FDA (U.S. Food & Drug Administartion)

Draft Guidance: Assay Development and Validation for Immunogenicity Testing of Therapeutic Protein Products. April 2016 Pharmaceutical Quality/CMC Revision 1.

Guidance for Industry: Potency Tests for Cellular and Gene Therapy Products. January 2011

EMA (European Medicines Agency)

Draft guideline/ Guidance for Industry: Immunogenicity assessment of biotechnology-derived therapeutic proteins. EMEA/CHMP/BMWP/14327/2006 Rev. 1.

Guideline on development, production, characterisation and specification for monoclonal antibodies and related products. 21 July 2016 EMA/CHMP/BWP/532517/2008.



Lallemand C, Kavrochorianou N, Steenholdt C, Bendtzen K, Ainsworth MA, Meritet JF, Blanchard B, Lebon P, Taylor P, Charles P, Alzabin S, Tovey MG. Reporter gene assay for the quantification of the activity and neutralizing antibody response to TNFalpha antagonists. J. Immunol. Methods. 373,229-239 (2011).

Lallemand C, Meritet JF, Erickson R, Grossberg SE, Roullet E, Lyon-Caen O, Lebon P, Tovey MG. Quantification of neutralizing antibodies to human type I interferons using division-arrested frozen cells carrying an interferon-regulated reporter-gene. J. Interferon Cytokine Res. 28, 393-404 (2008).

Lallemand C, Meritet JF, Erickson R, Lebon P, Tovey MG. Characterization of neutralizing antibodies to Interferon ß using a novel gene-reporter assay: Neutralization titer is dependent upon specific activity of the Interferon β Subtype. J Interferon Cytokines Res 28, 393-404 (2008).

Ravnborg M, Bendtzen K, Christensen O, Jensen PEH, Hesse D, Tovey MG, Sorensen PS. Treatment with azathioprine and cyclic methylprednisolone has little or no effect on bioactivity in anti-interferon beta antibody-positive patients with multiple sclerosis. Mult. Scler. 15, 323-328 (2009).

Bendtzen K, Svenson M. Enzyme immunoassays and radioimmunoassays for quantification of anti-TNF biopharmaceuticals and anti-drug antibodies. In: Tovey MG, editor. Detection and quantification of antibodies to biopharmaceuticals. Practical and applied considerations. West Sussex, UK: A. John Wiley & Sons, Inc; 2011. p. 83-101.

Bendtzen K. Anti-TNF-α biotherapies: perspectives for evidence-based personalized medicine. Immunotherapy. 4, 1167-1179 (2012).

Steenholdt C, Ainsworth MA, Tovey M, Klausen TW, Thomsen O, Brynskov J, Bendtzen K. Comparison of techniques for monitoring infliximab and antibodies against infliximab in Crohn’s disase. Ther. Drug Monit. 35, 530-538, (2013).

Bendtzen K. Personalized medicine: theranostics (therapeutics diagnostics) essential for rational use of tumor necrosis factor-alpha antagonists. Discov Med. 15, 201–211, (2013).

Article in Genetic Engineering & Biotechnology News (URL: (2015-11-01)

Pavlov IY, Carper J, Lázár-Molná E and Delgado JC. Clinical Laboratory application of a reporter-gene assay for measurement of functional activity and neutralizing antibody response to infliximab. Clinica Chimica Acta 453, 147-153 (2016).

Anti-CCP2, Gold Standard