The Verigene® Enteric Pathogens Nucleic Acid Test (EP) is a multiplexed. qualitative test for simultaneous detection and identification of common pathogenic enteric bacteria and genetic virulence markers from liquid or soft stool preserved in Cary-Blair media, collected from individuals with signs and symptoms of gastrointestinal infection. The test is performed on the automated Nanosphere Verigene System utilizing reverse transcription (RT), polymerase chain reaction (PCR), and array hybridization to detect specific gastrointestinal microbial nucleic acid gene sequences associated with the following pathogenic bacteria:

Campylobacter Group (comprised of C. coli. C. jejuni. and C. lari) .
. Salmonella species
Shigella species (including S. dysenteriae, S. boydii, S. sonnei, and S. flexneri) .
Vibrio Group (comprised of V. cholerae and V. parahaemolyticus) .
. Yersinia enterocolitica

In addition, EP detects the Shiga toxin 1 gene and Shiga toxin 2 gene virulence markers. Shiga toxin producing E. coli (STEC) typically harbor one or both genes that encode for Shiga Toxins l and 2.

EP is indicated as an aid in the diagnosis of specific agents of gastrointestinal illness, in conjunction with other clinical, laboratory, and epidemiological information; however, is not to be used to monitor these infections. EP also aids in the detection and identification of acute gastroenteritis in the context of outbreaks.

Due to the limited number of positive specimens collected for certain organisms during the prospective clinical study, performance characteristics for Yersinia enterocolitica, Vibrio Group and Shigella species were primarily established with contrived specimens.

Concomitant culture is necessary for organism recovery and further typing of bacterial agents.

EP results should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Confirmed positive results do not rule out co-infection with other organisms that are not detected by this test, and may not be the sole or definitive cause of patient illness. Negative EP results in the setting of clinical illness compatible with gastroenteritis may be due to infection by pathogens that are not detected by this test or non-infectious causes such as ulcerative colitis, irritable bowel syndrome, or Crohn's disease.

Device Description

The Verigene Enteric Pathogens Nucleic Acid Test (EP) is a molecular assay which relies on detection of specific nucleic acid targets in a microarray format. For each of the bacterial nucleic acid sequences detected by EP, unique Capture and Mediator oligonucleotides are utilized, with gold nanoparticle probe-based endpoint detection. The Capture oligonucleotides are covalently bound to the microarray substrate and hybridize to a specific portion of the nucleic acid targets. The Mediator oligonucleotides have a region which bind to a different portion of the same nucleic acid targets and also have a sequence which allows binding of a gold nanoparticle probe. Specific silver enhancement of the bound gold nanoparticle probes at the capture sites results in gold-silver aggregates that scatter light with high efficiency and provide accurate detection of target capture.

The EP test is performed on the Verigene System, a "sample-to-result", fully automated, bench-top molecular diagnostics workstation. The System enables automated nucleic acid extraction from unformed stool specimens (liquid or soft) preserved in Cary-Blair media and detection of bacterial-specific target DNA. The Verigene System consists of two components: the Verigene Reader and the Verigene Processor SP.

The Reader is the Verigene System's user interface, which serves as the central control unit for all aspects of test processing, automated imaging, and result generation using a touchscreen control panel and a barcode scanner. The Verigene Processor SP executes the test procedure, automating the steps of (1) Sample Preparation and Target Amplification – cell lysis and magnetic bead-based bacterial DNA isolation and amplification, and (2) Hybridizationdetection and identification of bacterial-specific DNA in a microarray format by using gold nanoparticle probe-based technology. Once the specimen is loaded by the operator, all other fluid transfer steps are performed by an automated pipette that transfers reagents between wells of the trays and finally loads the specimen into the Test Cartridge for hybridization. Single-use disposable test consumables and a self-contained Verigene Test Cartridge are utilized for each sample tested with the EP assay.

To obtain the test results after test processing is complete, the user removes the Test Cartridge from the Processor SP, and inserts the substrate holder into the Reader for analysis. Light scatter from the capture spots is imaged by the Reader and intensities from the microarray spots are used to make a determination regarding the presence (Detected) or absence (Not Detected) of a bacterial nucleic acid sequence/analyte. This determination is made by means of software-based decision algorithm resident in the Reader.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:

Device: Verigene® Enteric Pathogens Nucleic Acid Test (EP)
Purpose: Multiplexed, qualitative test for simultaneous detection and identification of common pathogenic enteric bacteria and genetic virulence markers from liquid or soft stool preserved in Cary-Blair media.

1. Acceptance Criteria and Reported Device Performance

The document describes analytical and clinical performance studies, which serve to establish the device's meeting of performance criteria. The tables provided in the original document directly illustrate the reported performance against implied acceptance metrics (e.g., target agreement percentages).

Table of Acceptance Criteria and Reported Device Performance:

Since specific acceptance criteria values (e.g., "must achieve X% sensitivity") are not explicitly stated as distinct criteria, I will list the performance metrics presented in the document as reported performance, implying they met the internal acceptance thresholds for regulatory submission. The precision and reproducibility results are strong indicators of meeting defined criteria for consistency.

