The Cepheid Xpert® C. difficile Assay, performed on the Cepheid GeneXpert® Dx System, is a qualitative in vitro diagnostic test for rapid detection of toxin B gene sequences from unformed (liquid or soft) stool specimens collected from patients suspected of having Clostridium difficile infection (CDI). The test utilizes automated real-time polymerase chain reaction (PCR) to detect toxin gene sequences associated with toxin producing C. difficile. The Xpert C. difficile Assay is intended as an aid in the diagnosis of CDI. Concomitant culture is necessary only if further typing or organism recovery is required.

Device Description

The Cepheid Xpert C. difficile Assay is a rapid, automated in vitro diagnostic test for qualitative detection of Clostridium difficile directly from unformed (liquid or soft) stool specimens of patients suspected of having Clostridium difficile infection (CDI). The assay detects the toxin B gene (tcdB), and is performed on the Cepheid GeneXpert Dx System.

The Xpert C. difficile Assay system performs sample preparation and real-time, multiplex polymerase chain reaction (PCR) for detection of target-specific DNA.

The GeneXpert Dx System consists of a GeneXpert® instrument, personal computer, and disposable fluidic cartridges. Each instrument contains 1-16 randomly accessible modules that are each capable of performing separate sample preparation and real-time PCR tests for detection of C. difficile toxin B gene sequences in less than 45 minutes. Each module contains a syringe drive for dispensing fluids, an ultrasonic horn for lysing cells or spores, and I-CORE® thermocycler for performing real-time PCR and detection.

A swab is inserted into the stool specimen and then is placed in a tube containing elution reagent. Following brief vortexing, the eluted material and two single-use reagents (Reagent 1 and Reagent 2) that are provided with the Assay are transferred to different, uniquely-labeled chambers of the disposable fluidic cartridge (the Xpert C. difficile cartridge). The user initiates a test from the system user interface and places the cartridge into the GeneXpert® Dx System instrument platform, which performs hands-off realtime, multiplex polymerase chain reaction (PCR) for detection of DNA. In this platform, additional sample preparation, amplification, and real-time detection are all fullyautomated and completely integrated.

The Xpert C. difficile Assay includes reagents for the detection of toxin B gene (tcdB). In addition, the assay reagents include an internal sample processing control (SPC) to ensure adequate processing of the target bacteria and to monitor the presence of inhibitor(s) in the PCR Assay. The SPC also ensures that the PCR conditions (temperature and time) are appropriate for the amplification reaction and that the PCR reagents are functional. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.

AI/ML Overview

Here's a summary of the acceptance criteria and the study details for the Cepheid Xpert C. difficile Assay, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" with numerical thresholds in a dedicated table format. Instead, it describes the performance observed in various studies. Based on the "Overall Results" and "Performance vs. Reference Culture" sections of the clinical study, the following can be inferred as the key performance metrics evaluated and achieved:

Acceptance Criteria (Implied)	Reported Device Performance (Xpert C. difficile Assay vs. Reference Culture)
High Sensitivity for Toxigenic C. difficile	93.49%
High Specificity for Toxigenic C. difficile	94.02%
High Accuracy for Toxigenic C. difficile	93.95%
Acceptable Positive Predictive Value (PPV) for Toxigenic C. difficile	72.98%
High Negative Predictive Value (NPV) for Toxigenic C. difficile	98.82%
Reproducible Results (Total Agreement)	98.1% (across 3 sites, all samples; for specific low positive samples, it was 90.0% and 96.7%)
Analytical Inclusivity (detection of diverse C. difficile strains)	100% (all 13 tested toxinotypes correctly identified)
Analytical Sensitivity / Limit of Detection (LoD)	Positively detects C. difficile 95% of the time with 95% confidence for a fecal sample containing 460 CFU. Lower LoD observed for specific toxinotypes (e.g., 23 CFU/swab for LUMC-1).
Analytical Specificity (no cross-reactivity)	100% (all 55 non-C. difficile strains/species correctly reported as negative)
No significant interference from common substances	19 tested substances showed no detectable interference

