(144 days)
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 B, Respiratory Syncytial Virus subtype A, Respiratory Syncytial Virus subtype B, Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 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 laboratory findings.
xTAG RVP can also differentiate the hemagglutinin (HA) gene of some Influenza A subtypes H1 and H3 strains. Differentiation of Influenza A HA subtypes is based on both a positive result for the Influenza A matrix gene and an accompanying positive result for the Influenza A HA subtype H1 (circulating prior to the emergence of 2009 H1N1pdm) or Influenza A HA subtype H3. This device cannot differentiate the Influenza A HA subtype 2009 H1N1pdm by design, and may not be able to differentiate potential newly emerging Influenza A HA subtypes.
The modified RVP is a PCR-based test system for detecting the presence / absence of viral DNA / RNA in clinical specimens. The modified device is the same as the predicate device, except for a reformulation of the PCR primer mix.
The Luminex xTAG® Respiratory Viral Panel (RVP) is a qualitative nucleic acid multiplex test designed for the simultaneous detection and identification of multiple respiratory virus nucleic acids in nasopharyngeal swabs. The device was modified to improve reactivity to influenza A/H3 strains. The study referenced primarily focuses on demonstrating the substantial equivalence of the modified device to its predicate devices, especially concerning the improved detection of Influenza A H3.
1. A table of acceptance criteria and the reported device performance
The document does not explicitly state pre-defined acceptance criteria in terms of specific percentages for Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) to consider the device successful. However, the performance metrics observed in the clinical comparison study serve as the reported device performance, and the FDA's clearance implies these results were acceptable for demonstrating substantial equivalence. The key comparison is between the modified xTAG RVP and the original xTAG RVP, as well as against sequencing for Influenza A H3.
| Analyte | Reported PPA (Modified RVP vs. Original RVP) | Confidence Interval (PPA) | Reported NPA (Modified RVP vs. Original RVP) | Confidence Interval (NPA) | Additional Criteria/Performance (where available) |
|---|---|---|---|---|---|
| Influenza A | 98.09% (154/157) | 94.52%-99.60% | 99.06% (210/212) | 96.63%-99.89% | |
| Influenza A H1 | 100% (4/4) | 39.76%-100.00% | 100% (365/365) | 98.99%-100.00% | |
| Influenza A H3 | 100% (80/80) | 95.49%-100.00% | 85.47% (247/289) | 80.87%-89.32% | PPA for Modified RVP vs. Sequencing: 91.7% (121/132) CI: 87.82%-96.91% |
| Influenza B | 100% (30/30) | 88.43%-100.00% | 100% (339/339) | 98.92%-100.00% | |
| RSV A | 100% (23/23) | 85.18%-100.00% | 99.71% (345/346) | 98.40%-99.99% | |
| RSV B | 96.30% (26/27) | 81.03%-99.91% | 100% (342/342) | 98.93%-100.00% | |
| Parainfluenza 1 | 100% (6/6) | 54.07%-100.00% | 99.72% (362/363) | 98.47%-99.99% | |
| Parainfluenza 2 | 100% (8/8) | 63.06%-100.00% | 99.72% (360/361) | 98.47%-99.99% | |
| Parainfluenza 3 | 100% (24/24) | 85.75%-100.00% | 100% (345/345) | 98.94%-100.00% | |
| hMPV | 96.43% (27/28) | 81.65%-99.91% | 100% (341/341) | 98.92%-100.00% | |
| Rhinovirus | 92.16% (47/51) | 81.12%-97.82% | 99.69% (317/318) | 98.26%-99.99% | |
| Adenovirus | 100% (5/5) | 47.82%-100.00% | 100% (364/364) | 98.99%-100.00% |
2. Sample size used for the test set and the data provenance
- Test Set Sample Size: A total of 369 retrospectively collected left-over clinical samples (nasopharyngeal swabs) were used for the clinical comparison studies (accuracy).
- Data Provenance:
- Country of Origin: The samples were collected from 14 clinical sites in the United States and Canada.
- Retrospective or Prospective: The samples were retrospectively collected (primarily from the 2010-2011 influenza season).
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
The document does not explicitly state the number or qualifications of experts used to establish the ground truth for the clinical comparison test set. The ground truth for direct comparisons between the original and modified RVP was the original RVP's result. For Influenza A H3 subtyping, bi-directional sequencing was used as the ground truth. This process typically involves laboratory personnel but does not necessarily imply "expert" adjudication in the clinical sense with specific qualifications mentioned in the document.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set
The document does not describe an adjudication method involving multiple human readers (e.g., 2+1, 3+1). The primary comparison in the clinical study was between the modified device and the original device, and for Influenza A H3, against sequencing results. This is a direct comparison of assay results, not a process of adjudicating differing human interpretations.
