Xpert Carba-R

K152614 · Cepheid · PMY · Mar 7, 2016 · Microbiology

Device Facts

• Record ID: K152614
• Device Name: Xpert Carba-R
• Applicant: Cepheid
• Product Code: PMY · Microbiology
• Decision Date: Mar 7, 2016
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1640
• Device Class: Class 2

Intended Use

The Xpert® Carba-R Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test for the detection and differentiation of the blaKPC, blaNDM, blaVIM, blaOXA-48, and blaIMP gene sequences associated with carbapenem-non-susceptible pure colonies of Enterobacteriaceae, Acinetobacter baumannii, or Pseudomonas aeruginosa grown on blood agar or MacConkey agar. The test utilizes automated real-time polymerase chain reaction (PCR). A negative Xpert Carba-R Assay result does not preclude the presence of other resistance mechanisms. The Xpert Carba-R Assay should be used in conjunction with other laboratory tests including phenotypic antimicrobial susceptibility testing. The Xpert Carba-R Assay is intended as an aid for infection control in detecting and differentiating genetic markers of resistance to monitor the spread of carbapenem-non-susceptible organisms in healthcare settings. The Xpert Carba-R Assay is not intended to guide or monitor treatment for carbapenem-non-susceptible bacterial infections.

Device Story

Device performs qualitative in vitro diagnostic testing for specific carbapenem-resistance gene sequences (blaKPC, blaNDM, blaVIM, blaOXA-48, blaIMP) in bacterial isolates. Input: pure culture isolates from blood or MacConkey agar. Process: automated real-time multiplex PCR using single-use, multi-chambered fluidic cartridges on GeneXpert Instrument Systems (Dx, Infinity-48/s, Infinity-80). Cartridges contain reagents for amplification and detection; internal Sample Processing Control (SPC) and Probe Check Control (PCC) monitor reaction integrity. Instrument automates cell lysis via ultrasonic horn, fluid movement via syringe drive/rotary valve, and thermocycling via I-CORE® module. Output: automated report of detected/not-detected gene sequences. Used in clinical laboratories by trained personnel. Results aid infection control by identifying resistance markers to monitor spread of carbapenem-non-susceptible organisms; results do not guide patient treatment.

Clinical Evidence

Multi-site clinical study evaluated 467 isolates (Enterobacteriaceae, P. aeruginosa, A. baumannii) against reference bi-directional sequencing. Overall sensitivity 100% (95% CI: 99.0-100) and specificity 98.1% (93.2-99.5) for blood agar; 100% sensitivity and 97.1% (91.8-99.0) specificity for MacConkey agar. Reproducibility study across 3 sites, 2 operators, and 3 cartridge lots showed high agreement (>98%).

Technological Characteristics

Real-time PCR assay; disposable multi-chambered fluidic cartridge; TaqMan probe detection; internal controls (SPC, PCC); automated sample prep/amplification; GeneXpert Instrument Systems (1-80 modules); 50-minute runtime; storage 2°C-28°C.

Indications for Use

Indicated for qualitative detection/differentiation of blaKPC, blaNDM, blaVIM, blaOXA-48, and blaIMP gene sequences in carbapenem-non-susceptible pure colonies of Enterobacteriaceae, Acinetobacter baumannii, or Pseudomonas aeruginosa. For prescription use only. Not for bacterial identification or treatment monitoring.

Regulatory Classification

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.

Predicate Devices

• Xpert® vanA Assay (K092953)

Submission Summary (Full Text)

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

March 7, 2016

CEPHEID JIM KELLY, Ph.D. EXECUTIVE DIRECTOR, REGULATORY AFFAIRS 904 CARIBBEAN DRIVE SUNNYVALE CA 94089-1189

Re: K152614

Trade/Device Name: Xpert® Carba-R Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial susceptibility test powder Regulatory Class: II Product Code: PMY, OOI Dated: February 5, 2016 Received: February 8, 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 (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.

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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 [phone] or [phone] 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 [phone] or [phone] 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)

#### K152614

Device Name

#### Xpert Carba-R

Indications for Use (Describe)

The Xpert® Carba-R Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test for the detection and differentiation of the blaχρι, blaკγι blaკγൂ and blânup gene sequences associated with carbapenem-non-susceptible pure colonies of Enterobacteriaceae, Acinetobacter baumannii, or Pseudomonas aeruginosa grown on blood agar or MacConkey agar. The test utilizes automated real-time polymerase chain reaction (PCR).