2. Sample Size Used for the Test Set and Data Provenance:

Sample Size for the Clinical Study (Test Set): A total of 2296 specimens were tested.
Data Provenance: The study was a "multisite prospective investigation study at seven US and Canadian institutions." This indicates a prospective design with data collected from multiple locations across the US and Canada.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications:

The document describes the ground truth for the clinical study as "reference culture followed by cell cytotoxicity testing on the isolates." It does not explicitly mention the number of experts or their specific qualifications (e.g., "radiologist with 10 years of experience") involved in performing and interpreting these reference methods. The reference culture and cytotoxin B isolate testing would typically be performed and interpreted by trained laboratory personnel or microbiologists.

4. Adjudication Method for the Test Set:

The document does not describe a formal "adjudication method" involving multiple expert readers for the ground truth. The ground truth was established by the "reference culture method followed by cell cytotoxicity testing on the isolates." This implies a definitive laboratory result rather than a subjective interpretation requiring adjudication among human readers.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and its effect size:

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study compared the device (Xpert C. difficile Assay) directly against a laboratory reference standard (culture and cytotoxicity testing), not against human readers with and without AI assistance.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done:

Yes, the studies described are standalone performance evaluations of the Xpert C. difficile Assay. The device is a "qualitative in vitro diagnostic test for rapid detection of toxin B gene sequences... The test utilizes automated real-time polymerase chain reaction (PCR) to detect toxin gene sequences." The results presented (sensitivity, specificity, LoD, etc.) reflect the performance of the automated algorithm and system without human interpretation as part of the primary diagnostic output. Human involvement is limited to specimen collection, preparation (swab elution, reagent transfer), and initiating the test on the GeneXpert Dx System.

7. The Type of Ground Truth Used:

The primary ground truth used for the clinical comparison study was:

Reference culture method followed by cell cytotoxicity testing on the isolates.

Specifically:

Stool specimens were inoculated onto CCFA-D and CCMB-TAL.
If C. difficile was isolated from CCFA-D and positive by cell cytotoxicity assay, it was classified as "toxigenic C. difficile positive."
If not, further analysis was done on CCFA-E (subcultured from CCMB-TAL).
If CCFA-E was positive for C. difficile and the isolate positive for cell cytotoxicity assay, it was classified as "toxigenic C. difficile positive."
Otherwise, it was reported as "negative."

8. The Sample Size for the Training Set:

The document does not explicitly mention a separate "training set" or its sample size. The focus is on the analytical and clinical validation of the device. Diagnostic PCR assays typically do not have a "training set" in the same way machine learning algorithms do. Instead, they are developed and optimized (which could be considered analogous to training) using various strains and concentrations during the research and development phase. The analytical inclusivity, sensitivity (LoD), and specificity studies describe the validation of the device's ability to detect different strains and concentrations.

9. How the Ground Truth for the Training Set was Established:

As there is no explicitly defined "training set" in the context of this document, there's no description of how its ground truth was established. For the analytical studies, the ground truth was established by:

Known characteristics of bacterial strains: Analytical inclusivity used 13 C. difficile strains of different toxinotypes, with their toxinotype status being the known ground truth.
Known concentrations: Analytical sensitivity (LoD) involved preparing C. difficile at known CFU concentrations in a fecal matrix, with these known concentrations serving as the ground truth.
Confirmed identity of microorganisms: Analytical specificity used 55 strains (including non-toxigenic C. difficile and other Clostridium species) whose identities were confirmed from reputable culture collections or institutions, acting as the ground truth for their presence or absence.

Summary

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Cepheid.

CONFIDENTIAL

K091109

JUL - 9 2009

510(k) Summary

As required by 21 CFR Section 807.92(c).

