The Cepheid® Xpert® MRSA/SA Blood Culture Assay, 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 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 Assay 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 Assay is not intended to monitor treatment for MRSA/SA infections.

Device Description

The Cepheid Xpert® MRSA/SA Blood Culture Assay (Xpert MRSA/SA Blood Culture Assay) is a rapid, automated DNA test for the simultaneous qualitative detection of MRSA and SA DNA directly from blood culture bottle specimens 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 Assay 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 specimen for testing with the Xpert MRSA/SA Blood Culture Assay consists of an aliquot 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 "S" chamber of the disposable fluidic cartridge (the Xpert MRSA/SA Blood Culture Assay cartridge), after which the cartridge is ready to place on the instrument.

The assay is performed on the Cepheid GeneXpert Instrument Systems, which automate and integrate sample purification, nucleic acid amplification 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, crosscontamination between samples is minimized. In this platform, additional sample preparation, amplification, and real-time detection are all fully-automated and completely integrated. The Xpert MRSA/SA Blood Culture Assay 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 real-time 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.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the Cepheid Xpert® MRSA/SA Blood Culture Assay:

Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance
Clinical Performance
MRSA Positive % Agreement (PPA)	98.1% (103/105, 95% CI: 93.3-99.8)
MRSA Negative % Agreement (NPA)	99.6% (684/687, 95% CI: 98.7-99.9)
SA Positive % Agreement (PPA)	99.6% (235/236, 95% CI: 97.7-99.9)
SA Negative % Agreement (NPA)	99.5% (553/556, 95% CI: 98.4-99.9)
Limit of Detection (LoD) (95% confidence)
SA	300 CFU/test (in 50 µL aliquot)
MRSA	400 CFU/test (in 50 µL aliquot)
Analytical Specificity (Exclusivity)	100% (no detection of 101 non-SA/MRSA strains)
Inclusivity (Reactivity)	All but 1 out of 250 SA strains correctly identified (1 SA strain with novel mecA not detected as MRSA)
Assay Success Rate	99.6% (792/795)
Reproducibility
MRSA-1 low pos: 100% agreement
MRSA-1 mod pos: 100% agreement
MRSA-2 low pos: 100% agreement
MRSA-2 mod pos: 100% agreement
MSSA low pos: 97.8% agreement
MSSA mod pos: 100% agreement
Negative-1: 100% agreement
Negative-2: 100% agreement

Study Details

Sample size used for the test set and the data provenance:
- Sample Size: A total of 792 specimens were tested for MRSA and SA.
- Data Provenance: The data was collected from a multi-site prospective study at eight US institutions.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not explicitly state the number of experts or their specific qualifications for establishing ground truth within the clinical comparison study.
- The ground truth was established by reference culture results and susceptibility testing, which are standard laboratory practices and would generally involve trained microbiologists or laboratory technicians rather than individual "experts" in the context of interpretation. Susceptibility testing was performed in accordance with CLSI documents M2-A11 and M100-S22, using cefoxitin disc as a surrogate for methicillin/oxacillin resistance, indicating reliance on established guidelines.
Adjudication method for the test set:
- The document does not specify an explicit adjudication method (like 2+1 or 3+1). The ground truth was determined by comparing the device's results to "reference culture results and susceptibility testing (the current standard of care)." This implies a direct comparison to established laboratory methods, rather than an expert consensus process for adjudication of conflicting results between readers.
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 done. This device is a Nucleic Acid Amplification Test (NAAT), which is an automated molecular diagnostic test producing a definitive positive/negative result, not an imaging-based AI system that would assist human readers in interpretation. Therefore, the concept of human readers improving with or without AI assistance is not applicable here.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, a standalone performance study was done. The entire clinical comparison study (792 specimens) directly evaluated the performance of the Xpert MRSA/SA Blood Culture Assay (an automated DNA test) against reference culture methods. The device's output is a definitive positive or negative result for MRSA and SA, generated automatically by the instrument system without human interpretive input for each individual test result.
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- The ground truth used was reference culture results and susceptibility testing. This represents established laboratory diagnostic methods considered the "standard of care" for identifying and characterizing Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus.
The sample size for the training set:
- The document focuses on the validation or test set performance rather than detailing a specific "training set" in the context of machine learning. The device is a NAAT, meaning its "learning" or development process involved analytical studies (inclusivity, LoD, specificity, etc.) and wet-lab experiments during its development, rather than observational data-driven machine learning.
- For analytical inclusivity (reactivity), 250 SA strains (47 MSSA and 203 MRSA) from multiple sources were tested. This could be considered part of the development/training of the assay's target detection capabilities, but it's not a "training set" in the common AI/ML sense.
How the ground truth for the training set was established:
- As noted above, a "training set" in the machine learning sense is not directly applicable. For the analytical studies that inform the assay's design and performance claims:
  - Analytical Inclusivity (Reactivity): Strains were characterized by methods like pulsed-field gel electrophoresis (PFGE) to confirm their USA types and classifications (e.g., USA100, USA300, USA400). The document also mentions a SA strain (LGA251) with a novel mecA gene (SCCmec type XI) which was incorrectly identified, implying that the ground truth for these strains was established through advanced genomic and microbiological characterization.
  - Limit of Detection (LoD): Ground truth was established by precise quantification of bacterial cells (CFU/mL, then CFU/test) using plate counts in triplicate.
  - Analytical Specificity (Exclusivity): Organisms were identified as Gram positive, Gram negative, or yeast, and specifically classified (e.g., methicillin-sensitive, coagulase negative Staphylococcus) based on standard microbiological techniques and sourced from reputable culture collections (ATCC, CCUG, NCTC, NARSA).

