(187 days)
Not Found
No
The device description and performance studies focus on immunofluorescence staining and manual microscopic examination for antigen detection. There is no mention of automated image analysis, pattern recognition, or any computational methods that would suggest the use of AI/ML.
No.
Explanation: The device is intended for the qualitative detection and identification of viral antigens, which means it is a diagnostic device, not a therapeutic one. It provides information for diagnosis but does not treat or alleviate a condition.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device "is intended for the qualitative detection and identification of influenza A, while screening for influenza B virus, respiratory syncytial virus, adenovirus, and parainfluenza virus types 1, 2 and 3 viral antigens...from patients with signs and symptoms of respiratory infection." This function of detecting and identifying specific viral antigens to provide information about a patient's condition falls directly under the definition of a diagnostic device.
No
The device is a diagnostic kit containing reagents, control slides, wash solution, and mounting fluid, which are physical components used in a laboratory procedure. 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 device is "intended for the qualitative detection and identification of influenza A, while screening for influenza B virus, respiratory syncytial virus, adenovirus, and parainfluenza virus types 1, 2 and 3 viral antigens, in nasal and nasopharyngeal swabs and aspirates or in cell culture." This describes a test performed on specimens taken from the human body to provide information for diagnosis.
- Methodology: The device uses immunofluorescence with monoclonal antibodies to detect viral antigens in biological specimens (nasal and nasopharyngeal swabs and aspirates, or cell culture). This is a common method for in vitro diagnostic tests.
- Specimen Type: The test is performed on specimens obtained from the human body (nasal and nasopharyngeal swabs and aspirates).
- Purpose: The purpose is to detect viral antigens from patients with signs and symptoms of respiratory infection, which is directly related to diagnosing or screening for these infections.
All these characteristics align with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The Diagnostic Hybrids, Inc. device, D3 Duet DFA Influenza A/Respiratory Virus Screening Kit, is intended for the qualitative detection and identification of influenza A, while screening for influenza B virus, respiratory syncytial virus, adenovirus, and parainfluenza virus types 1, 2 and 3 viral antigens. in nasal and nasopharyngeal swabs and aspirates or in cell culture. The assay detects viral antigens by immunofluorescence using monoclonal antibodies (MAbs), from patients with signs and symptoms of respiratory infection.
It is recommended that specimens found to be negative after examination of the direct specimen result be confirmed by cell culture. Negative results do not preclude influenza virus infection and should not be used as the sole basis for diagnosis, treatment or other management decisions.
Performance characteristics for influenza A virus detection and identification were established when influenza A H3N2 and influenza A H1N1 were the predominant influenza A strains circulating in the United States. When other Influenza A viruses are emerging, performance characteristics may vary. If infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent Influenza viruses and sent to a state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
Product codes
GNW
Device Description
The Diagnostic Hybrids, Inc. device, D3 Duet DFA Influenza A/Respiratory Virus Screening Kit, uses a blend of viral antigen-specific murine MAbs. MAbs for influenza A virus are directly labeled with R-phycoerythrin (R-PE) for the rapid detection and identification of influenza A virus. MAbs for influenza B virus, respiratory syncytial virus, adenovirus, and parainfluenza virus types 1, 2, and 3 are directly labeled with fluorescein isothiocyanate (FITC), for rapid detection of these agents.
Kit components:
- D3 Duet DFA Influenza A/Respiratory Virus Screening Reagent Rphycoerythrin-labeled murine MAbs directed against influenza A virus and a mixture of fluorescein-labeled murine MAbs directed against influenza B. respiratory syncytial virus, adenovirus, and parainfluenza virus types 1, 2, and 3. The buffered, stabilized, aqueous solution also contains Evans Blue as a counterstain and 0.1% sodium azide as preservative.
- Normal Mouse Gamma Globulin DFA Reagcnt a mixture of fluorescein labeled murine gamma globulin that has been shown to be non-reactive with any of the listed respiratory viruses. The buffered, stabilized, aqueous solution contains Evans Blue as a counter-stain and 0.1% sodium azide as preservative.
- Respiratory Virus Antigen Control Slides five individually packaged control slides containing wells with cell culture-derived positive and negative control cells. Each positive well is identified with the virus infected cells present, i.e., influenza A virus, influenza B virus, respiratory syncvtial virus, adenovirus, and parainfluenza virus types 1, 2 and 3. The negative well contains uninfected cultured cells. Each slide is intended to be stained only one time.
- Wash Solution Concentrate a 40X concentrate consisting of Tween 20 and 4% sodium azide (0.1% sodium azide after dilution in de-mineralized water) in a 40X phosphate buffered saline solution.
- Mounting Fluid an aqueous, buffered, stabilized solution of glycerol and . 0.1% sodium azide.
