(186 days)
Not Found
No
The description focuses on PCR-based detection and analysis of spectrofluorometric data using dedicated software, with no mention of AI or ML techniques for data interpretation or decision making.
No
The device is described as a diagnostic tool for identifying respiratory viruses, not for treating conditions.
Yes
Explanation: The "Intended Use / Indications for Use" section explicitly states that the device's output "aids in the diagnosis of respiratory viral infection if used in conjunction with other clinical and epidemiological information." Additionally, it performs "qualitative nucleic acid multiplex testing" for the "detection and identification of multiple respiratory virus nucleic acids," which are key characteristics of a diagnostic device.
No
The device description clearly states it is a PCR-based system that includes oligonucleotide primer/probe components and relies on the Luminex 100 or 200 instrument for analysis, indicating significant hardware components beyond just software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the device 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." This describes a test performed in vitro (outside the body) on a biological sample (nasopharyngeal swabs) to provide information for diagnosis.
- Purpose: The detection and identification of specific viral nucleic acids "aids in the diagnosis of respiratory viral infection if used in conjunction with other clinical and epidemiological information." This clearly indicates a diagnostic purpose.
- Device Description: The description details a "PCR-based system for detecting the presence / absence of viral DNA / RNA in clinical specimens." This further confirms it's a laboratory test performed on biological samples.
- Clinical Studies: The document includes detailed information about clinical studies conducted to establish the "clinical accuracy of the RVP FAST assay to detect the assay targets... in clinical specimens." This is a standard requirement for IVD devices to demonstrate their performance in a clinical setting.
- Performance Metrics: The inclusion of sensitivity and specificity data for various viruses is a key characteristic of IVD performance evaluation.
All these elements align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for 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.
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.
Product codes
OCC, OEM, OEP
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. The RVP FAST reagent components are described below.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Nasopharyngeal swabs
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
A total of 1191 prospectively collected clinical specimens (nasopharyngeal swabs (NPS)) 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. All clinical specimens were analyzed fresh, as per the clinical laboratory routine algorithm or as ordered by the referring physician. For annotation, Direct Fluorescent Antibody Test (DFA) and/or viral culture were used for Influenza B, RSV, and Adenovirus targets. 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.
Summary of Performance Studies
-
Analytical Performance:
- Precision/Reproducibility: A site-to-site reproducibility study was conducted at three independent sites. Two operators at each site performed fifteen separate EasyMag extraction runs and five xTAG RVP FAST runs on non-consecutive days for each of the 8 targets for single analyte targets. For each target, at each dilution, there were 90 data points (3 sites x 2 operators/site x 5 xTAG runs/operator x 3 replicates). For dual-analyte targets, two operators at three independent sites conducted 5 separate extractions and runs, on non-consecutive days, resulting in 30 replicates per sample type (3 sites x 2 operators/site x 5 runs/operator). Four different clinically relevant co-infections were represented.
- Limit of Detection (LoD): LoD was determined for each viral analyte target from simulated samples in a dilution series from a high titre stock. LoDs were provided in TCID50/mL.
- Adenovirus: $3.9 \times 10^2$
- Flu A H1: $7.6 \times 10^{-1}$
- Flu A H3: $1.8 \text{ (matrix)}, 3.6 \text{ (H3)}$
- Flu B: $2.9 \times 10^{-2}$
- Rhinovirus: $1.4 \times 10^{-2}$
- hMPV (sublineage A1): $3.4 \times 10^{-1}$
- hMPV (sublineage A2): $1.3 \times 10^1$
- hMPV (sublineage B1): 1.1
- hMPV (sublineage B2): 1.2
- RSV (RSV A Long strain): $1.6 \times 10^{-2}$
- RSV (RSV B Wash/18537/62): $1.6 \times 10^{-2}$
- Carryover Contamination Limit of Blank (LoB): This study utilized water blanks and replicate aliquots of purified viral nucleic acid (RSV B) prepared from a High Positive (HP) titre simulated sample in a checkerboard manner. The study consisted of 6 identical runs over six different days. No carryover contamination was observed.
