Meet the Expert: Mass Spectrometry for HCP Monitoring in GMP

Introduction

• A conversation with Somar Khalil, Principal Scientist at GSK Vaccines, on why the industry needed to move beyond immunoassays for monitoring residual host cell proteins (HCPs), and how his team demonstrated that untargeted, label-free mass spectrometry can finally take on that role in a regulated setting.
• Somar explains the motivation behind the paper: immuno-based assays like ELISA have been the default for HCP monitoring for years, but they only report a total, aggregate signal. Mass spectrometry, by contrast, can quantify HCPs at the individual protein level, information that matters directly for risk assessment.
• That’s the gap this paper closes. Somar and his co-authors set out to demonstrate, for the first time, that an untargeted label-free proteomics workflow could be validated according to ICH Q2(R2) and implemented in a GxP environment, a genuine alternative to immunoassays for HCP monitoring, not just a research-stage tool.

Key Learning Outcomes

• Individual-level data changes risk assessment: Unlike ELISA’s single aggregate readout, MS-based quantification resolves HCPs at the individual protein level, information that can be directly relevant to assessing clinical risk, not just total impurity burden.
• Untargeted MS had never reached release testing: A review of the literature showed that targeted MS assays and other mass-spec approaches for HCPs had not previously been shown to meet the bar for release or controlled-environment use; they remained tools for discovery and characterization.
• Full ICH Q2(R2) coverage, empirically demonstrated: Every validation parameter called for under ICH Q2(R2) was addressed using a total-error accuracy profile, with some parameters evaluated in ways that go beyond what the guidance, written with single analytes in mind, actually specifies.
• Built for two audiences: The paper speaks to anyone in industry looking for an orthogonal or replacement method for HCP monitoring, and just as much to anyone, in industry or academia, working with high-dimensional analytical methods (not necessarily proteomics) who needs a more structured way to evaluate method performance.
• A first step toward merging two worlds: Somar frames this as a step toward giving high-resolution, untargeted mass spectrometry a legitimate place in GMP and routine QC release testing, bridging what has traditionally been split between characterization/discovery work and regulated environments

About

Somar Khalil holds a PhD in pharmaceutical sciences and is a Principal Scientist at GSK Vaccines in the Mass Spectrometry and NMR group, Technical R&D. His work focuses on MS-based proteomics and mRNA analytics, with expertise in LC-MS host-cell protein quantification, glycoproteomics, and implementation of advanced LC-MS workflows in regulated settings. He has led method development and validation for HCP monitoring in vaccine and biologics programs, applying statistical modelling and data science to support CMC decision-making.