A negative Xpert Carba-R Assay result does not presence of other resistance mechanisms. The Xpert Carba-R Assay should be used in conjunction with other laboratory tests including phenotypic antimicrobial susceptibility testing. The Xpert Carba-R Assay is intended as an aid for infection control in detecting and differentiating genetic markers of resistance to monitor the spread of carbapenem-non-susceptible organisms in healthcare settings. The Xpert Carba-R Assay is not intended to quide or monitor treatment for carbapenem-non-susceptible bacterial infections.

| Type of Use (Select one or both, as applicable) | |
|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| <div> <span> <svg fill="none" height="16" viewbox="0 0 16 16" width="16" xmlns="http://www.w3.org/2000/svg"> <path d="M13.2222 3.77783L5.77778 11.2223L2.77778 8.22229" stroke="black" stroke-linecap="round" stroke-linejoin="round" stroke-width="1.5"></path> </svg> </span> Prescription Use (Part 21 CFR 801 Subpart D) </div> | <div> <span> <svg fill="none" height="16" viewbox="0 0 16 16" width="16" xmlns="http://www.w3.org/2000/svg"> </svg> </span> Over-The-Counter Use (21 CFR 801 Subpart C) </div> |

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## 510(k) Summary

As required by 21 CFR Section 807.92(c).

| Submitted by: | Cepheid<br>904 Caribbean Drive<br>Sunnyvale, CA 90489<br>Phone number: [phone]<br>Fax number: [phone] |
|---------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact: | Scott A. Campbell, PhD, MBA |
| Date of Preparation: | March 2, 2016 |
| Device: | |
| 510(k) Number: | K152614 |
| Trade name: | Xpert® Carba-R |
| Common name: | Xpert Carba-R Assay |
| Type of Test: | Qualitative nucleic acid amplification test of the blaKPC, blaNDM,<br>blaVIM, blaOXA-48, and blaIMP gene sequences from isolates of<br>pure cultures of carbapenem-non-susceptibility gram-negative<br>bacteria |
| Classification: | II |
| Regulation number | 866.1640 |
| Classification name:<br>Product code: | Antimicrobial susceptibility test powder<br>PMY, OOI |
| Classification<br>Advisory Panel | Microbiology (83) |
| Prescription Use | Yes |
| Predicate Device<br>Assay: | Cepheid Xpert® vanA<br>[510(k) #K092953] |

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#### Device Description:

The Xpert Carba-R Assay is an automated real-time polymerase chain reaction (PCR) in vitro diagnostic test for qualitative detection of the blaker, blaym, blaym, blagxa-a8, and blang gene sequences from isolates of pure cultures of carbapenem-non-susceptibility gram-negative bacteria. The Xpert Carba-R Assay is intended as an aid for infection control for monitoring the spread of carbapenem-non-susceptible organisms in healthcare settings.

The Xpert Carba-R 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 Carba-R 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 Carba-R Assay cartridges contain reagents for the detection of blaker, blayDM. blaym, blaoxa-as, and blansp gene sequences. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are controls utilized by the GeneXpert Instrument System platform. The SPC is present to control for adequate processing of the target bacteria and to monitor the presence of inhibitors in the real-time PCR reaction to reduce the possibility of false negative results. The PCC 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 the blakpc, blaNDM, blaviM, blaoxA-48, and blamp gene sequences from isolates of pure cultures of carbapenem-nonsusceptibility gram-negative bacteria in approximately 50 minutes. 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 processing and real-time PCR and RT-PCR tests. Each module contains a svringe 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.

The bacterial isolates from culture are placed into a sample reagent. The sample is transferred to the sample chamber of the disposable fluidic cartridge (the Xpert Carba-R cartridge). 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 the blaker, bland, blaym, blagx,-48, and blange gene sequences. The results are automatically generated at the end of the process in a report that can be viewed and printed.

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#### Device Intended Use:

The Xpert® Carba-R Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test for the detection and differentiation of the blakpor blands blayms blacks and bland gene sequences associated with carbapenem-nonsusceptible pure colonies of Enterobacteriaceae, Acinetobacter baumannii, or Pseudomonas aeruginosa grown on blood agar or MacConkey agar. The test utilizes automated real-time polymerase chain reaction (PCR).

A negative Xpert Carba-R Assay result does not preclude the presence of other resistance mechanisms. The Xpert Carba-R Assay should be used in conjunction with other laboratory tests including phenotypic antimicrobial susceptibility testing. The Xpert Carba-R Assay is intended as an aid for infection control in detecting and differentiating genetic markers of resistance to monitor the spread of carbapenem-nonsusceptible organisms in healthcare settings. The Xpert Carba-R Assay is not intended to guide or monitor treatment for carbapenem-non-susceptible bacterial infections.

#### Substantial Equivalence:

The Cepheid Xpert Carba-R Assay is substantially equivalent to the Xpert® vanA, 510(k) #K092953. The Xpert Carba-R Assay and the Xpert vanA Assay both detect target gene sequences from antibiotic-resistant bacteria and use real-time PCR amplification and fluorogenic target-specific hybridization detection. The performance of the Xpert Carba-R Assay was determined in a multi-site clinical study in which the performance of the Xpert Carba-R Assay was evaluated relative to reference DNA sequence analysis. The results of the study demonstrated that the performance of the Xpert Carba-R Assay is substantially equivalent to the predicate device.

Table 5-1 shows the similarities and differences between the Xpert Carba-R Assay and the predicate device.

