(84 days)
The Xpert® MRSA NxG Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test intended for the detection of methicillin-resistant Staphylococcus aureus (MRSA) DNA directly from nasal swabs in patients at risk for nasal colonization. The test utilizes automated real-time polymerase chain reaction (PCR) for the amplification of MRSA-specific DNA targets and fluorogenic target-specific hybridization probes for the real-time detection of the amplified DNA. The Xpert MRSA NxG Assay is intended to aid in the prevention and control of MRSA infections in healthcare settings. The Xpert MRSA NxG Assay is not intended to diagnose, guide, or monitor treatment for MRSA infections, or provide results of susceptibility to methicillin. A negative result does not preclude MRSA nasal colonization. Concomitant cultures are necessary to recover organisms for epidemiological typing or for further susceptibility testing.
The Xpert MRSA NxG Assay is an automated real-time polymerase chain reaction (PCR) in vitro diagnostic test for qualitative detection of methicillin-resistant Staphylococcus aureus (MRSA) directly from nasal swab specimens of patients at risk for colonization with MRSA in a healthcare setting. The Xpert MRSA NxG 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 MRSA NxG 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 MRSA NxG Assay includes reagents for the detection of target MRSA DNA. The primers and probes in the Xpert MRSA NxG Assay detect proprietary sequences for the gene for methicillin/oxacillin resistance (mecA and mecC), and staphylococcal cassette chromosome mec (SCCmec), which is inserted into the SA chromosomal attB site. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are internal controls utilized by the GeneXpert Instrument System platform. The SPC is present to control for adequate processing of the target bacteria and to monitor for the presence of inhibitor(s) in the PCR assay to avoid false-negative results. The Probe Check Control verifies reagent rehydration, real-time 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 PCR for the detection of genomic DNA from methicillinresistant Staphylococcus aureus (MRSA) in 70 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. Nasal swab specimens are collected using the Cepheid Sample Collection Device and are transported to the laboratory or designated GeneXpert testing area. The nasal swab specimen is placed in a tube containing 2 mL of Elution Reagent. Following a brief vortexing of the sample, the entire contents of the Elution Reagent tube are transferred to the sample chamber of the Xpert MRSA NxG cartridge using a transfer pipette. For nasal swab specimens that are collected using Copan Liquid Amies Elution Swab (ESwab) collection and transport system, 300 uL of liquid sample is transferred to a tube containing 2 mL of Elution Reagent. Following a brief vortexing of the sample, the entire contents of the Elution Reagent tube are transferred to the sample chamber of the Xpert MRSA NxG cartridge using 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 PCR for detection of DNA. The results are automatically generated at the end of the process in a report that can be viewed and printed.
Here's a breakdown of the acceptance criteria and the study details for the Xpert MRSA NxG device, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" for the clinical performance in a numerical format that would be directly comparable to the predicate device. Instead, it aims to demonstrate "substantial equivalence" to the predicate device (BD MAX™ MRSA XT assay). The primary performance metrics for this type of in vitro diagnostic test are analytical sensitivity (Limit of Detection), clinical sensitivity, and clinical specificity. I've extracted the relevant performance metrics from the clinical studies to serve as the reported device performance.
| Performance Metric | Acceptance Criteria (Implied for Substantial Equivalence to Predicate) | Reported Device Performance (Xpert MRSA NxG Assay) | Comments |
|---|---|---|---|
| Analytical Studies | |||
| Limit of Detection (LoD) | Not explicitly stated (demonstrated reproducibility at 95% confidence) | Rayon Swab: 95% positive at 302 CFU/swab | The study determined the lowest concentration of MRSA that can be reproducibly distinguished from negative samples 95% of the time with 95% confidence. This is a measure of analytical sensitivity. |
| ESwab: 95% positive at 812 CFU/swab | |||
| Analytical Specificity (Cross-reactivity) | 100% specificity for tested non-MRSA organisms | 100% for 152 potentially cross-reactive microorganisms and human cells | No cross-reactivity with methicillin-susceptible Staphylococcus aureus (MSSA), coagulase-negative staphylococci, or other nasal flora. |
| Inclusivity | 100% detection of diverse MRSA strains | 100% (all 196 MRSA strains correctly detected) | Assessed with a wide range of MRSA strains, including various SCCmec types and known USA types. |
| Microbial Interference | No interference or cross-reactivity observed | No interference or cross-reactivity observed | Tested with 9 common commensal bacteria found in nasal cavities. |
| Interfering Substances | No false negatives; delays in Ct values acceptable if results remain correct | Identified 3 substances causing Ct delays, but no false negatives. | Addressed as limitations in the package insert. |
| Carry-Over Contamination | 100% prevention of crossover contamination | 100% (no carry-over in 42 negative samples) | Demonstrated in a study with high positive and negative samples. |
| Clinical Studies | |||
| Clinical Sensitivity | Substantially equivalent to predicate device | Rayon Swab: 91.0% (95% CI: 84.6-94.9) | Based on two prospective, multi-site studies against reference culture and susceptibility testing. |
| ESwab: 92.9% (95% CI: 86.0-96.5) | |||
| Combined: 91.8% (95% CI: 87.4-94.8) | |||
| Clinical Specificity | Substantially equivalent to predicate device | Rayon Swab: 96.9% (95% CI: 95.7-97.8) | |
| ESwab: 97.6% (95% CI: 96.2-98.5) | |||
| Combined: 97.2% (95% CI: 96.3-97.9) | |||
| Positive Predictive Value (PPV) | Not explicitly stated (reported for context) | Rayon Swab: 78.7% (95% CI: 71.3-84.7) | |
| ESwab: 83.5% (95% CI: 75.4-89.3) | |||
| Combined: 80.8% (95% CI: 75.5-85.2) | |||
| Negative Predictive Value (NPV) | Not explicitly stated (reported for context) | Rayon Swab: 98.9% (95% CI: 98.0-99.4) | |
| ESwab: 99.1% (95% CI: 98.1-99.5) | |||
| Combined: 98.9% (95% CI: 98.3-99.3) | |||
| Reproducibility | High agreement across sites, days, lots, operators | 98.6-100% agreement for low-positive and negative samples | Demonstrated excellent reproducibility in % agreement and low variability in Ct values. |
2. Sample Sizes Used for the Test Set and Data Provenance
- Clinical Test Sets:
- Rayon Swab Study: 1103 eligible nasal swab specimens.
