Ultrafiltration Devices

Ultrafiltration modules are available in the same types of configurations used for microfiltration: flat-plate, hollow-fibre (including tubular) and spiral-wound. These devices are constructed so that they can be stacked or combined to allow for a range of filtration areas. The flow paths for these devices are described in the previous chapter; however, the advantages and disadvantages for protein ultrafiltration are briefly presented here.

Hollow-fibre devices are long cylindrical cases containing a large numbers of fibres (typically >10 000 fibres) bound to supports at either end. These devices have relatively high surface area-to-volume ratios and good mass transfer capabilities even at lower flow rates. Hollow-fibre modules have low hold-up volumes and can be flushed in reverse-flow mode to reduce the particulate fouling that tends to occur in their narrow channels. Disadvantages of this device format include limited operating pressures, high membrane replacement cost and tendency of the fibres to break. Detecting broken fibres is also often difficult.

Tubular modules are very similar in design to hollow-fibre devices except tubular devices have significantly larger tube diameters and smaller numbers of tubes in one bundle. Tube diameters ranging from 0.3 to 2.5 cm are common for tubular devices, compared with fibre diameters ranging from 200 to 2500 |im for hollow-fibre modules (van Reis & Zydney 1999). Tubular devices are available with single tubes or bundles of tubes within a cylindrical module. Advantages of these devices include low particulate plugging, good cleanability, and ease of membrane replacement. Disadvantages include large plant space requirements due to very low surface area to volume ratios, high feed flow rates and large hold-up volumes.

Spiral wound UF devices are typically used for large-volume processing due to their lower cost and high surface area-to-volume ratios. They also feature high mass transfer characteristics even at low feed flow rates. However, they are difficult to scale and can be difficult to clean due to their uneven flow paths and hard-to-reach spaces between the membrane and the housing. Since spiral wound modules are also prone to particulate fouling due to non-uniform flow distribution, they tend to require replacement more often than do hollow-fibre or flat-plate modules.

Flat-plate modules or cassettes are widely used for large-volume processing of high-value products due to their linear scalability, low hold-up volumes and high surface area-to-volume ratio. Flat-plate UF modules also offer either open or screened channels to improve mass transfer rates. The screened-channel devices are more prone to particulate fouling, but membrane regeneration is not as difficult as with spiral wound devices. Flat-plate cassettes are also relatively easy to customize into various size systems and membrane replacement is fairly simple.

Hollow-fibre and flat-plate devices are amongst the most widely used formats for industrial-scale protein concentration via ultrafiltration, due to their variety of membrane types, robust performance and lower plant space requirements for a given surface area. More detailed descriptions of each type of UF device are given in Zeman and Zydney (1996) and Dosmar and Brose (1998).

Regardless of the type of UF module chosen, the ability to predict industrial-scale performance from a small-scale device is necessary for developing a robust ultrafiltration process for high-value products such as therapeutic proteins. The creation of UF device formats, in which the fluid flow

Figure 17.2 Flat-plate ultrafiltration devices containing 0.1, 0.5 and 2.5 m2 of effective filtration area. These cassettes give linearly scalable performance and can be stacked together to create customized ultrafiltration systems. (Reproduced by permission from Millipore Corporation.)

paths and concentration and pressure profiles are constant as membrane area increases, has greatly improved the speed and accuracy of process development (van Reis et al. 1997). Figure 17.2 shows linearly scalable flat-plate membranes ranging in effective filtration area from 0.1 to 2.5 m2. van Reis and coworkers (1997) demonstrated more than 400-fold scale-up in performance of ultrafiltration and diafiltration of monoclonal antibodies using flat-plate modules.

This linear scaling benefit also extends to characterization and validation studies that may be performed at small scale instead of industrial scale. The Food and Drug Administration (FDA) and other regulatory agencies are more likely to accept pilot-scale data in lieu of production-scale data when it can be proven that the studies are performed under representative conditions (O'Leary et al. 2001). Using small-scale systems to generate validation data not only reduces material and labour requirements, but also enables process scientists to explore a wider range of parameters without risking the quality of the final product.

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