(82 days)
Not Found
No
The description focuses on automated RT-PCR technology and does not mention AI or ML.
No.
This device is an in vitro diagnostic test intended to aid in the diagnosis of norovirus infections by detecting viral RNA. It is not designed to treat or prevent disease.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is "a qualitative in vitro diagnostic test for the identification and differentiation of norovirus genogroup I and genogroup II RNA" and "is intended to aid in the diagnosis of norovirus infections."
No
The device is an in vitro diagnostic test that utilizes hardware components (GeneXpert Instrument Systems, cartridges, reagents) to perform RT-PCR and detect norovirus RNA. While software is involved in controlling the instrument and processing results, it is not a standalone software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "The Cepheid Xpert Norovirus Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test for the identification and differentiation of norovirus genogroup I and genogroup II RNA from raw or unpreserved unformed stool specimens collected from individuals with symptoms of acute gastroenteritis."
The "Device Description" section also reiterates: "The Xpert Norovirus Assay is an automated in vitro diagnostic test for detection and differentiation of nucleic acid sequences for norovirus genogroup I and genogroup II from raw or unpreserved unformed (liquid or soft) stool specimens collected from individuals with symptoms of acute gastroenteritis."
These statements clearly identify the device as an in vitro diagnostic test.
N/A
Intended Use / Indications for Use
The Cepheid Xpert Norovirus Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test for the identification and differentiation of norovirus genogroup I and genogroup II RNA from raw or unpreserved unformed stool specimens collected from individuals with symptoms of acute gastroenteritis. The test utilizes automated real-time reverse transcriptase polymerase chain reaction (RT-PCR) to detect norovirus RNA. The Xpert Norovirus Assay is intended to aid in the diagnosis of norovirus infections when used in conjunction with clinical evaluation, laboratory findings, and epidemiological information. The assay also aids in the detection and identification of norovirus infections in the context of outbreaks.
Product codes (comma separated list FDA assigned to the subject device)
PIQ, OOI
Device Description
The Xpert Norovirus Assay is an automated in vitro diagnostic test for detection and differentiation of nucleic acid sequences for norovirus genogroup I and genogroup II from raw or unpreserved unformed (liquid or soft) stool specimens collected from individuals with symptoms of acute gastroenteritis. The test utilizes automated, multiplex real-time, reverse transcriptase polymerase chain reaction (RT-PCR) to detect specific viral gene sequences associated with norovirus genogroup I and genogroup II. The Xpert Norovirus Assay is intended to aid in the diagnosis of norovirus infections when used in conjunction with clinical evaluation, laboratory findings, and epidemiological information. The assay also aids in the detection and identification of norovirus infections in the context of outbreaks.
The Xpert Norovirus Assay is performed on the Cepheid GeneXpert Instrument Systems (GeneXpert Dx, GeneXpert Infinity-48, GeneXpert Infinity-48s, and GeneXpert Infinity-80 systems). The GeneXpert Instrument System platform automates sample preparation, amplification and real-time detection.
The GeneXpert Instrument Systems require the use of single-use, disposable cartridges (the Xpert Norovirus Cartridges) that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained and specimens never come into contact with working parts of the instrument modules, cross-contamination between samples is minimized.
The Xpert Norovirus Assay includes reagents for the detection and differentiation of nucleic acid sequences for norovirus genogroup I and genogroup II from raw or unpreserved unformed human stool specimens collected from patients with signs and symptoms of acute gastroenteritis. All reagents except the Sample Reagent are contained pre-loaded in the cartridge. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge. The SPC is present to control for adequate processing of the target viruses and to monitor the presence of inhibitors in the PCR reaction. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity and dye stability.
The single-use, multi-chambered fluidic cartridges are designed to complete sample preparation and real-time RT-PCR for detection and differentiation of norovirus genogroup I and genogroup II viral RNA in 90 minutes or less. The GeneXpert Instrument Systems, comprised of the GeneXpert Dx Systems and the GeneXpert Infinity Systems, have 1 to 80 randomly accessible modules, depending upon the instrument, that are each capable of performing separate sample preparation and real-time PCR and RT-PCR tests. Each module contains a syringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE® thermocycler for performing real-time PCR and RT-PCR and detection.
