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Wise et al.

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multiple types of units that can be grouped into nonstandardized, standardized, or proprietary. The difference between standardized and nonstandardized extracts is discussed later this section. Potency of an allergen can have different meanings. Potency sometimes refers to the allergenicity of a source material’s proteins or the biologic activity. For example, grass pollens are generally more potent than tree pollens. The typical grass-allergic person would have a larger clinical reaction to grass pollen than a tree-allergic person to the same amount of tree pollen. However, a measure of potency of an allergen extract may also just refer to the strength or concentration measured in units. Nonstandardized allergen extracts.: Most allergen extracts available in the United States are nonstandardized. Allergen extracts are regulated by the Center for Biologics Evaluation and Research (CBER) under the FDA in the United States. 1576 Allergen extracts are required to list the biologic source, a potency unit, and an expiration date. • Weight/volume (wt/vol). Weight/volume refers to the ratio of grams of dry raw material to milliliters of extract solvent. Commonly this is 1/20 wt/vol, which means that for every 1 g of raw material (pollen for example) there is 20 mL of extract solvent. This does not provide direct information about the amount of allergenic proteins in the allergen extract nor its biologic activity. However, it implies a reproducible methodology was employed. 1571 • Protein nitrogen units (PNUs). This is the second most common nonstandardized unit currently used in the United States. PNU refers to an assay of the precipitable protein nitrogen by phosphotungstic acid which correlates with the total protein. While most of the protein is non-allergenic, the total protein is another method to quantitate an allergen extract’s content. 1571 In Europe, many manufacturers use proprietary units and internal quality controls which must utilize a validated assay. 1572 This European manufacturer-based quality control is known as “In House Reference Preparation.” 1573 However, the European Medical Agency has been developing a standardized framework based on protein homology rather than source species. 1577 The EU is also developing additional allergen standards with the WHO starting with Bet v 1 and Phl p 5a. 1577 Standardized allergen extracts.: In the United States, standardized allergen extracts are tested by the manufacturer to be within a reference range (70-140%) when compares to a standard provided by the CBER. The government’s standard is referenced to the reactivity in highly allergic individuals, creating a standard of biologic activity. The CBER creates the standard extract through testing in known “highly allergic” individuals. They use serial intradermal 3-fold titrations and measure potency by how many dilutions are needed to produce a flare reaction of a certain size. The size is determined by measuring the largest diameter and adding the length of a line 90 degrees to the largest diameter line. The orthogonal sums are plotted for each dilution and a best fit line drawn. The concentration that corresponds to where the orthogonal sum of the flare is 50 mm

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