Biomedical Engineering Reference
In-Depth Information
This operating mode is illustrated by the case study shown in Table 6.1, where the
operating time was reduced from 8.4 to 5.4 h. This operating mode will result in
additional buffer usage for diafiltration, and hence the cost benefit of time versus buffer
volume will ultimately determine the diafiltration operating mode.
6.7.1 QbD Principles for Operating Mode Design
Calculate number of diavolumes based on rejection coefficient.
Y
F
100
%
N ¼
ln
1
þ
2
ðR
1
Þ
Prepare a plot of permeate flux versus feed concentration to determine the optimal
diafiltration concentration.
C
D
¼
C
G
2
:
7
Tabulate operating time and diafiltration buffer volumes as a function of diafiltration
feed concentration. Select operating mode based on minimum operating time and
diafiltration volume.
6.8 SUMMARY
Applying theoretical principles and mechanistic modeling can be used to establish a
“quality” design for TFF operations. The proven design models for TFF can be used to
identify optimal operating conditions as well as a solid understanding of the system and
how the major operating parameters interact. The use of such mechanistic equations in a
planned stepwise fashionwill enable the user to optimize and understand the TFF system,
thus achieving the goals of a Quality by Design approach.
REFERENCES
[1] Food and Drug Administration. “Pharmaceutical cGMPs for the 21st Century—A Risk
Based Approach, Final Report, 2004. http://www.fda.gov/Cder/gmp/gmp2004/CGMP%
20report%20final04.pdf.
[2] Food and Drug Administration. Innovation and Continuous Improvement in Pharmaceutical
Manufacturing. Pharmaceutical CGMPs for the 21st Century. The PAT Team and
Manufacturing Science Working Group Report, 2004. http://www.fda.gov/Cder/gmp/
gmp2004/manufSciWP.pdf.
[3] Food and Drug Administration. Guidance for Industry PAT—A Framework for Innovative
Pharmaceutical Development, Manufacturing, and Quality Assurance, 2004. http://www.
fda.gov/cder/guidance/6419fnl.pdf.
