Review
Allergen-specific immunotherapy and evidence: A European regulatory perspective
Detlef Bartel, Andreas Bonertz, Diana Hartenstein, Stefan Kaul, Iris Lauer, Christina Reeb, Karen Rösner-Friese, Katja Sliva, Julia Zimmer, Stefan Vieths, and Vera Mahler
Volume 7 (2023) p. 198 - 210
Abstract
Allergologie select, Vol. 7/2023 (198-210)
Allergen-specific immunotherapy and evidence: A European regulatory perspective
Detlef Bartel, Andreas Bonertz, Diana Hartenstein, Stefan Kaul, Iris Lauer, Christina Reeb, Karen Rösner-Friese, Katja Sliva, Julia Zimmer, Stefan Vieths, and Vera Mahler
Paul-Ehrlich-Institut, Langen, Germany
Allergen immunotherapy (AIT) has been performed for 112 years. In this article we summarize regulatory standards and challenges based on scientific evidence on AIT. Most crucial and timely aspects concerning AIT are addressed from the regulatory perspective of the authors as employees of a national competent authority in Europe: (1) product specificity; (2) clinical efficacy; (3) treatment for adults and children (needs for extrapolation); (4) allergen exposure chambers; (5) biomarkers; (6) standardization; (7) real-world evidence; (8) independent official batch release (benefit and challenges); (9) harmonization on the EU level. The Paul-Ehrlich-Institut (PEI), the Federal Institute for Vaccines and Biomedicines, in Langen near Frankfurt/Main in Germany, examines and evaluates the benefits and risks of AIT products within the course of clinical development, marketing authorization, and subsequently throughout their entire life cycle to ensure high-quality, safe, and effective AIT products.Correspondence to:
Prof. Dr. Vera Mahler, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51 – 59, 63325 Langen, Germany
Email: [email protected]
Discussion
DGAKI and PEI in dialogue 2023: Diagnostics and allergen immunotherapy
Oliver Pfaar, Eckard Hamelmann, Christian Taube, Martin Wagenmann, Bettina Wedi, Thomas Werfel, Detlef Bartel, Andreas Bonertz, Diana Hartenstein, Susanne Kaul, Vera Mahler, and Margitta Worm
Volume 7 (2023) p. 229 - 235
Abstract
Allergologie select, Vol. 7/2023 (229-235)
DGAKI and PEI in dialogue 2023: Diagnostics and allergen immunotherapy
Oliver Pfaar1, Eckard Hamelmann2, Christian Taube3, Martin Wagenmann4, Bettina Wedi5, Thomas Werfel6, Detlef Bartel7, Andreas Bonertz7, Diana Hartenstein7, Susanne Kaul7, Vera Mahler7, and Margitta Worm8
1Section of Rhinology and Allergy, Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Marburg, Philipps-Universität Marburg, Marburg, 2Children’s Center Bethel, University Hospital OWL, Bielefeld University, Bielefeld, 3Department of Pulmonary Medicine, University Hospital Essen – Ruhrlandklinik, Essen, 4Department of Otorhinolaryngology, Düsseldorf University Hospital, Heinrich Heine University, Düsseldorf, 5Comprehensive Allergy Center, Department of Dermatology and Allergy, Hannover Medical School, Hannover, 6Department of Dermatology and Allergy, Hannover Medical School, Hannover, 7Paul-Ehrlich-Institut, Langen, 8Allergology and Immunology, Department of Dermatology, Venereology and Allergology, Charité-Universitätsmedizin Berlin, Berlin, Germany
A roundtable discussion on February 10, 2023 between the German Society for Allergology and Clinical Immunology (DGAKI) and the Paul-Ehrlich-Institut (PEI) aimed to discuss in detail current aspects of allergen immunotherapy (AIT), its regulatory framework under the transitional provision of the Therapy Allergen Ordinance (TAO), and the consequences for the planned guideline work of the DGAKI, regulatory challenges in the approval of AIT products for children and adolescents as well as allergy diagnostics. The content and discussion points of this dialogue are summarized and are set in context with the current literature.Correspondence to:
Prof. Dr. med. Oliver Pfaar, Section of Rhinology and Allergy, Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Marburg, Philipps-Universität, Marburg, Baldinger Strasse, 35043 Marburg, Germany
Email: [email protected]
Original
Procedure for a standardized preparation of skin prick test solutions for the diagnosis of occupational type I allergies in the absence of commercial extracts
Sabine Kespohl, Robin Jost, Silke Maryska, Lena-Maria Altin, Ingrid Sander, Stefan Schülke, Kathrin E. Paulus-Tremel, Andreas Bonertz, Thomas Klose, Vera Mahler, and Monika Raulf
Volume 8 (2024) p. 238 - 250
Abstract
Allergologie select, Vol. 8/2024 (238-250)
Procedure for a standardized preparation of skin prick test solutions for the diagnosis of occupational type I allergies in the absence of commercial extracts
Sabine Kespohl1, Robin Jost2, Silke Maryska1, Lena-Maria Altin3, Ingrid Sander1, Stefan Schülke2, Kathrin E. Paulus-Tremel2, Andreas Bonertz2, Thomas Klose3, Vera Mahler2, and Monika Raulf1
1Institute for Prevention and Occupational Medicine of the DGUV, Ruhr-University Bochum (IPA), Bochum, 2Division Allergology, Paul-Ehrlich-Institut, Langen, and 3Sonnenschein Apotheke, Koblenz, Germany
