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Automating Online Sampling of Bioprocesses
Unlike in the chemical and food industries, and even in small-molecule pharmaceutical manufacturing, which have well-established methods for automated online sampling, the biopharmaceutical sector remains in need of a reliable system that transfers bioprocess samples directly from bioreactors to analytical devices while maintaining process sterility. Such a system is necessary if biopharmaceutical companies are to effectively take advantage of process analytical technology (PAT) and gain a more fundamental understanding of what is happening within bioreactors. While on-line Raman and dielectric spectroscopy provide some insight, there remains a need for integration of this data with off-line measurements, such as cell density, viability, metabolite levels, and titers.
To overcome this issue, Bend Research (part of Capsugel Dosage Form Solutions), in collaboration with major biopharmaceutical companies, including Pfizer, Eli Lilly, and Boehringer Ingelheim, has developed the Modular Automated Sampling Technology (MAST) platform. MAST consists of a sterile sampling system, a sample scheduler and navigator for automated sampling and delivery of samples to various analytical instruments, and a data-management system for collecting and analyzing the results, and if desired, providing feedback to the bioreactor for direct adjustment of reaction conditions.
Importantly, both systems can be sterilized in place (SIP), autoclave-sterilized, or gamma-sterilized depending on the model selected. “The entire system can be cleaned and sanitized between each sampling, and there is flexibility for users to adapt various cleaning procedures depending on their specific needs,” notes Lisa Graham, senior vice-president of Bend Research.
Sample and data management
The MAST Data Management system will maintain information on sampling activities and analysis results and has the ability to automatically adjust the feed rate of the bioreactor to meet desired growth rates according to the current condition of the cells. “With this data management system, it is possible to significantly reduce the time needed to process large sets of analytical results. Information on the state of cells and the process is obtained more rapidly, ” Pepper asserts.
On-line measurement combined with at-line analysis
MAST systems have been placed in nine client facilities (15 total units installed) with more than 2400 sterile samples collected without loss of sterility. “The major MAST product modules have moved out of the beta testing stage and are being sold to early adopters as pre-commercial products,” says Pepper.
In the near future, Bend Research plans to install the first multiplexed MAST system capable of collecting samples from up to eight bioreactors and sending those samples to as many as four analytical devices. “This solution should gain a lot of traction in the laboratory setting where banks of bioreactors are running at the same time,” says Pepper.
Enabling process control
“Our intention with the MAST platform is to help biopharmaceutical companies gain insight into what actually occurs in a bioreactor by providing a means for understanding how bioprocess variables affect overall product quality,” comments Graham. “We believe that by coupling the right tools, the MAST platform provides in-depth guidance for optimization of the reactor environment in order to meet cell needs for the production of the target product. Ultimately, we hope that the MAST platform will provide the meaningful real-time analytics, process measurements, and novel data management techniques that will enable the development of predictive control models that in turn will drive increased product consistency and batch-to-batch reproducibility,” she concludes.
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