SIBYLLE HEIDELBERGER
Sciex, United Kingdom

Abstract

The use of LC-MS can be a valuable tool, not just for characterization of biologics, but increasingly for monitoring attributes throughout the entire process. This multiple attribute methodology comprises monitoring of critical quality attributes as well as monitoring known and unknown impurities using a new peak detection analysis. The addition of this orthogonal assay to characterization and monitoring of biotherapeutics is the speed at which the analysis can be performed and the information that can be learned.This technology and its implementation align with both ICH and FDA guidelines towards quality by design (QbD) which involves monitoring of biotherapeutics throughout the production and into final processing, ensuring product quality. Here we discuss implementation of MAM for biotherapeutics.

The topic of a multiple attribute method (MAM) has gained significant attention recently as an overarching method for identification and tracking of product quality attributes related to protein-based biotherapeutics since it was first introduced (1).  

From the first reports, MAM relies on a peptide map of a biotherapeutic using high-resolution mass spectrometry. 

The objective is to characterize the target therapeutic and map post-translational modifications to specific peptides, and amino acids, for greater understanding of molecular properties and ultimately how these relate to the safety and efficacy of therapeutics. Given the interest in MAM it is worth discussing its benefits, how it applies to biopharmaceuticals and some consideration on how MAM may be implemented.

BENEFITS OF MAM

As biopharmaceutical companies face increasing pressure from competitors, innovators, and biosimilars, there is a push to increase speed to market, improve product quality, and lower the cost of quality by improving process understanding.