The cells to be tested, derived from a clinical specimen or cell culture, are placed onto a glass slide and allowed to air dry. The cells are fixed in acetone. The D3 Duet DFA Influenza A/Respiratory Virus Screening Reagent is added to the cells which are then incubated for 15 to 30 minutes at 35° to 37°C in a humidified chamber or humidified incubator. The stained cells are then washed with the diluted wash solution, a drop of the supplied Mounting Fluid is added and a coverslip is placed on the prepared cells. The cells are examined using a fluorescence microscope. The influenza A virus infected cells will fluoresce golden-yellow, while cells infected with any of the other six viruses will fluoresce apple-green. Uninfected cells will contain no fluorescence but will be stained rcd by the Evans Blue counter-stain. If only golden-yellow fluorescent cells are present the specimen can be reported as positive for influenza A antigen. If only apple-green fluorescent cells are present, the particular virus may be identified using the individual reagents from the DS Ultra™ DFA Respiratory Virus Screening & ID Kit (D3 Ultra) on new, separate cell preparations. If both golden-yellow and apple-green are present, the additional virus may be identified using the individual reagents from the D3 Ultra on new, separate cell preparations.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Nasal, Nasopharyngeal
Indicated Patient Age Range
0 - >90 years
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Non-Clinical Performance:
Staining patterns of the phycoerythrin-labeled influenza A virus MAbs on influenza A virus infected cells were similar to those of the Predicate device.
Precision/Reproducibility:
Assay precision, intra-assay variability and inter assay variability were assessed with a panel of proficiency-level antigen control slides. The panel consisted of slides spotted with cell preparations of the following:
- Low level influenza A (Victoria strain)
- Mid level influenza A (Victoria strain)
- Low level influenza A (Victoria strain) mixed with Mid level RSV (Washington strain)
- Mid level influenza A (Victoria strain) mixed with Low level RSV (Washington strain)
- Low level respiratory virus (either influenza virus B {Taiwan strain}, adenovirus type 1, Parainfluenza virus types 1, 2, or 3 (strains C35, Greer, C243 respectively). This panel member was rotated during the 5-days of testing so that cach virus is tested twice.
- Negative no infected cells present
The low level is estimated to contain between 4 to 10% infected cells per cell spot. The mid level is estimated to contain between 20 to 25% infected cells per cell spot. Both levels were below the level used in quality control slides. Each panel member was re-coded daily to prevent its identification. Each panel was stained twice per day for 5-days by three diffcrent laboratorics.
The following results were recorded for both the control slide and the panel slide: - Presence or absence of Yellow-gold fluorescence.
- Percent of cells exhibiting Yellow-gold fluorescence
- Presence or absence of Green fluorescence
- Percent of cells exhibiting Green fluorescence
The combined data for negative specimens -- no infected cells present - from the three sites demonstrates that the R-PF labeled and FITC labeled MAbs reproducibly do not stain uninfected cells. No fluorescent cells were scen in 100% (60/60) of the wells lacking infected cells.
The combined data from the three sites demonstrates reproducible detection of influenza A virus by the R-PE labeled MAbs. The presence of influenza A virus infected cells was reported in 95.3% (143/150) of the wells in which the infected cells were expected.
The combined data demonstrates the reproducibility of the detection of respiratory syncytial virus by the FITC labeled MAbs. The presence of respiratory syncytial virus infected cells was reported in 100% (90/90) of the wells in which the infected cells were expected.
The combined data demonstrates that the presence of R-PE fluorescent cells reproducibly does not interfere with the detection of respiratory syncytial virus by the FITC labeled MAbs. The presence of respiratory syncytial virus infected cells was reported in 100% (53/53) of the wells in which the R-PE stained infected cells were present.
The combined data from all three sites demonstrates that the presence of R-PE in the stain reproducibly does not interfere with the FITC staining of other viruses. The presence of influenza B virus infected cells was reported in 100% (36/36) of the wells in which the infected cells were expected. The presence of adenovirus infected cells was reported in 100% (36/36) of the wells in which the infected cells were expected. The presence of parainfluenza virus type 1 virus infected cells was reported in 100% (36/36) of the wells in which the infected cells were expected. The presence of parainfluenza virus type 2 virus infected cells was reported in 100% (36/36) of the wells in which the infected cells were expected. The presence of parainfluenza virus type 3 virus infected cells was reported in 100% (36/36) of the wells in which the infected cells were expected.
The reproducibility study data demonstrates that the presence of R-PE in the stain reproducibly does not interfere with the detection of the 5 respiratory viruses by their respective FITC labeled MAbs.
Analytical specificity:
Analytical detection limit for the seven viruses detected by the D3 Duet was reported in numbers of fluorescent cells per cell monolayer. Each master stock virus preparation was diluted in a ten-fold manner. Four wells of a 96-well cell culture plate were inoculated with each dilution. The plates were centrifuged at 700 xg for 60 minutes, and then incubated at 35° to 37°C for 24hours. Four wells from each dilution were stained with the D3 Duet. Each well was then examined at 200x magnification and the number of fluorescent cells counted.