Specimens are collected following the user's institution standard procedures for collecting stool specimens for norovirus testing and sent to the GeneXpert® testing area for processing. The specimen may be stored at 2-8℃ for up to two days prior to processing. When ready to process the specimen, a single-use disposable dry swab is used for transfer of the stool specimen to the Sample Reagent bottle that is provided with the Xpert Norovirus Assay kit. The user vortexes the capped Sample Reagent bottle for 10 seconds and transfers the entire contents to the sample chamber in the top of the disposable fluidic cartridge with a transfer pipette. The user initiates a test from the system user interface and places the cartridge into the GeneXpert instrument platform, which performs hands-off real-time, multiplex polymerase chain reaction (PCR) for detection of RNA. The results are automatically generated at the end of the process in a report that can be viewed and printed.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Clinical Studies: Performance characteristics of the Xpert Norovirus Assay were evaluated at seven institutions in the U.S. and the E.U. The study specimens consisted of raw or unpreserved unformed stool specimens from subjects with symptoms of acute gastroenteritis. The Xpert Norovirus Assay performance was compared to a composite reference test method performed at the CDC (Atlanta, GA).
A total of 1403 specimens were tested for Norovirus GI by the Xpert Norovirus Assay and the composite reference test. Of the 1403 specimens, 914 were fresh, prospectively collected and 489 were frozen, archived specimens. A total of 1401 specimens were tested for Norovirus GII by the Xpert Norovirus Assay and the composite reference test. Of the 1401 specimens, 914 were fresh, prospectively collected and 487 were frozen, archived specimens.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Clinical Performance:
Study type: Clinical Study
Sample size: 1403 specimens for Norovirus GI, 1401 specimens for Norovirus GII.
Standalone performance: Compared to a composite reference test method performed at the CDC.
Key results (Fresh, prospectively collected specimens):
Norovirus GI: 100% PPA, 99.6% NPA.
Norovirus GII: 98.5% PPA, 98.8% NPA.
Key results (Frozen, archived specimens):
Norovirus GI: 98.1% PPA, 94.6% NPA.
Norovirus GII: 100% PPA, 96.8% NPA.
Reproducibility Study:
Study type: Reproducibility Study
Sample size: A panel of 7 specimens tested two times on five different days by two different operators, at each of three sites (7 samples x 2 times/day x 5 days x 2 operators x 3 sites), total 60 runs per sample type for overall results.
Key results:
Neg: 100% (60/60)
GI - High Neg: 25.0% (15/60)
GI - Low Pos: 93.3% (56/60)
GI - Mod Pos: 100% (59/59)
GII - High Neg: 30.0% (18/60)
GII - Low Pos: 95.0% (57/60)
GII - Mod Pos: 98.3% (59/60)
Instrument System Precision:
Study type: In-house precision study
Sample size: A panel of 7 samples tested on 12 different days by two operators. Each operator conducted four runs of each panel of samples per day on each of the two instrument systems (7 samples x 4 times/day x 12 days x 2 operators x 2 instrument systems), total 192 runs per sample type for overall results.
Key results:
Neg: 100% (192/192)
GI - High Neg: 16.2% (31/192)
GI - Low Pos: 98.4% (189/192)
GI - Mod Pos: 100% (191/191)
GII - High Neg: 28.7% (55/192)
GII - Low Pos: 88.5% (170/192)
GII - Mod Pos: 100% (191/191)
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Clinical Performance:
Fresh Specimens (GI):
PPA % (95% CI): 100% (95% CI: 73.5-100)
NPA % (95% CI): 99.6% (95% CI: 98.9-99.9)
Fresh Specimens (GII):
PPA % (95% CI): 98.5% (95% CI: 91.7-100)
NPA % (95% CI): 98.8% (95% CI: 97.8-99.4)
Frozen Specimens (GI):
PPA % (95% CI): 98.1% (95% CI: 93.2-99.8)
NPA % (95% CI): 94.6% (95% CI: 91.8-96.6)
Frozen Specimens (GII):
PPA % (95% CI): 100% (95% CI: 96.7-100)
NPA % (95% CI): 96.8% (95% CI: 94.5-98.3)
Analytical Sensitivity (Limit of Detection):
GI.3: 5.7 x 10^5 (copies/mL)
GII.4: 3.0 x 10^5 (copies/mL)
Analytical Specificity (Cross-reactivity):
100% (All organisms tested were correctly reported as NORO GI NOT DETECTED; NORO GII NOT DETECTED).
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 866.3990 Gastrointestinal microorganism multiplex nucleic acid-based assay.
