Interferon immunogenicity: technical evaluation of interferon-alpha 2a.

Observations from some studies with interferon-alpha 2a (IFN-alpha 2a) have shown the presence of neutralizing antibodies in a proportion of patients. As a result, an investigation into the production of antibodies to IFN-alpha 2a was undertaken. A number of technical aspects of its production and storage were investigated, including the possibility of an incorrect structure, which could affect the immunogenicity of the IFN-alpha 2a molecule. These investigations demonstrated the presence, in vials of IFN-alpha 2a, of both interferon-interferon (IFN-IFN) aggregates and aggregates of interferon with human serum albumin (HSA), the excipient of the galenical form of IFN-alpha 2a (IFN-HSA) aggregates. The amount of aggregates is temperature dependent, there being very little increase in aggregate content over time when vials are stored at 4 degrees C. The relative immunogenicity of IFN-alpha 2a increased when the vials were stored at ambient temperature but not when stored at 4 degrees C. These findings demonstrate that the immunogenicity of IFN-alpha 2a is likely to be related to the storage temperature. Storage of IFN-alpha 2a vials at 2-8 degrees C is now recommended. A new formulation has been introduced that does not contain HSA as an excipient, removing the possibility of IFN-HSA aggregation.