Optimization & Process Simulation for Clarification

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At the process optimization stage, begin work on confirmatory sizing trials (pilot testing). Further confirmation of your initial sizing studies is important since the cell culture fluid has most likely been through optimization.

During sizing trials filters are typically run continuously in series, providing a more representative view of how your full-scale system will run. Depth filters should be run at a constant flow rate, allowing for proper sterile filtration evaluation downstream. Completing your testing using this methodology serves as confirmation of predicted performance from individual small-scale tests.

Performing Pilot Testing

While pilot testing can be performed at any scale, consider the following when preparing to complete pilot trials:

Bench Scale Studies
Complete bench scale studies on the day of screening trials or soon after. To obtain an accurate representation of how your large-scale system will perform, match filter area ratios at each filtration step.

For pilot scale, match filter surface area ratios between depth filters and the downstream sterile filter. At this time, incorporate other process steps into pilot testing such as:

• Centrifugation, TFF upstream
• Chromatography, TFF downstream

Once process volumes are sufficient, complete an initial evaluation of scaling and system factors. At the production scale, confirm scaling and system factors. By completing an initial evaluation and confirmation of scaling and system factors, you will ensure proper scaling and process robustness.

Completion of Pilot Testing

Upon completion of pilot testing, you should have confirmation of media grade(s), sizing, and configuration for large-scale production.

Process objectives, e.g., product quality, impurity removal, etc., can be achieved with your selected technology and design. At this point, confirm the required minimum surface area and the robustness of selected safety factors.

Merck  offers a full line of clarification products and services to help speed your MAb and plasma-derived products to market faster and more cost effectively.