Selection of the appropriate filter product for a given application in your bioprocess is critical, as an incorrect decision at the specification stage may have significant economic, quality and safety implications.
Normal flow filtration (NFF) products, covering a broad spectrum of application needs, are available from vendors in a wide range of membrane types, retention grades, sizes, and formats. Unfortunately, this diversity can also make the selection process a challenge for the inexperienced.
Starting with the end in mind
Installation of a non-sterilizing filter in an application where sterility is required has the potential to create severe problems, and for this reason, sterilizing-grade filtration is often viewed as an automatic selection in many cases.
However, if you opt to install a sterilizing-grade filter stage in an application where it is not truly required, this can significantly impact upon process efficiency, and will demand significant additional resources and expenditures to qualify and operate. Similarly, if you install an improperly sized filter, this will increase the risk of process interruption through blockage if the filter is undersized, or cause product loss through additional hold-up volume if the filter is over-sized.
An understanding of the true process objectives, and how best to achieve these through the use of a suitable filter product is therefore invaluable.
A data-driven selection approach
While it is generally a simple process to select the level of filtration required, selection of specific size, format and ultimately a vendor part-code for a filter product may be more complex. A technical consultation with representatives of your preferred filter vendor is usually advisable when developing a new filtration process.
If the filtrate from your application will enter a sterile system (for example a bioreactor, vial/syringe or long-term intermediate storage), then you will require a sterilizing-grade filter. Depending upon the physical characteristics of your process solution, a filter such as PROPOR SG may be appropriate or a high-capacity filter such as PROPOR HC if your solution is more difficult to process.
If your application requires retention of a specific diminutive organism, such as the removal of Mycoplasma species from cell growth media, then it might be that a more retentive sterilizing-grade filter such as PROPOR MR is more suitable.
If filtrate from your application will enter a non-sterile system (for example chromatography or short-term intermediate storage), then it is likely that a sterilizing-grade filter is not required. A bioburden reduction filter such as PROPOR BR would typically provide sufficient microbial and particulate control to protect downstream operations.
Once the basic type of filtration required has been determined, you can build upon this decision with further testing or with technical support from the vendor to select a specific filter size and format based upon process parameters and any other critical operating requirements.
At this stage it is good practice to confirm suitability and generate empirical scale-up performance data for the filter selection through additional testing on laboratory-scale or pilot-scale processes. If appropriate, some elements of process filter validation may also be incorporated into these studies in order to expedite completion of your project. A reputable filtration vendor will be capable of assisting in the design and performance of much of this testing.
If you're setting up a new NFF process step and considering taking a QbD approach, watch our latest webinar Application of QbD Concepts to a Final Sterile Filtration