(94 days)
Not Found
No
The description details a standard real-time PCR assay and its performance characteristics. There is no mention of AI or ML in the device description, intended use, or performance studies.
No.
Explanation: This device is an in vitro diagnostic test designed to detect and differentiate viruses, aiding in diagnosis. It does not provide any treatment or therapy.
Yes
The "Intended Use / Indications for Use" section explicitly states that the assay "is intended to aid in the differential diagnosis of Adenovirus, human Metapneumovirus, and Rhinovirus infections in humans."
No
The device is an in vitro diagnostic test that involves physical sample processing (lysis, nucleic acid capture and elution) and utilizes a hardware system (Panther Fusion system) for RT-PCR and detection. It is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the Panther Fusion® AdV/hMPV/RV assay is an "in vitro diagnostic test".
- Purpose: The test is designed for the "rapid and qualitative detection and differentiation of Adenovirus (AdV) human Metapneumovirus (hMPV), and Rhinovirus (RV)" from human specimens (nasopharyngeal swabs). This is a classic definition of an in vitro diagnostic device, which is used to examine specimens from the human body to provide information for diagnosis, treatment, or prevention of disease.
- Specimen Type: It uses "nasopharyngeal (NP) swab specimens obtained from individuals exhibiting signs and symptoms of a respiratory tract infection," which are specimens taken in vitro (outside the living body).
- Aid in Diagnosis: The intended use states it is "intended to aid in the differential diagnosis of Adenovirus, human Metapneumovirus, and Rhinovirus infections in humans." This directly aligns with the purpose of an IVD.
- Device Description: The "Device Description" further details the in vitro process of sample lysis, nucleic acid capture and elution, and multiplex RT-PCR performed on the specimen.
All these points confirm that the Panther Fusion® AdV/hMPV/RV assay is an in vitro diagnostic device.
N/A
Intended Use / Indications for Use
The Panther Fusion® AdV/hMPV/RV assay is a multiplex real-time PCR (RT-PCR) in vitro diagnostic test for the rapid and qualitative detection and differentiation of Adenovirus (AdV) human Metapneumovirus (hMPV), and Rhinovirus (RV). Nucleic acids are isolated and purified from nasopharyngeal (NP) swab specimens obtained from individuals exhibiting signs and symptoms of a respiratory tract infection.
This assay is intended to aid in the differential diagnosis of Adenovirus, human Metapneumovirus, and Rhinovirus infections in humans. Negative results do not preclude Adenovirus, human Metapneumovirus, and Rhinovirus infections and should not be used as the sole basis for treatment or other management decisions. This assay is designed for use on the Panther Fusion system.
Product codes (comma separated list FDA assigned to the subject device)
OOC, OEM, OOI
Device Description
The Panther Fusion AdV/hMPV/RV assay is a multiplex real-time PCR (RT-PCR) in vitro diagnostic test for the rapid and qualitative detection and differentiation of Adenovirus (AdV) human Metapneumovirus (hMPV), and Rhinovirus (RV). Nucleic acids are isolated and purified from nasopharyngeal (NP) swab specimens obtained from individuals exhibiting signs and symptoms of a respiratory tract infection.
The Panther Fusion AdV/hMPV/RV assay involves the following steps: sample lysis, nucleic acid capture and elution, and multiplex RT-PCR when analytes are simultaneously amplified, detected and differentiated. Nucleic acid capture and elution takes place in a single tube on the Panther Fusion system. The eluate is transferred to the Panther Fusion system reaction tube containing the assay reagents. Multiplex RT-PCR is then performed on the eluted nucleic acid on the Panther Fusion system.
Nucleic acid capture and elution: Prior to processing and testing on the Panther Fusion system, specimens are transferred to a Specimen Lysis Tube containing specimen transport media (STM) that lyses the viral particles, releases target nucleic acid and protects it from degradation during storage.
The Internal Control-S (IC-S) is added to each test specimen and controls via the working Panther Fusion Capture Reagent-S (wFCR-S). The IC-S in the reagent monitors specimen processing, amplification and detection.
Capture oligonucleotides hybridize to nucleic acid in the test specimen. Hybridized nucleic acid is then separated from the specimen in a magnetic field.
Wash steps remove extraneous components from the reaction tube. The elution step elutes purified nucleic acid. During the nucleic acid capture and elution step, total nucleic acid is isolated from specimens.
Elution transfer and RT-PCR: During the elution transfer step, eluted nucleic acid is transferred to a Panther Fusion reaction tube already containing oil and reconstituted mastermix.
For RV, hMPV, and internal control targets, amplification occurs via RT-PCR. A reverse transcriptase step generates DNA copies of the target sequence. For AdV, target amplification occurs via PCR. For all targets, specific forward and reverse primers and probes amplify targets while simultaneously detecting and discriminating multiple target types via multiplex PCR.
The Panther Fusion system compares the fluorescence signal to a predetermined cut-off to produce a qualitative result for the presence or absence of the analyte.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
nasopharyngeal (NP) swab specimens
Indicated Patient Age Range
Not Found. However, the demographic data in the clinical study shows subjects ranging from 0 to >65 years.
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
Analytical Sensitivity and Limit of Detection (LoD): Dilutions of AdV species A-F (strains 1, 3, 4, 9, 12, 40), four strains of hMPV and two strains of RV in pooled negative clinical Nasopharyngeal swab (NP) specimens. Tested with at least 12 replicates per concentration, using three reagent lots. Testing was performed on three Panther Fusion instruments per concentration and per reagent lot for a total of at least 36 replicates per virus type. Determined LoD value for each virus type was verified by testing newly prepared samples for at least 20 replicates using one lot of reagent.
Interference: Clinically relevant amounts of potentially interfering substances (medications, over the counter products, and other potentially interfering substances from Table 5) were added to simulated clinical matrix (SCM, VTM with Hela at 2 x 10^4 cells/mL) and tested unspiked or spiked with intended targets (AdV, hMPV and RV) at their respective 3X LoD concentrations.
Competitive Interference: Evaluated using a simulated clinical matrix (SCM) with pairs of target viruses at two different concentrations: 3X LoD and 1000X LoD.