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance
Analytical Sensitivity / Limit of Detection (LoD)	LoD defined as ≥95% positive result rate at a given concentration	LoD for 16 strains ranged from 4.10x10^3 to 3.33x10^5 CFU/mL of stool, confirmed with 20 replicates (further 20 if 100% initial detection).
Analytical Reactivity (Inclusivity)	Expected result for all 111 clinically relevant bacterial strains tested at 3x LoD.	All 111 strains generated the expected result when tested in triplicate at 3x LoD.
Analytical Specificity (Cross-reactivity)	No cross-reactivity with 161 non-target organisms (135 bacterial, 21 viruses, 4 parasites, 1 human cell line), besides defined exceptions.	All organisms yielded "Not Detected", except Campylobacter insulaenigrae (1/9 positive for "Campylobacter" - noted as potential low-level cross-reactivity).
Microbial Interference	No interference in presence of 14 common fecal microorganisms at high concentrations.	No interference observed for 14 microorganisms (including bacteria and parasites) tested at 10^7 CFU/mL (or 9x10^6/7x10^6 cells/mL for parasites).
Exogenous Substances Interference	No inhibitory effect from 22 potentially interfering substances at medically-relevant concentrations.	None of the 22 substances tested showed inhibitory effect.
Carryover / Cross-contamination	No carryover or cross-contamination from high positive to negative samples.	No carryover or cross-contamination observed when alternating high-titer (5x10^5 CFU/mL) positive with negative samples.
Competitive Inhibition	Correct detection of both organisms in co-infection scenarios.	Correct detection of both bacterial target organisms in 30 unique sample combinations, with one exception (low-titer Campylobacter coli sometimes missed in presence of high-titer E. coli/Stx2 in 1/3 replicates, but repeat testing ruled out competitive inhibition).
Precision (Within-lab)	High agreement with expected results for low and moderate positive samples across operators and days.	Agreement with Expected Result for low and moderate positive samples: all 100% (16/16) except Salmonella enterica (Low) at 93.8% (15/16).
Reproducibility (Inter-laboratory)	High agreement with expected results for low and moderate positive samples across 3 sites, operators, and days.	Agreement across 3 sites: varied slightly but generally high. Most moderate samples 100%. Low samples ranged from 83.3% (Y. enterocolitica at Site 3) to 100%. Negative samples were 100% across all sites.
PPA (Positive Percent Agreement)	High agreement between EP test and reference methods for positive specimens.	Varied by pathogen and specimen type (fresh, frozen, selected, simulated). Overall PPA for target organisms ranged from 91.5% to 100%.
NPA (Negative Percent Agreement)	High agreement between EP test and reference methods for negative specimens.	Varied by pathogen and specimen type. Overall NPA for target organisms ranged from 99.0% to 99.9%.

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

Clinical Study (Method Comparison):
- Total Specimens Tested with EP Test: 1975
- Valid/Evaluable Specimens: 1852 (after excluding 98 specimens and 25 indeterminate "No Call" specimens).
- Data Provenance:
  - Country of Origin: United States (7 U.S. institutions involved in prospective investigation study).
  - Retrospective/Prospective: Primarily prospective collection of fresh and frozen Cary-Blair specimens. Additionally, simulated frozen seeded Cary-Blair specimens were used (408 specimens, prepared from deidentified prospectively-collected glycerol stocks from 12 clinical specimen acquisition sites).
Precision Study (Internal): 14-member simulated sample panel tested daily in duplicate by 2 operators for 4 non-consecutive days, yielding 224 total results.
Reproducibility Study (External): 14 unique samples tested daily in triplicate by 2 operators for 5 non-consecutive days at 3 external sites, yielding 1260 total results.

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

The document does not specify the number or qualifications of experts used to establish the ground truth. It states that the EP test results were compared to "reference methods, including bacterial culture and automated phenotype identification for the bacterial targets and broth enrichment followed by EIA and PCR amplification/BDS for Stx1/Stx2 typing." This implies laboratory professionals following established protocols, but no specifics on "experts" or their qualifications for ground truth establishment beyond standard lab procedures.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method for discrepancies in the clinical test set results (e.g., by multiple experts). It simply states the comparison to reference methods. For the analytical studies (LoD, reactivity), "expected results" were confirmed by replicate testing and quantitative definitions.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

There is no indication of a multi-reader multi-case (MRMC) comparative effectiveness study being done, nor any mention of human readers assisting or being assisted by the AI/device. This device is a diagnostic test intended to be performed by laboratory personnel, not an AI for image interpretation or clinical decision support with physician assistance. Therefore, an effect size of human readers improving with AI vs. without AI assistance is not applicable to this type of device.

6. Standalone Performance

The entire clinical performance section (pages 10-11) describes the standalone performance of the Verigene EP test against reference methods. This means the algorithm/device's performance (results from the Verigene System) without human intervention in result interpretation beyond what is normally done in a lab setting (e.g., verifying automated calls as per standard operating procedures).

7. Type of Ground Truth Used

The ground truth for the clinical study was established using reference laboratory methods, specifically:

Bacterial targets: Bacterial culture and automated phenotype identification.
Stx1/Stx2 typing: Broth enrichment followed by EIA and PCR amplification/BDS.

For artificial/simulated specimens, the ground truth was the known composition of the seeded samples.

8. Sample Size for the Training Set

The document describes the analytical and clinical validation of the device. There is no information provided regarding a "training set" or the process of machine learning model development. This is a molecular diagnostic test, likely based on established probes and detection algorithms, not a deep learning AI model that requires a distinct training phase. The "Cutoff Verification" section mentions assessing 3800 data points (1120 expected positive) from LoD testing to verify the assay cutoff, which is more akin to internal algorithm parameter tuning rather than machine learning training.

9. How the Ground Truth for the Training Set Was Established

As noted above, there is no explicit mention of a training set in the context of machine learning model development. If "training" refers to internal development and optimization of the assay's detection parameters and algorithms, the ground truth would have been established through controlled laboratory experiments (e.g., precisely known concentrations of target organisms, pure cultures, etc.) similar to the analytical studies described.

Summary

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Image /page/0/Picture/0 description: The image shows the word "Nanosphere" in bold black font, with a stylized logo to the left. The logo is a circle, partially filled with black and partially filled with diagonal lines. The text is simple and clear, making it easily readable.

510(K) Summary

JUN 2 0 2014

The Summary for this 510(k) submission is submitted in accordance with the requirements of SMDA 1900 and CFR 807.92

510(k) Number:

Verigene® Enteric Pathogens Nucleic Acid Test (EP) K140083:

Summary Preparation Date:

June 18, 2014

Submitted by:

Nanosphere, Inc. 4088 Commercial Avenue Northbrook, IL 60062 Phone: 847-400-9000 Fax: 847-400-9176

Contact:

Noah Lermer, Ph.D. Director, Regulatory Affairs

Proprietary Names:

For the instrument: Verigene® System For the assay: Verigene® Enteric Pathogens Nucleic Acid Test (EP)

Common Names:

For the instrument:

Bench-top molecular diagnostics workstation

For the assay:

Enteric Pathogens Nucleic Acid Test Enteric Pathogens identification and differentiation system Enteric assay Enteric test

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Regulatory Information:

Regulation section:

3990 - Gastrointestinal microorganism multiplex nucleic acid-based assay

Classification:

Class II

Panel:

Microbiology (83)

Product Code(s):

Gastrointestinal Pathogen Panel Multiplex Nucleic Acid-Based Assay System PCH

Gastrointestinal Bacterial Panel Multiplex Nucleic Acid-based Assay System PCI

001 Real Time Nucleic Acid Amplification System

Other codes used by predicate device:

Instrumentation for clinical multiplex test systems NSU

TH Clinical Sample Concentrator

Predicate Devices:

xTAG® Gastrointestinal Pathogen Panel (GPP) (K121894) (Luminex Molecular Diagnostics, Inc.)