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| Similarities | | |
|-----------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Item | Device | Predicate Device |
| | Cepheid Xpert Carba-R Assay | Cepheid Xpert vanA Assay<br>K092953 |
| General Intended<br>Use | The Xpert® Carba-R Assay,<br>performed on the GeneXpert®<br>Instrument Systems, is a<br>qualitative <i>in vitro</i> diagnostic<br>test for the <b>detection</b> and<br>differentiation of the <i>bla</i> KPC,<br><i>bla</i> NDM, <i>bla</i> VIM, <i>bla</i> OXA-48, and<br><i>bla</i> IMP gene sequences<br>associated with carbapenem-<br>non-susceptible pure colonies of<br><i>Enterobacteriaceae</i> ,<br><i>Acinetobacter baumannii</i> , or<br><i>Pseudomonas aeruginosa</i><br>grown on blood agar or<br>MacConkey agar. The test<br>utilizes <b>automated real-time<br/>polymerase chain reaction<br/>(PCR)</b> .<br><br>A negative Xpert Carba-R<br>Assay result does not preclude<br>the presence of other resistance<br>mechanisms. The Xpert®<br>Carba-R Assay should be used<br>in conjunction with other<br>laboratory tests including<br>phenotypic antimicrobial<br>susceptibility testing. The Xpert<br>Carba-R Assay is intended as<br>an aid for infection control in<br>detecting and differentiating<br>genetic markers of resistance<br>to monitor the spread of<br>carbapenem-non-susceptible<br>organisms in healthcare<br>settings. The Xpert Carba-R<br>Assay is not intended to guide<br>or monitor treatment for<br>carbapenem-non-susceptible<br>bacterial infections. | The Cepheid Xpert® vanA Assay<br>performed in the GeneXpert® Dx<br>System is a qualitative <i>in vitro</i><br>diagnostic test designed for <b>rapid<br/>detection</b> of the <i>vanA</i> gene<br>sequence associated with<br>vancomycin resistance in<br>bacteria obtained from rectal<br>swab specimens from patients at<br>risk for intestinal colonization<br>with vancomycin-resistant<br><b>bacteria</b> . <b>The test utilizes<br/>automated real-time<br/>polymerase chain reaction<br/>(PCR)</b> to detect the <i>vanA</i> gene<br>that is frequently associated with<br>vancomycin-resistant enterococci<br>(VRE). The Xpert <i>vanA</i> Assay is<br>intended to aid in the recognition,<br>prevention, and control of<br>vancomycin resistant organisms<br>that colonize patients in<br>healthcare settings. The Xpert<br><i>vanA</i> Assay is not intended to<br>diagnose infections caused by<br>vancomycin-resistant bacteria<br>nor to guide or monitor treatment<br>for vancomycin-resistant<br>bacterial infections. Concomitant<br>cultures are necessary to recover<br>organisms for confirmatory<br>identification of vancomycin-<br>resistant bacteria, antimicrobial<br>susceptibility testing, and for<br>epidemiological typing. |
| Similarities | | |
| Item | Device | Predicate Device |
| | Cepheid Xpert Carba-R Assay | Cepheid Xpert vanA Assay<br>K092953 |
| Type of test | Same | Qualitative |
| Technological<br>Principles | Same | Fully-automated nucleic acid<br>amplification (DNA); real-time<br>PCR |
| Test Cartridge | Same | Disposable single-use, multi-<br>chambered fluidic cartridge |
| Probes | Same | TaqMan® Probes |
| Controls | Same | Internal sample processing<br>control (SPC) and probe<br>check control (PCC)<br>External controls available |
| Instrument<br>System | GeneXpert Instrument System<br>(includes GeneXpert Dx,<br>Infinity-48, Infinity-48s, and<br>Infinity-80) | GeneXpert Dx |
| Time to obtain<br>test results | Approximately 50 minutes to<br>results | Approximately 45 minutes to<br>results |
| Interpretation of<br>test results | Diagnostic software of the<br>GeneXpert Instrument System | Diagnostic software of the<br>GeneXpert Dx |
| Laboratory Users | Operators in CLIA Moderate or<br>High Complexity labs | Operators in CLIA Moderate or<br>High Complexity labs |
| Differences | | |
| Item | New Device | Predicate Device |
| | Cepheid Xpert Carba-R Assay | Cepheid Xpert vanA Assay<br>K092953 |
| Sample Type | Bacterial isolates from culture | Rectal swabs |
| Assay Targets | Detects blaKPC, blaNDM, blaVIM,<br>blaOXA-48, and blaIMP gene<br>sequences | Detects gene sequences for the<br>vanA encoded resistance to<br>vancomycin/teicoplanin |
| Similarities | | |
| Item | Device | Predicate Device |
| | Cepheid Xpert Carba-R Assay | Cepheid Xpert vanA Assay<br>K092953 |
| Instrument<br>System | GeneXpert Instrument System<br>(includes GeneXpert Dx,<br>Infinity-48, Infinity-48s, and<br>Infinity-80)…