Submitted by:

Submitted by:	Cepheid904 Caribbean DriveSunnyvale, CA 90489Phone number: (408) 400-8230Fax number: (408) 541-6439
Contact:	Russel K. Enns, Ph.D.
Date of Preparation:	June 21, 2009
Device:
Trade name:	Xpert® C. difficile
Common names:	C. difficile Assay and Clostridrium difficile identificationand differentiation system
Type of Test:	Qualitative Nucleic Acid Amplification Test for C. difficiletoxin B gene sequences from unformed stool specimens.
Classification:	I
Classification name:	Device reagents, Clostridium difficile toxin; microorganismdifferentiation and identification device.
Regulation number:	866.2660
Procode:	LLH
Classification AdvisoryCommittee:	Microbiology
Panel:	83
Predicate Device:	BD GeneOhm™ Cdiff Assay [510(k) # K081920]

Device Description:

The Xpert C. difficile Assay system performs sample preparation and real-time, multiplex polymerase chain reaction (PCR) for detection of target-specific DNA.

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Device Intended Use:

The Cepheid Xpert® C. difficile Assay, performed on the Cepheid GeneXpert® Dx System, is a qualitative in vitro diagnostic test for rapid detection of toxin B gene sequences from unformed (liquid or soft) stool specimens collected from patients suspected of having Clostridium difficile infection (CDI). The test utilizes automated real-time polymerase chain reaction (PCR) to detect toxin gene sequences associated with toxin producing C. difficile. The Xpert C. difficile Assay is intended as an aid in the diagnosis of CDI. Concomitant testing is necessary only if further typing or organism recovery is required.

Substantial Equivalence:

The Xpert C. difficile Assay is substantially equivalent to the BD GeneOhm Cdiff Assay, manufactured by BD Diagnostics. Both Assays qualitatively detect C. difficile toxin B gene (tcdB) in unformed (liquid or soft) stool specimens. Both Assays use real-time PCR amplification and fluorogenic target-specific hybridization detection.

Table 5.1 shows the similarities and differences between the Xpert C. difficile Assay and the BD GeneOhm Cdiff Assay.

510(k) Summary Xpert C. difficile Assay Page 2 of 11

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The Xpert C. difficile is also substantially equivalent to the C. difficile reference culture method followed with strain identification of all C. difficile isolates as shown in a multicenter clinical comparison study.

The multi-center clinical comparison study was conducted on 2296 patients to evaluate the performance of the Xpert C. difficile Assay relative to the reference culture method and cytotoxin B isolate testing.

The test results showed the Xpert C. difficile Assay to be substantially equivalent to the current standard of care, the C. difficile reference culture method.

Item	Device	Predicate
	Xpert C. difficile Assay	BD GeneOhm Cdiff Assay(K081920)
Intended Use	An automated test for thequalitative detection oftoxigenic C. difficile inunformed (liquid or soft)stool specimens.	Same
Indication forUse	Identification of C. difficilefrom patients suspected ofhaving C. difficile Infection(CDI).	Same
TechnologicalPrinciples	Fully-automated nucleic acidamplification (DNA); real-time PCR	Same
Specimen Type	Unformed (liquid or soft)Stool	Same
Test Cartridge	Disposable single-use, multi-chambered fluidic cartridge.	Disposable single-use PCR tube
DNA TargetSequence(s)	C. difficile toxin B	Same
InstrumentSystem	Cepheid GeneXpert DxSystem	Cepheid SmartCycler DxSystem
SampleExtraction	Self-contained and automatedafter swab elution and twosingle-dose reagent additions.	Manual
Probes	TaqMan® Probes	Molecular Beacons

Table 5.1 Similarities and Differences Between the Xpert C. difficile Assay and the BD GeneOhm Cdiff Assay

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	Device	Predicate
Item	Xpert C. difficile Assay	BD GeneOhm C.diff Assay(K081920)
SampleExtraction	Automated	Manual
Rapid test results	Less than 45 minutes toresults.	Approximately 75-90 minutes toresults.
Users	Operators with no clinical labexperience to experiencedclinical laboratorytechnologists.	CLIA High ComplexityLaboratory Users

Non-Clinical Studies:

Analytical Inclusivity

The analytical inclusivity of the Xpert C. difficile Assay was determined using 13 Clostridium difficile strains of different toxinotypes selected to represent the range of genetic diversity found in C. difficile. Toxinotypes.0, I, III, IV, V, VI, VIII, IX, X, XII, XIV, XXI, and XXII were tested. All strains were tested in triplicate 9000 CFU per Assay. All tested toxinotypes were correctly reported as "Toxigenic C. diff POSITIVE".

