Journal ArticleDOI
Extractables analysis of single-use flexible plastic biocontainers.
Liliana Marghitoiu,Jian Liu,Hans Lee,Lourdes Perez,Kiyoshi Fujimori,Michael Ronk,Matthew R. Hammond,Heather Nunn,Asher Lower,Gary Rogers,Yasser Nashed-Samuel +10 more
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TLDR
An effective extraction solvent system was developed to evaluate the organic extractable profiles of single-use bioprocess equipment, which has been gaining increasing popularity in the biopharmaceutical industry because of the many advantages over the traditional stainless steel-based bioreactors and other fluid mixing and storage vessels.Abstract:
Studies of the extractable profiles of bioprocessing components have become an integral part of drug development efforts to minimize possible compromise in process performance, decrease in drug product quality, and potential safety risk to patients due to the possibility of small molecules leaching out from the components. In this study, an effective extraction solvent system was developed to evaluate the organic extractable profiles of single-use bioprocess equipment, which has been gaining increasing popularity in the biopharmaceutical industry because of the many advantages over the traditional stainless steel-based bioreactors and other fluid mixing and storage vessels. The chosen extraction conditions were intended to represent aggressive conditions relative to the application of single-use bags in biopharmaceutical manufacture, in which aqueous based systems are largely utilized. Those extraction conditions, along with a non-targeted analytical strategy, allowed for the generation and identification of an array of extractable compounds; a total of 53 organic compounds were identified from four types of commercially available single-use bags, the majority of which are degradation products of polymer additives. The success of this overall extractables analysis strategy was reflected partially by the effectiveness in the extraction and identification of a compound that was later found to be highly detrimental to mammalian cell growth. LAY 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.read more
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Journal ArticleDOI
Process-relevant concentrations of the leachable bDtBPP impact negatively on CHO cell production characteristics.
Paul S. Kelly,Shane McSweeney,Orla Coleman,Sara Carillo,Sara Carillo,Michael Henry,Deepak Chandran,Andrew Kellett,Jonathan Bones,Jonathan Bones,Martin Clynes,Paula Meleady,Niall Barron +12 more
TL;DR: It is demonstrated that this compound when spiked at meaningful concentrations 72 h into culture considerably reduces the maximum cell density achieved, reinforcing the requirement for the complete characterization of all potential leachable compounds from disposable materials to assess their risk not only to the patient but also to the production pipeline itself.
Journal ArticleDOI
Identification, analysis and safety assessment of leachables and extractables
TL;DR: In this article, the potential adverse effect of leachables on patient safety can be established via chemical safety risk assessment, which involves comparing a DP user's (patient) exposure to individual leachable with exposure thresholds which are toxicologically established for the individual leACHables.
Journal ArticleDOI
Materials in Manufacturing and Packaging Systems as Sources of Elemental Impurities in Packaged Drug Products: A Literature Review
TL;DR: A joint team from the Extractables and Leachables Safety Information Exchange (ELSIE) Consortium and the International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS) has conducted a review of the available literature on elemental entities in pharmaceutically relevant polymers and the presence of these elemental entity in material extracts and/or drug products.
Journal ArticleDOI
Qualitative assessment of extractables from single-use components and the impact of reference standard selection
Mark Anderson Jordi,Smriti Khera,Kevin Roland,Liuwei Jiang,Paige Solomon,Jenny Nelson,Syed Lateef,James Woods,Leland Martin,Samantha Martin,Frankie Aiello,Nina Chen +11 more
TL;DR: The results of this study demonstrate that significant care should be taken when selecting standards for LC/MS analysis to avoid under reporting of extractables and leachables.
Journal ArticleDOI
Large-Scale Assessment of Extractables and Leachables in Single-Use Bags for Biomanufacturing
Noemí Dorival-García,Sara Carillo,Christine Ta,Dominic Roberts,Kate Comstock,Simon Lofthouse,Elena Ciceri,Kyle D’Silva,Gerald Kierans,Christian Kaisermayer,Anna Lindeberg,Jonathan Bones,Jonathan Bones +12 more
TL;DR: The broad E&L database generated herein facilitates toxicological assessments from a biomanufacturing standpoint and provides practical guidelines for confident determination of E& Ls to enable screening and elimination of nonsatisfactory films for single use bioprocessing.
References
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Book ChapterDOI
Disposable bioreactor for cell culture using wave-induced agitation
TL;DR: A novel bioreactor system for the cultivation of animal, insect, and plant cells using wave agitation induced by a rocking motion that provides good nutrient distribution, off-bottom suspension, and excellent oxygen transfer without damaging fluid shear or gas bubbles is described.
Journal ArticleDOI
Disposable bioreactors: the current state-of-the-art and recommended applications in biotechnology.
TL;DR: Analysis of the data from computational fluid dynamic simulation studies and first cultivation runs confirms that this novel bioreactor system is a viable alternative to traditional cell culture bioreactors at benchtop scale.
Journal ArticleDOI
Disposable bioreactor for cell culture using wave-induced agitation.
TL;DR: In this article, a wave agitation system for the cultivation of animal, insect, and plant cells using wave agitation induced by a rocking motion is described, which provides good nutrient distribution, off-bottom suspension, and excellent oxygen transfer without damaging fluid shear or gas bubbles.
Journal ArticleDOI
Disposable bioprocessing: the future has arrived.
TL;DR: Progress made in the incorporation of disposable equipment with sensor technology in bioprocessing throughout the development cycle is focused on, noting that sensor patch technology is mostly being adapted to disposable cell culture devices, but future adaptation to downstream steps is conceivable.
Journal ArticleDOI
Optimisation of protein expression and establishment of the Wave Bioreactor for Baculovirus/insect cell culture.
TL;DR: The set-up and the optimisation of parameters essential for successful operation and growth of insect cells to high cell densities in the Wave Bioreactor are described and a rapid and simple protocol for assessing expression and production conditions for the Baculovirus/insect cell system applicable to many different genes/proteins is developed.