(176 days)
The Accula RSV Test performed on the Accula Dock is a molecular in vitro diagnostic test utilizing polymerase chain reaction (PCR) and lateral flow technologies for the qualitative, visual detection of respiratory syncytial virus (RSV) viral RNA. The Accula RSV Test uses a nasal swab specimen collected from patients with signs and symptoms of respiratory infection. The Accula RSV Test is intended as an aid in the diagnosis of RSV infection in children and adults in conjunction with clinical and epidemiological risk factors.
Negative results do not preclude RSV virus infection and should not be used as the sole basis for treatment or other patient management decisions.
The Accula RSV Test is a semi-automated, colorimetric, multiplex reverse-transcription polymerase chain reaction (RT-PCR) nucleic acid amplification test to qualitatively detect respiratory syncytial virus (RSV) viral RNA from unprocessed nasal swabs that have not undergone prior nucleic acid extraction. The system integrates nucleic acid extraction, reverse transcription, a novel Mesa Biotech PCR nucleic acid amplification technology named OscARTM, and hybridization-based visual detection into a completely self-contained and automated system. The Accula RSV system consists of a small reusable Dock to drive the automated testing process, and a single-use disposable test cassette that contains all the enzymes and reagents.
Accula RSV Test - Acceptance Criteria and Performance Study Analysis
This document outlines the acceptance criteria and the performance of the Accula RSV Test based on the provided 510(k) summary (K181443).
1. Table of Acceptance Criteria and Reported Device Performance
The 510(k) summary primarily focuses on clinical performance characteristics and analytical performance rather than explicitly stating pre-defined "acceptance criteria" numerical targets in the same way a device specification might. However, based on the studies conducted, the implicit acceptance criteria are that the device demonstrates comparable or superior performance to the FDA-cleared predicate device and meets predefined thresholds for analytical validity.
Here's a summary of the observed performance:
| Acceptance Criteria Category (Implicit) | Specific Performance Metric | Stated Acceptance Criteria (Implicit from Context) | Reported Device Performance | Study Type |
|---|---|---|---|---|
| Clinical Performance | Sensitivity (vs. FDA-cleared molecular comparator) | High sensitivity, comparable to predicate | 90.2% (95% CI: 84.2% - 94.1%) | Prospective Clinical Study |
| Specificity (vs. FDA-cleared molecular comparator) | High specificity, comparable to predicate | 95.6% (95% CI: 93.6% - 97.1%) | Prospective Clinical Study | |
| Reproducibility | Inter-site, inter-operator, intra-run agreement for Low Positive, Moderate Positive, and Negative samples | High agreement (e.g., >95%) | 100% agreement across all sites, operators, and days for all sample types | Reproducibility Studies |
| Limit of Detection (LoD) | Ability to consistently detect RSV at low concentrations | At least 19/20 positive results at the LoD level | 19/20 to 20/20 positive results for various RSV strains at specified LoD levels | Limit of Detection |
| Analytical Reactivity (Inclusivity) | Detection of various RSV-A and RSV-B subtypes | 100% detection of tested RSV strains at 2X LoD | 100% detection (3/3) for all 9 tested RSV strains | Analytical Reactivity |
| Analytical Specificity (Cross-Reactivity) | No false positives with common respiratory pathogens and flora | 0/3 RSV positive results for all tested non-RSV organisms | 0/3 RSV positive results for all 41 tested organisms | Analytical Specificity |
| Interfering Substances | No negative impact from common interfering substances | 100% agreement with expected results in presence of interferents | 100% agreement with expected results for all tested interferents | Interfering Substances |
| Performance Near Cut-off (Untrained Users) | Consistent detection of low positive samples by untrained users | High agreement (e.g., >95%) | 100% agreement for Low Positive and True Negative samples across all sites | Near-Cutoff Study (CLIA Waiver) |
2. Sample Size Used for the Test Set and Data Provenance
-
Clinical Performance Test Set:
- Sample Size: 694 evaluable specimens (out of 749 subjects enrolled).
- Data Provenance: Prospective clinical study conducted in the U.S. during the 2017-2018 RSV season. Specimens were collected from patients presenting at ten investigational sites with RSV-like symptoms.
-
Reproducibility Test Set:
- Sample Size: For each sample type (RSV Negative, RSV Low Positive, RSV Moderate Positive), there were 30 observations per site (2 operators x 1 run x 3 swabs x 5 non-consecutive days). With 4 sites, this totals approximately 120 observations per sample type.
- Data Provenance: Contrived nasal swabs tested at three CLIA-waived sites and one moderately complex site based in the United States.
-
Limit of Detection Test Set:
- Sample Size: 20 replicates for each virus strain and concentration tested.
