Biomedical Engineering Reference
In-Depth Information
The reduction in buffer volume is necessary because of the high cost of
the water used in preparing buffers. While it is acceptable to use Purified
Water USP to prepare buffers, many large manufacturing operations used
water for injection (WFI) instead because often this is the only choice avail-
able. Recently, a new manufacturing facility in Chicago (
www.theraproteins.
system for biological manufacturing, saving almost 90% of the cost of water
used, from about US$3/L for WFI based on the stainless steel system to less
than 5 cents per liter.
Buffer storage was one of the first unit operations to transition to single-use
systems. Recent analyses have confirmed that there is a clear economic advan-
tage to this methodology over traditional hard-piped systems. Buffer mixing,
however, continues to rely on more traditional technology. This is partially due
to the scale of many buffer preparation processes and partially due to a reliance
on existing infrastructure. However, as new facilities are commissioned and
as new technologies are introduced that limit the volume of buffers required,
single-use mixers are being chosen over traditional technologies. The shift to
single use is driven by the needs to minimize capital investment, enable more
rapid process setup, reduce downtime, and provide increased flexibility.
The largest disposable holding bags currently have a 3,000 L capacity
(Sartorius Palletank), while mixing with disposables is limited to 5,000 L
(Hynetics Disposable Mixing System), with more systems available at the
1,000 to 2,000 L scale. Preconfigured, disposable stand-alone systems for buf-
fer preparation have been launched recently with 500 and 1,000 L capacities
(e.g., Mobius). However, most of these packaged systems are very expensive
and do not add any real value to the bioprocess since a simple system such as
a Dixie Poly Drum 330 Gallon Economy Tank with a polyethylene (PE) liner
would do the job as well (the cost of the entire system is less than US$1,500);
Class VI USP liners are readily available even in a sterile state, though that
is not necessary. For companies starting out, it is recommended that they
develop their own configured system for storage of buffers and also use the
same tanks for mixing purposes. Often, a built-in system of a cage that will
accommodate a liner is sufficient for the purpose.
As an example of integrated systems, for buffer preparation steps, GE
Healthcare (
www.gelifesciences.com
) offers its WAVE™ Mixer. The WAVE
Mixer provides efficient mixing in a sterile, sealed bag by an innovative
method. Instead of using a pump or invasive impeller to induce circulation
flow, it uses waves generated in the liquid by a precisely regulated rocking
motion. The system has been optimized for extremely efficient mixing and
dispersion. Wave motion moves large volumes of fluid and disperses solids.
The WAVE Mixer eliminates the need for a mixing tank and conventional
mixer. This also eliminates equipment cleaning, sterilization, and validation.
The WAVE Mixer system comprises two main components: a special rock-
ing platform that induces a wave motion in the liquid without an impeller or
other invasive mixer and the M*Bag™, which contains the ingredients to be
