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Round Lake, Illinois 60073

COVER PAGE

REPORT
Study Number Class Type of Document

45273 Data Transmittal Report 1


Title

Analytical Testing for Samples from CUNO 70CP Resin Changes for Albumin, IGIV and A1PI Processes
Period Covered (report) Optional Tracking Number(s)

     
Project Number Customer Customer’s Division

36819555 Mo Azari       Bioscience


Additional Distribution (Original to Archives)

Mahmood Azari, WESTLAKE VILLAGE CA., Todd Wielgos, Chyung Cook and Jim Catarello, WG2-2S,
Technology Resources Archives, WG1-1S

APPROVALS
Name Division Signature Date
Study Director
Jim Catarello Technology Resources

Study Director’s Management


Todd Wielgos Technology Resources

Verifier Technology Resources

     

     

     

     

     
     
     
For Reports: Authorized for appropriate use outside the company in compliance with Baxter policies regarding
use of BAXTER CONFIDENTIAL information? Yes, _______Initials of Study Director’s Department Head
or designee and approval signature required above.
Contributing Individuals (applicable for reports)
Liqiong Fang, Bev Johnson, Anthony Tomaso, Chris Cullen
The date that the last person signs this document is to be used when referencing this document.
For Protocols: Study must not begin until all approval signatures are obtained
For Reports: Report must not be issued until all approval signatures are obtained

Page 1 of 19
BAXTER CONFIDENTIAL
Reference Document: YY-005-003, YY-005-005 Form Number: FORM179
(current version) Form Issue Date: 04-14-2003
Study Number: 45273 Page 2 of 19
Data Transmittal Report 1

BACKGROUND

The Baxter Bioscience division at the Los Angeles, California manufacturing facility (reference 1) is currently
evaluating the impact of change in the resin of the CUNO depth filter media 70 CP grade on the efficiency and
product quality at pilot scale. CUNO reports that supply of the current resin is constrained and that there will be
no more supply of the current resin on January 1st, 2009. The supply of pads fabricated from the current resin is
estimated to extend as short as March 31st, 2009.

The change in resin include that CUNO’s replacement resin is supplied dispersed in a liquid a liquid while the
current resin is supplied as a powder. In melamine formaldehyde resins, the formaldehyde to melamine ration in
the current resin has a target ratio of 2.7 while the replacement resin has a target ratio of 3.2. The replacement
vendor methylates the resin to improve stability in its liquid dispersed form. The vendor further reports that these
methyl groups are removed during the resin preparation process.

The structures of the current and replacement resins as provided by the vendor are shown below, showing the
presence of the methyl groups (-R) which the vendor reports are released during the resin preparation (curing)
process.

Figure 1: Melamine Formaldehyde Resin Structure

A diagram for the showing the location of the CUNO pads is shown below.
Weighing
Scale

WI
Temperature Pressure Pressure
Sensor Sensor Sensor
Cuno pads Sampling Valve
TI PI PI
Product Tank Sample
Feed Tank Port

Feed Valve Alsop 8" x 8" Filter Press


Pump

BAXTER CONFIDENTIAL
Study Number: 45273 Page 3 of 19
Data Transmittal Report 1

PURPOSE

The objective of this data transmittal report is to report the results from analytical testing on various process
samples from the productions of Albumin, IGIV or A1PI (Alpha-1 Phosphatase Inhibitor) from the Baxter
Bioscience facility in Los Angles, California. Size Exclusion Chromatography coupled with Multi-Angled Laser
Light Scattering (SEC-MALLS) was used to evaluate product integrity and Mass Spectroscopy methods were
used to evaluate all “control” and “test” resin stability samples. NMR (Nuclear Magnetic Resonance)
Spectroscopy was only performed on samples were there were differences between the control and test samples.

It was determined that FTIR (Fourier Transform Infrared Resonance) was not needed for this study. However,
used to evaluate resin stability.

TEST ARTICLES

Four sets of samples were received from the Baxter Bioscience Division located in Los Angeles, California. Set 1
was received on 10-17-08 and contained 23 samples. Set 2 was received 10/30/08 and contained 32 samples.
Set 3 was received 11-13-08 and contained 57 samples. Set 4 was received 12-11-08 and contained 78
samples. Sample sets 1 to 3 were immediately placed in 2-8°C storage upon their arrival. On 12-2-08, sample
sets 1 and 2 were moved to -80°C storage and on 12-6-08 set 3 was moved to -80°C storage. Sample set 4 was
immediately placed in -80°C storage upon its arrival. All samples were logged in and given Round Lake numbers
as a reference.

Control and Test samples from the Baxter Bioscience Facility in Los Angles, California that were collected during
the production of Suspension B @ 17%, II+III Extract and Fr IV-4 @ 40% for the production of albumin and IGIV
were received for testing. In addition, WFI and Buffer samples were also received for testing. A detailed
description and sample clarification of the labeled samples received is described below:

Sample Clarification

Label Clarification Proposed


Alternate
Label
Starting Material Raw Material sample (either II+III Extract, Fr IV-4 @ 40%, or Susp. B No
(Suspension before at 17%) from manufacturing that never came into contact with CUNO
CUNO clarification) media.
WFI Rinse Water for Injection (WFI) that was run through the CUNO filter No
media. WFI is run to wet the pads.
Pooled Pre-Wash Buffer run through the CUNO filter media prior to filtering the protein Pre-filtration
Solution solution. Buffer is run to equilibrate the pads and filter press to the Wash
desired temperature and pH.
Pre-Wash Solution Buffer run through the CUNO filter media prior to filtering the protein Pre-filtration
solution. Buffer is run to equilibrate the pads and filter press to the Wash
desired temperature and pH. Identical to “Pooled Pre-Wash
Solution”
Filtrate at the End of Sample of filtered protein solution at the end of filtration. Filtrate of Filtrate
Filtration the II+III extract, Fr IV-4 @ 40%, or Susp. B @ 17%.
Pooled Filtrate Sample Sample of the wash solution used to flow through the filter media Post-Filtration
after Post Wash after filtering the protein solution. This ensures full recovery of the Buffer Wash
product. Post wash uses the same buffer as the Pre-Wash.
Buffer Buffer Control that had never came into contact with the CUNO
Media

The samples received from each sample set (1 to 4) are described the Tables 1 to 4 in the Results section of this
data transmittal report.

BAXTER CONFIDENTIAL
Study Number: 45273 Page 4 of 19
Data Transmittal Report 1

EXPERIMENTAL DESIGN

All samples were centrifuged at either 2000 or 5000 rpm prior to analytical evaluation to separate precipitated
protein. The supernatants of the centrifuged samples were submitted for analysis. The WFI and buffer samples
were not centrifuged since there was no protein in those samples.