Analytical reactivity (inclusivity) of the D3 Duet was evaluated using 10 influenza A virus and 4 influenza B virus strains. Four wells of a 96-well cell culture plate were inoculated with each viral strain (diluted to less than 20-TCID50 per 0.2-mL inoculum). The plates were centrifuged at 700xg for 60 minutes, and then incubated at 35° to 37°C for 24-hours. Four wells from cach strain were stained with the D3 Duet, and each well was then examined at 200x magnification and the number of fluorescent cells counted.
Based on the data presented, the assay can reliably detect influenza A virus and influenza B virus strains exhibiting both temporal and geographical diversity at viral levels near the limit of detection in cell culture. Analytical sensitivity of the phycoerythrin-labeled influenza A MAbs of the D3 Duet was determined, and compared to that of the fluorescein-labeled influenza A MAbs of the D' Ultra. Cell monolayers of R-Mix in 96-well plates were inoculated with prepared virus stock of influenza A virus, Victoria strain, VR-822 (H3N2), diluted to give a TCID50 of 1 per 0.2-mL inoculum. The plates were incubated at 37℃ for 24 hours. Monolayers were stained using the procedures in the D Ultra's labeling or the D Duet's draft labeling. The assay was performed four times. Results indicate that analytical sensitivities of the phycoerythrin-labeled and the fluorcscein-labeled influenza A MAbs are not statistically different, by a paired t-test.
Clinical Performance:
Direct fresh specimens:
A study was performed prospectively at three sites with 1203 fresh specimens that were received for respiratory virus testing. Each specimen was evaluated by the D3 Duet DFA Influenza A/Respiratory Virus Screening Kit and a cleared DSFA device for the presence of influenza A, influenza B, respiratory syncytial virus, adenovirus, parainfluenza 1, parainfluenza 2 and parainfluenza 3 in cells derived from clinical specimens. A total of nineteen specimens were excluded from analysis due to a site deviations, duplicate specimen, insufficient cell numbers, or high background. These exclusions left 1184 specimen results for analysis.
The D2 Duet's ability to identify influenza A virus using phycoerythrin in direct specimens was compared to the D3 Ultra's ability using fluorescein. The positive percent agreement was 99% (95% CI range of 94.5% to 99.8%). The negative percent agreement was 100% (95% CI range of 99.7% to 100%). When the ability of the D3 Duet to detect the six other respiratory viruses using fluorescein in direct specimens was compared to the D3 Ultra's ability using fluorescein, the positive percent agreement was 100% (95% CI range of 99.0% to 100%). The negative percent agreement was 100% (95% CI range of 99.5% to 100%).
Cultured specimens:
To evaluate the performance of this device using cultured clinical specimens, a fourth study was performed with 298 frozen specimens to compare performance of the D' Duet DFA Influenza A/Respiratory Virus Screening Kit with that of the predicate for the presence of Influenza A, Influenza B, Respiratory Syncytial Virus, Adenovirus, Parainfluenza 1, Parainfluenza 2 and Parainfluenza 3 (Para 3) from cultured clinical specimens. At Study Site 4, 298 frozen specimens were processed for cell culture testing in accordance with the procedure in the Comparator product insert (same procedure for both Subject and Comparator devices) using R-Mix Too™ FreshCells™ in 48/24-fill multi-well plates. All specimens at study site 4 were derived from nasopharyngeal specimens.
Study Site 4 (culture) - D3 Duet R-PE identification of influenza A virus positive specimens: Positive Percent Agreement (PPA) was 100% (67/67). Negative Percent Agreement (NPA) was 100% (231/231).
Study Site 4 (culture) - D3 Duet FITC detection of influenza B virus, respiratory syncytial virus, adenovirus, and parainfluenza virus types 1, 2, and 3 viruses: Positive Percent Agreement (PPA) was 100% (72/72). Negative Percent Agreement (NPA) was 100% (226/226).
