Beyond Convenience: Choosing the Right Filter for Your Bioprocesses 

In this blog, we will explore the impact of using suboptimal filters and provide guidance on how to choose the best filter for your final filtration process.

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In the biopharmaceutical industry, filtration, particularly the final filtration step, is critical to ensuring product purity and safety. However, filter selection is often overlooked during process development, with more focus given to optimizing other unit operations such as cell culture expansion, tangential flow filtration (TFF), or chromatography. This oversight can lead to significant operational inefficiencies and increased costs. 

The Common Pitfall: Convenience Over Optimization

In many biopharmaceutical processes, filters are often chosen based on what is readily available or easily accessible, rather than what is best suited for the specific application. This approach can lead to several issues, including increased total cost of operations, premature filter plugging, and challenges during post-use filter integrity testing.

Scenario 1: The Oversized Filter

One possible outcome is the selection of an oversized filter, which can result in high product loss due to increased surface area and hold-up in the filter. Additionally, using a larger filter than necessary increases operating costs. 

Scenario 2: The Readily Available Filter

Another common scenario involves using a readily available filter without proper evaluation. Recently, our partner requested our support to optimize their final filtration process, which currently employed a readily available filter. Our team visited their site and tested alternative filters, finding that a different filter type achieved twice the capacity (L/m²) with no negative impact on product quality. This change reduced product loss and operational costs, as a smaller, more suitable filter could be employed for the process.

Scenario 3: Post-Use Integrity Testing Challenges

Improper filter selection can also lead to challenges during post-use filter integrity testing. An improperly selected filter may exhibit high levels of adsorption, where product residues stick to the membrane, or filter plugging.  These scenarios require more extensive flushing procedures or even chemicals such as NaOH or IPA to ensure a successful post-use integrity test, resulting in increased operational costs.

Scenario 4: The PES Filter Assumption

A common misconception is assuming that all polyethersulfone (PES) filters are the same, given their widespread availability from nearly all filter suppliers. However, variations in surface modifications can significantly impact filter performance. Trials with low-adsorptive PES filters can help ensure minimal adsorption of active biopharmaceutical ingredients and excipients. This careful selection of PES filters can lead to improved product quality and process efficiency.

How to Evaluate and Choose the Best Filter

To avoid these issues, it is essential to properly evaluate and choose the best filter for your final filtration process. Here are some steps to guide you:

1. Small-Scale Filter Trials: Conduct small-scale filter trials to determine the optimal filter for final filtration. Evaluate various membrane chemistries and pore size combinations, then select the best performer based on process performance criteria such as product and excipient adsorption, filter capacity, and flow rate.
2. Performance Criteria: Consider additional performance criteria such as flushing volume for pre-use post-sterilization integrity testing (PUPSIT), leachables and extractables profile, and bacterial retention.
3. Define Critical Operating Conditions: Establish a maximum differential pressure (for constant flow filter operations) or maximum flow decay (for constant pressure operations) for the application. Use these parameters to perform scale-up calculations and define critical operating conditions such as differential pressure, process time, and flow rate.
4. Monitor Filtration Activities: Once the optimal filter is selected, use it for bacterial retention validation and monitor all filtration activities to ensure consistency and reliability in the filtration process.

Choosing the right filter is crucial for any stage of a bioprocess, but particularly for final filtration. Selecting a non-optimal filter can impact product purity, increase operational costs, and limit process efficiency. By taking the time to properly evaluate and select the best filter for your specific application, you can avoid the pitfalls of using suboptimal filters and achieve better overall results. 

Learn more about the next evolution in filtration technologies: Sartopore Evolution | Sartorius