- Data Provenance: Contrived samples prepared by spiking RSV strains into a pooled negative clinical matrix.
-
Analytical Reactivity Test Set:
- Sample Size: 3 replicates for each of the 9 RSV strains.
- Data Provenance: Contrived samples prepared by diluting virus in pooled clinical matrix and spiking onto a swab.
-
Analytical Specificity Test Set:
- Sample Size: 3 replicates for each of the 41 potentially cross-reacting organisms.
- Data Provenance: Contrived samples prepared by diluting organisms in a clinical matrix.
-
Interfering Substances Test Set:
- Sample Size: 3 replicates for two RSV strains (RSV A2, RSV B1) with each of the 13 interfering substances, plus negative controls.
- Data Provenance: Contrived samples with virus diluted into pooled negative clinical matrix and interfering substances added.
-
Near-Cutoff Study Test Set (CLIA Waiver):
- Sample Size: 60 samples per site (30 replicates of RSV Low Positive, 30 replicates of True Negative). With 3 sites, total of 180 samples.
- Data Provenance: Contrived samples (RSV Low Positive spiked into negative clinical matrix; True Negative from negative clinical matrix with no RSV virus) handled by untrained intended operators at three CLIA-waived sites in the U.S.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The 510(k) summary does not explicitly state the number or specific qualifications of experts used to establish the ground truth.
For the primary clinical performance comparison, the ground truth was established by:
- A FDA-cleared molecular RSV assay as the initial comparator method.
- An alternative FDA-cleared molecular RSV assay used to resolve all discrepant results (e.g., false positives and false negatives from the initial comparison).
This approach relies on the established accuracy of commercially available and FDA-cleared molecular assays as the "expert" or gold standard for diagnostic truth.
4. Adjudication Method for the Test Set
For the prospective clinical study:
- The Accula RSV Test results were compared to a primary FDA-cleared molecular comparator.
- All discrepant results between the Accula RSV Test and the primary comparator were adjudicated using an alternative FDA-cleared molecular RSV assay at a reference laboratory. This serves as a 2+1 adjudication method, where the two molecular assays determine the final truth.
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 done.
This device, the Accula RSV Test, is a semi-automated, colorimetric nucleic acid amplification test for the qualitative detection of RSV viral RNA. It is a diagnostic test where the result (presence or absence of colored lines on a test strip) is visually interpreted directly by a human, but the "reading" is of a molecular reaction, not an image requiring nuanced expert interpretation. The provided studies focus on the analytical and clinical accuracy of the device itself and its agreement with established molecular methods, and its reproducibility across different users and sites (including untrained users in the CLIA waiver study). There is no "AI assistance" component to human readers, as the output is a direct visual detection by a human of the test strip post-reaction, not an interpretation of complex data or images aided by AI.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the primary clinical and analytical performance studies can be considered standalone performance for the device's diagnostic capability.
While the final interpretation of the colored lines is visual (human-in-the-loop for reading the result), the underlying molecular amplification and detection mechanism (OscAR™ technology, hybridization-based visual detection) operates as a standalone algorithm/system to determine the presence or absence of RSV RNA. The "Performance Near the Cut-off" study with untrained users further investigates the robustness of this standalone performance even when subjected to diverse human operation, demonstrating that the device consistently performs at the Limit of Detection. The analytical studies (LoD, inclusivity, cross-reactivity, interfering substances) also represent standalone performance of the test's ability to detect or not detect specific targets under controlled conditions.
7. The Type of Ground Truth Used
The ground truth for the clinical performance evaluation was established using FDA-cleared molecular RSV assays. Specifically:
- An initial FDA-cleared molecular RSV assay as the primary comparator.
- An alternative FDA-cleared molecular RSV assay for adjudication of discrepant results.
For analytical studies (LoD, inclusivity, cross-reactivity, interfering substances, reproducibility, near-cutoff), the ground truth was based on known spiked concentrations of purified RSV virus strains or other organisms in a negative clinical matrix.
8. The Sample Size for the Training Set
The 510(k) summary does not explicitly describe a separate "training set" in the context of machine learning model development. This is typical for traditional in vitro diagnostic devices like the Accula RSV Test, which rely on established biochemical and molecular principles rather than AI/ML algorithms that require large training datasets.
The development and optimization of the Accula RSV Test (e.g., reagent concentrations, reaction conditions, LoD determination) would have involved extensive laboratory experimentation and optimization, which could be conceptually seen as internal "training" or development phases, but these are not datasets reported in the same way as a machine learning training set for regulatory submission.
9. How the Ground Truth for the Training Set Was Established
As noted above, a distinct "training set" for an AI/ML model is not described in this 510(k) summary. The ground truth for the analytical and clinical validation studies (which support the device's claims) was established as described in section 7:
- For clinical performance: FDA-cleared molecular RSV assays.
