Validation of a liquid chromatography-high-resolution mass spectrometry method to quantify peptide-related impurities in teriparatide.

With recent advances in quantitative high-resolution mass spectrometry (HRMS), there is growing interest in developing liquid chromatography (LC)-HRMS methods that can simultaneously quantify numerous critical impurities in a peptide or protein drug. This approach is attractive as it could reduce the total number of methods and instruments required during product development and quality control testing, while taking advantage of the technique's high specificity and sensitivity. To investigate the feasibility of this approach for peptide drugs, an LC-HRMS method was validated for the quantification of six peptide-related impurities in teriparatide, the 34-amino acid active ingredient in Forteo.

Assessment of monoclonal antibody glycosylation: a comparative study using HRMS, NMR, and HILIC-FLD.

Monoclonal antibodies (mAbs) represent the largest class of therapeutic protein drug products. mAb glycosylation produces a heterogeneous, analytically challenging distribution of glycoforms that typically should be adequately characterized because glycosylation-based product quality attributes (PQAs) can impact product quality, immunogenicity, and efficacy. In this study, two products were compared using a panel of analytical methods.

The Use of Mass Spectrometry in Therapeutic Protein Biologics License Applications: A Retrospective Review Revisited.

Biologic license applications (BLAs) for 93 therapeutic proteins approved between 2016 and 2020 were analyzed for use of mass spectrometry (MS) as a follow up to a previous study that assessed MS use in BLAs from 2000 to 2015. Thirty percent of these BLAs were biosimilars, while only one biosimilar BLA was approved prior to 2016. This analysis evaluated the use of a variety of MS techniques and instrumentation.

Method validation and new peak detection for the liquid chromatography-mass spectrometry multi-attribute method.

The multi-attribute method (MAM) is a liquid chromatography-mass spectrometry (LC-MS) peptide mapping technique that has been proposed as a replacement for several conventional quality control (QC) methods for therapeutic proteins. In addition to quantification of multiple product quality attributes (PQAs), MAM can also monitor impurities using a new peak detection (NPD) feature. Here, results are provided from method validation and NPD studies of an MAM approach applied to rituximab as a model monoclonal antibody (mAb).

Attribute Analytics Performance Metrics from the MAM Consortium Interlaboratory Study.

The multi-attribute method (MAM) was conceived as a single assay to potentially replace multiple single-attribute assays that have long been used in process development and quality control (QC) for protein therapeutics. MAM is rooted in traditional peptide mapping methods; it leverages mass spectrometry (MS) detection for confident identification and quantitation of many types of protein attributes that may be targeted for monitoring. While MAM has been widely explored across the industry, it has yet to gain a strong foothold within QC laboratories as a replacement method for established orthogonal platforms.