Analytical Specificity: A panel of 64 organisms, consisting of 30 viral, 32 bacterial, and 2 yeast strains representing common respiratory pathogens or flora commonly present in respiratory tract. Bacteria and yeast were tested at concentrations of 10^5 to 10^8 CFU/mL, except where noted. Viruses were tested at concentrations of 10^3-10^7 TCID50/mL.
Carry-Over/Contamination: Negative samples alternately placed between high titer AdV/hMPV/RV samples. High positive samples were prepared by spiked with RV A and AdV-1 at 10^4 TCID50/mL (over 10,000X LoD). A total of nine separate runs with negative samples and positive samples placed in a checkerboard pattern were tested over three different instruments for a combined total of 449 positive and 450 negative samples.
Assay Precision: A seven-member panel was tested by three operators on two separate runs per day, using three reagent lots on three Panther Fusion systems over 45 calendar days.
Clinical Performance Study: A prospective multicenter study where 2961 leftover, remnant nasopharyngeal (NP) swab specimens were obtained from male and female individuals of all ages exhibiting signs and/or symptoms of a respiratory tract infection from four participating US pediatric/adolescent, private and/or university hospitals. The samples were tested with the Panther Fusion AdV/hMPV/RV assay, with reference viral culture followed by direct fluorescent antibody (DFA) identification (for AdV), with an FDA-cleared assay for hMPV, and with 2 reverse transcriptase PCR assays followed by bi-directional sequencing (PCR/sequencing, for RV). FDA-cleared or validated PCR-based assays were used for discordant resolution testing for AdV and hMPV; no discordant resolution testing was performed for RV. Of the 2961 specimens, 31 were withdrawn, resulting in 2875 samples with valid Panther Fusion results from 2930 processed samples.
Reproducibility: Evaluated at three US sites using seven panel members. Testing was performed using one lot of assay reagents and six operators (two at each site). At each site, testing was performed for at least five days. Each run had three replicates of each panel member. A negative panel member was created using a matrix of simulated nasal swab specimen in viral transport medium (VTM). Positive panel members were created by spiking 1-2X LoD (low-positive) or 2-3X LoD (moderate-positive) concentrations of the target analyte into a matrix of simulated nasal swab specimen, composed of cultured human cells suspended in VTM.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Analytical Sensitivity and Limit of Detection (LoD):
- Multiple strains for each targeted virus: AdV, hMPV and RV.
- Details in Table 4 (Concentration (TCID 50/mL) values are provided for different strains of Adenovirus, hMPV, and Rhinovirus).
Interference:
- No interference in performance was observed at the concentrations tested for a variety of substances listed in Table 5.
Competitive Interference:
- Study type: Competitive Interference.
- Sample size: 6 replicates for each panel (total 6 panels).
- Key results: The presence of two viruses at varying concentrations in a single sample had no effect on the analytical sensitivity (100% detection for both targets) at the concentration tested. Details in Table 6.
Analytical Specificity:
- Study type: Analytical Specificity.
- Sample size: Panel of 64 organisms (30 viral, 32 bacterial, and 2 yeast strains).
- Key results: Analytical specificity was 100% (0/9 detected) for AdV/hMPV/RV. All tested organisms showed negative results for AdV, hMPV, and RV (refer to Table 7 for details).
Carry-Over/Contamination:
- Study type: Carry-Over/Contamination.
- Sample size: Combined total of 449 positive and 450 negative samples over three instruments.
- Key results: The carry-over rate was 0.2%.
Assay Precision:
- Study type: Assay Precision.
- Sample size: 7-member panel, tested over 45 calendar days, 160-162 valid N for each member (Table 8).
- Key results:
- RV: 100.0% agreement for 3X LoD and 1X LoD, 98.1% for 0.01X LoD, 99.4% for Negative.
- AdV: 100.0% agreement for 3X LoD and 1X LoD, 89.4% for 0.01X LoD, 99.4% for Negative.
- hMPV: 100.0% agreement for 3X LoD and 1X LoD, 82.1% for 0.01X LoD, 100.0% for Negative.
- Signal variability (CV%) for Ct values are detailed in Table 9.
Clinical Performance Study:
- Study type: Prospective multicenter study.
- Sample size: 2875 evaluable samples with valid Panther Fusion results from 2961 collected samples.
- Key results:
- Sensitivity/PPA for AdV: 97.9% (92.6-99.4)
- Specificity/NPA for AdV: 97.6% (96.9-98.1)
- Sensitivity/PPA for hMPV: 98.7% (92.8-99.8)
- Specificity/NPA for hMPV: 99.0% (98.5-99.3)
- Sensitivity/PPA for RV: 86.8% (83.9-89.2)
- Specificity/NPA for RV: 97.7% (97.0-98.2)
- Prevalence for AdV: 3.3% (2.7-4.0)
- Prevalence for hMPV: 2.6% (2.1-3.3)
- Prevalence for RV: 22.2% (20.7-23.7)
- Refer to Table 12 for full results.
Reproducibility:
- Study type: Reproducibility.
- Sample size: Seven panel members, 87-89 replicates for each (Table 13).
- Key results:
- Agreement with Expected Results (95% CI): 100% for all AdV (Low and Mod Pos), hMPV (Low and Mod Pos), RV (Low and Mod Pos), and Negative panel members.
- Total signal variability (measured as %CV) ranged from 1.70% to 4.90% for low and moderate positive panel members (Table 14).
- Signal variability (measured as %CV) for positive controls was ≤1.94% (Table 15).
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Clinical Performance Study (Table 12):
- AdV:
- Sensitivity/PPA: 97.9% (95% CI 92.6-99.4)
- Specificity/NPA: 97.6% (95% CI 96.9-98.1)
- Prevalence: 3.3% (95% CI 2.7-4.0)
- hMPV:
- Sensitivity/PPA: 98.7% (95% CI 92.8-99.8)
- Specificity/NPA: 99.0% (95% CI 98.5-99.3)
- Prevalence: 2.6% (95% CI 2.1-3.3)
- RV:
- Sensitivity/PPA: 86.8% (95% CI 83.9-89.2)
- Specificity/NPA: 97.7% (95% CI 97.0-98.2)
- Prevalence: 22.2% (95% CI 20.7-23.7)
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
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.