- For analytical performance: known spiked concentrations of purified virus/organisms.
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510(k) Summary
This 510(k) summary of safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned 510(k) number is: K181443
| 1. | Sponsor/Applicant Name and Address | ||
|---|---|---|---|
| Company Name: | Mesa Biotech, Inc. | ||
| Address: | 6190 Cornerstone Court, Suite 220 | ||
| San Diego, CA 92121 | |||
| Telephone: | 858-800-4929 | ||
| Contact Person: | Barbara Stevens | ||
| Regulatory Consultant | |||
| Date Summary Prepared: | 05/25/2018 | ||
| 2. | Device Name and Classification | ||
| Trade Name: | Accula RSV Test | ||
| Classification of Device: | 21 CFR 866.3980, Respiratory viralpanel multiplex nucleic acid assay | ||
| Product Code | OCC |
3. Predicate Device
K161375, Alere i RSV Assay
4. Device Description
Operating Principle
The Accula RSV Test is a semi-automated, colorimetric, multiplex reverse-transcription polymerase chain reaction (RT-PCR) nucleic acid amplification test to qualitatively detect respiratory syncytial virus (RSV) viral RNA from unprocessed nasal swabs that have not undergone prior nucleic acid extraction. The system integrates nucleic acid extraction, reverse transcription, a novel Mesa Biotech PCR nucleic acid amplification technology named OscARTM, and hybridization-based visual detection into a completely self-contained and automated system. The Accula RSV system consists of a small reusable Dock to drive the automated testing process, and a single-use disposable test cassette that contains all the enzymes and reagents.
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RSV Kit Contents
The Accula RSV Test Kit contains all the materials needed to run a test, except for the Accula Dock, which is provided separately. The Accula RSV Test Kit contains the following components.
- Puritan Rayon Swabs for nasal swab collection (25) ●
- Accula Nasal Swab Buffer (25)
- Accula Transfer Pipettes (25)
- Accula RSV Test Cassettes (25)
- RSV Positive Control Swab (1)
- Negative Control Swab (1)
- Instructions for Use
- Quick Reference Guide
Indications for Use 5.
The Accula RSV Test performed on the Accula Dock is a molecular in vitro diagnostic test utilizing polymerase chain reaction (PCR) and lateral flow technologies for the qualitative, visual detection of respiratory syncytial virus (RSV) viral RNA. The Accula RSV Test uses a nasal swab specimen collected from patients with signs and symptoms of respiratory infection. The Accula RSV Test is intended as an aid in the diagnosis of RSV infection in children and adults in conjunction with clinical and epidemiological risk factors.
Negative results do not preclude RSV virus infection and should not be used as the sole basis for treatment or other patient management decisions.
6. Comparison to Predicate Device
The following table provides a comparison of the characteristics of the Accula RSV Test to the predicate device, the Alere i RSV assay.
| Item | 510(k) Device:Mesa BiotechAccula RSV Test | Predicate Device:Alere i RSV(K161375) |
|---|---|---|
| Indications for Use | The Accula RSV Testperformed on the Accula Dockis a molecular in vitrodiagnostic test utilizingpolymerase chain reaction(PCR) and lateral flowtechnologies for thequalitative, visual detection ofrespiratory syncytial virus(RSV) viral RNA. The AcculaRSV Test uses a nasal swabspecimen collected from | The Alere i RSV assayperformed on the Alere iInstrument is a rapid,molecular, in vitro diagnostictest utilizing an isothermalnucleic acid amplificationtechnology for the qualitativedetection of respiratorysyncytial virus (RSV) viralRNA in direct nasopharyngealswabs and nasopharyngealswabs eluted in viral transport |
| patients with signs andsymptoms of respiratoryinfection. The Accula RSVTest is intended as an aid in thediagnosis of RSV infection inchildren and adults inconjunction with clinical andepidemiological risk factors.Negative results do notpreclude RSV virus infectionand should not be used as thesole basis for treatment orother patient managementdecisions. | media from patients with signsand symptoms of respiratoryinfection. It is intended for useas an aid in the diagnosis ofRSV in children < 18 years andadults > 60 years inconjunction with clinical andepidemiological risk factors. | |
| Assay Targets | Respiratory syncytial virus | Respiratory syncytial virus |
| Sample Type | Nasal swab | Nasopharyngeal swab |
| Assay Results | Qualitative | Qualitative |
| Intended Users andUse Locations | Clinical lab and point of care | Clinical lab and point of care |
| Nucleic AcidPurification | No | No |
| RSV Target | L viral polymerase gene | NS2 gene and nucleocapsidgene N |
| Internal Control | Yes | Yes |
| Positive andNegative ControlSwabs | Yes | Yes |
| Assay Technology | PCR amplification and visualidentification of amplificationproducts by hybridization to atest strip. | Isothermal nucleic acidamplification and detection ofspecific amplification productsusing molecular beacon probes |
| Detection | Multiplex assay using dyedmicroparticle conjugates tospecifically detect and identifyamplification reactionproducts. | Multiplex assay usingfluorescently-labeledmolecular beacons tospecifically identify amplifiedRNA targets. |
| Visual interpretation of thepresence or the absence ofcolored lines on a test strip. | Optical detection offluorescence | |
| Instrument | Amplification controlled bythe Accula Dock.No detection by theinstrument. | Amplification and detectionperformed on the Alere iinstrument |
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Performance Summary 7.
