(78 days)
The Quidel Molecular RSV + hMPV Assay is a multiplex Real-Time PCR (RT-PCR) assay for the qualitative detection and identification of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) ribonucleic acid (RNA) extracted from nasal and nasopharyngeal swab specimens from patients with signs and symptoms of respiratory infection. This in vitro diagnostic test is intended to aid in the differential diagnosis of RSV and hMPV infections in humans in conjunction with clinical and epidemiological risk factors. This test is not intended to differentiate the two subtypes of RSV or the four genetic sub-lineages of hMPV.
Negative results do not preclude RSV infection and/or hMPV infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.
Conversely, positive results do not rule-out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease. The use of additional laboratory testing and clinical presentation must be considered in order to obtain the final diagnosis of respiratory viral infection.
The Quidel Molecular RSV + hMPV Assay can be performed using either the Life Technologies QuantStudio™ Dx RT-PCR Instrument, the Applied Biosystems® 7500 Fast Dx RT-PCR Instrument, or the Cepheid SmartCycler® II System.
The Quidel Molecular RSV + hMPV Assay detects viral nucleic acids that have been extracted from a patient sample using the bioMérieux NucliSENS easyMAG automated extraction platform. A multiplex RT-PCR reaction is carried out under optimized conditions in a single tube generating amplicons for each of the target viruses present in the sample. This reaction is performed utilizing the Cepheid SmartCycler II, the Applied Biosystems 7500 Fast Dx. or the Life Technologies QuantStudio Dx. Identification of RSV, hMPV, and the process control (PRC) occurs by the use of target-specific primers and fluorescent-labeled probes that hybridize to conserved regions in the genomes of RSV and hMPV and the PRC.
Acceptance Criteria and Study for Quidel Molecular RSV + hMPV Assay
1. Table of Acceptance Criteria and Reported Device Performance
The provided document does not explicitly state pre-defined acceptance criteria (e.g., minimum PPA/NPA percentages or specific LoD values that must be met for approval). However, it implicitly demonstrates acceptable performance by comparing the device to FDA-cleared predicate devices and presenting the results of analytical and clinical studies. We can infer the "reported device performance" from the "Combined Clinical Site Data" table.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (RSV) | Reported Device Performance (hMPV) |
|---|---|---|---|
| Clinical Positive Percent Agreement (PPA) | High agreement with predicate device | 93.8% (95% CI: 87.7% to 96.9%) | 98.2% (95% CI: 90.6% to 99.7%) |
| Clinical Negative Percent Agreement (NPA) | High agreement with predicate device | 98.1% (95% CI: 96.7% to 99.0%) | 99.4% (95% CI: 98.4% to 99.8%) |
| Reproducibility (Detection %) | Consistent detection at various viral loads across sites | See detailed tables below for RSV and hMPV at different LoD multiples | See detailed tables below for RSV and hMPV at different LoD multiples |
| Limit of Detection (LoD) | Low concentration for reliable detection (95% positivity) | RSV A: 6.29E-01 TCID50/mL, RSV B: 2.25E-01 TCID50/mL | hMPV-A1: 8.73E+00 TCID50/mL, hMPV-A2: 2.91E+00 TCID50/mL, hMPV-B1: 2.25E+00 TCID50/mL, hMPV-B2: 2.25E+00 TCID50/mL |
Detailed Reproducibility Results (RSV):
| Panel Member ID | Detection % (Combined Sites) | Average Ct (Combined Sites) | %CV (Combined Sites) |
|---|---|---|---|
| RSV Medium Positive (5x LoD) | 100% | 30.6 | 4% |
| RSV Low Positive (2x LoD) | 98.9% | 33.1 | 6% |
| RSV High Negative (0.3x LoD) | 43.3% | 37.1 | 4% |
| RSV Negative | 0% | N/A | N/A |
| RSV Positive Control | 100% | 31.9 | 7% |
| RSV Negative Control | 0% | N/A | N/A |
Detailed Reproducibility Results (hMPV):
| Panel Member ID | Detection % (Combined Sites) | Average Ct (Combined Sites) | %CV (Combined Sites) |
|---|---|---|---|
| hMPV Medium Positive (5x LoD) | 100% | 28.6 | 3% |
| hMPV Low Positive (2x LoD) | 100% | 30.3 | 3% |
| hMPV High Negative (0.15x LoD) | 57.8% | 36.0 | 4% |
| hMPV Negative | 0% | N/A | N/A |
| hMPV Positive Control | 100% | 28.3 | 3.0% |
| hMPV Negative Control | 0% | N/A | N/A |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- RSV: 700 nasal or nasopharyngeal swab specimens (after removing 13 invalid specimens from an initial 713).