It was decided that FTIR (Fourier Transform Infrared Resonance) would not be performed. To minimize sample
testing, NMR (Nuclear Magnetic Resonance) Spectroscopy and GC-MS (Gas Chromatography–Mass
Spectrometry) would be only performed on samples that had chromatographic differences between the “control”
and “test” samples by LC-MS or SEC.

Size Exclusion Chromatography coupled with Multi-Angled Laser Light Scattering (SEC-MALLS) with refractive
index, UV at 220nm and 280nm detection was used to evaluate product integrity. LC-MS was used to evaluate
resin stability and extractable material.

Analytical Methods:

A. SEC-MALLS – Refractive Index (RI), UV at 220nm and 280nm Detection – PRODUCT INTEGRITY

SEC-MALLS was used to evaluate product integrity by comparing the molecular weight results for protein
samples before and after filtration obtained for the control and test CUNO resin process runs. The RI, UV at
220nm and 280nm chromatographic profiles were compared for samples collected at similar time-points during
the control and test sample runs. The SEC-MALLS method conditions used are described below:

Equipment

An Agilent 1100 HPLC System coupled with Wyatt Technology DAWN HELEOS, QELS (Quasi-Elastic Light
Scattering and Optilab rEX differential refractive index (dRI) and UV detector was used to evaluate the test
articles.

SEC-Conditions:
Analytical Columns: Superdex 200.
Mobile Phase: PBS Buffer, pH 7.4.
Flow Rate: 0.7 mL/minute.
Column Temperature: Room temperature.
Sample Temperature: 5ºC.
Injection Volume: 100µL.
Runtime : 50 minutes.
Detection : Light Scattering, Wyatt DAWN HELEOS, s/n. 263-H.
Refractive Index (RI), Wyatt Optilab rEX, s/n. 479-rEX.
Quasi-Elastic Light Scattering (QELS), s/n. QH-114.
UV at 220 and 280nm.

Test samples were injected (after centrifugation) directly into the SEC-MALLS system. No further dilution was
performed. A BSA sample was injected for detector alignment, band broadening and normalization purposes.

B. BCA Total Protein Assay

The assays were performed according to the manufacture instructions.

C. NMR Spectroscopy

Added 10% deuterium oxide to each sample prior to analysis. Followed Technology Resources Standard
Procedure PA011005, Operation and Maintenance of the Bruker Avance III 600 and Avance I 400 NMR
Spectrometers. Effective 9/26/07.

BAXTER CONFIDENTIAL
Study Number: 45273 Page 5 of 19
Data Transmittal Report 1

D. Mass Spectroscopy

Samples were assayed directly. No further dilutions or sample treatments were made prior to analysis.

Followed Technology Resources Standard Procedure 1109105, Calibration, Operation and Maintenance of Mass
Spectrometers and their Data Systems. Effective 2/17/08.

LC Conditions:

Column: Phenominex Synergi; Polar –RP

Mobile Phase: A = 25mM NH4OAc (Ammonium Acetate) / 25mM HOAc (Acetic Acid).
B = Acetonitrile
C = Methanol

Gradient: Time %A %B %C
0 90 5 5
2 90 5 5
20 5 90 5
23 5 90 5
24 90 5 5
30 90 5 5

Flow Rate: 0.5ml/min.


Column Temp.: 25°C
Inj. Volume: 50µ L
Detection: Water Q-tof Micro. Mass Spectrometer

E. GC-Mass Spectroscopy

Samples were assayed directly. No further dilutions or sample treatments were made prior to analysis.

Followed Technology Resources Standard Procedure PA009007, Operation and Maintenance of Gas
Chromatographs. Effective 8/17/08. Followed Technology Resources Standard Procedure 1109105, Calibration,
Operation and Maintenance of Mass Spectrometers and their Data Systems. Effective 2/17/08.

RESULTS

All samples were assayed by SEC-MALLS with RI, UV at 220nm and 280nm detection and by LC-MS. The RI, UV at
220nm and 280nm chromatographic profiles were compared for samples collected at similar time-points during
the control and test sample runs. Samples showing chromatographic differences between test and control at similar
time-points were submitted for NMR and GC-MS analysis. All samples were measured for protein content using the
BCA method. The results for the 4 sets of samples submitted are summarized in tables 1 to 4.

BAXTER CONFIDENTIAL
Study Number: 45273 Page 6 of 19
Data Transmittal Report 1

Table 1: Summary of Sample Set 1 (Received 10/17/08) from LA

RL BCA SEC-
Number Sample I.D. Suspension Lot Media Lot Date Time Control or (mg/mL) MALLS RI SEC SEC LC-MS NMR GC-
Number Number Test MW UV 280 UV 220 MS
g/mole
1 Starting Material (Suspension Before LB0820509 39214 10/7/08 11:38 CONTROL 5.387 122,600 --- --- --- --- NA NA
CUNO Clarification)
12 Starting Material (Suspension Before LB0820509 39446 10/7/08 11:38 TEST 5.282 125,600 X X X + 11M NA NA
CUNO Clarification)
2 Starting Material (Suspension before LB0850512 39214 10/10/08 14:20 CONTROL 13.815 60,230 --- --- --- --- NA NA
CUNO clarification)
13 Starting Material (Suspension before LB0850512 39446 10/10/08 14:20 TEST 13.888 56,200 X X X X NA NA
CUNO clarification)
14 Starting Material (Suspension before LB0890532 39446 10/14/08 13:12 TEST 10.484 197,700 NC NC NC NC NP NP
CUNO Clarification)
3 Pooled Pre-Wash Solution LB0820509 39214 10/7/08 14:04 CONTROL 0 NA --- --- --- --- NR ---
15 Pooled Pre-Wash Solution LB0820509 39446 10/7/08 14:04 TEST 0 NA X - 39M X Large NP Xc
20M
4 Pooled Pre-Wash Solution LB0850512 39214 10/13/08 09:21 CONTROL 0 NA --- --- --- --- NA NA
16 Pooled Pre-Wash Solution LB0850512 39446 10/13/08 09:22 TEST 0 NA X X X X NA NA
5 Pooled Pre-Wash Solution LB0890532 39214 10/15/08 09:12 CONTROL 0 NA --- --- --- --- --- ---
17 Pooled Pre-Wash Solution LB0890532 39446 10/15/08 09:22 TEST 3.028 142,900 10 to Large 18M, Large + 15 and Xa Xb
24M 39M 18M, 20M
6 Pooled Filtrate Sample After Post-Wash LB0820509 39214 10/7/08 15:38 CONTROL 4.351 123,000 --- --- --- --- NA NA
18 Pooled Filtrate Sample After post Wash LB0820509 39446 10/7/08 15:39 TEST 5.199 119,600 X X X + Small NA NA
11M
7 Pooled Filtrate Sample after Post Wash LB0850512 39214 10/13/08 11:49 CONTROL 14.513 53,580 --- --- --- --- NA NA
19 Pooled Filtrate Sample after Post-Wash LB0850512 39446 10/13/08 11:49 TEST 14.139 51,080 X X X X NA NA
8 Pooled Filtrate Sample After Post-Wash LB0890532 39214 10/15/08 11:10 CONTROL 5.811 152,600 --- --- --- --- NA NA
20 Pooled Filtrate Sample After Post-Wash LB0890532, 39446 10/15/08 11:10 TEST 10.969 162,100 X X X X NA NA
9 Filtrate Sample at the End of Filtration LB0820509 39214 10/7/08 15:15 CONTROL 4.389 125,300 --- --- --- --- NA NA
21 Filtrate Sample at the End of Filtrate LB0820509 39446 10/7/08 15:15 TEST 4.012 124,200 X X X X NA NA
10 Filtrate Sample at the End of Filtration LB0850512 39214 10/13/08 11:29 CONTROL 13.549 52,470 --- --- --- --- NA NA
22 Filtrate Sample at the End of Filtration LB0850512 39446 10/13/08 11:29 TEST 13.252 52,780 X X X X NA NA
11 Filtrate Sample at the End of Filtration LB0890532 39214 10/15/08 10:35 CONTROL 8.974 151,200 --- --- --- --- NA NA
23 Filtrate Sample at the end of Filtration LB0890532 39446 10/15/08 10:38 TEST 11.831 169,700 X X X X NA NA

