(30 days)
Not Found
No
The description focuses on automated real-time PCR and mentions "rules-based algorithms," which are not indicative of AI/ML.
No.
The device is an in vitro diagnostic test used to detect specific DNA targets (MRSA/SA) from blood cultures, aiding in diagnosis rather than directly treating a condition.
Yes
The device is described as a "qualitative in vitro diagnostic test intended for the detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) DNA directly from positive blood cultures." The term "in vitro diagnostic test" explicitly indicates its purpose in diagnosing conditions by performing tests outside of a living organism.
No
The device description clearly outlines a system that includes hardware components (GeneXpert Instrument Systems, disposable cartridges, pipettes, elution reagent tubes) in addition to the software. It is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the device is a "qualitative in vitro diagnostic test."
- Nature of the Test: The test is performed on biological samples (positive blood cultures) outside of the body ("in vitro") to detect specific DNA targets (MRSA/SA DNA) for diagnostic purposes.
- Purpose: The test is intended to be used "as an aid in the detection of MRSA/SA from positive blood culturing." This clearly indicates a diagnostic purpose.
N/A
Intended Use / Indications for Use
The Cepheid® Xpert® MRSA/SA Blood Culture test, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test intended for the detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococus aureus (MRSA) DNA directly from positive blood cultures. The assay utilizes automated real-time polymerase chain reaction (PCR) for the amplification of MRSA/SA specific DNA targets and fluorogenic target-specific hybridization probes for the real-time detection of the amplified DNA. The assay is performed directly on positive blood culture samples from BD BACTEC™ Plus Aerobic/F, BacT/ALERT® SA (Standard Aerobic) or VersaTREK REDOX 1® (aerobic) blood culture bottles that are determined by Gram Stain as Gram Positive Cocci in Clusters (GPCC) or as Gram Positive Cocci in singles (GPC). The Xpert MRSA/SA Blood Culture test is indicated for use in conjunction with other laboratory tests, such as culture, and clinical data available to the clinician as an aid in the detection of MRSA/SA from positive blood culturing of positive blood cultures is necessary to recover organisms for susceptibility testing or for epidemiological typing. The Cepheid Xpert MRSA/SA Blood Culture test is not intended to monitor treatment for MRSA/SA infections.
Product codes (comma separated list FDA assigned to the subject device)
NQX, OOI
Device Description
The Cepheid Xpert® MRSA/SA Blood Culture test is a rapid, automated DNA test for the simultaneous qualitative detection of MRSA and SA DNA directly from blood culture bottle samples that are detected as positive for microbial growth and shown to contain Gram Positive Cocci by Gram stain. The primers and probes in the Xpert MRSA/SA Blood Culture test detect nucleic acid sequences of the staphylococcal protein A (spa), the gene for methicillin/oxacillin resistance (mecA), and staphylococcal cassette chromosome (SCCmec) inserted in the SA chromosomal attB site.
The test includes a Sample Processing Control (SPC) to control for adequate processing of the target bacteria and to monitor the presence of inhibitor(s) in the PCR assay. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.
The sample for testing with the Xpert MRSA/SA Blood Culture test consists of an aliguot taken from a positive blood culture bottle. Using one of the disposable fixed 50 µL volume transfer pipettes provided with the test kit, an aliquot of the positive blood culture is transferred into a single-use tube of Elution Reagent, also provided with the kit. The Elution Reagent is briefly vortexed and the entire content is transferred to the sample chamber of the disposable fluidic cartridge (the Xpert MRSA/SA Blood Culture cartridge), after which the cartridge is ready to place on the instrument.
The assay is performed on the Cepheid GeneXpert Systems, which automate and integrate sample purification, nucleic acid amplification and detection of the target sequences in simple or complex samples using real-time PCR. The systems consist of an instrument, personal computer, and preloaded software for running the tests and viewing the results. The GeneXpert Instrument Systems require the use of single-use disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, cross-contamination between samples is minimized. In this platform, additional sample preparation, amplification, and real-time detection are all fullyautomated and completely integrated. The Xpert MRSA/SA Blood Culture test performed on the GeneXpert Instrument Systems provides results in approximately 60 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 preparation and realtime 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 detection.
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
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
The re-analyses of the original clinical performance data and a subset of the original analytical performance data, including LoD, inclusivity, exclusivity, potential interfering substances, reproducibility, and precision, showed the devices were substantially equivalent.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
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
§ 866.1640 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).
