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Major Allergen Content In Allergen Immunotherapy Products: The Limited Value of Numbers

Becker S1, Fassio F2, Muñoz-Cano R3, Klimek L4, Vidal C5, Heath MD6, Kündig TM7, Vogelberg C8, Toran C9, Jensen-Jarolim E10,11, Heffler E12,13, Tomazic PV14, Feindor M6,15, Hewings S6, Carreno T6, Morales M9, Mösges R16, Skinner MA6, Graessel A6,15, Hernandez D9, Kramer MF6,15

1Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Tübingen, Tübingen, Germany
2Centro Studi Allergie ETS, Pistoia, Italy
3Allergy Department, Hospital Clinic, Barcelona, Catalonia, Spain
4Center for Rhinology and Allergy, Wiesbaden, Germany
5Allergy Department, Complejo Hospitalario Universitario de Santiago, Faculty of Medicine, University of Santiago de Compostela, Spain
6Allergy Therapeutics (UK) Ltd, Worthing, United Kingdom
7Department of Dermatology, University of Zurich and University Hospital Zurich, Zurich, Switzerland
8Department of Pediatric Pulmonology and Allergy, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden, Germany
9Allergy Therapeutics Ibérica, Barcelona, Spain
10Institute of Pathophysiology and Allergy Research, Centre of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
11The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Vienna, Austria
12Personalized Medicine, Asthma and Allergy - IRCCS Humanitas Research Hospital - Rozzano (MI), Italy
13Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
14Department of General ORL, H&NS, Medical University of Graz, Austria
15Bencard Allergie GmbH, Munich, Germany
16Institute of Medical Statistics and Computational Biology Faculty of Medicine University of Cologne, Cologne, Germany

J Investig Allergol Clin Immunol 2022; Vol. 32(5)
doi: 10.18176/jiaci.0822

The prevalence of allergic disorders drastically increased over the last 50 years that today they can be considered epidemic. At present, allergen-specific immunotherapy (AIT) is the only therapy targeting the underlying cause of allergic disorders, and its superior evidence is based on accumulated data from clinical trials and observational studies demonstrating efficacy and safety. However, several aspects remain unsolved, such as harmonization and standardization of manufacturing and quantification procedures across manufacturers, homogeneous reporting of strength, and also the establishment of international reference standards for many allergens. This article discusses the issues related to the measurement of major allergen content in AIT extracts, raising the question of whether comparison of products by different manufacturers are appropriate as basis to choose among the different AIT products. Allergen standardization in immunotherapy products is critical to ensure quality and thereby safety and efficacy. However, lack of harmonization in manufacturing process, allergen quantification (methodologies and references), national regulatory differences, clinical practice, and labeling shows that the comparison of AIT products solely based on major allergen amounts is not rationale and, in fact, impossible. Moreover, further inherent characteristics of products and their clinical use such as their state of extract modification, addition of adjuvant or adjuvant-system, route of administration (sublingual/subcutaneous) and cumulative dose as per posology (including the volume per administration) need to be taken into account, when rating the information given for a specific product. Finally, only convincing clinical data can serve as the product-specific evaluation, or the basis for cross-product comparability, for individual products. 

Key words: AIT, Major allergen content, Immunotherapy, Standardization methods, Quality, Adjuvants, Product comparability