Expected Values
The prevalence of respiratory syncytial virus (RSV) varies from year to year, with outbreaks occurring during the fall and winter months. The RSV positivity rate is dependent upon many factors, including specimen collection, test method, and geographic location. Prevalence varies throughout the RSV season and from location to location.
The Accula RSV prospective clinical study was conducted during the 2017-2018 RSV season. The following table shows the prevalence of RSV observed in three subject age categories.
| Prospective Clinical Study during the 2017/2018 RSV Season | |||
|---|---|---|---|
| Age Group | Number of NasalSwab Specimens | Number of RSVPositives | RSV Positivity Rate |
| ≤ 5 Years of Age | 371 | 134 | 36.1% |
| 6 to 18 Years of Age | 134 | 9 | 6.7% |
| ≥ 19 Years of Age | 189 | 10 | 5.3% |
| Total | 694 | 153 | 22.0% |
Prospective Clinical Study: Accula™ RSV Test vs. a FDA-Cleared Molecular RSV Assav:
Clinical performance characteristics of the Accula RSV Test were evaluated in a multi-site prospective study during the 2017-2018 RSV seasons in the U.S. A total of ten investigational sites participated in the study. To be enrolled in the study, patients had to be presenting at the participating study centers with RSV-like symptoms. Two nasal swabs were collected, one from each nostril, from each subject using standard collection methods. One nasal swab was eluted in 5 mL of Accula Nasal Swab Buffer and tested with the Accula RSV Test according to the product instructions. The other nasal swab was eluted with 3 mL universal transport media (UTM) and transported to a central reference laboratory for testing using the comparator method. All discrepant results were analyzed using an alternative FDA-cleared molecular assay at the reference laboratory.
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A total of 749 subjects were enrolled in this study. Of those, 55 specimens are unevaluable (i.e. failed to meet inclusion/exclusion criteria, were not transported to the reference laboratory per the conditions required by the clinical protocol, had an invalid result for the comparative method, or had two invalid results on the Accula RSV Test. A total of 694 specimens were considered evaluable. The performance of the Accula RSV Test for RSV as compared to a FDA-cleared molecular comparator is presented in the table below.
| Accula RSVTest | Comparator | Positive | Negative | Total | |
|---|---|---|---|---|---|
| Positive | 129 | 24a | 153 | ||
| Negative | 14b | 527 | 541 | ||
| Total | 143 | 551 | 694 | ||
| Sensitivity: | 90.2% (95% CI: 84.2% - 94.1%) | ||||
| Specificity: | 95.6% (95% CI: 93.6% - 97.1%) |
Accula RSV Test Performance Compared to FDA-cleared Molecular Comparator
ª RSV was detected in 22/24 False Positives specimens using an alternative FDA-cleared molecular RSV assay
b RSV was not detected in 12/14 False Negative specimens using an alternative FDA-cleared molecular RSV assay
Reproducibility Studies
The reproducibility study was performed to demonstrate the reproducibility of the Accula RSV Test with contrived nasal swabs at three CLIA-waived sites and one moderately complex site based in the United States. The objective of the study was to demonstrate reproducibility of the assay in the hands of multiple users at multiple sites over multiple non-consecutive days.
The test panel consisted of three samples at varying virus concentrations (i.e. RSV Negative, RSV Low Positive, and RSV Moderate Positive). Each positive sample was prepared by spiking the RSV-A2 strain into clinical matrix. The targeted concentration for the Moderate Positive sample was approximately 3X the LoD, and the targeted concentration for the Low Positive sample was approximately 1X the LoD (C95 concentration). The Negative sample contained no RSV virus.
Samples were provided to testing operators in panels of 3 samples (RSV Low Positive, RSV Moderate Positive, and Negative). Samples were blinded and randomized. Each operator tested one panel per day, testing a maximum of three samples at a time. Each sample was tested in triplicate (from separate swabs): 2 operators x 1 run x 3 swabs x 5 non-consecutive days = 30 observations for each site per sample type. Results are reported as percent agreement: actual result/expected result x 100. Agreement was 100% across all sites, operators, and days. There were no significant differences observed within run, between sites, or between operators. Agreement by site is shown in the table below.