Summary

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130894

510(k) Summary 5.0

JUN 2 0 2013

As required by 21 CFR Section 807.92(c).

Submitted by:	Cepheid904 Caribbean DriveSunnyvale, CA 90489Phone number: (408) 400-8460Fax number: (847) 510-0539
Contact:	Kerry J. Flom, Ph.D.
Date of Preparation:	March 29, 2013
Device:
Trade name:	Xpert® MRSA/SA Blood Culture Assay
Common name:	Methicillin-resistant Staphylococcus aureus (MRSA) andStaphylococcus aureus (SA) from positive blood culturebottles assay.
Type of Test:	Nucleic Acid Amplification Test, DNA, Methicillin-resistantStaphylococcus aureus (MRSA) and Staphylococcus aureus(SA), qualitative
Regulation number/	866.1640
Classification name/Product code:	Antimicrobial susceptibility test powderNQX
ClassificationAdvisory Panel	Microbiology (83)
Predicate DevicesName(s):	Xpert MRSA/SA Blood Culture Assay (510(k) #K101879)BD GeneOhm™ StaphSR Assay (510(k) #K071026)

Device Description:

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The purpose of this submission is to submit documentation to support proposed improvements to the current assay and changes to the Intended Use.

Device Intended Use:

The Cepheid® Xpert® MRSA/SA Blood Culture Assay, 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 targetspecific 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 Assay 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 Assay is not intended to monitor treatment for MRSA/SA infections.

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Substantial Equivalence:

The Xpert MRSA/SA Blood Culture Assay is substantially equivalent to the BD GeneOhm™ StaphSR Assay (510(k) #K071026) and to the current Xpert MRSA/SA Blood Culture Assay (510(k) #K101879). All assays detect SA and MRSA from positive blood cultures and determine the presence of the target organisms through real-time PCR amplification and fluorogenic target-specific hybridization detection. A multi-center study was conducted to determine the performance characteristics of the device relative to the reference culture results and susceptibility testing (the current standard of care), and relative to the predicate devices. The test results showed the Xpert MRSA/SA Blood Culture Assay to be substantially equivalent to the current standard of care and the predicate devices.

Table 5.1 shows the similarities and differences between the Xpert MRSA/SA Blood Culture Assay and predicate assays.

Table 5.1
Similarities and Differences Between the Xpert MRSA/SA Blood Culture Assay
and the Predicate Devices

Similarities
Item	New DeviceXpert MRSA/SA Blood Culture Assay	Predicate Devices
		Current Xpert MRSA/SA Blood Culture Assay(510(k) #K101879)	BD GeneOhm™StaphSR Assay(510(k) #K071026)
Intended Use	Rapid detection of MRSA and SA	Same	Same
Indication for Use	Identification of MRSA and SA colonization	Same	Same
Specimen Type	Positive Blood Culture	Same	Same
Technological Principles	Fully-automated nucleic acid amplification (DNA); real-time PCR	Same	Same
DNA Target Sequence	Sequence incorporating the insertion site ( attB ) of Staphylococcal Cassette Chromosome mec (SCC mec ) for detection of MRSA.	Same	Same

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		Similarities
	New Device	Predicate Devices
Item	Xpert MRSA/SABlood Culture Assay	Current XpertMRSA/SA BloodCulture Assay(510(k) #K101879)	BD GeneOhm™StaphSR Assay(510(k) #K071026)
ClinicalComparisonResults:	Xpert MRSA/SA BloodCulture AssayPerformance vs.Reference Culture :MRSA:Positive % Agreement:98.1%Negative % Agreement:99.6%SA:Positive % Agreement:99.6%Negative % Agreement:99.5%	Xpert MRSA/SA BloodCulture AssayPerformance vs.Reference Culture :MRSA:Positive % Agreement:100.0Negative % Agreement:100.0SA:Positive % Agreement:100.0Negative % Agreement:99.4	BD GeneOhm™StaphSR AssayPerformance vs.Reference Culturemethods :MRSA:Positive %Agreement: 100.0Negative %Agreement: 98.2 -100.0SA:Positive %Agreement: 98.8 -100.0Negative %Agreement: 96.5 -100.0[Data obtained fromthe BD GeneOhmStaphSR Assay510(k) Summary]

September 19. 1.

1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 - 1999 -

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

		Differences
Item	New DeviceXpert MRSA/SA Blood Culture Assay	Predicate DevicesCurrent Xpert MRSA/SA Blood Culture Assay(510(k) #K101879)	BD GeneOhm™StaphSR Assay(510(k) #K071026)
Test Cartridge	Same as current Xpert assay.	Disposable single-use, multi-chambered fluidic cartridge.	Disposable single-use PCR tube
InstrumentSystem	Cepheid GeneXpert Dx Systems and GeneXpert Infinity Systems	Cepheid GeneXpert Dx System	Cepheid SmartCycler
		Differences
	New Device	Predicate Devices
Item	Xpert MRSA/SABlood Culture Assay	Current XpertMRSA/SA BloodCulture Assay(510(k) #K101879)	BD GeneOhm™StaphSR Assay(510(k) #K071026)
SamplePreparation	Self-contained andautomated after mixedspecimen is added tocartridge. All otherreagents are containedin the cartridge.	Self-contained andautomated after mixedspecimen and twosingle-dose reagents areadded to cartridge.	Manual
Probes	Same as current Xpertassay.	TaqMan® Probes	Molecular Beacons
InternalControls	Same as current Xpertassay.	Sample processingcontrol (SPC) and probecheck control (PCC).	One internal reagentcontrol and externalpositive and negativecontrols required per run
DNA TargetSequence	Same as current Xpertassay.	Sequence specific tomethicillin/oxacillinresistance (mecA gene)	N/A
Users	Same as current Xpertassay.	Operators with noclinical lab experienceto experienced clinicallaboratorytechnologists.	CLIA High ComplexityLaboratory Users
DNA TargetSequence	Same as current Xpertassay.	Sequence specific toStaphylococcus aureusspecies (spa gene)	Sequence specific toStaphylococcus aureusspecies (nuc gene)
Ability toidentifycorrectly"EmptyCassetteVariants"	Same as current Xpertassay.	Yes, sequence specificto Staphylococcusaureus species (mecAgene)	No
Rapid testresults	Approximately 60minutes to result.	Approximately 50minutes to result.	Approximately 60-75minutes to result.

