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- Brinson, Robert G., et al.
(author)
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Enabling adoption of 2D-NMR for the higher order structure assessment of monoclonal antibody therapeutics
- 2019
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In: mAbs. - : Informa UK Limited. - 1942-0862 .- 1942-0870. ; 11:1, s. 94-105
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Journal article (peer-reviewed)abstract
- The increased interest in using monoclonal antibodies (mAbs) as a platform for biopharmaceuticals has led to the need for new analytical techniques that can precisely assess physicochemical properties of these large and very complex drugs for the purpose of correctly identifying quality attributes (QA). One QA, higher order structure (HOS), is unique to biopharmaceuticals and essential for establishing consistency in biopharmaceutical manufacturing, detecting process-related variations from manufacturing changes and establishing comparability between biologic products. To address this measurement challenge, two-dimensional nuclear magnetic resonance spectroscopy (2D-NMR) methods were introduced that allow for the precise atomic-level comparison of the HOS between two proteins, including mAbs. Here, an inter-laboratory comparison involving 26 industrial, government and academic laboratories worldwide was performed as a benchmark using the NISTmAb, from the National Institute of Standards and Technology (NIST), to facilitate the translation of the 2D-NMR method into routine use for biopharmaceutical product development. Two-dimensional H-1,N-15 and H-1,C-13 NMR spectra were acquired with harmonized experimental protocols on the unlabeled Fab domain and a uniformly enriched-N-15, 20%-C-13-enriched system suitability sample derived from the NISTmAb. Chemometric analyses from over 400 spectral maps acquired on 39 different NMR spectrometers ranging from 500 MHz to 900 MHz demonstrate spectral fingerprints that are fit-for-purpose for the assessment of HOS. The 2D-NMR method is shown to provide the measurement reliability needed to move the technique from an emerging technology to a harmonized, routine measurement that can be generally applied with great confidence to high precision assessments of the HOS of mAb-based biotherapeutics.
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| 2. |
- Swart, Sebastiaan, 1983, et al.
(author)
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Constraining Southern ocean air-sea-ice fluxes through enhanced observations
- 2019
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In: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6
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Research review (peer-reviewed)abstract
- © 2019 Swart, Gille, Delille, Josey, Mazloff, Newman, Thompson, Thomson, Ward, Du Plessis, Kent, Girton, Gregor, H, Hyder, Pezzi, De Souza, Tamsitt, Weller and Zappa. Air-sea and air-sea-ice fluxes in the Southern Ocean play a critical role in global climate through their impact on the overturning circulation and oceanic heat and carbon uptake. The challenging conditions in the Southern Ocean have led to sparse spatial and temporal coverage of observations. This has led to a 'knowledge gap' that increases uncertainty in atmosphere and ocean dynamics and boundary-layer thermodynamic processes, impeding improvements in weather and climate models. Improvements will require both process-based research to understand the mechanisms governing air-sea exchange and a significant expansion of the observing system. This will improve flux parameterizations and reduce uncertainty associated with bulk formulae and satellite observations. Improved estimates spanning the full Southern Ocean will need to take advantage of ships, surface moorings, and the growing capabilities of autonomous platforms with robust and miniaturized sensors. A key challenge is to identify observing system sampling requirements. This requires models, Observing System Simulation Experiments (OSSEs), and assessments of the specific spatial-temporal accuracy and resolution required for priority science and assessment of observational uncertainties of the mean state and direct flux measurements. Year-round, high-quality, quasi-continuous in situ flux measurements and observations of extreme events are needed to validate, improve and characterize uncertainties in blended reanalysis products and satellite data as well as to improve parameterizations. Building a robust observing system will require community consensus on observational methodologies, observational priorities, and effective strategies for data management and discovery.
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