Indications for Use:

Campylobacter Group (comprised of C. coli. C. jejuni. and C. lari) .
. Salmonella species
Shigella species (including S. dysenteriae, S. boydii, S. sonnei, and S. flexneri) .
Vibrio Group (comprised of V. cholerae and V. parahaemolyticus) .
. Yersinia enterocolitica

In addition, EP detects the Shiga toxin 1 gene and Shiga toxin 2 gene virulence markers. Shiga toxin producing E. coli (STEC) typically harbor one or both genes that encode for Shiga Toxins l and 2.

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Concomitant culture is necessary for organism recovery and further typing of bacterial agents.

Technological Characteristics:

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Performance Data - Analytical Testing

Analytical Sensitivity / Limit of Detection (LoD)

Analytical sensitivity (LoD) of the EP test was determined for 16 strains of enteric pathogens, representing all seven (7) EP test reportable target analytes. The LoD was defined as the concentration at which the test produces a positive result at least 95% of the time. Serial dilutions of the strains were tested and the putative LoD confirmed with 20 replicates. To ensure the accuracy of the LoD determination, if the initial detection rate was 100%, a further 20 replicates were performed at the next lower concentration until <95% was achieved. The LoDs for the 16 strains tested, and the corresponding LoD ranges for the EP test reportable target, are shown in the table below. Overall, the LoDs range from 4.10x10 to 3.33x10 CFU/mL of stool.

Representative Organism Tested	ATCCSourceNumber	OrganismLoD(CFU/mL)	ReportableTarget	EP Test TargetLoD(CFU/mL Stool)
Campylobacter jejuni subsp jejuni	43429	$3.70x10^4$
Campylobacter coli	43482	$1.11x10^5$	Campylobacter	$3.70x10^4$ - $1.11x10^5$
Campylobacter lari	35222	$3.70x10^4$
Salmonella enterica subsp enterica serovar typhi	9993	$3.33x10^5$	Salmonella	$3.33x10^5$
Salmonella enterica subsp arizonae	13314	$3.33x10^5$
Shigella dysenteriae / Shiga Toxin 1	29026	$3.70x10^4$	Shigella, Stx1
Shigella flexneri	25929	$1.11x10^5$		$3.70x10^4$ - $1.11x10^5$
Shigella sonnei	29030	$3.70x10^4$	Shigella
Shigella boydii	12035	$1.11x10^5$
Vibrio cholerae	39315	$1.11x10^5$
Vibrio parahaemolyticus	49398	$3.70x10^4$	Vibrio	$3.70x10^4$ - $1.11x10^5$
Yersinia enterocolitica	70082223715	$3.33x10^5$$1.11x10^5$	Yersiniaenterocolitica	$1.11x10^5$ - $3.33x10^5$
E. coli - Shiga Toxin I	43890	$4.10x10^3$	Stx1	$4.10x10^3$ - $3.70x10^4$
E. coli - Shiga Toxin 2	BAA-176	$1.11x10^5$	Stx2	$3.70x10^4$ - $1.11x10^5$
E. coli - Shiga Toxin 1 / Shiga Toxin 2	43895	$3.70x10^4$

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Analytical Reactivity (Inclusivity)

Analytical reactivity of the EP test was demonstrated with a comprehensive panel of 111 clinically relevant bacterial strains representing temporal, and phylogenic diversity for each claimed target (see table below). For the Stx2 targets, Shiga toxin producing organisms tested included the vast majority of serotypes isolated in the U.S and those that are outbreak-related. All 111 strains generated the expected result when tested in triplicate at a concentration of three times LoD.

	Total Number of	Species Tested
Reportable Target	Organisms/Strains	Name	Total
	Tested	(No. of Strains)	Number
Campvlobacter	ો રે	C. coli (5). C. jejuni subsp jejuni (4). C. jejunisubsp dovlei (1), C. lari (5)	3
Salmonella	31	S. bongori (1), S. enterica subsp various (5),	2
		S. enterica subsp enterica serovar various (25)
Shigella	20	S. bovdii (5), S. dysenteriae (5) , S. flexneri (5),	4
		S. sonnei (5)
Vibrio	10	I'. cholerae (5), V. parahaemolvticus (5)	2
Yersinia enterocolitica	7	Y, enterocolitica (7)
Shiga toxin 1	19	S. dysenteriae (2)a. E. coli (17)0	2
Shiga toxin 2	16	E. coli (16) "

Two (2) strains contain Stx I

Five (5) strains contain both Stx1 and Stx2

Analytical Specificity (Cross-reactivity)

One-hundred and sixty-one (161) organisms, consisting of 135 bacterial organisms, 21 viruses, four (4) parasites and one (1) human cell line were tested with the EP test to determine analytical specificity (see table below). Eight (8) organisms, including Astrovirus and Sapovirus (2 strains). Campylobacter hominis and all four parasites were tested as genomic DNA/RNA. In addition, to rule out cross-reactivity between the analytes detected by the EP test, six organisms representing all of the EP test detected targets, were tested at elevated concentrations of 5 x 10° CFU/mL. The exclusivity of 15 species of Vibrio not associated with human infection, four (4) non-pathogenic strains of Escherichia coli, Yersinia pestis, and Clostridium botulinum were evaluated by in silico analysis alone.