5. 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 conducted. This device is a molecular diagnostic test for detecting viral nucleic acids, not an AI-assisted diagnostic device that a human reader would interpret. Therefore, the concept of "human readers improving with AI vs without AI assistance" is not applicable.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the performance presented in the tables for both the modified and original xTAG RVP are standalone (algorithm only) performances. These are in vitro diagnostic tests, where the instrument and reagents provide a result (qualitative positive/negative), without human interpretive "reading" in the way an imaging study would be read. The comparison to sequencing for Influenza A H3 also represents a standalone assessment against a molecular gold standard.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth used depends on the specific comparison:
- For demonstrating equivalence across most targets: The results from the original xTAG RVP assay served as the comparator (ground truth) for evaluating the modified xTAG RVP's performance.
- For Influenza A H3 subtyping: Bi-directional sequencing was used as the definitive ground truth.
8. The sample size for the training set
The document does not explicitly describe a training set sample size for the device itself. For molecular diagnostic tests, "training" often refers to internal development and optimization by the manufacturer using various known positive and negative controls and clinical samples, rather than a distinct, quantifiable "training set" in the context of machine learning. The focus of this submission is on the performance of a reformulated PCR primer mix and its equivalence to a predicate device, as demonstrated through analytical and clinical comparison studies.
9. How the ground truth for the training set was established
As there is no distinct "training set" explicitly identified or described in the context of machine learning or algorithm development for this molecular diagnostic device in this document, the method for establishing its ground truth is not detailed. The development process would have involved establishing the analytical accuracy of the primers against known viral strains, which would implicitly form the "ground truth" for ensuring the primer mix works as intended.
{0}------------------------------------------------
FEB '1 7 2012
Luminex.
Luminex Molecular Diagnostics
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: K112781
Purpose for Submission: Modification to PCR primer mix of the previously cleared xTAG® RVP (K112199) originally cleared under K063765 to improve reactivity to influenza A/H3 strains.
Measurand: 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 Metapneumovirus, Rhinovirus, and Adenovirus
Type of Test: Qualitative nucleic acid multiplex test
Applicant: Luminex Molecular Diagnostics Inc.
Proprietary and Established Names: xTAG Respiratory Viral Panel (RVP)
Regulatory Information:
| Product Code | Classification | Regulation Section | Review Panel |
|---|---|---|---|
| OCC, OEM,OEP, NSU, JJH | Class II | 21 CFR 866.3980 Respiratory viral panelmultiplex nucleic acid assay | Microbiology(83) |
Intended Use:
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 B, Respiratory Syncytial Virus subtype A, Respiratory Syncytial Virus subtype B, Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 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 laboratory findings.
xTAG RVP can also differentiate the hemagglutinin (HA) gene of some Influenza A subtypes H1 and H3 strains. Differentiation of Influenza A HA subtypes is based on both a positive result for the Influenza A matrix gene and an accompanying positive result for the Influenza A HA subtype H1 (circulating prior to the emergence of 2009 H1N1pdm) or Influenza A HA subtype H3. This device cannot differentiate the Influenza A HA subtype 2009 H1N1pdm by design, and may not be able to differentiate potential newly emerging Influenza A HA subtypes.
{1}------------------------------------------------
Luminex Molecular Diagnostics
Positive results do not rule out bacterial 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.
Negative results do not preclude respiratory virus infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.
The RVP assay cannot adequately detect Adenovirus species C, or serotypes 7a and 41. It is recommended that specimens found to be negative for Adenovirus after examination using RVP be confirmed by an alternate method (e.g., FDA cleared molecular test or cell culture). 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).
Performance characteristics for Influenza A virus were established when Influenza A HA subtype H3, subtype H1 (prior to the emergence of 2009 H1N1pdm), and when subtype 2009 H1N1pdm were the predominant Influenza A 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 conditions for use statement(s): N/A
Special instrument requirements: Luminex 100 or 200 instrument with IS or xPONENT software
Device Description:
The modified RVP is a PCR-based test system for detecting the presence / absence of viral DNA / RNA in clinical specimens. The modified device is the same as the predicate device, except for a reformulation of the PCR primer mix.
Substantial Equivalence Information:
a. Predicate device name(s): xTAG Respiratory Viral Panel
b. Predicate 510(k) number(s): K063765, K081843, K091667 and K112199
c. Comparison with predicate:
The following table compares the modified xTAG Respiratory Viral Panel with the xTAG Respiratory Viral Panel (K063765, K081843, K091667, K112199).
{2}------------------------------------------------
Luminex.
