Filtration is commonly used in biopharmaceutical manufacturing to remove or control bioburden within the production process. However, filtration costs within manufacturing facilities can be optimized — and significantly reduced — by the appropriate use of prefilters.
A correctly selected and sized prefilter positioned upstream of a sterilizing grade or bioburden control filter can greatly reduce the required area of these membrane filters — and the cost of operating a prefilter and sterile filter with a low membrane area is generally less than the cost of operating high-membrane area sterile filters without an upstream filter.
Prefiltration media and their applications
Prefilters suitable for use in biopharmaceutical applications can contain different types of filtration media. The appropriate media to use will depend on the application.
Typical prefiltration media are described in Table 1 along with their properties and when they should be used.
Sizing prefilters can be a difficult and time-consuming activity because of the large number of variables and parameters to be optimized.
Recommendations for the sizing of filtration systems that incorporate prefilters include:
- Establish the requirement for prefiltration by first sizing the downstream membrane filter.
- Where possible, gather information about the properties of the process stream by collating all existing relevant data and by performing experiments to determine the concentration and particle size of particulates and the viscosity of the process solution.
- Next, select the likely prefilter media based on the properties of the process stream and whether retention, compatibility or capacity is likely to be an issue.
- Based on previous knowledge and process stream analysis, select the prefilter grades expected to be the most effective at protecting the membrane filter. A 0.2-micron filter is likely to require a prefilter with a micron rating of 0.5 to 0.6 microns, while a high-capacity membrane filter with integral prefiltration layer is likely to benefit from a prefilter with a more open pore structure.
- Use the constant flow sizing method to compare the capacities of the grades selected and retain the filtrate to allow resizing of the downstream membrane filter. Constant pressure filtration can be used for prefiltration screening, but operators should use low pressures in the range of 5 to 10 psig to mimic likely operating conditions.
- Additional prefiltration stages should be considered for process fluid with a high solids content. In these cases, an initial coarse prefilter that provides high solids-holding capacity followed by a finer secondary stage to protect membrane filtration can provide a cost-effective solution.
- Confirm the results using a pleated filter format to give greater confidence in the performance at the larger scale.
Using prefilters to reduce total filtration costs in biopharmaceutical manufacturing can have major benefits, but sizing prefilters can be a technically difficult operation.
Therefore, it is advisable to gain further support from filtration suppliers in performing this task.
Andrew Kelly is product manager, Filtration, for Parker Bioscience. Part of Parker Hannifin Corporation, Parker Bioscience provides integrated bioprocessing solutions to speed up development times, increase efficiency and safety, and enable reproducible quality. Incorporating SciLog and domnick hunter, Parker combines filtration, single-use fluid handling systems and sensors into automated single-use solutions. Visit parker.com/bioscience for more information.