- ESwab Study: 846 eligible nasal swab specimens.
- Combined: 1949 total specimens.
- Data Provenance: The clinical studies were prospective, multi-site investigational studies.
- The Rayon Swab study involved "eight investigational sites within the US and outside of the US."
- The ESwab study involved "six investigational sites within the US."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
The ground truth for the clinical test set was established using a reference culture and susceptibility testing method, not expert consensus in the traditional sense of medical image interpretation (e.g., radiologists). The document does not specify the number or qualifications of laboratory personnel performing these culture and susceptibility tests. However, the FDA's acceptance of this method implies that these are standard, qualified laboratory procedures.
4. Adjudication Method (for the test set)
The adjudication method was based on the reference culture and susceptibility testing.
- A specimen was considered positive for MRSA if the presence of MRSA was confirmed in either direct culture on MRSA selective chromogenic medium or via an enriched culture (Trypticase Soy Broth (TSB) with 6.5% Sodium Chloride followed by subculture on Blood Agar (BA) and MRSA selective chromogenic medium).
- Identification of presumptive S. aureus colonies was confirmed with Gram stain, catalase, and coagulase testing.
- MRSA confirmation was done by susceptibility testing with a Cefoxitin disk (30µg).
- For discrepancies (e.g., false positives/negatives by the device), repeat subculture of the enrichment broth was performed, as noted in the footnotes to Tables 8-7 and 8-8. This acts as a form of "adjudication" for discrepant results.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed. This device is an automated, standalone diagnostic assay (real-time PCR) for detecting MRSA DNA. It does not involve human "readers" in the interpretation of results in a way that would be typical for image-based AI tools. Therefore, there's no "human improvement with AI vs without AI assistance" to report.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, a standalone performance evaluation was conducted. The Xpert MRSA NxG Assay is an automated qualitative in vitro diagnostic test, and its performance (sensitivity, specificity) was directly compared against the reference method without human interpretation of the assay's output itself. The device itself performs sample preparation, amplification, and real-time detection, automatically generating results.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth used was laboratory culture and susceptibility testing, specifically:
- Direct culture on MRSA selective chromogenic medium.
- Enriched culture (TSB with 6.5% NaCl, followed by subculture on BA and MRSA selective chromogenic medium).
- Confirmation of S. aureus by Gram stain, catalase, and coagulase testing.
- Confirmation of MRSA by Cefoxitin disk susceptibility testing.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning model development. This is an in vitro diagnostic device based on PCR technology, which typically does not involve machine learning training in the same way an AI imaging model would. The "training" here would refer to the development and optimization of the PCR primers and probes, and the cartridge and instrument system, which is part of the product development process rather than a distinct "training set" for an algorithm.
However, if we consider "training" in the sense of analytical development, the following data points could be relevant to the development and optimization of the assay's internal logic and performance parameters:
- Analytical Sensitivity (LoD) Study: Used 13 individual MRSA strains (representing various SCCmec types).
- Analytical Specificity (Cross-reactivity) Study: Tested 152 potentially cross-reactive microorganisms and human cells.
- Analytical Reactivity (Inclusivity) Study: Evaluated 196 methicillin-resistant Staphylococcus aureus strains.
These studies technically inform and confirm the performance of the developed assay, which is analogous to a validation set in traditional software, but not a training set for an AI/ML algorithm.
9. How the Ground Truth for the Training Set Was Established
As noted in point 8, the concept of a "training set" in the context of an AI/ML algorithm, along with its ground truth, is not applicable here. The assay's analytical parameters (e.g., LoD, specificity, inclusivity) were established through rigorous laboratory testing using well-characterized microbial strains and samples, where the "ground truth" for each analytical study (e.g., presence/absence of a specific MRSA strain, concentration, presence of interfering substance) was defined by standard microbiological and chemical methods.
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Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
November 23, 2016
CEPHEID JIM KELLY, Ph.D. EXECUTIVE DIRECTOR, REGULATORY AFFAIRS 904 CARRIBEAN DRIVE SUNNYVALE CA 94089
Re: K162444 Trade/Device Name: Xpert MRSA NxG Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial test powder Regulatory Class: II Product Code: NQX, OOI Dated: August 30, 2016 Received: August 31, 2016
Dear Dr. Kelly:
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 (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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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,
Ribhi Shawar -S
For Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K162444
Device Name Xpert MRSA NxG
Indications for Use (Describe)
The Xpert® MRSA NxG Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test intended for the detection of methicillin-resistant Staphylococcus aureus (MRSA) DNA directly from nasal swabs in patients at risk for nasal colonization. The test utilizes automated real-time polymerase chain reaction (PCR) for the amplification of MRSA-specific DNA targets and fluorogenic target-specific hybridization probes for the real-time detection of the amplified DNA. The Xpert MRSA NxG Assay is intended to aid in the prevention and control of MRSA infections in healthcare settings. The Xpert MRSA NxG Assay is not intended to diagnose, guide, or monitor treatment for MRSA infections, or provide results of susceptibility to methicillin. A negative result does not preclude MRSA nasal colonization. Concomitant cultures are necessary to recover organisms for epidemiological typing or for further susceptibility testing.
| Type of Use (Select one or both, as applicable) |
|---|
| ------------------------------------------------- |
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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510(k) Summary
As required by 21 CFR Section 807.92(c).
