Developing A Novel Approach To Real-Time Monitoring Of Antibody Titer
Optimizing process efficiency is an ongoing goal of the biomanufacturing industry. Improved processes have a direct impact on lowering operating costs, reducing risk of production failures and can improve product quality which all leads to getting drugs to patients efficiently, cost-effectively and in a timely manner. A key step toward achieving this goal is the application of advanced manufacturing methods, such as continuous processing, and the use of automation and data integration to improve operational efficiency and increase flexibility and speed to market.
As the industry continues to apply innovative tools and solutions for manufacturing, it also needs to have real-time monitoring in place that is robust enough to keep up with a modern production suite. In the case of measuring antibody concentration, or “titer,” the current standard method is through offline methods, such as sending samples to quality control labs that take at least 24 hours to return results, or by using the traditional method of high-performance liquid chromatography (HPLC). However, these approaches present challenges to the goal of improved efficiency, leading to the development of a new tool, the Tridex™ from IDEX Health & Science.1
The Tridex offers reliable titer measurements in less than 5 minutes, as opposed to HPLC, which can take anywhere from 10 to 30 minutes. It requires only a reagent pack and analysis module. These consumables, which last for 1,000 analyses, do not require tools to be changed out and can be done quickly to limit delays in production. The Tridex's trap and elute technique samples directly out of the bioreactor and into the system, quantifying the amount of Immunoglobulin G in a cell-free sample. Using a tool such as this facilitates monitoring and control of drug development and gives biomanufacturers an advantage in what has become a complex and costly process that requires the consistent delivery of high-quality products.
A Solution To HPLC Challenges
With HPLC, a sample mixture is sent through a column of chromatographic packing material at a high pressure. HPLC instrumentation is expensive and requires highly trained employees to run the system and analyze the results, and due to its size, can be difficult to put into a production suite. IDEX recognized the limitations of this method and wanted to develop a solution that delivered the results of HPLC but in something that is small, compact, and easy to use.
IDEX was new to the biomanufacturing space as their expertise is in the engineering industry. The team realized they needed a partner with not just a well-known and solid reputation in biomanufacturing but one that could also offer the advantage of using the Tridex on a bioreactor that was running cells in an actual customer setting. With an industry that is often skeptical of change and hesitant to share proprietary details, finding a partner who was willing to share information was critical to the development of IDEX's tool. After vetting its options, IDEX partnered with Aragen Bioscience, an industry-leading contract research organization (CRO) with experience in end-to-end capabilities from in vivo efficacy models through antibody discovery and humanization, recombinant protein production, purification, and analysis to stable cell line development.2 Because of Aragen's large client base, they can provide insights as to what is generally happening in the industry and can answer questions based on what they have seen. Aragen's extensive experience and knowledge in bioprocessing also presented an advantage to IDEX, as proper development of a solution would require real customer experiences and honest feedback.
Aragen was familiar with the cumbersome and difficult techniques typically used for determining titer during and/or after harvest and was eager to work with IDEX on their solution. Aragen knew the benefits a tool, such as Tridex, could offer clients value through fast and accurate data. The result was a collaboration that benefited the companies involved and had the potential to provide an exciting and much-needed solution for the biomanufacturing industry.
The Development Of Tridex
Initial discussions between IDEX and Aragen centered on brainstorming the best approaches to deliver cost-effective antibody measurements. Developing a plan required careful consideration of cost and time, and the right pace, for each stakeholder. The project was ultimately organized in phases, with the understanding that more extensive testing would be needed once IDEX produced an initial proof of concept.
As the project progressed, Aragen and IDEX maintained open lines of communication, with Aragen providing details and information whenever the tool did not perform as expected, such as small deviations in the concentrations of titer. Although the deviations were able to be accounted for easily and collectively, having information ahead of time allowed IDEX to prepare for troubleshooting and quickly resolve any issues upon arrival. Aragen was also willing to run processes simultaneously using other capabilities, so IDEX could draw accurate comparisons between its product and other methods on the market. These included Protein A with HPLC for target determination and the use of biolayer interferometry using the ForteBio™ Octet™ Red platform. Upon comparison, Aragen found Tridex to be the fastest and most accurate method for offline titer of cell harvest or real-time harvest for titer determination.
In August 2019, after two years of working with Aragen, IDEX announced the launch of the Tridex Protein Analyzer to the bioprocessing industry.3 It is considered the first protein analyzer on the market built specifically for bioprocess monitoring and can be used in the development of a wide range of drugs for several diseases, demonstrating the innovative solutions possible through collaborations across the drug development and manufacturing network.
- IDEX Health & Science, Real-Time Protein Titer Measurement for Bioprocessing, Retrieved from https://www.idex-hs.com/wpcontent/uploads/2019/06/Tridex-Brochure.pdf
- Aragen Bioscience, https://www.aragenbio.com
- IDEX Corporation, IH&S Launches Tridex™ Protein Analyzer for Bioprocessing, (2019) Retrieved from https://www.idexcorp.com/news/news-item/ihslaunches-tridex-protein-analyzer-for-bioprocessing/