Biomedical Engineering Reference
In-Depth Information
(a)
Term
Scaled estimate
Prob>|t|
Intercept
pH (induction)
DO%
Feed-2
Biomass (OD)
pH (induction) -7)*(DO% -59.8)
pH (induction) -7)*(Feed-2 -389)
pH (induction) -7)*(Biomass (OD) -62.5)
92.236232
-8.10461
2.4183974
-0.528828
3.815735
0.0396003
-3.161254
-1.278127
<.0001*
0.0034*
0.2959
0.8165
0.1126
0.9861
0.1815
0.5769
(b)
Term
Scaled estimate
Prob>|t|
Intercept
pH (induction)
DO%
Feed-2
Biomass (OD)
pH (induction) -7)*(DO% -59.8)
pH (induction) -7)*(Feed-2 -389)
pH (induction) -7)*(Biomass (OD) -62.5)
109.62848
-2.218539
17.120627
5.7275542
-5.572755
-1.664087
9.4427245
9.3653251
<.0001*
0.6285
0.0022*
0.2235
0.2355
0.7157
0.0559
0.0577
(c)
Term
Scaled estimate
Prob>|t|
Intercept
pH (induction)
DO%
Feed-2
Biomass (OD)
pH (induction) -7)*(DO% -59.8)
pH (induction) -7)*(Feed-2 -389)
pH (induction) -7)*(Biomass (OD) -62.5)
124.66667
23.35098
-4.335532
10.208333
-8.125
11.875
12.708333
4.375
<.0001*
0.0009*
0.4265
0.0784
0.1516
0.0449*
0.0338*
0.4257
Figure
5.9. Scaled estimates of main effects of induction-phase operational parameters on
product yield (a), product quality 1 (b), and product quality 2 (c) performance from a fractional
factorial DOE study. Note: Data have been normalized against the average small-scale model
performance at set point operating conditions.
final purified bulk product. This supports the demonstration of process robustness even
under worst case operating conditions.
5.7 DEFINITION OF DESIGN SPACE
Figure 5.12 illustrates the concept of design space. The characterized space is examined in
the process characterization studies, and the outcome of the studies defines the acceptable
range for the operational parameters. For robust processes, it is expected that the normal
operating ranges (NORs) for these parameters will be well nested within the respective
acceptablerange(AR).Thecombinationof theARsdefines thedesignspaceforaprocess. It
means thatvariabilityintheoperationalparameterswithintheARwouldstill leadtoprocess
performancemeetingexpectations. Theexpectations are outlinedby the process validation
acceptance criteria (PVAC) for the critical quality attributes of the product. As mentioned
