The xTAG® Respiratory Viral Panel Fast (RVP FAST) is a qualitative nucleic acid multiplex test intended for the simultaneous detection and identification of multiple respiratory virus nucleic acids in nasopharyngeal swabs from individuals suspected of respiratory tract infections. The following virus types and subtypes are identified using RVP FAST: Influenza A, Influenza A subtype H1, Influenza A subtype H3, Influenza B, Respiratory Syncytial Virus, Human Metapneumovirus, Rhinovirus, and Adenovirus. The detection and identification of specific viral nucleic acids from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection if used in conjunction with other clinical and epidemiological information.

Negative results do not preclude respiratory viral infection and should not be used as the sole basis for diagnosis, treatment or other management decisions. Positive results do not rule out bacterial infection or co-infection with other organisms. The agent detected may not be the definite cause of disease. The use of additional laboratory testing (e.g. bacterial and viral culture, immunofluorescence, and radiography) and clinical presentation must be taken into consideration in order to obtain the final diagnosis of respiratory infection.

Due to the genetic similarity between human Rhinovirus and Enterovirus, the RVP FAST primers for the detection of rhinovirus cross react with enterovirus. A rhinovirus reactive result should be confirmed by an alternate method (e.g. cell culture).

Performance characteristics for Influenza A Virus were established when Influenza A/H3 and A/H1 were the predominant Influenza A viruses in circulation. When other Influenza A viruses are emerging, performance characteristics may vary. If infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent Influenza viruses and sent to a state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.

Device Description

RVP FAST is a PCR-based system for detecting the presence / absence of viral DNA / RNA in clinical specimens. The oligonucleotide primer / probe components of the RVP FAST have been designed to specifically target unique regions in the RNA / DNA of each molecular species listed in the intended use. Amplified products are then sorted and analyzed on the Luminex 100 or 200 instrument, which generates signals based on the acquisition of spectrofluorometric data. The raw signals are median fluorescence intensities (MFI) which are acquired in a Luminex Output.csv file that is subsequently analyzed by the xTAG Data Analysis Software (TDAS RVP FAST) to establish the presence of all viral types / subtypes for which a Luminex microsphere population has been dedicated.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the xTAG® RVP FAST device, based on the provided document:

Acceptance Criteria and Device Performance

The provided document details the performance characteristics through clinical sensitivity and specificity. While explicit quantitative "acceptance criteria" tables are not presented as separate targets, the FDA's clearance implies these performance metrics were deemed acceptable for the device's intended use. The table below summarizes the reported clinical performance.

Virus (Analyte)	Reported Sensitivity (%)	Lower-Bound 95% CI for Sensitivity (%)	Reported Specificity (%)	Lower-Bound 95% CI for Specificity (%)
Human Influenza A	94.2	88.8	95.5	94.0
H1	96.3	87.3	98.2	97.2
H3	96.1	89.0	97.8	96.8
Human Influenza B	94.3	84.3	98.8	98.0
RSV	90.9	84.3	97.7	96.6
Rhinovirus	95.6	84.9	92.5	90.8
Adenovirus	85.7	57.2	99.3	98.6
Metapneumovirus (hMPV)	97.2	85.5	98.9	98.2
Adenovirus (Supplemented)	97.06 (PPA)	86.47	N/A	N/A