- hMPV: 707 nasal or nasopharyngeal swab specimens (after removing 6 invalid specimens from an initial 713).
- Data Provenance: Prospective study conducted during the 2013 respiratory virus season (January to March 2013) at three sites across the United States.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The ground truth for the clinical performance study was established by two FDA-cleared RT-PCR assays (Prodesse ProFlu+ and Pro hMPV+), rather than human experts. Thus, information about the number and qualifications of experts is not applicable to this study design.
4. Adjudication Method for the Test Set
The ground truth was established by two FDA-cleared predicate RT-PCR assays. The document does not describe an explicit adjudication method between these predicate devices or between the predicate devices and an independent reference standard. For each virus (RSV and hMPV) separately, the results of the Quidel Molecular assay were compared directly against the respective predicate device's results.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This study compares the performance of a molecular diagnostic assay against other molecular diagnostic assays, not the performance of human readers with and without AI assistance.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, the study describes the "standalone" performance of the Quidel Molecular RSV + hMPV Assay. It is a molecular diagnostic test that produces a qualitative result (positive/negative) based on the detection of viral nucleic acids through RT-PCR, without human interpretation of complex images or data that would typically involve a "human-in-the-loop" decision process. The output is directly generated by the instrument based on the fluorescent signal.
7. The Type of Ground Truth Used
The ground truth for the clinical performance study was established using comparison to FDA-cleared RT-PCR predicate devices. Specifically:
- For RSV, the predicate device was Prodesse ProFlu+.
- For hMPV, the predicate device was Prodesse Pro hMPV+.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" for the purpose of algorithm development or machine learning in the conventional sense. This is a molecular diagnostic assay where primers and probes are designed to target specific viral genes. The "development" of the assay involves optimizing reaction conditions, not training a machine learning model. Therefore, providing a sample size for a training set in this context is not applicable.
9. How the Ground Truth for the Training Set Was Established
As noted above, the concept of a "training set" for this type of molecular diagnostic assay is not directly applicable. The "ground truth" for developing the analytical performance characteristics (like LoD, inclusivity, specificity) would have been established through controlled laboratory experiments using known quantities and strains of viruses, and known negative samples. These are standard methods in the development of PCR-based diagnostics.
{0}------------------------------------------------
. . .
Page 1 of 12
510(k) Summary
Applicant:
Quidel Corporation 10165 McKellar Court San Diego. California 92121 Telephone: 858-552-7910 Fax: 858-646-8045
Contact Information:
Ronald H. Lollar. Senior Director Clinical and Quality Affairs 1055 East State Street Suite 100 Athens, Ohio 45701 740-589-3300 - Corporate number 740-589-3373 - Desk phone . 740-593-8437 - Fax lollar@dhiusa.com
SEP 06 2013
Date of preparation of 510(k) summary:
June 11, 2013
Device Name:
Trade name - Quidel Molecular RSV + hMPV Assay Classification name - Respiratory viral panel multiplex nucleic acid assay Product Code - OEM, OCC Regulation - 21 CFR 866.3980 Classification - Class II
Device Description:
The Quidel Molecular RSV + hMPV Assay detects viral nucleic acids that have been extracted from a patient sample using the bioMérieux NucliSENS easyMAG automated extraction platform. A multiplex RT-PCR reaction is carried out under optimized conditions in a single tube generating amplicons for each of the target viruses present in the sample. This reaction is performed utilizing the Cepheid SmartCycler II, the Applied Biosystems 7500 Fast Dx. or the Life Technologies QuantStudio Dx. Identification of RSV, hMPV, and the process control (PRC) occurs by the use of target-specific primers and fluorescent-labeled probes that hybridize to conserved regions in the genomes of RSV and hMPV and the PRC.
