Biomedical Engineering Reference
In-Depth Information
8
Downstrea m Processing
Remember, a dead fish can float downstream, but it takes a live one to swim
upstream.
W. C. Fields
The adoption of disposable components in downstream bioprocessing has
been an evolutionary process with a few revolutionary peaks here and
there. It started with buffer bags and devices for normal flow filtration,
including virus filtration and guard filters for chromatographic columns,
but gradually, more complex concepts have been introduced, including dis-
posable devices for tangential flow filtration and chromatography in down-
stream processing. Today, the consensus of the industry is that while many
of the upstream operations can be converted to fully disposable systems, at
least some elements of downstream processing will remain traditional, and
the reasons quoted for this assertion is that columns and resins will always
be too expensive to throw away. Also, since columns can be of a very large
size, it will be difficult to find a suitable disposable substitution.
However, as history tells, these were the same arguments presented just
15 years ago opposing the conversion of bioreactors to disposable devices.
Today, downstream processing science is developing more rapidly than
upstream science; more recently, the use of membrane adsorbers has been
recommended for large-scale purification of antibodies. These membranes
are much cheaper than classical resins.
For cell harvesting and debris removal, disposable filtration systems are avail-
able. Benefits include the ease of scale-up and the availability of presterilized
filter capsules that can be integrated directly into production lines. Though this
stage is generally completed by centrifugation or lenticular filtration, Millipore's
Pod systems provide the first available alternative in disposable lenticular fil-
ters. This combines two distinct separation technologies in an adsorptive depth
filter to enhance filter capacity and retention, while compressing multiple filtra-
tion steps into one efficient operation. Scale-up is achieved by inserting multiple
pods into a holder, with formats allowing 1-5 or 5-30 pods as required. Further
disposable depth filter formats include the Stax-System from Pall Life Science,
encapsulated Zeta Plus from Cuno, and the L-Drum from Sartorius-Stedim.
The next step is cross-flow filtration to reduce the volume, but the build-up
of debris extends the time for filtration and while this process is not a sterile
process, use of disposable filter prevents the problem of cross-contamination.
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