All of the organisms tested yielded the expected "Not Detected" results, indicating that there was no cross-reactivity with the EP test. with the exception of Campylobacter insulaenigrae which yielded a single positive result (1/9) for "Campylobacter". In silico analysis also indicates a potential for low-level cross-reactivity. While Campylobacter insulaenigrae has been isolated primarily from marine mammals, in rare cases it may cause septicemia and gastroenteritis in humans. 11

[1] J Med Microbiol. 2007 Nov;56(Pt 11):1565-7.

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Organisms Tested for Analytical Specificity
Bacterial Non-Test Panel Members		Bacterial EP Test Panel Members
Genus	Species	Genus	Species
Abiotrophia	defectiva	Campylobacter	concisus
Acinetobacter	baumannii		curvus
	Iwoffli		fetus
Acrobacter	butzleri		gracilis
	cryaerophilus		hominis
	allosaccharophila		hyointestinalis
	bestiarum		insulaenigrae
	caviae		lanienae
	encheleia		mucosalis
	enteropelogenes		rectus
Aeromonas	eucrenophila		showae
	hydrophilia		sputorum
	jandaei		upsaliensis
	salmonicida*	Vibrio	alginolyticus
	veronii		campbellii
Alcaligenes	faecalis		cincinnatiensis
Bacillus	cereus		fluvialis
	caccae		furnissii
Bacteroides	fragilis		harvevi
	merdae		metschnikovii
	stercoris		mimicus
Candida	albicans		tubiashii
Cedecea	davisae		vulnificus (3 strains)
	amalonaticus	Yersinia	aldovae
Citrobacter	freundii		aleksiciae
	sedlakii		bercovieri
	bifermentans		frederiksenii
	bolteae		intermedia
	butyricum		kristensenii
	difficile (2 strains)		mollaretii
	difficile, non-tox		pseudotuberculosis
	haemolyticum		ruckeri
	methylpentosum		rohdei
Clostridium	nexile	Viruses
	novvi	Name	Serovar / Group
	orbiscindens	Adenovirus	Type 1/Group C
	perfringens		Type 2/Group C
	scindens		Type 3/Group B1
	septicum		Type 4/Group E
	sordellii		Type 5/Group C
	spiroforme		Type 14/Group B2
	sporogenes		Type 26/Group D
Colinsella	aerofaciens		Type 31/Group A
Desulfovibrio	piger		Type 37/Group D
Edwardsiella	tarda		Type 40/Group F
Enterobacter	aerogenes		Human 4
Enterobacter	cloacae	Human Cell Line
Enterococcus	faecalis	Astrovirus	-
	faecium	Coxsackievirus B4	-
* Sub-species masoucida and sub-species salmonicida (2 strains)		Cytomegalovirus	-
		Echovirus 11	-
		Enterovirus 68	-
		Norovirus	Genogroup GI
			Genogroup GII
		Rotavirus	Genogroup A
		Sapovirus	-
Fusobacterium	varium	Lactobacillus	acidophilus
Helicobacter	hepaticus		reuteri
	pylori (4 strains)		rhamnosus
Escherichia	coli (3 strains)	Lactococcus	lactis
	coli (EAEC)	Leminorela	grimontii
	coli (EPEC) (2)	Listeria	gravi
	coli (ETEC) (2)		monocytogenes
	fergusonii	Morganella	morganii
	hermannii	Peptostreptococcus	anaerobius
Klebsiella	oxytoca	Plesiomonas	shigelloides
	pneumoniae	Porphyromonas	asaccharoluticus
Lactobacillus	acidophilus	Prevotella	melaniogenica
	reuteri	Proteus	mirabilis
	rhamnosus		vulgaris
Lactococcus	lactis		penneri
Leminorela	grimontii		stuartii
Listeria	gravi	Providencia	alcalifaciens
	monocytogenes		rettgeri
Morganella	morganii	Pseudomonas	aeruginosa
Peptostreptococcus	anaerobius		fluroescenes
Plesiomonas	shigelloides		putida
Porphyromonas	asaccharoluticus	Ruminococcus	aeruginosa
Prevotella	melaniogenica		bromii
Proteus	mirabilis	Serratia	liquefaciens
	vulgaris		marcescens
	penneri	Staphylococcus	aureus
	stuartii		epidermidis
Providencia	alcalifaciens		agalactiae, O90R
	rettgeri	Streptococcus	dysgalactiae
Pseudomonas	aeruginosa		mutans
	fluroescenes	Parasites
	putida	Blastocystis	hominis
Ruminococcus	aeruginosa	Cryptosporidium	parvum
	bromii	Entamoeba	histolytica
Serratia	liquefaciens	Giardia	lamblia
	marcescens	Colon epithelial cells (colorectal adenocarcinoma)
Staphylococcus	aureus
	epidermidis
	agalactiae, O90R
Streptococcus	dysgalactiae
	mutans

・

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Microbial Interference

Two representative bacterial organisms detected by the EP test, Campylobacter jejuni and Escherichia coli (Shiga toxin 1), were evaluated for potential interference in the presence of 14 potentially interferent microorganisms not detected by the EP test, including Bacteroides fragilis, Prevotella oralis, Prevotella melaninogenicus, Bifidobacterium bifidum, Clostridium perfringens, Enterobacter aerogenes, Enterococcus faecalis, Escherichia coli, Klebsiella pneumonia, Lactobacillus, Staphylococcus aureus, Blastocystis hominis, Entamoeba histolytica, and Candida albicans. These 14 microorganisms represent the most prevalent bacteria known to be present in the human colon and therefore are the most likely to be encountered in stool specimens tested with the EP test. These normal flora bacteria were tested at a concentration of 10' CFU/mL with the exception of the parasites Blastocystis hominis and Entamoeba histolytica which were tested at 9x10 cells/mL and 7x10 cells/mL respectively. No interference was observed with the EP test for any of the samples tested.

Interference (Exogenous Substances)

A comprehensive interfering substances study was performed to assess the potential inhibitory effect of endogenous and exogenous substances that can commonly be found in clinical stool specimens. Two organisms representative of the target analytes detected by the EP test, i.e., Campvlobacter jejuni and Escherichia coli (Shiga toxin 1), were individually challenged with 22 potentially interfering substances (shown in the following table) at high, medically-relevant concentrations. None of the 22 substances tested showed any inhibitory effect on the detection of target enteric pathogens using the EP test.