The following is a summary of the procedure:
{1}------------------------------------------------
- Sample Collection: Obtain nasal or nasopharyngeal swab specimens using | . standard techniques from symptomatic patients. Transport, store, and process these specimens according to established laboratory procedures.
-
- Nucleic Acid Extraction: Extract nucleic acids from the specimens with the BioMérieux NucliSENS easyMAG System following the manufacturer's instructions and using the appropriate reagents.
Prior to the extraction procedure. add 20 uL of the PRC to each 180 uL aliquot of specimen. The PRC serves to monitor inhibitors in the extracted specimen, assures that adequate amplification has taken place, and confirms that the nucleic acid extraction was sufficient.
-
- Rehydration of Master Mix: Rehydrate the lyophilized Master Mix using the Rehydration Solution. The Master Mix contains oligonucleotide primers and fluorophore/quencher-labeled probes that target conserved regions of RSV and hMPV. as well as the PRC.
-
- Nucleic Acid Amplification and Detection: Add 15 uL of the rehydrated Master Mix to each reaction tube or plate well. Then add 5 µL of extracted nucleic acids (specimen with PRC) to the plate well or appropriately labeled reaction tube. Place the tube or plate into the SmartCycler II, 7500 Fast Dx, or the Life Technologies QuantStudio Dx instruments.
Once the reaction tube or plate is added to the instrument, initiate the assay protocol. This protocol initiates reverse transcription of the RNA targets. generating complementary DNA and the subsequent amplification of the target amplicons. The Quidel Molecular RSV + hMPV Assay is based on TagMan chemistry and uses an enzyme with reverse transcriptase. DNA polymerase, and 5'-3' exonuclease activities. During DNA amplification, this enzyme cleaves the probe bound to the complementary DNA sequence, separating the quencher dye from the reporter dye. This step generates an increase in fluorescent signal upon excitation by a light source of the appropriate wavelength. With each cycle, additional dye molecules are separated from their quenchers resulting in additional signal. If sufficient fluorescence is achieved, the sample is reported as positive for the detected nucleic acid.
Intended Use:
The Quidel Molecular RSV + hMPV Assay is a multiplex Real-Time PCR (RT-PCR) assay for the qualitative detection and identification of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) ribonucleic acid (RNA) extracted from nasal and nasopharyngeal swab specimens from patients with signs and symptoms of respiratory infection. This in vitro diagnostic test is intended to
{2}------------------------------------------------
aid in the differential diagnosis of RSV and hMPV infections in humans in conjunction with clinical and epidemiological risk factors. This test is not intended to differentiate the two subtypes of RSV or the four genetic sub-lineages of hMPV.
Negative results do not preclude RSV infection and/or hMPV infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.
Conversely, positive results do not rule-out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease. The use of additional laboratory testing and clinical presentation must be considered in order to obtain the final diagnosis of respiratory viral infection.
The Quidel Molecular RSV + hMPV Assay can be performed using either the Life Technologies QuantStudio" Dx RT-PCR Instrument, the Applied Biosystems® 7500 Fast Dx RT-PCR Instrument, or the Cepheid SmartCycler® II System.
Conditions for Use:
For prescription use only.
