Measurement of impurities to support process development and manufacture of biopharmaceuticals

• Published in: TrAC, Trends in analytical chemistry (Regular ed.) Trends in analytical chemistry (Regular ed.), 2018-04, Vol.101, p.120-128
• Main Authors: Oshinbolu, Sheun, Wilson, Louisa J., Lewis, Will, Shah, Rachana, Bracewell, Daniel G.
• Format: Article
• Language: English
• Subjects: Aggregation; Biopharmaceuticals; Glycosylation; Host cell proteins; Recombinant therapeutics; Regulation
• ISSN: 0165-9936; 1879-3142
• DOI: 10.1016/j.trac.2017.10.026

The biopharmaceutical industry is a growing market relying on analytical methods to bring safe and efficacious drugs from conception to market. Analytical methods are required during the entire drug life cycle as it plays a vital role during decision making. Impurities influence product quality, stability and efficacy, so their levels need to be minimised. There are regulatory guidelines that set out principles for consideration in meeting product quality specifications. Analytical methods have limits in their sensitivity and accuracy of measurement, their sample throughput and/or range of detection. This highlights the need to have orthogonal assays that can confidently quantify critical impurities to the appropriate levels. In this review, we discuss three major analytically challenging critical quality attributes – two product related impurities (aggregates and incorrect glycosylation) and one process related impurity (host cell proteins) – and the analytical assays that are commonly used to measure their quantity and quality. •Impurities in biopharmaceuticals affect drug quality, efficacy and patient safety.•These impurities need to be tightly controlled to meet ICH regulatory guidelines.•Aggregates, HCPs and glycosylation are typical critical quality attributes.•Critical quality attributes need to be controlled with appropriate analytical assays.