Tuesday, September 24, 2024 - Day One of Main ConferenceTuesday, 24 September 2024 - ET (Eastern Time, GMT-05:00)

• Using Online LC to monitor and control diverse CQAs for Continuous and Fed-Batch Processes for DS batches
• Using Online LC to control CQAs utilizing High-throughput (HT)-PAT methods for DP batches

Triton™ X-100 (octyl phenol ethoxylate) has been widely used as a detergent in the biologics space for decades. Its application expands from cell lysis reagents to various lab-scale assays and biopharmaceutical production. Additionally, its ability to inactivate viruses is widely used in the bioprocessing sector as well as in the treatment of human or animal-derived plasma. Even though Triton™ X-100 has been effective in these applications, its environmental impact has led to its European ban starting in January 2021. However, it can still be used for existing pharmaceutical applications under a public exemption or for small-scale laboratory research. This ban has caused the industry to search for biodegradable detergents that meet cGMP standards and are acceptable for use in Europe's manufacturing of new cell-based drugs. Alternatives to Triton^TM X-100 must perform equally in regard to cell lysis and protein compatibility in order to ensure global applicability in a wide range of bioprocessing applications. Using a Xenotropic murine leukemia virus (XmuLV) and the Feline catus PG4 cell line as a model, we identified Virodex™ TXR-1 and TXR-2 (out of 40 different detergents) as having the same level of effectiveness as Triton^TM X-100 in reducing the viability of XmuLV. Further, Virodex™ TXR-1 and TXR-2 performed equal to or better than Triton™ X-100 with regards to its ability to lyse cells without negatively affecting protein function (alkaline phosphatase). Croda has developed a reliable and sensitive chromatography method that detects and quantifies Virodex™ TXR-1 and TXR-2 at low parts per billion (ppb) concentrations using standard reversed-phase ultrahigh-pressure chromatography and mass spectrometry (UHPLC-MS) methodology. For Virodex™ TXR-1 the method achieved a 5 ppb limit of detection (LOD), a 10 ppb limit of quantification (LOQ) and a linear quantification response between 5 ppb and 100 ppb (R2 - 0.9998). The same method achieved a 2 ppb LOD, a 5 ppb LOQ and a linear quantification response between 2 ppb – 1000 ppb (R2 - 0.9992) for Virodex™ TXR-2. Further, the chromatography method we developed also demonstrated when Virodex™ TXR-1 and Virodex™ TXR-2 were tested for their affinity to a Protein A column* verses no column using typical loading, washing, elution and cleaning buffers, neither Virodex had any affinity to the Protein A resin. The study has successfully identified two viable detergent alternatives to Triton™ X-100 that are biodegradable and GMP compliant. Additionally, these alternatives have an established track record of pharmaceutical use and compendial compliance. These detergents represent exciting new options in the biopharmaceutical manufacturing tool kit.

• Integration of high-throughput technologies, along with digitalization of analytical results, facilitates faster and more meaningful processing decisions.
• Leveraging these platforms allows for higher volumes of data to be generated for more robust process and product understanding without incurring timeline delays.

• Automated solutions in today's laboratories need to be an integrated approach that integrates sample handling(robotics), data movement, and data processing.
• Too much automation can be just as limiting as too little automation.
• The best reason to automate your laboratory is to achieve "compliance through code".

In developing methods for our AAV analytical panel, we aimed to build a platform which could accommodate any project, from off-the-shelf productions to deep-dive investigations. We then optimized the panel to eliminate redundancies and provide faster turnaround times without loss of critical information, while staying flexible on project-specific needs. In this talk, we share insights and lessons learned from developing our analytical platform as it applies to process development and tech transfer for method qualification and release testing. By taking a platform approach, the need for product-specific method development was reduced or removed to keep pace with process development timelines, requiring minimal qualification effort for tech transfer. Generating relevant and versatile platform reagents permits full and robust method qualifications that can then be broadly applied to all sponsor projects.

• Artificial Intelligence can have a transformative impact within the biopharmaceutical manufacturing industry.
• AI can unlock the ability to optimize the selection of plasma, representing a very diverse population, based on multiple criteria to create a optimal, repeatable pools.
• By standardizing plasma pools, machine learning can be utilized to predict final batch yields by leveraging historical data and combining real-time process parameters, enabling adjustment for future batches to optimize yield and reduce waste.

• Grab a 'Cloud Spritz' (Aperol Spritz)
  • Culture Bioscience's booth (328)
• Grab a SmartLabs 75 (French 75)
  • SmartLabs Booth (1824)