Assesment of Immunogenicity


The term “immunogenicity” defined as the immune response of the immune system to exogenous protein is the most important reliability criteria of all the biotechnological drugs including reference biotechnological and biosimilar drugs. Generally, biotechnological drugs can create immune response in the body due to their large and complex structures.

Authorities request the assessment of immunogenicity before licensing since it has a lethal risk although occurred in few cases.

Immunogenicity risks are assessed in small molecule chemical drugs by preclinical studies while it cannot be assessed in preclinical studies since the immune response in biotechnological drugs having a protein structure vary based on species. Therefore, a detailed assessment must be carried out and the immunogenicity must be included in risk management plans before licensing.

Immunogenicity is related to the following factors according to the EMA guide. Therefore, it is considered that taking these factors account for the monitoring of the product reliability in especially clinical phase studies will provide convenience.

  • 1. Patient and disease related factors
  • Genetic factors affecting immune response
  • Age
  • Disease related factors
  • Simultaneous treatment programs
  • Treatment period, administration mode, treatment methods
  • Previous exposure to similar or related protein
  • 2. Product related factors
  • Antigenic structure of protein
  • Formulation
  • Attachments formed outside the aggregation and protein structure
  • Impurities
  • Physicochemical interactions related to primer package
  • Variables depending on storage conditions