A variety of viral respiratory pathogens were isolated. Virus identification of De Duet FITC Positive Specimens using D3 Ultra Identification Reagents yiclded the following isolates: influenza A virus [prevalence 22.5% (67/298)], influenza B virus [prevalence 6.7% (20/298)], respiratory syncytial virus [prevalence 11.1% (33/298)], adenovirus [prevalence 3.4% (10/298)], parainfluenza type 1 virus [prevalence 1.7% (5/298)], parainfluenza type 2 virus [prevalence 1.0% (3/298)], and parainfluenza type 3 virus [prevalence 3.0% (9/298)]. There were sixteen co-infections.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Clinical Performance (Direct Specimen - 1184 Specimens):
D3 Duet R-PE (influenza A virus):
Positive Percent Agreement (PPA): 99% (99/100), 95% CI: 94.5, 99.8%
Negative Percent Agreement (NPA): 100% (1084/1084), 95% CI: 99.7, 100%
D3 Duet FITC (influenza B virus, respiratory syncytial virus, adenovirus, and parainfluenza virus types 1, 2 and 3 viruses):
Positive Percent Agreement (PPA): 100% (386/386), 95% CI: 99.0, 100%
Negative Percent Agreement (NPA): 100% (798/798), 95% CI: 99.5, 100%
Virus Follow-up Identification of 386 D3 Duet FITC Positive Specimens:
Influenza B virus: Sensitivity 100% (11/11), Specificity 100% (1173/1173)
Adenovirus: Sensitivity 100% (52/52), Specificity 100% (1132/1132)
Parainfluenza type 1: Sensitivity 100% (4/4), Specificity 100% (1180/1180)
Parainfluenza type 2: Sensitivity 100% (1/1), Specificity 100% (1183/1183)
Parainfluenza type 3: Sensitivity 100% (19/19), Specificity 100% (1165/1165)
Respiratory Syncytial Virus: Sensitivity 100% (299/299), Specificity 100% (885/885)
Clinical Performance (Cultured Specimens - 298 Specimens):
Study Site 4 (culture) - D3 Duet R-PE identification of influenza A virus positive specimens:
Positive Percent Agreement (PPA): 100% (67/67)
Negative Percent Agreement (NPA): 100% (231/231)
Study Site 4 (culture) - D3 Duet FITC detection of influenza B virus, respiratory syncytial virus, adenovirus, and parainfluenza virus types 1, 2, and 3 viruses:
Positive Percent Agreement (PPA): 100% (72/72)
Negative Percent Agreement (NPA): 100% (226/226)
Predicate Device(s)
K061101, D3 Ultra DFA Respiratory Virus Screening & ID Kit
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 866.3330 Influenza virus serological reagents.
(a)
Identification. Influenza virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to influenza in serum. The identification aids in the diagnosis of influenza (flu) and provides epidemiological information on influenza. Influenza is an acute respiratory tract disease, which is often epidemic.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.
0
D3 DUET DFA INFLUENZA A/RESPIRATORY VIRUS SCREENING KIT
SECTION 05, 510(K) SUMMARY
Applicant:
DIAGNOSTIC HYBRIDS, INC. 1055 East State Street Suite 100 Athens, OHIO 45701
DEC 2 3 2008
Contact Information:
Gail R. Goodrum Vice President, Regulatory Affairs E-mail: goodrum(@dhiusa.com Telephone: 740-589-3300 Desk Extension: 740-589-3380 FAX: 740-593-8437
Date of preparation of 510(k) summary:
June 13, 2008
Device Name:
Trade name - D3 Duet DFA Influenza A/Respiratory Virus Screening Kit Common name - Fluorescent antibody test for screening Influenza A Classification name - Antisera, Cf, Influenza Virus A, B, C Product Code - GNW Regulation - 21 CFR 866.3330, Class I, Influenza virus serological reagents; Panel Microbiology (83)
Legally marketed device to which equivalence is claimed:
K061101, D3 Ultra DFA Respiratory Virus Screening & ID Kit
Intended Use: The Diagnostic Hybrids, Inc. device, D3 Duet DFA Influenza A/Respiratory Virus Screening Kit, is intended for the qualitative detection and identification of influenza A, while screening for influenza B virus, respiratory syncytial virus, adenovirus, and parainfluenza virus types 1, 2 and 3 viral antigens. in nasal and nasopharyngeal swabs and aspirates or in cell culture. The assay detects viral antigens by immunofluorescence using monoclonal antibodies (MAbs), from patients with signs and symptoms of respiratory infection.
1
It is recommended that specimens found to be negative after examination of the direct specimen result be confirmed by cell culture. Negative results do not preclude influenza virus infection and should not be used as the sole basis for diagnosis, treatment or other management decisions.
Performance characteristics for influenza A virus detection and identification were established when influenza A H3N2 and influenza A H1N1 were the predominant influenza A strains circulating in the United States. When other Influenza A viruses are emerging, performance characteristics may vary. If infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent Influenza viruses and sent to a state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
Device Description:
The Diagnostic Hybrids, Inc. device, D Duet DFA Influenza A/Respiratory Virus Screening Kit, uses a blend of viral antigen-specific murine MAbs. MAbs for influenza A virus are directly labeled with R-phycoerythrin (R-PE) for the rapid detection and identification of influenza A virus. MAbs for influenza B virus, respiratory syncytial virus, adenovirus, and parainfluenza virus types 1, 2, and 3 are directly labeled with fluorescein isothiocyanate (FITC), for rapid detection of these agents.
Kit components:
- · D3 Duet DFA Influenza A/Respiratory Virus Screening Reagent Rphycoerythrin-labeled murine MAbs directed against influenza A virus and a mixture of fluorescein-labeled murine MAbs directed against influenza B. respiratory syncytial virus, adenovirus, and parainfluenza virus types 1, 2, and 3. The buffered, stabilized, aqueous solution also contains Evans Blue as a counterstain and 0.1% sodium azide as preservative.
- Normal Mouse Gamma Globulin DFA Reagcnt a mixture of fluorescein labeled murine gamma globulin that has been shown to be non-reactive with any of the listed respiratory viruses. The buffered, stabilized, aqueous solution contains Evans Blue as a counter-stain and 0.1% sodium azide as preservative.