Luminex Molecular Diagnostics
| Item | Modified Device(K112781) | Predicates(K063765, K081483, K091667, K112199) |
|---|---|---|
| xTAG® RVP | 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 array sortingon Luminex 100/200 instrument |
| Detection Method | Fluorescence based | Fluorescence based |
| Quality Control | Internal Control (E. coli phage MS2),Run Control (bacteriophage LambdaDNA), rotating analyte control andnegative controls | Internal Control (E. coli phage MS2) and RunControl (bacteriophage Lambda DNA),rotating analyte control and negative controls |
| Results | Qualitative | Qualitative |
| Instrument | LX100 or LX200 with xMAP system (ISor xPONENT) | LX100 or LX200 with xMAP system (IS orxPONENT) |
| Intended Use | Same as predicate | See above |
| Targets Reported | Influenza A, Influenza A subtype H1,Influenza A subtype H3, Influenza B,Respiratory Syncytial Virus A,Respiratory Syncytial Virus B,Parainfluenza 1, Parainfluenza 2,Parainfluenza 3, HumanMetapneumovirus, Rhinovirus, andAdenovirus | Influenza A, Influenza A subtype H1, InfluenzaA subtype H3, Influenza B, RespiratorySyncytial Virus A, Respiratory Syncytial VirusB, Parainfluenza 1, Parainfluenza 2,Parainfluenza 3, Human Metapneumovirus,Rhinovirus, and Adenovirus |
| Sample Preparation | QIAGEN QIAamp MinElute, BiomérieuxNucliSENS® EasyMag®, and BiomérieuxMiniMag™ | QIAGEN QIAamp MinElute, BiomérieuxNucliSENS® EasyMag®, and BiomérieuxMiniMag™ |
| Amplification Enzyme | xTAG® OneStep Enzyme Mix andancillary reagent TaKaRa Taq™ Hot Start | xTAG® OneStep Enzyme Mix and ancillaryreagent TaKaRa Taq™ Hot Start |
| Primer Mixes | Two primer mixes (1 for PCR and 1 forTSPE). Modified PCR primer mix | Two primer mixes (1 for PCR and 1 for TSPE) |
| Software | xTAG Data Analysis Software RVP (US) | xTAG Data Analysis Software RVP (US) |
| Table 1: Comparison between Modified (New) Device and Predicate |
|---|
| ----------------------------------------------------------------- |
{3}------------------------------------------------
Standards/Guidance Documents referenced (if applicable):
Table 2: 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 |
Table 3: Standards
| StandardsNo. | RecognitionNumber(FDA) | Standards Title | Date | |
|---|---|---|---|---|
| 1 | MM13-A | 7-191 | Collection, Transport, Preparation andStorage of Specimens | 03/18/2009 |
| 2 | MM03-A2 | 7-132 | Molecular Diagnostic Methods for InfectiousDiseases (2nd edition) | 09/09/2008 |
| 3 | EP12-A2 | 7-152 | User Protocol for Evaluation of QualitativeTest Performance (2nd edition) | 09/09/2008 |
| 4 | ISO14971 | 5-40 | Medical devices - Application of riskmanagement to medical devices | 09/12/2007 |
Test Principle:
Same as predicate
Performance Characteristics:
Analytical Performance:
Precision/Reproducibility: Same as predicate.
{4}------------------------------------------------
Image /page/4/Picture/0 description: The image shows the word "Luminex" in a bold, sans-serif font. The word is black and slightly slanted to the right. There is a small dot above the "i" in "Luminex". The word appears to be a logo or brand name.
Luminex Molecular Diagnostics
Limit of Detection (LoD):
The LoD for Influenza A subtype H3 was determined using two strains of influenza A comparing results of the predicate for these analytes to those of the modified device (see Table 4).
| Strain ID | Analyte | Modified xTAG ® RVP | Original xTAG ® RVP | ||
|---|---|---|---|---|---|
| TCID50/mL(atestimatedLoD) | Average MFIfrom 22replicates atLoD | TCID50/mL (atestimatedLoD) | Average MFIfrom 22replicates atLoD | ||
| A/Victoria/3/75 | Flu AMatrix | 0.4768 | 1806.84 | 0.4768 | 1776.05 |
| A/Victoria/3/75 | Flu A H3 | 0.4768 | 974.36 | 7.629 | 1219.64 |
| A/Perth/16/2009 | Flu AMatrix | 0.1347 | 1225.16 | 0.5388* | 2796.07 |
| A/Perth/16/2009 | Flu A H3 | 0.1347 | 706.39 | 8.621 | 1441.16 |
| Table 4: Comparison of (LoD) for Influenza A H3 between Modified and Original RVP | ||
|---|---|---|
*Note: This LoD level was achieved with 22 out of 22 replicates making the correct Flu A Matrix POS call. At 0.1347 TCID30/mL (one dilution below 0.5388 TCID5/mL level), 18 out of 22 replicates made the correct Flu A Matrix POS call with the original xTAG RVP assay. The remaining 4 replicates displayed MFI values of 226, 295, 249, 219, just below the cut-off, thus generating "No Call" results for Flu A Matrix.
In addition, the limit of detection study compared the LoD of the modified xTAG RVP assay with the original xTAG RVP assay for all targets in the RVP panel using one strain for each target (Table 5). For each strain, 20 replicates of the dilutions at the estimated LoD level and at least the two bracketing levels were tested.
