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Tutorials : Jul 1, 2009 ( )
Expanding Disposable Depth-Filter Applications
Pall Focuses on the Improvement of Process Clarification Operations!--h2>
The initial applications of single-use filtration products were for small-scale processes in laboratories where total process volumes were either quite small or exhibited low solids content. Today, single-use filtration systems are evolving quickly to address expanding applications, ranging from sterile filtration in final filling to the handling of hazardous or toxic products. Further, new frontiers such as virus filtration are leading the call for continued development.
The cellulose-based Seitz® depth filter product line from Pall Life Sciences has undergone such a technological evolution. Specifically, the new Pall Stax™ single-use depth filter platform was developed to address the biopharmaceutical industry’s current and future demands.
A vital requirement for any large-scale filtration system is that the performance scales up from development trials to commercial-scale production. Due to batch-to-batch variability and uncertainty in scale-up performance of a filtration solution, process developers typically apply a safety margin of 30% or greater for filtration area.
Although allowing for process variability is a good engineering practice, adding additional filtration area based on uncertain scale-up performance leads to poor economics of the clarification step.
In developing a design concept for a large-scale, single-use depth filter platform, Pall considered ease-of use and process aspects to derive a system design based on stacking depth-filter capsules vertically within a chassis. This design was preferred to that of a horizontal arrangement to aid installation, venting, and draining of the assembly as well as minimize the footprint needed.
The design of the inlet/outlet manifold (distribution manifold) enables the greatest flexibility in the way the process-scale chassis can be operated (Figure 1). In bottom in/bottom out configuration, the process flow is through the distribution manifold at the bottom of the stack. The alternative operating mode of bottom in/top out or top in/bottom out allows for the process flow to enter and exit from opposite ends of the assembly.
Switching between operating configurations is achieved by the simple addition or removal of the second distribution manifold at the top of the stack. The use of the bottom in/top out or top in/bottom out operating mode is potentially applicable for large area, single-layer systems operated at high feed flow flux rates and/or for ease of product handling. The bottom in/bottom out operating mode will otherwise apply.
Additionally the design of the Pall Stax platform provides users with the flexibility to operate the stack in a serial flow mode, whereby two grades of filter media can be operated in series within one chassis. Furthermore, because of the small footprint, multiple chassis can be placed into a small area.
Filterability trials were conducted to assess the scalability of the Stax platform. The trials focused on operating with single-layer modules, which require a higher feed flow rate through the filter assembly than double layer filters, and will amplify the effect of any hydrodynamic losses through the filter assembly. This provided for the worst-case scenario.
The test program included a comparison of the performance of the Pall Stax assembly with other Pall sheet filter formats to provide scalability data across the product range.
Test Fluid: Homogenized Yeast Test Solution, developed to be representative of a postcentrifuge mammalian cell type process solution.
The test results demonstrated excellent scale-up performance of the Stax assembly with a volumetric throughput at a differential pressure of 1.0 bar within 2% for the Stax 20 m2 compared to the 2 m2 system. The results also demonstrated that the Stax filter scaled to within 3% of the other sheet filter formats.
Prior to full product launch of the Pall Stax product range, trials with prototype filter assemblies were conducted with several leading biotech companies to assess performance and gain valuable feedback on the design. One such application was the clarification of a bacterial toxin for use in production of a vaccine product.
Due to the hazardous nature of the product, the process developers wanted to assess the feasibility of transferring the existing process to a single-use depth-filtration system.
The current process is validated with Seitz depth-filter modules for the clarification of the toxin from the bacteria. A two-stage depth-filtration system is used with a coarser prefilter grade followed by a finer-grade prior to a sterile-filtration step. Trials were performed using the same grade of filter media contained within the Pall Stax capsule format and operated within a Stax lab-scale chassis.
The trials took place with a scaled-down product batch volume, while operating under the same parameters as those used for the production process, i.e., filter sheet rating, feed volume per unit area of filter, and feed flow rate (l/m2/hr) were maintained constant.
The trials were run until the feed volume had been processed or when a differential pressure of 1.0 bar was reached. The results are shown in Figure 3.
Batch 1 ran successfully with little or no increase in differential pressure to maintain the flow rate with either filter media grade. Due to the scale of the process and the capacity of the Stax system, it was concluded that the clarification process could be operated within one Pall Stax process-scale chassis.
To demonstrate this, batch 2 was operated in serial flow mode within the lab chassis with the prefilter installed on the lower level and the final filter installed on the upper level. The filters were connected in series by the addition of a distribution manifold. All process parameters were kept constant.
From this case study, a number of conclusions were drawn. The trials demonstrated comparable performance to current processes. The serial flow concept within one chassis was demonstrated, thus simplifying the customer’s process. The single-use system was set up as per the schematic shown in Figure 4.
The drive toward single-use systems and improvement in process economics has again revolutionized process clarification technology.
The Pall Stax platform provides cost-effective depth filtration while eliminating nonvalue-added activities such as costly cleaning and cleaning validation, enabling higher productivity and better filtration efficiency.
Reliably scalable design and performance and intuitive operation by a single individual are added values end-users expect with disposable systems. Flexibility in handling and processing coupled with constructive robustness are key criteria for success.
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