- · Respiratory Virus Antigen Control Slides five individually packaged control slides containing wells with cell culture-derived positive and negative control cells. Each positive well is identified with the virus infected cells present, i.e., influenza A virus, influenza B virus, respiratory syncvtial virus, adenovirus, and parainfluenza virus types 1, 2 and 3. The negative well contains uninfected cultured cells. Each slide is intended to be stained only one time.
- · Wash Solution Concentrate a 40X concentrate consisting of Tween 20 and 4% sodium azide (0.1% sodium azide after dilution in de-mineralized water) in a 40X phosphate buffered saline solution.
2
- Mounting Fluid an aqueous, buffered, stabilized solution of glycerol and . 0.1% sodium azide.
The cells to be tested, derived from a clinical specimen or cell culture, are placed onto a glass slide and allowed to air dry. The cells are fixed in acetone. The D3 Duet DFA Influenza A/Respiratory Virus Screening Reagent is added to the cells which are then incubated for 15 to 30 minutes at 35° to 37°C in a humidified chamber or humidified incubator. The stained cells are then washed with the diluted wash solution, a drop of the supplied Mounting Fluid is added and a coverslip is placed on the prepared cells. The cells are examined using a fluorescence microscope. The influenza A virus infected cells will fluoresce golden-yellow, while cells infected with any of the other six viruses will fluoresce apple-green. Uninfected cells will contain no fluorescence but will be stained rcd by the Evans Blue counter-stain. If only golden-yellow fluorescent cells are present the specimen can be reported as positive for influenza A antigen. If only apple-green fluorescent cells are present, the particular virus may be identified using the individual reagents from the DS Ultra™ DFA Respiratory Virus Screening & ID Kit (D3 Ultra) on new, separate cell preparations. If both golden-yellow and apple-green are present, the additional virus may be identified using the individual reagents from the D3 Ultra on new, separate cell preparations.
Technological Characteristics:
The DHI device, D3 Duet, has been compared directly to the DHI device, D3 Ultra, as the legally marketed device. The technology used in both devices is based on a standard immunofluorescence assay technique utilizing either R-PF. or FITC-labeled MAbs. A summary is provided in Table 5.1 below:
| TABLE 5.1: Technological Characteristics Comparison | |||
|---|---|---|---|
| Characteristic | D3 Duet DFA Influenza A/ | ||
| Respiratory Virus Screening Kit | D3 Ultra DFA Respiratory Virus | ||
| Screening & ID Kit | |||
| Monoclonal antibodies (MAbs) | The Influenza A/Respiratory Virus | ||
| DFA Screening Reagent | |||
| contains 12 MAbs to 6 different | |||
| respiratory viruses (influenza B virus, | |||
| respiratory syncytial virus, adenovirus, | |||
| parainfluenza virus type 1, | |||
| parainfluenza virus type 2, | |||
| parainfluenza virus type 3), plus 2 | |||
| MAbs to influenza A virus. | |||
| One of the 2 MAbs to influenza A | |||
| virus is different from either of those | |||
| used in the D3 Ultra Reagent; the | |||
| second is the same. | The Respiratory Virus DFA Screening | ||
| Reagent | |||
| contains 12 MAbs to 6 different | |||
| respiratory viruses (influenza B virus, | |||
| respiratory syncytial virus, adenovirus, | |||
| parainfluenza virus type 1, | |||
| parainfluenza virus type 2, | |||
| parainfluenza virus type 3), plus 2 | |||
| MAbs to influenza A virus. | |||
| TABLE 5.1: Technological Characteristics Comparison | |||
| Characteristic | D3 Duet DFA Influenza A/ | ||
| Respiratory Virus Screening Kit | D3 Ultra DFA Respiratory Virus | ||
| Screening & ID Kit | |||
| Labeling method | Direct labeling, |
- using R-phycoerythrin (R-PE) to
label the MAbs to influenza A virus
antigens - using fluorescein isothiocyanate
(FITC) to label all other MAbs with
fluorescein moiety | Direct labeling, - using fluorescein isothiocyanate
(FITC) to label all other MAbs with
fluorescein moiety |
| Fluorescein-labeled MAbs | | Influenza B virus, respiratory syncytial
virus, adenovirus, parainfluenza virus
type 1, parainfluenza virus type 2,
parainfluenza virus type 3 | Influenza A virus, influenza B virus,
respiratory syncytial virus, adenovirus
parainfluenza virus type 1,
parainfluenza virus type 2,
parainfluenza virus type 3 |
| Phycoerythrin-labeled MAbs | | Influenza A virus
(Phycoerythrin-labeled influenza A
virus MAbs stain with golden-yellow
fluorescence) | None
(Fluorescein-labeled influenza A virus
MAbs stain with apple-green
fluorescence) |
| Cell Fixative | | Cell Fixative is the same for both devices:
Acetone | |
| Performance characteristics | | | |
| Staining patterns | | Staining patterns are the same for both devices:
Influenza A and B: The fluorescence is cytoplasmic, nuclear or both.