{5}------------------------------------------------
Image /page/5/Picture/0 description: The image shows the word "Luminex." in a bold, sans-serif font. The word is black against a white background. There is a dot above the "i" in "Luminex."
| Dilution Levels (L1 andL3 are at 4 fold belowand above theestimated LOD,respectively) | Original xTAG® RVP | Modified xTAG® RVP | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Analyte | Strain ID | TCID50/mL (atestimatedLoD) | Average MFIfrom 20replicates atLoD | No. of POSCalls from 20replicates | TCID50/mL (atestimatedLoD) | Average MFIfrom 20replicates atLoD | No. of POSCalls from 20replicates | ||
| Flu A Matrix | Solomon Island/3/2006 | L1 | 1.91E+00 | 3464.9 | 20 | 1.91E+00 | 2914.9 | 20 | |
| L2 (LOD Level) | 4.77E-01 | 3059.4 | 20 | 4.77E-01 | 2099.6 | 19 | |||
| L3 | 1.19E-01 | 229.8 | 2 | 1.19E-01 | 209.9 | 1 | |||
| Flu A H1 | Solomon Island/3/2006 | L1 | 1.91E+00 | 944.3 | 20 | 1.91E+00 | 721.9 | 19 | |
| L2 (LOD Level) | 4.77E-01 | 857.1 | 20 | 4.77E-01 | 492.9 | 19 | |||
| L3 | 1.19E-01 | 72.7 | 0 | 1.19E-01 | 74.2 | 0 | |||
| Influenza B | Brisbane/33/08 | L1 | 7.82E-01 | 1872.8 | 20 | 7.82E-01 | 2101.9 | 20 | |
| L2 (LOD Level) | 1.96E-01 | 923.9 | 20 | 1.96E-01 | 753.1 | 20 | |||
| L3 | 4.89E-02 | 187.5 | 2 | 4.89E-02 | 206.4 | 2 | |||
| RSV A | Long | L1 | 7.63E-02 | 2473.4 | 20 | 7.63E-02 | 2694.7 | 20 | |
| L2 (LOD Level) | 1.91E-02 | 595.4 | 20 | 1.91E-02 | 595.9 | 20 | |||
| L3 | 4.77E-03 | 159.4 | 0 | 4.77E-03 | 212.3 | 1 | |||
| RSV B | Wash/18537/62 | L1 | 4.88E+00 | 2820.2 | 20 | 4.88E+00 | 3604.8 | 20 | |
| L2 (LOD Level) | 1.22E+00 | 923.5 | 20 | 1.22E+00 | 921.2 | 20 | |||
| L3 | 3.05E-01 | 202.0 | 2 | 3.05E-01 | 337.8 | 12 | |||
| hMPV | CDC Isolate | L1 | 1.60E+00 | 5844.5 | 20 | 1.60E+00 | 6284.475 | 20 | |
| L2 (LOD Level) | 4.00E-01 | 1395.625 | 20 | 4.00E-01 | 1494.4 | 20 | |||
| L3 | 1.00E-01 | 345.5 | 14 | 1.00E-01 | 466.125 | 16 | |||
| Para-1 | C-35 | L1 | 3.91E-01 | 2188.2 | 20 | 3.91E-01 | 2062.5 | 20 | |
| L2 (LOD Level) | 9.77E-02 | 865.7 | 20 | 9.77E-02 | 749.5 | 20 | |||
| L3 | 2.44E-02 | 164.8 | 4 | 2.44E-02 | 240.9 | 6 | |||
| Para-2 | Greer | L1 | 7.63E-01 | 5113.1 | 20 | 7.63E-01 | 5889.8 | 20 | |
| L2 (LOD Level) | 1.91E-01 | 4238.5 | 20 | 1.91E-01 | 5340.9 | 20 | |||
| L3 | 4.77E-02 | 467.0 | 14 | 4.77E-02 | 675.3 | 15 | |||
| Para-3 | Zeptometrix 0810016CF | L1 | 1.00E+01 | 3206.1 | 20 | 1.00E+01 | 2524.6 | 20 | |
| L2 (LOD Level) | 2.51E+00 | 729.5 | 20 | 2.51E+00 | 1148.5 | 20 | |||
| L3 | 6.27E-01 | 38.8 | 0 | 6.27E-01 | 8.3 | 0 | |||
| Adenovirus | Type 1 | L1 | 4.07E+01 | 1272.1 | 20 | 4.07E+01 | 737.8 | 20 | |
| L2 (LOD Level) | 1.02E+01 | 494.1 | 20 | 1.02E+01 | 468.3 | 19 | |||
| L3 | 2.54E+00 | 193.6 | 2 | 2.54E+00 | 158.6 | 0 | |||
| Rhinovirus | Type 54 | L1 | 3.00E-02 | 3052.7 | 20 | 3.00E-02 | 3773.0 | 20 | |
| L2 (LOD Level) | 7.50E-03 | 1006.6 | 20 | 7.50E-03 | 1387.2 | 20 | |||
| L3 | 1.88E-03 | 399.6 | 13 | 1.88E-03 | 366.3 | 13 |
Table 5: Summary of Limit of Detection (LoD) for the non-H3 Targets
The results from this LoD study indicate that the modified xTAG® RVP is equivalent to that of the original xTAG® RVP for all target calls.