0
Image /page/0/Picture/0 description: The image contains the logos of the Department of Health and Human Services and the Food and Drug Administration (FDA). The Department of Health and Human Services logo is on the left, and the FDA logo is on the right. The FDA logo is a blue square with the letters "FDA" in white, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue.
April 25, 2019
Cepheid Sudhakar Marla Senior Director, Regulatory Affairs 904 Caribbean Drive Sunnyvale, California 94089
Re: K190771
Trade/Device Name: Xpert MRSA/SA Blood Culture, GeneXpert Dx System, GeneXpert Infinity-48s System, GeneXpert Infinity-80 System Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial Susceptibility Test Powder Regulatory Class: Class II Product Code: NOX, OOI Dated: March 25, 2019 Received: March 26, 2019
Dear Sudhakar Marla:
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 mav, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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
1
requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
Steven R. Gitterman -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
2
Indications for Use
510(k) Number (if known)
Device Name
Xpert MRSA/SA Blood Culture
Indications for Use (Describe)
The Cepheid® Xpert® MRSA/SA Blood Culture test, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test intended for the detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococus aureus (MRSA) DNA directly from positive blood cultures. The assay utilizes automated real-time polymerase chain reaction (PCR) for the amplification of MRSA/SA specific DNA targets and fluorogenic target-specific hybridization probes for the real-time detection of the amplified DNA. The assay is performed directly on positive blood culture samples from BD BACTEC™ Plus Aerobic/F, BacT/ALERT® SA (Standard Aerobic) or VersaTREK REDOX 1® (aerobic) blood culture bottles that are determined by Gram Stain as Gram Positive Cocci in Clusters (GPCC) or as Gram Positive Cocci in singles (GPC). The Xpert MRSA/SA Blood Culture test is indicated for use in conjunction with other laboratory tests, such as culture, and clinical data available to the clinician as an aid in the detection of MRSA/SA from positive blood culturing of positive blood cultures is necessary to recover organisms for susceptibility testing or for epidemiological typing. The Cepheid Xpert MRSA/SA Blood Culture test is not intended to monitor treatment for MRSA/SA infections.
| Type of Use (Select one or both, as applicable) |
|---|
| ------------------------------------------------- |
| Prescription Use (Part 21 CFR 801 Subpart D) |
|---|
| Over-The-Counter Use (21 CFR 801 Subpart C) |
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3
510(k) Summary
As required by 21 CFR Section 807.92(c). The purpose of this submission is to submit documentation to support a change to the assay definition file (ADF) for use with the Xpert MRSA/SA Blood Culture test.
| Submitted by: | Cepheid
904 Caribbean Drive
Sunnyvale, CA 90489
Phone number: (847) 228-3299
Fax number: (847) 890-6589 |
|----------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------|
| Contact: | Sudhakar Marla, Ph.D. |
| Date of Preparation: | April 25, 2019 |
| Proprietary/Trade name: | Xpert® MRSA/SA Blood Culture |
| Common name: | Xpert MRSA/SA Blood Culture |
| Type of Test: | Nucleic Acid Amplification Test, DNA, Methicillin-resistant
Staphylococcus aureus (MRSA) and Staphylococcus aureus
(SA), qualitative |
| Regulation number: | 21 CFR 866.1640 |
| Classification name: | Antimicrobial susceptibility test powder |
| Primary Product code: | NQX; Class II |
| Secondary Product code: | OOI; Class II |
| Classification Advisory
Panel | Microbiology (83) |
| Prescription Use | Yes |
| Predicate Device Assay: | Cepheid Xpert MRSA/SA Blood Culture
[510(k) #K130894] |
DEVICE DESCRIPTION
The Cepheid Xpert® MRSA/SA Blood Culture test is a rapid, automated DNA test for the simultaneous qualitative detection of MRSA and SA DNA directly from blood culture bottle samples that are detected as positive for microbial growth and shown to contain Gram Positive Cocci by Gram stain. The primers and probes in the Xpert MRSA/SA Blood Culture test detect nucleic acid sequences of the staphylococcal protein A (spa), the gene for methicillin/oxacillin resistance (mecA), and staphylococcal cassette chromosome (SCCmec) inserted in the SA chromosomal attB site.