Cytoplasmic staining is often punctate with large inclusions while nuclear
staining is uniformly bright.
Respiratory Syncytial Virus: The fluorescence is cytoplasmic and punctate
with small inclusions in the syncytia.
Parainfluenza 1, 2, 3: The fluorescence is cytoplasmic and punctate with
irregular inclusions. Types 2 and 3 cause the formation of syncytia.
Adenovirus: The fluorescence is cytoplasmic and punctate or bright nuclear or
both. | |
| Analytical sensitivity, according
to 96-well cell culture plates
infected with Flu A diluted to
give a TCID50 of 1 per 0.2-mL
inoculum (reported as average
of 4 runs) | | There is no significant difference between the two devices for analytical
sensitivity.
34.3 ± 12.0
culture positives out of 96 | |
| | | | 34.8 + 9.7
culture positives out of 96 |
| Analytical specificity (for
influenza A virus strains; MAbs
are reactive with all listed
strains) | | Mabs to influenza A virus were shown to be reactive with these virus strains: | |
| | | 9 Flu A strains (Aichi, VR-547
(H3N2); Mal, VR-98 (H1N1); Hong
Kong, VR-544 (I13N2); Denver, VR-
546 (H1N1); Port Chalmers, VR-810
(H3N2); Victoria, VR-822 (H3N2);
New Jersey, VR-897(H1N1); WS, VR-
1520 (H1N1); PR, VR-95 (H1N1)) | 9 Flu A strains (Aichi, VR-547
(H3N2); Mal, VR-98 (H1N1); Hong
Kong, VR-544 (H3N2); Denver, VR-
546 (H1N1); Port Chalmers, VR-810
(H3N2); Victoria, VR-822 (H3N2);
New Jersey, VR-897(H1N1); WS, VR-
1520 (H1N1); PR, VR-95 (H1N1)) |
| | | | |
| | | | |
| | | | |
| | | | |
| Analytical
specificity (cross
reactivity studies;
various strains of
microorganisms | | Device Screening Reagent is not reactive with these microorganisms: | |
| | Viruses | 32 | 31 |
| | Bacteria | 25 | 18 |
| | Chlamydia
spp. | 3 | 1 |
| Characteristic
and cell lines) | D3 Duet DFA Influenza A/
Respiratory Virus Screening Kit | D3 Ultra DFA Respiratory Virus
Screening & ID Kit | |
| Yeast | 1 | 0 | |
| Protozoan | 1 | 0 | |
| Cell lines | 17 | 17 | |
3
·
4
D³ DUET DFA INFLUENZA A/RESPIRATORY VIRUS SCREFNING KIT Page 5 of 13
Non-Clinical Performance:
Staining patterns of the phycoerythrin-labeled influenza A virus MAbs on influenza A virus infected cells were similar to those of the Predicate device.
Precision/Reproducibility:
Assay precision, intra-assay variability and inter assay variability were assessed with a panel of proficiency-level antigen control slides. The panel consisted of slides spotted with cell preparations of the following:
-
- Low level influenza A (Victoria strain)
-
- Mid level influenza A (Victoria strain)
-
- Low level influenza A (Victoria strain) mixed with Mid level RSV (Washington strain)
-
- Mid level influenza A (Victoria strain) mixed with Low level RSV (Washington strain)
-
- Low level respiratory virus (either influenza virus B {Taiwan strain}, adenovirus type 1, Parainfluenza virus types 1, 2, or 3 (strains C35, Greer, C243 respectively). This panel member was rotated during the 5-days of testing so that cach virus is tested twice.
-
- Negative no infected cells present
The low level is estimated to contain between 4 to 10% infected cells per cell spot. The mid level is estimated to contain between 20 to 25% infected cells per cell spot. Both levels were below the level used in quality control slides. Each panel member was re-coded daily to prevent its identification. Each panel was stained twice per day for 5-days by three diffcrent laboratorics.
The following results were recorded for both the control slide and the panel slide:
-
- Presence or absence of Yellow-gold fluorescence.
-
- Percent of cells exhibiting Yellow-gold fluorescence
-
- Presence or absence of Green fluorescence
- Percent of cells exhibiting Green fluorescence
The combined data for negative specimens -- no infected cells present - from the three sites demonstrates that the R-PF labeled and FITC labeled MAbs reproducibly do not stain uninfected cells. No fluorescent cells were scen in 100% (60/60) of the wells lacking infected cells.
