When developing and manufacturing biologics, issues such as yield, purity and quality are crucial. In order to optimize these parameters, scientists need to establish robust processes, improve workflows and maintain critical control over operations. These are the moments when osmolality testing comes into play, bringing significant advantages to key steps of bioprocessing. Osmolality testing can provide a broader and deeper understanding of your system, resulting in higher efficiency and a higher quality final product.
From upstream to downstream
“Osmolality is a flexible and robust analytical tool,” explains Kendal Studd, UK Scientific Application Specialist at Advanced Instruments. “It is considered a critical process parameter in bioprocessing and is required to achieve consistent results.” From upstream processing – where culture conditions and media composition need to be optimized to ensure proper growth and health of cells – to downstream processing – where buffer composition needs to be monitored and buffer exchange verified – there is a growing acceptance of use of osmolality into process methodologies. Osmolality is a standard, and invaluable, tool for assessing culture and process specifications.
Osmolality testing also plays an important role during process development as it allows the identification of optimal conditions and the definition of quality parameters for later GMP manufacturing. “Osmolality is very useful when companies work on validating new and innovative techniques and on overcoming challenges in bioprocessing,“ remarks Mark Rothenberg, US Associate Director Scientific Applications at Advanced Instruments. “It has a great impact on ensuring the highest quality and yield of biologics and can be used across the entire workflow.”
Upstream processing: promoting maximal cell density and yield
Upstream processing includes cell line development, media preparation and cell culture monitoring. During this phase osmolality testing is most often used as a quality check for media or cell culture formulations, in order to ensure optimal cell health and product yield. When taking a look at cutting edge therapies such as Cell and Gene therapy, it is remarkable how introducing osmolality testing as a control parameter can help overcome many challenges that remain to be solved despite the compelling clinical success and the ongoing investments. “Low or inconsistent yields are the major drawbacks in the manufacturing of viral vectors,” says Rothenberg. “A joint project of Advanced Instruments and the UK Cell and Gene Therapy Catapult (CTG Catapult) center of excellence has recently shown how osmolality testing can potentially improve efficiency, yields and quality of AAV1 (Adeno-associated virus 1).”1 In fact, osmolality of the media is crucial to ensure optimal cell growth, clonal expansion and vector stability, and to boost cell longevity. Therefore, a close monitoring of the cell culture process can result in a significant improvement of the manufacturing workflow and, ultimately, in a greater therapeutic efficacy. “We are excited to see how our customers in the Cell and Gene Therapy manufacturing space use this data in their own process workflows. We are confident that our findings will show exciting improvements in AAV upstream manufacturing, and are looking forward to seeing how osmolality can impact downstream processes as well” says Dr. Rothenberg.
Downstream processing: monitoring key buffer preparation
During downstream processing checking for proper buffer composition ensures efficient processing as well as optimal quality and yield. Biologics must maintain their purity throughout processing since any deviation could compromise their final yield. Purity is extremely important, especially during the buffer exchange procedure, where the highest quality needs to be guaranteed. “Monitoring osmolality as a concentration measurement significantly contributes to making the downstream step of the bioprocessing workflow more efficient,” explains Studd. “In fact, osmolality testing provides a complete and comprehensive picture of downstream buffers and processes and is a predictive parameter for process deviations. It also can be used to easily and quickly confirm the success of buffer exchange.”
