Disposable Biopharmaceutical Processes–Myth or Reality? - - BioPharm International


Disposable Biopharmaceutical Processes–Myth or Reality?

BioPharm International

Figure 4. Filter and bag manifold assembly
From the mixing system, media are then sterile filtered into a presterilized filter and bag assembly. The filter capsule can be supplied connected to either a single bag, or if media are required for future use, to a manifold of bags. Either way, the assembly comes gamma-sterilized and ready-to-use. Disposable filter and bag assemblies (Figure 4) eliminate the need for stainless steel filter housings and storage vessels, which require capital outlays, storage, and maintenance. Furthermore, cleaning and sterilization of stainless steel components are eliminated. Filter and bag assemblies are typically available in standard configurations stocked by the supplier, but are also highly customizable, with a full line of bag chamber and manifold options, filter capsules, tubing, sampling ports, outlet fittings, clamps, connectors, and so on.

Figure 5. Welder and sealer systems for tubing connection
After filtration, individual media bags are removed by thermally sealing the tubing and cutting from the manifold (Figure 5). Media bags are released based on the filter passing a post-use integrity test. Later, the media storage bags are sterile welded onto bioreactor bags and the media are pumped into the bioreactor bag. The blades used to weld the tubing sections are single-use, and discarded after the 60–90 second welding process.

Cell Culture

Disposable cell culture options at the laboratory scale have been in use for decades. From volumes of several mLs to several liters, roller bottles, spinner flasks, and hollow fiber membrane bioreactors have been used in small-scale MAb applications. These systems have typically lacked the sensors and controls to create an environment optimal for cell growth.

Figure 6. Rocking motion bioreactor (Source: Wave AG)
First sighted in the 1970s, turn-key, single-use bioreactors using the rocking motion platform (Figure 6) have been gaining popularity in recent years for medium-scale cell culture, at working volumes from 50 mL to 500 L. In the coming years, it is expected that these low shear systems will become available at larger volumes. Additionally, significant development continues on other platforms, including impeller-based disposable bioreactors.

Figure 7. Single-use bioreactor chamber (Source: Wave AG)
With the exception of the controller and drive platform (not in contact with product), all components of these rocking motion bioreactors are disposable, including the bag chamber, vent filter(s), pH probes, dissolved oxygen probes, tubing, fittings, etc. (Figure 7). The culture bags are available in standard configurations, or customized to meet the exact needs of the application.

Downstream Processing

While downstream purification processes vary from process to process, most of the unit operations typically found are available in disposable formats, including cell removal and harvest clarification, buffer preparation, pH titration and low pH hold viral inactivation, S- and Q-chromatography steps, viral filtration, ultrafiltration–diafiltration, and final formulation. Each of these operations will be discussed briefly.

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