Device Comparison
The Quidel Molecular RSV + hMPV Assay was compared to two FDA cleared RT-PCR assays. The characteristics of Quidel Molecular RSV + hMPV Assay ("Subject Device") and the Prodesse ProFlu + and Pro hMPV+ ("Predicate Devices") are described in the table below:
| Subject Device and Comparator Device Comparison | |||
|---|---|---|---|
| Item | Subject DeviceQuidel MolecularRSV + hMPV Assay | Predicate DeviceProdesse ProFlu+(K092500) | Predicate DeviceProdesse Pro hMPV+(K082688) |
| Intended Use | The QuidelMolecular RSV +hMPV Assay is amultiplex Real-TimePCR (RT-PCR)assay for thequalitative detectionand identification ofrespiratory syncytial | The ProFlu TM+ Assayis a multiplex Real-Time PCR (RT-PCR)in vitro diagnostictest for the rapid andqualitative detectionand discrimination ofInfluenza A Virus,Influenza B Virus,and RespiratorySyncytial Virus | The Pro hMPV+Assay is a Real-TimeRT-PCR in vitrodiagnostic test for thequalitative detectionof humanMetapneumovirus(hMPV) nucleic acidisolated and purifiedfrom nasopharyngealswab (NP) specimens |
| Subject Device and Comparator Device Comparison | |||
| Item | Subject DeviceQuidel MolecularRSV + hMPV Assay | Predicate DeviceProdesse ProFlu+(K092500) | Predicate DeviceProdesse Pro hMPV+(K082688) |
| virus (RSV) andhumanmetapneumovirus(hMPV) ribonucleicacid (RNA)extracted from nasaland nasopharyngealswab specimensfrom patients withsigns and symptomsof respiratoryinfection. This invitro diagnostic testis intended to aid inthe differentialdiagnosis of RSVand hMPVinfections in humansin conjunction withclinical andepidemiological riskfactors. This test isnot intended todifferentiate the twosubtypes of RSV orthe four genetic sub-lineages of hMPV.Negative results donot preclude RSVinfection and/orhMPV infection andshould not be usedas the sole basis fordiagnosis, treatmentor other patientmanagement | (RSV) nucleic acidsisolated and purifiedfrom nasopharyngeal(NP) swab specimensobtained fromsymptomatic patients.This test is intendedfor use to aid in thedifferential diagnosisof Influenza A,Influenza B and RSVviral infections inhumans and is notintended to detectInfluenza C.Negative results donot precludeinfluenza or RSVvirus infection andshould not be used asthe sole basis fortreatment or othermanagementdecisions.Conversely, positiveresults do not rule-out bacterial infectionor co-infection withother viruses. Theagent detected maynot be the definitecause of disease. Theuse of additionallaboratory testing andclinical presentationmust be considered inorder to obtain thefinal diagnosis ofrespiratory viralinfection. | obtained fromindividuals exhibitingsigns and symptomsof acute respiratoryinfection. This assaytargets a highlyconserved region ofthe Nucleocapsidgene of hMPV. Thedetection of hMPVnucleic acid fromsymptomatic patientsaids in the diagnosisof human respiratoryhMPV infection ifused in conjunctionwith other clinicaland laboratoryfindings. This test isnot intended todifferentiate the fourgenetic sub-lineagesof hMPV.Negative results donot preclude hMPVinfection and shouldnot be used as thesole basis fordiagnosis, treatmentor other managementdecisions. | |
| Subject Device and Comparator Device Comparison | |||
| Item | Subject DeviceQuidel MolecularRSV + hMPV Assay | Predicate DeviceProdesse ProFlu+(K092500) | Predicate DeviceProdesse Pro hMPV+(K082688) |