Intralipid	Vaseline Original 100% Pure Petroleum Jelly
Cholesterol	Tums Antacid with Calcium Extra Strength 750
Whole Blood	Gaviscon Extra Strength Liquid Antacid
Mucus (Nasopharyngeal swab sample in UTM)	Mesalazine
Nystatin Suspension	Immodium® AD Anti-Diarrheal
Preparation H® Anti-itch Hydrocortisone 1%	Pepto-Bismol Max Strength
Desitin Maximum Strength Original Paste	Metronidazole Topical Cream (0.75%)
Preparation H® Hemorrhoidal Ointment	Naproxen Sodium
Options Conceptrol®Vaginal Contraceptive Gel	Mucin from bovine submaxillary glands, Type I-S
Wet Ones® Antibacterial Hand Wipes	Barium Sulfate
K-Y®Personal Lubricant Jelly	Amoxicillin (Antibiotic)

Carryover / Cross-contamination

The potential for carryover and cross-contamination of the EP test on the Verigene system was assessed by alternately testing six representative high positive enteric pathogen samples (Yersinia enterocolitica, Shigella dysenteriae / Stx1, Escherichia coli / Stx2, Salmonella enterica enterica, Campylobacter jejuni , and Vibrio cholera) at 5x10° CFU/mL, followed by testing a negative stool sample. The high-titer sample was alternated with the negative sample three times on six unique Verigene SP Processors. No carryover or cross-contamination was observed.

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Competitive Inhibition

Binary combinations of all six of the EP test panel organisms representing all possible dual infections were evaluated, using simulated samples prepared in Negative Stool Matrix (NSM), with one panel organism present at a Low Positive titer (3x LoD) and a second organism present at a High Positive titer (> 106 CFU/mL stool). The performance of the EP test was evaluated with each of the 30 unique sample combinations tested in replicates of three (3). The EP test correctly detected both bacterial target organisms present in the co-infection combinations tested with one exception. For the Low Titer Campylobacter coli and High Titer E. coli/Stx2 sample, the EP test did not detect Campylobacter in one of the three replicates, although Shiga Toxin 2 was correctly identified in all cases. However, repeat testing indicated that this observation was not indicative of competitive inhibition.

Cutoff Verification

Target mean intensity values observed with the EP test were examined for the testing of the sixteen bacterial samples used to establish the Limit of Detection of the assay. In addition, the cut-off data set included the test results of three negative control samples. With replicates of 20 for each sample and ten target spot groups evaluated per test, a total of 3800 data points (1120 expected positive) were assessed to verify the assay cut-off.

Precision

The precision study was conducted in-house by Nanosphere, during which a fourteen-member simulated sample panel was tested daily in duplicate by two (2) operators for four (4) non-consecutive days for a total of sixteen (16) tests per sample. In total, the study yielded 224 test results. The fourteen (14) sample panel comprised six (6) different strains at two (2) different concentrations (12 positive samples) and two (2) negative samples (Negative Stool Matrix and Clostridium difficile). This panel included for each strain, a "Low Positive" sample (defined as approximately 1-2x LoD), which would be expected to produce a positive result approximately 95% of the time, and a "Moderate Positive" sample (defined as approximately 2-5x LoD). which would be expected to yield a positive result approximately 100% of the time. Results are summarized below.

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Sample	EP Test ExpectedCall	Conc.	Agreementw/ ExpectedResult(95 % CI)ª	Sample	EP TestExpected Call	Conc.	Agreementw/ ExpectedResult(95 % CI) ª
Escherichiacoli/Stx2	E. coliStx2	Moderate	100%16/16(79.4%-100%)	Campvlobacter	Campylobacter	Moderate	100%16/16(79.4%-100%)
		Low	100%16/16(79.4%-100%)	jejuni		Low	l 00%16/16(79.4%-100%)
Sulmonellaenterica	Salmonella	Moderate	100%16/16(79.4%-100%)	Vibrioparahaemolyticus	Vibrio	Moderate	100%16/16(79.4%-100%)
		Low	93.8%15/16 p(69.8%-99.8%)			Low	100%16/16(79.4%-100%)
ShigelladysenteriaeStrl	ShigcllaStx I	Moderate	100%I ୧/ I ୧(79.4%-100%)	Negative StoolMatrix	All Targets NotDetected	NA	100%16/16(79.4%-100%)
		Low	100%16/16(79.4%-100%)	Clostridiumdifficile	All Targets NotDetected	NA	100%16/16(79.4%-100%)
Yersiniaenterocolitica	Y. enterocolitica	Moderate	100%16/16(79.4%-100%)
		Low	100%16/16(79.4%-100%)

4 95% Two-sided Exact Binomial Confidence Interval calculation using the exact Clopper-Pearson method.

b One sample called "Salmonella" and "Stx2."

Performance Data - Clinical Testing

Reproducibility

The inter-laboratory reproducibility of the EP test was determined by conducting a reproducibility study at three external sites. Fourteen (14) unique samples were tested daily in triplicate by two (2) operators for five (5) non-consecutive days at three (3) sites for a total of ninety (90) tests per sample. The study tested a total of 1260 samples. The fourteen (14) sample panel was the same panel described previously for the precision study comprising six (6) different strains at two (2) different concentrations (12 positive samples) and two (2) negative samples (Negative Stool Matrix and Clostridium difficile). The results of the Reproducibility Study are provided in the table below.