| Submitted by: | Cepheid904 Caribbean DriveSunnyvale, CA 90489Phone number: (847) 228-3299Fax number: (847) 890-6589 |
|---|---|
| Contact: | Scott A. Campbell, PhD, MBA |
| Date of Preparation: | November 8, 2016 |
| Device: | |
| Trade name: | Xpert® MRSA NxG |
| Common name: | Xpert MRSA NxG Assay |
| Type of Test: | Qualitative real-time polymerase chain reaction (PCR) assayfor the amplification and detection of methicillin-resistantStaphylococcus aureus (MRSA) DNA. |
| Regulation number/Classification name/Product code: | 866.1640 /System, Nucleic acid amplification test, DNA,methicillin resistant Staphylococcus aureus , Directspecimen/NQX862.2570/Instrumentation for clinical multiplex testsystems/OOI |
| ClassificationAdvisory Panel | Microbiology (83) |
| Prescription Use | Yes |
| Predicate DeviceAssay: | BD MAXTM MRSA XT[510(k) # K133605] |
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Device Description:
The Xpert MRSA NxG Assay is an automated real-time polymerase chain reaction (PCR) in vitro diagnostic test for qualitative detection of methicillin-resistant Staphylococcus aureus (MRSA) directly from nasal swab specimens of patients at risk for colonization with MRSA in a healthcare setting.
The Xpert MRSA NxG 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 MRSA NxG 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 MRSA NxG Assay includes reagents for the detection of target MRSA DNA. The primers and probes in the Xpert MRSA NxG Assay detect proprietary sequences for the gene for methicillin/oxacillin resistance (mecA and mecC), and staphylococcal cassette chromosome mec (SCCmec), which is inserted into the SA chromosomal attB site. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are internal controls utilized by the GeneXpert Instrument System platform. The SPC is present to control for adequate processing of the target bacteria and to monitor for the presence of inhibitor(s) in the PCR assay to avoid false-negative results. The Probe Check Control verifies reagent rehydration, real-time 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 PCR for the detection of genomic DNA from methicillinresistant Staphylococcus aureus (MRSA) in 70 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.
Nasal swab specimens are collected using the Cepheid Sample Collection Device and are transported to the laboratory or designated GeneXpert testing area. The nasal swab specimen is placed in a tube containing 2 mL of Elution Reagent. Following a brief vortexing of the sample, the entire contents of the Elution Reagent tube are transferred to the sample chamber of the Xpert MRSA NxG cartridge using a transfer pipette. For nasal
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swab specimens that are collected using Copan Liquid Amies Elution Swab (ESwab) collection and transport system, 300 uL of liquid sample is transferred to a tube containing 2 mL of Elution Reagent. Following a brief vortexing of the sample, the entire contents of the Elution Reagent tube are transferred to the sample chamber of the Xpert MRSA NxG cartridge using 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 PCR for detection of DNA. The results are automatically generated at the end of the process in a report that can be viewed and printed.
Device Intended Use:
The Xpert® MRSA NxG Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test intended for the detection of methicillin-resistant Staphylococcus aureus (MRSA) DNA directly from nasal swabs in patients at risk for nasal colonization. The test utilizes automated real-time polymerase chain reaction (PCR) for the amplification of MRSA-specific DNA targets and fluorogenic target-specific hybridization probes for the real-time detection of the amplified DNA. The Xpert MRSA NxG Assay is intended to aid in the prevention and control of MRSA infections in healthcare settings. The Xpert MRSA NxG Assay is not intended to diagnose, guide, or monitor treatment for MRSA infections, or provide results of susceptibility to methicillin. A negative result does not preclude MRSA nasal colonization. Concomitant cultures are necessary to recover organisms for epidemiological typing or for further susceptibility testing.
Substantial Equivalence:
The Xpert MRSA NxG Assay is substantially equivalent to the BD MAX™M MRSA XT assay [510(k) #K133605]. The performance of the Xpert MRSA NxG Assay was evaluated in two multi-site prospective clinical studies in which the performance of the Xpert MRSA NxG Assay was determined relative to culture and susceptibility testing. The results of the studies demonstrated that the performance of the Xpert MRSA NxG Assay is substantially equivalent to the predicate device.
Table 8-1 shows the similarities and differences between the Xpert MRSA NxG Assay and the predicate device.
