2023 FDA Science Forum
Rapid Glycan Profiling with a Nine-Lectin Microarray for Therapeutic IgG1 Monoclonal Antibodies
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Contributing OfficeCenter for Drug Evaluation and Research
Abstract
Glycosylation is a critical quality attribute (CQA) of many therapeutic monoclonal antibodies (mAbs), and therefore must be adequately analyzed and controlled to ensure product quality and manufacturing consistency. Here, we describe a lectin microarray that comprises nine distinct lectins for detecting glycan epitopes of therapeutic IgG1 mAbs, a dominant class of biopharmaceuticals that are often produced as glycoproteins by living cell systems. We first analyzed the glycosylation patterns for 70 commercially marketed therapeutic IgG1 mAbs approved by the US Food and Drug Administration (FDA) based on the relevant information in the Biologic License Applications (BLAs). A set of nine abundant glycan epitopes was found to be consistently present across all therapeutic IgG1 mAbs produced by different expression systems and was used as a benchmark for analytical method development. After screening a large lectin library, we identified nine lectins that specifically recognize the benchmark glycan epitopes of IgG1 mAbs. We then developed a lectin microarray comprising the nine lectins and proved its suitability for high-throughput glycan profiling of IgG1 mAbs utilizing intact glycoprotein samples, which enables comparative glycosylation analyses for batch-to-batch or biosimilar-to-innovator products.
