Pleated Membrane Filters Improve Process Economics

Drug manufacturers can take advantage of the better, faster, and smaller paradigm.
Jan 01, 2005

Monica Cardona
The drive to develop better, faster, and smaller — in other words, more efficient — products is a universal trend in the modern world. This trend has profoundly impacted many industries from microelectronics to packaging equipment. In the biopharmaceutical industry, the need to speed and simplify the long and complex drug manufacturing processes brings additional challenges, such as meeting regulatory requirements.

Biopharmaceutical filtration is one area in which significant strides have been made in the better, faster, and smaller paradigm. Since most steps in biopharmaceutical manufacturing involve some form of filtration, innovations in this area can significantly compress the time to manufacture modern biological products, including biotechnology, blood products, and vaccines. New filter designs have contributed to faster flow rates, smaller filter and housing sizes, improved microorganism and particle retention, longer service life, and broader application. Advances in the speed, size, and performance of new-generation membrane filters translate into significant cost and time savings for biopharmaceutical manufacturers.

Figure 1 (Top). Asymmetric Membrane with 3-to-1 Gradient in Average Pore Size, Figure 2 (Middle). Deep-Pleat Design with Increased Surface Area, Figure 3 (Below). Traditional Pleated Filter with Less Surface Area and Non-Uniform Flow
ASYMMETRIC CONSTRUCTION IMPROVES CAPACITY Asymmetric polyethersulfone (PES) membranes have contributed significantly to the performance of new-generation membrane filters. They offer a 3-to-1 average pore-size gradient through the depth of the membrane, resulting in higher porosity and dirt-holding capacity (Figure 1). This gradient captures larger particles in the outer portion of the filter, providing efficient removal of smaller microorganisms and biological haze within the inner parts. Whereas traditional membranes have a homogeneous pore-size distribution, the asymmetric structure with its large void volume is able to capture solids across the entire depth and pore gradient of the membrane, improving total filter capacity.

Table 1. Economic Benefits of New Generation Filters with 10 in. Modules
Membrane materials also play a critical role in the advancement of filters for biologic fluids. Compared to other traditional membrane materials, such as polyvinylidene fluoride (PVDF), cellulose esters, and nylon, PES filters have broader pH compatibility, are resistant to gamma radiation, and are easier to wet. Broad pH compatibility is essential given the universal role that bacterial- and particle-reduction filters play in a wide range of applications including fermentation and cell culture, downstream processing, and formulation and filling. PES's hydrophilicity and resistance to gamma irradiation further broaden the scope of applications and sterilization methods with which these filters are compatible. Gamma-radiation resistance is becoming increasingly important as the use of disposable capsule filters pre-sterilized by gamma irradiation grows. Since not all PES filter membranes are gamma irradiation resistant, it is important to consider this characteristic when selecting a filter.

Filter integrity tests provide another measure of performance. Bacterial-reduction filters, as well as sterilizing-grade filters, must be 100% integrity testable with a forward flow test. This test confirms that the filter is operating to the supplier's specifications. In the case of a bacterial-reduction filter with asymmetric construction and deep-pleat design, the integrity test correlates to titer reductions in excess of 1 x 106 when challenged with aqueous suspensions of Brevundimonas diminuta.