| decisions.Conversely, positiveresults do not ruleout bacterialinfection or co-infection with otherviruses. The agentdetected may not bethe definite cause ofdisease. The use ofadditional laboratorytesting and clinicalpresentation must beconsidered in orderto obtain the finaldiagnosis ofrespiratory viralinfection.The QuidelMolecular RSV +hMPV Assay can beperformed using theLife TechnologiesQuantStudioTM DxRT-PCR Instrument,the AppliedBiosystems® 7500Fast Dx RT-PCRInstrument, or theCepheidSmartCycler® IISystem. | Performancecharacteristics forInfluenza A Viruswere establishedwhen Influenza A/H3and A/H1 were thepredominantInfluenza A virusesin circulation (2006-2007 respiratoryseason). Performancecharacteristics forInfluenza A wereconfirmed whenInfluenza A/H1,Influenza A/H3, andInfluenza A/2009HiNi were thepredominantInfluenza A virusesin circulation (2008and 2009). Whenother Influenza Aviruses are emerging,performancecharacteristics mayvary.If infection with anovel Influenza Avirus is suspectedbased on currentclinical andepidemiologicalscreening criteriarecommended bypublic healthauthorities,specimens should becollected with | ||
| Subject Device and Comparator Device Comparison | |||
| Item | Subject DeviceQuidel MolecularRSV + hMPV Assay | Predicate DeviceProdesse ProFlu+(K092500) | Predicate DeviceProdesse Pro hMPV+(K082688) |
| appropriate infectioncontrol precautionsfor novel virulentInfluenza viruses andsent to state or localhealth department fortesting. Viral cultureshould not beattempted in thesecases unless a BSL3+ facility isavailable to receiveand culturespecimens. | |||
| Assay Target | RSV, hMPV | Influenza A virus,influenza B virus,RSV | hMPV |
| Sample Types | Nasal swab,nasopharyngealswab | Nasopharyngeal swab | Nasopharyngeal swab |
| Instrument/AssayPlatform | Life TechnologiesQuantStudio Dx RT-PCR Instrument, theApplied Biosystems7500 Fast Dx RT-PCR Instrument, orthe CepheidSmartCycler IISystem | Cepheid SmartCyclerII System | Cepheid SmartCyclerII System |
| Assay Controls | An internal RNAcontrol is provided | Influenza A,Influenza B, RSV A,RSV B positive RNAtranscript controlsand an internal RNAcontrol are provided | hMPV positive RNAtranscript control andan internal RNAcontrol are provided |
| ExtractionMethods | bioMérieuxNucliSENSeasyMAG System | Roche MagNA PureLC Total NucleicAcid Isolation Kit or | Roche MagNA PureLC Total NucleicAcid Isolation Kit or |
| Subject Device and Comparator Device Comparison | |||
| Item | Subject DeviceQuidel MolecularRSV + hMPV Assay | Predicate DeviceProdesse ProFlu+(K092500) | Predicate DeviceProdesse Pro hMPV+(K082688) |
| the bioMérieuxNucliSENSeasyMAG System | the bioMérieuxNucliSENSeasyMAG System | ||
| AssayMethodology | RT-PCR-basedsystem for detectingthe presence orabsence of viralRNA in clinicalspecimens | RT-PCR-basedsystem for detectingthe presence orabsence of viral RNAin clinical specimens | RT-PCR-basedsystem for detectingthe presence orabsence of viral RNAin clinical specimens |
| Viral Targets | RSV: L viralpolymerase and NS2geneshMPV: RNApolymerase gene | Influenza A: MatrixGene;Influenza B: Non-structural NS1 andNS2RSV A and RSV B:polymerase | Nucleocapsid gene |
{3}------------------------------------------------
{4}------------------------------------------------
.
.
{5}------------------------------------------------
.
{6}------------------------------------------------
Analytical Performance:
Reproducibility:
The reproducibility of the Quidel Molecular RSV + hMPV Assay using the Life Technologies QuantStudio Dx Real-Time PCR Instrument was evaluated at 3 laboratory sites (two external, one in-house). Reproducibility was assessed using a panel of 4 simulated samples that include medium positive, low positive, high negative, and negative samples. Separate panels were constructed for RSV and hMPV, using the RSV-A Long strain and hMPV-A2 strain respectively. Panels and controls were extracted using the bioMérieux NucliSENS easyMAG System and tested at each site by 2 operators for 5 days (triplicate testing x 2 operators x 5 days x 3 sites = 90 results per level for each virus). The LoD values are based on the values obtained in the LoD study.
