Fig. 3. Characteristics that have been implicated in contributing to total aggregate immunogenicity. The protein immunogenicity fraction highlights how individual proteins (represented by different colors) and their corresponding aggregates can vary regarding their intrinsic immunogenicity. The native structure fraction represents that the degree of structural modifications (represented by darker colors), such as unfolding or oxidation, occurring during aggregation can affect the resulting total immunogenicity of the aggregate formulation. Regarding the fractions pertaining to physical aggregation properties; size, particle number and morphology have all been implicated to contribute to overall aggregate immunogenicity. The research regarding these three latter factors indicate that a high total surface area increases total aggregate immunogenicity. Servier Medical Art PowerPoint image bank was used to construct this diagram.