Do plasticized polyvinylchloride and polyurethane infusion sets promote infliximab adsorption?

Philip Chennell,Valérie Sautou,Nicolas Tokhadzé

doi:10.1515/pthp-2020-0008

Abstract

AbstractObjectivesInfliximab diluted solutions have been shown to be physicochemically stable for long periods, however the adsorption of infliximab during infusions has not been readily investigated. This study aimed to evaluate potential adsorption phenomena of infliximab during administration through Polyvinylchloride (PVC) and Polyurethane (PU) infusion sets.MethodsInfliximab (INFLECTRA®) solutions at 0.4 mg/mL and 2 mg/mL were submitted to static (at T0, 24 and 96 h) and dynamic contact (flow rate of 2 mL/min during 2 h with analysis times at T0, 5 min, 30 min, 60 min and 120 min) with three different infusion sets. Two contained PVC plasticized with tris(2-ethylhexyl) trimellitate (TOTM) tubings and one set was in PU tubing. Infliximab was quantified at each analytical time by protein total quantification using UV-spectroscopy according to European Pharmacopeia Monography (2.5.33) and size exclusion chromatography (SEC) which allowed a specific quantification of the monomeric form and was able to highlight potential modification such as aggregation or oligomer formation.ResultsFor all analysis times and conditions, infliximab concentrations remained unchanged with a maximum variation of 2.81 and 4.63% from the initial concentrations assessed by SEC and UV spectroscopy and the percentage of monomeric form remained unaltered.ConclusionsOur study showed that there was no significant loss of infliximab. According to these results each of the three infusion sets could be used for the administration of infliximab solutions without causing any loss of active substance.

Highlights

Infliximab is an IgG1 monoclonal antibody that binds and inhibits transmembrane and soluble forms of Tumor Necro-sis Factor alpha (TNF-α)
Even though polymeric-based surfaces are always found in medical devices used for infusion, and that they are known for interacting with small peptides, like cyclosporine or insulin [4,5,6], their potential interactions in clinical situations with monoclonal antibody (mAb) has not been fully studied
No loss of monomeric infliximab was noted by size exclusion chromatography (SEC) for either studied concentration or infusion tubing

Summary

Introduction

Infliximab is an IgG1 monoclonal antibody (mAb) that binds and inhibits transmembrane and soluble forms of Tumor Necro-sis Factor alpha (TNF-α). This biological medicine is approved for use in a wide range of diseases from diverse medical disciplines such as rheumatology, gastroenterology and dermatology, such as for example rheumatoid arthritis, spondylitis ankylosing and psoriatic arthritis, Crohn’s Disease, ulcerative colitis and psoriasis. Even though polymeric-based surfaces (polyvinyl chloride, silicone, polyurethane) are always found in medical devices used for infusion, and that they are known for interacting with small peptides, like cyclosporine or insulin [4,5,6], their potential interactions in clinical situations with mAbs has not been fully studied.

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