purification process steps and is usually achieved with some
type of agitator. In the stainless steel world, top-mounted
shaft mixer technology is common. In the single-use world,
magnetic or levitating mixer technology is more common—
with an impeller at the bottom of the tank. However, as the
volumes drop the impeller functions far less effectively,
hence the heavy reliance on recirculation.
Wand mixers provide another alternative and are effective
right down to volumes below one liter. This type of technology was invented specifically for single-use systems where a
three-dimensional bag sits inside a plastic tank (which gives
it a degree of rigidity), and a wand descends into the liquid
from the top of the bag. The wand – essentially a bent stainless steel rod enclosed within a silicone tube – swirls gently
around in the tank, stirring the solution like a finger. This
moves the product around effectively and gently enough to
ensure the products are kept homogeneous and in solution,
but is not robust enough to mix powders with liquids.
SINGLE-USE OVERCOMES RISK
The main advantage of single-use systems over stainless
steel systems is the fact that the system vessels are disposable. This is a key benefit as a biological product becomes
more concentrated in the downstream, rendering it much
more difficult to remove residual product from surfaces. In
the simplest of terms, the technology removes the possibility of cross-contamination from one batch to the next.
This is especially useful since the closer a product is
to the final dosage form, the more critical the processes
become and the more sensitive it is to contamination from
sterility breaches, particulates, or leachables from the plastics. Because of the increasing value and importance of the
product, it is imperative that no additional contaminants are
introduced during biopharmaceutical purification.
Of the contamination risks, particulates are especially notable. It is necessary to ensure that bags, tubing and any other
single-use components are reliable and do not have any risk of
contamination or breach of security (i.e.: holes, tears, or ill-fit-ting connections). Additionally, it is important to consider and
monitor any particulate risk that may arise during mixing.
As noted before, the biggest challenge comes from handling the low volumes towards the end of a biomanufacturing process. Biological products are notoriously sensitive to
shear, and much gentler mixing is needed for downstream
As single-use technologies continue to advance, more
innovation is sure to come. Larger-scale mixers designed to
monitor critical parameters such as conductivity and pH are
already available. The increasing value of the product as it
moves downstream is paving the way for the next generation of technologies that will excel in low shear, low volume
downstream single-use mixing. ■
Your biggest threat is measured in microns.
Integrity® cleanroom garments offer triple barrier protection against contamination with a pore
size of only three microns. Our fabric is lightweight and comfortable without compromising
worker or product safety. The difference between success and shutdown is Integrity.
For more information on Integrity Fabrics, contact Steve Glosson
at 1-888-733-5759 or Steve. Glosson@PrecisionFabrics.com.