August 29, 2003 - ASM Responds to CMS/CDC Request Regarding Quality Controls for Antigen Tests

Rhonda Whalen, Chief
Laboratory Practice Standards Branch
Division of Laboratory Systems
Public Health Practice Program Office
Centers for Disease Control and Prevention
4770 Buford Highway, NE, Mailstop F-11
Atlanta, GA 30341-3717

Re: CLIA required quality control for antigen tests with an extraction phase

Dear Ms. Whalen:

Thank you for contacting the American Society for Microbiology (ASM) soliciting our position on the current regulations which require quality control testing of microbial antigen detection tests that include an extraction step in their procedures. ASM is the largest educational, professional, and scientific society dedicated to the advancement of the microbiological sciences and their application for the common good. The Society represents more than 40,000 microbiologists, including scientists and science administrators working in a variety of areas, including biomedical, environmental, and clinical microbiology.

One of the intents of the 1988 Clinical Laboratory Improvement Amendments (CLIA ’88) is to ensure that laboratory testing is performed correctly with appropriate quality systems in place. ASM supports this intent and believes that the frequency of quality control testing should be evidenced-based where feasible.

In general, microbial antigen detection tests that include extraction steps fall into two categories. The first category includes assays rated under CLIA ’88 as highly complex and that require a considerable training and laboratory experience to perform. These tests almost always lack internal controls to assure that assay procedures were performed correctly. An example is the fungal exoantigen test used to identify dimorphic fungi growing in culture. This test is an immunodiffusion assay in which antigens extracted from the cell walls of fungi interact with specific antibodies in an agarose gel matrix. The appearance of a visible band of precipitation indicates a positive reaction. Other examples include the identification of anaerobic bacteria by gas-liquid chromatography and the MIDI system that identifies microorganisms based on their unique cell wall composition. Because these and similarly complicated assays are difficult to perform and subject to many procedural pitfalls, ASM recommends that quality control verification of the antigen extraction step be performed with each assay run.

The second category of tests is rated moderately complex or waived under CLIA ’88. They are simple to perform, include internal controls, and are commercially available. They are used for rapid detection of microorganisms or their products in clinical specimens or after growing in cultures. Examples include detection of Streptococcus pyogenes (Group A Streptococcus) antigen in throat swabs, influenza A and B antigens in respiratory tract secretions, respiratory syncytial virus from respiratory secretions, and Clostridium difficile toxins in stool samples. These tests generally employ simple extraction steps that consist of mixing stable reagents with specimens to solubilize microbial antigens. The extracted material is then used in the next step of the procedure. Some tests verify the correct addition of extraction reagents by exhibiting color changes.

ASM polled members who direct clinical microbiology laboratories on the ease of performing these tests and the observed quality control failure rate. All respondents agreed that the tests are simple to perform and seldom, if ever, fail quality control. Based on their ease of performance, the inclusion of internal controls, and a lack of quality control failures in actual practice, ASM recommends that positive and negative external controls be performed upon receipt of each new test kit lot or a separate shipment of the same test kit lot to ensure adequate control of the extraction phase. This recommendation is in agreement with the College of American Pathologists’ (CAP) accreditation standard MIC.21760.

ASM appreciates the opportunity to comment on this matter and would be happy to respond to any additional questions or concerns that you may have.

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