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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo is in blue and includes the letters "FDA" in a square and the words "U.S. Food & Drug Administration".
Decmber 4, 2018
Hologic, Inc. Anila Tarte Regulatory Affairs Specialist 10210 Genetic Center Drive San Diego, California 92121
Re: K172629
Trade/Device Name: Panther Fusion AdV/hMPV/RV Assay Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory Viral Panel Multiplex Nucleic Acid Assay Regulatory Class: Class II Product Code: OOC, OEM, OOI Dated: August 31, 2017 Received: September 1, 2017
Dear Anila Tarte:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You 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 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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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.
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,
Steven R. Gitterman -S for
Uwe Scherf, Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K172629
Device Name Panther Fusion AdV/hMPV/RV Assay
Indications for Use (Describe)
The Panther Fusion® AdV/hMPV/RV assay is a multiplex real-time PCR (RT-PCR) in vitro diagnostic test for the rapid and qualitative detection and differentiation of Adenovirus (AdV) human Metapneumovirus (hMPV), and Rhinovirus (RV). Nucleic acids are isolated and purified from nasopharyngeal (NP) swab specimens obtained from individuals exhibiting signs and symptoms of a respiratory tract infection.
This assay is intended to aid in the differential diagnosis of Adenovirus, human Metapneumovirus, and Rhinovirus infections in humans. Negative results do not preclude Adenovirus, human Metapneumovirus, and Rhinovirus infections and should not be used as the sole basis for treatment or other management decisions. This assay is designed for use on the Panther Fusion system.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) | ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
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T
510(k) SUMMARY Panther Fusion AdV/hMPV/RV Assay
I. SUBMITTER
Hologic. Inc. 10210 Genetic Center Drive San Diego, CA 92121
| Contact Person: | Anila K. Tarte, MS
Regulatory Affairs Specialist
anila.tarte@hologic.com
Phone: (858) 410-8536
Fax: (858) 410-5557 |
| ----------------- | -------------------------------------------------------------------------------------------------------------------------------- |
|---|
Date Prepared: August 31, 2017
II. DEVICE
| Proprietary Name of Device: | Panther Fusion AdV/hMPV/RV Assay |
|---|---|
| Classification Name: | Respiratory viral panel multiplex nucleic acid assay |
| Regulation Number: | 21 CFR 866.3980 and 862.2570 |
| Regulatory Class: | Class II |
| Product Code: | OEM and OCC |
III. PREDICATE DEVICE
The predicate device is the FilmArray® Respiratory Panel 2 (RP2) (K170604; cleared May 30, 2017, BioFire Diagnostics, LLC, Salt Lake City, UT).
IV. DEVICE DESCRIPTION
The Panther Fusion AdV/hMPV/RV assay is a multiplex real-time PCR (RT-PCR) in vitro diagnostic test for the rapid and qualitative detection and differentiation of Adenovirus (AdV) human Metapneumovirus (hMPV), and Rhinovirus (RV). Nucleic acids are isolated and purified from nasopharyngeal (NP) swab specimens obtained from individuals exhibiting signs and symptoms of a respiratory tract infection.
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The Panther Fusion AdV/hMPV/RV assay involves the following steps: sample lysis, nucleic acid capture and elution, and multiplex RT-PCR when analytes are simultaneously amplified, detected and differentiated. Nucleic acid capture and elution takes place in a single tube on the Panther Fusion system. The eluate is transferred to the Panther Fusion system reaction tube containing the assay reagents. Multiplex RT-PCR is then performed on the eluted nucleic acid on the Panther Fusion system.
Nucleic acid capture and elution: Prior to processing and testing on the Panther Fusion system, specimens are transferred to a Specimen Lysis Tube containing specimen transport media (STM) that lyses the viral particles, releases target nucleic acid and protects it from degradation during storage.
The Internal Control-S (IC-S) is added to each test specimen and controls via the working Panther Fusion Capture Reagent-S (wFCR-S). The IC-S in the reagent monitors specimen processing, amplification and detection.
Capture oligonucleotides hybridize to nucleic acid in the test specimen. Hybridized nucleic acid is then separated from the specimen in a magnetic field.
Wash steps remove extraneous components from the reaction tube. The elution step elutes purified nucleic acid. During the nucleic acid capture and elution step, total nucleic acid is isolated from specimens.
Elution transfer and RT-PCR: During the elution transfer step, eluted nucleic acid is transferred to a Panther Fusion reaction tube already containing oil and reconstituted mastermix.
For RV, hMPV, and internal control targets, amplification occurs via RT-PCR. A reverse transcriptase step generates DNA copies of the target sequence. For AdV, target amplification occurs via PCR. For all targets, specific forward and reverse primers and probes amplify targets while simultaneously detecting and discriminating multiple target types via multiplex PCR.
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The Panther Fusion system compares the fluorescence signal to a predetermined cut-off to produce a qualitative result for the presence or absence of the analyte.
The analytes and the channel used for their detection on the Panther Fusion system are summarized in the table below.
| Analyte | Gene Targeted | Instrument Channel |
|---|---|---|
| Adenovirus | Hexon | HEX |
| human | ||
| Metapneumovirus | Nucleocapsid | ROX |
| Rhinovirus | 5' UTR | FAM |
| Internal Control | Not applicable | RED677 |
Assay Components
The reagents required to perform the Panther Fusion AdV/hMPV/RV assay are packaged and sold separately. There are 7 boxes containing 9 reagents which are required for sample processing. A description of the components that are required to perform the Panther Fusion AdV/hMPV/RV assay are detailed in Table 1. In addition, there is one ancillary kit, Panther Fusion Specimen Lysis Tubes, which is required for processing of specimens prior to testing on the Panther Fusion system.
| Box | Components Description |
|---|---|
| 1 | Panther Fusion AdV/hMPV/RV Assay Cartridges |
| 2 | Panther Fusion Extraction Reagent-S Box Contains: Panther Fusion Capture Reagent-S Panther Fusion Enhancer Reagent-S |
| 3 | Panther Fusion Internal Control-S |
| 4 | Panther Fusion Reconstitution Buffer I |
| 5 | Panther Fusion Elution Buffer |
| 6 | Panther Fusion Oil |
| 7 | Panther Fusion AdV/hMPV/RV Assay Controls Box Contains: Panther Fusion AdV/hMPV/RV Positive Control Panther Fusion Negative Control |
Table 1: Reagents Required to Perform the Panther Fusion AdV/hMPV/RV Assay
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In addition, select components can also be ordered in the following bundles:
- . Panther Fusion Universal Fluids Kit: (contains Panther Fusion Oil and Panther Fusion Elution Buffer).
