Unknown

Dataset Information

0

Enabling adoption of 2D-NMR for the higher order structure assessment of monoclonal antibody therapeutics.


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 1H,15N and 1H,13C NMR spectra were acquired with harmonized experimental protocols on the unlabeled Fab domain and a uniformly enriched-15N, 20%-13C-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.

SUBMITTER: Brinson RG 

PROVIDER: S-EPMC6343768 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

Enabling adoption of 2D-NMR for the higher order structure assessment of monoclonal antibody therapeutics.

Brinson Robert G RG   Marino John P JP   Delaglio Frank F   Arbogast Luke W LW   Evans Ryan M RM   Kearsley Anthony A   Gingras Geneviève G   Ghasriani Houman H   Aubin Yves Y   Pierens Gregory K GK   Jia Xinying X   Mobli Mehdi M   Grant Hamish G HG   Keizer David W DW   Schweimer Kristian K   Ståhle Jonas J   Widmalm Göran G   Zartler Edward R ER   Lawrence Chad W CW   Reardon Patrick N PN   Cort John R JR   Xu Ping P   Ni Feng F   Yanaka Saeko S   Kato Koichi K   Parnham Stuart R SR   Tsao Desiree D   Blomgren Andreas A   Rundlöf Torgny T   Trieloff Nils N   Schmieder Peter P   Ross Alfred A   Skidmore Ken K   Chen Kang K   Keire David D   Freedberg Darón I DI   Suter-Stahel Thea T   Wider Gerhard G   Ilc Gregor G   Plavec Janez J   Bradley Scott A SA   Baldisseri Donna M DM   Sforça Mauricio Luis ML   Zeri Ana Carolina de Mattos ACM   Wei Julie Yu JY   Szabo Christina M CM   Amezcua Carlos A CA   Jordan John B JB   Wikström Mats M  

mAbs 20181222 1


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 manu  ...[more]

Similar Datasets

| S-EPMC6066182 | biostudies-literature
| S-EPMC9607506 | biostudies-literature
| S-EPMC8204403 | biostudies-literature
| S-EPMC5886730 | biostudies-literature
| S-EPMC6057790 | biostudies-literature
| S-EPMC5916549 | biostudies-literature
| S-EPMC6512938 | biostudies-literature
| S-EPMC8307401 | biostudies-literature
2020-10-15 | GSE158969 | GEO
| S-EPMC6178931 | biostudies-literature