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]
Review
Regulatory framework for development and marketing authorization of allergen products for diagnosis of rare type I and type IV allergies: The current status
Julia Zimmer and Vera Mahler
Volume 8 (2024) p. 212 - 219
Abstract
Allergologie select, Vol. 8/2024 (212-219)
Regulatory framework for development and marketing authorization of allergen products for diagnosis of rare type I and type IV allergies: The current status
Julia Zimmer and Vera Mahler
Paul-Ehrlich-Institut, Division of Allergology, Langen, Germany
Development, production, and marketing authorization of allergen products is generally challenging due to several specific characteristics, including the natural source as well as the multitude of allergenic materials. Also, depending on the frequency of sensitization in the population, the number of patients available for inclusion in clinical trials can be a limiting factor for product development. In the development of allergen products for diagnosis of type I and type IV allergies these challenges are particularly demanding because, in contrast to certain products for allergen-specific immunotherapy, no exemptions from marketing authorization are foreseen for this product group in Directive 2001/83/EC. Thus, the regulatory framework is constantly adapted within the legal scope in order to balance necessary regulatory requirements ensuring quality, safety, and efficacy with the clinical need for a comprehensive range of diagnostic allergen products. In this article, we give an overview on the current regulatory framework for development and marketing authorization of allergen products for diagnosis of rare type I and type IV allergies.Correspondence to:
Prof. Dr. med. Vera Mahler, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51 – 59, 63325 Langen, 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]
Original
Therapy Allergen Ordinance (TAO): The final stretch
Vera Mahler, Diana Hartenstein, Iris Lauer, Stefan Vieths, Claudia Ruoff, Julia Zimmer, and Susanne Kaul
Volume 9 (2025) p. 93 - 99
Abstract
Allergologie select, Vol. 9/2025 (93-99)
Therapy Allergen Ordinance (TAO): The final stretch
Vera Mahler1, Diana Hartenstein1, Iris Lauer1, Stefan Vieths2, Claudia Ruoff3, Julia Zimmer1, and Susanne Kaul1
1Allergology Division, 2President of the Paul-Ehrlich-Institut; Molecular Allergology Research Group, and 3Legal Affairs Section, Safety of Biomedicines and Diagnostics Division, Paul-Ehrlich-Institut, Langen, Germany
The Therapy Allergen Ordinance (TAO) aims to migrate allergen immunotherapy (AIT) products for the treatment of common allergies, which were previously marketed in Germany as named patient products (NPPs), into authorized products provided their quality, efficacy, and safety are adequately shown. The TAO applies to all NPPs containing active ingredients based on the following allergen sources: house dust mites, bee venom, wasp venom, pollen from sweet grasses (excluding maize), birch, alder, or hazel. The last product-specific deadlines granted under the TAO for the submission of clinical data relevant to the marketing authorization process will expire in 2026. The subsequent final assessment of the updated marketing authorization application (MAA) is carried out by the competent authority, the Paul-Ehrlich-Institut. During this period of processing by the competent authority, the products remain marketable until a decision regarding the MAA has been reached. Currently (as of August 08, 2025), 40 AIT products are still marketable under the transitional provisions of the TAO (10 preparations for the treatment of allergies to house dust mites, 10 against tree pollen allergies, 16 against grass pollen allergies, and 4 mixed preparations containing non-homologous allergen groups). For 8 of these products, pharmaceutical companies have initiated the withdrawal of MAA as of October 01, 2025 or January 31, 2026, respectively. Prior to the final assessment of the updated MAAs, the competent authority is unable to make any public statements as to whether the individual applications for the remaining 32 products under the transitional provision will be concluded positively with the granting of the marketing authorization or its rejection. With the rejection of a marketing authorization, the product-specific marketability ends immediately, i.e., there is no additional sell-off period for the TAO products concerned. If a marketing authorization is granted, the marketability of the specific product is perpetuated.Correspondence to:
Prof. Vera Mahler, MD, Abteilung Allergologie, Paul-Ehrlich-Institut, Paul-Ehrlich-Str. 51-59, 63225 Langen, Germany
Email: [email protected]