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| Similarities | ||
|---|---|---|
| Item | Device | Predicate Device |
| Cepheid Xpert MRSA NxGAssay | BD MAX™ MRSA XT Assay | |
| 510(k) Number | To be assigned | K133605 |
| Regulation | Same | 866.1640 |
| Product Code | Same | NQX |
| Device Class | Same | II |
| Intended Use | The Xpert® MRSA NxG Assay,performed on the GeneXpert®Instrument Systems, is aqualitative in vitro diagnostic testintended for the detection ofmethicillin-resistantStaphylococcus aureus (MRSA)DNA directly from nasal swabsin patients at risk for nasalcolonization. The test utilizesautomated real-time polymerasechain reaction (PCR) for theamplification of MRSA-specificDNA targets and fluorogenictarget-specific hybridizationprobes for the real-time detectionof the amplified DNA. The XpertMRSA NxG Assay is intended toaid in the prevention and controlof MRSA infections inhealthcare settings. The XpertMRSA NxG Assay is notintended to diagnose, guide, ormonitor treatment for MRSAinfections, or provide results ofsusceptibility to methicillin. Anegative result does not precludeMRSA nasal colonization.Concomitant cultures arenecessary to recover organismsfor epidemiological typing or forfurther susceptibility testing. | The BD MAX™ MRSA XT assayperformed on the BD MAX™System is an automatedqualitative in vitro diagnostic testfor the direct detection ofmethicillin-resistantStaphylococcus aureus (MRSA)DNA from nasal swabs inpatients at risk for nasalcolonization. The test utilizesreal-time polymerase chainreaction (PCR) for theamplification of MRSA DNA andfluorogenic target-specifichybridization probes for thedetection of the amplified DNA.The BD MAX™ MRSA XT assayis intended to aid in theprevention and control of MRSAinfections in healthcare settings.It is not intended todiagnose MRSA infections norguide or monitor treatment forMRSA infections. A negativeresult does not preclude nasalcolonization. Concomitantcultures are necessary to recoverorganisms for epidemiologicaltyping or for further susceptibilitytesting. |
| Similarities | ||
| Item | Device | Predicate Device |
| Cepheid Xpert MRSA NxG Assay | BD MAX™ MRSA XT Assay | |
| Mode of Detection of Methicillin Resistance in S. aureus | Same | Presence of SCCmec cassette at orfX junction (specific to S. aureus) and mecA or mecC genes |
| Specimen Type | Same | Nasal swabs |
| Technological Principles | Same | Nucleic acid amplication (DNA); real-time PCR; fluorogenic target-specific hybridization probes |
| Assay Controls | Same | Specimen Processing Control (SPC) |
| Assay Results | Same | Qualitative |
| Laboratory Users | Same | CLIA Moderate Complexity and High Complexity labs |
Table 8-1: Comparison of Similarities and Differences of the Xpert MRSA NxG Assay with the Predicate Device
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| Primary Differences | ||
|---|---|---|
| Item | New Device | Predicate Device |
| Cepheid Xpert MRSA NxGAssay | BD MAX™ MRSA XTAssay | |
| Instrument System | Cepheid GeneXpertInstrument System | BD MAX System |
| Early assaytermination function | Yes(for positive samples) | No |
The Xpert MRSA NxG Assay has the same general intended use as the predicate device and has the same technological characteristics as the predicate device. The differences between the Xpert MRSA NxG Assay and the predicate device do not raise different questions of safety and effectiveness. The clinical study demonstrates that the Xpert MRSA NxG Assay is acceptable for its intended use with inexperienced lab users and is substantially equivalent to the predicate device described above.
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Non-Clinical Studies:
Analytical Sensitivity (Limit of Detection)
Studies were performed to determine the analytical sensitivity or Limit of Detection (LoD) of the Xpert MRSA NxG Assay using two different collection kits (the Cepheid Sample Collection Device P/N 900-0370 or Copan P/N 139CFA, referred to as the "rayon swab" and the ESwab collection kit, Copan P/N 480C or Becton Dickinson P/N 220245 referred to as the "ESwab" refer to Section 6.3). The LoD is the lowest concentration of sample (reported as CFU/swab or CFU/mL in Elution Reagent) that can be reproducibly distinguished from negative samples 95% of the time with 95% confidence. This study determined the lowest concentration of methicillin-resistant Staphylococcus aureus (MRSA) cells diluted into simulated nasal matrix that can be detected using the Xpert MRSA NxG Assay The simulated nasal matrix consisted of 5% (w/v) porcine mucin and 1% (v/v) human whole blood in a 1X Phosphate Buffered Saline (PBS) solution with 15% (v/v) glycerol.
The analytical sensitivity of the Xpert MRSA NxG Assay was assessed following the guidance in Clinical and Laboratory Standards Institute (CLSI) document EP17-A2 using two lots of reagents tested across three testing days with thirteen (13) individual MRSA strains and the two types of swabs (rayon swab and ESwab). The 13 individual strains represent SCCmec types I, II, III, IV, IVa, V, VI, VIII, IX, X and XI. These strains in the LoD study represent the most common healthcare-acquired (USA100) and most common community-acquired (USA400) MRSA strains that are characterized by pulsedfield gel electrophoresis (PFGE). Strains that contained heterogeneous subpopulations with respect to their oxacillin resistance phenotype were also included in the study.
The LoD was established by testing five concentration levels with two reagent lots. The LoD and 95% confidence interval (CI) were then estimated for each lot using logistic regression analysis. The logistic regression analysis does not rely on a single concentration but utilizes the logit function to incorporate the information from all levels tested in the model. The point estimates were calculated using a method of maximum likelihood estimates (MLE) of the logistic regression model parameters. The maximum estimated LoD observed per strain from the logistic regression analysis was used to establish the LoD claim. The LoD point estimates and 95% upper and lower confidence intervals for each MRSA SCCmec type tested are summarized in Table 8-2 and Table 8-3.
The results of this study indicate that the Xpert MRSA NxG Assay will produce a positive MRSA result 95% of the time with 95% confidence for a nasal swab (Rayon) containing 302 CFU (Table 8-2).
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| MRSA Strain | PFGE IDª | LOD Estimate(Logistic Regression) (CFU/Swab) | LoD EstimateIn ElutionReagent(CFU/mL) | ||
|---|---|---|---|---|---|
| Lower 95%CI | LoD PointEstimate | Upper 95%CI | |||
| Type I | USA500 | 72 | 91 | 136 | 46 |
| Type II | USA100 | 127 | 161 | 236 | 81 |
| Type III | unknown | 50 | 64 | 96 | 32 |
| Type IVa | USA400 | 46 | 58 | 84 | 29 |
| Type IV (Fin 7) | unknown | 256 | 302 | 392 | 151 |
| Type IVa | USA300 | 143 | 182 | 282 | 91 |
| Type V | USA1000 | 85 | 102 | 138 | 51 |
| Type VI | USA800 | 32 | 42 | 64 | 21 |
| Type VII | unknown | 95 | 128 | 235 | 64 |
| Type VIII | unknown | 139 | 163 | 233 | 82 |
| Type IX | unknown | 142 | 169 | 227 | 85 |
| Type X | unknown | 86 | 97 | 119 | 49 |
| Type XI (mecC) | unknown | 219 | 266 | 358 | 133 |
Table 8-2: 95% Confidence Intervals for Analytical LoD - MRSA (Ravon swab)
a. PFGE = Pulsed-field gel electrophoresis
The results of this study indicate that the Xpert MRSA NxG Assay will produce a positive MRSA result 95% of the time with 95% confidence for a nasal swab (ESwab) containing 812 CFU (Table 8-3).