Study Details

Sample Size used for the test set and the data provenance:
- Sample Size: 1191 prospectively collected clinical specimens (nasopharyngeal swabs).
- Data Provenance: Specimens were collected during the 2007/2008 and 2008/2009 flu seasons from enrolled clinical sites. They were a mix of "left-over, fresh and frozen." An additional 34 banked, pre-selected positive clinical specimens for Adenovirus were used to supplement the prospective set. Furthermore, 77 clinical specimens confirmed positive for Novel 2009/H1N1 (swine flu) were also tested.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not specify the number or qualifications of experts directly. Ground truth was established using comparator methods such as Direct Fluorescent Antibody Test (DFA), viral culture, and well-characterized RT-PCR amplification followed by bidirectional sequencing. These methods are laboratory-based and generally performed by trained laboratory personnel, rather than explicitly "experts" in the context of clinical interpretation.
Adjudication method for the test set:
- The document does not describe an adjudication method in the sense of multiple human readers resolving discrepancies. The ground truth was established by laboratory-based comparator methods.
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 qualitative nucleic acid multiplex test for direct detection of viral RNA/DNA, not an imaging or diagnostic support system for human readers.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, the performance characteristics (sensitivity and specificity) presented in Table 10 represent the standalone performance of the xTAG RVP FAST assay itself. The assay utilizes multiplex RT-PCR and Luminex technology, with data analyzed by the xTAG Data Analysis Software (TDAS RVP FAST) to provide a qualitative summary. There is no human interpretation of image data or similar involved in the reported performance.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Laboratory-based Comparator Methods:
  - For Influenza B, RSV, and Adenovirus: Direct Fluorescent Antibody Test (DFA) and/or viral culture.
  - For Influenza A subtyping, hMPV, and Rhinovirus: Well-characterized RT-PCR amplification followed by bidirectional sequencing.
  - For the additional Adenovirus samples: Culture.
  - For the Novel 2009/H1N1 samples: CDC real-time PCR test.
The sample size for the training set:
- The document does not explicitly state a "training set" in the context of machine learning or AI models. This device is a molecular diagnostic assay where primers and probes are designed based on known viral genetic sequences. The development and optimization process for such assays typically involves laboratory experimentation with known positive and negative controls and clinical samples, rather than a distinct "training set" in the AI sense for which performance metrics against a held-out test set would be reported for FDA submission.
How the ground truth for the training set was established:
- As there isn't a stated "training set" for a machine learning model, the concept of establishing ground truth for it is not directly applicable in the terms usually associated with AI/ML device submissions. The assay itself is designed based on known biological targets, and its analytical and clinical performance is validated against established laboratory reference methods and clinical outcomes.

Summary

{0}------------------------------------------------

JUL - 1 - 1

Luminex Molecular Diagnostics

xTAG® RVP FAST Traditional 510(k) Submission

510(k) SUMMARY

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.

510(k) Number: K103776

Submission Type: Traditional 510(k), New Device

Measurand: A panel of viruses including: Influenza A, Influenza A subtype H1, Influenza A subtype H3, Influenza B, Respiratory Syncytial Virus, Human Metapneumovirus, Rhinovirus, and Adenovirus

Type of Test: Qualitative nucleic acid multiplex test

Applicant: Luminex Molecular Diagnostics Inc., Toronto, Ontario, Canada

Proprietary and Established Names: xTAG Respiratory Viral Panel FAST (RVP FAST)

Regulatory Information:

Product Code	Classification	Regulation Section	Review Panel
OCC, OEM,OEP	Class II	21 CFR 866.3980 Respiratory viral panelmultiplex nucleic acid assay	Microbiology(83)

Intended Use:

The xTAG Respiratory Viral Panel Fast (RVP FAST) is a qualitative nucleic acid multiplex test intended for the simultaneous detection and identification of multiple respiratory virus nucleic acids in nasopharyngeal swabs from individuals suspected of respiratory tract infections. The following virus types and subtypes are identified using RVP FAST: Influenza A subtype H1, Influenza A subtype H3, Influenza B, Respiratory Syncytial Virus, Human Metapneumovirus, Rhinovirus, and Adenovirus. The detection and identification of specific viral nucleic acids from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection if used in conjunction with other clinical and epidemiological information.

{1}------------------------------------------------

Luminex Molecular Diagnostics

Indication(s) for use: Same as intended use.

Special instrument requirements: Luminex 100 or 200 instrument with IS or xPONENT software

Device Description:

xTAG RVP Fast Primer Mix
xTAG RVP Fast Bead Mix
xTAG OneStep Enzyme Mix
xTAG OneStep Buffer, 5X
xTAG dNTP Mix
xTAG RNase-Free Water
xTAG Reporter Buffer
xTAG Streptavidin, R-Phycoerythrin G15
xTAG MS2
xTAG Bacteriophage Lambda DNA
xTAG TDAS RVP FAST (US) software

{2}------------------------------------------------

Luminex Molecular Diagnostics

Substantial Equivalence Information:

a. Predicate device name(s): xTAG Respiratory Viral Panel

b. Predicate 510(k) number(s): K063765, K081843, K091667

c. Comparison with predicate:

The following tables compare the xTAG Respiratory Viral Panel FAST with the xTAG Respiratory Viral Panel (K063765, K081843, K091667). The first table shows similarities between the new device and the predicate, while the second table shows the differences.

