scope:

This guideline defines the current state of serological assay technology that is used to measure total IgE and IgE antibodies of defined allergen specificities. The focus of this document includes IgE assay design and calibration, methods used in the validation and quality assurance of component reagents, quality control strategies, and clinical applications.

The document is designed for use by laboratorians/clinicians (users), manufacturers (producers), and governmental regulators (inspectors, legislators, reviewers). The guideline summarizes the current state of technology, biological specimens that are routinely tested, practical methods for the evaluation of reagents, diagnostic allergy laboratory quality control strategies, and the clinical interpretation of IgE antibody results. This guideline emphasizes achievable qualification practices that have been employed by manufacturers to validate the quality and test the performance of component reagents and configured assay systems. I/LA20 also outlines methods that can be performed by clinical laboratory workers to supplement manufacturer testing and quality control practices with the ultimate goal of optimizing overall quality assurance. In addition, the document serves as a guideline for inspectors and regulators who are involved in qualifying diagnostic laboratories for IgE analysis.

The specific goals of this guideline can be summarized as follows:

To define performance criteria and list current methods for qualification of component reagents (source allergens, final allergen-containing reagents, antihuman IgE) and configured immunoassays (analytical sensitivity and specificity, limits of detection, parallelism, precision, reproducibility) that are designed to quantify human total IgE and IgE antibody of defined allergen specificities.

To define reasons why different IgE antibody assays may not yield comparable results.

To outline practical manufacturer, intralaboratory, and interlaboratory quality control measures that can be incorporated into an overall quality assurance scheme to ensure valid and reproducible IgE antibody measurements.

Total serum IgE assays are discussed in this guideline to illustrate the high degree of standardization and interlaboratory agreement that can be achieved when immunoassays use a common calibration system and an internationally recognized reference preparation as a primary calibrator. All efforts have been made to provide recommendations that do not conflict with good manufacturing practices or with guidelines currently in use by regulatory agencies for clearance of new or modified allergy products.

The clinical utility of IgE antibody measurements has over the past 40 years clearly been demonstrated by research and clinical studies. The primary goal of this document is to provide the reader with unambiguous guidelines as to how reagents are validated and configured into optimized clinical assays for the measurement of total serum IgE and human IgE antibody. Potential solutions to technical challenges yet remaining are discussed in a manner that is intended to facilitate improved intermethod standardization and interlaboratory agreement in IgE antibody measurements among diagnostic allergy laboratories using the commercially available assay methods. A new feature of the revised guideline is an overview of recent evidence that supports the predictability of IgE antibody measurements in the assessment of clinical allergic disease.