Optimizing a Cell Culture Media Filtration Process | Case Study

Optimizing a Cell Culture Media Filtration Process_Parker PROPOR MURUS Capsule Filters_Parker Bioscience FilrationA biopharmaceutical customer was reviewing its process for tryptone soya broth (TSB) and vegetable soya broth (VSB) production. The existing process incorporated five-step filtration, using three different media (glass fibre, cellulose and PVDF) at four different porosities.

Parker Bioscience Filtration's Technical Support Group (TSG) was tasked with optimizing and simplifying the customer's process. 


The challenge

The customer required the filtration system to filter a 2000 L batch within a six-hour time window and the line needed to be capable of filling both TSB and VSB.

Our testing also needed to ascertain whether the five-step process could be reduced - ideally to a single step - and as a result, the materials of construction could be simplified in order to reduce the number of materials in contact with the product. 

The customer also wanted to move to a single-use capsule format to enable greater flexibility and asked if data on Mycoplasma retention could be supplied as part of the process validation. 


Optimizing a Cell Culture Media Filtration Process_Preventing Mycoplasma Contamination White Paper_Parker Bioscience Filtration


If you'd like to learn more about Mycoplasma contamination and how to tackle it read our white paper: Preventing Mycoplasma Contamination.





Optimizing a Cell Culture Media Filtration Process_Parker SciLog FilterTec Normal Flow Filtration Laboratory System_Parker Bioscience Filtration

The trials

Disc trials using Parker's SciLog® FilterTec unit were performed to provide initial recommendations. This simulated the customer's process, which allowed our team to establish the maximum capacity of the filters. 

The SciLog® FilterTec unit is a dead-end laboratory-scale filtration system that allows filtration to be conducted under controlled pressure and flow rate conditions. It is used to assess the volume throughput of specific filter combinations. 

In this case, the system was used to measure filtrate quantity collected under a constant flow rate.

The SciLog® FilterTec unit is also capable of maintaining a set feed pressure, measuring the permeate flow and the total throughput. In addition, it allows measurement of the differential pressure over each stage. 

Measurements are automatically taken and recorded, and the results of the simulation can be related to a full-scale system, based on the relative filtration areas. 

On-site testing was conducted using 25 mm disc housings and small 500 cm2 capsules. Parker's 0.1 micron PROPOR SG, 0.2 micron PROPOR HC and 0.1 micron PROPOR MR filters were tested, with and without prefiltration. At the customer's request, the 0.2 micron filter was included for comparison even though the final system would require a 0.1 micron filter for Mycoplasma removal. 

For this application, we chose a set-up that allowed the system to run at a set flow rate of 16.0 ml/min over a 25 mm disc until the inlet pressure reached a maximum level of 1500 mbar. This was the equivalent to a flow rate of 20.8 L/min per 10" sterile filter and was higher than the actual flow rate in the application.

Crucially, by using higher flow rates, we ensured that the testing was conducted under worst-case conditions, as blockage occurs at a higher rate as the relative flow rate increases. The unit measures blockage as the increase in upstream pressure. 

Parker advised the customer that prefiltration should be employed to guard against the potentially variable mixing process. Dual sterile stages are used as standard by the customer. 


Optimizing a Cell Culture Media Filtration Process_Parker PROPOR MR Filter Capsule_Parker Bioscience FiltrationTrial results

The filter trains were allowed to either run to blockage or stopped at around 800 grams, which ensured that the correct batch size was reached.

Blockage was assumed when the differential pressure over the filter train reached 1.5 bar, and/or the flow rate was reduced to 20 percent of the initial flow rate.

All tests reached the required 800 grams - equivalent to 200 kg over a 20" filter system, with the exception of the 0.1 micron PROPOR SG filter which did not reach the required volume; the trial was stopped after filtering only 68% of the required batch size. This was to be expected of a single layer 0.1 mciron filter without prefiltration.

In the subsequent capsule trials, 100 L of both samples were filtered through PROPOR MR capsules with and without prefiltration. PROPOR MR 0.1 micron filters feature an integral PES prefilter layer offering increased throughput compared to the single-layer 0.1 micron PROPOR SG. 

There was no change in differential pressure across the filters throughout the trials indicating that filter combination could successfully fulfil the customer's requirements. 

Based on the results, a final system of either 0.6 micron prefiltration (to avoid any batch to batch inconsistencies) or a 20" PROPOR MR without any prefiltration could be used to filter a 2000 L batch. 

As the customer uses dual-stage final filtration as standard, a system of 20" PROPOR MR on to 20" PROPOR MR was installed. 


What did this system achieve?

  • A six-hour process time - based on the system design, the process runs comfortably within this time frame. This made scheduling more predictable and meant that re-work or unplanned downtime could be avoided.
  • The system can accommodate both medias (TSB and VSB).
  • Single-stage filtration, albeit with redundant filtration as required by the customer's QA has been achieved.
  • The number of product contact materials have been reduced to the polyethersulphone PROPOR MR membrane.
  • Parker is able to support the use of this membrane and share the validation data supporting the Mycoplasma log reduction values.
  • All of this is now in a single-use capsule format, allowing for quicker turnaround times, a reduction in utilities, and scope for flexibility should batch sizes be decreased or increased. 


By working together with the customer, Parker was able to simplify their process, remove a number of filtration steps, reduce the time to process and, although it was not part of the initial remit, reduce the overall cost of the process step. Parker would welcome the opportunity to work together to optimize your bioprocess.


If you'd like to learn Mycoplasma Contamination - Why So Serious?_Preventing Mycoplasma Contamination White Paper_Parker Bioscience Filtrationmore about Mycoplasma contamination and how to tackle it read our white paper: Preventing Mycoplasma Contamination.



Optimizing a Cell Culture Media Filtration Process_Guy Matthews Division Marketing Manager_Parker Bioscience Filtration

This post was contributed by Guy Matthews, division marketing manager at Parker Bioscience Filtration, UK.

Parker Bioscience Filtration specializes in automating and controlling bioprocesses. By integrating sensory and automation technology into a process, a biopharmaceutical manufacturer can control the process more effectively ensuring the quality of the final product. Visit to find out more.




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