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and the comments of the comments of the comments of the contraction of the contribution of the contribution of the contribution of the contribution of the contribution of the

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Non-Clinical Studies:

Analytical Inclusivity (Reactivity)

Two hundred fifty (250) SA strains (47 MSSA and 203 MRSA) from multiple sources were tested using the Xpert MRSA/SA Blood Culture Assay. Selections were made to represent the primary lineages with emphasis placed on the specific clonal complexes within which MRSA is predominantly observed. Lineages that contain MRSA and MSSA, as well as those that contain MSSA exclusively were included. When characterized by pulsed-field gel electrophoresis (PFGE), numerous USA types including USA100, the most common healthcare-acquired strain and USA300 and USA400, the most common communityacquired strains were also included.1 Strains representing "Empty Cassette" variants and heterogeneous strains identified as borderline oxacillin-resistant Staphylococcus aureus or BORSA were also tested.

All strains were tested in triplicate using 10 ul of stationary phase cell suspension diluted 1 million-fold. Colony forming units per assay (CFU/test) were determined by plate counts in triplicate. All results were reported correctly by the Xpert MRSA/SA Blood Culture Assay, except one specimen. The Xpert MRSA/SA Blood Culture Assay incorrectly identified one (1) SA strain (LGA251) as MSSA instead of MRSA. LGA251 contains a novel mecA gene representing a divergent mecA homologue (mecALGA25)) located in a novel staphylococcal chromosome mec element, designated SCCmec type XI. The mecA primers and probes in the MRSA/SA Blood Culture Assay will not detect the novel mecA gene in this strain due to mutations in the primer/probe binding regions. The mecA gene in this strain is only 70% homologous to the mecA gene in other known MRSA strains.

Limit of Detection

Studies were performed to determine the two-sided 95% confidence intervals for the analytical limit of detection (LoD) of SA cells and methicillin-resistant SA (MRSA) cells diluted into a blood culture matrix that can be detected by the Xpert MRSA/SA Blood Culture Assay. The matrix consisted of SA-free whole blood and MSSE (methicillinsusceptible Staphylococcus epidermidis) cells at 10° CFU/mL added to blood culture medium. The limit of detection is defined as the lowest number of colony forming units (CFU) per sample that can be reproducibly distinguished from negative samples with 95% confidence or the lowest concentration at which 19 of 20 replicates were positive.

For MRSA. 20 replicates were evaluated at each MRSA concentration tested (CFU/test) for 10 individual isolates representing SCCmec types I, II, III, IVa, IVd, V, VI, VII, and VIII. When characterized by pulsed-field gel electrophoresis (PFGE), USA100, the most common healthcare-acquired strain and USA400, one of the most common communityacquired strains were represented.

Cooper, J E and Feil, E J. 2006. The phylogeny of Staphylococcus aureus - which genes make the best intra-species markers? Microbiology 152:1297 - 1305.

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For SA, 20 replicates were evaluated at each SA concentration (CFU/test) for 3 individual SA isolates. USA types USA900 and USA1200 were represented.

Point estimates and confidence intervals were determined by probit regression using data (i.e., the number of positive results per number of replicates at each level) spanning a range of CFU/test loadings. The confidence intervals were determined using maximum likelihood estimates on the probit model parameters using the large sample variancecovariance matrix. The LoD point estimates and 95% upper and lower confidence intervals for each SA and each MRSA SCCmec type tested are summarized in Tables 5.2 and 5.3.

SA StrainID	PFGE ID	ConfirmedLoD(CFU/test)[at least 19/20positive]	LoD Estimate (Probit RegressionAnalysis) (CFU/test)
			Lower95% CI	LoD Estimate	Upper95% CI
102-04a	USA 1200	100 (19/20)	60.4	74.5	101.6
29213b	unknown	150 (19/20)	120.1	138.2	172.7
N7129a	USA900	300 (19/20)	224.2	255.2	314.8

Table 5.2: LoD and 95% Confidence Intervals - SA

Strain Source:

· American Type Culture Collection (ATCC), Manassas, VA., USA

Centers for Disease Control and Prevention (CDC), Atlanta, GA., USA

MRSA Strain ID	PFGE ID	Confirmed LoD(CFU/test)[at least 19/20positive]	Lower 95%CI	LoD Estimate	Upper95% CI
Type I (64/4176)a	USA500	350 (19/20)	332.3	366.8	433.5
Type II (N315)b	USA100e	175 (19/20)	113.7	137.0	178.1
Type III (11373)b	unknown	225 (19/20)	191.9	222.6	273.9
Type IVa (MW2)b	USA400e	350 (19/20)	313.1	356.1	427.0
Type V (ST59)c	USA1000e	250 (19/20)	218.2	243.1	282.3
Type VI (HDE288)d,f	USA800e	250 (19/20)	222.2	246.0	385.0
Type VII (JCSC6082)a	unknown	300 (19/20)	264.1	288.0	347.1
Type VIII (WA MRSA-16)c	unknown	400 (19/20)	348.7	386.7	499.1
Type II (BK2464)b	USA100g	125 (19/20)	94.3	116.1	162.0
Type IVd (BK2529)b,f	USA500g	200 (19/20)	120.8	148.8	202.5