Item	New Device(Ref. No. to be determined)xTAG RVP FAST	Predicate(K063765, K081483, K091667)xTAG RVP
Manufacturer	Luminex Molecular Diagnostics	Luminex Molecular Diagnostics
Specimen Types	Nasopharyngeal swabs	Nasopharyngeal swabs
Amplification Method	Multiplex end point RT-PCR	Multiplex end point RT-PCR
Test Format	Multiplex bead-based universal arraysorting on Luminex 100/200 instrument	Multiplex bead-based universal arraysorting on Luminex 100/200 instrument
Detection Method	Fluorescence based	Fluorescence based
Quality Control	Internal Control (E. coli phage MS2), andRun Control (bacteriophage LambdaDNA), rotating analyte control andnegative controls	Internal Control (E. coli phage MS2) andRun Control (bacteriophage LambdaDNA), rotating analyte control andnegative controls
Results	Qualitative	Qualitative
Instrument	LX100 or LX200	LX100 or LX200

Table 1 · Similarities between New Device and Predicate

Item	New Device(K103776)xTAG RVP FAST	Predicate(K063765, K081483, K091667)xTAG RVP
Intended Use	The xTAG® Respiratory Viral PanelFast (RVP FAST) is a qualitativenucleic acid multiplex test intendedfor the simultaneous detection andidentification of multiple respiratoryvirus nucleic acids in nasopharyngealswabs from individuals suspected ofrespiratory tract infections. Thefollowing virus types and subtypesare identified using RVP FAST:Influenza A, Influenza A subtype H1,Influenza A subtype H3, Influenza B,Respiratory Syncytial Virus, HumanMetapneumovirus, Rhinovirus, andAdenovirus. The detection andidentification of specific viral nucleic	The xTAG® Respiratory Viral Panel(RVP) is a qualitative nucleic acidmultiplex test intended for thesimultaneous detection andidentification of multiple respiratoryvirus nucleic acids in nasopharyngealswabs from individuals suspected ofrespiratory tract infections. Thefollowing virus types and subtypes areidentified using RVP: Influenza A,Influenza A subtype H1, Influenza Asubtype H3, Influenza B, RespiratorySyncytial Virus subtype A, RespiratorySyncytial Virus subtype B,Parainfluenza 1, Parainfluenza 2, andParainfluenza 3 virus, Human
acids from individuals exhibiting signsand symptoms of respiratoryinfection aids in the diagnosis ofrespiratory viral infection if used inconjunction with other clinical andepidemiological information.	Metapneumovirus, Rhinovirus, andAdenovirus. The detection andidentification of specific viral nucleicacids from individuals exhibiting signsand symptoms of respiratory infectionaids in the diagnosis of respiratoryviral infection if used in conjunctionwith other clinical and laboratoryfindings. It is recommended thatspecimens found to be negative forInfluenza B, Respiratory Syncytial Virussubtype A and B, Parainfluenza 1,Parainfluenza 2, Parainfluenza 3 andAdenovirus, after examination usingRVP be confirmed by cell culture.
Negative results do not precluderespiratory viral infection and shouldnot be used as the sole basis fordiagnosis, treatment or othermanagement decisions. Positiveresults do not rule out bacterialinfection or co-infection with otherorganisms. The agent detected maynot be the definite cause of disease.The use of additional laboratorytesting (e.g. bacterial and viralculture, immunofluorescence, andradiography) and clinicalpresentation must be taken intoconsideration in order to obtain thefinal diagnosis of respiratoryinfection.	Negative results do not precluderespiratory virus infection and shouldnot be used as the sole basis fordiagnosis, treatment or othermanagement decisions. Positiveresults do not rule out bacterialinfection, or co-infection with otherviruses. The agent detected may notbe the definite cause of disease. Theuse of additional laboratory testing(e.g. bacterial culture,immunofluorescence, radiography)and clinical presentation must betaken into consideration in order toobtain the final diagnosis ofrespiratory viral infection. Due toseasonal prevalence, performancecharacteristics for Influenza A/H1 wereestablished primarily withretrospective specimens. The RVPassay cannot adequately detectAdenovirus species C, or serotypes 7aand 41. The RVP primers for detectionof rhinovirus cross-react withenterovirus. A rhinovirus reactiveresult should be confirmed by analternate method (e.g. cell culture).
Due to the genetic similarity betweenhuman Rhinovirus and Enterovirus,the RVP FAST primers for thedetection of rhinovirus cross reactwith enterovirus. A rhinovirusreactive result should be confirmedby an alternate method (e.g. cellculture).	Performance characteristics forInfluenza A Virus were establishedwhen Influenza A/H3 and A/H1 werethe predominant Influenza A viruses incirculation. When other Influenza Aviruses are emerging, performancecharacteristics may vary. If infectionswith a novel Influenza A virus issuspected based on current clinicaland epidemiological screening criteria
Performance characteristics forInfluenza A Virus were establishedwhen Influenza A/H3 and A/H1 werethe predominant Influenza A virusesin circulation. When other InfluenzaA viruses are emerging, performancecharacteristics may vary. If infectionwith a novel Influenza A virus issuspected based on current clinicaland epidemiological screeningcriteria recommended by publichealth authorities, specimens shouldbe collected with appropriateinfection control precautions fornovel virulent Influenza viruses andsent to a state or local healthdepartments for testing. Viral culture	when Influenza A/H3 and A/H1 werethe predominant Influenza A viruses incirculation. When other Influenza Aviruses are emerging, performancecharacteristics may vary. If infectionswith a novel Influenza A virus issuspected based on current clinicaland epidemiological screening criteria
	cases unless a BSL 3+ facility isavailable to receive and culturespecimens.	recommended by public healthauthorities, specimens should becollected with appropriate infectioncontrol precautions for novel virulentInfluenza viruses and sent to a state orlocal health department for testing.Viral culture should not be attemptedin these cases unless a BSL 3+ facility isavailable to receive and culturespecimens.
Targets Reported	Influenza A, Influenza A subtype H1,Influenza A subtype H3, Influenza B,Respiratory Syncytial Virus, HumanMetapneumovirus, Rhinovirus, andAdenovirus	Influenza A, Influenza A subtype H1,Influenza A subtype H3, Influenza B,Respiratory Syncytial Virus, HumanMetapneumovirus, Rhinovirus,Adenovirus, Parainfluenza 1,Parainfluenza 2 and Parainfluenza 3
Sample Preparation	Biomérieux NucliSENS® EasyMag®	QIAGEN QIAamp MiniElute,Biomérieux NucliSENS® EasyMag®, andBiomérieux MiniMag™
Amplification Enzyme	xTAG® OneStep Enzyme Mix	xTAG® OneStep Enzyme Mix andancillary reagent TaKaRa Taq™ HotStart
Primer Mixes	One primer mix (PCR and TSPEcombined)	Two primer mixes (1 for PCR and 1 forTSPE)
Software	xTAG Data Analysis Software RVPFAST (US)	xTAG Data Analysis Software RVP (US)