| PFGE IDª | LoD Estimate(Logistic Regression) (CFU/swab) | LoD EstimateIn Elution | |||
|---|---|---|---|---|---|
| MRSA Strain | Lower95% CI | LoD PointEstimate | Upper95% CI | Reagent(CFU/mL) | |
| Type I | USA500 | 285 | 343 | 469 | 45 |
| Type II | USA100 | 184 | 218 | 293 | 28 |
| Type III | unknown | 215 | 254 | 338 | 33 |
| Type IVa | USA400 | 134 | 167 | 245 | 22 |
| Type IV (Fin 7) | unknown | 656 | 812 | 1145 | 106 |
| Type IVa | USA300 | 470 | 563 | 733 | 73 |
| Type V | USA1000 | 378 | 465 | 671 | 61 |
| Type VI | USA800 | 71 | 89 | 128 | 12 |
| Type VII | unknown | 201 | 245 | 338 | 32 |
| Type VIII | unknown | 520 | 631 | 851 | 82 |
| Type IX | unknown | 311 | 377 | 533 | 49 |
| Type X | unknown | 149 | 166 | 215 | 22 |
| Type XI (mecC) | unknown | 597 | 734 | 998 | 96 |
Table 8-3: 95% Confidence Intervals for Analytical LoD — MRSA (ESwab)
a. PFGE = Pulsed-field gel electrophoresis
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Analytical Specificity (Cross-reactivity)
The analytical specificity of the Xpert MRSA NxG Assay was evaluated by testing a panel of one hundred and fifty-two potentially cross-reactive microorganisms that are methicillin-susceptible Staphylococcus aureus (MSSA), organisms phylogenetically related to Staphylococcus aureus (SA), and members of the nasal commensal microflora (e.g., other bacteria, viruses, and yeast) with the potential to cross-react with the Xpert MRSA NxG Assay. The one hundred and fifty two organisms tested were identified as either gram-positive (104), gram-negative (25), yeast (3), viruses (17), or Gram reaction indeterminate (3). Of these organisms, eighty-four were characterized as follows: twenty-three (23) were methicillin-susceptible, coagulase-negative Staphylococcus (MSCoNS). five (5) were methicillin-resistant, coagulase-negative Staphylococcus (MRCoNS), forty-seven (47) were methicillin-susceptible Staphylococcus aureus (MSSA), including two (2) empty cassette MSSA, and seven (7) borderline oxacillinresistant Staphylococcus aureus (BORSA) strains. Human cells were also tested in the study.
Evaluation of BORSA Strains: The seven well-characterized borderline oxacillinresistant Staphylococcus aureus (BORSA) strains that were tested included one "empty cassette" MSSA strain. Methicillin-resistant Staphylococcus aureus is resistant to all ßlactam drugs (with the exception of ceftaroline) through the alternative penicillin-binding protein PBP2a encoded by mecA or mecC. BORSA strains do not carry mecA/mecC gene, but exhibit an oxacillin minimum inhibitory concentration (MIC) > 2 and < 8 ug/mL. It is especially valuable to distinguish MRSA from BORSA to aid in implementing appropriate management and isolation precaution options for patients infected with methicillin-susceptible strains of S. aureus. BORSA strains tested with Xpert MRSA NxG assay were reported as MRSA NOT DETECTED.
All potentially cross-reactive microorganisms were tested in triplicate in Elution Reagent containing simulated nasal matrix at >106 CFU/mL for bacteria and >105 TCIDe6/mL for viruses. Human cells were tested at 10° cells/mL.
All microorganisms and the human cells were reported as MRSA NOT DETECTED by the Xpert MRSA NxG Assay. For the panel of one hundred and fifty-two potentially cross-reactive microorganisms and human cells evaluated in the study, the analytical specificity of the Xpert MRSA NxG Assay was 100%.
In silico analysis indicates that the Xpert MRSA NxG Assay may produce positive results with strains of Staphylococcus argenteus, a recently described species of Staphylococcus that is closely related to S. aureus, that carry an SCCmec cassette and mecA or mecC.
Microbial Interference
A study was conducted to assess the inhibitory effects of commensal microorganisms in nasal swab specimens on the performance of the Xpert MRSA NxG Assay. A panel of nine (9) bacterial strains, reported to be present in 10% or more of nasal cavities of healthy subjects, were evaluated using the Xpert MRSA NxG Assay (Table 8-4).
The nine commensal bacteria were spiked into the simulated nasal matrix at
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approximately 1.0 x 10° CFU/ mL in Elution Reagent and tested in the presence of MRSA (cross-reactivity) or in the absence of MRSA (interference). Two MRSA strains (Table 8-5) were used in this study and these strains prepared at approximately 3X LoD and tested in replicates of four. None of the potentially interfering microorganisms evaluated in the study were found to cross-react or interfere with the detection of any of the MRSA strains using the Xpert MRSA NxG Assay.
| Strain | Strain ID |
|---|---|
| Staphylococcus aureus (MSSA) | 15280 |
| Staphylococcus epidermidis (MSSE) | ATCC 35984 |
| Corynebacterium bovis | ATCC 7715 |
| Streptococcus mutans | ATCC 25175 |
| Proteus vulgaris | ATCC 29905 |
| Haemophilus influenzae | ATCC 9007 |
| Neisseria meningitidis | ATCC 700111 |
| Moraxella catarrhalis | ATCC 43628 |
| Streptococcus pneumoniae | ATCC 6303 |
Table 8-4: Commensal Bacterial Strains Tested in Microbial Interference
Table 8-5: MRSA Strains
| Target | Strain ID |
|---|---|
| MRSA ( mecA ) | MRSA Type II (NRSA70,N315) |
| MRSA ( mecC ) | MRSA Type XI LGA251 |
Analytical Reactivity (Inclusivity)
One hundred and ninety-six methicillin-resistant Staphylococcus aureus strains were tested in this study. The strains tested represented Cooper and Feil Groups 1A, 1B, and 2, SCCmec types and subtypes (I, IA, II, III, IIIA, III-Hg, IV, IVa, IVb, IVc, IVc, V, VI, VII, VIII, IX, X and XI), - sequence types (STs), spa-types, PFGE types, and clonal complexes (CC). Known USA100, USA200, USA300, USA400, USA500, USA600, USA700. USA800. USA1000. USA1100. IBERIAN strains, heteroresistant strains, and novel mecC strain MRSALGA251 were also included in this study. A "challenge panel" of 59 well characterized MRSA strains that have Minimum Inhibitory Concentrations (MIC) for cefoxitin/oxacillin that span the measurable dynamic range were also included in this study. Oxacillin MIC values for these 59 strains ranged from 0.5 to >32 µg/mL.
