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Feature|Videos|August 5, 2026

Controlling Aggregation at Bioconjugate Manufacturing Scale-Up

Key Takeaways

  • Understand why GMP control strategies for bioconjugates must be tailored to the specific linker, payload, and conjugate type rather than applied as a fixed platform.
  • Identify why aggregation is often the hardest CQA to control during conjugation scale-up.
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As bioconjugate drug manufacturing moves to scale, certain critical quality attributes (CQAs) are hardest to control.

Episodes in this series

Sponsored by Waters Corporation

Translating high-resolution characterization strategies into GMP-ready manufacturing controls is complicated by the fact that small shifts during conjugation scale-up can increase aggregation in ways that drug-to-antibody ratio (DAR) measurement alone won’t reveal. Lance Cadang, Scientist, Synthetic Molecule Analytical Chemistry at Genentech, explains that determining which methods belong in a control system depends on the specific linker, payload, and conjugate type involved, since platform methods don’t always transfer cleanly between programs. Understanding a molecule’s impurities and degradation pathways ahead of time is essential to building an appropriate control strategy. Zhengqi Zhang, Associate Principal Scientist at Merck & Co., describes aggregation as the hardest CQA to control at scale for high-DAR conjugates as even small shifts in DAR distribution or reaction conditions can increase aggregation. Integrating mass spectrometry (MS) based workflows, such as size exclusion chromatography mass spectrometry (SEC-MS) has allowed his team to link specific high-DAR populations to aggregation risk. This manufacturing strategy tightens DAR distribution and limits high-DAR species.

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