4
The test includes a Sample Processing Control (SPC) to control for adequate processing of the target bacteria and to monitor the presence of inhibitor(s) in the PCR assay. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.
The sample for testing with the Xpert MRSA/SA Blood Culture test consists of an aliguot taken from a positive blood culture bottle. Using one of the disposable fixed 50 µL volume transfer pipettes provided with the test kit, an aliquot of the positive blood culture is transferred into a single-use tube of Elution Reagent, also provided with the kit. The Elution Reagent is briefly vortexed and the entire content is transferred to the sample chamber of the disposable fluidic cartridge (the Xpert MRSA/SA Blood Culture cartridge), after which the cartridge is ready to place on the instrument.
The assay is performed on the Cepheid GeneXpert Systems, which automate and integrate sample purification, nucleic acid amplification and detection of the target sequences in simple or complex samples using real-time PCR. The systems consist of an instrument, personal computer, and preloaded software for running the tests and viewing the results. The GeneXpert Instrument Systems require the use of single-use disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, cross-contamination between samples is minimized. In this platform, additional sample preparation, amplification, and real-time detection are all fullyautomated and completely integrated. The Xpert MRSA/SA Blood Culture test performed on the GeneXpert Instrument Systems provides results in approximately 60 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 preparation and realtime 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 detection.
INTENDED USE
The Intended Use is identical to the predicate device with the exception of the device name changed from Xpert® MRSA/SA Blood Culture Assay to Xpert® MRSA/SA Blood Culture.
Device Intended Use
The Cepheid® Xpert® MRSA/SA Blood Culture test, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test intended for the detection of
5
Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) DNA directly from positive blood cultures. The assay utilizes automated real-time polymerase chain reaction (PCR) for the amplification of MRSA/SA specific DNA targets and fluorogenic target-specific hybridization probes for the real-time detection of the amplified DNA. The assay is performed directly on positive blood culture samples using BD BACTECTM Plus Aerobic/F, BacT/ALERT® SA (Standard Aerobic) or VersaTREK REDOX 1® (aerobic) blood culture bottles that are determined as Gram Positive Cocci in Clusters (GPCC) or as Gram Positive Cocci in singles (GPC) by Gram stain. The Xpert MRSA/SA Blood Culture test is indicated for use in conjunction with other laboratory tests, such as culture, and clinical data available to the clinician as an aid in the detection of MRSA/SA from positive blood cultures. Subculturing of positive blood cultures is necessary to recover organisms for susceptibility testing or for epidemiological typing. The Cepheid Xpert MRSA/SA Blood Culture test is not intended to monitor treatment for MRSA/SA infections.
TECHNOLOGICAL CHARACTERISTICS
The Xpert MRSA/SA Blood Culture test has the same intended use as the predicate device and the same technological characteristics as the predicate device.
DEVICE COMPARISON
The purpose of this Special 510(k) submission is to request a modification of the assay definition file (ADF) for use with the Xpert MRSA/SA Blood Culture test. The updated Assay Definition File with rules-based algorithms and release of new GeneXpert software to support this update have been validated by the re-analyses of the original clinical performance data and a subset of the original analytical performance data, including LoD, inclusivity, exclusivity, potential interfering substances, reproducibility, and precision. The re-analyses showed the devices were substantially equivalent.
Table 8-1 shows the similarities and differences between the Xpert MRSA/SA Blood Culture test and predicate assay. The differences between Xpert MRSA/SA Blood Culture test and the predicate device do not raise different questions of safety and effectiveness.