Carryover Contamination Limit of Blank (LoB): Same as predicate
Analytical Specificity (Reactivity, Cross-Reactivity and Competitive Inhibition):
A total of 48 potentially cross-reactive pathogens (bacterial and viral) were assessed in replicates with RVP. Each replicate underwent a single EasyMag (bioMerieux NucliSENS ) extraction prior to testing.
{6}------------------------------------------------
Image /page/6/Picture/0 description: The image shows the word "Luminex." in a bold, sans-serif font. Below the word "Luminex" is the phrase "Luminex Molecular Diagnostics" in a smaller, regular font. The text is black against a white background.
Table 6: Bacterial pathogens assessed as potential cross-reactive species in the RVP Assay
| Organism | Strain | TiterTested | TiterUnits | Flu A matrix | Flu A H1 | Flu A H3 | Flu B | Para 1 | Para 2 | Para 3 | RSV A | RSV B | Rhinovirus | Metapneumovirus | Adenovirus |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Bordetella pertussis | NEQAS 1505 | 13.66 | Ct* | - | - | - | - | - | - | - | - | - | - | - | - |
| Corynebacterium glutamicum | Type strain 534 [NCIB10025] | $6.00 \times 10^8$ | cfu/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Escherichia coli | ATCC 8739 | $5.60 \times 10^8$ | cfu/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Haemophilus influenzae | Type b (Zeptometrix0801680) | $2.63 \times 10^8$ | cfu/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Lactobacillus casei | 03 [7, IAM 12473, Orland L-323, R.P. Tittsler 303] | $6.00 \times 10^8$ | cfu/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Legionella pneumophila | ATCC 33152 | 15.42 | Ct* | - | - | - | - | - | - | - | - | - | - | - | - |
| Moraxella (Branhamella)catarrhalis | Ne 11 | $5.00 \times 10^4$ | cfu/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Mycobacterium avium subsp.avium | ATCC 15769 | $2.50 \times 10^4$ | cfu/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Mycobacterium intracellulare | ATCC 13209 | $2.50 \times 10^4$ | cfu/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Mycoplasma pneumoniae | M129 | $5.63 \times 10^6$ | TCID50/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Neisseria elongata subsp.elongata | NCTC 10660 | $2.50 \times 10^4$ | cfu/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Neisseria meningitides | Zeptometrix 0801511 | $3.37 \times 10^8$ | cfu/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Pseudomonas aeruginosa | ATCC15442 | $4.00 \times 10^8$ | cfu/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Staphylococcus aureus | Zepto 0801638 | $4.00 \times 10^8$ | cfu/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Staphylococcus epidermidis | ATCC 12228 | $4.00 \times 10^8$ | cfu/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Streptococcus pneumoniae | Type 59 | 15.95 | Ct | - | - | - | - | - | - | - | - | - | - | - | - |
| Streptococcus pyogenes | ATCC 51500 | $2.0 \times 10^8$ | cfu/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Streptococcus salivarius | 75 [NCTC 8618] | $6.00 \times 10^8$ | cfu/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Analyte, Results Positive (+) or Negative (-) forReactivity | |||||||||||||||
| Organism | Strain | TiterTested | TiterUnits | Flu A matrix | Flu A H1 | Flu A H3 | Flu B | Para 1 | Para 2 | Para 3 | RSV A | RSV B | Rhinovirus | Metapneumovirus | Adenovirus |
| Flu A H1 (Seasonal) | A/New Caledonia/20/99 | 5.00 x 10³ | TCID50/mL | + | + | - | - | - | - | - | - | - | - | - | - |
| Influenza B | B/Russia/69 | 3.16 x 106 | TCID50/mL | - | - | - | + | - | - | - | - | - | - | - | - |
| Influenza B | B/Mass/3/66 | 3.16 x 102 | TCID50/mL | - | - | - | + | - | - | - | - | - | - | - | - |
| Parainfluenza 1 | C-35 | 1.58 x 105 | TCID50/mL | - | - | - | - | + | - | - | - | - | - | - | - |
| Parainfluenza 2 | Greer | 5.00 x 105 | TCID50/mL | - | - | - | - | - | + | - | - | - | - | - | - |
| Parainfluenza 3 | C-243 | 5.00 x 104 | TCID50/mL | - | - | - | - | - | - | + | - | - | - | - | - |
| Parainfluenza 4A | Unknown | 4.17 x 105 | TCID50/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Parainfluenza 4B | Unknown | 2.45 x 105 | TCID50/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| RSV A | Long | 5.00 x 104 | TCID50/mL | - | - | - | - | - | - | - | + | - | - | - | - |