{3}------------------------------------------------

1

Luminex Molecular Diagnostics

{4}------------------------------------------------

Image /page/4/Picture/0 description: The image shows the word "Luminex." in a bold, italicized font. The word is black and is set against a white background. The dot above the "i" is a perfect circle.

xTAG® RVP FAST Traditional 510(k) Submission

Standards/Guidance Documents referenced (if applicable):

Table 3: Guidance Documents

	Title	Date
1	Class II Special Controls Guidance: Respiratory Viral Panel MultiplexNucleic Acid Assay	Oct. 9, 2009
2	Class II Special Control Guidance Document: Testing for Detection andDifferentiation of Influenza A Virus Subtypes Using Multiplex Assays	Oct. 9, 2009
3	Guidance (Draft) for Establishing the Performance Characteristics of InVitro Diagnostic Devices for the Detection or Detection andDifferentiation of Influenza Viruses	Feb. 15, 2008
4	Guidance for In Vitro Diagnostic Devices to Detect Influenza A Viruses:Labeling and Regulatory Path	May 1, 2007
5	Class II Special Controls Guidance: Reagents for Detection of SpecificNovel Influenza A Viruses	Mar. 22, 2006
6	Class II Special Control Guidance Document: "Testing for HumanMetapneumovirus (hMPV) Using Nucleic Acid Assays"	Oct. 9, 2009
7	Guidance for the Content of Premarket Submissions for SoftwareContained in Medical Devices	May 11, 2005
8	Guidance document for Format for Traditional and Abbreviated 510(k)s	Aug. 12, 2005