Table 5.3. LoD and 95% Confidence Intervals - MRSA

Strain Source:

"Teruyo Ito, Department of Bacteriology, School of Medicine Juntendo University, Tokyo, Japan

Barry Kreiswirth, Director Public Health Research Institute (PHRI), Newark, NJ., USA

"Geoffrey Coombs, Department of Microbiology and Infectious Diseases, Royal Perth Hospital, Perth WA

1 Herminia de Lancaste, Laboratory of Molecular Genetics, Instituto de Tecnologia (ITQB), Universidade Nova de Lisboa, Oeiras, Portugal

6K, Bonnstetter, et al., J Clin Micro 2007, p. 141-146; L. McDougal, et al., J Clin Micro 2003, p. 51 13-5120

THeterogeneous oxacillin-resistant isolates

8Barry Kreiswirth, personal communication

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The results of this study indicate that the Xpert MRSA/SA Blood Culture Assay will produce a positive SA result 95% of the time in a positive blood culture aliquot (50 µL) containing 300 CFU and a positive MRSA result 95% of the time for a positive blood culture aliquot (50 µL) containing 400 CFU.

Linearity

Not applicable, the Xpert MRSA/SA Blood Culture Assay is a qualitative assay.

Analytical Specificity (Exclusivity)

One hundred and one (101) strains were collected, quantitated, and tested using the Xpert MRSA/SA Blood Culture Assay. Of the 101 strains tested, 91 cultures were obtained from the American Type Culture Collection (ATCC), 1 was obtained from Culture Collection, University of Göteborg, Sweden (CCUG), 1 was obtained from Teruyo Ito. Juntendo University, Tokyo, Japan, 1 carbapenemase (KPC) producing Klebsiella pneumoniae strain was obtained from National Collection of Type Cultures (NCTC), UK and 7 strains were obtained from the Network on Antimicrobial Resistance in SA (NARSA). These strains represent species phylogenetically related to SA or those potentially encountered in the hospital environment.

The organisms tested were identified as either Gram positive (74), Gram negative (24), or yeast (3). Methicillin-sensitive, coagulase negative Staphylococcus, MSCoNS (27) and methicillin- resistant, coagulase negative Staphylococcus, MRCoNS (12) were included. The organisms were further classified as either aerobic (94) or anaerobic (7).

Three replicates of each isolate were tested at 1.7 - 3.2 McFarland units. Under the conditions of the study, all isolates were reported MRSA NEGATIVE; SA NEGATIVE; none of the isolates were detected by the Xpert MRSA/SA Blood Culture Assay. The analytical specificity was 100%.

Potentially Interfering Substances

Substances that may be present in blood cultures with potential to interfere with the Xpert MRSA/SA Blood Culture Assay were tested in the interfering substance study. Potentially interfering substances include, but are not limited to, anticoagulated whole blood with ACD, EDTA, Heparin, and Sodium Citrate, human plasma, three blood culture media bottles (Becton Dickinson BACTEC™ Plus Aerobic/F, BioMérieux BacT/ALERT SA (Standard Aerobic), and TREK Diagnostics VersaTREK REDOXI (Aerobic), bilirubin, y-globulin, hemoglobin, triglycerides, and sodium polyanetholesulfonate (SPS). Bilirubin, y-globulin, hemoglobin, and triglycerides were tested at concentrations approximately one log higher than reference levels. SPS was tested at a 10 fold higher concentration than found in blood culture media. Negative samples (n=8) were tested in each substance to determine the effect on the performance of the sample processing control (SPC). Positive samples (n=8) were tested per substance with two clinical isolates each of MSSA (29213 and 102-04) and MRSA (SCCmec types II and HII) spiked near the analytical LoD determined for each isolate. All results were compared to positive and negative buffer controls. All negative specimens were correctly reported "MRSA NEGATIVE; SA NEGATIVE" using the Xpert MRSA/SA Blood Culture Assay. None of the

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potentially interfering substances had a statistically significant inhibitory effect on SPC performance in negative samples (p-value =>0.05). All of the positive MSSA specimens were correctly reported "MRSA NEGATIVE; SA POSITIVE" using the Xpert MRSA/SA Blood Culture Assay. All of the positive MRSA specimens were correctly reported "MRSA POSITIVE: SA POSITIVE" using the Xpert MRSA/SA Blood Culture Assay. None of the potentially interfering substances resulted in a Ct difference of ≥1 cycle relative to the buffer controls and no false-negative results were reported.

Clinical Studies

Clinical Comparison Study

· Performance characteristics of the Xpert MRSA/SA Blood Culture Assay were determined in a multi-site prospective study at eight US institutions by comparing the Xpert MRSA/SA Blood Culture Assay with culture.

Subjects included individuals whose routine care called for blood culture testing. If the blood culture sample was positive for microbial growth and the Gram stain showed Gram positive cocci (singles or in clusters), the sample was eligible for inclusion in the clinical study, and aliquots of leftover culture material were obtained for testing by the Xpert MRSA/SA Blood Culture Assay. Culture and Gram stain procedures, and patient management continued at the sites per the standard practice. Susceptibility testing was performed in accordance with the CLSI documents M2-A11 and M100-S22. Cefoxitin disc was used as a surrogate for detecting methicillin/oxacillin resistance.