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| Site | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| SampleCategory | ADP | GVP | LBC | NAZ | Overall PercentAgreement and95% CI | ||||
| PercentAgreement | Count | PercentAgreement | Count | PercentAgreement | Count | PercentAgreement | Count | ||
| Low PosRSV | 100% | 30/30 | 100% | 30/30 | 100% | 30/30 | 100% | 30/30 | 100%(120/120)(95.9%, 100%) |
| Mod PosRSV | 100% | 30/30 | 100% | 30/30 | 100% | 31/31* | 100% | 30/30 | 100%(121/121)(96.0%, 100%) |
| True Neg | 100% | 30/30 | 100% | 30/30 | 100% | 29/29* | 100% | 30/30 | 100%(119/119)(95.9%, 100%) |
| * One negative swab was mistakenly spiked with MP RSV |
Site to Site Reproducibility: Percent Agreement and Total Counts (Observed/Expected)
Limit of Detection
Multiple analyte levels were tested in 20 replicates until the LoD was determined (the level at which at least 19/20 results are positive). Two RSV A subtype strains and two RSV B subtype strains were tested in replicates of twenty (20) for each concentration. Virus was serially diluted into a pooled negative clinical matrix and spiked onto a swab to create the contrived samples for each technical replicate for LoD determination.
Results are summarized in the table below.
Limit of Detection: Observed Positives/Number of Replicates
| Virus | LOD level | Observed Positives/ Replicates |
|---|---|---|
| RSV A2 | 300 TCID50/mL | 20/20 |
| RSV A Long | 300 TCID50/mL | 20/20 |
| RSV B1 | 10 TCID50/mL | 20/20 |
| RSV B 18537 | 0.5 PFU/mL | 19/20 |
Analytical Reactivity
Inclusivity verification was evaluated for the Accula RSV test at Mesa Biotech. The panel consisted of nine (9) RSV strains, representing both RSV-A and RSV-B subtypes. Each strain was tested in triplicate at a concentration of approximately 2X LoD. Virus was diluted in pooled clinical matrix and spiked onto a swab to create contrived swab samples. Test results are shown in the table below.
| Identification Code | Subtype | Test Level * | Percent Detection(# Positive / 3) |
|---|---|---|---|
| RSV 2012-10 | RSV-B | 1 PFU/mL | 100% (3/3) |
| RSV 2012-11 | RSV-B | 1 PFU/mL | 100% (3/3) |
| RSV A 12/2014 | RSV-A | 600 TCID50/mL | 100% (3/3) |
| RSV A 3/2015 | RSV-A | 600 TCID50/mL | 100% (3/3) |
Inclusivity Results by RSV Strain: Target Conceptrations and Test Results
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| Identification Code | Subtype | Test Level * | Percent Detection(# Positive / 3) |
|---|---|---|---|
| RSV B 12/2014 | RSV-B | 20 TCID50/mL | 100% (3/3) |
| RSV 2006 Isolate | RSV-A | 600 TCID50/mL | 100% (3/3) |
| RSV CH93(18)-18 | RSV-B | 20 TCID50/mL | 100% (3/3) |
| RSV 9320 | RSV-B | 20 TCID50/mL | 100% (3/3) |
| RSV B 3/2015 | RSV-B | 20 TCID50/mL | 100% (3/3) |
| * Concentration of contrived sample after 10uL of virus dilution Spiked onto Swab and Swirled in 5mLpooled clinical matrix assuming 100% viral elution recovery. |
Analytical Specificity (Cross-Reactivity)
Cross-reactivity was performed by testing 41 potentially cross-reacting organisms with the Accula RSV Test. Each organism was diluted in a clinical matrix and tested in triplicate. The organisms, concentrations, and test results are shown in the table below. All 41 organisms were negative at the concentrations tested.
