Single-Use Technologies—A Contract Biomanufacturer's Perspective - Disposable technology presents an attractive opportunity for CMOs to cut down production costs. - BioPharm International


Single-Use Technologies—A Contract Biomanufacturer's Perspective
Disposable technology presents an attractive opportunity for CMOs to cut down production costs.

BioPharm International Supplements

Virus-Removal Filters

Table 1. A comparison of four types of filters commonly used in a post-chromatography purification process for virus removal. Flux rates, recovery, and convenience of use were studied for each filter for different processes.
We use different types of disposable filters mentioned below for virus removal (Table 1).

Hollow Fiber Filters

In a disposable HF filter, the product is ideally filtered through the hollow fiber membrane by pressure at 14 psi. Total yields are greater than 95% and membranes are scalable to 4.0 m2 . However, a pressure tank is necessary if pressure feeds are used and therefore, this system is not fully disposable in its ideal configuration. We have observed that this system can function at 120–150 L/H/m2 and can achieve greater than 6.7 log removal of polio virus (vendor study).

TFF Membrane Filters

TFF membrane filter cartridges are composed of three disposable membrane modules connected in parallel. However, stainless steel membrane holders are needed for setup and therefore, this system is not fully disposable as it has nondisposable parts. The TFF system functions at 50–80 L/H/m2 and achieves greater than 6.0 log removal of retrovirus (vendor study).

Cartridge Filters

Polyvinylidene difluoride (PVDF) filters are completely disposable cartridge filters that can be hooked up directly to pumps or chromatography systems. The product is pumped through the filter in a single or parallel channel configuration. The filters are scalable to 30 inches and can be connected in tandem to polishing columns, if needed. We have observed that these filters function at flow rates ranging from 5–20 L/H/m2 . The PVDF filters are commonly used in the industry and have successfully removed greater than 6 logs of retrovirus in our processes and in other commercial applications. However, backpressure issues are common, resulting in slower and less efficient virus removal steps.

Polyether sulfone (PES) cartridge filters are also available for viral removal steps. PES filters are hooked up to pumps or chromatography systems in the same fashion as PVDF. Scalable to 30", these filters are completely disposable and can be hooked in tandem to polishing columns, if applicable. Our studies confirm that PES filter flow rates are higher than PVDF filters at 90–180 L/H/m2 . We performed a virus validation study using PES filters by pumping virus-spiked product through small-scale cartridge membranes at >30 L/m2 for all runs. Results show that the product spiked separately with either 1% or 5% (v/v) of four viruses (Reo, MVM, MuLV, or PRV) behaved in a manner consistent with our scaled-down processes. In all cases, the flow-rate curves were linear, suggesting that the filters never exceeded the virus binding capacities. Studies also confirmed greater than 6 log reduction in all of the above named viruses.

Aseptic Filling

Figure 3
For aseptic filling of liquid parenteral products we use completely disposable sterile bags as bulk product containers and have seen excellent recovery. One caveat to using disposable bags for aseptic filling is that the users must confirm that the product solution is fully compatible with the plastic material of the bag. Our linear peristaltic pump systems have completely disposable parts, including hoses and filling needles to accommodate vials from 0.2 to 100 mL in size with fill volumes of 0.1 to 100 mL (Figure 3).

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