Biotech companies are running into production bottlenecks because standard purification and separation technologies lack the
capability to remove the elevated levels of biomass from high titer solutions. Recent developments in filter technology offer
the biotech industry a cost-effective solution to processing challenges by reducing bottlenecks, thereby accelerating the
time-to-market of new drugs.
This article focuses on new designs of sterilizing-grade filters that remove bacteria, toxins, and other contaminants from
initial purification steps to final formulation and filling. We discuss these important parameters in filter selection: materials,
compatibility, wettability, sterilization, adsorption, and membrane and filter construction.
Materials and Compatibility
Three hydrophilic sterilizing-grade membrane materials are readily available: Nylon 6,6, polyvinylidene fluoride (PVDF), and
polyether sulfone (PES). Table 1 summarizes the general compatibilities for each membrane type. PES and PVDF are low binding,
water wettable and can be gamma irradiated. The membrane with the broadest pH compatibility is PES.
Table 1. General compatibility of polymers for filtration
The ability to wet a filter completely is important, because the objective is to use the full filtration area. If a significant
portion of the membrane is not wetted properly, then the filtration flow can be impaired. In addition, it is necessary to
have a fully wetted membrane during the performance of an integrity test. If the filter membrane is not completely wetted,
then even a very small non-wetted area of the filter could cause a failure of the integrity test, causing process delays and
In terms of wettability of membrane material, Nylon 6,6 is the most easily wetted because it is naturally hydrophilic. PVDF
is naturally hydrophobic, and for liquid applications will under go some sort of modification to make the membrane hydrophilic.
This version is close to Nylon 6,6 in terms of wettability. Most common PES filters do not wet easily and usually require
backpressure to wet completely, making integrity testing more difficult and time consuming. However, recent improvements in
PES wetting chemistry have rendered its wettability comparable to PVDF membrane filters.
Integrated single-use bioprocess systems incorporating filters, tubing, and bags can play a key role in helping companies
to increase manufacturing capacity. A single-use capsule does not require cleaning or cleaning validation because it can be
pre-sterilized via gamma irradiation by the manufacturer. This simplifies process operations because pre-sterilized filters
do not require assembly or steam sterilization. The housing material used in capsule filters is also often polypropylene.
For capsules that will be sterilized by gamma irradiation, the polypropylene must be gamma stable to ensure structural strength,
compatibility, and low extractables.
Figure 1. This diagram depicts an asymmetric membrane with a 3:1 gradient in average pore size
The purpose of filtration is to remove a particular contaminant or groups of contaminants from the process feed. The filter
system should not be adding anything significant (extractables) to the process fluid, nor should it remove a desired product
component from the fluid that is being filtered.