- Analytical Specificity (Interference and Cross-Reactivity): 26 potentially cross-reactive pathogens (bacterial and viral) were assessed in replicates; no cross-reaction or interference was observed. 14 combinations of analyte and potential interferent were assessed in replicate; no interference was observed.
-
Clinical Studies (Clinical Sensitivity and Specificity):
- Study Type: Multi-site study to establish clinical accuracy.
- Sample Size: 1191 prospectively collected clinical specimens (fresh or frozen nasopharyngeal swabs). An additional 34 banked, pre-selected, positive clinical adenovirus specimens and 77 clinical specimens positive for Novel 2009/H1N1 were also tested.
- Key Results:
- Adenovirus (supplemental data): Percent positive agreement of 97.06% (95% lower bound confidence interval of 86.47% - 99.93%) compared to the reference method (culture).
- Novel 2009/H1N1 (supplemental data): Of 77 CDC-confirmed positive specimens, 75 were Flu A unsubtypeable by RVP FAST (97.40%, LB 95% Cl 90.93%), and 2 specimens were Flu A H1 (2.60%). None were negative for Flu A.
Key Metrics
| Virus (Analyte) | Sensitivity (%) | 95% CI for Sensitivity (Lower-Bound) | Specificity (%) | 95% CI for Specificity (Lower-Bound) |
|---|---|---|---|---|
| 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 | 97.2% | 85.5% | 98.9% | 98.2% |
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 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.
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 panel | |
| multiplex 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.
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.
1
Luminex Molecular Diagnostics
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.
Indication(s) for use: Same as intended use.
Special instrument requirements: Luminex 100 or 200 instrument with IS or xPONENT software
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. The RVP FAST reagent components are described below.
| 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 array
sorting on Luminex 100/200 instrument | Multiplex bead-based universal array
sorting on Luminex 100/200 instrument |
| Detection Method | Fluorescence based | Fluorescence based |
| Quality Control | Internal Control (E. coli phage MS2), and
Run Control (bacteriophage Lambda
DNA), rotating analyte control and
negative controls | Internal Control (E. coli phage MS2) and
Run Control (bacteriophage Lambda
DNA), rotating analyte control and
negative 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 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 | The xTAG® Respiratory Viral Panel
(RVP) 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: Influenza A,
Influenza A subtype H1, Influenza A
subtype H3, Influenza B, Respiratory
Syncytial Virus subtype A, Respiratory
Syncytial Virus subtype B,
Parainfluenza 1, Parainfluenza 2, and
Parainfluenza 3 virus, Human |
| 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. | 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 laboratory
findings. It is recommended that
specimens found to be negative for
Influenza B, Respiratory Syncytial Virus
subtype A and B, Parainfluenza 1,
Parainfluenza 2, Parainfluenza 3 and
Adenovirus, after examination using
RVP be confirmed by cell culture. | |
| 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. | Negative results do not preclude
respiratory virus 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
viruses. The agent detected may not
be the definite cause of disease. The
use of additional laboratory testing
(e.g. bacterial culture,
immunofluorescence, radiography)
and clinical presentation must be
taken into consideration in order to
obtain the final diagnosis of
respiratory viral infection. Due to
seasonal prevalence, performance
characteristics for Influenza A/H1 were
established primarily with
retrospective specimens. The RVP
assay cannot adequately detect
Adenovirus species C, or serotypes 7a
and 41. The RVP primers for detection
of rhinovirus cross-react with
enterovirus. A rhinovirus reactive
result should be confirmed by an
alternate method (e.g. cell culture). | |
| 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 infections
with a novel Influenza A virus is
suspected based on current clinical
and epidemiological screening criteria | |
| 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
departments for testing. Viral culture | 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 infections
with a novel Influenza A virus is
suspected based on current clinical
and epidemiological screening criteria | |
