A View on the Importance of “Multi-Attribute Method” for Measuring Purity of Biopharmaceuticals and Improving Overall Control Strategy

Today, we are experiencing unprecedented growth and innovation within the pharmaceutical industry. Established protein therapeutic modalities, such as recombinant human proteins, monoclonal antibodies (mAbs), and fusion proteins, are being used to treat previously unmet medical needs. Novel therapies such as bispecific T cell engagers (BiTEs), chimeric antigen T cell receptors (CARTs), siRNA, and gene therapies are paving the path towards increasingly personalized medicine. This advancement of new indications and therapeutic modalities is paralleled by development of new analytical technologies and methods that provide enhanced information content in a more efficient manner. Recently, a liquid chromatography-mass spectrometry (LC-MS) multi-attribute method (MAM) has been developed and designed for improved simultaneous detection, identification, quantitation, and quality control (monitoring) of molecular attributes (Rogers et al. MAbs 7(5):881–90, 2015). Based on peptide mapping principles, this powerful tool represents a true advancement in testing methodology that can be utilized not only during product characterization, formulation development, stability testing, and development of the manufacturing process, but also as a platform quality control method in dispositioning clinical materials for both innovative biotherapeutics and biosimilars.

[1]  Zhongqi Zhang,et al.  G/U and certain wobble position mismatches as possible main causes of amino acid misincorporations. , 2013, Biochemistry.

[2]  Brittney Livingston,et al.  Real‐time product attribute control to manufacture antibodies with defined N‐linked glycan levels , 2015, Biotechnology progress.

[3]  George M. Hilliard,et al.  Validation of a peptide mapping method for a therapeutic monoclonal antibody: what could we possibly learn about a method we have run 100 times? , 2000, Journal of pharmaceutical and biomedical analysis.

[4]  Liang-Yu Shih,et al.  An improved trypsin digestion method minimizes digestion-induced modifications on proteins. , 2009, Analytical biochemistry.

[5]  N. Lundell,et al.  Sample preparation for peptide mapping--A pharmaceutical quality-control perspective. , 1999, Analytical biochemistry.

[6]  D. Keire,et al.  A Retrospective Evaluation of the Use of Mass Spectrometry in FDA Biologics License Applications , 2017, Journal of The American Society for Mass Spectrometry.

[7]  Yun Zhang,et al.  Characterization and QC of biopharmaceuticals by MS-based 'multi-attribute method': advantages and challenges. , 2017, Bioanalysis.

[8]  Richard S Rogers,et al.  Development of a quantitative mass spectrometry multi-attribute method for characterization, quality control testing and disposition of biologics , 2015, mAbs.

[9]  J. Zhu-Shimoni,et al.  Identification of a single base-pair mutation of TAA (Stop codon) → GAA (Glu) that causes light chain extension in a CHO cell derived IgG1 , 2012, mAbs.

[10]  A. Gaggioli,et al.  Implementing quality by design for biotech products: Are regulators on track? , 2015, mAbs.

[11]  Terrence M. Dobrowsky,et al.  Quick generation of Raman spectroscopy based in‐process glucose control to influence biopharmaceutical protein product quality during mammalian cell culture , 2016, Biotechnology progress.

[12]  G. K. Raju,et al.  Understanding Pharmaceutical Quality by Design , 2014, The AAPS Journal.

[13]  Davy Guillarme,et al.  Chromatographic, Electrophoretic, and Mass Spectrometric Methods for the Analytical Characterization of Protein Biopharmaceuticals. , 2016, Analytical chemistry.

[14]  Alain Van Dorsselaer,et al.  Characterization of therapeutic antibodies and related products. , 2013, Analytical chemistry.

[15]  W. G. Hill,et al.  Genome partitioning of genetic variation for complex traits using common SNPs , 2011, Nature Genetics.

[16]  Yi Wang,et al.  Simultaneous monitoring of oxidation, deamidation, isomerization, and glycosylation of monoclonal antibodies by liquid chromatography-mass spectrometry method with ultrafast tryptic digestion , 2016, mAbs.

[17]  Hongcheng Liu,et al.  Forced degradation of recombinant monoclonal antibodies: A practical guide , 2017, mAbs.

[18]  Junzhi Wang,et al.  Identification of a Recombinant Human Interleukin-12 (rhIL-12) Fragment in Non-Reduced SDS-PAGE , 2019, Molecules.

[19]  John R. Engen,et al.  Analytical tools for characterizing biopharmaceuticals and the implications for biosimilars , 2012, Nature Reviews Drug Discovery.

[20]  Nitin Agarwal,et al.  A Quadrupole Dalton-based multi-attribute method for product characterization, process development, and quality control of therapeutic proteins , 2017, mAbs.

[21]  Ning Li,et al.  LC-MS multi-attribute method for characterization of biologics , 2017 .

[22]  Zhongqi Zhang,et al.  Large-scale identification and quantification of covalent modifications in therapeutic proteins. , 2009, Analytical chemistry.

[23]  Zhongqi Zhang,et al.  LC-MS/MS Peptide Mapping with Automated Data Processing for Routine Profiling of N-Glycans in Immunoglobulins , 2014, Journal of The American Society for Mass Spectrometry.

[24]  Ken Lawson,et al.  Application of a Quantitative LC-MS Multiattribute Method for Monitoring Site-Specific Glycan Heterogeneity on a Monoclonal Antibody Containing Two N-Linked Glycosylation Sites. , 2017, Analytical chemistry.

[25]  Christopher Jones,et al.  Quality control and analytical techniques for biopharmaceuticals. , 2011, Bioanalysis.

[26]  L. Corsini,et al.  Robust Approaches for the Production of Active Ingredient and Drug Product for Human Phage Therapy , 2019, Front. Microbiol..

[27]  Patrick Swann,et al.  Application of mass spectrometry to facilitate advanced process controls of biopharmaceutical manufacture , 2015 .

[28]  Alain Van Dorsselaer,et al.  Biosimilar, biobetter, and next generation antibody characterization by mass spectrometry. , 2012, Analytical chemistry.

[29]  J. Shaver,et al.  Evaluation of Crystal Zenith Microtiter Plates for High-Throughput Formulation Screening , 2020, Journal of pharmaceutical sciences.

[30]  Susan Callahan,et al.  A framework for real‐time glycosylation monitoring (RT‐GM) in mammalian cell culture , 2015, Biotechnology and bioengineering.