EMA plots new guidance on immunogenicity assessment of biotech therapeutic proteins

The European Medicines Agency (EMA) is to develop new expanded guidance on the immunogenicity assessment of biotechnology-derived therapeutic proteins.

EMA said more specific guidance for presenting immunogenicity data was needed, along with advice on data requirements for antibody assays; the role of in vitro and in vivo non-clinical studies; the risk-based approach to immunogenicity; using clinical data to study correlations of induced antibodies to allergic and anaphylactic/anaphylactoid reactions; delayed immunological reactions; pharmacokinetics; lack of efficacy; comparative immunogenicity studies; and post-licensing immunological studies.

The Agency explained that the requirements of immunogenicity assays might need clarifying, since its committee for medicinal products for human use (CHMP) 'has frequently had questions concerning the sensitivity of such assays and the use of ligand-binding and cell-based assays to demonstrate neutralising antibodies'.

It added that most marketing authorisation applications 'lack a clear strategy to approach immunogenicity'. EMA advised that such a strategy 'should be based on a comprehensive analysis of all data that may be related to the immunogenicity'.

Quality issues, such as impurities, aggregates, xenogeneic structures and leachables, need to be assessed, said the EMA, which added that the risk of immunogenicity could be affected by dosing and the frequency, duration and route of administration, underlying disease and concomitant medication.

It said risk analysis might help estimate the extent of immunogenicity studies, plus the length of follow up pre- and post-licensing.

'Comparative immunogenicity studies may require more guidance on the assays and on the criteria for possible immune-related adverse effect,' said EMA.