In order to ensure valid diagnostics for occupational test allergen solutions despite the ongoing reduction in the availability of commercial test extracts, a plan B was initiated for the possible production of skin prick test (SPT) solutions in public pharmacies. For important occupational allergen sources (wheat and rye, storage mites, animal epithelia, mold material) laboratory extraction methods were analyzed in comparison to pharmacy compatible extraction methods regarding protein quantity and quality in SDS-PAGE combined with silver staining. Subsequently, using the example of bovine epithelia, adapted extraction procedures as well as in-process and final product controls were transferred to a public pharmacy. Allergen sources with a high protein content, such as wheat and rye grains as well as storage mites, showed good comparability of the extractable protein quantity and protein pattern, regardless of the applied extraction method. In contrast, allergen source materials with a low total protein content, such as animal epithelia and molds, can benefit from laboratory extraction conditions such as mechanical disruption and specific buffer additives. In the qualitative protein silver staining, characteristic protein patterns were identified for each allergen source. Depending on the extraction method, only minor differences in total protein patterns were observed in animal epithelia and molds. Using source materials from two suppliers, the resulting allergen extracts displayed clear differences in protein content in storage mites and quantitative and qualitative differences in molds. A practical preparation attempt of SPT solutions in a public pharmacy was successful. SPT solutions prepared with adapted pharmacy extraction methods showed a comparable protein and Bos d 2 allergen content and equivalent qualities in the protein pattern compared to a previously available commercial SPT solution. Accordingly, it can be assumed that standardized SPT solutions with sufficient allergen quality for occupational allergen sources can be prepared in public pharmacies if certified allergen sources with appropriate protein content are available.Correspondence to:
Dr. Sabine Kespohl, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Department Competence Center Allergology/Immunology, Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany
Email: [email protected]
Review
Possible manufacture of test allergens in public pharmacies for the diagnosis of type I allergies: Legal aspects
Robin Jost, Sabine Kespohl, Kathrin E. Paulus-Tremel, Julia Zimmer, Andreas Bonertz, Ingrid Sander, Thomas Klose, Lena-Maria Altin, Simone Heller, Ralph Heimke-Brinck, Frank Dörje, Susanne Philippus, Matthias Meyer, Sabrina Segebrecht, Torsten Wessel, Dieter Starke, Stefan Schülke, Monika Raulf, and Vera Mahler
Volume 8 (2024) p. 251 - 264
Abstract
Allergologie select, Vol. 8/2024 (251-264)
Possible manufacture of test allergens in public pharmacies for the diagnosis of type I allergies: Legal aspects
Robin Jost1,2, Sabine Kespohl3, Kathrin E. Paulus-Tremel1, Julia Zimmer1, Andreas Bonertz1, Ingrid Sander3, Thomas Klose4, Lena-Maria Altin4, Simone Heller4, Ralph Heimke-Brinck5, Frank Dörje5, Susanne Philippus6, Matthias Meyer7, Sabrina Segebrecht8, Torsten Wessel9, Dieter Starke10, Stefan Schülke1, Monika Raulf3, and Vera Mahler1,2
1Allergology Division, Paul-Ehrlich-Institut (PEI), Langen (Hesse), 2Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, 3Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (DGUV), Institute of the Ruhr-Universität Bochum (IPA), Bochum, 4Sonnenschein Apotheke, Koblenz, 5Pharmacy Department, Erlangen University Hospital, Erlangen, 6Thuringian State Authority for Consumer Protection, Department Pharmacy, Bad Langensalza, 7Bundeswehr Commissioner for the Surveillance of Medicinal Products, Supervisory Agency for Public Law Tasks of the Bundeswehr Medical Service South, Munich, 8Drug Supervision, State Social Services Agency of Land Schleswig-Holstein, Neumünster, 9Pharmacy Inspector, Local inspectorate for pharmacies, District of Wesel, Moers, and 10 State Agency for Social Affairs, Youth and Care, Rhineland-Palatinate, Koblenz, Germany
The availability of high-quality skin test allergens is a prerequisite for the reliable diagnosis of occupational type I allergies. Due to the withdrawal of existing marketing authorizations (MAs) by pharmaceutical companies and the lack of new MAs for commercial test allergens, there is an increasing diagnostic gap in Germany and other EU member states, which makes it necessary to investigate alternative ways of providing in vivo diagnostics. The German Medicinal Products Act (Arzneimittelgesetz = AMG) allows for the possibility of preparing medicinal products in pharmacies without the need for an MA or a manufacturing authorization pursuant to Section 13 (2) No. 1 in conjunction with Section 13 (2a) Sentence 2 No. 3 AMG. This also includes test allergens. In addition to the AMG, the requirements of the German Ordinance on the Operation of Pharmacies (Apothekenbetriebsordnung – ApBetrO) and the European Pharmacopoeia apply in particular. Medicolegal and practical challenges, as well as potentials of manufacturing skin prick test solutions in public pharmacies are presented based on examples of different allergen source materials.Correspondence to:
Prof. Dr. Vera Mahler, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225 Langen, Germany
Email: [email protected]