| RSV B | Wash/18537/62 | 1.00 x 104 | TCID50/mL | - | - | - | - | - | - | - | - | + | - | - | - |
| Enterovirus (Echo 13) | Del Carmen | 5.00 x 107 | TCID50/mL | - | - | - | - | - | - | - | - | - | + | - | - |
| Enterovirus (Coxsackie B) | Unknown | 5.00 x 106 | TCID50/mL | - | - | - | - | - | - | - | - | - | + | - | - |
| Enterovirus Type 68 | Fermon | 1.00 x 106 | TCID50/mL | - | - | - | - | - | - | - | - | - | + | - | - |
| Enterovirus Type 69 | Toluca-1 | 2.00 x 104 | TCID50/mL | - | - | - | - | - | - | - | - | - | + | - | - |
| Rhinovirus | Strain 1A | 1.26 x 105 | TCID50/mL | - | - | - | - | - | - | - | - | - | + | - | - |
| Rhinovirus | Type 60 | 5.00 x 107 | TCID50/mL | - | - | - | - | - | - | - | - | - | + | - | - |
| HMPV | CAN97-83 (CDC Isolate26583) | 5.00 x 103 | TCID50/mL | - | - | - | - | - | - | - | - | - | - | + | - |
| Adenovirus | Type 1, Adenoid 71 | 5.00 x 105 | TCID50/mL | - | - | - | - | - | - | - | - | - | - | - | + |
| Adenovirus | Type 1 | 4.17 x 106 | TCID50/mL | - | - | - | - | - | - | - | - | - | - | - | + |
| Adenovirus | Type 7A | 5.37 x 106 | TCID50/mL | - | - | - | - | - | - | - | - | - | - | - | + |
| Coronavirus 229E | 229E | 5.00 x 106 | TCID50/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Coronavirus NL63 | NL63 | 5.00 x 106 | TCID50/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Coronavirus OC43 | OC43 | 5.00 x 106 | TCID50/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Varicella Zoster virus | Isolate A | 1.86 x 104 | TCID50/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Measles virus | Unknown | 1.26 x 106 | TCID50/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Cytomegalovirus | AD-169 | 9.55 x 106 | TCID50/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Epstein-Barr virus | B95-8 | 3.00 x 109 | cp/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Mumps virus | N/A (Zeptometrix) | 7.57 x 104 | TCID50/mL | - | - | - | - | - | - | - | - | - | - | - | - |
| Mumps virus | N/A (Cultured fromparotid swab) | 16.36 | Ct | - | - | - | - | - | - | - | - | - | - | - | - |
| Herpes simplex virus | McIntyre | 1.45 x 1010 | TCID50/mL | - | - | - | - | - | - | - | - | - | - | - | - |
These bacterial pathogens did not cross-react or interfere with any viral target probed by RVP in either the original or modified device.
{7}------------------------------------------------
Image /page/7/Picture/0 description: The image shows the word "Luminex." in bold, black font. The font is sans-serif and the letters are closely spaced together. The word is positioned at the top of the image and is the main focus.
Table 7: Viral pathogens assessed as potential cross-reactive species in the RVP Assay
The original and modified xTAG RVP assays did not generate non-specific positive calls for these viral strains with the following exceptions (where a contaminated sample is suspected in each instance since the result was observed in both the original and modified devices): Flu A H1 (Seasonal) demonstrated some signal for the run control near the cutoff (lambdoid DNA);
{8}------------------------------------------------
Luminex.
Luminex Molecular Diagnostics
Parainfluenza 3 demonstrated a low-level influenza A signal; Enterovirus (Echo 13) and Enterovirus (Coxsackie B) showed an Adenovirus signal; and Adenovirus (Type 1. Adenoid 71) showed an H3 (but not influenza A matrix) signal.
For the reactivity study, the initial stocks were diluted to approximately 2x to 3x the LoD established for the two reference strains in the LoD study. At least three replicates per strain were evaluated starting from the extraction step with both original and modified xTAG `RVP assays. Both were able to successfully detect all five H3 strains tested (see Table 8).
Table 8: Influenza A Subtype H3 Strains Tested in the Reactivity Study
| A/Port Chalmers/1/73 |
|---|
| A/Hong Kong/8/68 |
| A2/Aichi2/68 |
| A/Alice |
| MRC2 |
The following four additional strains were identified from the clinical sample data set in the accuracy study (Table 9).