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Sample	Expected Call	Conc.	Total Agreement with Expected Result (95 % CI)
			Site 1	Site 2	Site 3
Escherichiacoli/Stx2	E. coliStx2	Moderate	30/30100%(88.4-100)	30/30100%(88.4-100)	30/30100%(88.4-100)
		Low	29/3096.7%(82.8-99.9)	30/30100%(88.4-100)	30/30100%(88.4-100)
Salmonellaenterica	Salmonella	Moderate	28/3093.3%(77.9-99.2)	30/30100%(88.4-100)	30/30100%(88.4-100)
		Low	26/3086.7%(69.3-96.2)	30/30100%(88.4-100)	30/30100%(88.4-100)
Shigelladysenteriae/Stx1	ShigellaStx1	Moderate	30/30100%(88.4-100)	28/3093.3%(77.9-99.2)	30/30100%(88.4-100)
		Low	29/3096.7%(82.8-99.9)	29/3096.7%(82.8-99.9)	28/3093.3%(77.9-99.2)
Yersiniaenterocolitica	Y. enterocolitica	Moderate	29/3096.7%(82.8-99.9)	30/30100%(88.4-100)	30/30100%(88.4-100)
		Low	28/3093.3%(77.9-99.2)	27/3090.0%(73.5-97.9)	25/3083.3%(65.3-94.4)
Campylobacterjejuni	Campylobacter	Moderate	30/30100%(88.4-100)	30/30100%(88.4-100)	30/30100%(88.4-100)
		Low	30/30100%(88.4-100)	30/30100%(88.4-100)	30/30100%(88.4-100)
Vibrioparahaemolyticus	Vibrio	Moderate	30/30100%(88.4-100)	30/30100%(88.4-100)	30/30100%(88.4-100)
		Low	30/30100%(88.4-100)	30/30100%(88.4-100)	30/30100%(88.4-100)
Negative StoolMatrix	Negative	NA	30/30100%(88.4-100)	30/30100%(88.4-100)	30/30100%(88.4-100)
Clostridiumdifficile	Negative	NA	30/30100%(88.4-100)	30/30100%(88.4-100)	30/30100%(88.4-100)

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Clinical Study - Method Comparison

The performance characteristics of the EP test were determined in a multi-site prospective investigation study at seven (7) U.S. institutions by comparing the Verigene EP test results to reference methods, including bacterial culture and automated phenotype identification for the bacterial targets and broth enrichment followed by EIA and PCR amplification/BDS for Stx1/Stx2 typing. The study included the testing of prospectively collected fresh and frozen Cary-Blair specimens and simulated frozen seeded Cary-Blair specimens. Deidentified prospectively-collected specimens were enrolled from individuals receiving routine care requiring enteric pathogens testing. Twelve (12) clinical specimen acquisition sites were used to provide glycerol stocks to seed 408 simulated specimens. These specimens were blinded and shipped to the testing sites and tested alongside prospectively collected specimens.

A total of 1975 specimens were tested with the EP test. Ninety-eight (98) specimens were excluded; 95 prospectively collected and selected specimens and three simulated specimens. Of the remaining 1877 valid specimens, 25 specimens had a final "No Call," resulting in 25 indeterminate specimens. Therefore, a total of 1852 evaluable specimens were used to calculate the performance characteristics for the study. The following table provides a summary of demographic information for 1262 of the 1277 prospectively collected specimens in the valid dataset (age was not recorded for 15 specimens).

Age Range	No. of Specimens	Percentage
0-1	61	4.8%
>1-5	47	3.7%
>5-12	84	6.7%
>12-21	139	11.0%
>21-65	609	48.3%
>65	322	25.5%
Total	1262	100%

The table below provides a summary of the clinical performance, stratified by specimen type, of the EP test for the detection of five (5) bacterial targets and Stx2 (n=1852), compared to the above-described reference methods.

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Specimen Type	n	% Agreement (95% CI)		Specimen Type	n	% Agreement (95% CI)
Campylobacter spp.		Positive	Negative	Salmonella spp.		Positive	Negative
Clinical Specimens	ProspectivelyCollected	Fresh	1243	90.5%19/21(69.6-98.8)	98.8%1207/1222(98.0-99.3)	Clinical Specimens	ProspectivelyCollected	Fresh	1243	85.7%18/21(63.7-97.0)	99.4%1215/1222(98.8-99.8)
		Frozen	34	100%2/2(15.8-100)	100%32/32(89.1-100)			Frozen	34	100%1/1(2.5-100)	97.0%32/33(84.2-99.9)
		Selected	166	97.5%39/40(86.8-99.9)	99.2%125/126(95.7-100)			Selected	166	98.2%53/54(90.1-100)	99.1%111/112(95.1-100)
		All	1443	95.2%60/63(86.7-99.0)	98.8%1364/1380(98.1-99.3)			All	1443	94.7%72/76(87.1-98.6)	99.3%1358/1367(98.8-99.7)
	Simulated		409	98.5%67/68(92.1-100)	100%341/341(98.9-100)		Simulated		409	100%67/67(94.6-100)	100%342/342(98.9-100)
	All			1852	97.0%127/131(92.4-99.2)	99.1%1705/1721(98.5-99.5)		All			1852	97.2%139/143(93.0-99.2)	99.5%1700/1709(99.0-99.8)
Shigella spp.					Vibrio spp.
Clinical Specimens	ProspectivelyCollected	Fresh	1243	66.7%2/3(9.4-99.2)	98.7%1224/1240(97.9-99.3)	Clinical Specimens	ProspectivelyCollected	Fresh	1242	100%1/1(2.5-100)	100%1242/1242(99.7-100)
		Frozen	34	-	97.1%33/34(84.7-99.9)			Frozen	34	100%1/1(2.5-100)	100%33/33(89.4-100)
		Selected	166	100%6/6(54.1-100)	99.4%159/160(96.6-100)			Selected	166	100%1/1(2.5-100)	100%165/165(97.8-100)
		All	1443	88.9%8/9(51.8-99.7)	98.7%1416/1434(98.0-99.3)			All	1443	100%3/3(29.2-100)	100%1440/1440(99.7-100)
	Simulated		409	100%50/50(92.9-100)	100%359/359(99.0-100)		Simulated		409	91.1%51/56(80.4-97.0)	99.7%352/353(98.4-100)
	All			1852	98.3%58/59(90.9-100)	99.0%1775/1793(98.4-99.4)		All			1852	91.5%54/59(81.3-97.2)	99.9%1792/1793(99.7-100)
Y. enterocolitica					StxI
Clinical Specimens	ProspectivelyCollected	Fresh	1243	100%6/6(54.1-100)	99.8%1235/1237(99.4-100)	Clinical Specimens	ProspectivelyCollected	Fresh	1243	100%4/4(39.8-100)	99.7%1236/1239(99.2-99.9)
		Frozen	34	-	100%34/34(89.7-100)			Frozen	34	-	100%34/34(89.7-100)
		Selected	166	100%9/9(66.4-100)	100%157/157(97.7-100)			Selected	166	100%9/9(66.4-100)	99.4%156/157(96.5-100)
		All	1443	100%13/13(75.3-100)	99.7%1426/1430(99.3-99.9)			All	1443	100%1/1(2.5-100)	100%1442/1442(99.7-100)
	Simulated		409	100%51/51(93.0-100)	99.4%356/358(98.0-99.9)		Simulated		409	100%59/59(93.9-100)	100%350/350(99.0-100)
	Y. enterocolitica	All			Clinical Specimens	Prospectively Collected		1852	All	100%64/64(94.4-100)	1852	99.7%1782/1788(99.3-99.9)	58/59(90.9-100)	1775/1793(98.4-99.4)	All	1852	100%60/60(94.0-100)	100%1792/1792(99.8-100)
		Fresh	1243	-			100%1243/1243(99.7-100)
		Frozen	34	-			100%34/34(89.7-100)
		Selected	166	100%1/1(2.5-100)			100%165/165(97.8-100)
			All	1443	100%1/1(2.5-100)	100%1442/1442(99.7-100)
			Simulated	409	100%59/59(93.9-100)	100%350/350(99.0-100)
			All	1852	100%60/60(94.0-100)	100%1792/1792(99.8-100)
Stx2		Clinical Specimens	Prospectively Collected		Fresh	1243	100%6/6(54.1-100)
					Frozen	34	-
					Selected	166	100%9/9(66.4-100)
					All	1443	100%15/15(78.2-100)
				Simulated	409	96.7%58/60(88.5-99.6)	99.7%348/349(98.4-100)
				All	1852	97.3%73/75(90.7-99.7)	99.8%1774/1777(99.5-100)
	Stx1	Clinical Specimens	Prospectively Collected		Fresh	1243	100%4/4(39.8-100)
						Frozen	34
					Selected	166	100%9/9(66.4-100)
					All	1443	100%13/13(75.3-100)
				Simulated	409	100%51/51(93.0-100)	99.4%356/358(98.0-99.9)
				All	1852	100%64/64(94.4-100)	99.7%1782/1788(99.3-99.9)