{5}------------------------------------------------

Luminex Molecular Diagnostics

	StandardsNo.	RecognitionNumber(FDA)	Standards Title	Date
1	MM13-A	7-191	Collection, Transport, Preparation andStorage of Specimens	03/18/2009
2	EP15-A2	7-153	User Verification of Performance forPrecision and Trueness (2nd edition)	09/09/2008
3	EP05-A2	7-110	Evaluation of Precision Performance ofQuantitative measurement Methods (2nd ed.)	10/31/2005
4	EP07-A2	7-127	Interference Testing in Clinical Chemistry (2nd edition)	05/21/2007
5	EP12-A2	7-152	User Protocol for Evaluation f QualitativeTest Performance (2nd edition)	09/09/2008
6	EP17-A	7-194	Protocol for Determination of Limits ofDetection and Limits of Quantitation	03/18/2009
7	EP14-A2	7-128 and7-143	Evaluation of Matrix Effects (2nd edition)	06/01/2004
8	MM03-A2	7-132	Molecular Diagnostic Methods for InfectiousDiseases (2nd edition)	09/09/2008

Table 4: Standards

Test Principle:

RVP FAST incorporates multiplex Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) with Luminex's proprietary Universal Tag sorting system on the Luminex platform. The assay also detects an internal control (E. coli phage MS2) which should be added to each sample prior to extraction, and a run control (bacteriophage Lambda DNA) which should be added as a separate RT-PCR reaction in each run performed.

For each sample, viral extract (RNA or DNA) is amplified in a single multiplex RT-PCR reaction. For each of the viruses/subtypes or internal control present in the sample, PCR amplimers are produced.

The RT-PCR product is then added to a hybridization/detection containing the universal array (Bead Mix) and the Streptavidin-R-Phycoerythrin reporter. Each Luminex bead population detects a specific viral target or assay control through a highly specific anti-tag/tag hybridization. Following the incubation of the RT-PCR products with the bead mix and reporter, the hybridization/detection reactions are then sorted and read on the Luminex instrument. Signal (median fluorescence intensity, MFI) is generated for each bead population (viral target or assay control). These fluorescence values are then analyzed to establish the presence of viral targets and/or controls in each sample tested.

{6}------------------------------------------------

minex Molecular Diagnostics

All viruses are identified in a single multiplex reaction. The data generated by the xMAP instrument is analyzed by the xTAG Data Analysis Software RVP Fast (TDAS RVP FAST) to provide a qualitative summary report on which viruses are present in the sample, if any.

Performance Characteristics:

Analytical Performance:

Precision/Reproducibility:

The site-to-site reproducibility (single analyte targets) study was conducted at three independent sites. Each of two operators performed fifteen separate EasyMag extraction runs and five xTAG RVP FAST runs on non-consecutive days for each of the 8 targets in the assay. For each target, at each dilution, there were 90 data points: 3 sites x 2 operator / site x 5 xTAG runs / operator x 3 replicates (EasyMag extraction runs).

Site-to-site reproducibility for dual-analyte targets was investigated by two operators employing the bioMerieux NucliSENS® EasyMag extraction kit and the RVP FAST test at three independent sites. Each operator conducted 5 separate extractions and runs, on non-consecutive days. There were a total of 30 replicates for each sample type: (3 sites) x (2 operators/site) x (5 runs/operator) = 30 runs. Four different clinically relevant co-infections were represented by the dual-analyte samples.

RVP FAST was reproducible across all sites, operators and targets.

Limit of Detection (LoD):

The LoD was determined for each of the following viral analyte targets from simulated samples arranged in a dilution series from a high titre stock: Flu A H3, Flu B, Adenovirus, RSV (A and B subtypes). Rhinovirus, and hMPV (subtypes A1, A2, B1 and B2). For each reference strain, the LoD is provided in Column 3 of the following table in TCIDso/mL.