(a)
Identification. A gastrointestinal microorganism multiplex nucleic acid-based assay is a qualitativein vitro diagnostic device intended to simultaneously detect and identify multiple gastrointestinal microbial nucleic acids extracted from human stool specimens. The device detects specific nucleic acid sequences for organism identification as well as for determining the presence of toxin genes. The detection and identification of a specific gastrointestinal microbial nucleic acid from individuals exhibiting signs and symptoms of gastrointestinal infection aids in the diagnosis of gastrointestinal infection when used in conjunction with clinical evaluation and other laboratory findings. A gastrointestinal microorganism multiplex nucleic acid-based assay also aids in the detection and identification of acute gastroenteritis in the context of outbreaks.(b)
Classification. Class II (special controls). The special controls are set forth in FDA's guideline document entitled: “Class II Special Controls Guideline: Gastrointestinal Microorganism Multiplex Nucleic Acid-Based Assays for Detection and Identification of Microorganisms and Toxin Genes from Human Stool Specimens.” For availability of the guideline document, see § 866.1(e).
0
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle or bird symbol, with three curved lines forming the body and wings. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the bird symbol.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
Cepheid Scott Campbell, Ph.D., MBA Executive Director, Clinical Affairs 904 Caribbean Drive Sunnyvale CA 94089-1189
November 26, 2014
Re: K142501
Trade/Device Name: Xpert® Norovirus Regulation Number: 21 CFR 866.3990 Regulation Name: Gastrointestinal Microorganism Multiplex Nucleic Acid-Based Assay Regulatory Class: II Product Code: PIO. OOI Dated: September 4, 2014 Received: September 5, 2014
Dear Dr. Campbell:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21. Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
1
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours.
Uwe Scherf -S for
Sally A. Hojvat, M. Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K142501
Device Name Xpert Norovirus
Indications for Use (Describe)
The Cepheid Xpert Norovirus Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test for the identification and differentiation of norovirus genogroup I and genogroup II RNA from raw or unpreserved unformed stool specimens collected from individuals with symptoms of acute gastroenteritis. The test utilizes automated real-time reverse transcriptase polymerase chain reaction (RT-PCR) to detect norovirus RNA. The Xpert Norovirus Assay is intended to aid in the diagnosis of norovirus infections when used in conjunction with clinical evaluation, laboratory findings, and epidemiological information. The assay also aids in the detection and identification of norovirus infections in the context of outbreaks.
Type of Use (Select one or both, as applicable)
2 Prescription Use (Part 21 CFR 801 Subpart D)
_ Over-The-Counter Use (21 CFR 801 Subpart C)
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FOR FDA USE ONLY
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3
510(k) Summary
As required by 21 CFR Section 807.92(c).
| Submitted by: | Cepheid
904 Caribbean Drive
Sunnyvale, CA 90489
Phone number: (408) 400-8460
Fax number: (847) 510-0539 |
|-------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact: | Kerry J. Flom, Ph.D. |
| Date of Preparation: | October 28, 2014 |
| Device: | |
| Trade name: | Xpert® Norovirus |
| Common name: | Xpert Norovirus Assay |
| Type of Test: | Automated real-time reverse transcription-polymerase chain
reaction (RT-PCR) assay intended for the in vitro qualitative
detection and differentiation of norovirus genogroup I and
genogroup II RNA. |
| Regulation number/
Classification name/
Product code: | 866.3990/Gastrointestinal pathogen panel multiplex nucleic
acid-based assay system /PIQ
Instrumentation for clinical multiplex test systems/OOI |
| Classification
Advisory Panel | Microbiology (83) |
| Prescription Use | Yes |
| Predicate Devices
Name(s): | Luminex Molecular Diagnostics, Inc., xTAG®
Gastrointestinal Pathogen Panel (GPP) (510(k) #K121894) |
4
Device Description:
The Xpert Norovirus Assay is an automated in vitro diagnostic test for detection and differentiation of nucleic acid sequences for norovirus genogroup I and genogroup II from raw or unpreserved unformed (liquid or soft) stool specimens collected from individuals with symptoms of acute gastroenteritis. The test utilizes automated, multiplex real-time, reverse transcriptase polymerase chain reaction (RT-PCR) to detect specific viral gene sequences associated with norovirus genogroup I and genogroup II. The Xpert Norovirus Assay is intended to aid in the diagnosis of norovirus infections when used in conjunction with clinical evaluation, laboratory findings, and epidemiological information. The assay also aids in the detection and identification of norovirus infections in the context of outbreaks.