- Panther Fusion Assay Fluids I-S: (contains Panther Fusion Extraction Reagents-S, . Panther Fusion Internal Control-S, and Panther Fusion Reconstitution Buffer I).
Instrumentation
The Panther Fusion AdV/hMPV/RV assay has been designed for and validated on the Panther Fusion system. The Panther Fusion system is an integrated hardware and software system that together with the Panther Fusion AdVhMPV/RV assay fully automates all the steps necessary to perform the assay.
The Panther Fusion system integrates Hologic's commercialized Panther instrument system with an add-on sidecar, the Panther Fusion module, which extends the functionality of the Panther system by increasing the assay processing capabilities to include multiplex RT-PCR. The Panther Fusion module includes instrument hardware and can be installed on existing Panther instruments or ordered with new Panther instruments.
The Panther Fusion system employs non-specific target capture (NSTC) for the purification of total nucleic acids from the sample, followed by nucleic acid amplification and real-time fluorescent detection. The process involves sample loading and preparation (i.e. nucleic acid extraction) on the Panther instrument using the same workflow and processing steps as for other commercialized Hologic Aptima TMA assays. The extracted nucleic acid for each sample is transferred to the Panther Fusion module where amplification and detection occur.
V. INDICATIONS FOR USE
Intended Use
The Panther Fusion® AdV/hMPV/RV assay is a multiplex real-time PCR (RT-PCR) in vitro diagnostic test for the rapid and qualitative detection and differentiation of Adenovirus (AdV) human Metapneumovirus (hMPV), and Rhinovirus (RV). Nucleic acids are isolated and purified
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from nasopharyngeal (NP) swab specimens obtained from individuals exhibiting signs and symptoms of a respiratory tract infection.
This assay is intended to aid in the differential diagnosis of Adenovirus, human Metapneumovirus, and Rhinovirus infections in humans. Negative results do not preclude Adenovirus, human Metapneumovirus, and Rhinovirus infections and should not be used as the sole basis for treatment or other management decisions. This assay is designed for use on the Panther Fusion system.
VI. COMPARISON OF TECHNOLOGICAL CHARACTERISTICS WITH THE PREDICATE DEVICE
A comparison of the Panther Fusion AdV/hMPV/RV assay to the predicate FilmArray® Respiratory Panel 2 (RP2) (K170604) is summarized in Table 2 (similarities) and Table 3 (differences).
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| Item | FilmArray Respiratory Panel 2 Assay
(Predicate Device) | Panther Fusion AdV/hMPV/RV
Assay
(Subject Device) |
|--------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The FilmArray Respiratory Panel 2
(RP2) is a multiplexed nucleic acid test
intended for use with FilmArray 2.0 or
FilmArray Torch systems for the
simultaneous qualitative detection and
identification of multiple respiratory
viral and bacterial nucleic acids in
nasopharyngeal swabs (NPS) obtained
from individuals suspected of respiratory
tract infections. The following organism
types and subtypes are identified using
the FilmArray RP2: Adenovirus,
Coronavirus 229E, Coronavirus HKU1,
Coronavirus NL63, Coronavirus OC43,
Human Metapneumovirus, Human
Rhinovirus/Enterovirus, Influenza A,
Influenza A subtype H1, Influenza A
subtype H3, Influenza A subtype H1-
2009, Influenza B, Parainfluenza Virus 1,
Parainfluenza Virus 2, Parainfluenza
Virus 3, Parainfluenza Virus 4,
Respiratory Syncytial Virus, Bordetella
parapertussis, Bordetella pertussis,
Chlamydia pneumoniae, and
Mycoplasma pneumoniae. | The Panther Fusion AdV/hMPV/RV
assay is a multiplex real-time PCR
(RT-PCR) in vitro diagnostic test
for the rapid and qualitative
detection and differentiation of
Adenovirus (AdV) human
Metapneumovirus (hMPV), and
Rhinovirus (RV). Nucleic acids are
isolated and purified from
nasopharyngeal (NP) swab
specimens obtained from
individuals exhibiting signs and
symptoms of a respiratory tract
infection.
This assay is intended to aid in the
differential diagnosis of
Adenovirus, human
Metapneumovirus, and Rhinovirus
infections in humans. Negative
results do not preclude
Adenovirus, human
Metapneumovirus, and Rhinovirus
infections and should not be used as
the sole basis for treatment or
other management decisions. This
assay is designed for use on the
Panther Fusion system. |
| Organisms Detected | Adenovirus, human Metapneumovirus,
Rhinovirus
See below for differences. | Same |
| Assay Controls | Internal control in each sample. External
control processed at periodic intervals. | Same |
| Patient Population | Male and female patients with
signs/symptoms of respiratory infection | Same |
| Specimen Types | Nasopharyngeal (NP) swab specimens | Same |
| Analyte | RNA/DNA | Same |
| Technology Principle
of Operation | Multiplex nucleic acid amplification
(RT-PCR) | Same |
| Item | FilmArray Respiratory Panel 2
(Predicate Device) | Panther Fusion AdV/hMPV/RV Assay
(Subject Device) |
| Organisms Detected | Adenovirus, human Metapneumovirus,
Rhinovirus. Can also detect
Coronavirus 229E, Coronavirus
HKU1, Coronavirus NL63,
Coronavirus OC43, Influenza A,
Influenza A subtype H1, Influenza A
subtype H3, Influenza A subtype H1-
2009, Influenza B, Parainfluenza Virus
1, Parainfluenza Virus 2, Parainfluenza
Virus 3, Parainfluenza Virus 4,
Respiratory Syncytial Virus,
Bordetella parapertussis, Bordetella
pertussis, Chlamydia pneumoniae, and
Mycoplasma pneumoniae. Cannot
distinguish Rhinovirus and Enterovirus. | Adenovirus, human Metapneumovirus,
Rhinovirus * |
| Platform | Automated nested multiplex PCR
platform.