| OrganismKey # | Organism Name | Test Level | Test Results (# ofRSV Pos / 3) |
|---|---|---|---|
| 1 | Adenovirus Type 1 | 5.10E+05 TCID50/mL | 0/3 |
| 2 | Adenovirus Type 7 | 3.31E+04 TCID50/mL | 0/3 |
| 3 | Coronavirus | 1.10E+04 TCID50/mL | 0/3 |
| 4 | Coronavirus | 2.95E+05 TCID50/mL | 0/3 |
| 5 | Cytomegalovirus | 1.10E+04 TCID50/mL | 0/3 |
| 6 | Cytomegalovirus | 1.90E+04 TCID50/mL | 0/3 |
| 7 | Cytomegalovirus | 2.52E+04 TCID50/mL | 0/3 |
| 8 | Echovirus | 2.95E+05 TCID50/mL | 0/3 |
| 9 | Enterovirus | 1.04E+04 TCID50/mL | 0/3 |
| 10 | Human Metapneumovirus | 1.01E+04 TCID50/mL | 0/3 |
| 11 | Measles virus | 2.95E+05 TCID50/mL | 0/3 |
| 12 | Mumps virus | 9.75E+04 TCID50/mL | 0/3 |
| 13 | Parainfluenza Type 1 | 2.52E+04 TCID50/mL | 0/3* |
| 14 | Parainfluenza Type 2 | 1.10E+04 TCID50/mL | 0/3 |
| 15 | Parainfluenza Type 3 | 1.18E+04 TCID50/mL | 0/3 |
| 16 | Rhinovirus | 3.31E+04 TCID50/mL | 0/3 |
| 17 | Rhinovirus | 3.31E+04 TCID50/mL | 0/3 |
| 18 | Rhinovirus | 3.02E+04 TCID50/mL | 0/3 |
| 19 | Epstein-Barr virus | 3.98E+07 cp/mL | 0/3 |
| 20 | Bordetella pertussis | 4.22E+06 cfu/ml | 0/3 |
| 21 | Candida albicans | 9.80E+05 cfu/ml | 0/3 |
| 22 | Escherichia coli | 1.92E+07 cfu/ml | 0/3 |
| 23 | Haemophilus influenzae | 1.20E+06 cfu/ml | 0/3 |
| 24 | Klebsiella pneumoniae | 4.15E+07 cfu/ml | 0/3 |
| 25 | Lactobacillus sp. | 3.00E+06 cfu/ml | 0/3 |
| 26 | Legionella longbeachae | 9.65E+06 cfu/ml | 0/3 |
| 27 | Moraxella catarrhalis | 1.99E+05 cfu/ml | 0/3 |
| 28 | Mycobacterium tuberculosis | 3.62E+06 cfu/ml | 0/3 |
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| Test Results of Possible Cross-Reactive Organisms | |||
|---|---|---|---|
| OrganismKey # | Organism Name | Test Level | Test Results (# ofRSV Pos / 3) |
| 29 | Neisseria gonorrhoeae | 6.30E+06 cfu/ml | 0/3 |
| 30 | Neisseria meningitidis | 1.28E+06 cfu/ml | 0/3 |
| 31 | Neisseria subflava | 7.30E+06 cfu/ml | 0/3 |
| 32 | Proteus vulgaris | 2.07E+07 cfu/ml | 0/3 |
| 33 | Pseudomonas aeruginosa | 6.05E+05 cfu/ml | 0/3 |
| 34 | Staphylococcus aureus | 6.95E+07 cfu/ml | 0/3 |
| 35 | Staphylococcus epidermidis | 3.24E+07 cfu/ml | 0/3 |
| 36 | Streptococcus pneumonia | 2.09E+06 cfu/ml | 0/3 |
| 37 | Streptococcus pyogenes | 2.72E+07 cfu/ml | 0/3 |
| 38 | Streptococcus salivarius | 2.32E+06 cfu/ml | 0/3 |
| 39 | Mycoplasma pneumoniae | 2.81E+05 CCU/ml | 0/3 |
| 40 | Influenza A/California/07/2009 | 2.15E+04 TCID50/mL | 0/3 |
| 41 | InfluenzaB/Massachusetts/2/2012 | 5.00E+05 TCID50/mL | 0/3 |
| *Replicate 3 of Organism # 13 Parainfluenza Type 1 was repeated due to an Invalid. |
Interfering Substances
To assess substances with the potential to interfere with the performance of the Accula RSV Test, two (2) RSV strains were tested in replicates of three (3) with each interfering substance at the "worst case" concentration. For each sample, virus was diluted into a pooled negative clinical matrix to achieve a 1.5X LoD concentration. Each RSV strain was tested with an interferent concentration representing the highest concentration likely to be found in a respiratory sample. Additionally, each strain was tested without the interfering substance as a control. Potential interferents, their concentrations, samples tested, and test results are summarized in the table below. The Accula RSV Test performance is not negatively affected by the potentially interfering substances tested.