Table 9: Influenza A Subtype H3 Strains Tested in the Accuracy Study
| A/District of Columbia/WRAIR0301/2010(H3N2) |
|---|
| A/Texas/NHRC0001/2011(H3N2) |
| A/South Carolina/AF2724/2011(H3N2) |
| A/lasi/47326/2010(H3N2) |
Eight additional strains representing other cleared analytes were tested in the analytical reactivity study (Table 10). The initial stocks were diluted to approximately 3 times the LoD established for reference strains. Three replicates per strain were evaluated with both original and modified xTAG RVP assays. Both devices were able to successfully detect all eight strains tested.
| Flu A H1 | A/New Caledonia/20/99(H1N1) |
|---|---|
| Flu B | B/Malaysia/2506/04 |
| RSV A | AUS/A2/61 |
| RSV B | B WV/14617/'85 |
| Parainfluenza 3 | C-243 |
| Rhinovirus | Type 39 |
| hMPV | Type 8, strain Peru6-2003 B2 |
| Adenovirus | Type 3 |
Table 10: Additional Strains Tested in the Reactivity Study
{9}------------------------------------------------
Luminex Molecular Diagnostics
Competitive Inhibition Study
The combinations of analytes tested in the competitive inhibition study are listed in Table 11. Each analyte was tested at two different concentrations, High Positive (HP, approximately at 1.3 to 4-fold dilution of the original stock) and Low Positive (LP, approximately at 2 to 4 times LoD for that analyte). The results show that the modifications made to the device did not inhibit the detection of the competing analytes. The performance of the Original and Modified devices was equivalent. All expected positive calls were present.
| Count | Analyte 1 | Concentration | Analyte 2 | Concentration |
|---|---|---|---|---|
| 1 | Flu A H3, strainA/Victoria/3/75 | HP | RSV A, strain Long | LP |
| 2 | Flu A H3, strainA/Victoria/3/75 | LP | RSV A, strain Long | HP |
| 3 | Flu A H3, strainA/Victoria/3/75 | HP | RSV B, strainWash/18537/62 | LP |
| 4 | Flu A H3, strainA/Victoria/3/75 | LP | RSV B, strainWash/18537/62 | HP |
| 5 | Flu A H3, strainA/Victoria/3/75 | HP | Rhinovirus, Type54 | LP |
| 6 | Flu A H3, strainA/Victoria/3/75 | LP | Rhinovirus, Type54 | HP |
| 7 | Flu A H3, strainA/Victoria/3/75 | HP | hMPV 5, Peru3-2003 B1 | LP |
| 8 | Flu A H3, strainA/Victoria/3/75 | LP | hMPV 5, Peru3-2003 B1 | HP |
| 9 | Flu A H3, strainA/Victoria/3/75 | HP | Adenovirus, Type1 | LP |
| 10 | Flu A H3, strainA/Victoria/3/75 | LP | Adenovirus, Type1 | HP |
Table 11. Analyte Combinations Tested in the Competitive Inhibition Study
No differences between the modified and the original xTAG "RVP were observed in reactivity, cross-reactivity or competitive inhibition studies.
Clinical Comparison Studies (Accuracy)
The accuracy study evaluated the positive agreement and negative agreement between the original and modified xTAG RVP devices. Table 12 shows the list of analytes tested by both the original and modified xTAG RVP Assays.
{10}------------------------------------------------
Table 12: Analytes Tested
| Human Influenza A |
|---|
| Human H1 seasonal subtype of Influenza A |
| Human H3 subtype of Influenza A |
| Influenza B |
| RSV A |
| RSV B |
| Human Metapneumovirus |
| Rhinovirus / Enterovirus |
| Parainfluenza 1 |
| Parainfluenza 2 |
| Parainfluenza 3 |
| Adenovirus |
A total of 369 retrospectively collected left-over clinical samples (nasopharyngeal swabs) obtained primarily from the 2010-2011 influenza season were collected from 14 clinical sites in the United States and Canada. To preserve the confidentiality of the subjects, clinical specimens were individually numbered so the identity of the subject could not be readily ascertained by the investigator or any other individual associated with the study. Nucleic acid extraction was performed either by the clinical site or at Luminex Molecular Diagnostics (LMD), using one of the following methods: BioMerieux EasyMAG, BioMerieux MiniMAG or QIAGEN MinElute Viral Spin Kit, as directed in the instructions for use of the original device. Extracted samples were stored frozen at a temperature of -70℃ until used in the study.
All Flu A matrix positive samples (158) from either the original or modified xTAG "RVP device were bi-directionally sequenced for Flu A subtype H3. 132 of the 158 samples were found to be Flu A H3 sequence positive (see Table 13), leaving 26 samples that were Flu A H3 sequence negative. Four out of these 26 Flu A H3 sequencing negative samples were H1 positive by both the original RVP and the modified RVP assays. Three samples out of the 26 did not have adequate sample left over and therefore could not be sequenced. The remaining 19 samples (4+3+19=26) were sequenced with an in-house designed set of 2009 H1N1pdm primers and the majority of these samples (13) were 2009 H1N1pdm positive.
| 95% CI | |||
|---|---|---|---|
| Sequencing POS for H3 | 132 Samples | ||
| Modified xTAG® RVP POS | 121 Samples | Lower | Upper |
| Percent Positive Agreement(TP/TP+FN) | 121/132=91.7% | 87.82% | 96.91% |
Table 13: Positive agreement for Influenza A H3 Target. Modified xTAG RVP against Sequencing
Positive agreement and negative agreement for each analyte were evaluated between the original and modified xTAG RVP devices (see Table 14).
