precision, selectivity, and sensitivity of HPLC systems for accessing specific data or answering certain questions. Yet newer, more modular instruments and consumables have emerged to bridge this gap – for example, systems like Beckman Coulter Life Sciences' Valita Titer assays can measure IgG in less than 15 minutes. With readouts comparable to those produced by an HPLC system, Valita Titer is the most efficient assay for minimizing cost and time to results, as it works in the presence of cells, minimizes dilutions, eliminates wash steps, and easily integrates into automated and semi-automated high-throughput CLD and process development workflows. Used in combination with a plate reader like Molecular Devices’ SpectraMax microplate readers, Valita Titer is one of the fastest IgG tests available, going from start to data in as little as 15 minutes.
There may also be analytical workflows for which larger, more sophisticated in-house instruments are necessary. In these cases, being able to automate and optimize preparation steps associated with these technologies can be crucial to enabling consistency and maximizing their utility. For example, those seeking to incorporate mass spectrometry into their workflow may choose a best-in-class system like an Intabio ZT system, which can further accelerate insights and minimize user burden when compared to other MS systems. The Intabio, an automated sample preparation system coupled to a cutting-edge mass spectrometer, can help to streamline candidate selection, combining separation, quantitation, and direct identification of biopharmaceutical charge variants and their proteoforms to achieve access to integral, multifaceted data in minutes. Moreover, its enhanced capabilities, automation, and user-friendly interface all serve to lower the expertise necessary to operate it.
In some cases, the decision to outsource may hinge on the number of samples needed in parallel to inform decision-making. Most capillary electrophoresis systems, for example, can run only one sample at a time, which can greatly impact the time needed to perform candidate selection. In contrast, systems such as the SCIEX Biophase 8800 System facilitate the processing of up to eight samples simultaneously, allowing for more rapid insights into the CQAs of molecules. This increased capacity without compromising accuracy can be a critical improvement for CLD labs during antibody screening, helping them to identify the best candidates for further analysis more quickly.
Incorporating Improved Analytics for Comprehensive CLD Optimization
Enabling improved analytics for a CLD workflow is a crucial component to supporting successful process development and downstream scaling. By focusing on connecting an optimized analytical paradigm with improved automation and integrated, actionable data insights, CLD labs can realize compounding benefits to their workflows. From vector construction to transfection, screening, characterization, scale-up, and establishment of a master cell bank, the Life Sciences companies of Danaher have a technology portfolio designed to improve the cohesion of a CLD process across workflow steps, tying instruments, analytical methods, and data management platforms together to create an end-to-end bespoke solution.
In addition to its companies’ existing portfolio of technologies and instruments, with the strategic partner Genedata, a biopharma software solutions company, helps streamline workflow management through its software designed to automate and harmonize data across workflows and instruments. Genedata Expressionist is an open, scalable, and customizable software for MS analysis and Genedata Selector is an end-to-end solution that automates sample registration, NGS data processing, and analysis-to-reporting. These analytical software packages are each designed to support simplified, automated data analysis and presentation, and represent an integral facet of an overarching data management paradigm. Platforms like Expressionist and Selector can be further complemented by software that can efficiently parse and interpret the new data streams enabled by more sensitive and high-throughput instruments, integrating information from across every processing step to create a truly comprehensive digital ecosystem. This is where solutions like IDBS Polar, the world’s first BioPharma Lifecycle Management (BPLM) platform, can transform a workflow, connecting automated process steps together and curating all the resultant data to support both a CLD workflow and subsequent process design, scale-up, and tech transfer.
Ultimately, establishing a CLD workflow that can proactively advance mAb candidates to the clinic and beyond requires an equally proactive evaluation of the analytics that support it. While the industry’s increasing demand for greater output while maintaining constant budget and FTE workflows has made bringing many integral CLD assays in-house infeasible in the past, there now exist more modular, less expensive technology solutions capable of providing key insights previously limited to more complex systems. Combining these more streamlined analytics to complementary automation and data solutions is likewise important to supporting accurate, comprehensive CLD while more effectively addressing resourcing, human error, turnaround times, redundancies, and data inconsistencies.