In the move to Bioprocessing 4.0, more samples will be monitored online, but that’s not an easy task.
“The complexity and fragility of biologics require sensitive analytical technologies that can monitor the integrity and heterogeneity of biomolecules during bioprocessing,” says Daniel Kutscher, PhD, product manager, strategic marketing, Agilent Technologies. For such analyses, bioprocessors often use high-performance and ultra-high-performance liquid chromatography (LC ). Kutscher says that these technologies have been “widely adopted in the biopharmaceutical industry and used as a gold standard to monitor a great variety of critical quality attributes, CQAs, and critical process parameters, CPPs.”
In particular, Kutscher points out that online LC provides key capabilities in continuous bioprocessing. “This includes automated monitoring of CQAs, real-time process insight, and faster and better data,” he explains. “As a result, online LC allows for real-time decision-making and direct process feedback, which supports real-time release testing.”
Achieving these goals depends on automating the complete LC workflow. “This includes various steps from sampling to analyzing the sample and providing feedback to the bioprocess,” Kutscher notes. For the most part, each step creates challenges in automation.
“Maintaining a sterile barrier to the bioreactor is, for example, imperative during the sampling step,” Kutscher says. “Also, due to the complexity of the biomolecules, it is vital to monitor multiple CQAs with an appropriate sensitivity during the bioprocess to obtain high-quality data. Then, that data must be made available for real-time decision-making and feedback control.” So, putting LC online in bioprocessing depends on solving a range of issues.
Despite the collection of challenges in putting LC online in bioprocessing, it can be done, and solutions are already commercially available. So, it’s possible to develop an LC workflow that “supports design, analysis, and control of processes through real-time measurement of CPPs and CQAs,” notes Kutscher. “Assessing CPPs and CQAs closely, in turn, contributes towards quality by design, QbD.”