Glycoconjugate vaccine batch consistency assessed by objective comparison of circular dichroism spectra.

Circular dichroism (CD) spectra of biopharmaceutical protein, or protein conjugate, products contain information about their secondary and tertiary structures, which can answer to increasing regulatory interest in demonstrating consistent higher order structures of production batches. Widespread routine use of CD in a regulatory environment requires objective, statistically based, and validated methods to analyse and compare spectra against product specifications. Correlation approaches to compare spectra, developed and tested on monoclonal antibodies, are here used to assess the consistency of Hib PRP-CRM197 glycoconjugate immunogen batches, by analysis of historical data sets. Deconvolution of spectra into Gaussian peaks was used to model the spectrum and allow a more detailed description of spectral differences. Two groups of spectra [and hence samples] were distinguished. The analyses are discussed in the context of spectral comparison approaches, inter-laboratory studies, potential regulatory use and sources of uncertainty between spectra. Data analysis methods implemented here can also support stability and formulation studies.