The Xpert Norovirus Assay is performed on the Cepheid GeneXpert Instrument Systems (GeneXpert Dx, GeneXpert Infinity-48, GeneXpert Infinity-48s, and GeneXpert Infinity-80 systems). The GeneXpert Instrument System platform automates sample preparation, amplification and real-time detection.
The GeneXpert Instrument Systems require the use of single-use, disposable cartridges (the Xpert Norovirus Cartridges) that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained and specimens never come into contact with working parts of the instrument modules, cross-contamination between samples is minimized.
The Xpert Norovirus Assay includes reagents for the detection and differentiation of nucleic acid sequences for norovirus genogroup I and genogroup II from raw or unpreserved unformed human stool specimens collected from patients with signs and symptoms of acute gastroenteritis. All reagents except the Sample Reagent are contained pre-loaded in the cartridge. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge. The SPC is present to control for adequate processing of the target viruses and to monitor the presence of inhibitors in the PCR reaction. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity and dye stability.
The single-use, multi-chambered fluidic cartridges are designed to complete sample preparation and real-time RT-PCR for detection and differentiation of norovirus genogroup I and genogroup II viral RNA in 90 minutes or less. The GeneXpert Instrument Systems, comprised of the GeneXpert Dx Systems and the GeneXpert Infinity Systems, have 1 to 80 randomly accessible modules, depending upon the instrument, that are each capable of performing separate sample preparation and real-time PCR and RT-PCR tests. Each module contains a syringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores', and a
1 Although sonication is a fundamental capability of every GeneXpert module, sonication is not used in the Xpert Norovirus Assay.
5
proprietary I-CORE® thermocycler for performing real-time PCR and RT-PCR and detection.
Specimens are collected following the user's institution standard procedures for collecting stool specimens for norovirus testing and sent to the GeneXpert® testing area for processing. The specimen may be stored at 2-8 ℃ for up to two days prior to processing. When ready to process the specimen, a single-use disposable dry swab is used for transfer of the stool specimen to the Sample Reagent bottle that is provided with the Xpert Norovirus Assay kit. The user vortexes the capped Sample Reagent bottle for 10 seconds and transfers the entire contents to the sample chamber in the top of the disposable fluidic cartridge with a transfer pipette. The user initiates a test from the system user interface and places the cartridge into the GeneXpert instrument platform, which performs hands-off real-time, multiplex polymerase chain reaction (PCR) for detection of RNA. The results are automatically generated at the end of the process in a report that can be viewed and printed.
Device Intended Use:
The Cepheid Xpert Norovirus Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test for the identification and differentiation of norovirus genogroup I and genogroup II RNA from raw or unpreserved unformed stool specimens collected from individuals with symptoms of acute gastroenteritis. The test utilizes automated real-time reverse transcriptase polymerase chain reaction (RT-PCR) to detect norovirus RNA. The Xpert Norovirus Assay is intended to aid in the diagnosis of norovirus infections when used in conjunction with clinical evaluation, laboratory findings, and epidemiological information. The assay also aids in the detection and identification of norovirus infections in the context of outbreaks.
Substantial Equivalence:
The Xpert Norovirus Assay is substantially equivalent to the Luminex Molecular Diagnostics, Inc., xTAG® Gastrointestinal Pathogen Panel (Luminex xTAG GPP) [510(k) #K121894]. The Xpert Norovirus Assay and the Luminex xTAG GPP both detect norovirus genogroup I and genogroup II from human stool specimens using multiplex nucleic acid-based technology. A multi-center clinical study was conducted to determine the performance characteristics of the Xpert Norovirus Assay relative to a composite comparator method that consisted of a combination of Center for Disease Control and Prevention (CDC) RT-PCR assays and bi-directional sequencing for norovirus. The Luminex xTAG GPP used the same composite comparator method in a clinical study to determine its performance characteristics. The Xpert Norovirus Assay study results showed the Xpert Norovirus Assay is acceptable for its intended use and is as safe and effective as the predicate device.
Table 5-1 shows the similarities and differences between the Xpert Norovirus Assay and the predicate device.
