News
New US Pharmacopeia General Chapter: 1132.1
Residual Host Cell Protein Measurement in Biopharmaceuticals by Mass Spectrometry
Host Cell Protein (HCP) analysis by mass spectrometry (MS) is our passion and mission, so we are excited that the USP 1132 chapter has been updated with the new 1132.1 chapter on identifying and quantifying HCPs using MS. The first draft, posted on 1 May 2023, received more than 100 public comments that have been reviewed by the USP expert panel and committee. The complete chapter will be available on the USP website on December 1st, 2024, and become official on May 1st, 2025.
The United States Pharmacopeia (USP) is the most comprehensive source for standards about drug quality, purity, strength, and identity worldwide. The FDA widely uses USP standards as a reference, outlining the recomended processes, tests, and procedures for developing, manufacturing, and regulating pharmaceutical products.
What's new in chapter 1132.1?
The original USP 1132 chapter on Residual Host Cell Protein Measurement in Biopharmaceuticals focuses almost exclusively on immunoassay methods, with only a limited discussion on supporting/orthogonal technologies.
The new USP 1132.1 chapter, Residual Host Cell Protein Measurement in Biopharmaceuticals by Mass Spectrometry, contains general guidance and best practices for MS-based identification and quantification of individual HCPs.
Contents of the new USP chapter 1132.1
Chapter 1132.1 will include sections on
- Sample preparation (denatured digestion, product protein depletion, or HCP enrichment),
- Chromatographic separation
- Mass spectrometry analysis
The latter section will include:
- Methods for HCP quantitation (relative to product protein, spiked-in proteins, and spiked-in peptides)
- Method validation
- System suitability
- Best practices for reporting ELISA vs. LC-MS/MS data
Further, a case study on low-abundance HCP detection will be presented to show normal variation in analyst and instrument performance.
At the recent BEBPA 2024 HCP conference, Niomi Peckham from the USP discussed the changes to the chapter. You can find a summary of her talk here: Insights from the 2024 BEBPA HCP Conference
Impact of chapter 1132.1
How will the biopharma industry change on May 1, 2025?
The regulatory landscape for biologics is changing. Health authorities increasingly demand orthogonal data such as mass spectrometry analysis to support ELISA – pushing for more thorough and reliable documentation.
In this video, CEO Thomas Kofoed asked CMC Executive Bryant McLaughlin how he anticipates the new USP chapter will affect the industry.
The update of the USP 1132 chapter paves the way for significant changes in the pharmaceutical industry
The new chapter 1132.1 will mark a shift in how HCP analysis is perceived and executed.
ELISA remains the most widespread method for HCP analysis, but it will increasingly be supported by characterization and coverage analysis by MS. Some of our clients have already been required by the FDA and EMA to support their ELISA HCP data with MS data.
Moving towards more use of MS-based HCP analysis will probably also result in a shift away from examining total HCP content to evaluating specific HCPs of concern.
The purpose of monitoring HCP levels in drug substances is to avoid the harmful effects of HCPs with enzymatic or immunogenic activity. While most protein impurities do not impact patient safety or drug stability, a few can cause problems even at low levels, so you will need to document and control those.
Learn more about how to investigate HCPs in biologics using mass spectrometry >>
What prompted the development of USP 1132-1?
Ejvind Mortz, COO at Alphalyse, has examined the content of the upcoming US Pharmacopeia General Chapter 1132.1, which is set to transform protein impurity analysis in the biopharma industry next year.
- What prompted the USP to develop this addition to chapter 1132?
- Which analytical methods will be covered by 1132.1?
On demand webinar
Q&A with CMC executive Bryant McLaughlin
Bryant McLaughlin is an industry CMC expert with 15 years of experience in process optimization and IND documentation. Get his input on your concerns and queries on the power of MS-based host cell protein analysis:
- Navigate FDA guidelines confidently: Learn about Bryant's experience with the FDA's - and EMA's - stance on MS-based HCP analysis.
- Learn from real-world experience: Discover how Bryant has utilized MS-based HCP analysis to overcome challenges.
- Explore the comparative value of MS-based analysis: Delve into how MS-based HCP analysis complements traditional methods like ELISAs.
Talk to us
Whatever protein-related challenge or question you may have, we would love to help. Our experts can help you decide on the best analytical approach for your project by email or online meeting - providing advice without obligation.