All 196 MRSA strains were correctly reported as MRSA DETECTED using the Xpert MRSA NxG Assay.
Interfering Substances Study
Nineteen substances that may be present in nasal swab specimens with the potential to interfere with the performance of the Xpert MRSA NxG Assay were evaluated. The
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potentially interfering substances included mucous, human blood, nasal sprays or drops, nasal gels, nasal corticosteroids, FluMist, oral nasal anesthetics or analgesics, nasal antibiotics, antibacterials and antivirals. The substances, active ingredients, and concentrations tested are listed in Table 8-6. All interfering substances, with the exception of mucin, were initially tested at 50% (v/v) in a simulated nasal matrix for Negative (simulated matrix only) and MRSA-positive samples. Mucin was tested at 7% (w/v) in simulated nasal matrix for Negative (simulated matrix only) and MRSA-positive samples.
Buffer Controls (negative and positive) without interfering substances were included.
Positive samples were tested per interfering substance with two clinical MRSA strains. SCCmec Type II (mecA) and SCCmec Type XI (mecC1GA251), spiked at approximately 3X analytical LoD in simulated nasal matrix.
Replicates of eight positive and negative samples with each interfering substance were evaluated in this study. Negative samples in the presence of potentially interfering substance were tested to determine the impact on the performance of the sample processing control (SPC).
The effect of each potentially interfering substance on positive and negative samples was assessed by comparing the target cycle threshold (Ct) values generated in the presence of the potentially interfering substance to the Ct values of the buffer controls in the absence of the potentially interfering substance.
The positive and negative samples for 16 potentially interfering substances were correctly identified. Potentially inhibitory effects were observed in positive samples tested with Nasonex 50% (v/v), Flonase 50% (v/v), and Beconase at 40% (v/v) and 50% (v/v) due to delay in Ct values; however, none of the substances reported false negative test results. No interference was observed in positive samples tested with Nasonex 40% (v/v), Flonase 40% (v/v), and Beconase at 30% (v/v). This is addressed in Section 16, Limitations, in the package insert.
| Substance | Active Ingredient | ConcentrationTested |
|---|---|---|
| Mucous (Mucin) | Porcine mucin representing denselyglycosylated proteins (mucous) | 7% (w/v) |
| Blood | Blood (Human) | 50% (v/v) |
| Aneferin Decongestant Spray | 0.05% Oxymetazoline Hydrochloride | 50% (v/v) |
| Azelastin Antihistamine Spray | 0.1% Azelastine Hydrochloride | 50% (v/v) |
| NasalCrom Allergy Symptom | 5.2 mg Cromolyn Sodium | 50% (v/v) |
| Neo-Synephrine Decongestant Spray | 0.5% Phenylephrine Hydrochloride | 50% (v/v) |
| Saline Nasal Moisturizing Spray | 0.65% Sodium Chloride | 50% (v/v) |
Table 8-6. Potential Interfering Nasal Substances Tested
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| Substance | Active Ingredient | ConcentrationTested |
|---|---|---|
| Zicam Nasal Gel(Upper Respiratory AllergySymptom Relief) | 4x, 12x, 30x Luffaoperculata 12x, 30xGalphimia glauca12x, 30x, 200x Histaminumhydrochloricum 12x, 30x, 200x Sulphur | 50% (v/v) |
| Nasonex (Nasal AllergySymptom Medication, inhaled | 0.05% Mometasone Furoate Monohydrate | 40%(v/v),50% (v/v)a |
| Flonase | 0.05% Fluticasone Propionate | 40% (v/v),50% (v/v)a |
| FluMist | Live intranasal influenza virus vaccine | 50% (v/v) |
| Finafta Multioral | 7.5% Benzocaine | 50% (v/v) |
| TobraDex | 0.3% Tobramycin, 0.1% Dexamethasone | 50% (v/v) |
| Bactroban | 2% Mupirocin | 50% (v/v) |
| Relenza | 5 mg Zanamivir | 50% (v/v) |
| Beconase® AQ | 0.05% or 3.6x10-5 g Beclomethasone | 30% (v/v),40% (v/v)a,50% (v/v)a |
| Nasacort® AQ | 0.06% or 4.4x10-5 g Triamcinoloneacetonide | 50% (v/v) |
| Rhinocort aqua® | 0.06% or 4.4x10-5 g Budesonide | 50% (v/v) |
| Flunisolide Nasal Solution USP,0.025% | 0.03% or 1.9x10-5 g Flunisolide | 50% (v/v) |
a. Potential inhibitory effect observed for the concentration tested due to delay in Ct values.
Carry-Over Contamination
A study was conducted to demonstrate that single-use, self-contained GeneXpert cartridges prevent carry-over contamination in negative samples tested following very high MRSA-positive samples in the same GeneXpert module. The study consisted of a negative sample processed in the same GeneXpert module immediately following a very high positive sample. The MRSA-negative samples were composed of MSSE prepared in a simulated nasal matrix at a concentration ≥1.0 x 10 CFU/mL in the Elution Reagent. The MRSA-positive samples were composed of MRSA in a simulated nasal matrix at a concentration ≥1 x 10' CFU/mL in the Elution Reagent. The testing scheme was repeated 40 times between 2 GeneXpert instruments (one module per instrument) for a total of 41 runs per instrument (20 high positive samples per instrument and 21 negative samples per instrument). All 40 positive samples were correctly reported as MRSA DETECTED. All 42 negative samples were correctly reported as MRSA NOT DETECTED.
