Forced degradation studies, where a putative drug substance or drug product is subjected to elevated chemical and environmental stress, are a regulatory requirement. These studies serve to identify and understand product degradation pathways and potential impact on efficacy or safety, as well as to challenge the sensitivity and specificity of analytical methods from the development stage onwards.
These studies are made more challenging by the lack of defined procedures in regulatory guidance for most of the required degradation conditions, with those procedures that are defined often being too severe for biotherapeutics. Therefore, Covance is developing a standardised forced degradation strategy, resulting in defined degradation conditions and timepoints, with analysis using the most appropriate analytical methods for the stress conditions applied.
LC-MS multi-attribute monitoring (MAM) is an integral component of the forced degradation strategy developed. This analytical approach, which Covance has developed in line with GMP regulatory standards, allows assessment of various product characteristics in one assay, reducing overall testing requirements, and is suitable for use to support batch release and formal stability assessments.
This presentation will detail Covance's approach to such studies and feature a comprehensive, demonstrative data set.
Presented by
Rachel Smith,
Assay Development Scientist - Mass Spectrometry, Covance
Following a PhD at the University of York in small molecule analysis by mass spectrometry, using platforms including MALDI-MS, LC-MS and GC-MS, Rachel joined Covance biopharmaceutical CMC solutions in 2016. As a member of the mass spectrometry assay development team she has developed workflows for intact and middle-up LC-MS characterisation of mAbs and derivative fusion proteins, as well as gaining experience in other biopharmaceutical characterisation methods including peptide mapping and released N-glycan analysis. Whilst at Covance, Rachel has also taken on a key role in the planning and development of forced degradation studies.