FDA team describes lectin microarray for rapid glycan‑epitope profiling of intact antibodies
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Summary
Dr. Bao Lin Zhang outlined a first‑ and second‑generation lectin microarray that the FDA team developed to profile glycan epitopes on intact antibodies, reporting high specificity in engineered anti‑HER2 tests and comparable epitope profiles across adalimumab biosimilars.
At FDA Grand Rounds, Dr. Bao Lin Zhang described the development and qualification of a lectin microarray platform intended to provide rapid, release‑free glycan‑epitope profiling of intact therapeutic antibodies.
Zhang said his group qualified a first‑generation lectin microarray containing 45 lectins and, after observing nonspecific signals related to research‑grade designs, refined a second‑generation panel featuring nine lectins chosen for selective recognition of glycan epitope structures relevant to licensed products.
"We have developed a first in class lectin microarray that allows the rapid glycan epitope profiling of intact antibodies," Zhang said, describing a workflow in which samples are labeled, applied to the chip and read by a fluorescent detection system without washing steps. He noted the approach addresses low lectin binding affinity and that the platform reports epitope‑level information complementary to mass spectrometry.
In validation work with chemoenzymatically engineered anti‑HER2 glycoforms (prepared in collaboration with Lishi Wang's laboratory), mass spectrometry confirmed the engineered glycoform uniformity and the 9‑lectin array produced high‑specificity signals distinguishing core fucosylation and linkage differences. Zhang said the microarray showed sensitivity sufficient to distinguish 2‑6 versus 2‑3 sialic‑acid linkages and reported a dynamic range up to ~1,000 ng/ml with prototype intermediate precision under 20% CV.
Zhang also presented a case study comparing adalimumab (three lots) and eight biosimilars. Using a statistical acceptance window of reference ±3 SD, he reported that all biosimilars’ lectin‑epitope profiles fell within the preset acceptance range, supporting comparability at the epitope level in that dataset.
Zhang framed the lectin microarray as a complementary tool to intact‑protein and released‑glycan MS approaches and suggested that, when qualified and justified, the assay could augment analytical characterization and release testing strategies for therapeutic antibodies.