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Substantial Equivalence

The Verigene® Enteric Pathogen Nucleic Acid Test (EP test) has been shown to be substantially equivalent to the xTAG Gastrointestinal Pathogen Panel (GPP). The EP test has similar intended use and indications, technological characteristics, and performance characteristics. The minor differences between the EP test and its predicate devices raise no new issues of safety or effectiveness. Performance data demonstrate that the EP test is as safe and effective as the predicate device. Thus, the EP test is substantially equivalent to the predicate device.

Similarities
Element	New Device:Enteric Pathogens Nucleic Acid Test(EP)K140083	Predicate:xTAG® Gastrointestinal PathogenPanel (GPP)K121894
Intended Use	The Verigene Enteric Pathogens NucleicAcid Test (EP) is a multiplexed,qualitative test for simultaneous detectionand identification of common pathogenicenteric bacteria and genetic virulencemarkers from liquid or soft stoolpreserved in Cary-Blair media, collectedfrom individuals with signs andsymptoms of gastrointestinal infection.The test is performed on the automatedNanosphere Verigene System utilizingreverse transcription (RT), polymerasechain reaction (PCR), and arrayhybridization to detect specificgastrointestinal microbial nucleic acidgene sequences associated with thefollowing pathogenic bacteria:• Campylobacter Group (comprised of C.coli, C. jejuni, and C. lari)• Salmonella species• Shigella species (including S.dysenteriae, S. boydii, S. sonnei, and S.flexneri)• Vibrio Group (comprised of V. choleraeand V. parahaemolyticus)• Yersinia enterocoliticaIn addition, EP detects the Shiga toxin 1gene and Shiga toxin 2 gene virulencemarkers. Shiga toxin producing E. coli(STEC) typically harbor one or bothgenes that encode for Shiga Toxins 1 and2.EP is indicated as an aid in the diagnosisof specific agents of gastrointestinalillness, in conjunction with other clinical,laboratory, and epidemiologicalinformation; however, is not to be used tomonitor these infections. EP also aids in	The xTAG® GastrointestinalPathogen Panel (GPP) is a multiplexednucleic acid test intended for thesimultaneous qualitative detection andidentification of multiple viral,parasitic, and bacterial nucleic acids inhuman stool specimens fromindividuals with signs and symptomsof infectious colitis or gastroenteritis.The following pathogen types,subtypes and toxin genes are identifiedusing the xTAG® GPP:• Campylobacter (C. jejuni, C. coliand C. lari only)• Clostridium difficile (C. difficile)toxin A/B• Cryptosporidium (C. parvum and C.hominis only)• Escherichia coli (E. coli) 0157• Enterotoxigenic Escherichia coli(ETEC) LT/ST• Giardia (G. lamblia only - alsoknown as G. intestinalis and G.duodenalis)• Norovirus GI/GII• Rotavirus A• Salmonella• Shiga-like Toxin producing E. coli(STEC) stx 1/stx 2• Shigella (S. boydii, S. sonnei, S.flexneri and S. dysenteriae)The detection and identification ofspecific gastrointestinal microbialnucleic acid from individualsexhibiting signs and symptoms ofgastrointestinal infection aids in thediagnosis of gastrointestinal infectionwhen used in conjunction with clinicalevaluation, laboratory findings and
	Similarities
	New Device:Enteric Pathogens Nucleic Acid Test(EP)K140083	Predicate:xTAG® Gastrointestinal PathogenPanel (GPP)K121894
Element	the detection and identification of acutegastroenteritis in the context of outbreaks.Due to the limited number of positivespecimens collected for certain organismsduring the prospective clinical study,performance characteristics for Yersiniaenterocolitica, Vibrio Group and Shigellaspecies were primarily established withcontrived specimens.Concomitant culture is necessary fororganism recovery and further typing ofbacterial agents.EP results should not be used as the solebasis for diagnosis, treatment, or otherpatient management decisions.Confirmed positive results do not rule outco-infection with other organisms that arenot detected by this test, and may not bethe sole or definitive cause of patientillness. Negative EP results in the settingof clinical illness compatible withgastroenteritis may be due to infection bypathogens that are not detected by thistest or non-infectious causes such asulcerative colitis, irritable bowelsyndrome, or Crohn's disease.	epidemiological information. Agastrointestinal microorganismmultiplex nucleic acid-based assayalso aids in the detection andidentification of acute gastroenteritisin the context of outbreaks.xTAG® GPP positive results arepresumptive and must be confirmedby FDA cleared tests or otheracceptable reference methods.The results of this test should not beused as the sole basis for diagnosis,treatment, or other patientmanagement decisions. Confirmedpositive results do not rule outcoinfection with other organisms thatare not detected by this test, and maynot be the sole or definitive cause ofpatient illness. Negative xTAGGastrointestinal Pathogen Panelresults in the setting of clinical illnesscompatible with gastroenteritis may bedue to infection by pathogens that arenot detected by this test or non-infectious causes such as ulcerativecolitis, irritable bowel syndrome, orCrohn's disease. xTAG GPP is notintended to monitor or guide treatmentfor C. difficile infections.The xTAG GPP is indicated for usewith the Luminex MAGPIXinstrument.
Specimen Type	Human Stool sample in Cary-Blair Media	Same
DNAAmplification	PCR	Same
Organisms/NATargets Detected	Campylobacter Group(C. coli, C. jejuni, and C. lari)Salmonella speciesShigella species(S. dysenteriae, S. boydii, S. sonnei, and S.flexneri)Vibrio Group (comprised of V. choleraeand V. parahaemolyticus)Yersinia enterocoliticaShiga toxin 1 gene and Shiga toxin 2 genevirulence markers	Same with additional analytes(excluding Vibrio Group and Yersiniaenterocolitica).
Differences
Element	New Device:Enteric Pathogens Nucleic Acid Test(EP)K140083	Predicate:xTAG® Gastrointestinal PathogenPanel (GPP)K121894
Time to Result	~ 2 hours	5 hours
Sample prep	On-board, automated NA extraction andamplification	Off-line NA Extraction andamplification
DetectionMethod	Gold/Silver nanoparticle probe detectionof bacterial-specific DNA oncomplementary oligo- microarray	Specific microbial target or controlbead populations coupled to sequencesfrom Universal Array streptavidin, R-phycoerythrin conjugate
OpticalDetection	Light scatter	Multi-color fluorescence