6
| Similarities | ||
|---|---|---|
| Device | Predicate Device | |
| Item | Xpert Norovirus (K142501) | Luminex xTAG GPP (K121894) |
| Regulation | 21 CFR 866.3990 | 21 CFR 866.3990 |
| Device | ||
| Class | Class II | Class II |
| Technology | ||
| Principle of | ||
| Operation | Real-time reverse transcriptase | |
| polymerase chain reaction (RT-PCR) | Real-time reverse transcriptase | |
| polymerase chain reaction (RT-PCR) | ||
| General | ||
| Intended | ||
| Use | The Cepheid Xpert Norovirus Assay, | |
| performed on the GeneXpert® | ||
| Instrument Systems, is a qualitative | ||
| in vitro diagnostic test for the | ||
| identification and differentiation of | ||
| norovirus genogroup I and genogroup | ||
| II RNA from raw or unpreserved | ||
| unformed stool specimens collected | ||
| from individuals with symptoms of | ||
| acute gastroenteritis. The test utilizes | ||
| automated real-time reverse | ||
| transcriptase polymerase chain | ||
| reaction (RT-PCR) to detect | ||
| norovirus RNA. The Xpert | ||
| Norovirus Assay is intended to aid in | ||
| the diagnosis of norovirus infections | ||
| when used in conjunction with | ||
| clinical evaluation, laboratory | ||
| findings, and epidemiological | ||
| information. The assay also aids in | ||
| the detection and identification of | ||
| norovirus infections in the context of | ||
| outbreaks. | The xTAG®Gastrointestinal Pathogen | |
| Panel (GPP) is a multiplexed nucleic | ||
| acid test intended for the simultaneous | ||
| qualitative detection and identification | ||
| of multiple viral, parasitic, and | ||
| bacterial nucleic acids in human stool | ||
| specimens from individuals with signs | ||
| and symptoms of infectious colitis or | ||
| gastroenteritis. The following pathogen | ||
| types, subtypes and toxin genes are | ||
| identified using the xTAG® GPP: | ||
| • Campylobacter ( C. jejuni, C. coli | ||
| and C. lari only) | ||
| • Clostridium difficile ( C. difficile ) | ||
| toxin A/B | ||
| • Cryptosporidium ( C. parvum and C. |
hominis only)
• Escherichia coli ( E. coli ) 0157
• Enterotoxigenic Escherichia coli
(ETEC) LT/ST
• Giardia ( G. lamblia only - also
known as G. intestinalis and G.
duodenalis )
• Norovirus GI/GII
• Rotavirus A
• Salmonella
• Shiga-like Toxin producing E. coli
(STEC) stx 1/stx 2
• Shigella ( S. boydii, S. sonnei, S.
flexneri and S. dysenteriae )
The detection and identification of |
| Similarities | | |
| | Device | Predicate Device |
| Item | Xpert Norovirus (K142501) | Luminex xTAG GPP (K121894) |
| | | specific gastrointestinal microbial
nucleic acid from individuals
exhibiting signs and symptoms of
gastrointestinal infection aids in the
diagnosis of gastrointestinal infection
when used in conjunction with clinical
evaluation, laboratory findings and
epidemiological information. A
gastrointestinal microorganism
multiplex nucleic acid-based assay also
aids in the detection and identification
of acute gastroenteritis in the context
of outbreaks. |
| | | xTAG® GPP positive results are
presumptive and must be confirmed
by FDA-cleared tests or other
acceptable reference methods. |
| | | The results of this test should not be
used as the sole basis for diagnosis,
treatment, or other patient management
decisions. Confirmed positive results
do not rule out co-infection with other
organisms that are not detected by this
test, and may not be the sole or
definitive cause of patient illness.
Negative xTAGGastrointestinal
Pathogen Panel results in the setting of
clinical illness compatible with
gastroenteritis may be due to infection
by pathogens that are not detected by
this test or non-infectious causes such
as ulcerative colitis, irritable bowel
syndrome, or Crohn's disease. |
| | | xTAG® GPP is not intended to
monitor or guide treatment for C.
difficile infections. |
| | | The xTAG® GPP is indicated for use
with the Luminex® MAGPIX®
instrument. |
| Similarities | | |
| | Device | Predicate Device |
| Item | Xpert Norovirus (K142501) | Luminex xTAG GPP (K121894) |
| Specimen
Types | Human stool | Human stool |
| Differences | | |
| | New Device | Predicate Device |
| Item | Xpert Norovirus (K142501) | Luminex xTAG GPP (K121894) |
| Product
Code | PIQ | PCH |
| Assay
Results | Qualitative detection of Norovirus
GI/GII | Qualitative detection of norovirus |
| Analyte
Detected | Detects and differentiates between
Norovirus GI/GII. | Detects norovirus but does not
differentiate between Norovirus
GI/GII. |
| Technology
Principles of
Operation | Amplification: multiplex real-time
RT-PCR
Detection: fluorogenic target-
specific hybridization | Multiplex RT-PCR and multiplex
Target Specific Primer Extension
followed by Fluorescence-activated
sorting of labeled beads coupled to
streptavidin-conjugated biotinylated
products. |
| Sample Pre-
treatment | Place swab dipped in specimen into
provided tube of sample reagent.