X = Same Profile as the Control.

X c = Same GC-MS Profile as the Control. Peaks at approximately 19m = methanol, 23m = ethanol, 33.5m = 1-propanol.
X a = Similar NMR spectrum as control plus resonances between 2.5 and 3.2 ppm. Sample was submitted for GC-MS analysis.
X b = Similar GC-MS Profile as the Control, however, larger peaks in “Test” than “Control” at approximately 19m = Methanol, 23m = ethanol, 33.5m = 1-propanol.
NA = No testing required; NP = Performed; NC = No Control for Comparison; NA = Not Applicable (No Light Scattering Response to Determine Molecular Weight).
M = Peak Elution time in “Minutes”.
(-) = Peak Absent
(+) = Additional Peak Present.

BAXTER CONFIDENTIAL
Study Number: 45273 Page 7 of 19
Data Transmittal Report 1

The results in Table 1 show that the majority of samples showed no differences in the chromatographic profiles for
SEC-RI, SEC-UV at 280nm, SEC-UV at 220nm or LC-MS. In addition, the molecular weight results and SEC
profiles were consistent between the “test” and “control” samples indicating that the “test” CUNO resin had no impact
on the products integrity. Therefore, the “test” CUNO resin had no impact on the samples produced during the
production of Lots LB0820509, LB0850512and LB0890532.

There were a few differences between test and control samples. Results in Table 1 show that the profiles and results
for test samples of the “Pooled Pre-Wash Solutions“ for RL numbers 15 and 17 were different than their
corresponding controls (RL numbers 3 and 5).

The BCA results for RL number 17 showed the presence of protein. In addition, the SEC-RI (see figure 1), UV at
280nm (see figure 2) and 220nm profiles for “test” sample, RL number 17, were different than there corresponding
control (RL number 5). The results for the UV at 280nm also confirms the presence of protein in sample the “Pooled
Pre-Wash Solution“ sample for RL number 17.

Figure 1: SEC Refractive Index Overlay of Pooled Pre-Wash Solutions from Lot LB0890532.

RL-17, Test

RL-5, Control

Figure 2: UV at 280nm Overlay of Pooled Pre-Wash Solutions from Lot LB0890532.


1 - 26544099_JC #11 [modified by catarej] 5 UV_VIS_1
180 2 - 26544099_JC #23 [modified by catarej] 17 UV_VIS_1
mAU WVL:280 nm
MinAr = 5.000

150

RL-17, Test
125

100

75

RL-5, Control
50

25

7 - 38.824
1 1 - 13.008 2 - 17.949 3 - 30.313
4 - 32.332 6 - 35.595
5 - 33.727
0 2

-20 min
0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0 45.0 50.0

Since the Pooled Pre-Wash Solution samples were collected before the protein was filtered through the CUNO
resin, it was determined that RL sample 17 was most likely contaminated with protein and was not attributed t othe
CUNO resin.

BAXTER CONFIDENTIAL
Study Number: 45273 Page 8 of 19
Data Transmittal Report 1

To look for other non-protein differences between the “control” (RL number 5) and “test” (RL number 17) samples,
the samples were submitted for LC-MS analysis. The results for the LC-MS are shown in figure 3.

Figure 3: LC-MS Stacked Spectra of Pooled Pre-Wash Solutions from Lot LB0890532.
C-5
FK050806 1: TOF MS ES+
22.63 TIC
Control, RL # 5 3.82e4

11.21
7.26 7.69 8.29 17.01
8.54
2.47
8.71
13
4.00 6.00 8.00 10.00 12.00 14.00 16.00 18.00 20.00 22.00
FK050820 1: TOF MS ES+
20.51 TIC
1.91e5
Test, RL # 17 20.80

21.11
Spectral Differences
22.49
%

18.85
15.08

15.99

7.23 7.69 8.01 8.29 15.57


11.37
3 Time
4.00 6.00 8.00 10.00 12.00 14.00 16.00 18.00 20.00 22.00

The LC-MS profile showed the presence of peaks in the “test” solution at approximately 15 and 20 minutes that were
not present in its corresponding control. To investigate the differences seen in the LC-MS spectra, “test” sample RL
number 17 and “control” sample RL number 5 was submitted for NMR analysis. The results for the NMR spectra
difference are shown in figure 4.