Analyte	Strain ID	TCID50/mL(corresponding tothe estimated LoD)
Adenovirus	Type 1 Strain Adenoid 71DHI 20-4740010 (original ATCC VR-1)	3.9 × 102
Flu A H1	A/Solomon Islands/3/2006 (NML)	7.6 × 10-1
Flu A H3	A/Victoria/3/75DHI 20-4710010 (original ATCC VR-822)	1.8 (matrix)3.6 (H3)
Flu B	Influenza B/Malaysia/2506/04(PHL)	2.9 × 10-2
Rhinovirus	FO 1-3774, Type 54	1.4 × 10-2

Table 5: Summary Limit of Detection (LoD) for RVP FAST analytes

{7}------------------------------------------------

Molecular Diagnostics

	ATCC 1164
	University of Iowa, Dept. Public Health.(hMPV sublineage A1, Isolate # 16, Iowa, January 2003)	$3.4 x 10^{-1}$
hMPV	CAN97-83(hMPV sublineage A2, CDC isolate 26583)	$1.3 x 10^{1}$
	University of Iowa, Dept. Public Health.(hMPV sublineage B1, Isolate #5, Iowa)	1.1
	University of Iowa, Dept. Public Health.(hMPV sublineage B2, Isolated October, 2003, Cusco,Peru)	1.2
	RSV	RSV A Long strainATCC VR-26
RSV B Wash/18537/62DHI 20-4730010 (original ATCC VR-1401)		$1.6 x 10^{-2}$

Carryover Contamination Limit of Blank (LoB):

This study was conducted using water blanks (DNase and RNase free distilled water) and replicate aliquots of a solution of purified viral nucleic acid (RSV B; Wash/18537/62DHI 20-4730010; original ATCC VR-1401)) prepared from a High Positive (HP) titre simulated sample in a checkerboard manner. This titre was selected to fall far above the assay cut-off, so that positive calls would be obtained 100% of the time and to experimentally maximize the potential for 'cross contamination'. RSV B was selected as the high titre analyte for the study, since it is commonly observed in clinical specimens at a high titre (Chidgey and Broadley, 2005)*. This titre was selected to fall far above the assay cut-off, so that positive calls would be obtained 100% of the time. The high titer purified viral nucleic acid replicates were tested to assess the probability of carryover contamination in adjacent wells containing water blanks. This study consisted of 6 identical runs tested over six (6) different days each performed by one operator, using a single kit lot and equipment set. The mean MFI of the High Positive RSV B specimen used in the carryover part of this evaluation was 10,860. No carryover contamination with RSV B was observed as the MFI values obtained in the blank positions was not significantly greater than the LoB in one or more blank position on the checkerboard plate layout. LoB was set as equal to the 95° percentile of the observed MFI distribution generated from NEGATIVE calls for each analyte target in uncontaminated blanks and replicates of the high titre intact viral organisms

1 Chidgey, Sharon M.; Broadley, Kenneth J (2005). Respiratory syncytial virus infections: characteristics and treatment. Journal of Pharmacy and Pharmacology, 57/11:1371-1382.

{8}------------------------------------------------

ex Molecular Diagnostics

Analyte (Virus)	# Calls Included		Limit of Blank
	# Calls Included	# Calls Excluded	95th Percentile ofMFI distribution
Flu A	576	0	75
H1	576	0	80
H3	576	0	76.125
Flu B	576	0	115.625
RSV (probe 1)	576	0	75.125
RSV (probe 2)	288*	0	82.825
Adenovirus	576	0	79
hMPV	576	0	71.125
Rhinovirus	576	0	74.5

Table 6a: Limit of Blank per analyte in xTAG RVP FAST

*Since the target selected for HP is RSV (probe 2) the LoB for this target was calculated based on the total number of blank samples for the plate (whereas for all other targets, the LoB is calculated from all samples on the plate).

Analytical Specificity (Interference and Cross-Reactivity):

A total of 26 potentially cross-reactive pathogens (bacterial and viral) were assessed in replicates with RVP FAST. Each replicate underwent a single EasyMag (bioMerieux NucliSENS®) extraction prior to testing. These bacterial and viral pathogens did not cross-react or interfere with any viral target probed by RVP FAST.