| Interfering Substances - Agreement of Observed/Expected | |||
|---|---|---|---|
| Potential Interferent | InterferentConcentration forMaking ContrivedSwab | Sample Tested | % Agreement withExpected Results |
| Controls | NA | Negative | 100% (2/2) |
| NA | RSV A2 at 450 TCID50/ml | 100% (3/3) | |
| NA | RSV B1 at 15 TCID50/mL | 100% (3/3) | |
| Blood (Human) | 1% (v/v) | Negative | 100% (3/3) |
| 1% (v/v) | RSV A2 at 450 TCID50/ml | 100% (3/3) | |
| 1% (v/v) | RSV B1 at 15 TCID50/mL | 100% (3/3) | |
| Phenylephrine nasal spray | Neat | Negative | 100% (3/3) |
| Neat | RSV A2 at 450 TCID50/ml | 100% (3/3) | |
| Neat | RSV B1 at 15 TCID50/mL | 100% (3/3) | |
| Oxymetazoline nasalspray | Neat | Negative | 100% (3/3) |
| Neat | RSV A2 at 450 TCID50/ml | 100% (3/3) | |
| Interfering Substances - Agreement of Observed/Expected | |||
| Potential Interferent | InterferentConcentration forMaking ContrivedSwab | Sample Tested | % Agreement withExpected Results |
| Neat | RSV B1 at 15 TCID50/mL | 100% (3/3) | |
| Neat | Negative | 100% (3/3) | |
| Ocean Saline Nasal Spray | Neat | RSV A2 at 450 TCID50/ml | 100% (3/3) |
| Neat | RSV B1 at 15 TCID50/mL | 100% (3/3) | |
| Neat | Negative | 100% (3/3) | |
| Chloraseptic Max | Neat | RSV A2 at 450 TCID50/ml | 100% (3/3) |
| Neat | RSV B1 at 15 TCID50/mL | 100% (3/3) | |
| Neat | Negative | 100% (3/3) | |
| Nasacort (Triamcinolone,nasal corticosteroid) | Neat | RSV A2 at 450 TCID50/ml | 100% (3/3) |
| Neat | RSV B1 at 15 TCID50/mL | 100% (3/3) | |
| Zicam (Nasal gel, | Neat | Negative | 100% (3/3) * |
| homeopathic allergy relief | Neat | RSV A2 at 450 TCID50/ml | 100% (3/3) |
| medicine) | Neat | RSV B1 at 15 TCID50/mL | 100% (3/3) ** |
| 1 lozenge/5mL | Negative | 100% (3/3) | |
| Cepacol (throat lozenge) | 1 lozenge/5mL | RSV A2 at 450 TCID50/ml | 100% (3/3) |
| 1 lozenge/5mL | RSV B1 at 15 TCID50/mL | 100% (3/3) | |
| 5 mg/mL | Negative | 100% (3/3) | |
| Mucin, Type II | 5 mg/mL | RSV A2 at 450 TCID50/ml | 100% (3/3) |
| 5 mg/mL | RSV B1 at 15 TCID50/mL | 100% (3/3) | |
| 1.6 mg/mL | Negative | 100% (3/3) | |
| Beclomethasone | 1.6 mg/mL | RSV A2 at 450 TCID50/ml | 100% (3/3) |
| 1.6 mg/mL | RSV B1 at 15 TCID50/mL | 100% (3/3) | |
| 3.2 mg/mL | Negative | 100% (3/3) | |
| Budesonide | 3.2 mg/mL | RSV A2 at 450 TCID50/ml | 100% (3/3) |
| 3.2 mg/mL | RSV B1 at 15 TCID50/mL | 100% (3/3) | |
| 30 mg/mL | Negative | 100% (3/3) | |
| Dexamethasone | 30 mg/mL | RSV A2 at 450 TCID50/ml | 100% (3/3) |
| 30 mg/mL | RSV B1 at 15 TCID50/mL | 100% (3/3) * | |
| 1.6 mg/mL | Negative | 100% (3/3) | |
| Flunisolide | 1.6 mg/mL | RSV A2 at 450 TCID50/ml | 100% (3/3) |
| 1.6 mg/mL | RSV B1 at 15 TCID50/mL | 100% (3/3) | |
| Fluticasone Propionate | 0.25 mg/mL | Negative | 100% (3/3) |
| 0.25 mg/mL | RSV A2 at 450 TCID50/ml | 100% (3/3) | |
| 0.25 mg/mL | RSV B1 at 15 TCID50/mL | 100% (3/3) | |
| 1 mg/mL | Negative | 100% (3/3) | |
| Mometasone furoate | 1 mg/mL | RSV A2 at 450 TCID50/ml | 100% (3/3) |
| 1 mg/mL | RSV B1 at 15 TCID50/mL | 100% (3/3) | |
| 20 mg/mL | Negative | 100% (3/3) | |
| Mupirocin (antibiotic) | 20 mg/mL | RSV A2 at 450 TCID50/ml | 100% (3/3) |
| Interfering Substances - Agreement of Observed/Expected | |||
| Potential Interferent | InterferentConcentration forMaking ContrivedSwab | Sample Tested | % Agreement withExpected Results |
| 20 mg/mL | RSV B1 at 15 TCID50/mL | 100% (3/3) | |
| Tobramycin(antibacterial) | 75 mg/mL | Negative | 100% (3/3) |
| 75 mg/mL | RSV A2 at 450 TCID50/ml | 100% (3/3) | |
| 75 mg/mL | RSV B1 at 15 TCID50/mL | 100% (3/3) | |
| Triamcinolone | 0.05 mg/mL | Negative | 100% (3/3) |
| 0.05 mg/mL | RSV A2 at 450 TCID50/ml | 100% (3/3) * | |
| 0.05 mg/mL | RSV B1 at 15 TCID50/mL | 100% (3/3) | |
| Zanamivir (anti-viraldrug) | 50 mg/mL | Negative | 100% (3/3) * |
| 50 mg/mL | RSV A2 at 450 TCID50/ml | 100% (3/3) | |
| 50 mg/mL | RSV B1 at 15 TCID50/mL | 100% (3/3) | |
| One replicate was repeated due to an invalid result* Two replicates were repeated due to invalid results |
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CLIA Waiver Studies
