Compliant CQA monitoring of therapeutic proteins for manufacturing control
Modern biopharmaceutical drugs, such as monoclonal antibodies (mAbs) and antibody drug conjugates (ADCs), are tremendously complex molecules manufactured inside living cells. Characterizing and monitoring these compounds in chemistry, manufacturing and controls (CMC), and quality control environments can present a significant challenge, but the use of high resolution accurate mass (HRAM) mass spectrometry offers a powerful way of overcoming these challenges.
The additional dimension of separation combined with the sensitivity and specificity of Orbitrap MS yields deeper product knowledge than a combined battery of conventional characterization tests, eliminating a large number of traditional lot release testing.
By directly measuring critical quality attributes at the individual residue level, understanding how changes in process or production affect a drug product becomes part of a "quality by design" approach. Together, the results provided by HRAM MS enable safer and more potent drugs to be manufactured, delivering a truly powerful research-to-routine workflow.
Mass spectrometry in QC bottom-up workflow
The adoption of mass spectrometry (MS) in quality control workflows is discussed in this Chemical & Engineering News article. MS experts talk about using mass spectrometry in pilot plants to replace some of the more traditional quality control assays. MS allows the detection of slight changes in biotherapeutics due to its increased sensitivity and specificity: “…the only instrument able to consistently detect these new peaks is the Orbitrap…”
How can HRAM MS reduce the number of individual CQA assessments?
Adapted from Rogers, R. et al. MS in QC: A Single Multi-attribute Method for Quality Control and Release Testing of Biologics. Presented at CASSS MS 2013, Boston, September 24 2013.
|Critical Quality Attribute Assessment||Covered by MAM||SEC||CEX||rCE-SDS||nrCE-SDS||HILIC||ID ELISA||HCP ELISA|
|CDR Tryptophan Degradation||Indirect|
|Fragmentation (Peptide Bond)|
|Mutations & Misincorporations|
|Non-glycosylated Heavy Chain|
|Residual Protein A|
|= Yes||= No||= Sometimes|
To adequately cover the numerous different critical quality attributes required during QC analysis, several different analytical strategies are typically performed. Many of these analyses are time intensive and only serve to provide one piece of information.
Multi-attribute method (MAM) analysis (via peptide mapping) serves to provide significant amounts of information for biotherapeutic drugs, both reducing the number of analyses and different experiments required to be performed whilst increasing the product quality profile.
Powerful and compliant informatics for MAM of biotherapeutic drugs
Take protein characterization data from discovery with the identification of critical quality attributes using Thermo Scientific BioPharma Finder software seamlessly into routine GMP compliant monitoring using the powerful MS processing features in Thermo Scientific Chromeleon 7.2 Chromatography Data System (CDS) software. Confidently and robustly monitor multiple critical quality attributes in a single sequence in high resolution to ensure that your biotherapeutic drugs are adequately controlled.
Chromeleon software unifies workflows for chromatography and MS analysis, providing full integration of LCMS data acquisition, auditing, processing, and reporting—you even manage third party LC systems. Quickly and easily process and report UV and MS data in one application with the ability to run your analyses in an enterprise environment, while complying with GxP regulatory requirements such as 21 CFR Part 11.
Integral components of a robust and sensitive MAM workflow
Highly recommended for peptide mapping of biotherapeutics proteins
Thermo Scientific Accucore Vanquish C18+ UHPLC Columns offer excellent separations and helping to ensure sharp peaks. The Accucore Vanquish C18+ UHPLC Columns feature an ultrapure silica substrate with extremely low metal content to minimize tailing effects and deliver symmetrical peak shapes, while particle sizes of 1.5 µm provide unrivaled peak separation.
Obtain confident peptide separations, every time
The Thermo Scientific Vanquish Flex Binary UHPLC and the Vanquish Horizon UHPLC platforms offers ultimate biocompatible state-of-the-art binary or quaternary solvent blending, along with new benchmarks in accuracy, precision, and sensitivity in peptide chromatography. With rock-steady retention times, you can be confident in the identity of every peptide in discovery, development, and QC environments.
Class-leading resolution, sensitivity, and accuracy
The Q Exactive Plus Hybrid Quadrupole-Orbitrap Mass Spectrometer delivers everything you need, and more, for demanding QC environments where the right results matter. Whether it is the identification of low abundance peptides in complex matrix, robust and reliable mass accuracy or just being simple to set up and operate, the Q Exactive Plus system delivers.
Learn more about MS in QC and how innovation and monitoring strategies can reduce the number of tests and enhance the methodology of validating impurity.
Extending the capabilities of a MS-based multi-attribute characterization method to promote quality by design In biotherapeutic drugs.