Analytical Sensitivity (Limit of Detection)

Studies were performed to determine the 95% confidence intervals for the analytical limit of detection (LoD) of C. difficile diluted into a fecal matrix of human origin that can be detected by the Xpert C. difficile Assay. The fecal matrix consisted of human liquid feces (C. difficile negative by Xpert C. difficile Assay) diluted in PBS with 15% glycerol. The LoD is defined as the lowest number of colony forming units (CFU) per swab that can be reproducibly distinguished from negative samples with 95% confidence.

Replicates of 20 were evaluated at each C. difficile concentration tested (CFU/swab) for 7 different C. difficile strains representing toxinotypes 0 (two strains), III (two strains), IV, V and VIII (one of each strain).

The estimate and confidence intervals were determined using logistic regression with data (number of positive results per number of replicates at each level) over the range of CFU loadings. The confidence intervals were determined using maximum likelihood estimates on the logistic model parameters using the large sample variance-covariance matrix. The LoD point estimates and 95% upper and lower confidence intervals for each C. difficile toxinotype tested are summarized in Table 5.2.

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Strain ID	Toxinotype	LoD95%(CFU/swab)	Lower95% CI	Upper95% CI
VPI 10463 (CCUG19126)	0	255	190	632
90556-M6S (ATCC9689)	0	460	419	587
LUMC-1 (027/NAP1/BI)a	III	23	19	31
LUMC-5 (027/NAP1/BI)a	III	75	45	176
LUMC-7	V	45	34	104
LUMC-6	VIII	60	50	74
9101	XII	41	34	49

Table 5.2 - 95% Confidence Intervals for Analytical LoD - C. difficile

By PCR-ribotyping/pulse-field gel electrophoresis/restriction endonuclease analysis

The results of this study indicate that the Xpert C. difficile Assay will produce a positive C. difficile result 95% of the time with 95% confidence for a fecal sample containing 460 CFU.

In addition to the LoD determination, eighteen C. difficile strains representing 12 variant toxinotypes, including four 027/NAP1/BI toxinotype III isolates, were tested using the Xpert C. difficile Assay. C. difficile strains were selected to broadly represent the majority of C. difficile toxinotypes encountered in practice. Stock cultures were prepared by suspending the bacterial growth from agar plates in PBS buffer containing 15% glycerol. The concentration of each stock was adjusted to 1.4-5.9 McFarland units. All strains were serially diluted to approximately 900 CFU/swab and tested in triplicate.

Under the conditions of this study, the Xpert C. difficile Assay correctly identified all 18 toxinotypes tested as "Toxigenic C. diff POSITIVE". Included in the panel were 8 toxinotypes reported to be positive for binary toxin (CDT) production as well. All were CDT positive using the Xpert C. difficile Assay. All four 027/NAP1/BI isolates representing toxinotype III were correctly identified as "Toxigenic C. diff POSITIVE".

Linearitv

A study was conducted to define the reportable range of the Xpert C. difficile Assay and demonstrated a linear relationship.

Analytical Specificity

Fifty-five (55) strains were collected, quantitated and tested using the Xpert C. difficile Assay. The strains originated from the American Type Culture Collection (ATCC), Culture Collection University of Göteborg (CCUG), German Collection of Microorganisms and Cell Cultures (DSMZ), the Centers for Disease Control and Prevention (CDC), the Institute of Public Health, Maribor, Slovenia and Swedish Institute for Infectious Disease Control (SMI).

