O Pfaar1,2, M A Calderon3,4, C P Andrews5, E Angjeli6, K C Bergmann7, J H Bønløkke8, F de Blay9,10, P Devillier11, A K Ellis12,13, R Gerth van Wijk14, J M Hohlfeld15, F Horak16, R L Jacobs5, L Jacobsen17, M Jutel18,19, S Kaul20, M Larché21, D Larenas-Linnemann22,23, R Mösges24, H Nolte25, P Patel26, L Peoples6, R L Rabin27, C Rather5, A M Salapatek26, T Sigsgaard8, S Thaarup28, J Yang29, P Zieglmayer16, T Zuberbier30, P Demoly31,32. 1. Department of Otorhinolaryngology, Head and Neck Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. 2. Center for Rhinology and Allergology, Wiesbaden, Germany. 3. Section of Allergy and Clinical Immunology, Imperial College London, London, UK. 4. National Heart & Lung Institute, Royal Brompton Hospital, London, UK. 5. Biogenics Research Chamber LLC, San Antonio, TX, USA. 6. Ora, Inc., Andover, MA, USA. 7. Allergy-Centre-Charité, Charité Universitätsmedizin Berlin, Berlin, Germany. 8. Department of Public Health, Section for Environment, Occupation and Health, Danish Ramazzini Center, Aarhus University, Aarhus, Denmark. 9. ALYATEC, Strasbourg, France. 10. Chest Disease Department, University Hospital of Strasbourg and Federation of Translational Medicine, EA3072, Strasbourg University, Strasbourg, France. 11. UPRES EA 220, Airway Diseases Department, Hôpital Foch, Université Versailles Saint Quentin, University Paris Saclay, Suresnes, France. 12. Department of Medicine, Queen's University, Kingston, ON, Canada. 13. Environmental Exposure Unit, Kingston General Hospital, Kingston, ON, Canada. 14. Section of Allergology, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. 15. Department of Clinical Airway Research, Fraunhofer Institute of Toxicology and Experimental Medicine (ITEM), Hannover, Germany, Member of the German Center for Lung Research. 16. Vienna Challenge Chamber, Vienna, Austria. 17. Allergy Learning and Consulting (ALC), Copenhagen, Denmark. 18. ALL-MED Medical Research Institute, Wrocław, Poland. 19. Wroclaw Medical University, Wrocław, Poland. 20. Division of Allergology, Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, Langen, Germany. 21. Firestone Institute for Respiratory Health, Department of Medicine, St. Joseph's Hospital Healthcare, McMaster University, Hamilton, ON, Canada. 22. Department of Investigation, Hospital Médica Sur, Mexico City, Mexico. 23. Center for Excellence in Asthma and Allergy, Mexico City, Mexico. 24. Institute of Medical Statistics, Informatics and Epidemiology (IMSIE), University Hospital of Cologne, University at Cologne, Cologne, Germany. 25. Merck&Co, Kenilworth, NJ, USA. 26. Inflamax Research Inc., Mississauga, ON, Canada. 27. Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USA. 28. Mobile Chamber Experts GmbH (MCX), Berlin, Germany. 29. Red Maple Trials, Ottawa, ON, Canada. 30. Global Allergy and Asthma European Network (GA2LEN), Department of Dermatology & Allergy, Charité Universitätsmedizin Berlin, Berlin, Germany. 31. Département de Pneumologie et Addictologie, Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, Montpellier, France. 32. UPMC Paris 06, UMR-S 1136, IPLESP, Equipe EPAR, Sorbonne Universités, Paris, France.
Abstract
BACKGROUND: Allergen exposure chambers (AECs) are clinical facilities allowing for controlled exposure of subjects to allergens in an enclosed environment. AECs have contributed towards characterizing the pathophysiology of respiratory allergic diseases and the pharmacological properties of new therapies. In addition, they are complementary to and offer some advantages over traditional multicentre field trials for evaluation of novel therapeutics. To date, AEC studies conducted have been monocentric and have followed protocols unique to each centre. Because there are technical differences among AECs, it may be necessary to define parameters to standardize the AECs so that studies may be extrapolated for driving basic immunological research and for marketing authorization purposes by regulatory authorities. METHODS: For this task force initiative of the European Academy of Allergy and Clinical Immunology (EAACI), experts from academia and regulatory agencies met with chamber operators to list technical, clinical and regulatory unmet needs as well as the prerequisites for clinical validation. RESULTS: The latter covered the validation process, standardization of challenges and outcomes, intra- and interchamber variability and reproducibility, in addition to comparability with field trials and specifics of paediatric trials and regulatory issues. CONCLUSION: This EAACI Position Paper aims to harmonize current concepts in AECs and to project unmet needs with the intent to enhance progress towards use of these facilities in determining safety and efficacy of new therapeutics in the future.
BACKGROUND: Allergen exposure chambers (AECs) are clinical facilities allowing for controlled exposure of subjects to allergens in an enclosed environment. AECs have contributed towards characterizing the pathophysiology of respiratory allergic diseases and the pharmacological properties of new therapies. In addition, they are complementary to and offer some advantages over traditional multicentre field trials for evaluation of novel therapeutics. To date, AEC studies conducted have been monocentric and have followed protocols unique to each centre. Because there are technical differences among AECs, it may be necessary to define parameters to standardize the AECs so that studies may be extrapolated for driving basic immunological research and for marketing authorization purposes by regulatory authorities. METHODS: For this task force initiative of the European Academy of Allergy and Clinical Immunology (EAACI), experts from academia and regulatory agencies met with chamber operators to list technical, clinical and regulatory unmet needs as well as the prerequisites for clinical validation. RESULTS: The latter covered the validation process, standardization of challenges and outcomes, intra- and interchamber variability and reproducibility, in addition to comparability with field trials and specifics of paediatric trials and regulatory issues. CONCLUSION: This EAACI Position Paper aims to harmonize current concepts in AECs and to project unmet needs with the intent to enhance progress towards use of these facilities in determining safety and efficacy of new therapeutics in the future.
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