| | cases unless a BSL 3+ facility is
available to receive and culture
specimens. | 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. |
| Targets Reported | Influenza A, Influenza A subtype H1,
Influenza A subtype H3, Influenza B,
Respiratory Syncytial Virus, Human
Metapneumovirus, Rhinovirus, and
Adenovirus | Influenza A, Influenza A subtype H1,
Influenza A subtype H3, Influenza B,
Respiratory Syncytial Virus, Human
Metapneumovirus, Rhinovirus,
Adenovirus, Parainfluenza 1,
Parainfluenza 2 and Parainfluenza 3 |
| Sample Preparation | Biomérieux NucliSENS® EasyMag® | QIAGEN QIAamp MiniElute,
Biomérieux NucliSENS® EasyMag®, and
Biomérieux MiniMag™ |
| Amplification Enzyme | xTAG® OneStep Enzyme Mix | xTAG® OneStep Enzyme Mix and
ancillary reagent TaKaRa Taq™ Hot
Start |
| Primer Mixes | One primer mix (PCR and TSPE
combined) | Two primer mixes (1 for PCR and 1 for
TSPE) |
| Software | xTAG Data Analysis Software RVP
FAST (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 Multiplex | |
| Nucleic Acid Assay | Oct. 9, 2009 | |
| 2 | Class II Special Control Guidance Document: Testing for Detection and | |
| Differentiation of Influenza A Virus Subtypes Using Multiplex Assays | Oct. 9, 2009 | |
| 3 | Guidance (Draft) for Establishing the Performance Characteristics of In | |
| Vitro Diagnostic Devices for the Detection or Detection and | ||
| Differentiation 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 Specific | |
| Novel Influenza A Viruses | Mar. 22, 2006 | |
| 6 | Class II Special Control Guidance Document: "Testing for Human | |
| Metapneumovirus (hMPV) Using Nucleic Acid Assays" | Oct. 9, 2009 | |
| 7 | Guidance for the Content of Premarket Submissions for Software | |
| Contained 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
| | Standards
No. | Recognition
Number
(FDA) | Standards Title | Date |
|---|------------------|--------------------------------|--------------------------------------------------------------------------------------|------------|
| 1 | MM13-A | 7-191 | Collection, Transport, Preparation and
Storage of Specimens | 03/18/2009 |
| 2 | EP15-A2 | 7-153 | User Verification of Performance for
Precision and Trueness (2nd edition) | 09/09/2008 |
| 3 | EP05-A2 | 7-110 | Evaluation of Precision Performance of
Quantitative 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 Qualitative
Test Performance (2nd edition) | 09/09/2008 |
| 6 | EP17-A | 7-194 | Protocol for Determination of Limits of
Detection and Limits of Quantitation | 03/18/2009 |
| 7 | EP14-A2 | 7-128 and
7-143 | Evaluation of Matrix Effects (2nd edition) | 06/01/2004 |
| 8 | MM03-A2 | 7-132 | Molecular Diagnostic Methods for Infectious
Diseases (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 to
the estimated LoD) |
|------------|-----------------------------------------------------------------|------------------------------------------------------|
| Adenovirus | Type 1 Strain Adenoid 71
DHI 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/3/75
DHI 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 strain | |
| ATCC VR-26 | ||
| RSV B Wash/18537/62 | ||
| DHI 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.
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| Analyte (Virus) | # Calls Included | Limit of Blank | |
|---|---|---|---|
| # Calls Included | # Calls Excluded | 95th Percentile of | |
| MFI 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 |
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| 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
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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 for | ||||
| Sensitivity | TN/ | |||||
| (TN+FP) | percent | 95% Cl for | ||||
| Specificity | ||||||
| Human Influenza A | 129/13 | |||||
| 7 | 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 | 110/12 | |||||
| 1 | 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.
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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.
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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
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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
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Indications for Use
510(k) Number (if known):
Device Name: xTAG® RVP FAST
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.
| 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)
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Office of In Vitro Diagnostic Device
Evaluation and Safety
510(k) K103776
5.0K)