Of the tested species, ten (10) non-toxigenic C. difficile strains and eleven (11) non C. difficile Clostridium species were included. The organisms tested were identified as

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either Gram positive (37) or Gram negative (18). The organisms were further classified as aerobic (24), anaerobic (29) or microaerophillic (2).

Each strain was tested in triplicate from cultures adjusted to 0.5 - 4.7 McFarland units. Positive and negative controls were included in the study. Under the conditions of the study, all isolates were reported "Toxigenic C. diff NEGATIVE". The analytical specificity was 100%.

Interfering Substances

Twenty-one (21) biological and chemical substances occasionally used or round in stool specimens were tested for interference with the Xpert C. difficile Assay. Potentially interfering substances include, but are not limited to. Vagisil cream and zinc oxide paste. The 19 substances listed in Table 5.3 showed no detectable interference with the Xpert C. difficile Assay.

Substance	Substance
Whole Blood	K-Y Jelly/Gelée®
Karolinska University Hospital	McNeil-PPC
Mucin (porcine)	Vaseline
Sigma	Unilever
Kaopectate®	Dulcolax®
Chattem	Boehringer Ingelheim Pharmaceuticals
Imodium®	Preparation H Portable Wipes
McNeil-PPC	Wyeth Consumer Healthcare
Pepto-Bismol®	Vaginal Contraceptive Film (VCF)
Procter & Gamble	Apothecus Pharmaceutical
Preparation H®	Vancomycin
Wyeth Consumer Healthcare	Fluka
Fleet®	Metronidazole
CB Fleet Company	Actavis
Fecal fats	Anusol® Plus
Karolinska University Hospital	TM Warner-Lambert Company
Monistat®	E-Z-HD™ High Density Barium Sulfatefor suspension
McNeil-PPC	E-Z-EM Canada
Hydrocortisone Cream
Longs Drugs

Table 5.3 - Substances Tested and Showing No Assay Interference

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Clinical Studies

Clinical Comparison Study

Performance characteristics of the Xpert C. difficile Assay were determined in a multisite prospective investigation study at seven US and Canadian institutions by comparing the Xpert C. difficile Assay to reference culture followed by cell cytotoxicity testing on the isolates.

Subjects included individuals whose routine care called for C. difficile testing. A portion of the leftover unformed stool specimens were obtained for testing by the Xpert. C. difficile Assay. The remaining excess specimen was sent to a central laboratory for reference culture and cytotoxin B isolate testing. Each stool specimen was inoculated onto pre-reduced CCFA-D (cycloserine-cefoxitin-fructose agar -direct plate) and Cycloserine cefoxitin mannitol broth with taurocholate lysozyme cysteine (CCMB-TAL). After 24 hours the CCMB-TAL was subcultured on to a second CCFA-E plate (CCFA-Enriched). This direct-enriched culture method is referred to hereafter as "reference culture".

If C. difficile was isolated from the CCFA-D plate and the isolate was positive by cell cyotoxicity assay, the specimen was classified as "toxigenic C. difficile positive" and CCFA-E plate was not further analyzed. If no C. difficile was isolated from the CCFA-D plate or if the isolate was negative by cell cytotoxicity assay, the CCFA-E plate was further analyzed.

If CCFA-E was positive for C. difficile and the isolate was positive for cell cytotoxicity assay, the specimen was classified as "toxigenic C. difficile positive". The specimen was reported as "negative" if CCFA-E is negative for C. difficile or the isolate was tested negative by cell cytotoxicity assay.

Performance of the Xpert C. difficile Assay was calculated relative to the results of direct culture and reference culture.

Overall Results

A total of 2296 specimens were tested by Xpert C. difficile Assay and culture.

Performance vs. Direct Culture

Relative to direct culture with REA strain typing, the Xpert C. difficile Assay demonstrated a sensitivity and specificity for toxigenic C. difficile of 98.79% and 90:82%, respectively (Table 5.4).