| Reproducibility Results – QuantStudio Dx | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| PanelMemberID | Site 1 | Site 2 | Site 3 | TotalResults | ||||||
| Results | AVECt | %CV | Results | AVECt | %CV | Results | AVECt | %CV | ||
| RSVHighNegative0.3x | 15/30 | 37.6 | 3.7 | 1/30 | 37.7 | N/A | 23/30 | 36.7 | 3.7 | 39/90 |
| Reproducibility Results -QuantStudio Dx | ||||||||||
| PanelMemberID | Site 1 | Site 2 | Site 3 | TotalResults | ||||||
| LoD | Results | AVECt | %CV | Results | AVECt | %CV | Results | AVECt | %CV | |
| RSVLowPositive2x LoD | 30/30 | 32.3 | 5.3 | 29/30 | 34.9 | 5.0 | 30/30 | 32.1 | 2.7 | 89/90 |
| RSVMedPositive5x LoD | 30/30 | 30.3 | 1.9 | 30/30 | 31.5 | 5.5 | 30/30 | 29.9 | 1.6 | 90/90 |
| RSVNegative | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/90 |
| RSVNegativeControl | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/90 |
| RSVPositiveControl | 30/30 | 30.9 | 1.7 | 30/30 | 33.0 | 5.1 | 30/30 | 31.9 | 10.2 | 90/90 |
| hMPVHighNegative0.15xLoD | 20/30 | 35.9 | 4.0 | 11/30 | 35.2 | 5.9 | 21/30 | 36.6 | 4.0 | 52/90 |
| hMPVLowPositive2x LoD | 30/30 | 30.3 | 5.0 | 30/30 | 30.2 | 2.5 | 30/30 | 30.4 | 2.1 | 90/90 |
| hMPVMedPositive5x LoD | 30/30 | 28.9 | 2.0 | 30/30 | 28.4 | 1.2 | 30/30 | 28.3 | 3.7 | 90/90 |
| hMPVNegative | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/90 |
| hMPVNegative | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/90 |
| Reproducibility Results -QuantStudio Dx | ||||||||||
| PanelMemberID | Site 1 | Site 2 | Site 3 | TotalResults | ||||||
| Results | AVECt | %CV | Results | AVECt | %CV | Results | AVECt | %CV | ||
| Control | ||||||||||
| hMPVPositiveControl | 30/30 | 28.7 | 0.6 | 30/30 | 28.1 | 2.3 | 30/30 | 28.3 | 4.4 | 90/90 |
{7}------------------------------------------------
Page 8 of 12
·
{8}------------------------------------------------
Page 9 of 12
The data from the combined sites indicates that the Quidel Molecular RSV + hMPV Assay generates reproducible results for RSV and hMPV when tested with the Life Technologies QuantStudio Dx.
| Combined Sites RSV | ||||||
|---|---|---|---|---|---|---|
| 5X LoD | 2X LoD | 0.3X LoD | Negative | PositiveControl | NegativeControl | |
| Detection % | 100% | 98.9% | 43.3% | 0% | 100% | 0% |
| Ave. | 30.6 | 33.1 | 37.1 | N/A | 31.9 | N/A |
| STDEV | 1.3 | 1.9 | 1.4 | N/A | 2.3 | N/A |
| %CV | 4% | 6% | 4% | N/A | 7% | N/A |
| Combined Sites hMPV | ||||||
|---|---|---|---|---|---|---|
| 5X LoD | 2X LoD | 0.15X LoD | Negative | PositiveControl | NegativeControl | |
| Detection % | 100% | 100% | 57.8% | 0% | 100% | 0% |
| Ave. | 28.6 | 30.3 | 36.0 | N/A | 28.3 | N/A |
| STDEV | 0.8 | 1.0 | 1.6 | N/A | 0.8 | N/A |
| %CV | 3% | 3% | 4% | N/A | 3.0% | N/A |
Precision
The precision of the Quidel Molecular RSV + hMPV Assay using the Life Technologies QuantStudio Dx Real-Time PCR Instrument was determined using quantified dilutions of RSV and hMPV stocks (10X, 3X, and 0.15X LoD). These dilutions were tested by two operators for twelve days. The data from this study indicates that when tested on the Life Technologies QuantStudio Dx Real-Time PCR Instrument, the Quidel Molecular RSV + hMPV Assay produces repeatable, precise results.