5
The combined data from the three sites demonstrates reproducible detection of influenza A virus by the R-PE labeled MAbs. The presence of influenza A virus infected cells was reported in 95.3% (143/150) of the wells in which the infected cells were expected:
| Influenza A virus detection Summary | ||||
|---|---|---|---|---|
| Positive | ||||
| Control Slide | Low Level | |||
| Slide | Mid-Level | |||
| Slide | Low Level with | |||
| Mid-Level RSV | Mid-Level with | |||
| Low Level RSV | ||||
| 100% (30/30) | 100% (30/30) | 100% (30/30) | 83.3% (25/30) | 93.3% (28/30) |
The combined data demonstrates the reproducibility of the detection of respiratory syncytial virus by the FITC labeled MAbs. The presence of respiratory syncytial virus infected cells was reported in 100% (90/90) of the wells in which the infected cells were expected:
Respiratory syncytial virus detection Summary
| Positive Control Slide | Low Level Influenza A
with Mid-Level RSV | Mid-Level Influenza A
with Low Level RSV |
|------------------------|---------------------------------------------|---------------------------------------------|
| 100% (30/30) | 100% (30/30) | 100% (30/30) |
The combined data demonstrates that the presence of R-PE fluorescent cells reproducibly does not interfere with the detection of respiratory syncytial virus by the FITC labeled MAbs. The presence of respiratory syncytial virus infected cells was reported in 100% (53/53) of the wells in which the R-PE stained infected cells were present:
Respiratory syncytial virus detection in the presence of R-PE positive cells Summary
| Low Level R-PE stained cells with Mid-
Level RSV | Mid-Level R-PE stained cells with Low
Level RSV |
|-----------------------------------------------------|----------------------------------------------------|
| 100% (25/25) | 100% (28/28) |
The combined data from all three sites demonstrates that the presence of R-PE in the stain reproducibly does not interfere with the FITC staining of other viruses. The presence of influenza B virus infected cells was reported in 100% (36/36) of the wells in which the infected cells were expected. The presence of adenovirus infected cells was reported in 100% (36/36) of the wells in which the infected cells were expected. The presence of parainfluenza virus type 1 virus infected cells was reported in 100% (36/36) of the wells in which the infected cells were expected. The presence of parainfluenza virus type 2 virus infected cells was reported in 100% (36/36) of the wells in which the infected cells were expected. The presence of parainfluenza virus type 3 virus infected cells was reported in 100% (36/36) of the wells in which the infected cells were expected.
| Respiratory virus detection in the presence of R-PE Summary | |||||
|---|---|---|---|---|---|
6
D³ DUET DFA INFLUENZA A/RESPIRATORY VIRUS SCREENING KIT Page 7 of 13
| Adenovirus
Control Slide | Low Level
Adenovirus | Influenza B
Virus Control
Slide | Low Level
Influenza B
Virus | Parainfluenza
type 1
Control Slide | Low Level
Parainfluenza
type 1 |
|------------------------------------------|--------------------------------------|------------------------------------------|--------------------------------------|------------------------------------------|--------------------------------------|
| 100% (30/30) | 100% (6/6) | 100% (30/30) | 100% (6/6) | 100% (30/30) | 100% (6/6) |
| Parainfluenza
type 2
Control Slide | Low Level
Parainfluenza
type 2 | Parainfluenza
type 3
Control Slide | Low Level
Parainfluenza
type 3 | | |
| 100% (30/30) | 100% (6/6) | 100% (30/30) | 100% (6/6) | | |
The reproducibility study data demonstrates that the presence of R-PE in the stain reproducibly does not interfere with the detection of the 5 respiratory viruses by their respective FITC labeled MAbs.
Analytical specificity
Results for analytical detection limit for the seven viruses detected by the D3 Duet were reported in numbers of fluorescent cells per cell monolayer. Each master stock virus preparation was diluted in a ten-fold manner. Four wells of a 96-well cell culture plate were inoculated with each dilution. The plates were centrifuged at 700 xg for 60 minutes, and then incubated at 35° to 37°C for 24hours. Four wells from each dilution were stained with the D3 Duet. Each well was then examined at 200x magnification and the number of fluorescent cells counted. The table below lists the virus identity and strain along with the fluorescent cell count.