510(k) Summary Xpert C. difficile Assay Page 7 of 11

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		Direct Culture
		C. diff	NEG	Total
Xpert C. difficile	Toxin B+	245 (240)	188 (183)	433 (423)
	NEG	3 (3)	1860 (1795)	1863 (1798)
	Total	248 (243)	2048 (1978)	2296 (2221)
Sensitivity: 98.79%Specificity: 90.82%Accuracy: 91.68%PPVa: 56.58%NPVb: 99.83%Prevalence: 10.80%

Table 5.4 - Xpert C. difficile Assay Performance vs. Direct Culture

()Xpert C. difficile results on first attempt

4Positive predictive value

Negative predictive value

Performance vs. Reference Culture

ﺎ ﺗﻌﻠﻴ . ..

Reference (enriched) culture is a more sensitive method for detection of C. difficile in symptomatic patients, for example it allows detection of low number of organism due to prior antibiotic treatment and potential lost of viability due to specimen transport.

Relative to reference culture, the Xpert C. difficile Assay demonstrated a sensitivity and specificity for toxigenic C. difficile of 93.49% and 94.02%, respectively (Table 5.5).

Table 5.5 - Xpert C. difficile Assay Performance vs. Reference Culture
------------------------------------------------------------------------	--	--	--

	Reference Culture
	C. diff	NEG	Total
Xpert C. difficile	Toxin B+	316 (310)	117 (113)	433 (423)
	NEG	22 (22)	1841 (1776)	1863 (1798)
	Total	338 (332)	1958 (1889)	2296 (2221)
		Sensitivity:Specificity:Accuracy:PPVa:NPVb:Prevalence	93.49%94.02%93.95%72.98%98.82%14.72%

()Xpert C. difficile results on first attempt

4Positive predictive value

6Negative predictive value

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Antibiotic Usage

Among the 2296 cases included in the main dataset, antibiotic use within the 2 months prior to sample collection was reported for 1633 and no antibiotic use was confirmed for 570; for 93 cases, antibiotic status was unknown. Antibiotic use did not cause a statistically significant difference in assay performance.

Reproducibility

Reproducibility of the Xpert C. difficile Assay was demonstrated using a panel of 7 specimens with varying concentrations of a toxigenic C. difficile strain, a toxigenic C. difficile 027/NAP1/BI strain and a negative that were tested in duplicate on 10 different days at each of the three sites (7 specimens x 2 times/ day x 10 days x 3 sites). One lot of Xpert C. difficile kit was used at each of the 3 testing sites. Xpert C. difficile Assays were performed according to the Xpert C. difficile procedure.

A panel of 7 specimens with varying concentrations of C. difficile and C. difficile, 027/NAP1/BI were tested on 10 different days by two different operators at each of the three sites (7 specimens x 2 operators/ day x 10 days x 3 sites). One lot of Xpert C., difficile Assay was used at each of the 3 testing sites. Xpert C. difficile Assays were performed according to the Xpert C. difficile Assay procedure. Results are summarized in Table 5.6.

Specimen ID	Site 1	Site 2	Site 3	% Total Agreement by Sample
Negative	100%(20/20)	100%(20/20)	100%(20/20)	100%(60/60)
Toxigenic C. difficile High Negative	100%(20/20)	100%(20/20)	100%(20/20)	100%(60/60)
Toxigenic C. difficile Low Positive	100%(20/20)	85%(17/20)	85%(17/20)	90.0%(54/60)
Toxigenic C. difficile Moderate Positive	100%(20/20)	100%(20/20)	100%(20/20)	100%(60/60)
027/NAP1/BI High Negative	100%(20/20)	100%(20/20)	100%(20/20)	100%(60/60)
027/NAP1/BI Low Positive	100%(20/20)	95%(19/20)	95%(19/20)	96.7%(58/60)
027/NAP1/BI Moderate Positive	100%(20/20)	100%(20/20)	100%(20/20)	100%(60/60)
% Total Agreement by Site	100%(140/140)	97.1%(136/140)	97.1%(136/140)	98.1%(412/420)

