Cepheid this week announced that the US Food and Drug Administration designated its Xpert test for rapid detection of methicillin-resistant Staphylococcus aureus as a "moderate complexity" diagnostic under the Clinical Laboratory Improvement Amendments.
The FDA in April approved the test, which is designed to rapidly detect MRSA, a common cause of nosocomial infections.
The MRSA diagnostic is the first nucleic acid test system to receive the “moderate complexity” designation, allowing Cepheid to market the product to laboratories and approximately 4,000 hospitals in the US.
The test’s status will allow Cepheid to broadly market the product. “With the ‘moderate complexity’ categorization of Xpert MRSA, hospitals will have increased flexibility as to deploying the system for maximum patient benefit and cost benefit,” CEO John Bishop said in a statement.
According to the FDA’s Office of In Vitro Diagnostics Director Steven Gutman, “the majority of tests cleared by FDA are designated moderate complexity under CLIA.” While the moderate complexity designation may be routine at the FDA, Cepheid’s product is the first nucleic acid test to receive the distinction.
Additionally, the issue of regulatory oversight based on complexity of laboratory-developed tests is currently a hot topic of discussion between the FDA and test developers. The FDA has said it wants to regulate in vitro diagnostic multivariate index assays, tests which operate based on mathematical algorithms, since they are more complicated than regular lab-developed assays [see PGx Reporter 02-14-07].
Gutman explained that the FDA regulates tests based on their intended use. While the complexity of a device is a factor in the agency’s determinations, that aspect alone may or may not impact the level of FDA oversight on the product.
The MRSA Test
The Xpert MRSA test runs on Cepheid's automated GeneXpert platform, which combines on-board sample preparation with real-time PCR amplification and detection.
According to the company, the system is designed to purify, concentrate, detect, and identify targeted nucleic-acid sequences, which would provide answers “directly from unprocessed samples." Cepheid added that GeneXpert’s modular design can be configured “to meet the broad range of testing demands of any clinical environment.”
The company also touted the test’s ability to rapidly identify MRSA carriers in as little as two hours.
“With Xpert MRSA we are able to get results back within two hours, 24 hours a day, seven days a week,” Beverly Sturgill, Infection Control Officer for Roanoke, Va.-based Carilion Roanoke Memorial Hospital, said in a statement. "Our goal is to screen all patients entering our hospital to determine their risk of carrying MRSA, and then conduct a swab test on all high risk patients,"
The ability to rapidly identify carriers of MRSA will allow hospitals to take measures to control the infection and potentially lower nosocomial infection rates.
It was not immediately clear how fast the results of the MRSA test are available compared to competing products. Cepheid was not able to comment before deadline.
MRSA is resistant to methicillin, oxacillin, penicillin, and amoxicillin. Hospital patients and nursing home employees with weakened immune systems are particularly susceptible to the bacterium.
Cepheid is currently working with public and private healthcare organizations to launch MRSA surveillance programs.
Cepheid said its test is currently being used by 10 Veterans Affairs Medical Centers, and an additional 30 centers are considering implementing the test in their procedures.
“The implementation of MRSA surveillance programs is demonstrating effectiveness in reducing hospital-acquired infections [and] thereby improving patient welfare and reducing the significant cost associated with HAI,” Bishop said in a statement.
In addition to the Xpert MRSA test, Cepheid has two other FDA cleared tests on the GeneXpert system, including the Xpert EV test for the detection of enterovirus RNA in cerebrospinal fluid, and the Xpert GBS test to detect Group B Streptococcus DNA from vaginal/rectal swabs.
“With the ‘moderate complexity’ categorization of Xpert MRSA, hospitals will have increased flexibility as to deploying the system for maximum patient benefit and cost benefit.”
The US Postal Service currently uses Cepheid’s GeneXpert system to test for the bacteria that causes anthrax. In addition, the company said it is working with the Centers for Disease Control and Prevention to develop a rapid point-of-care diagnostic to detect influenza A and B, and the H5N1 avian flu virus in human respiratory specimens. Cepheid also is working with the Foundation for Innovative Diagnostics to develop a new, rapid molecular diagnostic for tuberculosis.
FDA’s Risk-Based Assessment
In its decision to categorize a product as moderate complexity for CLIA the FDA considers seven technical features, including knowledge, training and experience, reagents preparation, operational steps, quality control, troubleshooting and maintenance, and interpretation and judgment. “These have been used for the past decade in this decision-making process and are not likely to be changed at this time,” Gutman said.
FDA’s Gutman explained in his e-mail that the FDA’s regulation of diagnostic tests is risk based. Depending on the device’s intended use, the relative complexity of a test may or may not lead to increased oversight.
“While it is possible for complexity in some cases to contribute to risk, it is certainly possible for some complex tests to be quite low risk and to be considered Class I exempt products,” Gutman said. “This determination is likely to be based on the intended use of the test.”
How the complexity of a diagnostic may be a factor in the level of FDA oversight is currently playing out as FDA tries to regulate IVDMIAs.
The FDA has expressed its intention to regulate IVDMIAs, reasoning that such tests are more complex than other lab-developed tests. This has drawn criticism from laboratory test developers who have noted that FDA’s draft guidance defining the tests is not specific enough about which tests it would regulate, and how FDA regulations will dovetail with exiting CLIA regs.
The agency has recently acted to dispel some of the confusion regarding the level of regulation developers can expect for their products.
Two weeks ago, the agency said in a special controls guidance that prognostic breast cancer recurrence tests are Class II products, which will only require 510(k) premarket notification, whereas predictive tests will need to receive full premarketing approval.
This differentiation came as good news to makers of predictive breast cancer recurrence tests such as Agendia, Exagen, and Quest. However, the situation may not be as rosy for Genomic Health, whose Oncotype DX test is both prognostic for breast cancer recurrence and predictive for chemotherapy benefit [see related story, this issue, and PGx Reporter 05-16-2007].