In our blog series we have looked at the idea of orthogonality in various aspects of structural characterization (read more here). We’ve already seen how this approach is a powerful tool for strengthening structural conclusions drawn from individual techniques, as well as being a requirement from the regulatory authorities. One area that we haven’t discussed yet, and that I would like to discuss in this blog, is the assessment of aggregation.
Aggregates are noted as being either product or process related in the ICH Q6B structural characterization guidelines (1) and as such are expected to be assessed. Aggregation is also specifically mentioned in the EMA and FDA guidelines on biosimilar structural characterization along with the idea, in each case, of orthogonal assessment of this structural feature (2,3). In addition, the assessment of degradation profiles (e.g. in Forced Degradation studies) of the product is also detailed and includes the use of aggregation assessments as part of this investigation (2, 3).
So, what is the best way to examine aggregation in a manner that draws on the expectation of orthogonality in this context?