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Wise et al.

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(ID 50 EAL) determines the units listed in either Allergy Units (AU) or Biologic Allergy Units (BAU). AU is used for dust mites. A mean ID 50 EAL of 14 threefold dilutions is defined as 100,000 BAU/mL and 12 threefold dilutions 10,000 BAU/mL. 1577 The FDA allergen standards are compared to the produced allergen extracts by the manufacturers. The process is different for extracts where the major allergen reactivity correlates with overall allergen reactivity (cat and ragweed) than for extracts that do not have a major allergen that correlates as strongly. A major allergen is defined as a specific protein epitope that more than 50% of individuals allergic to that species react. If there is a major allergen that correlates strongly with the population’s clinical reactivity, the manufacturer can compare their extract to the standard extract by gel electrophoresis with the gel having monoclonal IgG antibodies to the major allergen protein. If there is not a single allergen that correlates well with the reactivity of the population, the manufactured extract and the standard are compared through competition enzyme-linked immunosorbent assay (ELISA) using pooled serum IgE from known allergic subjects. The manufacturer’s extract must fall within a 70% to 140% range of the FDA’s reference. 1576 The amount of major allergen is sometimes listed in μ g/mL, Fel d 1 units (cat), or Antigen E units (ragweed). Standardized inhalant allergens within the United States include cat, Dermatophagoides pteronyssinus, Dermatophagoides farinae , short ragweed, and multiple grass species. 1577 Some allergen extracts in Europe use the Nordic method where 10,000 biologically standardized units/mL is comparable to a skin reaction elicited by 10 mg/mL of histamine. 1577 In conclusion, an international consensus has not been established for allergen units or standardization of allergen extracts. While standardization and transparent potency assays increase manufacturing costs, it is widely agreed that greater standardization and consistency across manufacturers would be beneficial. Variations in allergen extracts between manufacturers may discourage medical providers from changing between vendors reducing the effect of price on competition. The multitude of allergen extract units and variability also complicates the interpretation and application of published studies between the United States, the EU, and other countries. The WHO has identified allergen standardization as a problem and the EU funded a project known as CREATE, “Development of Certified Reference Materials for Allergenic Products and Validation of Methods for the Quantification.” 1578 But as of 2017, multiple allergen units are still in use worldwide. IX.D.2. Modified allergen extracts— The goal of AIT is to suppress the underlying inflammatory diathesis and induce a state of clinical tolerance to the relevant allergen. This thereby attenuates, if not completely arrests, the inflammation that manifests as AR. Traditional AIT with native, unmodified extracts is successful but has several limitations. Immunotherapy can lead to adverse reactions which rarely can be life-threatening. Besides the risks, allergen extracts have significant production costs with limitations of availability and consistency between batches. Variations exist in pharmaceutical-produced native extracts in the allergen amounts, potencies, and immunogenicity of individual allergen molecules that cannot be controlled in the manufacturing process. 1579

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Int Forum Allergy Rhinol . Author manuscript; available in PMC 2020 June 10.