Vortex 10 seconds. | 30-45 minutes of manual sample pre-
treatment preparation. |
| Nucleic
Acid
Isolation
and
purification | Self-contained and automated in the
GeneXpert Cartridge and GeneXpert
Instrument Systems. No reagent
preparation - all reagents are
contained in the cartridge. | Multi-step manual reagent
preparation for use with
NucliSENS® EasyMAG extraction
Kit (BioMerieux). |
| Instrument
Systems | Cepheid GeneXpert Dx Systems and
GeneXpert Infinity Systems | Nucleic Acid Purification System
PCR Thermocycler
Luminex® 100/200® or MAGPIX®
instruments |
Table 5-1: Comparison of Similarities and Differences of the
7
8
9
| Differences | ||
|---|---|---|
| New Device | Predicate Device | |
| Item | Xpert Norovirus (K142501) | Luminex xTAG GPP (K121894) |
| Internal | ||
| Controls | Sample processing control (SPC) | |
| and probe check control (PCC) | ||
| integrated in assay/instrument | ||
| system. | ||
| External controls available but not | ||
| provided. | Internal control added to each | |
| sample. External control processed | ||
| with each batch of samples. | ||
| Time to | ||
| obtain test | ||
| results | Test results: 90 minutes or less for | |
| sample preparation and RT-PCR. | Test results in 3.0 x 108 CFU/mL | |
| Anaerococcus prevotiia | ATCC 9321 | 6.7 x 108 CFU/mL |
| Bacteriocides fragilisa | ATCC 25285 | 1.4 x 109 CFU/mL |
| Campylobacter coli | ATCC 43478 | 1.8 x 108 CFU/mL |
| Campylobacter jejuni | ATCC 33560 | 1.3 x 108 CFU/mL |
| Campylobacter lari | ATCC 35221 | 3.4 x 107 CFU/mL |
| Citrobacter freundii | ATCC 33128 | 1.5 x 109 CFU/mL |
| Clostridium difficilea | ATCC 9689 | 2.2 x 108 CFU/mL |
| Organism | Strain ID | Concentration |
| Clostridium sordellia | DSMZ 2141 | 2.0 x 108 CFU/mL |
| Eggerthella lenta | ATCC 43055 | >3.0 x 107 CFU/mL |
| Enterobacter cloacae | ATCC 70021 | 1.0 x 109 CFU/mL |
| Enterococcus casseliflavus | ATCC 25788 | 1.0 x 109 CFU/mL |
| Enterococcus faecalis | ATCC 29212 | 5.4 x 108 CFU/mL |
| Enterococcus faecium | ATCC 9756 | 8.2 x 108 CFU/mL |
| Enterococcus gallinarium | ATCC 49573 | 4.5 x 108 CFU/mL |
| Escherichia coli O157:H7 | ATCC 43888 | 8.4 x 108 CFU/mL |
| Escherichia coli O26:H11 | CDC 033014 | 7.4 x 108 CFU/mL |
| Escherichia coli O45:H2 | CDC 003039 | 3.3 x 108 CFU/mL |
| Escherichia coli O103:H11 | CDC 063008 | 5.4 x 108 CFU/mL |
| Escherichia coli 011 | CDC 201114 | 6.9 x 108 CFU/mL |
| Escherichia coli 0121 | CDC 023211 | 1.4 x 109 CFU/mL |
| Escherichia coli 0145 | CDC 993311 | 7.1 x 108 CFU/mL |
| Escherichia hermannii | ATCC 33650 | 1.5 x 109 CFU/mL |
| Fusobacterium necrophoruma | ATCC 31647 | 9.6 x 108 CFU/mL |
| Helicobacter pylori | CCUG 1784 | 1.5 x 108 CFU/mL |
| Klebsiella pneumoniae | ATCC 70063 | 1.2 x 109 CFU/mL |
| Lactobacillus jensenii | ATCC 25258 | 4.0 x 108 CFU/mL |