Table 7: Bacterial pathogens assessed as potential cross-reactive species in the RVP-FAST Assay

Bacterial (n=20)
Bordetella pertussis	Legionella pneumophilia
Chlamydia pneumoniae	Neisseria meningitides
Haemophillus influenzae	Staphylococcus aureus
Pseudomonas aeruginosa	Staphylococcus epidermidis
Streptococcus pneumoniae	Streptococcus Group B
Moraxella cartarrhalis	Acinetobacter baumanii (calcoaceticus)
Mycobacterium intracellulare	Streptococcus pyogenes
Mycoplasma bovis(substitute for M. tuberculosis)	Mycobacterium avium
Mycoplasma pneumoniae	Serratia marcescens
Klebsiella pneumoniae	Escherichia coli

{9}------------------------------------------------

Image /page/9/Picture/0 description: The image shows the word "Luminex." in bold, black font. The word is slightly slanted to the right. There is a small dot after the word.

			Table 8: Viral pathogens assessed as potential cross-reactive species in the RVP-FAST Assay
--	--	--	---------------------------------------------------------------------------------------------

Viral (n=6)
Herpes simplex virus Type 1	Mumps
Cytomegalovirus	Rubeola (Measles)
Varicella-zoster virus	Epstein Barr virus

A total of 14 combinations of analyte and potential interferent were assessed in replicate with RVP FAST. Each replicate underwent a single EasyMag (bioMerieux NucliSENS®) extraction prior to testing. These potential interfering agents were tested in the presence of targets meant to be detected by RVP FAST.

Target analyte	Potential interferent
RSV	Streptococcus pneumoniae
	Bordetella pertussis
	Haemophilus influenzae
	CMV
	Adenovirus
	CMV
	Chlamydia pneumoniae
	Influenza A (H3)
	Staphylococcus aureus
	Bordetella pertussis
	Chlamydia pneumoniae
	Rhinovirus
	Mycoplasma pneumoniae
	Haemophilus influenzae

Table 9: Combinations of Analytes & Interferents tested in the interference branch.

These substances did not cross-react or interfere with any viral target probed by RVP FAST.

Comparison Studies:

Clinical Studies: a. Clinical Sensitivity and Specificity:

The purpose of this multi-site study was to establish the clinical accuracy of the RVP FAST assay to detect the assay targets Influenza A, Influenza A subtype H1, Influenza A subtype H3, Influenza B, Respiratory Syncytial Virus (RSV), Human Metapneumovirus (hMPV), Rhinovirus, and Adenovirus in clinical specimens, across three independent sites.

Specimens tested included left-over, fresh and frozen, nasopharyngeal swabs (NPS) prospectively collected during the 2007/2008 and 2008/2009 flu seasons (i.e. all-comers accrued at enrolled clinical sites). All clinical specimens were analyzed fresh, as per the clinical laboratory routine

{10}------------------------------------------------

Luminex Molecular Diagnostics

algorithm or as ordered by the referring physician, using Direct Fluorescent Antibody Test (DFA) and/or viral culture for the following targets: Influenza B, RSV, and Adenovirus. Well characterized RT-PCR amplification followed by bidirectional sequencing was used as the comparator method for Influenza A subtyping, hMPV and Rhinovirus. To the extent possible, amplification primers used in comparator methods targeted regions distinct from those targeted by the RVP FAST Assay primers.

RVP FAST was performed on a total of 1191 prospectively collected clinical specimens that had been extracted from the fresh or frozen states were included in the performance calculations. Total extracted nucleic acid material was stored at -70°C.

	Sensitivity		Lower-Bound	Specificity		Lower-Bound
Virus (Analyte)	TP /(TP+FN)	percent	95%Cl forSensitivity	TN/(TN+FP)	percent	95% Cl forSpecificity
Human Influenza A	129/137	94.2%	88.8%	989/1036	95.5%	94.0%
H1	52/54	96.3%	87.3%	1116/1137	98.2%	97.2%
H3	74/77	96.1%	89.0%	1090/1114	97.8%	96.8%
Human Influenza B	50/53	94.3%	84.3%	1107/1120	98.8%	98.0%
RSV	110/121	90.9%	84.3%	1028/1052	97.7%	96.6%
Rhinovirus	43/45	95.6%	84.9%	1047/1132	92.5%	90.8%
Adenovirus	12/14	85.7%	57.2%	1151/1159	99.3%	98.6%
Metapneumovirus	35/36	97.2%	85.5%	1121/1133	98.9%	98.2%

Table 10: xTAG® RVP FAST Sensitivity / Specificity per Target (Combined Data set)

b. Other clinical supportive data.