Figure 4: NMR Stacked Spectra of Pooled Pre-Wash Solutions from Lot LB0890532.
Control, RL # 5

======== CHANNEL f1 ========


PROBHD 5 m m CPDCH 13C

0.18 3399 Hz

0 .000020 00 sec
20.00000000 sec
12019.23 0 Hz

2.7263 477 sec

0 .400000 01 sec
41.600 usec

11.10 usec
cca081124

7.78 usec
presat

D2O
spect

5 0.00 dB
20081125

0.00 dB
1

300.0 K
2

1H
65536

1600
5.06

18

1
0
PULPROG

SOLVENT
INSTRUM
PROCNO

FIDRES
EXPNO
NAM E

Date _

NUC1
SWH
Time

D12
TD0

PL1
PL9
DW
AQ
RG
NS
DS

DE
TE
TD

D1
D2

P1
25706-171-A, MS-5 control, 1H, Catarello, 36819555, 45273

9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

======== CHANNEL f1 ========


PROBHD 5 m m CPDCH 13C

Test, RL # 17 0.183399 Hz

0.000 02000 sec


20.0 0000000 sec
12 019.230 Hz

0.40000001 sec
2.7 263477 sec

41.600 usec

11.10 usec
cca081124

presat

7.78 usec
D2 O
spect

50.00 dB
2008112 4

0.00 dB
1

29 8.1 K
1

1H
11.05

65536

1239

18

1
0
PULPROG

SOLVENT
INSTRUM
PROCNO

FIDRES
EXPNO
NAME

NUC1
Date_

SWH
Time

D12
TD0

PL1
PL9
DW
RG
AQ
NS
DS

DE
TD

D2
TE
D1

P1
25706-171-B, MS-17 test, 1H, Catarello, 36819555, 45273
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

Baxter Technology Resources, Round Lake IL 60073,


AV400 RLS27611/AV600 RLS25079, SOP PA-011-005 (9/26/07)
-FOR BAXTERUSEONLY-

Results from the NMR spectra comparison showed additional small resonances between 2.5 and 3.2ppm for test
sample RL number 17 that were not seen in its corresponding control (RL number 5). The samples were then
submitted for GC-MS analysis determine whether or not there was further contamination besides the additional
protein observed in sample 17.

BAXTER CONFIDENTIAL
Study Number: 45273 Page 9 of 19
Data Transmittal Report 1

The GC-MS results for the control (RL number 5) and test (RL number 17) are shown in Figures 5a and 5b.

Figure 5a: GC-MS Overlay Profile of Pooled Pre-Wash Solutions from Lot LB0890532.

Abundance
TIC: tj020209010.D\data.ms
TIC: tj020209012.D\data.ms (*)
5000000

4500000 1-propanol
4000000

3500000
Ethanol
3000000

Sample 17
2500000

2000000

1500000

Methanol
1000000
Acetamide
500000 Sample 5

0
10.00 15.00 20.00 25.00 30.00 35.00 40.00
Time-->

Figure 5b: GC-MS Overlay Profile of Pooled Pre-Wash Solutions from Lot LB0890532 - ENLARGED.
Abundance

TIC: tj020209010.D\data.ms Unknowns


TIC: tj020209012.D\data.ms (*)

450000

400000

350000 Methyl Acetate

300000

250000

Sample 17
200000

150000

100000
Sample 5

10.00 15.00 20.00 25.00 30.00 35.00 40.00


Time-->

The 1-propanol is the internal standard. The results in figures 5a and 5b show the suspected methanol along with
the presence of acetamide, methyl acetate, and ethanol. Acetamide, methyl acetate, methanol and ethanol were
seen in both the “test” (RL number 17) and control samples (RL number 5), however, they were in higher
concentration in the test sample. There were some small “unknown peaks around 35minutes that were seen in
the test that were not seen in the control. In sample 17, the peak at ~19 minutes is most likely methanol, however
the spectrum has some larger ions that make it possible that it could be t-butanol.

Based on the analytical results for “test” RL sample17, the sample is contaminated with protein and has higher
methanol and ethanol amounts compared to its control. Since buffer is run through the CUNO filter media prior to
filtering the protein solution for the Pooled Pre-Wash Solution samples and there was no protein was passed
through the CUNO resin, the contamination of protein could not be due to the CUNO resin. The higher amounts
of methanol and ethanol observed in RL sample 17 compared to its control may be due to an incomplete filter wash
process.

BAXTER CONFIDENTIAL
Study Number: 45273 Page 10 of 19
Data Transmittal Report 1

The other “test” sample, RL sample 15, a “Pooled Pre-Wash Solution”, showed a large 20 minute peak in its LC-
MS profile that was much smaller in its corresponding “control” sample, RL sample 3 (see Figure 6).

Figure 6: LC-MS Stacked Spectra of Pooled Pre-Wash Solutions from Lot LB0820509.

Control, RL # 3

Test, RL # 15
Large 20-minute peak

This sample did not contain protein, but was sent for GC-MS analysis to investigate this large 20-minute peak in
its LC-MS profile. The GC-MS profile for “test” RL sample 15, a “Pooled Pre-Wash Solution”, and its
corresponding “control” sample, RL sample 3 is shown in Figure 7.

Figure 7: GC-MS Overlay Profile of Pooled Pre-Wash Solutions from Lot LB0820509.
Abundance
TIC: tj020209009.D \data.ms
TIC: tj020209011.D \data.ms (*)
ethanol
5000000
1-propanol
4500000

methanol
4000000

3500000

3000000 Sample 3 vs Sample 15

2500000
ethyl acetate
2000000

acetimide
1500000

1000000
methyl acetate

500000

0
10.00 15.00 20.00 25.00 30.00 35.00 40.00
Time-->

The results in the GC-MS profile showed the same profiles for both the “test” RL sample 15 and its corresponding
“control” sample, RL sample 3, therefore, the larger 20-minute peak in the LC-MS profile could not be attributed to
the components identified in figure 7 and there is no significant contribution from the CUNO resin.

A small peak at approximately 11 minutes was observed in the LC-MS profile for the “test” starting material (RL
number 12, Suspension Before CUNO Clarification) that was not seen in its corresponding “control” starting
material (RL number 1). Since this material was starting material and had not been exposed to the CUNO resin,
the small difference is not attributed to the CUNO resin material. The small 11-minute peak was seen again in
the “test” Pooled Filtrate Sample After Post Wash sample (RL number 18, Lot LB0820509). This was carried over
from the starting material (RL number 12, Lot LB0820509) and is not attributed to the CUNO resin material. In
addition, the small 11-minute was gone at the final product, Filtrate Sample at the End of the Filtration, RL number
21.

BAXTER CONFIDENTIAL
Study Number: 45273 Page 11 of 19
Data Transmittal Report 1

A second sample set was received 10-30-08. The results for sample set 2 are summarized in Tables 2a and 2b for Lots LB0850540, LB0850527 and
LB0890558.

Table 2a: Sample Set 2 – LA Samples, Received 10-30-08 (Lots LB0850540 and LB0850527).

