Anthrax Test, Developed By Army And CDC, Receives FDA Approval

The modified gamma phage method is the first diagnostic test to gainFDA approval for human use within the Laboratory Response Network(LRN). This network, established by the CDC, is charged withmaintaining an integrated system of state and local public health,federal, military, and international laboratories that can respond tobioterrorism, chemical terrorism and other public health emergencies.

According to USAMRIID senior scientist John W. Ezzell, theGamma Phage Assay is a classical bacteriological method that has beenused at USAMRIID and other laboratories for years as part of anextensive array of methods used to identify B. anthracis. The gammaphage is a virus capable of entering bacterial cells and causing celldestruction, or lysis--and it is specific to B. anthracis.

"Because of that specificity, the gamma phage gives a highlyreadable result," Ezzell explained. "Wherever the virus is added to thesurface of a culture plate that has been inoculated with suspiciousanthrax colony growth, you can see clear zones where the B. anthraciscells have been destroyed--whereas other bacterial cells growunaffected."

Well before the anthrax attacks of 2001, scientists at USAMRIIDand the CDC recognized the need for an FDA accepted method foridentifying B. anthracis in clinical specimens. In 2002, FDA's Divisionof Clinical Laboratory Devices agreed to recognize tests for B.anthracis as eligible for classification with a 510(k) premarketnotification process--the designation given to devices and othernon-biologics.

USAMRIID, with support from CDC, prepared and submitted a510(k) Premarket Notification using both USAMRIID and CDC data on useof the gamma phage method. With FDA recognition of the assay assubstantially equivalent to the classical assay used prior to 1976, itwill be available for use for testing in designated civilian andmilitary clinical laboratories.

"This is a big first step in helping to provide the LRN labswith FDA cleared assays," said Judy Sheldon, a regulatory affairsmicrobiologist with the CDC's Bioterrorism Preparedness and ResponseProgram. "The work done at USAMRIID and here at CDC provided a solidscientific basis for FDA to evaluate the assay performance. This workhas set a high bar for other tests to meet."

USAMRIID scientists standardized and validated the test tomake it more rugged, more reproducible across laboratories, and moreresistant to user error. They developed a clearly defined method forproduction of gamma phage that proved to be highly stable, as reflectedin the extended shelf life of the B. anthracis-specific virus. USAMRIIDthen provided sufficient gamma phage material to CDC for distributionwithin the LRN, so that each laboratory will have the same material tobe used in the test. In addition, USAMRIID developed Standard OperatingProcedures for the assay to ensure that each laboratory in the LRN willrun the test the same way. This also increases confidence in the finalresult.

"This represents a very significant milestone for both of ourorganizations, in that all of the medical diagnostic products that weare developing must eventually follow a similar pathway for approval toallow clinical diagnosticians to use these tests to positively identifypathogens," said Colonel George W. Korch, Jr., commander of USAMRIID."Successes such as these demonstrate that we can translate our researchefforts into products for our health care providers and clinicallaboratory professionals."

A study to document and validate the performance characteristics ofthe assay will be published in the September 2005 issue of the Journalof Clinical Microbiology. In the paper, authors Terry G. Abshire, J.Edward Brown, and John W. Ezzell of USAMRIID also describe how theystandardized production of the phage and determined the stability ofthe assay.

About USAMRIID
USAMRIID, located at Fort Detrick,Maryland, is the lead medical research laboratory for the U.S.Biological Defense Research Program, and plays a key role in nationaldefense and in infectious disease research. The Institute's mission isto conduct basic and applied research on biological threats resultingin medical solutions (such as vaccines, drugs and diagnostics) toprotect the warfighter. USAMRIID is a subordinate laboratory of theU.S. Army Medical Research and Materiel Command.

About the CDC
The CDC is one of the 13 majoroperating components of the Department of Health and Human Services(HHS), which is the principal agency in the United States governmentfor protecting the health and safety of all Americans and for providingessential human services. Since it was founded in 1946, CDC hasremained at the forefront of public health efforts to prevent andcontrol infectious and chronic diseases, injuries, workplace hazards,disabilities, and environmental health threats.

On the web:
www.usamriid.army.mil
www.cdc.gov