| Listeria monocytogenes | CCUG 3358 | 1.2 x 109 CFU/mL |
| Micrococcus luteus | ATCC 4698 | 1.8 x 108 CFU/mL |
| Morganella morganii | ATCC 49948 | 1.3x109 CFU/mL |
| Peptostreptococcus | ||
| anaerobiusa | CCUG 7835 | 1.5 x 109 CFU/mL |
| Plesiomonas shigelloides | ATCC 51903 | 3.1 x 108 CFU/mL |
| Prevotella oralisa | ATCC 33269 | 1.2 x 109 CFU/mL |
| Proteus mirabilis | ATCC 43071 | 1.1 x 109 CFU/mL |
| Proteus vulgaris | ATCC 49132 | 1.8 x 109 CFU/mL |
| Providencia alcalifaciens | CCUG 6325 | 1.8 x 109 CFU/mL |
| Providencia stuartii | ATCC 49809 | 1.3 x 109 CFU/mL |
| Organism | Strain ID | Concentration |
| Pseudomonas aeruginosa | ATCC 27853 | 6.3 x 108 CFU/mL |
| Pseudomonas fluorescens | ATCC 13525 | >3.0 x 108 CFU/mL |
| Pseudomonas putida | ATCC 49128 | 5.5 x 108 CFU/mL |
| Salmonella agona | ATCC 51957 | 1.2 x 109 CFU/mL |
| Salmonella bongori | ATCC 43975 | 1.7 x 109 CFU/mL |
| Salmonella enterica | ATCC 13314 | 9.2 x 108 CFU/mL |
| Serratia marcescens | ATCC 43862 | 3.8 x 108 CFU/mL |
| Shigella flexneri | ATCC 12022 | 8.1 x 108 CFU/mL |
| Shigella sonnei | ATCC 25931 | >3.0 x 108 CFU/mL |
| Staphylococcus aureus | ATCC 25923 | 8.8 x 108 CFU/mL |
| Staphylococcus epidermidis | ATCC 14990 | >3.0 x 107 CFU/mL |
| Streptococcus agalactiae | ||
| (GBS) | ATCC 12386 | 9.6 x 108 CFU/mL |
| Streptococcus dysgalactiae | ATCC 43078 | 7.2 x 108 CFU/mL |
| Streptococcus pyogenes | ATCC 19615 | 5.5 x 108 CFU/mL |
| Vibrio choleraeb | CCUG 9118 | 5.2 x 109 copies/µL |
| Vibrio parahaemolyticus | ATCC 17802 | 3.8 x 108 CFU/mL |
| Yersinia enterocolitica | ATCC 9610 | 7.1 x 108 CFU/mL |
| Adenovirus | Type 31 | 3.6 x 105 TCID50/mL |
| Adenovirus | Type 40 | 2.8 x 107 TCID50/mL |
| Adenovirus | Type 41 | 4.6 x 107 TCID50/mL |
| Astrovirusd | -- | Not applicablec |
| Coxsackie virus | Type B5 | 1.4 x 105 TCID50/mL |
| Echovirus | 11 | 3.3 x 109 TCID50/mL |
| Parechovirus | Type 6 | 1.9 x 107 TCID50/mL |
| Rotavirus | Type Wa | 1.0 x 106 TCID50/mL |
| Sapovirusd | -- | Not applicablee |
| Candida albicans | ATCC 10231 | >3.0 x 107 CFU/mL |
| Blastocystis hominisb | BT1 | 1.0 x 109 copies/mL |
| Cryptosporidium parvumb | Iowa | 6.1 x 109 copies/mL |
| Giardia lambliab | Portland-1 | 3.05 x 109 copies/mL |
| Entamoeba histolyticab | ATCC 30459D | 4.9 x 106 copies/mL |
Table 5-3: Analytical Specificity of Xpert Norovirus
11
12
Strictly anaerobic bacteria.
b Tested as genomic DNA.
ª Strictly anaerobic bacteria.
° Tested as genomic DNA.
° The concentration is not known for the Astrovirus clinical samples that were obtained from
13
KUL; the Ct values according to KUL assay were in the range of 12-27. d Clinical sample.
& The concentration is not known for the Sapovirus clinical samples that were obtained from KUL; the Ct values according to KUL assay were in the range of 19-23.