Performance of the Xpert MRSA/SA Blood Culture Assay was calculated relative to the reference culture results.

Overall Results

A total of 792 specimens were tested for MRSA and SA by Xpert MRSA/SA Blood Culture Assay and culture.

The Xpert MRSA/SA Blood Culture Assay identified 98.1% of the specimens positive for MRSA and 99.6% of the specimens negative for MRSA relative to culture.

The Xpert MRSA/SA Blood Culture Assay identified 99.6% of the specimens positive for SA and 99.5% of the specimens negative for SA relative to the reference culture method. The performance of the Xpert MRSA/SA Blood Culture Assay is summarized in Table 5.4.

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		Culture
		MRSA+	SA+/MRSA-	Neg/NoGrowth	Total
Xpert	MRSA+	103	2	1	106
	SA+/MRSA-	2	128	2	132
	SA-	0	1	553	554
	Total	105	131	556	792
Xpert Performance	MRSA:PPA: 98.1% (103/105, 95% CI: 93.3-99.8)
	NPA: 99.6% (684/687, 95% CI: 98.7-99.9 )
	SA:
	PPA: 99.6% (235/236, 95% CI: 97.7-99.9 )NPA: 99.5% (553/556, 95% CI: 98.4-99.9)

Table 5.4. MRSA/SA Performance vs. Reference Culture

Of the Xpert MRSA/SA Blood Culture Assay runs on eligible specimens, 96.1% (764/795) were successful on the first attempt. The remaining 31runs gave indeterminate results on the first attempt (1 "INVALID", 22 "ERROR" and 8 "NO RESULT"). Thirty of the 31 indeterminate cases were retested; one specimen was not retested. Twenty-eight of the 30 indeterminate cases that were retested yielded valid results upon repeat assay. The overall rate of assay success was 99.6% (792/795).

Reproducibility Study

Reproducibility of the Xpert MRSA/SA Assay was evaluated at three sites using samples comprised of cultured material spiked into a simulated matrix. The samples were prepared at concentration levels representing high negative (below LoD), low positive (~1 X LoD) and moderate positive (~2-3X LoD) for both MRSA and MSSA. Two different strains of MRSA were used. Negative panel members were also included and were comprised of Staphylococcus epidermidis spiked into a simulated matrix. A panel of 11 samples was tested on five different days by two different operators three times per day at three sites (11 samples x 2 operators x 5 days x 3 replicates per day x 3 sites). One lot of Xpert MRSA/SA reagents was included in the study. Xpert MRSA/SA Assays were performed according to the Xpert MRSA/SA Assay procedure. The rate of agreement for each panel member is presented in Table 5.5.

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Sample	Site 1/GX Dx	Site 2/Inf-80	Site 3/Inf-48	% Total Agreement
MRSA-1 high neg (below LOD)	56.7%(17/30)	60.0%(18/30)	66.7%(20/30)	61.1%(55/90)
MRSA-1 low pos (~1X LOD)	100.0%(30/30)	100.0%(30/30)	100.0%(30/30)	100.0%(90/90)
MRSA-1 mod pos (~2-3X LOD)	100.0%(30/30)	100.0%(30/30)	100.0%(29/29)	100.0%(89/89)a
MRSA-2 high neg (below LOD)	43.3%(13/30)	53.3%(16/30)	70.0%(21/30)	55.6%(50/90)
MRSA-2 low pos (~1X LOD)	100.0%(30/30)	100.0%(30/30)	100.0%(30/30)	100.0%(90/90)
MRSA-2 mod pos (~2-3X LOD)	100.0%(30/30)	100.0%(30/30)	100.0%(30/30)	100.0%(90/90)
MSSA high neg (below LOD)	60.0%(18/30)	48.3%(14/29)	70.0%(21/30)	59.6%(53/89)b
MSSA low pos (~1X LOD)	96.7%(29/30)	100.0%(30/30)	96.7%(29/30)	97.8%(88/90)
MSSA mod pos (~2-3X LOD)	100.0%(30/30)	100.0%(30/30)	100.0%(30/30)	100.0%(90/90)
Negative-1	100%(30/30)	100%(30/30)	100%(30/30)	100%(90/90)
Negative-2	100%(30/30)	100%(30/30)	100%(30/30)	100%(90/90)

Table 5.5. Summary of Reproducibility Results - Agreement by Study Site/Instrument

"One sample indeterminate after initial and retest.

One sample mistakenly not run.

The reproducibility of the Xpert MRSA/SA Assay was also evaluated in terms of the fluorescence signal expressed in cycle threshold (Ct) values for each target detected. The mean, standard deviation (SD), and coefficient of variation (CV) between-sites, betweenlots, between-days, and between-runs for each panel member are presented in Table 5.6.

