Effects of Transportation of IV Bags Containing Protein Formulations Via Hospital Pneumatic Tube System: Particle Characterization by Multiple Methods

Linkuvienė, Vaida; Ross, Emma L.; Crawford, Lindsey B.; Weiser, Sarah; Man, Damen; Kay, Stephen; Kolhe, Parag; Carpenter, John F.

doi:10.1016/j.xphs.2022.01.016

Cited by 18 publications

(11 citation statements)

References 139 publications

(258 reference statements)

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“…A key confounding factor related to the risk assessment is whether air is removed from the plastic bag. Indeed, here, at the opposite to what was previously performed 6 , the air was removed from the plastic bag to reduce as much as possible the air-liquid interface to minimize the risks of oxidations. This modification in the preparation method before using the PTS seems to be the most important factor to justify using the PTS to transport the mAbs in a routine environment.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the manufacturers recommend that the product is administered within 24h after the dilution to minimize the risk of mAbs being altered. ; In this study, the container is a plastic bag instead of a glass vial which exhibits a wider air-liquid interface that may induces aggregates and the formation of visible/subvisible particles due to the shaking of the container during transportation 6 . In addition, several studies have demonstrated that the lack of PS20 or PS80 increases the adhesion and aggregation of mAbs to the plastic bag in polyvinylchloride (PVC) or polyolefin [7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical validation of pneumatic transportation systems for monoclonal antibodies

Coliat

Erb

Diemer

et al. 2023

Preprint

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Pneumatic transportation systems (PTS) were recently proposed as a method to carry ready-for-injection diluted monoclonal antibodies (mAbs) from the pharmacy to the bedside of patients. This method reduces transportation time and improves the efficiency of drug distribution process. However, mAbs are highly sensitive molecules for which subtle alterations may lead to deleterious clinical effects. These alterations can be caused by various external factors such as temperature, pH, pressure, and mechanical forces that may occur during transportation. Hence, it is essential to ensure that the mAbs transported by PTS remain stable and active throughout the transportation process. This study aims to determine the safety profile of PTS to transport 11 routinely used mAbs in a clinical setting through assessment of critical quality attributes (CQA) and orthogonal analysis. Hence, we performed aggregation/degradation profiling, post-translational modifications identification using complementary mass spectrometry-based methods, along with visible and subvisible particle formation determination by light absorbance and dynamic light scattering measurements. Altogether, these results highlight that PTS can be safely used for this purpose when air is removed from the bags during preparation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical validation of pneumatic transportation systems for monoclonal antibodies

Coliat

Erb

Diemer

et al. 2023

Preprint

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“…Finally, one recent study addressed the effect of mechanical shock upon transportation of a diluted non‐specified mAb in an intravenous (iv) bag in a hospital pneumatic tube system on particle generation. [ 7 ] It could be shown that there is a general trend for an increase in particle size ≥1 µm after transportation compared to hand‐carried control bags.…”

Section: Introductionmentioning

confidence: 99%

An exploratory study on the effect of mechanical stress on particle formation in monoclonal antibody infusions

Abdel‐Tawab

Banerjee

Kirchner

et al. 2023

Archiv der Pharmazie

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Monoclonal antibody infusions (mAb-i) are administered for the treatment of various diseases. They are often transported over long distances from the compounding site to the site of administration. However, transport studies are typically carried out with the original drug product but not with compounded mAb-i. To address this gap, the impact of mechanical stress on the formation of subvisible/nanoparticles in mAb-i was investigated by dynamic light scattering and flow imaging microscopy. Different mAb-i concentrations were subjected to vibrational orbital shaking and stored at 2-8°C up to 35 days. The screening revealed that pembrolizumab and bevacizumab infusions show the highest propensity for particle formation. Especially bevacizumab at low concentrations exhibited an increase in particle formation. Because of the unknown health risks associated with the long-term application of subvisible particles (SVPs)/ nanoparticles in infusion bags, stability studies carried out in the frame of licensing application procedures should also focus on SVP formation in mAb-i. In general, pharmacists should minimize the time of storage and mechanical stress during transport, especially in the case of low-concentrated mAb-i. Moreover, if siliconized syringes are used, they should be washed once with saline solution to minimize particle entry.

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“…Linkuviene et al recently evaluated the impact of PTS transportation on the level of subvisible particle formation in intravenous immunoglobulin (IVIG) and mAb solutions as a function of diluents (compatible and noncompatible diluents) and infusion bag material (polyvinyl chloride and polyolefin) . The level of subvisible particle formation was found to be influenced by the sensitivity of the protein, infusion bag material and type of diluent (normal saline versus D5W) . The authors concluded that protein products for IV administration should not be transported in a hospital PTS .…”

Section: Introductionmentioning

confidence: 99%

“…34 The authors concluded that protein products for IV administration should not be transported in a hospital PTS. 34 However, the test products used in their study did not contain a surfactant. Upon dilution of mAb drug product containing a surfactant in the IV bag, the risk of impact to product quality such as subvisible particulate formation may be influenced by the final concentration of surfactant.…”

Section: Introductionmentioning

confidence: 99%

Transportation of mAb Dosing Solution in Intravenous Bag: Impact of Manual, Vehicle, and Pneumatic Tube System Transportation Methods on Product Quality

Desai,

Colandene,

Crotts

et al. 2023

Mol. Pharmaceutics

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Monoclonal antibody (mAb) products for intravenous (IV) administration generally require aseptic compounding with a commercial diluent within a pharmacy. The prepared dosing solution in the IV bag may be transported to the dosing location via manual, vehicular, pneumatic tube system (PTS), or a combination of these methods. In this study, the type and level of physical stresses associated with these three methods and their product quality impact for relatively sensitive and stable mAbs were assessed. Vibration was found to be the main stress associated with manual and vehicle transportation methods, although this was at a relatively low level (<1 GRMS/Root-Mean-Square Acceleration). Shock and drop events, at relatively low levels, were also observed with these methods. PTS transportation showed substantially more intense shock, vibration, and drop stresses and the measured levels were up to 91 G/force of acceleration or deceleration, 3.7 GRMS and 39 G, respectively. Using a foam padding insert for PTS transportation reduced the shock level considerably (91 G to 59 G). Transportation of mAb dosing solutions in IV bags via different methods including PTS transportation variables caused a small increase in the subvisible particle counts and there was no change in submicrometer particle distribution. No visible particles and no significant change to soluble aggregate levels were observed after transportation. Strategies such as removal of IV bag headspace prior to transport and in-line filtration poststress reduced the subvisible particles counts. All tested transportation conditions showed negligible impact on other product quality attributes tested. Removal of IV bag headspace prior to PTS transport prevented formation of micro air bubbles and foaming compared to the unaltered IV bag. This study shows examples where manual, vehicle, and PTS transport methods did not significantly impact product quality, and provides evidence that mAb products that are appropriately stabilized in the dosing solution (e.g., with a surfactant) can be transported via a PTS.

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Effects of Transportation of IV Bags Containing Protein Formulations Via Hospital Pneumatic Tube System: Particle Characterization by Multiple Methods

Cited by 18 publications

References 139 publications

Clinical validation of pneumatic transportation systems for monoclonal antibodies

Clinical validation of pneumatic transportation systems for monoclonal antibodies

An exploratory study on the effect of mechanical stress on particle formation in monoclonal antibody infusions

Transportation of mAb Dosing Solution in Intravenous Bag: Impact of Manual, Vehicle, and Pneumatic Tube System Transportation Methods on Product Quality

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