Uses the FilmArray Pouch Loading
Station to prepare FilmArray pouch
(add specimen and hydrate reagents).
Uses the FilmArray Instrument to
process prepared FilmArray pouch for
nucleic acid extraction, amplification,
end-point detection and result
processing. | Automated multiplex RT-PCR
platform.
Uses Panther Fusion system for all
steps including specimen addition,
reagent preparation, nucleic acid
extraction, amplification, detection and
result processing. |
| Time to Obtain Test
Results | About 45 minutes | Approximately 2.5 hours |
Table 2: Similarities Between Panther Fusion AdV/hMPV/RV Assay and Predicate Device
9
Table 3: Differences Between Panther Fusion AdV/hMPV/RV Assay and Predicate Device
- The Panther Fusion AdV/hMPV/RV assay is specific for Rhinovirus with no cross-reactivity with Enterovirus
VII. PERFORMANCE DATA
The following performance data were provided in support of the substantial equivalence determination.
Brief Description of Analytical (Non-Clinical) Studies
The following analytical studies (non-clinical) were conducted to support the clearance of the Panther Fusion AdV/hMPV/RV Assay on the Panther Fusion System.
10
Analytical Sensitivity and Limit of Detection (LoD) of Nasopharyngeal Swab Specimens Target specific LOD values were obtained using multiple strains for each targeted virus: AdV, hMPV and RV. Dilutions of AdV species A-F (strains 1, 3, 4, 9, 12, 40), four strains of hMPV and two strains of RV in pooled negative clinical Nasopharyngeal swab (NP) specimens and tested with at least 12 replicates per concentration, using three reagent lots. Testing was performed on three Panther Fusion instruments per concentration and per reagent lot for a total of at least 36 replicates per virus type. Determined LoD value for each virus type was verified by testing newly prepared samples for at least 20 replicates using one lot of reagent. Panel descriptions are shown in Table 4.
| Target Type | Organism | Concentration
(TCID 50/mL) |
|-------------|--------------------------------------------------------------------------------------|-------------------------------|
| Adenovirus | Strain: 1 (Species C)
Source and Mfg MN:
Zeptometrix, 0810050CF
LN: 307673 | $10^1.0$ |
| | | $10^0.5$ |
| | | $10^0.0$ |
| | | $10^-0.5$ |
| | | $10^-1.0$ |
| | Strain: 3 (Species B)
Source and Mfg MN:
Zeptometrix, 0810062CF
LN: 310503 | $10^1.0$ |
| | | $10^0.5$ |
| | | $10^0.0$ |
| | | $10^-0.5$ |
| | | $10^-1.0$ |
| | Strain: 4 (Species E)
Source and Mfg MN:
Zeptometrix, 0810070CF
LN: 309013 | $10^-2.0$ |
| | | $10^-2.5$ |
| | | $10^-3.0$ |
| | | $10^-3.5$ |
| | | $10^-4.0$ |
| | Strain: 9 (Species D)
Source and Mfg MN:
TriCore, Custom
LN: 112408 | $10^0.0$ |
| | | $10^-0.5$ |
| | | $10^-1.0$ |
| | | $10^-1.5$ |
| | | $10^-2.0$ |
| | Strain: 12 (Species A)
Source and Mfg MN:
TriCore, Custom
LN: 120108 | $10^0.0$ |
| | | $10^-0.5$ |
| | | $10^-1.0$ |
| | | $10^-1.5$ |
| | | $10^-2.0$ |
| Target Type | Organism | Concentration
(TCID 50/mL) |
| hMPV | Strain: 40 (Species F)
Source and Mfg MN:
Zeptometrix, 0810084CF
LN: 312745 | 10^-1.0 |
| | | 10^-1.5 |
| | | 10^-2.0 |
| | | 10^-2.5 |
| | | 10^-3.0 |
| | Strain: A1-16
Source and Mfg MN:
Zeptometrix, 0810161CF
LN: 308413 | 10^2.0 |
| | | 10^1.5 |
| | | 10^1.0 |
| | | 10^0.5 |
| | | 10^0.0 |
| | Strain: A2-20
Source and Mfg MN:
Zeptometrix, 0810163CF
LN: 308416 | 10^2.0 |
| | | 10^1.5 |
| | | 10^1.0 |
| | | 10^0.5 |
| | | 10^0.0 |
| | Strain: B1-3
Source and Mfg MN:
Zeptometrix, 0810156CF
LN: 309673 | 10^1.0 |
| | | 10^0.5 |
| | | 10^0.0 |
| | | 10^-0.5 |
| | | 10^-1.0 |
| | Strain: B2-8
Source and Mfg MN:
Zeptometrix, 0810159CF
LN: 308419 | 10^1.0 |
| | | 10^0.5 |
| | | 10^0.0 |
| | | 10^-0.5 |
| | | 10^-1.0 |
| Rhinovirus | Strain: A-18
Source and Mfg MN:
Zeptometrix, Custom
LN: 313820 | 10^0.0 |
| | | 10^-0.5 |
| | | 10^-1.0 |
| | | 10^-1.5 |
| | | 10^-2.0 |
| | Strain: B-26
Source and Mfg MN:
Zeptometrix, Custom
LN: 313819 | 10^1.0 |
| | | 10^0.5 |
| | | 10^0.0 |
| | | 10^-0.5 |
| | | 10^-1.0 |
Table 4: LoD Determination Panel Description
11
Interference
Medications, over the counter products, and other potentially interfering substances that may be present in the samples were evaluated in the Panther Fusion AdV/hMPV/RV assay.