Limit of Detection
The analytical sensitivity (limit of detection or LoD) of the Quidel Molecular RSV + hMPV Assay using the Life Technologies QuantStudio Dx Real-Time PCR Instrument was determined using quantified (TCID50mL) cultures of 2 RSV strains (RSV-A Long
{9}------------------------------------------------
and RSV-B Washington strains) and 4 hMPV strains (hMPV A1, hMPV A2, hMPV B1, and hMPV B2 strains) serially diluted in negative nasal matrix. Each dilution was extracted in replicates of 20 per concentration of virus using the bioMérieux NucliSENS easyMAG System. Analytical sensitivity (LoD) is defined as the lowest concentration at which 95% of all replicates tested positive.
| Virus | LoD TCID50/mLQuantStudio Dx |
|---|---|
| RSV A | 6.29E-01 |
| RSV B | 2.25E-01 |
| hMPV-A1 | 8.73E+00 |
| hMPV-A2 | 2.91E+00 |
| hMPV-B1 | 2.25E+00 |
| hMPV-B2 | 2.25E+00 |
Carryover and Cross-contamination Studies
In an internal study there was no evidence of carry-over/cross contamination on the OuantStudio Dx thermocycler platform when the Quidel Molecular RSV + hMPV Assay was used to detect the presence of high concentrations of RSV-B and hMPV-A1 (2.57E+06 and 3.16E+07. respectively) extracted with the BioMérieux NucliSENS easyMAG System.
Competitive Interference
A study was performed to determine whether competitive interference exists when both RSV and hMPV analytes are present in the same reaction when tested on the Life Technologies OuantStudio Dx Real-Time PCR Instrument. Results showed that at 2X LoD hMPV was inhibited at a level 10,000X above LoD of RSV-A when tested on the QuantStudio Dx. Inhibition was also seen at this concentration on the Applied Biosystems 7500 Fast Dx and Cepheid SmartCycler II (K122189).
Analytical Reactivity (Inclusivity):
Please see K122189 for Analytical Reactivity (Inclusivity) studies.
Analytical Specificity (Cross-Reactivity):
Please see K122189 for Analytical Specificity (Cross-Reactivity) studies.
Clinical Performance:
Performance characteristics of the Quidel Molecular RSV + hMPV Assay using the Life Technologies QuantStudio Dx Real-Time PCR Instrument was established during a prospective study during the 2013 respiratory virus season (January to March 2013). Seven hundred and thirteen (713) nasal or nasopharyngeal swab specimens that were collected and extracted fresh for routine respiratory virus testing were used for this study at three (3) sites across the United States. A single specimen was collected per patient.
{10}------------------------------------------------
The specimens were extracted with the bioMérieux NucliSENS easyMAG System and tested with the Quidel Molecular RSV + hMPV Assay using the Life Technologies QuantStudio Dx RT-PCR Instrument. Sites 1 and 2 also extracted each specimen with the bioMérieux NucliSENS easyMAG System and tested with the comparator devices. Aliquots of each specimen from Site 3 were sent to Site 1 for testing with the comparator devices. Sample extracts were stored at -70℃ until the time of testing.
Combined Clinical Site Data:
Seven hundred and thirteen (713) nasal or nasopharyngeal swab specimens were tested by both the subject and comparator device for RSV viral RNA. A total of thirteen (13) invalid specimens were removed from the analysis. Two (2) of these specimens were invalid on initial and repeat testing with the subject device (0.3%). Eleven (11) specimens were invalid on initial and repeat testing on the comparator device (1.5%). The table below details the results for the remaining seven hundred (700) specimens.
