How to systematically evaluate immunogenicity of therapeutic proteins - regulatory considerations

N Biotechnol. 2009 Jun;25(5):280-6. doi: 10.1016/j.nbt.2009.03.012. Epub 2009 Apr 5.


Antibody formation as an immune reaction to a 'foreign' protein antigen is an expected physiological reaction that is in many cases intentionally triggered, for example in the case of vaccinations. However, an unwanted immune response to a therapeutic protein may lead to a loss of efficacy and/or to severe side effects. The Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMEA) issued a multidisciplinary guideline providing general recommendations from a marketing authorisation perspective on how to assess an unwanted immune response following the administration of a biological drug. In this article, we provide an in-depth regulatory discussion on key principles of systematic evaluation of immunogenicity during development of biotechnological medicinal products, including examples.

Publication types

  • Review

MeSH terms

  • Biological Products / administration & dosage*
  • Biological Products / analysis
  • Biological Products / immunology
  • Biotechnology
  • Drug Approval / organization & administration*
  • Drug Industry
  • Drug-Related Side Effects and Adverse Reactions
  • Guidelines as Topic
  • Humans
  • Immunity*
  • Legislation, Drug
  • Marketing
  • Proteins / immunology*
  • Proteins / therapeutic use*
  • Risk Factors


  • Biological Products
  • Proteins