Chemic Laboratories Inc. 480 Neponset Street, Bldg. 7 Canton, MA 02021 781-821-5600 www.chemiclabs.com Extractables Evaluation of a Single-Use Bioprocess Bag According to Published Recommendations April 2016 Copyright Chemic Laboratories Inc., 2016 1
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Extractables Evaluation of a Single-Use Bioprocess Bag According to Published Recommendations
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Chemic Laboratories Inc.480 Neponset Street, Bldg. 7Canton, MA 02021781-821-5600www.chemiclabs.com
Extractables Evaluation of a Single-Use Bioprocess Bag
According to Published Recommendations
April 2016
Copyright Chemic Laboratories Inc., 20161
Study Objective
An independent evaluation comparing various SUS extractable study parameters .
To generate data sufficient to evaluate the merit of solvents, times, analytical techniques, and procedures.
To evaluate and optimize analytical methodologies with a consideration toward extract compatibility.
Commercially available 1-liter 2D bioprocess bags were γ-irradiated at 45-55 kGy and all associated components (ports, tubing, etc.) were removed and heat sealed with an internal wetted surface area of 726 cm2. Each test sample was filled with 121 mL of extraction solvent in order to achieve a 6:1 (cm2/mL) surface area: volume ratio.
Copyright Chemic Laboratories Inc., 20165
Study Design
Samples were prepared for each solvent & each time point, placed in secondary containment within an incubator. The study was staged in reverse within 5 weeks of γ-irradiation.
At termination the sample extracts and controls were placed into inert containers for analytical testing.
Copyright Chemic Laboratories Inc., 20166
Solvent
% Solvent Loss (w/w)
24 hours at 40°C
21 days at 40°C
30 days at 40°C
70 days at 40°C
50% EtOH 0.12% 2.6% 3.7% 8.7%
1% PS-80 0.093% 2.0% 2.6% 6.0%
5M NaCl 0.058% 1.1% 1.4% 3.3%
0.5N NaOH 0.078% 2.0% 2.4% 5.4%
0.1M H3PO4 0.080% 2.0% 2.7% 5.2%
USP H2O 0.087% 1.9% 2.6% 5.9%
HEX 0.0% 1.8% 2.1% 5.2%
100% EtOH - - - 12%
100% IPA - - - 0.0%
0.01M HCl - - - 6.0%
Solvent Loss
By ensuring the integrity of the sealing procedure and using secondary containment, solvent loss was not a significant concern.
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pH Results
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NVR Results
DescriptionExtraction
SolventMass Difference (initial vs. final)
NVR (μg/cm2)
Method Control USP H2O -0.0003 NA
Sample Extract USP H2O 0.0003 0.93
Method Control Hexane 0.0001 NA
Sample Extract Hexane 0.0982 300
70 day USP Water & Hexane extracts were transferred to appropriately cleaned vessels and evaporated to dryness.
Copyright Chemic Laboratories Inc., 20169
TOC Results Notables
Devitrification of quartz and catalyst poisoning due to sodium content of extract solutions.
Chemic has invested in 2 new state of the art TOC units, a combustion unit and a UV persulfate unit to resolve this issue.
The data demonstrated the presence of extractable peaks in all solvents with the exception of 5M NaCl, 0.1M H3PO4, USP H2O and 0.01M HCl.
n-Octane was initially evaluated and response was erratic due to its volatility.
An extraction surrogate is added to monitor the efficiency of the liquid-liquid exchange procedure. The behavior of the surrogate may not be representative of all “unknowns”.