Number Sample I.D. Suspension Media Lot Date Time Control or Total SEC-
Lot Number Number Test Protein MALLS RI SEC-UV SEC-UV LC-MS
(mg/mL) (MW = at 280nm at 220nm
g/mole)
1 Starting Material (Suspension LB0850540 39611 10/20/0 13:49 CONTROL 12.221 58,410 --- --- --- ---
Before CUNO Clarification) 8
13 Starting Material (Suspension LB0850527 39602 10/16/0 15:08 CONTROL 13.476 37,650 --- --- --- ---
Before CUNO Clarification) 8
5 Starting Material (Suspension LB0850540 39500 10/20/0 13:49 TEST 13.158 57,930 X X X X
Before CUNO Clarification) 8
9 Starting Material (Suspension LB0850527 39488 10/16/0 15:08 TEST 14.055 49,930 X X X X
Before CUNO Clarification) 8
2 Pooled Pre-Wash Solution LB0850540 39611 10/21/0 09:29 CONTROL 0.087 NA --- --- --- ---
8
14 Pooled Pre-Wash Solution LB0850527 39602 10/17/0 09:15 CONTROL 0.0675 NA --- --- --- ---
8
6 Pooled Pre-Wash Solution LB0850540 39500 10/21/0 09:29 TEST 0.0495 NA X X X X
8
10 Pooled Pre-Wash Solution LB0850527 39488 10/17/0 09:15 TEST 0.0525 NA X X X X
8
3 Pooled Filtrate Sample after LB0850540 39611 10/21/0 11:08 CONTROL 13.23 50,420 --- --- --- NC
Post Wash 8
15 Pooled Filtrate Sample after LB0850537 39602 10/17/0 11:04 CONTROL 13.541 48,040 --- --- --- NC
Post Wash 8
7 Pooled Filtrate Sample after LB0850540 39500 10/21/0 11:08 TEST 12.89 49,040 X X X NC
Post Wash 8
11 Pooled Filtrate Sample after LB0850527 39488 10/17/0 11:04 TEST 13.478 46,390 X X X NC
Post Wash 8
4 Filtrate Sample at the End of LB0850540 39611 10/21/0 10:50 CONTROL 12.679 51,630 --- --- --- ---
Filtration 8
16 Filtrate Sample at the End of LB0850527 39602 10/17/0 10:45 CONTROL 14.584 41,890 --- --- --- ---
Filtration 8
8 Filtrate Sample at the End of LB0850540 39500 10/21/0 10:50 TEST 13.975 48,580 X X X X
Filtration 8
12 Filtrate Sample at the End of LB0850527 39488 10/17/0 10:45 TEST 13.150 47,080 X X X X
Filtration 8

X = Same as Control Profile


NC = Not Compared
NA = Not Applicable, No RI signal to Accurately Determine Molecular Weight.

BAXTER CONFIDENTIAL
Study Number: 45273 Page 12 of 19
Data Transmittal Report 1

Table 2b: Sample Set 2 – LA Samples, Received 10-30-08 (Lot LB0890558)

Number Sample I.D. Suspension Media Lot Date Time Control or Total SEC-
Lot Number Number Test Protein MALLS RI SEC-UV SEC-UV LC-MS
(mg/mL) (MW = at 280nm at 220nm
g/mole)
17 Starting Material (Suspension LB0890558 39602 10/22/0 14:55 CONTROL 14.617 40,650,00 --- --- --- ---
Before CUNO Clarification) 8 0
19 Starting Material (Suspension LB0890558 39602 10/22/0 14:55 CONTROL 15.308 7,667,000 --- --- --- ---
Before CUNO Clarification) 8
18 Starting Material (Suspension LB0890558 39602 10/22/0 14:55 CONTROL 15.259 2,113,000 --- --- --- ---
Before CUNO Clarification) 8
30 Starting Material (Suspension LB0890558 39488 10/22/0 14:55 TEST 16.064 56,710,00 X X X X
Before CUNO Clarification) 8 0
20 Pooled Pre-Wash Solution LB0890558 39602 10/23/0 10:28 CONTROL 0.0660 NA --- --- --- ---
8
21 Pooled Pre-Wash Solution LB0890558 39602 10/23/0 10:28 CONTROL 0.0695 NA --- --- --- ---
8
22 Pooled Pre-Wash Solution LB0890558 39602 10/23/0 10:28 CONTROL 0.0675 NA --- --- --- ---
8
23 Pooled Pre-Wash Solution LB0890558 39602 10/23/0 10:28 CONTROL 0.0030 NA --- --- --- ---
8
24 Pooled Filtrate Sample after LB0890558 39602 10/23/0 11:35 CONTROL 9.891 472,600 --- --- --- ---
Post Wash 8
25 Pooled Filtrate Sample after LB0890558 39602 10/23/0 11:35 CONTROL 9.6595 397,100 --- --- --- ---
Post Wash 8
26 Pooled Filtrate Sample after LB0890558 39602 10/23/0 11:35 CONTROL 10.393 543,900 --- --- --- ---
Post Wash 8
31 Pooled Filtrate Sample after LB0890558 39488 10/23/0 11:29 TEST 9.761 565,900 X X X X
Post Wash 8
27 Filtrate Sample at the End of LB0890558 39602 10/23/0 11:08 CONTROL 11.506 626,200 --- --- --- ---
Filtration 8
28 Filtrate Sample at the End of LB0890558 39602 10/23/0 11:08 CONTROL 11.308 594,000 --- --- --- ---
Filtration 8
29 Filtrate Sample at the End of LB0890558 39602 10/23/0 11:08 CONTROL 11.521 696,600 --- --- --- ---
Filtration 8
32 Filtrate Sample at the End of LB0890558 39488 10/23/0 11:05 TEST 11.563 479,500 X X X X
Filtration 8

X = Same as Control Profile


NA = Not Applicable, No RI signal to Accurately Determine Molecular Weight.

The results in Tables 2a and 2b show that there was no differences found in the chromatographic profiles for SEC-RI, SEC-UV at 280nm, SEC-UV at
220nm or LC-MS. In addition, the molecular weight results and SEC profiles were consistent between the “test” and “control” samples indicating that the
“test” CUNO resin had no impact on the products integrity. Therefore, the “test” CUNO resin had no impact on the production of Lots LB0850540,
LB0850527 and LB0890558.

BAXTER CONFIDENTIAL
Study Number: 45273 Page 13 of 19
Data Transmittal Report 1

A third set of samples was received on 11-13-08 and 11-21-08. The results for sample set 3 are summarized in Table 3 for Lots LB0820580, LB0890585
and LB0820548.

