Extractables Analysis of Single-Use Flexible Plastic Biocontainers

Abstract

The usage of single-use bioreactors has been increasing in biopharmaceutical industry because of the appealing advantages that it promises regarding to the cleaning, sterilization, operational flexibility, and so on, during manufacturing of biologics. However, compared to its conventional counterparts based mainly on stainless steel, single-use bioreactors are more susceptible to potential problems associated with compound leaching into the bioprocessing fluid. As a result, extractable profiling of the single-use system has become essential in the qualification of such systems for its use in drug manufacturing. The aim of this study is to evaluate the effectiveness of an extraction solvent system developed to study the extraction profile of single-use bioreactors in which aqueous-based systems are largely used. The results showed that with a non-targeted analytical approach, the extraction solvent allowed the generation and identification of an array of extractable compounds from four commercially available single-use bioreactors. Most of extractables are degradation products of polymer additives, among which was a compound that was later found to be highly detrimental to mammalian cell growth.

Improvements in single‐use bioreactor film material composition leads to robust and reliable Chinese hamster ovary cell performance

“…The groups of compounds with specific functions that were identified in the samples are also reported in Table . Several of these compounds were already reported previously . Intact Irgafos®168 was not detected under any extraction condition.…”

“…Several of these compounds were already reported previously. [36][37][38] Intact Irgafos ® 168 was not detected under any extraction condition.…”

Identification of chemical species created during γ‐irradiation of antioxidant used in polyethylene and polyethylene‐co‐vinyl acetate multilayer film

“…3.1.13 in order to represent widely used primary sterically hindered phenolic AOs and secondary phosphite AOs. Additives 1-4 (Table 1) were purchased from Sigma-Aldrich (Saint-Quentin Fallavier, France) and sterilized in the glass flask at room temperature using a 60 Co γ-source providing a dose rate of 8-13 kGy/h-as given by Synergy Health Marseille, France, at 25 (± 5), 50 (± 5), and up 115 (± 5) and 270 (± 5) kGy. The doses at 115 kGy and 270 kGy were used to exaggerate the effect obtained at 25-45 kGy so that higher quantities were obtained and investigation was made easier.…”

Process‐relevant concentrations of the leachable bDtBPP impact negatively on CHO cell production characteristics

“…More emphasis has been placed on the identification and pharmacological testing of new leachable compounds and their risks to patient safety. 12 In this study, we provide for the first time insight into the mechanism by which bDtBPP inhibits cell proliferation.…”

“…However, despite it being established that this is a real‐time problem associated with single‐use technology, very little has been invested in deciphering the mechanism by which bDtBPP effects bioprocess critical CHO cell phenotypes, the quality of the produced product or if the compound itself remains present after downstream purification. More emphasis has been placed on the identification and pharmacological testing of new leachable compounds and their risks to patient safety . In this study, we provide for the first time insight into the mechanism by which bDtBPP inhibits cell proliferation.…”