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Silicone Pump Tubing for Fill Finish Applications

Sani-Tech® SPT-60L is tested against the competition, see how we compare.

Precision Final Fill Pump Tubing Performance White Paper

In assessing the suitability of tubing for peristaltic pump filling processes, important performance parameters for examination are pump life, spallation, and effect on dosing accuracy. The influence of tubing selection on the filling process can be evidenced through operational reliability (range of pump life with filling equipment), impact to product being transferred (particulate shedding or spall), and the ability to hit dosing targets correctly and consistently.

Silicone tubing is often chosen for fill finish pumping applications because of its compatibility with drug proteins, low extractables, and retention of physical properties over a wide temperature range (low compression set, flexibility, kink resistance, etc.). As silicone tubing differs in formulation and processing from supplier to supplier, differences can be expected in silicone tubing performance parameters as well. This paper focuses on the performance of five different platinum-cured silicone tubing products that are marketed for biopharma filling applications. The tests measure filling accuracy and precision, pump life, and the degree of spallation generation.
 

Saint-Gobain Sani-Tech® SPT-60L provides four times improvement in filling accuracy and two times improvement in precision over the closest performing competitor tubing."

Heidi Lennon
Senior Research Engineer, Saint-Gobain Bioprocess Solutions

Fill Precision and Accuracy (materials and methods)

Dispensed volume should correspond to the intended dose (accuracy) and be reproducible over time (precision). Providing the correct volume of drug product in the final container is critical for proper dose delivery aside from the cost impact of over/underfilling (excess product, rejected containers).

Saint-Gobain silicone tube testing
Saint-Gobain Life Sciences’ lab test environment
Silicone Tubing

Sani-Tech® SPT-60L was tested against four other silicone tubing products marketed for biopharma filling applications and tested for vial fill accuracy (dispensing target fill volume) and precision (repeatability of delivered volume). All silicone tubes were 1/16” x 3/16” ID x OD (1.6 x 4.8 mm). The silicone tubes and size were selected to represent tubing used in final fill drug manufacturing. Tubing was tested as non-irradiated and after gamma irradiation. Gamma irradiation was performed by STERIS (Libertyville, IL USA) at a delivered dose of average 42 kiloGray (kGy).

Data Collection

Vial fill precision and accuracy was automated with the OHAUS® Explorer® EX4202 electronic scale paired with Winwedge software for data collection of a RS232 instrument directly into Excel. Water was dispensed into a 2,000 ml flask with a mineral oil trap to avoid evaporation using a stainless steel AISI 316 L filling nozzle 30-030-016 (Watson-Marlow Flexicon A/S Ringsted, Denmark). The filling nozzle (1/16” ID (1.6 mm)) was chosen for the targeted fill volume of 1.8 ml.

Benchtop Filler

A Flexicon® PF7 peristaltic filling machine by Watson Marlow was used in the study. Settings for the filling system were speed 300 and 400 RPM, acceleration of 100, deceleration of 100, and 10 sec fill delay. The fill delay was to allow time for the scale to stabilize between readings. Gamma irradiated tubing was tested at both 300 and 400 RPM with the same 1.8 ml targeted fill volume. All other settings remained the same.

Results Non-Irradiated vs. Gamma Irradiated Tubing

A histogram fit shows the results of 1,000 vial fills performed in duplicate for both non-irradiated and irradiated pump tubes. The histograms allow for visualization of the accuracy (target fill) and precision (repeatability) of filling performance at 400 RPM for the 1.8 ml target volume. 

All tubes were calibrated to hit the target of 1.8mL on the first dispense. The deviation from the target and the deterioration of the tubing is measured here.
All tubes were calibrated to hit the target of 1.8mL on the first dispense. The deviation from the target and the deterioration of the tubing is measured here.

Pump Life (materials and methods)

Extended pump life provides assurance that tubing will deliver continued performance under a variety of pump conditions without rupturing.

Pump life was tested via an internal test method for determining the life of tubing until failure on non-irradiated tubing. This procedure used a Cole-Parmer® Masterflex® L/S® drive with a Masterflex® L/S® standard pump head (3 rollers) or an Easy-Load® II (4 rollers) pump head. Three different test conditions were used as shown in table (B.1) below.

Sani-Tech® SPT-60L was tested against competitive silicone tubing for pump life on a Cole-Parmer® Masterflex® L/S® drive with either a Masterflex® L/S® standard pump head (3 rollers) or an Easy-Load® II (4 rollers) pump head under different test conditions.

Sani-Tech SPT-60L was shown to have longer pump life over other platinum-cured silicone tubing. Sani-Tech SPT-60L’s long pump life provides customers with assurance that the tubing will provide continued performance under a variety of pump conditions.

Sani-Tech® SPT-60L Pump LIfe
Discover More Testing Details

Dive into the data of this white paper to see exactly how Sani-Tech® SPT-60L stacks up against the competition.

- Fill Precision and Accuracy

- Pump Life

- Spallation

Spallation (materials and methods)

Spallation (or particle shedding) results from the shear-compression force in a peristaltic pump causing the release of particles from tubing. For injectable products, industry guidance provides the target of drug products that are ‘essentially free’ of particles, while current regulations establish the number and size of particles allowable per volume. Selecting a peristaltic pump tubing for final filling with low spallation is critical because the filling operation occurs after the final sterile filtration step.

Silicone Tubing

Five different silicone tubes that are used in biopharma were selected to evaluate spallation. All silicone tubes were 1/16” x 3/16” ID x OD (1.6 x 4.8 mm). The silicone tubes and size were selected to represent tubing used in final fill drug manufacturing. Tubing was tested as non- irradiated and after gamma irradiation. Gamma irradiation was performed by STERIS (Libertyville, IL USA) at a delivered dose of average 42 kiloGray (kGy).