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Table 5.6. Summary of Reproducibility Data
Target	Sample	Conc	Agree/N	Agrmt(%)	MeanCt	Between-Instrument		Between-Day		Between-Run1	Within-Run		Total
						SD	CV(%)	SD	CV(%)	SD	CV(%)	SD	CV(%)	SD	CV(%)
spa	MRSA-1	high neg	55/90	61.1	35.6	0.18	0.5	0.21	0.6	0.00	0.0	0.95	2.7	0.99	2.8
	MRSA-1	low pos	90/90	100.0	32.8	0.27	0.8	0.00	0.0	0.00	0.0	0.62	1.9	0.67	2.1
	MRSA-1	mod pos	89/89	100.0	31.2	0.11	0.4	0.00	0.0	0.00	0.0	0.58	1.9	0.59	1.9
	MRSA-2	high neg	50/90	55.6	35.3	0.15	0.4	0.00	0.0	0.00	0.0	0.99	2.8	1.00	2.8
	MRSA-2	low pos	90/90	100.0	32.3	0.11	0.4	0.00	0.0	0.13	0.4	0.63	1.9	0.65	2.0
	MRSA-2	mod pos	90/90	100.0	30.7	0.00	0.0	0.00	0.0	0.00	0.0	0.55	1.8	0.55	1.8
	MSSA	high neg	53/89	59.6	36.3	0.00	0.0	0.00	0.0	0.00	0.0	1.26	3.5	1.26	3.5
	MSSA	low pos	88/90	97.8	33.5	0.07	0.2	0.18	0.5	0.00	0.0	0.89	2.7	0.91	2.7
	MSSA	mod pos	90/90	100.0	31.7	0.08	0.2	0.20	0.6	0.17	0.6	0.48	1.5	0.56	1.8
	NEG-1	Neg	90/90	100.0	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	NEG-2	Neg	90/90	100.0	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
mec	MRSA-1	high neg	55/90	61.1	35.8	0.00	0.0	0.36	1.0	0.00	0.0	0.83	2.3	0.91	2.5
	MRSA-1	low pos	90/90	100.0	33.4	0.12	0.4	0.19	0.6	0.00	0.0	0.55	1.6	0.59	1.8
	MRSA-1	mod pos	89/89	100.0	31.9	0.08	0.2	0.00	0.0	0.00	0.0	0.46	1.4	0.47	1.5
	MRSA-2	high neg	50/90	55.6	35.8	0.00	0.0	0.34	0.9	0.00	0.0	1.03	2.9	1.08	3.0
	MRSA-2	low pos	90/90	100.0	32.8	0.11	0.3	0.00	0.0	0.16	0.5	0.51	1.6	0.54	1.7
	MRSA-2	mod pos	90/90	100.0	31.5	0.00	0.0	0.16	0.5	0.00	0.0	0.49	1.5	0.51	1.6
	MSSA	high neg	53/89	59.6	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	MSSA	low pos	88/90	97.8	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	MSSA	mod pos	90/90	100.0	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	NEG-1	Neg	90/90	100.0	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	NEG-2	Neg	90/90	100.0	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
SCC	MRSA-1	high neg	55/90	61.1	37.2	0.20	0.5	0.37	1.0	0.35	1.0	0.82	2.2	0.98	2.6
	MRSA-1	low pos	90/90	100.0	34.5	0.19	0.5	0.23	0.7	0.00	0.0	0.59	1.7	0.66	1.9
	MRSA-1	mod pos	89/89	100.0	33.0	0.16	0.5	0.00	0.0	0.00	0.0	0.45	1.4	0.48	1.5
	MRSA-2	high neg	50/90	55.6	36.8	0.23	0.6	0.24	0.6	0.10	0.3	1.00	2.7	1.06	2.9
	MRSA-2	low pos	90/90	100.0	33.7	0.11	0.3	0.00	0.0	0.26	0.8	0.57	1.7	0.64	1.9
	MRSA-2	mod pos	90/90	100.0	32.4	0.00	0.0	0.09	0.3	0.00	0.0	0.45	1.4	0.46	1.4
	MSSA	high neg	53/89	59.6	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	MSSA	low pos	88/90	97.8	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	MSSA	mod pos	90/90	100.0	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	NEG-1	Neg	90/90	100.0	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	NEG-2	Neg	90/90	100.0	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
SPC	MRSA-1	high neg	55/90	61.1	32.7	0.00	0.0	0.00	0.0	0.20	0.6	0.65	2.0	0.68	2.1
	MRSA-1	low pos	90/90	100.0	33.0	0.00	0.0	0.16	0.5	0.10	0.3	0.61	1.8	0.63	1.9
	MRSA-1	mod pos	89/89	100.0	33.0	0.27	0.8	0.00	0.0	0.00	0.0	0.83	2.5	0.87	2.6
	MRSA-2	high neg	50/90	55.6	33.1	0.23	0.7	0.00	0.0	0.10	0.3	0.85	2.6	0.89	2.7
	MRSA-2	low pos	90/90	100.0	32.9	0.15	0.5	0.00	0.0	0.00	0.0	0.78	2.4	0.79	2.4
	MRSA-2	mod pos	90/90	100.0	32.8	0.00	0.0	0.23	0.7	0.00	0.0	0.66	2.0	0.70	2.1
	MSSA	high neg	53/89	59.6	32.8	0.18	0.5	0.15	0.5	0.00	0.0	0.74	2.2	0.77	2.4
	MSSA	low pos	88/90	97.8	32.9	0.00	0.0	0.00	0.0	0.00	0.0	0.72	2.2	0.72	2.2
	MSSA	mod pos	90/90	100.0	33.0	0.00	0.0	0.31	0.9	0.00	0.0	0.69	2.1	0.76	2.3
	NEG-1	Neg	90/90	100.0	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	NEG-2	Neg	90/90	100.0	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA

Summary of Reproducibility Data Table 56

Agreement, Conc-concentration, CV=coefficient of variation, NA=Not Applicable for negative samples, SD=standard deviation Note: The variance estimate from some ically negative, which can occur if the variability due to those factors is very small. When this occurs, the variability as measured with SD and CV is set to 0.

