USP initiatives for enhancing the quality and consistency of MS-based HCP analysis

US Pharmacopeia chapter <1132.1>

Initiatives for enhancing the quality and consistency of MS-based HCP analysis

Derrick Zhang, US Pharmacopeia, USA

Residual host cell proteins (HCPs) are critical quality attributes in biotherapeutics, impacting patient safety and product efficacy. Mass spectrometry (MS) is gaining prominence for its precision in identifying and quantifying individual HCPs, playing a vital role in risk assessment, process optimization, and quality control of biotherapeutic products.

This presentation will delve into the USP's initiatives to enhance the quality and consistency of MS-based HCP analysis.

Key developments include:

• The introduction of a new general chapter, <1132.1> 'Residual Host Cell Protein Measurement in Biopharmaceuticals by Mass Spectrometry.'
• Documentary and physical standards for MS HCP analysis

This chapter, currently under review by the USP Expert Panel following public comments, outlines best practices for HCP identification and quantification by LC-MS/MS.

The USP's strategy for developing and characterizing physical standards, including intact protein and peptide standards for high-risk and abundant HCPs, will be discussed in this presentation.

Highlights include the release of the first Analytical Reference Material;

• Purified Recombinant CHO Phospholipase B-like 2 protein (PLBL2), and
• The upcoming first six SIL Peptides for Clusterin and Lipoprotein Lipase

Additionally, the presentation will cover a USP internal study on the quantification of Clusterin and Lipoprotein Lipase in monoclonal antibody (mAb) samples from CHO cells using LC-MRM, employing USP SIL peptides. This study aims to validate the effectiveness of USP HCP peptides for specific HCP quantification in line with USP General Chapter <1132.1>, ultimately enhancing the accuracy and reliability of HCP measurement in biopharmaceutical manufacturing.