title: Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium.
abstract: Biopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, including inflammatory and autoimmune diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affecting clinical safety or efficacy, remain among the most common negative effects associated with this important class of drugs. To manage and reduce risk of unwanted immunogenicity, diverse communities of clinicians, pharmaceutical industry and academic scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk and elucidation of underlying causes. Collaboration and alignment of efforts across these communities is made difficult due to lack of agreement on concepts, practices and standardized terms and definitions related to immunogenicity. The Innovative Medicines Initiative (IMI; www.imi-europe.org), ABIRISK consortium [Anti-Biopharmaceutical (BP) Immunization Prediction and Clinical Relevance to Reduce the Risk; www.abirisk.eu] was formed by leading clinicians, academic scientists and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation and establish common definitions around terms and concepts related to immunogenicity. These efforts are expected to facilitate broader collaborations and lead to new guidelines for managing immunogenicity. To support alignment, an overview of concepts behind the set of key terms and definitions adopted to date by ABIRISK is provided herein along with a link to access and download the ABIRISK terms and definitions and provide comments (http://www.abirisk.eu/index_t_and_d.asp).
authors.affiliation: Pfizer, Immunogenicity Sciences Disciple, Pharmacokinetics, Dynamics and Metabolism.
authors.forename: B
authors.initials: B
authors.lastname: Rup
authors.affiliation: INSERM, UMR996, Faculté Pharmacie, Université Paris Sud, France.
authors.forename: M
authors.initials: M
authors.lastname: Pallardy
authors.affiliation: GlaxoSmithKline, Clinical Immunology-Biopharm, King of Prussia, PA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Sikkema
authors.affiliation: Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Albert
authors.affiliation: Hôpital Saint-Louis, Department of Gastroenterology, GETAID, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Allez
authors.affiliation: INSERM, UMR669, University of Paris Sud, France.
authors.forename: P
authors.initials: P
authors.lastname: Broet
authors.affiliation: Pfizer, Early Biotech Clinical Development, Cambridge, MA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Carini
authors.affiliation: Centre for Neuroscience and Trauma, Blizard Institute, Queen Mary University of London, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Creeke
authors.affiliation: GlaxoSmithKline, Worldwide Epidemiology, Southall, UK.
authors.forename: J
authors.initials: J
authors.lastname: Davidson
authors.affiliation: Clinical Immunology and Rheumatology, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: De Vries
authors.affiliation: Pfizer, Drug Safety R&D, Groton, CT, USA.
authors.forename: D
authors.initials: D
authors.lastname: Finco
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Fogdell-Hahn
authors.affiliation: Department of Neurology and Center for Clinical Neuroscience, MS Center, Charles University in Prague, Prague, Czech Republic.
authors.forename: E
authors.initials: E
authors.lastname: Havrdova
authors.affiliation: Sanofi-Aventis, Clinical Exploratory and Pharmacology, Chilly-Mazerin, FR.
authors.forename: A
authors.initials: A
authors.lastname: Hincelin-Mery
authors.affiliation: GlaxoSmithKline, Clinical Immunology-Biopharm R&D, King of Prussia, PA, USA.
authors.forename: M
authors.initials: M
authors.lastname: C Holland
authors.affiliation: Department of Neurology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: P E
authors.initials: PE
authors.lastname: H Jensen
authors.affiliation: Centre for Rheumatology, University College London, London, UK.
authors.forename: E C
authors.initials: EC
authors.lastname: Jury
authors.affiliation: UCB Pharma, Bioanalytical R&D, Slough, UK.
authors.forename: H
authors.initials: H
authors.lastname: Kirby
authors.affiliation: Merck-Serono, Institute of Drug Metabolism and Pharmacokinetics, Grafing, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Kramer
authors.affiliation: INSERM, UMR S 1138, Université Pierre et Marie Curie, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Lacroix-Desmazes
authors.affiliation: Ipsen Innovation, Pharmacokinetics Drug Metabolism Department, Les Ulis, France.
authors.forename: J
authors.initials: J
authors.lastname: Legrand
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Universita di Firenze, Firenze, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Maggi
authors.affiliation: CEA-Saclay Institute of Biology and Technologies, Gif sur Yvette, France.
authors.forename: B
authors.initials: B
authors.lastname: Maillère
authors.affiliation: INSERM, U1012, Hôpitaux Universitaires Paris Sud, Rhumatologie, Paris, France.
authors.forename: X
authors.initials: X
authors.lastname: Mariette
authors.affiliation: Centre for Rheumatology Research, University College London, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Mauri
authors.affiliation: Sanofi Aventis, Structural Biology, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Mikol
authors.affiliation: University of Tours Francois Rabelais, CNRS UMR 7292, Tours, France.
authors.forename: D
authors.initials: D
authors.lastname: Mulleman
authors.affiliation: Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Oldenburg
authors.affiliation: CNRS UMR 7292 'GICC', Faculty of Medicine, Tours, France.
authors.forename: G
authors.initials: G
authors.lastname: Paintaud
authors.affiliation: Novo Nordisk, Immunogenicity, Måløv, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: R Pedersen
authors.affiliation: Istituto Giannina Gaslini, Pediatria II, Rheumatology, Genova, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Ruperto
authors.affiliation: Division of Haematology/Transfusion Medicine, Paul-Ehrlich-Institut, Langen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Seitz
authors.affiliation: Drug Metabolism Pharmacokinetics-Biologics, Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Spindeldreher
authors.affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: F
authors.initials: F
authors.lastname: Deisenhammer
mesh_terms: D000486:Allergy and Immunology / Q000592:standards; D004342:Drug Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D004345:Drug Industry / Q000458:organization & administration / Q000592:standards; D015507:Drugs, Investigational / Q000009:adverse effects / Q000592:standards* / Q000627:therapeutic use; D017408:Guidelines as Topic / Q000592:standards*; D006801:Humans; D009936:Organizational Innovation; D016134:Organizational Policy; D012015:Reference Standards; D009626:Terminology as Topic
chemical_list: D015507:Drugs, Investigational
keywords: ABIRISK consortium; anti-drug antibodies; biopharmaceuticals; immunogenicity