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Linearity
Not applicable, the Xpert MRSA NxG Assay is a qualitative assay.
Clinical Studies
Clinical Performance
Performance characteristics of the Xpert MRSA NxG Assay were determined in two separate prospective, multi-site investigational studies using nasal specimens collected from individuals at risk for nasal colonization of methicillin-resistant S. aureus (MRSA). In the first study, eight investigational sites within the US and outside of the US tested the Xpert MRSA NxG Assay with nasal swabs collected using the Cepheid Sample Collection Device (Rayon Swab). In the second study, six investigational sites within the US tested the Xpert MRSA NxG Assay with nasal swabs collected using the Liquid Amies Elution Swab (ESwab) Collection and Transport System. Not more than one specimen per subject was included in the studies and analyses.
The Xpert MRSA NxG Assay results were compared to reference culture and susceptibility results.
The comparative reference method consisted of both a direct culture on MRSA selective chromogenic medium and enriched culture. Enrichment of the specimen was performed in Trypticase Soy Broth (TSB) with 6.5% Sodium Chloride followed by subculture of the TSB 6.5% NaCl on to Blood Agar (BA) and MRSA selective chromogenic medium. Identification of presumptive S. aureus colonies from BA and MRSA colonies from the selective chromogenic medium plates was confirmed with Gram stain, and catalase and coagulase testing. MRSA was confirmed by susceptibility testing with a Cefoxitin disk (30µg). The reference method result was considered positive for MRSA if the presence of MRSA was confirmed in either direct culture or enriched culture.
Results Obtained with the Xpert MRSA NxG Assay in Comparison to the Reference Method using the Rayon Swab
A total of 1103 eligible Rayon swab specimens were tested by the Xpert MRSA NxG Assay and by the reference method. Relative to the reference method, the Xpert MRSA NxG Assay demonstrated a sensitivity and specificity of 91.0% and 96.9%, respectively (Table 8-7). For the population tested, the MRSA positive predictive value (PPV) was 78.7% and the negative predictive value (NPV) was 98.9%.
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| Reference Method | ||||
|---|---|---|---|---|
| MRSA | Positive | Negative | Total | |
| Xpert MRSA NxG | Positive | 111 | 30a | 141 |
| Negative | 11b | 951 | 962 | |
| Total | 122 | 981 | 1103 | |
| Sensitivity: 91.0% (95% CI: 84.6-94.9) | ||||
| Specificity: 96.9% (95% CI: 95.7-97.8) | ||||
| PPV: 78.7% (95% CI: 71.3-84.7) | ||||
| NPV: 98.9% (95% CI: 98.0-99.4) |
Table 8-7: Xpert MRSA NxG Assay with Rayon Swab vs. Reference Method
a. 30/30 specimens with Xpert MRSA NxG false positive results were also
MRSA culture negative upon repeat subculture of the enrichment broth. b. 11/11 specimens with Xpert MRSA NxG false positive results were MRSA culture positive upon repeat subculture of the enrichment broth.
Results Obtained with the Xpert MRSA NxG Assay in Comparison to the Reference Method using the ESwab
A total of 846 eligible ESwab specimens were tested by the Xpert MRSA NxG Assay and by the reference method. Relative to the reference method, the Xpert MRSA NxG Assay demonstrated a sensitivity and specificity of 92.9% and 97.6%, respectively (Table 8-8). For the population tested. the MRSA positive predictive value (PPV) was 83.5% and the negative predictive value (NPV) was 99.1%.
| Reference Method | ||||
|---|---|---|---|---|
| MRSA | Positive | Negative | Total | |
| Xpert MRSANxG | Positive | 91 | 18a | 109 |
| Negative | 7b | 730 | 737 | |
| Total | 98 | 748 | 846 | |
| Sensitivity: 92.9% (95% CI: 86.0-96.5) | ||||
| Specificity: 97.6% (95% CI: 96.2-98.5) | ||||
| PPV: 83.5% (95% CI: 75.4-89.3) | ||||
| NPV: 99.1% (95% CI: 98.1-99.5) |
Table 8-8: Xpert MRSA NxG Assay with ESwab vs. Reference Method
a. 17/18 specimens with Xpert MRSA NxG false positive results were also MRSA culture negative after repeat of subculture of the enrichment broth.
b. 6/7 specimens with Xpert MRSA NxG false negative results were MRSA culture positive after repeat subculture of the enrichment broth.
Results Obtained with the Xpert MRSA NxG Assay in Comparison to the Reference Method for the Rayon Swab and ESwab Combined
Table 8-9 shows the sensitivity and specificity analyses of the combined Xpert MRSA NxG Assay results with Rayon Swab and ESwab relative to the reference method.
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| Reference Method | ||||
|---|---|---|---|---|
| MRSA | Positive | Negative | Total | |
| Xpert MRSANxG | Positive | 202 | 48 | 250 |
| Negative | 18 | 1681 | 1699 | |
| Total | 220 | 1729 | 1949 | |
| Sensitivity: 91.8% (95% CI: 87.4-94.8) | ||||
| Specificity: 97.2% (95% CI: 96.3-97.9) | ||||
| PPV: 80.8% (95% CI: 75.5-85.2) | ||||
| NPV: 98.9% (95% CI: 98.3-99.3) |
Table 8-9: Xpert MRSA NxG Assay with Rayon Swab and ESwab Combined vs. Reference Methodª
a. Using the data from Tables 8-7 and 8-8, the Fisher's Exact Test (p-value = 0.81 for sensitivity and p-value = 0.46 for specificity) demonstrated that the data are poolable across collection devices (Rayon Swab and ESwab).