| RSV | |||
|---|---|---|---|
| Comparator: FDA Cleared RT-PCR device | |||
| Quidel Molecular | Positive | Negative | Total |
| Positive | 105 | 11 | 116 |
| Negative | 7 | 577 | 584 |
| Total | 112 | 588 | 700 |
| 95% CI | |||
| Positive Percent Agreement | 105/112 | 93.8% | 87.7% to 96.9% |
| Negative Percent Agreement | 577/588 | 98.1% | 96.7% to 99.0% |
Seven hundred and thirteen (713) nasal or nasopharyngeal swab specimens were tested by both the subject and comparator device for hMPV viral RNA. A total of six (6) invalid specimens were removed from the analysis. Two (2) of these specimens were invalid on initial and repeat testing with the subject device (0.3%). Four (4) specimens were invalid on initial and repeat testing on the comparator device (0.6%). The table below details the results for the remaining seven hundred and seven (707) specimens.
| hMPV | |||
|---|---|---|---|
| Comparator: FDA Cleared RT-PCR device | |||
| Quidel Molecular | Positive | Negative | Total |
| Positive | 55 | 4 | 59 |
| Negative | 1 | 647 | 648 |
| Total | 56 | 651 | 707 |
| 95% CI | |||
| Positive Percent Agreement | 55/56 | 98.2% | 90.6% to 99.7% |
| Negative Percent Agreement | 647/651 | 99.4% | 98.4% to 99.8% |
Conclusions:
{11}------------------------------------------------
The results of the analytical and clinical performance studies submitted in this premarket notification are complete and demonstrate that, when performed on the Life Technologies QuantStudio Dx RT-PCR Instrument, the Quidel Molecular RSV + hMPV Assay was substantially equivalent compared to the two FDA 510(k) cleared molecular devices.
{12}------------------------------------------------
DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/12/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized depiction of an abstract caduceus, which is a symbol often associated with healthcare and medicine. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the symbol.
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-C609 Silver Spring, MI) 20993-0002
September 6, 2013
QUIDEL CORPORATION C/O RONALD H. LOLLAR SENIOR DIRECTOR CLINICAL AND QUALITY AFFAIRS DIAGNOSTIC HYBRIDS, INC. 1055 EAST STATE STREET. SUITE 100 ATHENS OH 45701
Rc: K131813
Trade/Device Name: Ouidel Molecular RSV + hMPV Assay Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory viral panel multiplex nucleic acid assay Regulatory Class: II Product Code: OEM. OCC Dated: June 19. 2013 Received: June 20, 2013
Dear Mr. Lollar:
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 10 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. Iisting of devices, good manufacturing practice. labeling, and prohibitions against misbranding and adulteration. Please note: CDRFI 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 Parts 801 and 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.
{13}------------------------------------------------
Page 2-Mr. Lollar
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.
Sincerely yours,
Sally A. Hojvat -S
Sally Hojvat, M.Sc., Ph.D. Director, Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
{14}------------------------------------------------
Indications for Use
510(k) Number: K131813
Device Name: Quidel Molecular RSV + hMPV Assay
Indications for Use:
The Quidel Molecular RSV + hMPV Assay is a multiplex Real-Time PCR (RT-PCR) assay for the qualitative detection and identification of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) ribonucleic acid (RNA) extracted from nasal and nasopharyngeal swab specimens from patients with signs and symptoms of respiratory infection. This in vitro diagnostic test is intended to aid in the differential diagnosis of RSV and hMPV infections in humans in conjunction with clinical and epidemiological risk factors. This test is not intended to differentiate the two subtypes of RSV or the four genetic sub-lineages of hMPV.
Negative results do not preclude RSV infection and/or hMPV infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.
Conversely, positive results do not rule-out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease. The use of additional laboratory testing and clinical presentation must be considered in order to obtain the final diagnosis of respiratory viral infection.
The Quidel Molecular RSV + hMPV Assay can be performed using either the Life Technologies QuantStudio™ Dx RT-PCR Instrument, the Applied Biosystems® 7500 Fast Dx RT-PCR Instrument, or the Cepheid SmartCycler® II System.
Prescription Use __________________________________________________________________________________________________________________(21 CFR 801 Subpa (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of Center for Devices and Radiological Health (CDRH)
Tamara V. Feldblyum -S 2013.09.04 16:11:21 -04'00'
§ 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.