Table 3: Set 3 – LA Samples, Received 11-13-08 and 11-21-08

Sample I.D. Suspension Media Lot Date Time Control or Total SEC-
RL Lot Number Number Test Protein MALLS RI SEC-UV at SEC-UV at LC-MS NMR
Number (mg/mL) (MW = 280nm 220nm
g/mole)
2 Starting Material (Suspension LB0820580 39611 11/7/08 14:35 CONTROL 5.643 128,800 --- --- --- --- NA
Before CUNO Clarification)
9 Starting Material (Suspension LB0820580 39611 11/7/08 14:35 CONTROL 5.779 128,300 --- --- --- --- NA
Before CUNO Clarification)
13 Starting Material (Suspension LB0820580 39500 11/07/08 14:35 TEST 5.732 124,700 X X X X NA
Before CUNO Clarification)
20 Starting Material (Suspension LB0820580 39500 11/7/08 14:35 TEST 5.618 133,000 X X X X NA
Before CUNO Clarification)
21 Starting Material (Suspension LB0890585 39611 10/28/08 17:03 CONTROL 15.017 213,300 --- --- --- --- NA
Before CUNO Clarification)
27 Starting Material (Suspension LB0890585 39611 10/28/08 17:03 CONTROL 15.247 336,500 --- --- --- --- NA
Before CUNO Clarification)
29 Starting Material (Suspension LB0890585 39500 10/28/08 17:03 TEST 6.587 314,200 X X X No 15.1 and NA
Before CUNO Clarification) 16.1 Peaks2
35 Starting Material (Suspension LB0890585 39500 10/28/08 17:03 TEST 14.916 316,600 X X X X NA
Before CUNO Clarification)
45 Starting Material (Suspension LB0820548 39602 10/27/08 13:57 CONTROL 6.867 151,300 --- --- --- --- NA
Before CUNO Clarification)
43 Starting Material (Suspension LB0820548 39602 10/27/08 13:57 CONTROL 7.231 154,700 --- --- --- --- NA
Before CUNO Clarification)
37 Starting Material (Suspension LB0820548 39488 10/27/08 13:57 TEST 6.815 153,900 X X X X NA
Before CUNO Clarification)
39 Starting Material (Suspension LB0820548 39488 10/27/08 13:57 TEST 14.554 133,900 X X X Peaks at 15.1 NA
Before CUNO Clarification) and 16.13
11 Pooled Pre-Wash Solution LB0820580 39611 11/10/08 10:05 CONTROL BDL CNBD --- --- --- --- NA
12 Pooled Pre-Wash Solution LB0820580 39611 11/10/08 10:05 CONTROL BDL CNBD --- --- --- --- NA
14 Pooled Pre-Wash Solution LB0820580 39500 11/10/08 10:05 TEST BDL CNBD Smaller 47m X Smaller 45m X NA
19 Pooled Pre-Wash Solution LB0820580 39500 11/10/08 10:05 TEST BDL CNBD Smaller 47m X Smaller 45m X NA
48 Pooled Pre-Wash Solution LB0820548 39602 10/28/08 09:28 CONTROL BDL CNBD --- --- --- --- NA
49 Pooled Pre-Wash Solution LB0820548 39602 10/28/08 09:28 CONTROL BDL CNBD --- --- --- --- NA
38 Pooled Pre-Wash Solution LB0820548 39488 10/28/08 09:28 TEST BDL CNBD X X X X NA
46 Pooled Pre-Wash Solution LB0820548 39488 10/28/08 09:28 TEST BDL CNBD X X X X NA
22 Pooled Pre-Wash Solution LB0890585 39611 10/29/08 13:30 CONTROL BDL CNBD --- --- --- --- NA
30 Pooled Pre-Wash Solution LB0890585 39611 10/29/08 13:30 CONTROL BDL CNBD --- --- --- --- NA
26 Pooled Pre-Wash Solution LB0890585 39500 10/29/08 13:30 TEST BDL CNBD X Small 4-10 Smaller 45m X NA
m
31 Pooled Pre-Wash Solution LB0890585 39500 10/29/08 13:30 TEST BDL CNBD X No 4-10 m Smaller 45m X NA
1 Pooled Pre-Wash Solution LB0890558 39488 10/23/08 10:29 TEST 0.721 546,800 Large 10-25 X1 Large 10-25 X1 NA
m m
6 Pooled Pre-Wash Solution LB0890558 39488 10/23/08 10:29 TEST BDL 321,400 Small 10-25m X1 Small 10-25m X1 NA

X = Same Chromatographic Profiles as the Control.


X1 = Same Chromatographic Profiles as the other Test Sample, No Control to Compare.
2 = No peaks at 15.1 and 16.1. Those peaks are present in both “controls” and the other “test”.
3 = Peaks at 15.1 and 16.1 that were not present in the “controls” or the other “test”.
m = minute peak

BAXTER CONFIDENTIAL
Study Number: 45273 Page 14 of 19
Data Transmittal Report 1

NA = Not Applicable
CNBD = Could Not Be Determined due to No or Low Refractive Index Response.