Flow Microscopy

Spallation was analyzed using imaging flow cytometry (IFC). FlowCam™ 8000 (Fluid-Imaging Technologies Scarborough, ME) is a flow imaging cytometer (particle counter) and particle analyzer that is paired with image analysis software VisualSpreadsheet® Particle Analysis Software Version 4. A flowrate of 5 ml/ min was used at a magnification of 4x. No size filter and an auto image rate of 50 frames/second was used. The flow cell (FC300FV) had a 300 μm flow cell depth and a 1500 μm flow cell width.

Benchtop Filler

A Flexicon® PF7 peristaltic filling machine by Watson Marlow was used in the study with a speed of 300 RPM, acceleration of 100, and deceleration of 100 with a fill delay of 1 second. Targeted fill volume for this study was 1.8 ml. The benchtop filler, along with the IFC, was placed in an Air Science® LF Series laminar flow cabinet to avoid contamination. Water was dispensed from a Milli-Q® IQ 7000 (Millipore Sigma) Ultrapure Lab water system setup with a 0.22 μm filter.

Method

Surface Roughness

Surface roughness was examined along the cross-section of the tube before pumping, using a Nanovea 3D Surface Profilometer (white light chromatic aberration technique). One area was scanned on the surface of each tube, two tubes for each sample.

SEM

A Zeis Merlin SEM was used to take high resolution images of the cross-section of the tubes that was within the pump head before and after pumping. Samples were prepped with a Quorum Q Series 150T ES sputter coater to deposit a thin layer of conducting Au material on the specimen surface.

Sani-Tech® SPT-60L Tube WallTubs C Wall
SPT-60L after pumping view of material shedding from tubing
Sani-Tech® SPT-60L after pumping. The center of the image is the inner surface of the tubing.
After pumping view of material shedding from tubing
Tube C after pumping shows material shedding from the tubing. The center of the image is the inner surface of the tubing.

Spallation

Spallation measurement methods typically sample a small amount of recirculated fluid (<10%) during pump tests (1-3). This methodology was not chosen because it was found that the particles that come off are not homogeneous in the fluid. In this study, small differences between silicone tubes were being investigated. After 1,000 cycles there may only be 1-5 large particles (>100 µm) in the entire fluid (100 ml) that was recirculated. It was important to be able to count these particles when they come off the tube to be able to make an accurate analysis.

To provide a more accurate representation of the particles generated over time, a modified method was created to compare the silicone tubes. 25 ml of UltraPure water was run through the FlowCam® 8000 as a blank first. Tubing was loaded on the Flexicon® PF7 pump and the first 3 vial fills of 1.8 ml was discarded to rinse the tubing of any contamination. The test was done without a needle at the end of the tubing. 100 ml of Ultrapure water was recirculated through the pump for 1,000 cycles at 300 RPM. The entire flask of 100 ml of recirculated (pumped) water was sampled through the IFC at a rate of 5 ml/min and at a magnification of 4x. This was repeated for 1,000 cycles and then another 1,000 cycles, each time with new 100 ml of UltraPure water. The IFC sampled the entire fluid pumped for the first 1,000, second 1,000, and third 1,000 cycles of vial fills. The tubing was not touched during the entire test to complete a total cycle of 3,000 vial fills. This test was done in duplicate for all 5 of the silicone pump tubes that were selected.

After 1,000 cycles there may only be 1-5 particles > 100 µm in the entire fluid (100 ml) that was recirculated.

References:

  1. Cheng Her, L. M. (2020). Effects of Tubing Type, Operating Parameters, and Surfactants on Particle Formation During Peristaltic Filling Pump Processing of a mAb Formulation. Journal of Pharmaceutical Sciences, 1439-1448.
  2. Romansky, S. M. (2002). Spalling and Sorption of Tubing for Peristaltic Pumps. Pharmaceutical Development and Technology, 317-323.
  3. Verena Saller, J. M.-P.-C. (2014). Particle Shedding from Peristaltic Pump Tubing in Biopharmaceutical Drug Product Manufacturing. Pharmaceutics, Drug Delivery and Pharmaceutical Technology, 1440-1450.

Saint-Gobain Tested Materials, Trusted Performance

Sani-Tech® SPT-60L was shown to have both similar surface roughness and SEM morphology images as other silicone tubes chosen in this study prior to pumping, but the SEM images and spallation after pumping show a significant difference between silicone pump tubes. Tube C showed clear abrasion of the surface that was consistent with spallation data. Non- irradiated Sani-Tech SPT-60L was shown to have both low spallation counts and total area of spallation released. After gamma irradiation, Sani-Tech SPT-60L and Tube A have a similar particle count, but the total area of particles released shows that Tube A released larger particles than Sani-Tech SPT-60L. Sani- Tech SPT-60L produced smaller particles, and Tube A produced larger particles. Tube C’s spallation was the largest of all of the tubes and was visible in SEM images with clear deterioration of the surface after pumping. Sani-Tech SPT-60L produced low spall when compared to other silicone pump tubes, both before and after gamma irradiation.

Precise filling, long pump life, and low spallation generation has shown Sani- Tech® SPT-60L fill finish tubing to be a superior final fill pump tubing when compared against other silicone tubing marketed for biopharma filling. With up to 250 hr pumping (depending on the fluid and pumping conditions), filling accuracy and precision was maintained over time with low spallation generation. Sani-Tech SPT-60L has been recommended by key filling equipment manufacturers for their customers based on these properties. Download the white paper for the full details.
 

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