Since Adenovirus does not show seasonality, the prospective sample set was supplemented with 34 banked, pre-selected, positive clinical specimens collected at selected sites and tested by RVP FAST. All pre-selected specimens were frozen clinical samples which had originally been tested in the fresh-state using culture. The percent positive agreement of the test compared to the reference method was 97.06% (95% lower bound confidence interval of 86.47% - 99.93%).

An additional 77 clinical specimens (NP swabs) confirmed positive for Novel 2009/H1N1 (swine flu) by the CDC real-time PCR test were tested by RVP FAST. Of these, seventy-five (75) were Flu A unsubtypeable (97.40%, LB 95% Cl 90.93%), two (2) specimens were Flu A H1 by RVP FAST (2.60%). None were negative for Flu A. In addition, none of the confirmed Flu A H1 or Flu A H3 clinical specimens in the clinical data set were unsubtypeable for Influenza A by RVP FAST.

Clinical Cut-off: Not applicable.

{11}------------------------------------------------

Luminex Molecular Diagnostics

Expected values/ reference range: Not applicable.

Conclusion: The information submitted in this premarket notification demonstrates that the device is equivalent to the predicate device.

{12}------------------------------------------------

Image /page/12/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an abstract symbol resembling a stylized caduceus or a representation of human figures, with three wavy lines extending from the right side of the symbol.

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

Luminex Molecular Diagnostics, Inc. c/o Ms. Lubna Syed Director, Regulatory Affairs 439 University Avenue, Suite 900 Toronto, Ontario MSG 1Y8 Canada

JUL - 1 2011

Re: K103776

Trade/Device Name: xTAG® Respiratory Viral Panel FAST (RSP FAST) Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory viral panel multiplex nucleic acid assay Regulatory Class: Class II Product Code: OCC, OEM, OEP Dated: June 3, 2011 Received: June 10, 2011

Dear Ms. Syed

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 class II (Special Controls), 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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter

{13}------------------------------------------------

Page 2 - Ms. Lubna Syed

will allow you to begin marketing your device as described in your Section 51.0(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 Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-545(). Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of 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/cdrh/industry/support/index.html.

Sincerely yours,

Vayartogms

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

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

Indications for Use

510(k) Number (if known):

Device Name: xTAG® RVP FAST

Negative results do not preclude respiratory viral infection and should not be used as the sole basis for diagnosis, treatment or other management decisions. Positive results do not rule out bacterial infection, or co-infection with other organisms. The agent detected may not be the definite cause of disease. The use of additional laboratory testing (e.g., bacterial and viral culture, immunofluorescence, and radiography) and clinical presentation-must-be taken into consideration in order to obtain the final diagnosis of respiratory infection.

Due to the genetic similarity between human Rhinovirus and Enterovirus, the RVP FAST primers for the detection of rhinovirus cross-react with enterovirus. A rhinovirus reactive result should be confirmed by an alternate method (e.g., cell culture).

Prescription Use	X
(Part 21 CFR 801 Subpart D)

AND/OR

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

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

Division Sign-Off

Office of In Vitro Diagnostic Device
Evaluation and Safety

510(k) K103776
5.0K)

Regulation Number and Section

§ 866.3980 Respiratory viral panel multiplex nucleic acid assay.

(a)
Identification. A respiratory viral panel multiplex nucleic acid assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or viral culture. The detection and identification of a specific viral nucleic acid from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection when used in conjunction with other clinical and laboratory findings. The device is intended for detection and identification of a combination of the following viruses:(1) Influenza A and Influenza B;
(2) Influenza A subtype H1 and Influenza A subtype H3;
(3) Respiratory Syncytial Virus subtype A and Respiratory Syncytial Virus subtype B;
(4) Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus;
(5) Human Metapneumovirus;
(6) Rhinovirus; and
(7) Adenovirus.
(b)
Classification. Class II (special controls). The special controls are:(1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid Assay;”
(2) For a device that detects and identifies Human Metapneumovirus, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Human Metapneumovirus (hMPV) Using Nucleic Acid Assays;” and
(3) For a device that detects and differentiates Influenza A subtype H1 and subtype H3, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Detection and Differentiation of Influenza A Virus Subtypes Using Multiplex Nucleic Acid Assays.” See § 866.1(e) for the availability of these guidance documents.