{11}------------------------------------------------
Image /page/11/Picture/0 description: The image shows the logo for Luminex Molecular Diagnostics. The word "Luminex" is in a bold, sans-serif font, with a black dot above the "i". Below the word "Luminex" is the text "Luminex Molecular Diagnostics" in a smaller, regular font. The logo is simple and professional, and it is likely used to represent the company in its marketing and branding materials.
| Analyte | PositivePercentAgreement(PPA) | Confidence Interval | NegativePercentAgreement(NPA) | Confidence Interval |
|---|---|---|---|---|
| Influenza A | 98.09%(154/157) | 94.52%-99.60% | 99.06%(210/212) | 96.63%-99.89% |
| Influenza A H1 | 100%(4/4) | 39.76% - 100.00% | 100%(365/365) | 98.99% - 100.00% |
| Influenza A H3 | 100%(80/80) | 95.49%-100.00% | 85.47%(247/289) | 80.87%-89.32% |
| Influenza B | 100%(30/30) | 88.43% - 100.00% | 100%(339/339) | 98.92% - 100.00% |
| RSV A | 100%(23/23) | 85.18% - 100.00% | 99.71%(345/346) | 98.40%-99.99% |
| RSV B | 96.30%(26/27) | 81.03%-99.91% | 100%(342/342) | 98.93% - 100.00% |
| Parainfluenza 1 | 100%(6/6) | 54.07% - 100.00% | 99.72%(362/363) | 98.47%-99.99% |
| Parainfluenza 2 | 100%(8/8) | 63.06% - 100.00% | 99.72%(360/361) | 98.47%-99.99% |
| Parainfluenza 3 | 100%(24/24) | 85.75% - 100.00% | 100%(345/345) | 98.94% - 100.00% |
| hMPV | 96.43%(27/28) | 81.65%-99.91% | 100%(341/341) | 98.92% - 100.00% |
| Rhinovirus | 92.16%(47/51) | 81.12%-97.82% | 99.69%(317/318) | 98.26%-99.99% |
| Adenovirus | 100%(5/5) | 47.82% - 100.00% | 100%(364/364) | 98.99% - 100.00% |
Table 14: Clinical Comparison of Modified xTAG® RVP and Original xTAG® RVP
Clinical Cut-off: Not applicable.
Expected values/ reference range: Not applicable.
{12}------------------------------------------------
Image /page/12/Picture/1 description: The image shows the logo for the Department of Health & Human Services (HHS). The logo consists of a stylized depiction of an eagle or bird-like figure with outstretched wings, rendered in black. The bird is positioned to the right of a circular border containing the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" in a sans-serif font. The text is arranged around the circumference of the circle, with the bird figure centered within the circle's right side.
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. M5G 1Y8. CANADA
FEB 1 7 2012
Re: K112781
. Trade Name: xTAG®Respiratory Viral Panel (RVP) Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory Viral Panel Multiplex Nucleic Acid Assay Regulatory Class: Class II Product Code: OCC, OEM, OEP, NSU, JJH Dated: December 19, 2011 Received: December 22, 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 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 - Lubna Syed
will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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 vours.
Uve Saf for
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): K112781
xTAG® Respiratory Viral Panel (RVP) Device Name:
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 B, Respiratory Syncytial Virus subtype A. Respiratory Syncytial Virus subtype B. Parainfluenza 1. Parainfluenza 2. and Parainfluenza 3 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 laboratory findings.
xTAG RVP can also differentiate the hemagglutinin (HA) gene of some Influenza A subtypes H1 and H3 strains. Differentiation of Influenza A HA subtypes is based on both a positive result for the Influenza A matrix gene and an accompanying positive result for the Influenza A HA subtype HI (circulating prior to the emergence of 2009 HIN1pdm) or Influenza A HA subtype H3. This device cannot differentiate the Influenza A HA subtype 2009 H1N1pdm by design, and may not be able to differentiate potential newly emerging Influenza A HA subtypes.
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.
Negative results do not preclude respiratory virus infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.
The RVP assay cannot adequately detect Adenovirus species C, or serotypes 7a and 41. It is recommended that specimens found to be negative for Adenovirus after examination using RVP be confirmed by an alternate method (e.g., FDA cleared molecular test or cell culture). 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).
Performance characteristics for Influenza A virus were established when Influenza A-HA subtype H3, subtype H1 (prior to the emergence of 2009 H1N1pdm), and when subtype 2009 H1N1pdm were the predominant Influenza A 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.
{15}------------------------------------------------
Prescription Use __ X (Part 21 CFR 801 Subpart D)
Over-The-Counter Use AND/OR (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
Taruna Feldble
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K112781
§ 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.