GEN: How do bioprocessors achieve efficient, economic large-scale filtration?
Today, bioprocessors can choose from a large variety of filter material combinations for their specific applications. The trick to achieve efficient large-scale filtration is to identify the optimal filter system in filterability trials that can be carried out with the support of vendors that have automated screening systems in place.
The use of small-scale, flat-filter discs minimizes the amount of highly valuable products needed for testing purposes. Particular attention during filter screening should be paid to selection of an optimal prefilter in front of a final filter, especially for fluid streams with a high concentration of contaminants. Prefilters protect more expensive final filters highly effectively and can prolong the lifetime by a factor of three to five, which results in a significant reduction of filtration costs for highly effective large-scale filtration.
Bioprocessors can achieve efficient large-scale filtration by looking to other industries to see how they have been doing it. For example, hollow fiber filtration has been the standard in such large-scale unit operations as water purification at the municipal level and food and beverage applications, such as juice, wine, and beer clarification.
Membrane suppliers now offer scale-up assistance and technology, allowing bioprocessors to perform research and development on the bench (at the microliter and milliliter level) and then to scale that work up, to pilot and process development and then manufacturing (thousands of liters), all using the same membrane.
Asymmetric or hybrid layer membrane filters, along with advanced high-area pleat geometries enable downsizing of direct flow filtration assemblies or reduced operating costs for large-scale filtration processes. Higher efficiency 0.1 µm-rated mycoplasma filters with improved capacities for cell culture media reduce the risk of costly contamination while controlling media filtration costs.
Reusable TFF cassettes with improved cleanability reduce turnaround time and bioburden contamination risks. Single-pass TFF cassettes cut costs by eliminating recirculation loops and allowing in-line processing. And automated filtration systems enable greater process control while reducing operator error.
The major factors in achieving efficient, economical filtration at production scale are understanding and minimizing process variation. Efficiency is defined in terms of cost per unit of product. Thus, the first step is to conduct a vigorous evaluation process at development scale to select technology that is consistent and economical. Next, it is important for the selected filter to show consistent filtration performance, without variation in throughput or flux, at commercial-scale production.
Minimizing variations in filter performance characteristics in scale-up decreases or obviates the need for expensive and time-consuming process exceptions, putting the resources of the facility toward production rather than problem-solving. Technical support throughout this process is indispensable.
As with any unit operation, the key is to perform enough optimization so that waste is minimized without creating a situation where every molecule in the pipeline needs to be completely redesigned from scratch.
Standardization of methods and SOPs goes a long way toward achieving economic large-scale filtration. Early PD efforts to create unit operations (where filters from multiple vendors can be used interchangeably) can lead to better long-term efficiency in manufacturing. Such efforts can also reduce the risk of downtime.
By careful selection of the highest capacity filters, without sacrificing the ease of implementation and use, it is possible to achieve robust performance in the process while minimizing the risk of impact on cleanliness and quality of the product. This needs to be assessed holistically from “cradle to grave,” starting from efficient process development tools, through easy scaling, good documentation for process validation to ease of inventory handling, integrity testing, and disposal.