12
Clinically relevant amounts of the potentially interfering substances were added to simulated clinical matrix (SCM, VTM with Hela at 2 x 10^4 cells/mL) and tested unspiked or spiked with intended targets (AdV, hMPV and RV) at their respective 3X LoD concentrations. The substances consisted of nasal sprays or drops, lozenges, exogenous and endogenous substances. No interference in performance of the Panther Fusion AdV/hMPV/RV assay was observed in the presence of a representative brand of the following potentially interfering substances at the concentrations stated in Table 5.
| Type | Potentially
Interfering Substance | Active Ingredient(s) | Concentration |
|-------------------------------|--------------------------------------|-------------------------------------------------------------------------------|---------------|
| Endogenous | Mucin | Purified mucin protein | 60 µg/mL |
| | Human blood | NA | 2% v/v |
| | Neo-Synephrine® | Phenylephrine | 15% v/v |
| Nasal sprays or
drops | Anefrin | Oxymetazoline HCl .05% | 15% v/v |
| | Saline | Sodium chloride with
preservatives | 15% v/v |
| | Ventolin® HFA | Albuterol (Albuterol Sulfate) | 15% v/v |
| | QVAR®, Beconase
AQ | Beclomethasone
(Beclomethasone
(Dipropionate)) | 5% v/v |
| | Dexacort | Dexamethasone | 5% v/v |
| Nasal
corticosteroids | AEROSPAN® | Flunisolide | 5% v/v |
| | Nasacort | Triamcinolone | 5% v/v |
| | Rhinocort | Budesonide | 5% v/v |
| | Nasonex | Mometasone (Mometasone
furoate) | 5% v/v |
| | Flonase | Fluticasone (Fluticasone
(propionate)) | 5% v/v |
| Nasal gel | Zicam® (Allergy
Relief) | Luffa opperculata, Galphimia,
Glauca, Histaminum
hydrochloricum, Sulfur | 5% v/v |
| Throat lozenges | Chloraseptic Throat
Lozenges | Benzocaine
Menthol | 0.63 mg/mL |
| | Relenza® | Zanamivir | 3.3 mg/mL |
| Anti-viral drugs | TamiFlu | Oseltamivir | 25 mg/mL |
| | Rebitol | Ribavirin | 20 mg/mL |
| Antibiotic, nasal
ointment | Bactroban cream | Mupirocin | 10 mg/mL |
| Antibiotic,
systemic | Tobramycin | Tobramycin | 4.0 µg/mL |
Table 5: Potentially Interfering Substances
13
Competitive Interference
Competitive Interference of the Panther Fusion AdV/hMPV/RV assay was evaluated using a simulated clinical matrix (SCM) with pairs of target viruses at two different concentrations. One of the concentrations was near the Limit of Detection (3X LoD) while the other concentration was high (1000X LoD). The presence of two viruses at varying concentrations in a single sample had no effect on the analytical sensitivity (100% detection for both targets) at the concentration tested (see Table 6).
| Panel
Member | Target
1
(Low) | Target
2
(High) | Detection Channel (Target), % Positive (reactive n/valid n) | | | |
|-----------------|----------------------|-----------------------|-------------------------------------------------------------|--------------|---------------|--------------|
| | | | FAM (RV) | HEX (AdV) | ROX
(hMPV) | RED677 (IC) |
| 1 | AdV | hMPV | 0.0% (0/6) | 100.0% (6/6) | 100.0% (6/6) | 100.0% (6/6) |
| 2 | AdV | RV | 100.0% (6/6) | 100.0% (6/6) | 0.0% (0/6) | 100.0% (6/6) |
| 3 | hMPV | AdV | 0.0% (0/6) | 100.0% (6/6) | 100.0% (6/6) | 100.0% (6/6) |
| 4 | hMPV | RV | 100.0% (6/6) | 0.0% (0/6) | 100.0% (6/6) | 100.0% (6/6) |
| 5 | RV | AdV | 100.0% (6/6) | 100.0% (6/6) | 0.0% (0/6) | 100.0% (6/6) |
| 6 | RV | hMPV | 100.0% (6/6) | 0.0% (0/6) | 100.0% (6/6) | 100.0% (6/6) |
Table 6: Co-Infection Concentrations and Results
Analytical Specificity
The analytical specificity of the Panther Fusion AdV/hMPV/RV assay was evaluated by testing a panel of 64 organisms, consisting of 30 viral, 32 bacterial, and 2 yeast strains representing common respiratory pathogens or flora commonly present in respiratory tract. Bacteria and yeast were tested at concentrations of 10^5 to 10^8 CFU/mL, except where noted. Viruses were tested at concentrations of 10^3-10^7 TCID50/mL. Analytical specificity of the Panther Fusion AdV/hMPV/RV assay was 100% (0/9 detected) for AdV/hMPV/RV (see Table 7).