Analytical Reactivity (Inclusivity)
The analytical reactivity of the Xpert Norovirus Assay was evaluated against thirty-one genotypes representing both norovirus genogroups (GI and GII). The thirty-one norovirus strains evaluated in this study were tested near the LoD concentration of the assay (Table 5-4). Three replicates were tested for each strain.
| Norovirus Strain | Estimated
Concentration
(copies/mL)a | Result | |
|--------------------------|--------------------------------------------|--------|-----|
| | | GI | GII |
| GI.1 | $9.0 x 10^6$ | POS | NEG |
| GI.2 | $3.7 x 10^8$ | POS | NEG |
| GI.3 | $1.4 x 10^6$ | POS | NEG |
| GI.4 | $1.0 x 10^5$ | POS | NEG |
| GI.5b | $2.5 x 10^5$ | POS | NEG |
| GI.6b | $2.5 x 10^5$ | POS | NEG |
| GI.7b | $2.5 x 10^5$ | POS | NEG |
| GI.8 | $3.7 x 10^5$ | POS | NEG |
| GI.14 | $3.0 x 10^6$ | POS | NEG |
| GII.1 | $3.6 x 10^6$ | NEG | POS |
| GII.2 | $1.1 x 10^5$ | NEG | POS |
| GII.3b | $1.3 x 10^3$ | NEG | POS |
| GII.4 (2006a) | $1.2 x 10^5$ | NEG | POS |
| GII.4 (2006b) | $2.4 x 10^5$ | NEG | POS |
| GII.4 (2008) | $4.3 x 10^5$ | NEG | POS |
| GII.4 (2009) New Orleans | $1.7 x 10^5$ | NEG | POS |
| GII.4 (2010) | $9.6 x 10^4$ | NEG | POS |
| GII.4 (2012) Sydney | $1.2 x 10^5$ | NEG | POS |
| GII.5b | $1.3 x 10^3$ | NEG | POS |
| GII.6b | $1.3x 10^3$ | NEG | POS |
| GII.7 | $8.0 x 10^4$ | NEG | POS |
Table 5-4: Analytical Reactivity Results of the Xpert Norovirus Assay
14
| Norovirus Strain | Estimated
Concentration
(copies/mL)a | Result | |
|------------------|--------------------------------------------|--------|-----|
| | | GI | GII |
| GII.8b | 1.3 x 103 | NEG | POS |
| GII.9b | 1.3 x 103 | NEG | POS |
| GII.10b | 1.3 x 103 | NEG | POS |
| GII.11 | 2.6 x 105 | NEG | POS |
| GII.12 | 5.7 x 105 | NEG | POS |
| GII.13 | 6.9 x 105 | NEG | POS |
| GII.14 | 1.5 x 105 | NEG | POS |
| GII.15 | 1.7 x 105 | NEG | POS |
| GII.16b | 1.3 x 103 | NEG | POS |
| GII.17b | 1.3 x 103 | NEG | POS |
4 An estimated concentration or titer was provided based on a Ct value (because of the difficulty in culturing norovirus particles, an exact concentration cannot be provided). The Ct value for each clinical specimen in the inclusivity study was extrapolated to the titer obtained from the LoD study for wellcharacterized GI and GII samples using a standard curve at CDC.
b Naked RNA transcripts were used for these strains; clinical samples were not available at the time of testing.
Potentially Interfering Substances
Potentially interfering substances that may be present in the stool were evaluated directly relative to the performance of the Xpert Norovirus Assay. Potentially interfering substances included hemoglobin, mucin, cholesterol, triglycerides and whole blood, plus additional endogenous and exogenous substances listed in Table 5-5.
Negative samples were tested in replicates of 8 with each substance in a negative stool matrix to determine the effect on the performance of the sample processing control (SPC). Positive samples were tested in replicates of 8 per substance with one Norovirus GI and one Norovirus GII clinical isolate near the LoD.
All results were compared to positive and negative controls prepared in negative stool matrix. All valid positive and negative control samples were correctly reported using the Xpert Norovirus Assay.
Inhibition of the Xpert Norovirus Assay was observed in the presence of Benzalkonium chloride (1% w/v, 0.2% w/v, and 0.04% w/v). False-negative test results were reported for the Norovirus GII target at (1% w/v) Benzalkonium chloride. In the presence of Barium sulfate (5% w/w), a statistically significant inhibitory effect was observed on the Norovirus GII Ct in positive samples relative to the control (p-value