6
| of Xpert MRSA/SA Blood Culture with the Predicate Device | ||
|---|---|---|
| Similarities | ||
| Item | New Device | |
| Xpert MRSA/SA Blood Culture | Predicate | |
| Current Xpert MRSA/SA Blood | ||
| Culture | ||
| 510(k) #K130894 | ||
| Intended Use | The Cepheid® Xpert® MRSA/SA Blood | |
| Culture test, performed on the | ||
| GeneXpert® Instrument Systems, is a | ||
| qualitative in vitro diagnostic test | ||
| intended for the detection of | ||
| Staphylococcus aureus (SA) and | ||
| methicillin-resistant Staphylococcus | ||
| aureus (MRSA) DNA directly from | ||
| positive blood cultures. The assay | ||
| utilizes automated real-time polymerase | ||
| chain reaction (PCR) for the | ||
| amplification of MRSA/SA specific | ||
| DNA targets and fluorogenic target- | ||
| specific hybridization probes for the | ||
| real-time detection of the amplified | ||
| DNA. The assay is performed directly | ||
| on positive blood culture samples using | ||
| BD BACTECTTM Plus Aerobic/F, | ||
| BacT/ALERT® SA (Standard Aerobic) | ||
| or VersaTREK REDOX 1® (aerobic) | ||
| blood culture bottles that are determined | ||
| as Gram Positive Cocci in Clusters | ||
| (GPCC) or as Gram Positive Cocci in | ||
| singles (GPC) by Gram stain. The Xpert | ||
| MRSA/SA Blood Culture test is | ||
| indicated for use in conjunction with | ||
| other laboratory tests, such as culture, | ||
| and clinical data available to the | ||
| clinician as an aid in the detection of | ||
| MRSA/SA from positive blood cultures. | ||
| Subculturing of positive blood cultures | ||
| is necessary to recover organisms for | ||
| susceptibility testing or for | ||
| epidemiological typing. The Cepheid | ||
| Xpert MRSA/SA Blood Culture test is | ||
| not intended to monitor treatment for | ||
| MRSA/SA infections. | Same | |
| Similarities | ||
| New Device | Predicate | |
| Item | Xpert MRSA/SA Blood Culture | Current Xpert MRSA/SA Blood |
| Culture | ||
| 510(k) #K130894 | ||
| Specimen Type | Positive Blood Culture | Same |
| Technological Principles | Fully automated nucleic acid | |
| amplification (DNA); real-time PCR | Same | |
| DNA Target Sequence | Sequence incorporating the insertion site | |
| (attB) of Staphylococcal Cassette | ||
| Chromosome mec (SCC mec ) for | ||
| detection of MRSA. | Same | |
| Test Cartridge | Disposable single-use, multi-chambered | |
| fluidic cartridge. | Same | |
| Sample Preparation | Self-contained and automated after | |
| mixed specimen is added to cartridge. | ||
| All other reagents are contained in the | ||
| cartridge. | Same | |
| Probes | TaqMan® Probes | Same |
| Internal Controls | Sample processing control (SPC) and | |
| probe check control (PCC). | Same | |
| DNA Target Sequence | Sequence specific to | |
| methicillin/oxacillin resistance ( mecA | ||
| gene) | Same | |
| DNA Target Sequence | Sequence specific to Staphylococcus aureus species ( spa gene) | Same |
| Ability to identify | ||
| correctly "Empty | ||
| Cassette Variants" | Yes, sequence specific to | |
| Staphylococcus aureus species ( mecA | ||
| gene) | Same | |
| Time to Results | Approximately 60 minutes to result. | Same |
Table 8-1: Comparison of Similarities and Differences of Xpert MRSA/SA Blood Culture with the Predicate Device
7
8
| Differences | ||
|---|---|---|
| New Device | Predicate | |
| Item | Xpert MRSA/SA Blood Culture | Current Xpert MRSA/SA Blood Culture |
| 510(k) # K130894 | ||
| Instrument System | Cepheid GeneXpert Dx Systems and | |
| GeneXpert Infinity-48s and Infinity-80 | ||
| Systems | Cepheid GeneXpert Dx Systems, | |
| GeneXpert Infinity-48 System, and | ||
| GeneXpert Infinity-48s and Infinity-80 | ||
| Systems | ||
| Minimum software | ||
| requirements | GeneXpert Dx software version 5.3 and | |
| higher, GeneXpert Infinity-48s and | ||
| Infinity-80 Xpertise software version 6.8 | ||
| and higher | GeneXpert Dx software version 4.3 and | |
| higher, GeneXpert Infinity-48 Xpertise | ||
| 4.3 and higher, GeneXpert Infinity-48s | ||
| and Infinity-80 Xpertise software | ||
| version 6.0 and higher | ||
| Assay Definition File | Rules-based algorithms incorporating | |
| delta Ct values between targets within a | ||
| valid Ct range and algorithms based on | ||
| the Ct value for the targets falling within | ||
| a valid Ct range | Algorithms based on the Ct value for | |
| the targets falling within a valid Ct | ||
| range |
Conclusion
The Xpert MRSA/SA Blood Culture test is substantially equivalent to the predicate device.