| Organis | Concentration | AdV | hMPV | RV |
|---|---|---|---|---|
| Acinetobacter baumannii 307-0294 | 1x107 CFU/mL | - | - | - |
| Bordetella bronchiseptica | 1x107 CFU/ml | - | - | - |
| Bordetella parapertussis | 1x107 CFU/ml | - | - | - |
| Bordetella pertussis | 1x107 CFU/mL | - | - | - |
| Burkholderia cepacia Z066 | 1x106 CFU/mL | - | - | - |
| Candida albicans | 1x107 CFU/mL | - | - | - |
| Candida glabrata | 1x106 CFU/mL | - | - | - |
| Chlamydia pneumoniae | 1x105 CFU/mL | - | - | - |
| Chlamydia trachomatis | 1x104 CFU/mL | - | - | - |
| CMV Strain AD 169 | 1x104 TCID50/mL | - | - | - |
| Coronavirus 229E | 1x105 TCID50/mL | - | - | - |
| Coronavirus OC43 | 1x105 TCID50/mL | - | - | - |
| Corynebacterium diphtheria | 1x107 CFU50/mL | - | - | - |
| Coxsackie B3 | 1x106 TCID50/mL | - | - | - |
| Coxsackie B4 | 1x104 TCID50/mL | - | - | - |
| Coxsackie B5/10/2006 | 1x105 TCID50/mL | - | - | - |
| Coxsackievirus A10 | 1x104 TCID50/mL | - | - | - |
| Coxsackievirus A21 | 1x104 TCID50/mL | - | - | - |
| Escherichia coli | 1x107 CFU/mL | - | - | - |
| EBV | 1x106 TCID50/mL | - | - | - |
| Echovirus 11 | 1x106 TCID50/mL | - | - | - |
| Echovirus 2 | 1x106 TCID50/mL | - | - | - |
| Echovirus 3 | 1x104 TCID50/mL | - | - | - |
| Echovirus 6 | 1x106 TCID50/mL | - | - | - |
| Enterovirus 68 | 1x105 TCID50/mL | - | - | - |
| Enterovirus 70 | 1x104 TCID50/mL | - | - | - |
| Haemophilus influenzae | 1x107 TCID50/mL | - | - | - |
| HPIV-1 | 1x104 TCID50/mL | - | - | - |
| HPIV-2 | 1x105 TCID50/mL | - | - | - |
| HPIV-3 | 1x105 TCID50/mL | - | - | - |
| HPIV-4a | 1x104 TCID50/mL | - | - | - |
| HSV-1 Macinytre Strain | 1x105 TCID50/mL | - | - | - |
| HSV-2 Type 2G Strain | 1x105 TCID50/mL | - | - | - |
| Influenza A (H1N1) | 1x103 TCID50/mL | - | - | - |
| Influenza A (H3N2) | 1x103 TCID50/mL | - | - | - |
| Influenza B | 1x103 TCID50/mL | - | - | - |
| Klebsiella pneumonia | 1x107 CFU/mL | - | - | - |
| Lactobacillus acidophilus Z048 | 1x106 CFU/mL | - | - | - |
| Lactobacillus plantarum | 1x106 CFU/mL | - | - | - |
| Legionella pneumophila | 1x107 CFU/mL | - | - | - |
| Measles/7/2000 | 1x104 TCID50/mL | - | - | - |
| Moraxella catarrhalis | 1x107 CFU/mL | - | - | - |
| Mumps virus | 1x105 CFU/mL | - | - | - |
| Mycobacterium intracellulare | 5x1010 rRNA copies/mL | - | - | - |
| Mycobacterium tuberculosis | 5x109 rRNA copies/mL | - | - | - |
| Mycoplasma pneumoniae | 1x106 CFU/mL | - | - | - |
| Neisseria gonorrhea | 1x107 CFU/mL | - | - | - |
| Neisseria meningitides | 1x107 CFU/mL | - | - | - |
| Neisseria mucosa | 1x107 CFU/mL | - | - | - |
| Polio virus 1 | 1x106 TCID50/mL | - | - | - |
| Proteus mirabilis | 1x107 CFU/mL | - | - | - |
| Proteus vulgaris | 1x107 CFU/mL | - | - | - |
| Pseudomonas aeruginosa | 1x107 CFU/mL | - | - | - |
| RSV A | 1x105 TCID50/mL | - | - | - |
| RSV B | 1x105 TCID50/mL | - | - | - |
| Serratia marcescens Z053 | 1x107 CFU/mL | - | - | - |
| Staphylococcus aureus | 1x107 CFU/mL | - | - | - |
| Staphylococcus epidermidis | 1x107 CFU/mL | - | - | - |
| Streptococcus agalactiae | 1x107 CFU/mL | - | - | - |
| Streptococcus pneumoniae | 1x107 CFU/mL | - | - | - |
| Streptococcus pyogenes | 1x107 CFU/mL | - | - | - |
| Streptococcus salivarius | 1x107 CFU/mL | - | - | - |
| Tatlockia micdadei (Legionella | ||||
| micdadei) | 1x106 CFU/mL | - | - | - |
| Varicella Zoster Virus | 1x104 TCID50/mL | - | - | - |
Table 7: Specificity Results
14
15
Carry-Over/Contamination
The carry-over/cross-contamination study was performed with negative samples alternately placed between high titer AdV/hMPV/RV samples and tested. High positive samples were prepared by spiked with RV A and AdV-1 at 10^4 TCID50/mL (over 10,000X LoD). A total of nine separate runs with negative samples and positive samples placed in a checkerboard pattern
16
were tested over three different instruments for a combined total of 449 positive and 450 negative samples. The carry-over rate was 0.2%.
Assay Precision
Panther Fusion AdV/hMPV/RV assay precision was evaluated with a seven-member panel. The panel was tested by three operators on two separate runs per day, using three reagent lots on three Panther Fusion systems over 45 calendar days. The panel members, along with a summary of the agreement with expected results for each target is presented in Table 8. The mean and variability analysis between instruments, between reagent lots, between operators, between days, between runs and within runs, and overall (total) for Ct are also presented in Table 9.
| Target | Panel
Description | Member
ID | Valid N | % Positive
(pos n/valid n) | % Agreement
(95% CI) | | | | | | | | | | | | | | | |
|----------|----------------------|-------------------|---------|-------------------------------|-------------------------|------------------------|---|-----|------------------|------------------------|-------------------|----|-----|----------------|--------------------|----------|---|-----|--------------|------------------------|
| RV | RV 3X LoD | 5 | 161 | 100.0% (161/161) | 100.0% (97.7-100.0%) | | | | | | | | | | | | | | | |
| | RV 1X LoD | 6 | 162 | 100.0% (162/162) | 100.0% (97.7-100.0%) | | | | | | | | | | | | | | | |
| | RV 0.01X LoD | 2 | 160 | 1.9% (3/160) | 98.1% (94.6-99.4%) | | | | | | | | | | | | | | | |
| | Negative | 7 | 162 | 0.6% (1/162) | 99.4% (96.6-99.9%) | | | | | | | | | | | | | | | |
