The FDA has mandated standardization testing for a limited number of extracts. The purpose of standardization is to minimize the amount of variability between lots and manufacturers of the same extract.
Extracts that have been standardized by the FDA include the northern pasture grasses (Timothy, June, Meadow Fescue, Orchard, Redtop, Perennial Rye, Sweet Vernal) and Bermuda, a southern grass. In addition to these grasses, the FDA has also standardized Dust Mite, Cat, Short Ragweed and Hymenoptera Venom.
Below are described each type of standardized product with their respective potency units in parentheses.
The potency of both the grass and dust mite extracts is estimated by in vitro bioequivalence testing using an ELISA method that measures the inhibition of binding of serum (non-specific IgE) to estimate the extract’s potency relative to the FDA reference. A relative potency ratio of 1.0 (acceptance range = 0.7 – 1.4) indicates that the newly manufactured lot is bioequivalent to the FDA reference. The extract is then assigned a potency value relative to the FDA reference depending on where it falls in the acceptance criteria.
Grasses are standardized in Bioequivalent Allergy Units (BAU). Dust Mites are standardized in Allergy Units (AU). Since the analytical methods are the same, AU is conceptually equivalent to BAU. It has a separate naming convention for historical reasons.
Standardized cat extracts are also labelled in BAU but are analysed using a different method than grass and dust mite. Unfortunately it has not been scientifically determined whether BAU from cat is equivalent to BAU from grass. However, in a practical setting, these units can be considered interchangeable in terms of dosing.
The biological strength of cat extracts has been shown to significantly correlate with the concentration of the major allergenic protein Fel d 1. Fel d 1 is measured with a radial immunodiffusion (RID) assay. This assay uses a polyclonal sheep serum to measure “units” of Fel d 1 based on a series of standard reference samples. An extract that contains 10 – 19.9 units of Fel d 1 is labelled 10,000 BAU. It should be noted that Fel d 1 units and the microgram concentration of Fel d 1 are not equivalent. The units are a multiple of the micrograms, which varies depending on the reference used.
All standardized cat extracts should contain similar amounts of Fel d 1 though the presence and/or concentration of other allergenic proteins may vary between lots and between manufacturers.
Short Ragweed (Major Allergen):
Short Ragweed extracts are each analysed for the concentration of the major allergenic protein Amb a 1 (formerly known as Antigen E). The concentration of this major allergen is simply reported on the labels of each lot as "units" of Amb a 1, which is a 1:1 representation of the microgram concentration. In other words, 100 units of Amb a 1 = 100 micrograms.
While the FDA has not defined a specific release value for Amb a 1, and while newly manufactured lots are not targeted to a specific value, source material is analysed to ensure at least a minimum concentration of allergen is present in all lots. Historically, major allergen concentrations have fallen within a predictable range between lots.
Hymenoptera Venom (Total Protein):
To produce venom extracts, Hymenoptera, such as Bees and Wasps, are collected and their venom sacs are isolated. From these venom sacs pure venom is extracted. To ensure the quality of the venom a number of protein assays are performed to verify the quantity and activity of several important allergenic proteins. In particular, the total protein is measured and each manufactured lot is adjusted to produce a consistent protein concentration of 100 µg/mL for individual species and 300 µg/mL for mixed species.
Standardized extracts along with their assigned potency labels and the method used for relative potency determination.
|Allergen||Units||Assay||Potency Determination||Available Concentration|
|Grass||BAU/ml||Competition ELISA||Total lgE Binding||100,000 BAU/mL
|Dust Mite||AU/mL||Competition ELISA||Total lgE Binding||10,000 AU/mL
|Cat||BAU/mL||Radial Immunodiffusion||Major Allergen Content (Fel d 1)||10,000 BAU/mL|
|Short Ragweed||Major Allergen Units/mL||Radial Immunodiffusion||Major Allergen Content (Fel d 1)||Lot-specific values indicated on vial|
|Hymenoptera Venom**||μ/mL||Lowry Method||Total protein concentration||100μ/mL or
**Concentration values are following reconstitution