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・

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Image /page/15/Picture/0 description: The image shows the seal of the Department of Health and Human Services (HHS) of the United States. The seal features the department's name encircling a symbol. The symbol consists of a stylized caduceus, a traditional symbol of medicine, with three parallel lines representing health, services, and people.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

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

NOAH LERMER, Ph.D. DIRECTOR, REGULATORY AFFAIRS NANOSPHERE, INC. 4088 COMMERCIAL AVENUE NORTHBROOK IL 60062

June 20, 2014

Re: K140083

Trade/Device Name: Verigene Enteric Pathogen Nucleic Acid Test Regulation Number: 21 CFR 866.3990 Regulation Name: Gastrointestinal pathogen panel multiplex nucleic acid-based assay system Regulatory Class: II Product Code: PCH, PCI, OOI Dated: May 21, 2014 Received: May 22, 2014

Dear Dr. Lermer:

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 misst 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 (Scctions 531-542 of the Act); 21 CFR 1000-1050.

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Page 2-Dr. Lermer

If you desire specific advice for your device on our labeling regulations (21 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/ReportalProblem/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 ®r

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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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

510(k) Number (if known) K140083

Device Name

Verigene® Enteric Pathogens Nucleic Acid Test (EP)

Indications for Use (Describe)

The Verigene® Enteric Pathogens Nucleic Acid Test (EP) is a multiplexed, qualitative test for simultaneous detection and identification of common pathogenic enteric bacteria and genetic virulence markers from liquid or soft stool preserved in Cary-Blair media, collected from individuals with signs and symptoms of gastrointestinal infection. The test is performed on the automated Nanosphere Verigene System utilizing reverse transcription (RT), polymerase chain reaction (PCR), and аттау hybridization to detect specific gastrointestinal microbial nucleic acid gene sequences associated with the following pathogenic bacteria:

· Campylobacter Group (comprised of C. coli, C. jejuni, and C. lari)
· Salmonella species
· Shigella species (including S. dysenteriae, S. boydii, S. sonnei, and S. flexneri)
· Vibrio Group (comprised of V. cholerae and V. parahaemolyticus)
· Yersinia enterocolitica

In addition, EP detects the Shiga toxin 1 gene and Shiga toxin 2 gene virulence markers. Shiga toxin producing E. coli (STEC) typically harbor one or both genes that encode for Shiga Toxins 1 and 2.

Concomitant culture is necessary for organism recovery and further typing of bacterial agents.

Type of Use (Select one or both, as applicable)

2 Prescription Use (Part 21 CFR 801 Subpart D)

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

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

John Hobson -S 2014.06.19 09:56:26 -04'00'

FORM FDA 3881 (1/14)

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Regulation Number and Section

§ 866.3990 Gastrointestinal microorganism multiplex nucleic acid-based assay.

(a)
Identification. A gastrointestinal microorganism multiplex nucleic acid-based assay is a qualitativein vitro diagnostic device intended to simultaneously detect and identify multiple gastrointestinal microbial nucleic acids extracted from human stool specimens. The device detects specific nucleic acid sequences for organism identification as well as for determining the presence of toxin genes. The detection and identification of a specific gastrointestinal microbial nucleic acid from individuals exhibiting signs and symptoms of gastrointestinal infection aids in the diagnosis of gastrointestinal infection when used in conjunction with clinical evaluation and other laboratory findings. A gastrointestinal microorganism multiplex nucleic acid-based assay also aids in the detection and identification of acute gastroenteritis in the context of outbreaks.(b)
Classification. Class II (special controls). The special controls are set forth in FDA's guideline document entitled: “Class II Special Controls Guideline: Gastrointestinal Microorganism Multiplex Nucleic Acid-Based Assays for Detection and Identification of Microorganisms and Toxin Genes from Human Stool Specimens.” For availability of the guideline document, see § 866.1(e).