New mass spectrometry Chapter could “revolutionise” biopharma quality assurance

New guidelines from the The US Pharmacopeia (USP) on mass spectrometry-based quantification of host cell protein (HCP) impurities in biologic drugs are available, as of 1 December.

This follows an announcement by USP about its intent to revise General Chapter <1132.1> Residual Host Cell Protein Measurement in Biopharmaceuticals by Liquid Chromatography-Mass Spectrometry.

“It is an industry-wide challenge to control [host cell proteins] HCPs to ensure the safety and quality of biopharmaceutical products” stated Derrick Zhang, Senior Scientist, US Pharmacopeia. This new method USP chapter aims to standardise the use of mass spectrometry in the industry, Zhang explained.

Compared to the approximate 24-month development timeline with enzyme-linked immunosorbent assay (ELISA) analysis, mass spectrometry-based HCP analysis, takes less than three months, according to contract research organisation (CRO) Alphalyse A/S.

Considering its numerous benefits, such as the above, regulators therefore encourage drug manufacturers to use mass spectrometry together with ELISA analysis, or mass spectrometry analysis by itself, for control and documentation of product impurities, explained Alphalyse.

Revolutionising drug impurity analysis with mass spectrometry

“We’re facing a breakthrough in the pharmaceutical industry. Mass spectrometry is a quick and effective method that can identify tens of thousands of different host cell proteins while detecting their respective amounts, allowing the targeted removal of harmful impurities in drugs. This method is also suitable for complex products such as cell and gene therapies for the treatment of cancers, Alzheimer’s, and genetic disorders,” commented Ejvind Mørtz, PhD, co-founder of Alphalyse A/S.

“Achieving regulatory approval for complex drugs has been difficult because conventional analytical methods are unable to detect all types of impurities. The recognition of mass spectrometry as a complementary method opens the door for us to support biopharmaceutical developers in getting their drugs approved for clinical trials and patient treatment,” Mørtz continued.

“Even the best of the conventional methods can only measure around 80–90 percent of the impurities that could potentially be in a drug. There is a risk that the authorities might reject a drug due to the lack of documentation of impurities, which is why some drug manufacturers have never been able to release their product to the market. The opportunity to use mass spectrometry-based protein analysis as documentation for drug purity is therefore a great leap forward for all companies struggling with the limitations of earlier methods,” noted Bryant McLaughlin, Senior Biologics CMC & Process Development Consultant.