Reliable systems to transfer bioprocess samples directly from bioreactors to analytical devices while maintaining process sterility are crucial for biopharmaceutical companies to effectively take advantage of process analytical technology (PAT) and gain a more fundamental understanding of what is happening within bioreactors.
Bend Research (part of Capsugel Dosage Form Solutions) has collaborated with major biopharmaceutical companies, including Pfizer, Eli Lilly, and Boehringer Ingelheim, to develop 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.
The MAST platform includes the Sample Pilot, a sterile sampling unit that consists of a sampling module and an associated programmable logic controller (PLC). The SP100 Sample Pilot modules collects 50-mL samples for monitoring of pilot- and commercial-scale manufacturing operations, and the SP200 takes incremental 5-mL samples for analysis of development-scale reactions and reactions that run in smaller laboratory-scale bioreactors and pilot-scale, single-use bioreactors. Each sample assembly consists of proprietary valves and a pump and is designed to draw samples from the bioreactor and push them out to user-defined destinations, according to Clint Pepper, a director at Bend Research. "Because we use positive displacement, rather than pulling the samples out with a vacuum, it is possible to deliver even viscous culture samples with high cell densities to analytical instruments more than 50 feet away."
To maximize the potential of sterile biopharmaceutical sampling, the MAST platform design includes software systems for managing sample scheduling, delivery of the samples, processing of the analytical results, and adjustment of bioreactor parameters if desired. The MAST Sample Scheduler and Navigator modules will work together to facilitate sample collection from bioreactors and transfer to analytical testing systems.
The steam-sterilized SP100 module has been successfully demonstrated in five different bioreactors in three different facilities. "During recent development runs on pilot-scale bioreactors, the MAST platform and SP100 successfully delivered more than 480 samples without contamination, including more than 200 cumulative days of successful operation at the 30-L to 500-L scales in both cell culture and microbial applications," reports Pepper. "The sanitant-sterilized SP200 module has been deployed in five different facilities ranging in scale from bench reactors to large-scale, single-use bioreactors. The SP200 units have collected over 2000 samples in more than 240 accumulative days of operation with no contamination or loss of sample integrity." 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 precommercial products," says Pepper.
The MAST platform offers biopharmaceutical manufacturers several advantages, according to Pepper, including the ability to collect reproducible samples more frequently and automatically without operator involvement, which reduces the risk of contamination and operator exposure. The ability to integrate analytical results from numerous sources provides more insight into cell behavior and the impact of process parameters, enabling the use of more sophisticated process-control strategies.
Cynthia Challener, PhD, is a contributing editor to Pharmaceutical Technology.
This article was excerpted from an article that will appear in the July issue of Pharmaceutical Technology.