Biomedical Engineering Reference
In-Depth Information
6.6.1 QbD Operating Parameter Design Principles
1. Prepare Flux versus TMP curve for a given cross-flow rate.
.
Identify the transition region.
.
Calculate the mass transfer coefficient for the system.
J
filtrate
¼ k
TMP
.
Calculate product retention coefficient and verify contaminant clearance at
high TMP.
.
Select the maximum TMP within the transition region.
2. Prepare flux versus TMP curves at increasing cross-flow rates.
.
Select cross-flow (CFF) that maximizes permeate fluxwithin systempumping,
piping, and cooling constraints.
¼
Q
R
A
CFF
membrane module area (m
2
).
3. Evaluate effect of temperature on product yield and stability. Select highest
operating temperature to maximize filtrate flux.
where Q
R
¼
retentate flow rate (L/min) and A
¼
6.7 TFF DIAFILTRATION OPERATING MODE DESIGN
Diafiltration is most commonly employed to transport contaminants from the retentate to
the permeate, thereby removing them from the product. It can also be used to fractionate
the product from larger or higher molecular weight species. Quality design of the
diafiltration operating mode is critical to minimizing operating time, buffer volume, and
for shear sensitive products, product recovery. Continuous diafiltration involves feeding
diafiltration buffer to the retentate, while maintaining a constant retentate volume.
Continuous diafiltration is more efficient than discontinuous diafiltration, and current
equipment design and control have made discontinuous diafiltration largely obsolete.
To specify the number of continuous diafiltration volumes (diavolumes) required to
reduce contaminants to acceptable levels, the rejection coefficient for the contaminant(s)
should be determined at the selected operating parameters [22]. The contaminant
rejection coefficient must be determined at this stage since it somewhat depends on
the gel layer that is impacted by the transmembrane pressure and cross-flow flux. The
number of diavolumes (with an over design factor of two diavolumes) can be calculated
from
Y
F
100
%
ln 1
N ¼
þ
2
ð
R
1
Þ
where N
¼
number of diavolumes, Y
F
¼
% solute in permeate, and R
¼
solute rejection
coefficient.