Reproducibility Study
A panel of five samples with varying concentrations of MRSA was tested four times per day on six different days by two different operators, at three sites (5 samples x 4 times/day x 6 days x 2 operators x 3 sites). Three lots of Xpert MRSA NxG Assay cartridges were used, with each representing two days of testing. The Xpert MRSA NxG Assay was performed according to the Xpert MRSA NxG Assay procedure. Each of the 5 samples was prepared in simulated nasal matrix at the concentration levels in Table 8-10. Results are summarized in Table 8-11.
Table 8-10: Reproducibility Panel
| Panel Sample | Concentration Level |
|---|---|
| Neg | True negative (no target) |
| ModPos1, MRSA Type XI (mecC) | Moderate positive (~2-3x LoD) |
| LowPos1, MRSA Type XI (mecC) | LOD (~1x LoD) |
| ModPos2, MRSA Type II (mecA) | Moderate positive (~2-3x LoD) |
| LowPos2, MRSA Type II (mecA) | LoD (~1x LoD) |
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| Site Operator | Site Operator | Site Operator | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sample | Op 1 | Op 2 | Site | Op 1 | Op 2 | Site | Op 1 | Op 2 | Site | % TotalAgreement bySample | ||
| Neg | 100%(24/24) | 100%(24/24) | 100%(48/48) | 100%(24/24) | 100%(24/24) | 100%(48/48) | 100%(24/24) | 100%(24/24) | 100%(48/48) | 100%(144/144) | ||
| ModPos1 | 100%(24/24) | 100%(24/24) | 100%(48/48) | 100%(24/24) | 100%(24/24) | 100%(48/48) | 100%(24/24) | 100%(24/24) | 100%(48/48) | 100%(144/144) | ||
| LowPos1 | 100%(24/24) | 100%(24/24) | 100%(48/48) | 100%(24/24) | 100%(24/24) | 100%(48/48) | 100%(24/24) | 100%(24/24) | 100%(48/48) | 100%(144/144) | ||
| ModPos2 | 100%(24/24) | 100%(24/24) | 100%(48/48) | 100%(24/24) | 100%(24/24) | 100%(48/48) | 100%(24/24) | 100%(24/24) | 100%(48/48) | 100%(144/144) | ||
| LowPos2 | 95.8%(23/24) | 100%(24/24) | 97.9%(47/48) | 100%(24/24) | 100%(24/24) | 100%(48/48) | 100%(24/24) | 95.8%(23/24) | 97.9(47/48) | 98.6%(142/144) |
Table 8-11: Summary of Reproducibility Results: % Agreement by Study Site/Operator
The reproducibility of the Xpert MRSA NxG Assay was also evaluated in terms of the fluorescence signal expressed in Ct values for each target detected. The mean, standard deviation (SD), and coefficient of variation (CV) between-sites, between-days, betweenlots, between-operators and within-assay for each panel member are presented in Table 8-12.
| Sample | AssayChannel(Analyte) | Nb | MeanCt | Between-Site | Between-Day | Between-Lot | Between-Operator | Within-Assay | Total | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | CV(%)c | SD | CV(%)c | SD | CV(%)c | SD | CV(%)c | SD | CV(%)c | SD | CV(%)c | ||||
| Neg | SPC | 144 | 32.3 | 0.0 | 0.0 | 0.0 | 0.0 | 0.3 | 0.9 | 0.3 | 0.8 | 0.8 | 2.3 | 0.8 | 2.6 |
| mec | 144 | 29.9 | 0.0 | 0.0 | 0.0 | 0.0 | 0.4 | 1.4 | 0.0 | 0.0 | 1.1 | 3.5 | 1.1 | 3.8 | |
| ModPos1 | SCC | 144 | 32.6 | 0.0 | 0.0 | 0.0 | 0.0 | 0.5 | 1.5 | 0.0 | 0.0 | 1.0 | 3.0 | 1.1 | 3.3 |
| mec | 144 | 31.7 | 0.0 | 0.0 | 0.0 | 0.0 | 0.4 | 1.4 | 0.0 | 0.0 | 1.0 | 3.2 | 1.1 | 3.5 | |
| LowPos1 | SCC | 144 | 34.3 | 0.0 | 0.0 | 0.0 | 0.0 | 0.5 | 1.5 | 0.0 | 0.0 | 0.9 | 2.7 | 1.1 | 3.1 |
| mec | 144 | 31.2 | 0.0 | 0.0 | 0.3 | 0.9 | 0.2 | 0.5 | 0.0 | 0.0 | 0.9 | 3.0 | 1.0 | 3.1 | |
| ModPos2 | SCC | 144 | 32.8 | 0.0 | 0.0 | 0.3 | 0.8 | 0.3 | 1.0 | 0.0 | 0.0 | 0.9 | 2.7 | 1.0 | 3.0 |
| mec | 144 | 32.7 | 0.0 | 0.0 | 0.4 | 1.1 | 0.0 | 0.0 | 0.2 | 0.6 | 1.0 | 3.0 | 1.1 | 3.2 | |
| LowPos2 | SCC | 144 | 34.4 | 0.0 | 0.0 | 0.4 | 1.1 | 0.0 | 0.0 | 0.1 | 0.3 | 1.0 | 3.0 | 1.1 | 3.3 |
Table 8-12: Summary of Reproducibility Data4
a. There were a total of 12 indeterminate results over the study (11 reported as "Error" and 1 as "Invalid"). All 12 produced valid test results upon repeat.
b. Results with non-zero Ct values out of 144.
c. (%) is contribution of variance of component to overall CV.
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Conclusions
The results of the nonclinical analytical and clinical performance studies summarized above demonstrate that the Xpert MRSA NxG Assay is substantially equivalent to the predicate device.
§ 866.1640 Antimicrobial susceptibility test powder.
(a)
Identification. An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).