1 A run is defined as the three samples per panel member run by one operator at one site on one day.

Instrument System Precision Study

An in-house precision study was conducted to compare the performance of the GeneXpert Dx, the Infinity-48 and the Infinity-80 Instrument Systems using samples comprised of cultured material spiked into a simulated matrix. The samples were prepared at concentration levels representing high negative (below LoD), low positive (~1X LoD) and moderate positive (~2-3X LoD) for both MRSA and MSSA. Two different strains of MRSA were used. Negative panel members were also included and were comprised of Staphylococcus epidermidis spiked into a

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simulated matrix. A panel of 11 specimens was tested on 12 different days by two different operators four times per day per instrument (11 specimens x 12 days x 4 replicates per day x 3 instruments). One lot of Xpert MRSA/SA reagents was included in the study. Xpert MRSA/SA Assays were performed according to the Xpert MRSA/SA Assay procedure. The rate of agreement for each panel member is presented in Table 5.7.

Sample	GX Dx	Inf-48	Inf-80	% Total Agreement
MRSA-1 high neg (below LOD)	50.0%(48/96)	51.6%(49/95)	35.4%(34/96)	45.6%(131/287)a
MRSA-1 low pos (~1X LOD)	96.9%(93/96)	99.0%(95/96)	99.0%(95/96)	98.3%(283/288)
MRSA-1 mod pos (~2-3X LOD)	100.0%(96/96)	100.0%(96/96)	99.0%(95/96)	99.7%(287/288)
MRSA-2 high neg (below LOD)	80.2%(77/96)	78.1%(75/96)	80.2%(77/96)	79.5%(229/288)
MRSA-2 low pos (~1X LOD)	100.0%(96/96)	100.0%(96/96)	100.0%(96/96)	100.0%(288/288)
MRSA-2 mod pos (~2-3X LOD)	100.0%(96/96)	100.0%(96/96)	99.0%(95/96)	99.7%(287/288)
MSSA high neg (below LOD)	76.0%(73/96)	71.9%(69/96)	81.3%(78/96)	76.4%(220/288)
MSSA low pos (~1X LOD)	96.9%(93/96)	99.0%(95/96)	100.0%(96/96)	98.6%(284/288)
MSSA mod pos (~2-3X LOD)	100.0%(96/96)	100.0%(96/96)	100.0%(96/96)	100.0%(288/288)
Negative-1	100.0%(96/96)	100.0%(96/96)	100.0%(96/96)	100.0%(288/288)
Negative-2	100.0%(96/96)	100.0%(96/96)	100.0%(96/96)	100.0%(288/288)

Table 5.7: Summary of Precision Results - Agreement by Instrument

One sample was indeterminate after initial and retest.

The precision study results were 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-instruments, between-days, and between-runs for each panel member are presented in Table 5.8.

