The Therapy Allergen Ordinance (TAO) came into force in Germany in 2008 in order to ensure proven and tested quality, efficacy and safety of therapy allergens for the treatment of allergies to frequent allergen sources (birch, alder, hazel, sweet grasses (without maize), bee-, yellow jacket-venom). It excludes exemptions from marketing authorizations (MA) for AIT-products containing these allergens. Due to the particular nature of the therapeutic allergens, rather long transitional periods are legally defined to resolve deficient clinical data. The aim was to analyze the status quo of AIT products developed according to TAO.
Quality data and clinical trials of AIT products subjected to TAO (obtained until 2019) were analyzed and findings were clustered.
The first two AIT products (for tree-pollen allergy) received a national MA in 2018. Of the 123 initial MA applications submitted, 65 are still active (26 for grass-, 17 for tree-, 5 for grass-/tree-pollen-mix and 17 for house dust mite allergy). Quality issues frequently identified were: Lack of comparability of the drug due to extensive changes in the manufacturing process, insufficient/missing stability data or process validation, insufficiently validated analytical methods, unsuitable in-house reference preparations, inadequate specifications and/or in-process controls. Dose-finding and phase III studies are required for MA. Doses of best benefit/risk balance were recommended for phase III studies. PEI takes measures to ensure that products of presumptive lacking efficacy based on study results do not gain access to the market.
In Germany, TAO ensures that all previously untested named patient products for the treatment of frequent allergies are subjected to an assessment of their risk/benefit ratio according to the current state of science.