Anaquant HCP analysis I Protein characterisation I Protein analysis
Regulatory Expectations and ANAQUANT Compliance
Introduction to USP 1132.1
USP Chapter 1132.1, “Residual Host Cell Protein Measurement in Biopharmaceuticals by Mass Spectrometry”, represents a major regulatory milestone in the control of process-related impurities in biotherapeutic products. Published by the United States Pharmacopeia (USP), this chapter provides guidance on the use of LC–MS/MS–based methods for the identification and quantification of Host Cell Proteins (HCPs), either as a complement to or an alternative to traditional immunoassays such as ELISA.
The introduction of USP 1132.1 reflects the growing recognition by regulatory authorities that mass spectrometry offers superior specificity, transparency, and molecular-level information, particularly for complex biologics, next-generation modalities, and advanced manufacturing processes.
Why USP 1132.1 Matters for Biopharmaceutical Development
Residual HCPs can impact product quality, patient safety, and long-term immunogenicity risk. While ELISA remains widely used, its intrinsic limitations—such as antibody coverage bias, lack of protein-level identification, and limited comparability across products—are well documented.
USP 1132.1 addresses these limitations by outlining best practices for MS-based HCP workflows, enabling:
– Protein-level identification of residual HCPs
– Improved process understanding and risk assessment
– Support for comparability studies and lifecycle management
– Enhanced confidence in regulatory submissions
This chapter is particularly relevant for monoclonal antibodies, recombinant proteins, viral vectors, and other complex biologics, where residual HCP profiles may evolve throughout development and scale-up.
Key Principles of USP 1132.1
Rather than prescribing a single analytical method, USP <1132.1> defines regulatory expectations and scientific principles that should govern MS-based HCP analysis. These include:
– A fit-for-purpose analytical strategy, aligned with the development stage
– Robust sample preparation and digestion workflows
– Transparent protein identification criteria
– Quantification approaches that are scientifically justified and well controlled
Method validation concepts consistent with USP 1225, 1226, and ICH Q2(R2)
Importantly, USP 1132.1 emphasizes that method performance, traceability, and data interpretability are central to regulatory acceptance.