| Title: | Large-Scale Assessment of Extractables and Leachables in Single-Use Bags for Biomanufacturing |
| Author(s): | Dorival-Garcia N; Carillo S; Ta C; Roberts D; Comstock K; Lofthouse S; Ciceri E; D'Silva K; Kierans G; Kaisermayer C; Lindeberg A; Bones J; |
| Address: | "Characterization and Comparability Laboratory , NIBRT-The National Institute for Bioprocessing Research and Training , Foster Avenue, Mount Merrion, Blackrock, Co. , Dublin , Ireland. Thermo Fisher Scientific , Manor Park, Tudor Rd , Cheshire , Runcorn WA7 1TA , United Kingdom. Thermo Fisher Scientific , 355 River Oaks Pkwy , San Jose , California 95134 , United States. Thermo Fisher Scientific , Stafford House, Boundary Park , Hemel Hempstead HP2 7GE , United Kingdom. Thermo Fisher Scientific , Via Milano, 4 , 20090 Rodano , MI , Italy. Pfizer Ireland Pharmaceuticals , Grange Castle Business Park, Nangor Road , Clondalkin , Dublin 22 D22 V8F8 , Ireland. BioMarin International Limited , Shanbally, Ringaskiddy , Co. Cork P43 R298 , Ireland. School of Chemical and Bioprocess Engineering , University College Dublin , Belfield, Dublin 4 , Ireland" |
| DOI: | 10.1021/acs.analchem.8b01208 |
| ISSN/ISBN: | 1520-6882 (Electronic) 0003-2700 (Linking) |
| Abstract: | "Single-use technologies (SUTs) are widely used during biopharmaceutical manufacture as disposable bioreactors or media and buffer storage bags. Despite their advantages, the risk of release of extractable and leachable (E&Ls) substances is considered an important drawback in adopting disposables in the biomanufacturing process. E&Ls may detrimentally affect cell viability or productivity or may persist during purification and present a risk to the patient if remaining in the final drug product. In this study, 34 plastic films from single-use bags (SUBs) for cell cultivation were extracted with selected solvents that represent reasonable worst-case conditions for most typical biomanufacturing applications. SUBs were incubated at small-scale under accelerated-aging conditions that represented standard operational conditions of use. Leachables analysis was performed following dispersive liquid-liquid microextraction (DLLME) for analyte preconcentration and removal of matrix interference. Resulting extracts were characterized by GC-headspace for volatiles, high resolution GC-Orbitrap-MS/MS for semivolatiles, high resolution LC-Orbitrap-MS/MS for nonvolatiles, and ICP-MS for trace elemental analysis. Multivariate statistical analysis of the analytical data revealed significant correlations between the type and concentration of compounds and bags features including brand, manufacturing date and polymer type. The analytical data demonstrates that, over recent years, the nature of E&Ls has been altered due to the implementation of manufacturing changes and new types of polymers and may change further with the future advent of regulations that will limit or ban the use of certain raw materials and additives. 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" |
| Keywords: | "Biological Products/chemistry Chromatography, Liquid/instrumentation/methods *Drug Contamination/prevention & control Drug Packaging/instrumentation/*methods Equipment Design Gas Chromatography-Mass Spectrometry/instrumentation/methods Humans Liquid Phase;" |
| Notes: | "MedlineDorival-Garcia, Noemi Carillo, Sara Ta, Christine Roberts, Dominic Comstock, Kate Lofthouse, Simon Ciceri, Elena D'Silva, Kyle Kierans, Gerald Kaisermayer, Christian Lindeberg, Anna Bones, Jonathan eng Research Support, Non-U.S. Gov't 2018/06/27 Anal Chem. 2018 Aug 7; 90(15):9006-9015. doi: 10.1021/acs.analchem.8b01208. Epub 2018 Jul 13" |