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				Tamle 3.0. Outlimary of I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1
Target	Sample	Сопс	Agree/N	Agrmt(%)	MeanCt	Between-		Between-		Between-		Within-Run		Total
						Instrument		Day		Run'
						SD	CV	SD	CV	SD	CV	SD	CV	SD	CV
							(%)		(%)		(%)		(%)		(%)
spa	MRSA-I	high neg	131/287	45.6	34.4	0.00	0.0	0.00	0.0	0.00	0.0	1.09	3.2	1.09	3.2
	MRSA-I	low pos	283/288	98.3	32.9	0.02	0.1	0.16	0.5	0.00	0.0	0.78	2.4	0.80	2.4
	MRSA-1	mod pos	287/288	99.7	32.0	0.06	0.2	0.10	0.3	0.00	0.0	0.62	1.9	0.63	2.0
	MRSA-2	high neg	229/288	79.5	36.2	0.14	0.4	0.00	0.0	0.00	0.0	1.19	3.3	1.35	3.7
	MRSA-2	low pos	288/288	100.0	32.4	0.03	0.1	0.00	0.0	0.00	0.0	0.57	1.8	0.62	1.9
	MRSA-2	mod pos	287/288	99.7	31,1	0.12	0.4	0.00	0.0	0.00	0.0	0.49	1.6	0.21	1.7
	MSSA	high neg	220/288	76.4	36.4	0.2 1	0.6	0.00	0.0	0.00	0.0	1.36	3.7	। 'ਤੇਖੋ	4.4
	MSSA	low pos	284/288	98.6	33.8	0.09	0.3	0.18	0:5	0.00	0.0	0.87	2.6	0.90	2.7
	MSSA	mod pos	288/288	100.0	32.2	0.08	0.3	0.00	0.0	0.00	0.0	0.70	2.2	0.74	2.3
	NEG-I	Neg	288/288	100.0	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	NEG-2	Neg	288/288	100.0	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	MRSA-I	high neg	131/287	45.6	34.5	0.00	0.0	0.11	0.3	0.00	0.0	0.86	2.5	0.87	2.5
mec	MRSA-I	low pos	283/288	98.3	33.4	0.07	0.2	0.14	0.4	0.00	0.0	0.61	1.8	0.63	1.9
	MRSA-I	mod pos	287/288	99.7	32.5	0.08	0.2	0.00	0.0	0.00	0.0	0.55	1.7	0.56	1.7
	MRSA-2	high neg	229/288	79.5	35.9	0.00	0.0	0.28	0.8	0.00	0.0	1.02	2.8	1 .06	2.9
	MRSA-2	low pos	288/288	100.0	32.8	0.06	0.2	0.00	0.0	0.00	0.0	0.49	ાં .ડ	0.53	1.6
	MRSA-2	mod pos	287/288	99.7	31.5	0.14	0. ર	0.05	0.2	0.00	0.0	0.45	1.4	0.47	રે
	MSSA	high neg	220/288	76.4	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	MSSA	low pos	284/288	98.6	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	MSSA	mod pos	288/288	100.0	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	NEG-I	Neg	288/288	1 00.0	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	NEG-2	Neg	288/288	100.0	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	MRSA-1	high neg	131/287	45.6	36.7	0.18	0.5	0.00	0.0	0.00	0.0	1 .5 l	4.1	1.52	4.1
	MRSA-I	low pos	283/288	98.3	34.7	0.00	0.0	0.20	0.6	0.00	0.0	1.11	3.2	1,13	3.2
SCC	MRSA-1	mod pos	287/288	99.7	33.7	0.12	0.3	0.00	0.0	0.00	0.0	0.78	2.3	0.78	2.3
	MRSA-2	high neg	229/288	79.5	37.3	0.00	0.0	0.32	0.8	0.00	0.0	1.03	2.8	1.17	3.1
	MRSA-2	low pos	288/288	1 00.0	34.2	0.02	0.1	0.00	0.0	0.00	0.0	0.44	1.3	0.50	। .ડ
	MRSA-2	mod pos	287/288	99.7	33.0	0.12	0.4	0.03	0.1	0.00	0.0	0.49	1.5	0.50	1.5
	MSSA	high neg	220/288	76.4	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	MSSA	low pos	284/288	૭૪.6	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	MSSA	mod pos	288/288	100.0	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	NEG-1	Neg	288/288	100.0	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
	NEG-2	Neg	288/288	100.0	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA	NA
SPC	MRSA-1	high neg	131/287	45.6	33.4	0.00	0.0	0.17	0.5	0.00	0.0	0.84	2.5	0.86	2.6
	MRSA-I	low pos	283/288	98.3	33.4	0.10	0.3	0.21	0.6	0.00	0.0	0.77	2.3	0.80	2.4
	MRSA-1	mod pos	287/288	99.7	33.4	0.08	0.2	0.15	0.5	0.00	0.0	0.72	2.2	0.74	2.2
	MRSA-2	high neg	229/288	79.5	33.4	0.00	0.0	0.00	0.0	0.00	0.0	0.82	2.4	0.82	2.4
	MRSA-2	low pos	288/288	100.0	33.4	0.02	0. I	0.00	0.0	0.00	0.0	0.73	2.2	0.77	2.3
	MRSA-2	mod pos	287/288	99.7	33.3	0.00	0.0	0.09	0.3	0.00	0.0	0.74	2.2	0.75	2.2
	MSSA	high neg	220/288	76.4	33.4	0.00	0.0	0.20	0.6	0.00	0.0	0.83	2.5	0.85	2.6
	MSSA	low pos	284/288	98.6	33.5	0.00	0.0	0.00	0.0	0.00	0.0	0.86	2.6	0.87	2.6
	MSSA	mod pos	288/288	100.0	33.1	0.11	0.3	0.00	0.0	0.00	0.0	0.75	2.2	0.77	2.3
	NEG-1	Neg	288/288	100.0	33.4	0.00	0.0	0.13	0.4	0.00	0.0	0.85	2.6	0.87	2.6
	NEG-2	Neg	288/288	100.0	33.5	0.00	0.0	0.02	0.1	0.00	0.0	0.84	2.5	0.84	2.5

Table 58. Summary of Precision Data

Agrow=Agreement, Conc=concentration, CV=coefficient of variation, N/A=Not Applicable for negative samples, SD=standard deviation

Note: The variance estimate from some factors may be numerically negative, which can occur if the variability due to those factors is very small. When this occurs, the variability as measured with SD and CV is set to 0.

I A run is defined as the four samples per panel member run by one operator at one site on one day.

Conclusions

The results of the nonclinical analytical and clinical performance studies summarized above demonstrate that the Xpert MRSA/SA Blood Culture Assay is substantially equivalent to the predicate devices.

{14}------------------------------------------------

Image /page/14/Picture/0 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an emblem of an eagle with three lines representing the bird's body and wings.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G60 Silver Spring, MD 20993-0002

RAINER ZIERMANN, PH.D. VICE PRESIDENT, CLINICAL AFFAIRS CEPHEID 904 CARRIBEAN DRIVE SUNNYVALE CA 94089

June 20, 2013

Re: K130894

Trade/Device Name: Xpert MRSA/SA Blood Culture Assay Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial susceptibility test powder Regulatory Class: II Product Code: NOX Dated: March 29, 2013 Received: April 02, 2013

Dear Dr. Ziermann:

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. .

{15}------------------------------------------------

Page 2-Dr. Ziermann

If you desire specific advice for your device on our labeling regulations (2) CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance 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. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Uwe Scherf - S for

Sally A. Hojvat, M.Sc., Ph.D. Director, Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use ·4.0

Indications for Use Form

510(k) Number (if known): K130894

Device Name: Xpert® MRSA/SA Blood Culture Assay

Indications for Use:

The Cepheid Xpert® MRSA/SA Blood Culture Assay, 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 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 Assay 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 Assay is not intended to monitor treatment for MRSA/SA infections.

Prescription Use X	AND/OR	Over-The-Counter Use
(Part 21 CFR 801 Subpart D)		(21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

{17}------------------------------------------------

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

John Holosen 2013.06 18 13.06 si -04'00'

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k)_k130894

Page 2 of 2

Regulation Number and Section

§ 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).