Table 3 (Continued): Set 3 – LA Samples, Received 11-13-08 and 11-21-08

RL Sample I.D. Suspension Lot Media Lot Date Time Control or Total SEC-MALLS
Number Number Number Test Protein (MW = RI SEC-UV at SEC-UV LC-MS
(mg/mL) g/mole) 280nm at
220nm
4 Pooled Filtrate Sample after Post Wash LB0820580 39611 11/10/08 11:40 CONTROL 4.884 119,500 --- --- --- ---
8 Pooled Filtrate Sample after Post Wash LB0820580 39611 11/10/08 11:40 CONTROL 4.708 128,000 --- --- --- ---
17 Pooled Filtrate Sample after Post Wash LB0820580 39500 11/10/08 11:40 TEST 4.923 116,000 X X X X
18 Pooled Filtrate Sample after Post Wash LB0820580 39500 11/10/08 11:40 TEST 4.979 118,900 X X X X
23 Pooled Filtrate Sample after Post Wash LB0890585 39611 10/29/08 14:30 CONTROL 10.036 1,155,000* --- --- --- ---
28 Pooled Filtrate Sample after Post Wash LB0890585 39611 10/29/08 14:30 CONTROL 10.312 29,460,000* --- --- --- ---
32 Pooled Filtrate Sample after Post Wash LB0890585 39500 10/29/08 14:30 TEST 9.925 434,200,000* X X X X
34 Pooled Filtrate Sample after Post Wash LB0890585 39500 10/29/08 14:30 TEST 9.944 49,930,000* X X X X
44 Pooled Filtrate Sample after Post Wash LB0820548 39602 10/28/08 10:15 CONTROL 5.794 138,200 --- --- --- ---
51 Pooled Filtrate Sample after Post Wash LB0820548 39602 10/28/08 10:15 CONTROL 5.271 140,200 --- --- --- ---
40 Pooled Filtrate Sample after Post Wash LB0820548 39488 10/28/08 10:16 TEST 4.885 130,300 X X X X
42 Pooled Filtrate Sample after Post Wash LB0820548 39488 10/28/08 10:16 TEST 5.452 136,000 X X X X
10 Pooled Filtrate Sample after Post Wash LB0890558 39488 10/23/08 11:29 TEST 9.573 444,400 X2 X2 X2 X2
5 Filtrate Sample at the End of Filtration LB0820580 39611 11/10/08 11:08 CONTROL 4.921 125,300 --- --- --- ---
7 Filtrate Sample at the End of Filtration LB0820580 39611 11/10/08 11:10 CONTROL 5.084 130,000 --- --- --- ---
15 Filtrate Sample at the End of Filtration LB0820580 39500 11/10/08 11:08 TEST 4.818 119,900 X X X X
16 Filtrate Sample at the End of Filtration LB0820580 39500 11/10/08 11:08 TEST 5.158 121,400 X X X X
24 Filtrate Sample at the End of Filtration LB0890585 39611 10/28/08 14:05 CONTROL 12.401 37,360,000* --- --- --- ---
25 Filtrate Sample at the End of Filtration LB0890585 39611 10/29/08 14:05 CONTROL 12.318 3,196,000* --- --- --- ---
33 Filtrate Sample at the End of Filtration LB0890585 39500 10/29/08 14:05 TEST 11.862 274,800,000* X X X X
36 Filtrate Sample at the End of Filtration LB0890585 39500 10/29/08 14:05 TEST 12.562 364,900,000* X X X X
50 Filtrate Sample at the End of Filtration LB0820548 39602 10/28/08 10:00 CONTROL 5.623 141,600 --- --- --- ---
52 Filtrate Sample at the End of Filtration LB0820548 39602 10/28/08 10:00 CONTROL 5.682 137,700 --- --- --- ---
41 Filtrate Sample at the End of Filtration LB0820548 39488 10/28/08 10:03 TEST 5.358 132,200 X X X X
47 Filtrate Sample at the End of Filtration LB0820548 39488 10/28/08 10:03 TEST 5.501 142,500 X X X X
3 Filtrate Sample at the End of Filtration LB0890558 39488 10/23/08 11:05 TEST 11.213 10,160,000* X2 X2 X2 X2
53 11+ 111 EXTRACT BUFFER 705100323 --- 11/14/08 --- --- BDL CNBD Same as 54 25-35m 30m Same as
54
54 11+ 111 EXTRACT BUFFER 705100323 --- 11/14/08 --- --- BDL CNBD Same as 53 25-35m 30m Same as
53
55 40% POST WASH 702208318 --- 11/18/08 --- --- BDL CNBD Large 30-40m 10-15 m 30m Same as
and 25-35m 56
56 BUFFER FOR SUSPENSION B (17%) 702308099 --- 11/10/08 --- --- BDL CNBD Large 30-40m 25-35m 30m Same as
POST WASH 55
57 BUFFER FOR SUSPENSION B (17%) 702308099 --- 11/10/08 --- --- NA NT NT NT NT NT
POST WASH – NO SAMPLE,
CONTAINER BROKEN

X = Same Chromatographic Profiles as the Control.


X1 = Same Chromatographic Profiles as the other Test Sample, No Control to Compare.
X2 = No Control to Compare.
m = minute peak
NT = Not Tested

BAXTER CONFIDENTIAL
Study Number: 45273 Page 15 of 19
Data Transmittal Report 1

* = High molecular weights were obtained for Lot LB0890585. There was a significant light scattering response in the high molecular weight region for both the control and test samples.
This response was reduced after filtration, however, the molecular weights were still high and the RI profiles molecular weight s for Lot LB0890585 were consistent for both the control and
test samples.

BAXTER CONFIDENTIAL
Study Number: 45273 Page 16 of 19
Data Transmittal Report 1

The results in Table 3 show that the majority of samples showed no differences in the chromatographic profiles for
SEC-RI, SEC-UV at 280nm, SEC-UV at 220nm or LC-MS. There were some minor absences or presences of the
15 and 16 minutes peaks that were seen in the “test” Starting Material (Suspension before CUNO Clarification).
Since the starting materials had not passed through the CUNO resin, the “test” CUNO resin results had no impact
on the production of Lots LB0820580, LB0890585 and LB0820548. There were some differences observed for the
“test” Pooled Pre-Wash Solutions compared to its corresponding “control” samples. However, the majority of those
differences showed an absence of peak for the “test” sample compared to its control. Since there was an absence of
peak, no further testing was performed. For the “test” Pooled Pre-Wash solution samples for RL numbers 1 and 6,
there was the presence of peaks observed between 10 and 25 minutes. There was some protein measured in RL
sample 1, so the presence of those peaks was most likely due to protein contamination. The peaks were also
observed in much smaller concentration for RL sample 6 even though no protein was measured. For both “test”
samples, there was no corresponding “control” sample to compare.

In addition, the molecular weight results and SEC profiles were consistent between the “test” and “control” samples
indicating that the “test” CUNO resin had no impact on the products integrity and the differences observed from the
“test” CUNO resin had no impact on the production of Lots LB0820580, LB0890585 and LB0820548.

A fourth set of samples was received on 12-11-08. This sample set were either buffer of WFI resin washes.
Since these samples contained no protein, the BCA total protein method was not performed on these samples.
The results for sample set 4 are summarized in Table 4.

