Biomedical Engineering Reference
In-Depth Information
0
2
4
6
8
10
Retention time (min)
Figure
11.5.
Overlay of reverse-phase chromatograms for the six lots of hydrolysate. Wave-
lengths included are from 300 to 350 nm. This figure illustrates that results in Figs 11.3 and 11.4
are consistent with more traditional ways of summarizing analytical results. (Lot 1, gray; Lots
2-6, black).
all at once. Confirmation can then be targeted based on the results by plotting specific
wavelength/retention time segments, as shown in Fig. 11.5.
Similar types of data processing were performed for
1
H
NMR, LC-MS, and other
HPLC separations. Results from each test were then correlated to cell- culture perfor-
mance (Table 11.2). Not all analytical results correlate with cell culture performance.
Analytical tests that do correlate to cell-culture performance with squared correlations
above 0.25 are highlighted in green. Even after a test correlated to the use test when
6 hydrolysate lots were tested (like the HPLC example above), the correlation coefficient
could drop when more lots are tested. For example, aspartate has a correlation coefficient
of 0.5when the first 6 lots are included in the analysis. When the number of lots increased
2
) and Sign of the Correlation Between
Analytical Test Results and Cell-Culture Performance Data as a Function of the Number of
Lots Tested
TABL E 11.2. Square Correlation Coefficient (
R
R
2
Method
Factor
N
¼
6
N
¼
11
N
¼
22
Sign
AAA
Asp
0.5
0.4
0.0
þ
Ser
0.1
0.1
0.0
þ
Gln
0.0
0.3
0.0
þ
Trp
0.6
0.0
0.0
Glu
0.0
0.1
0.1
þ
Met
0.0
0.3
0.0
þ
Thr
0.0
0.1
0.0
þ
LC-Fluor
Unidentified Peak
0.6
0.1
0.0
þ
ICP-MS
Zn
0.7
0.8
0.5
þ
NMR
LV1 score
0.6
0.5
þ
LV2 score
0.8
0.3
þ
LC-MS
m/z 279.17 intensity
0.5
0.4
0.3
