In facilitating the move to continuous processing in biotherapeutic production, bioprocessing specialists are being driven to develop innovative analytical testing methods for key measurements of output and quality, such as antibody titer.
Technology Networks recently spoke with Max Geiger, Associate Product Solutions Manager, BioProcess Analytics at IDEX Health and Science, to learn more about the importance of determining antibody titer in bioprocessing and how the Tridex™ Protein Analyzer was developed with this in mind.
Holly Large (HL): Why is antibody titer monitoring important in bioprocessing?
Max Geiger (MG): Biotherapeutic production relies on engineered cell lines to express antibodies with predictable output and quality, so determining the titer of the antibodies at multiple points during the production process is essential. Analytical testing of cell culture in monoclonal antibody production calls for rapid, robust antibody titer measurements with a wide dynamic range, to monitor product yields throughout a bioreactor run. Generally considered a critical process parameter for characterizing upstream bioprocessing efficiency, titer measurements indicate the proportion of desired product relative to a given bioreactor volume.
Convenience and accuracy of protein titer data is key in instituting a process analytical technology approach, as this allows for monitoring critical process parameters and informs real-time decision making.
HL: Can you give a brief explanation of what the Tridex™ Protein Analyzer is and how it works?
MG: Tridex™ is the fastest, simplest solution for real-time antibody titer monitoring. Using a space-saving design, engineered for convenience, the Tridex™ Protein Analyzer is an innovative, compact device for at-line and on-line measurement of antibody titer directly from a bioreactor. Tridex™ performs a proprietary trap-and-elute chromatographic assay that quantifies the amount of IgG in a cell-free sample. The Tridex™ Analyzer is specifically designed to integrate directly into the bioprocessing suite to provide real-time data, without disrupting existing equipment and workflows.
Tridex™ allows the user to actively monitor titer and achieve accurate titer measurements, which correlate to off-line high-performance liquid chromatography (HPLC), in only five minutes. Tridex™ requires only two consumable parts: the reagent pack and the analysis module. This approach delivers fast and accurate results, without the need for extensive method development or specialized chromatography expertise. The sample flow path is completely enclosed, lending itself to the requirements of single use. It is a complete solution which transforms titer into actionable data, allowing for a more efficient process development, resulting in increased efficiency and productivity in bioprocessing.
HL: What were the driving forces behind the development of this analyzer?
MG: The measurement of antibody titer is a critical parameter for manufacturing biologics and biosimilars. The biopharma industry has long been seeking an alternative to time-consuming offline methods currently in use. The Tridex™ Protein Analyzer is purpose-built to deliver accurate titer measurements over a dynamic range of 0.1–10 g/L, with minimal sample manipulation for use in R&D and process development.
The Tridex™ Protein Analyzer is the first instrument on the market designed specifically for bioprocessing. Tridex™ provides actionable data quickly to enable real-time decision making and facilitate the transition to continuous bioprocessing, making it unique among titer solutions currently available. The Tridex™ is operated in just four simple steps: enter sample information, load the sample, start the analysis, and get the results quickly. The equipment and process were designed to deliver fast and accurate results without the need for method development or specialized training. It was also created with a compact design offering a small footprint with minimal connections for power and waste lines. Tridex™ is ideally suited to provide titer data where it is needed most: in the production suite. A fast titer measurement is particularly valuable during the transition from upstream to downstream processing where this data is required for production to move forward. This is one example of how Tridex™ eliminates production downtime due to slow off-line titer analysis.
HL: HPLC can also be used to monitor antibody titer in bioprocessing. What are the drawbacks of this method and how does the Tridex™ Protein Analyzer overcome these?
MG: Whilst the HPLC technique is powerful and sets the industry benchmark for accuracy and dynamic range, operating an HPLC requires a high level of training and expertise. Even after an HPLC method is developed, expertise are required to run a test and interpret the results.
Each analysis involves a significant amount of method development and calibration before running a single titer measurement. As a result, a titer measurement on an HPLC usually takes place off-line away from the bioreactor in a separate lab managed by a different department. As a result, it is common for HPLC titer analysis to have a 24 hour turn around – in comparison to just five minutes when using Tridex™.
Alternative, automated methods are increasingly being considered as a replacement for HPLC. Tridex™ delivers antibody titer which correlates to off-line HPLC measurement across an extraordinary dynamic range, ensuring full confidence in the titer data. The option to connect to an automated sampling system allows the Tridex™ system to integrate completely into a bioprocessing environment to deliver true online titer data. Access to fast, accurate, real-time titer data can help to make decisions quicker, which minimizes costly hold times and bottlenecks.
HL: Can the analyzer be utilized beyond measuring antibody titer?
MG: Tridex™ is designed specifically to meet the compelling need for real-time antibody titer measurement in bioprocessing applications. The instrument is based on an integrated platform which could be used to solve other analytical challenges in bioprocessing in the future.
Max Geiger was speaking to Holly Large, Editorial Assistant, Technology Networks.