Six considerations when creating large-diameter aseptic connections between bioreactors and Alternating Tangential Flow (ATF) systems

6 Considerations when creating large-diameter aseptic connections

Bioreactors are commonly used in bioprocessing to cultivate cells, microorganisms or biological molecules for various applications such as the production of biopharmaceuticals, enzymes or biofuels. Intensified cell cultures require the removal of spent media and replenishment with fresh media while retaining cells and/or the protein of interest.

One of the methods for separating these components from the bioreactor is by using an alternating tangential flow (ATF) system. The ATF system uses a filtration membrane to separate the components from the bioreactor. The system pumps the bioreactor fluid across the surface of the membrane, creating a tangential flow that helps prevent clogging of the membrane. The retained components are collected on one side of the membrane, while the cell-free permeate fluid passes through the membrane and is replenished with fresh media via a separate fill line.

Benefits of large-diameter aseptic connections and what you need to know

Large-diameter aseptic connections between bioreactors and ATF systems are crucial for several reasons:

  1. Sterilizability: Some ATF formats are not gamma sterilizable, so they must be sterilized separately from the single-use bioreactor with which they will be used.
  2. Ease of handling, use and packaging: ATF devices tend to be bulky and require relatively short connection lengths to the bioreactor. For this reason, it is convenient to connect the ATF to the single-use bioreactor after the bioreactor is installed.
  3. Flow rate: Bioreactors and ATF systems are used for large-scale production of biologics, such as vaccines, antibodies and recombinant proteins. These processes require high flow rates to achieve efficient mass transfer, and nutrient supply to support the growth and productivity of cells or microorganisms. Large-diameter connections allow for higher flow rates, reducing the risk of flow restrictions or pressure drops that could negatively impact process performance.
  4. Scalability: Bioprocesses are often scaled up from small laboratory-scale bioreactors to large production-scale bioreactors. ATF systems are also designed to handle large volumes of media or culture fluid. Large-diameter connections between bioreactors and ATF systems enable the use of ATF in larger-scale applications.
  5. Minimizing shear stress: Shear stress, caused by the mechanical forces applied to cells or microorganisms during fluid transfer, can adversely affect cell viability and product quality. Large-diameter connections help minimize shear stress by reducing the velocity through the connection, which can occur in small-diameter connections or tubing. This is particularly important for delicate cells, such as mammalian cells, which are sensitive to shear stress.
  6. Process contamination: Bioprocessing requires strict adherence to good manufacturing practices (GMP) to ensure product quality and safety. Reliable, large-diameter aseptic connections help minimize the risk of process contamination by eliminating open manipulations when connecting the ATF to the bioreactor.

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