FDA Proposes To Reclassify RIDTs As Class II Devices


Espicom View : The new proposals have the potential to take some of the older devices off the market unless they are improved. While this may leave the effective tests on the market, it will narrow the number of companies offering rapid influenza detection tests, giving more market share to companies such as Becton Dickinson, Alere and Quidel. Having more effective point-of-care diagnostics available on the market will increase confidence in rapid influenza detection tests. Unless the accuracy of a rapid influenza is equal to a 'gold-standard' laboratory test, they will take second place in the influenza testing market.

A hearing by the FDA's CDRH Microbiology Devices Advisory Committee Meeting, examined the FDA's proposal to reclassify rapid influenza detection tests (RIDTs) currently regulated as Class I devices, into Class II devices. According to the FDA, the 2009 flu pandemic highlighted the poor performance of currently approved RIDTs, which were widely used by physicians in a point-of-care setting. The use of some RIDTs led to misdiagnosed cases of influenza. In total there are 12 RIDTs on the US market; six of these are CLIA-waived, which facilitates the use of these tests outside of a clinical laboratory. The first CLIA-waived RIDT was approved in 2000, ten years after the first RIDT was cleared for use.

The proposal would increase performance requirements for RIDTs to attain at least a sensitivity of 90% for influenza A and 80% for influenza B versus viral culture and/or 80% versus polymerase chain reaction (PCR) methods. If these minimum clinical performance criteria are not met, marketed devices will need to be withdrawn from the market one year after the rule is finalised. This proposal culminates years of publications showing that many of the visual read RIDTs had poor sensitivity when compared with viral culture and to reverse transcription PCR methods. The FDA has stated that many studies have been published that show the poor sensitivity of RIDTs when compared with viral cultures and reverse transcriptase PCR.

Due to their low risk, almost all Class I devices have been exempted from the 510(k) requirement by the FDA, and diagnostics that fall into this class also not subject to design control requirements. Currently there are only three regulations governing influenza detection devices, these cover the influenza virus serological reagents; the reagents for detection of specific novel influenza A viruses; and respiratory viral panel multiplex nucleic acid assays. Under the proposal, the RIDTs will be classified as Class II. These devices are reviewed by the FDA under the 510(k) process, and are approved if they are deemed to be as safe and effective as a predicate device. The minimum controls of the devices will address the minimum acceptance performance criteria, an appropriate reference method to support 510(k) clearance and an annual monitoring of analytical reactivity after the product is cleared for market. If these proposals are approved, companies will have one for the date of approval to ensure their devices meet the new criteria. If the criteria are not met, the route of action would be to modify the device and submit a new 510(k) or withdraw the product from the market.

The majority of RIDTs can yield results in 15 minutes or less; this is a lot less than the time required for the more accurate 'gold-standard' tests such as the RT-PCR or a viral culture. The RIDTs are also the only tests to be CLIA-waived, making them the only diagnostics available at the point of care. Many of the issues surrounding RIDTs are the likelihood of giving false negative or positive results. When influenza activity is high, tests are more likely to give false negatives, conversely, when influenza activity is low, tests are more likely to give false positives. It seems that in order to ensure a correct diagnosis with some of the RIDTs, a confirmatory laboratory test must be undertaken, which makes the use of an RIDT beneficial for regions that do not have access to a laboratory but seemingly unnecessary in areas that have. However, if the tests are accurate enough not to warrant a second test then testing at the point of care will be able to make more of an impact in the influenza testing market.

The tests also have differences in accuracy with different specimen collection methods, such as nasal swabs and throat swabs. Each RIDT has different specification for acceptable specimens (eg nasopharyngeal, nasal or throat swab/aspirate). Some tests may require specimen collection using a special swab (some RIDTs must be used with a swab supplied with the test kit; some swab material can interfere with RIDT results). In addition, some RIDTs require that the entire collected specimen be used in the test; this will have an impact if it is determined that a second specimen is needed for a confirmatory test. Timing also determines the accuracy of the result. Testing specimens collected within 48-72 hours of illness onset (when influenza viral shedding is highest) is more likely to yield positive RIDT results.

Differences between influenza testing are detailed below:

Influenza Diagnostic Testing Methods
Method Types Detected Acceptable Specimens Test Time CLIA Waived
Centers for Disease Control and Prevention, Espicom
Viral cell culture (conventional) A and B NP swab, throat swab, NP or bronchial wash, nasal or endotracheal aspirate, sputum 3-10 days No
Rapid cell culture (shell vials; cell mixtures) A and B NP swab, throat swab, NP or bronchial wash, nasal or endotracheal aspirate, sputum 1-3 days No
Immunofluorescence, Direct (DFA) or Indirect (IFA) Antibody Staining A and B NP swab or wash, bronchial wash, nasal or endotracheal aspirate 1-4 hours No
RT-PCR (singleplex and multiplex; real-time and other RNA-based) and other molecular assays A and B NP swab, throat swab, NP or bronchial wash, nasal or endotracheal aspirate, sputum Varied (Generally 1-6 hours) No
Rapid Influenza Diagnostic Tests A and B NP swab, (throat swab), nasal wash, nasal aspirate <30 min. Yes/No

The Centers for Disease Control and Protection (CDC) has stated that the use of RIDTs is beneficial when testing during an outbreak of acute respiratory disease can determine if influenza is the cause, during influenza season, and testing of selected patients presenting with respiratory illnesses compatible with influenza can help establish whether influenza is present in a specific patient population and help healthcare providers determine how to use their clinical judgment for diagnosing and treating respiratory illness. Otherwise, rapid tests do not address the public health need for influenza virus isolated that can only be obtained through the collection of specimens for viral culture. Influenza virus isolates are essential for determining the match between circulating influenza viruses and those viruses contained in the vaccine and for aiding in the selection of new vaccine strains.

Becton Dickinson (BD) is one of the companies to welcome this change. This could be due to test standing up to the proposed regulation change, and it eliminating some of the competition. BD developed a higher performing test platform in 2011, with the launch of the BD Veritor system Flu A+B test. BD recognised the need for an improved test early and developed and launched the first CLIA-waived flu test referenced to PCR that provides objective results on an easy-to-read digital display. BD's system is currently the only system that uses PCR as a reference, while the other approved tests use culture as the reference method. However, other systems do have a higher sensitivity that BD's diagnostics. Quidel, Alere and Remel all have tests with a higher sensitivity than the Veritor system. Although, there is no data available on which systems have the higher number of false readings. The device that is less likely to give a false reading will have the advantage over it competitors. These diagnostic devices are less likely to be used on a day-to-day basis, just when there is an outbreak of influenza. Unless the accuracy of the tests beat laboratory standards, point-of-care devices will not take market share from laboratory diagnostics.

This article is tagged to:
Sector: Medical Devices
Geography: United States

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