| AdV | AdV 3X LoD | 3A | 162 | 100.0% (162/162) | 100.0% (97.7-100.0%) | | | | | | | | | | | | | | | |
| | AdV 1X LoD | 1 | 162 | 100.0% (162/162) | 100.0% (97.7-100.0%) | | | | | | | | | | | | | | | |
| | AdV 0.01X
LoD | 5 | 161 | 10.6% (17/161) | 89.4% (83.7-93.3%) | | | | | | | | | | | | | | | |
| | Negative | 7 | 162 | 0.6% (1/162) | 99.4% (96.6-99.9%) | | | | | | | | | | | | | | | |
| hMPV | hMPV 3X LoD | 2 | 160 | 100.0% (160/160) | 100.0% (97.7 - 100.0%) | hMPV 1X LoD | 4 | 161 | 100.0% (161/161) | 100.0% (97.7 - 100.0%) | hMPV 0.01X
LoD | 3A | 162 | 17.9% (29/162) | 82.1% (75.5-87.2%) | Negative | 7 | 162 | 0.0% (0/162) | 100.0% (97.7 - 100.0%) |
| | hMPV | hMPV 3X LoD | 2 | 160 | 100.0% (160/160) | 100.0% (97.7 - 100.0%) | | | | | | | | | | | | | | |
| | | hMPV 1X LoD | 4 | 161 | 100.0% (161/161) | 100.0% (97.7 - 100.0%) | | | | | | | | | | | | | | |
| | | hMPV 0.01X
LoD | 3A | 162 | 17.9% (29/162) | 82.1% (75.5-87.2%) | | | | | | | | | | | | | | |
| Negative | | 7 | 162 | 0.0% (0/162) | 100.0% (97.7 - 100.0%) | | | | | | | | | | | | | | | |
Table 8: Percent Positive and Agreement
17
| Target | Panel
Member | Member
ID | Mean
Ct | Between Instrument | | Between Reagent Lot | | Between Operator | | Between Days | | Between Runs | | Within Run | | Total | |
|--------|-------------------|--------------|------------|--------------------|--------|---------------------|--------|------------------|--------|--------------|-----------|--------------|--------|------------|-----------|-------|-----------|
| | | | | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV
(%) | SD | CV (%) | SD | CV
(%) | SD | CV
(%) |
| RV | RV 3X
LoD | 5 | 32.5 | 0.1 | 0.5 | 0.1 | 0.3 | 0.0 | 0.1 | 0.0 | 0.0 | 0.3 | 1.0 | 0.6 | 2.0 | 0.7 | 2.4 |
| | RV 1X
LoD | 6 | 33.8 | 0.1 | 0.5 | 0.1 | 0.5 | 0.0 | 0.0 | 0.1 | 0.4 | 0.0 | 0.0 | 0.8 | 2.6 | 0.9 | 2.8 |
| | RV 0.01X
LoD | 2 | 40.6 | 1.9 | 4.7 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.6 | 1.6 | 2.0 | 5.0 |
| AdV | AdV 3X
LoD | 3A | 33.5 | 0.1 | 0.4 | 0.0 | 0.1 | 0.0 | 0.0 | 0.1 | 0.3 | 0.2 | 0.7 | 0.4 | 1.2 | 0.5 | 1.5 |
| | AdV 1X
LoD | 1 | 35.2 | 0.2 | 0.6 | 0.0 | 0.0 | 0.0 | 0.2 | 0.1 | 0.3 | 0.3 | 0.8 | 0.5 | 1.5 | 0.6 | 1.9 |
| | AdV 0.01X
LoD | 5 | 40.4 | 0.3 | 0.8 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.9 | 2.4 | 0.7 | 1.9 | 1.3 | 3.2 |
| hMPV | hMPV 3X
LoD | 2 | 33.5 | 0.0 | 0.1 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.2 | 0.8 | 0.8 | 2.4 | 0.8 | 2.5 |
| | hMPV 1X
LoD | 4 | 35.1 | 0.0 | 0.1 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.1 | 0.7 | 2.0 | 0.7 | 2.0 |
| | hMPV
0.01X LoD | 3A | 40.3 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.3 | 0.7 | 0.5 | 1.4 | 1.2 | 3.1 | 1.4 | 3.5 |
| IC | Negative | 7 | 30.7 | 0.0 | 0.2 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.1 | 0.6 | 0.5 | 1.7 | 0.5 | 1.8 |
Table 9: Signal Variability Analysis Results
18
Brief Description of Clinical Studies
Clinical testing of the Panther Fusion AdV/hMPV/RV assay on the Panther Fusion system included performance and reproducibility testing. Substantial equivalence is based in part on the performance study.
Clinical Performance Study
This study was performed to demonstrate clinical performance characteristics for the Panther Fusion AdV/hMPV/RV assay. A prospective multicenter study was conducted with leftover, remnant nasopharyngeal (NP) swab specimens from male and female individuals of all ages exhibiting signs and/or symptoms of a respiratory tract infection. Four participating US pediatric/adolescent, private and/or university hospitals obtained 2961 leftover, remnant NP swab specimens. The samples were tested with the Panther Fusion AdV/hMPV/RV assay, with reference viral culture followed by direct fluorescent antibody (DFA) identification (for AdV), with an FDA-cleared assay for hMPV, and with 2 reverse transcriptase PCR assays followed by bi-directional sequencing (PCR/sequencing, for RV). FDA-cleared or validated PCR-based assays were used for discordant resolution testing for AdV and hMPV; no discordant resolution testing was performed for RV. Sensitivity and specificity (for AdV and hMPV) and negative and positive percent agreement (for RV) were estimated with corresponding 2-sided 95% Score Cls. Analyses were performed separately for each target analyte (AdV, hMPV, RV).
Of the 2961 specimens, 31 specimens/samples were withdrawn (due to incomplete reference testing results, insufficient volumes for testing, expiration prior to testing, or mishandling), 2930 samples were processed in valid Panther Fusion AdV/hMPV/RV runs, 2875 (98.1%) had final valid results, and 55 (1.9%) had final invalid results. Of the 2875 samples with valid Panther Fusion results, 1358 samples were from females and 1517 samples were from males (see Table 10). The positivity of each analyte by age group is presented in Table 11.
19
| N (%) | |
|---|---|
| Total | 2875 (100) |
| Sex | |
| Female | 1358 (47.2) |
| Male | 1517 (52.8) |
| Age Group | |
| 0 to 28 days | 82 (2.9) |
| 29 days to 65 years | 419 (14.6) |
Table 10: Summary of Subject Demographics for Prospective Samples in the Panther Fusion AdV/hMPV/RV Assay Evaluation
| Table 11: Panther Fusion AdV/hMPV/RV Positivity by Analyte and Age Group | |||
|---|---|---|---|
| % Positivity (n/N) | |||
| Analyte | AdV | hMPV | RV |
| All | 5.6% (160/2869) | 3.6% (103/2875) | 21.0% (604/2870) |
| 0 to 28 days | 1.2% (1/82) | 1.2% | 17.1% (14/82) |
| 29 days to |