Table 5.6 - Summary of Reproducibility Results (all)

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SPC
Level	Ave	StdDev	CV
Toxigenic C. diff high neg	32.17	0.59	1.83%
Toxigenic C. diff low pos	32.14	0.53	1.66%
Toxigenic C. diff mod pos	31.98	0.47	1.47%
027/NAP1/BI high neg	32.11	0.65	2.03%
027/NAP1/BI low pos	31.93	0.72	2.26%
027/NAP1/BI mod pos	31.96	0.61	1.90%
Neg	32.26	0.72	2.22%

Table 5.7 - Summary of Ct Value Results by Sample Level and Probe

tcdB
Level	Ave	StdDev	CV
Toxigenic C. diff high neg	39.59	0.70	1.77%
Toxigenic C. diff low pos	35.88	0.81	2.24%
Toxigenic C. diff mod pos	32.17	0.45	1.39%
027/NAP1/BI high neg	39.11	0.98	2.50%
027/NAP1/BI low pos	35.49	0.58	1.65%
027/NAP1/BI mod pos	32.10	0.63	1.97%

An additional panel of 6 specimens, three negative and three toxigenic C. difficile high negative, were tested on 5 different days by two different operators at each of the three sites (6 specimens x 2 operators/ day x 5 days x 3 sites). The high negative specimens were prepared at a concentration below LoD such that they were expected to give a negative result 20 to 80% of the time. One lot of Xpert C. difficile Assay was used at each of the 3 testing sites. Xpert C. difficile Assays were performed according to the Xpert C. difficile Assay procedure. Results are summarized in Table 5.8.

Specimen ID	Site 1	Site 2	Site 3	% TotalAgreementby Sample
Negative	100%(30/30)	100%(30/30)	100%(30/30)	100%(90/90)
Toxigenic C. difficile HighNegativea	60.0%(18/30)b	60.0%(18/30)b	53.3%(16/30)b	57.8%(52/90)b

Table 5.8 - Summary of Additional Reproducibility Specimen Results
--------------------------------------------------------------------	--

20-80% agreement expected for high negative sample

6(# negative results / total high negative samples run)

510(k) Summary Xpert C. difficile Assay Page 10 of 11

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Conclusions

The results of the nonclinical analytical and clinical performance studies summarized above demonstrate that the Xpert C. difficile Assay is as safe, as effective, and performs as well as or better than the predicate device.

. .

510(k) Summary Xpert C. difficile Assay

. .

: 上一篇:

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Image /page/11/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three stripes representing the department's mission. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993

JUL - 9 2009

Cepheid Russel K. Enns, Ph.D. Senior Vice President 904 Caribbean Drive Sunnyvale, CA 94089-1189

Re: K091109

Trade/Device Name: Xpert® C. difficile Regulation Number: 21 CFR 866.2660 Regulation Name: Microorganism differentiation and detection device Regulatory Class: Class I Product Code: LLH Dated: June 22, 2009 Received: June 23, 2009

Dear Dr. Enns:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 .

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at 240-276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. 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 (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours.

Sally attayma

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

Enclosure

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4.0 Indications for Use Statement

510(k) Number (if known): K091109

Device Name: Xpert® C. difficile

Indications for Use:

Prescription Use X (Part 21 CFR 801 Subpart D)

Over-The-Counter Use AND/OR (21 CFR 801 Subpart C)

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

Division Sign-Off

Office of In Vitro Diagnos Device Evaluation and Safety

NO 4110 510(k)

Regulation Number and Section

§ 866.2660 Microorganism differentiation and identification device.

(a)
Identification. A microorganism differentiation and identification device is a device intended for medical purposes that consists of one or more components, such as differential culture media, biochemical reagents, and paper discs or paper strips impregnated with test reagents, that are usually contained in individual compartments and used to differentiate and identify selected microorganisms. The device aids in the diagnosis of disease.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.