The performance of the Accula RSV Test was evaluated at ten intended use sites by nonlaboratory personnel in a prospective clinical study during the 2017-2018 RSV season in the U.S. Nasal swabs were collected from patients with RSV-like symptoms and were tested with the Accula RSV Test and the comparator method, a FDA-cleared molecular RSV assay. All specimens generating discrepant results were investigated by testing with an alternative FDAcleared molecular assay. The performance of the Accula RSV test compared with the comparator method is presented in the table below.
Accula RSV Test Performance Compared to FDA-cleared Molecular Comparator
| Accula RSVTest | Comparator | Positive | Negative | Total |
|---|---|---|---|---|
| Positive | 129 | 24a | 153 | |
| Negative | 14b | 527 | 541 | |
| Total | 143 | 551 | 694 | |
| Sensitivity: | 90.2% (95% CI: 84.2% - 94.1%) | |||
| Specificity: | 95.6% (95% CI: 93.6% - 97.1%) |
ª RSV was detected in 22/24 False Positives specimens using an alternative FDA-cleared molecular RSV assay
b RSV was not detected in 12/14 False Negative specimens using an alternative FDA-cleared molecular RSV assay
Performance Near the Cut-off
Three CLIA-waived sites that participated in the prospective clinical study also participated in the Near-Cutoff study. The testing was performed by three (3) untrained intended operators at each of the sites. This study was conducted to demonstrate that untrained intended users could
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perform the Accula RSV Test and consistently detect Low Positive samples at the Limit of Detection (LoD).
The test panel consisted of two contrived samples: RSV Low Positive and a True Negative. The Low Positive sample was prepared using the RSV-A2 strain spiked into negative clinical matrix at a concentration of approximately 1X LoD (C95 concentration). The Negative sample was prepared from negative clinical matrix with no RSV virus. Samples were applied to swabs, coded and blinded to the testing operators. Swab specimens were presented to the intended use operators throughout the course of a normal working day and were masked as subject samples. Testing took place during the course of two weeks on non-consecutive days, while the clinical study was in progress. Each site ultimately tested a panel of 60 samples: 30 replicates of each sample.
Test results are shown in the table below. The study demonstrates that untrained use operators are able to accurately perform and interpret the Accula RSV Test at the level of the LoD.
| Site | Sample Type | |
|---|---|---|
| RSV Positive | RSV Negative | |
| ADP | 30/30 | 30/30 |
| GVP | 30/30 | 30/30 |
| LBC | 30/30 | 30/30 |
| Total | 90/90 | 90/90 |
Near-Cutoff Study Test Results: Agreement of Observed/Expected
Conclusion 8.
The information presented in this Premarket Notification demonstrates that the performance of the Accula RSV Test is substantially equivalent in intended use, technological characteristics, and performance to the predicate device.
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Indications for Use
510(k) Number (if known)
Device Name
Indications for Use (Describe)
Prescription Use (Part 21 CFR 801 Subpart D)
| Over-The-Counter Use (21 CFR 801 Subpart C)
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November 23, 2018
Image /page/12/Picture/1 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which consists of the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG" in blue, and then the word "ADMINISTRATION" in a smaller font size, also in blue.
Mesa Biotech, Inc. Barbara Stevens Regulatory Consultant 6190 Cornerstone Court, Suite 220 San Diego, CA 92121
Re: K181443
Trade/Device Name: Accula RSV Test Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory viral panel multiplex nucleic acid assay Regulatory Class: Class II Product Code: OCC Dated: May 25, 2018 Received: May 31, 2018
Dear Barbara Stevens:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR
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- for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
§ 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.