BAXTER CONFIDENTIAL
Study Number: 45273 Page 17 of 19
Data Transmittal Report 1

Table 4: Set 4 – LA Samples, Received 12-11-08

Number Sample I.D. Suspension Media Lot Number Date Time Control or Test Refractive UV at UV at LC-MS NMR GC-MS
Lot Number Index 220nm 280nm
27 Pre-Wash NA 39611 12/05/0 11:46 CONTROL --- --- --- --- NA NA
Solution 8
64 Pre-Wash NA 39611 12/5/08 11:46 CONTROL --- --- --- 12.6 to 15.9m1 NA NA
Solution
1 Pre-Wash NA 39500 12/05/0 11:46 TEST X X X X NA NA
Solution 8
26 Pre-Wash NA 39500 12/05/0 11:46 TEST X X X X NA NA
Solution 8
61 Pre-Wash NA 39611 11/25/0 15:48 CONTROL --- --- --- --- NA NA
Solution 8
67 Pre-Wash NA 39611 11/25/0 15:48 CONTROL --- --- --- --- NA NA
Solution 8
68 Pre-Wash NA 39500 11/25/0 15:48 TEST X X X X NA NA
Solution 8
58 Pre-Wash NA 39500 11/25/0 15:48 TEST X X X X NA NA
Solution 8
10 Pre-Wash NA 39611 12/09/0 09:33 CONTROL --- --- --- --- TBD TBD
Solution 8
15 Pre-Wash NA 39611 12/09/0 09:33 CONTROL --- --- --- --- TBD TBD
Solution 8
20 Pre-Wash NA 39500 12/09/0 09:33 TEST X X X Peak at 20.82 TBD TBD
Solution 8
14 Pre-Wash NA 39500 12/09/0 09:33 TEST X X X Peak at 20.82 TBD TBD
Solution 8
17 Pre-Wash NA 39602 12/08/0 15:00 CONTROL --- --- --- --- NA NA
Solution 8
24 Pre-Wash NA 39602 12/08/0 15:00 CONTROL --- --- --- --- NA NA
Solution 8
4 Pre-Wash NA 39488 12/08/0 15:00 TEST X X X X NA NA
Solution 8
18 Pre-Wash NA 39488 12/08/0 15:00 TEST X X X X NA NA
Solution 8
31 Pre-Wash NA 39602 12/04/0 10:33 CONTROL --- --- --- --- NA NA
Solution 8
46 Pre-Wash NA 39602 12/04/0 10:33 CONTROL --- --- --- --- NA NA
Solution 8
37 Pre-Wash NA 39488 12/04/0 10:33 TEST X X X X NA NA
Solution 8
36 Pre-Wash NA 39488 12/04/0 10:33 TEST X X X X NA NA
Solution 8
53 Pre-Wash NA 39602 11/25/0 10:47 CONTROL --- --- --- --- NA NA
Solution 8
54 Pre-Wash NA 39602 11/25/0 10:47 CONTROL --- --- --- --- NA NA
Solution 8
59 Pre-Wash NA 39488 11/25/0 10:47 TEST X X X X NA NA
Solution 8

BAXTER CONFIDENTIAL
Study Number: 45273 Page 18 of 19
Data Transmittal Report 1

74 Pre-Wash NA 39488 11/25/0 10:47 TEST X X X X NA NA


Solution 8
21 Pre-Wash NA 39214 12/08/0 10:04 CONTROL --- --- --- --- NA NA
Solution 8
3 Pre-Wash NA 39214 12/08/0 10:04 CONTROL --- --- --- --- NA NA
Solution 8
6 Pre-Wash NA 39446 12/08/0 10:04 TEST X X X X NA NA
Solution 8
7 Pre-Wash NA 39446 12/08/0 10:04 TEST X X X X NA NA
Solution 8
38 Pre-Wash NA 39214 12/03/0 11:23 CONTROL --- --- --- --- NA NA
Solution 8
30 Pre-Wash NA 39214 12/03/0 11:23 CONTROL --- --- --- --- NA NA
Solution 8
34 Pre-Wash NA 39446 12/03/0 11:23 TEST X X X X NA NA
Solution 8
43 Pre-Wash NA 39446 12/03/0 11:23 TEST X X X X NA NA
Solution 8
52 Pre-Wash NA 39214 11/24/0 15:05 CONTROL --- --- --- --- NA NA
Solution 8
66 Pre-Wash NA 39214 11/24/0 15:05 CONTROL --- --- --- --- NA NA
Solution 8
56 Pre-Wash NA 39446 11/24/0 15:10 TEST X X X X NA NA
Solution 8
57 Pre-Wash NA 39446 11/24/0 15:10 TEST Peak at ~ X X X NA NA
Solution 8 12min

1= Peaks in “control” from 12.6 to 15.9miutes but not seen in the other “control” or either “Test”.
2 = Strong Peak at 20.8 minutes. Sample was submitted for NMR and GC-MS Anlaysis.
NA = Not Applicable
TBD = To be Determined.

BAXTER CONFIDENTIAL
Study Number: 45273 Page 19 of 19
Data Transmittal Report 1

The results in Table 4 show that the majority of samples showed no differences in the chromatographic profiles for
SEC-RI, SEC-UV at 280nm, SEC-UV at 220nm or LC-MS. The only sample that showed a difference was RL
samples 20 and 14. These “test” samples along with their corresponding “control” were submitted for NMR and
GC-MS analyses and will be reported in the final report. The only other observation was a peak observed in the
SEC-RI profile at ~ 12 minutes for “test” RL sample 57. No differences were found for this sample when
compared by SEC-UV at 220nm, SEC-UV at 280nm or LC-MS. Since the other control (RL sample 56) was
consistent with its corresponding “controls” no further test was performed.

CONCLUSION

Based on the testing performed in this study, the “test” CUNO resin has no impact on product integrity during the
production of Suspension B @ 17%, II+III Extract and Fr IV-4 @ 40% for albumin and IGIV from the LA facility.
The few differences observed from the “test” CUNO resin when compared to its corresponding control can be
attributed to ether protein contamination or higher alcohol content.

DOCUMENTATION

Original data and reports associated with this study will be archived following SOP 190501027, Multi-Divisional
Archive Service Procedure.

References:

1. Feasibility Study of Resin Change for CUNO 70CP, by Trang Huynh, Bioscience. Test Protocol
LB08EXP141. Project Number 36819555. September 26th, 2008.

Procedures:

1. Technology Resources Standard Procedure YY-005-004, Recording Original Data. Current Issue.

2. Technology Resources Standard Procedure YY-005-005, Writing Reports. Current Issue.

3. Multi-Divisional Archive Service Procedure Specification 190501027. Current Issue.

4. Technology Resources Standard Procedure PB-011-001. Use and Operation of High Performance Liquid
Chromatography Systems. Current Issue.

5. Technology Resources Standard Procedure PA-011-005, Operation and Maintenance of the Bruker
Avance III 600 AND Avance I 400 NMR Spectrometers. Current Issue.

6. Technology Resources Standard Procedure 1109105, Calibration, Operation and Maintenance of Mass
Spectrometers and their Data Systems. Current Issue.

7. Technology Resources Standard Procedure 1096378, Operation and Calibration of the Digilab FTS 7000
Fourier Transform Infrared Spectrometer. Current Issue.

BAXTER CONFIDENTIAL