Regulatory Aspects of Allergen-Specific Immunotherapy: Europe Sets the Scene for a Global Approach

After 100 years from its introduction in the treatment of allergic patients, regulatory aspects of allergen-specific immunotherapy (ASI) are still incompletely defined and very heterogeneous among different countries. To better understand the scenario of regulatory documents applying to ASI in Europe and their different compelling value, it might be useful, for pure didactic purposes of this article and in agreement with the thoughtful paper of Kaul et al, to classify them according to a hierarchic scale (from A to D), as in the Shekelle ranking of the level of evidence of scientific statements. Type A documents are represented by European Community (EC) Regulations, which are valid and compelling for all Member States. The same value can be assigned to the European Pharmacopeia, which includes a specific Monograph on Allergen Products. Among Type B documents, we can include EC Directives. These are not compelling for Member States, which however are obliged to adapt to the Directives by producing national laws within a given period. Type C documents may be represented by the European Medicine Agency (EMA) Guidelines. These have only value of orientation, mainly for clinical trials (which should however justify, in case of discrepancies, why guidelines were not followed). A special type of guideline is represented by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceutical for Human Use (ICH), a consensus document agreed on by the European, American, and Japanese Regulatory Agencies. Position Papers or Practice Parameters of Expert Panels or of Scientific Societies can be considered as Type D documents because they only represent individual opinions, even if evidence based, certainly useful for clinical practice but of no regulatory value. As in the Shekelle classification, the different types of evidence imply a corresponding level of strength of recommendations, documents on immunotherapy have a different regulatory impact, mandatory for European Regulations and National Laws following EC Directives, of orientation only for Types C and D documents. Table 1 reports some examples of regulatory documents for IAS distinguished according to the categories described above.