Unlike ELISA, LC‑MS does not produce a single total HCP value but instead delivers a multi‑dimensional output that supports a more risk‑based specification. It typically includes an overall HCP level, often calculated as the sum of quantified proteins and expressed relative to the drug substance (e.g. ppm or ng/mg).

In addition, LC‑MS provides identification and quantification of individual HCPs, enabling detailed insight into which proteins are present and at what levels. This allows specific monitoring of high‑risk HCPs, such as proteases, lipases, or potentially immunogenic proteins, which can be assessed individually against defined acceptance criteria.

Finally, the data supports evaluation of process consistency, allowing comparison of HCP profiles across batches, purification steps, or process changes, making LC‑MS both a quantification and process understanding tool.

Thomas Kofoed, PhD, CEO of Alphalyse in Denmark, discussed key factors in implementing GMP-compatible LC-MS methods for release assays and highlighted successful cases where this approach has replaced traditional ELISA methods. Don’t miss his presentation and expert insights at the panel discussion.