| Analytical Sensitivity of D3 Duet compared with that of
| D3 Ultra MAbs | |||
|---|---|---|---|
| (values are numbers of fluorescent cells per cell | |||
| monolayer) | |||
| Virus strain | Virus | ||
| Dilutions from | |||
| master stock | Fluorescent staining cells/well | ||
| D3 Duet | D3 Ultra | ||
| Influenza A virus | |||
| (PR, VR-95 H1N1) | 1x10-5 | 1, 3, 2, 6 | 1, 3, 0, 5 |
| 1x10-6 | 1, 0, 1, 1 | 0, 0, 1, 0 | |
| 1x10-7 | 0, 0, 0, 0 | 0, 0, 0, 0 | |
| Influenza B virus | |||
| (Hong Kong, VR-823) | 1x10-4 | 4, 1, 6, 2 | 0, 4, 3, 5 |
| 1x10-5 | 1, 0, 1, 1 | 0, 0, 2, 2 | |
| 1x10-6 | 0, 0, 0, 0 | 0, 0, 0, 0 | |
| Adenovirus (Type | |||
| 8, VR-8) | 1x10-6 | 1, 1, 3, 5 | 1, 3, 2, 4 |
| 1x10-7 | 0, 0, 0, 0 | 0, 0, 0, 0 | |
| RSV (Washington, | 1x10-2 | 1, 0, 3, 4 | 2, 3, 2, 0 |
7
| Analytical Sensitivity of D3 Duet compared with that of
| D3 Ultra MAbs | |||
|---|---|---|---|
| (values are numbers of fluorescent cells per cell monolayer) | |||
| Virus strain | Virus | ||
| Dilutions from | |||
| master stock | Fluorescent staining cells/well | ||
| D3 Duet | D3 Ultra | ||
| VR-1401) | 1x10-3 | 0, 1, 1, 0 | 2, 1, 0, 0 |
| 1x10-4 | 0, 0, 0, 0 | 0, 0, 0, 0 | |
| Parainfluenza 1 (C- | |||
| 35, VR-94) | 1x10-4 | 7, 7, 6, 8 | 9, 8, 4, 6 |
| 1x10-5 | 2, 2, 3, 0 | 1, 0, 2, 1 | |
| 1x10-6 | 0, 0, 0, 0 | 0, 0, 0, 0 | |
| Parainfluenza 2 | |||
| (Greer, VR-92) | 1x10-4 | 4, 0, 3, 1 | 4, 3, 1, 2 |
| 1x10-5 | 0, 2, 0, 0 | 0, 1, 1, 1 | |
| 1x10-6 | 0, 0, 0, 0 | 0, 0, 0, 0 | |
| Parainfluenza 3 (C | |||
| 243, VR-93) | 1x10-6 | 3, 3, 0, 6 | 1, 1, 3, 5 |
| 1x10-7 | 1, 0, 1, 1 | 1, 1, 1, 0 | |
| 1x10-8 | 0, 0, 0, 0 | 0, 0, 0, 0 |
Analytical reactivity (inclusivity) of the D3 Duet was evaluated using 10 influenza A virus and 4 influenza B virus strains. Four wells of a 96-well cell culture plate were inoculated with each viral strain (diluted to less than 20-TCID50 per 0.2-mL inoculum). The plates were centrifuged at 700xg for 60 minutes, and then incubated at 35° to 37°C for 24-hours. Four wells from cach strain were stained with the D3 Duet, and each well was then examined at 200x magnification and the number of fluorescent cells counted. The table below lists the virus identity and strain along with the fluorescent cell count.
| Analytical Reactivity (inclusivity) of D³ Duet
with various influenza A virus and
influenza B virus strains
(values are numbers of fluorescent cells
| per cell monolayer) | |
|---|---|
| Influenza | |
| strain | Fluorescent staining cells/cell |
| monolayer | |
| Influenza A | |
| Wisconsin/56/ | |
| 2005 | 3, 2, 1, 0 |
| Influenza A WS, | |
| VR-1520 (H1N1) | 6, 6, 6, 4 |
| Influenza A Hong | |
| Kong, VR-544 | |
| (H3N2) | 3, 4, 5, 5 |
| Influenza A New | |
| Jersey, VR-897 | 9, 12, 14, 15 |
8
| Analytical Reactivity (inclusivity) of D³ Duet
with various influenza A virus and
influenza B virus strains
(values are numbers of fluorescent cells
| per cell monolayer) | |
|---|---|
| Influenza | |
| strain | Fluorescent staining cells/cell |
| monolayer | |
| Influenza A Victoria, VR-822 (H3N2) | 3, 3, 3, 5 |
| Influenza A PR, VR-95 (H1N1) | 3, 9, 9, 6 |
| Influenza A Port Chalmers, VR-810 (H3N2) | 6, 6, 9, 10 |
| Influenza A Aichi, VR-547 (H3N2) | 3, 7, 9, 11 |
| Influenza A Denver, VR-546 (H1N1) | 13, 14, 11, 10 |
| Influenza A Mal, VR-98 (H1N1) | 8, 3, 6, 4 |
| Influenza B GL/1739/54, VR-103 | 7, 6, 7, 7 |
| Influenza B Taiwan/2/62, VR-295 | 3, 1, 2, 5 |
| Influenza B Hong Kong/5/72, VR-823 | 3, 2, 0, 1 |
| Influenza B Maryland/1/59, VR-296 | 5, 6, 6, 8 |
Based on the data presented above, the assay can reliably detect influenza A virus and influenza B virus strains exhibiting both temporal and geographical diversity at viral levels near the limit of detection in cell culture. Analytical sensitivity of the phycoerythrin-labeled influenza A MAbs of the D3 Duet was determined, and compared to that of the fluorescein-labeled influenza A MAbs of the D' Ultra. Cell monolayers of R-Mix in 96-well plates were inoculated with prepared virus stock of influenza A virus, Victoria strain, VR-822 (H3N2), diluted to give a TCID50 of 1 per 0.2-mL inoculum. The plates were incubated at 37℃ for 24 hours. Monolayers were stained using the procedures in the D Ultra's labeling or the D Duet's draft labeling. The assay was performed four times. Results indicate that analytical sensitivities of the phycoerythrin-labeled and the fluorcscein-labeled influenza A MAbs are not statistically different, by a paired t-test".
DHI-Duct_FluARespi_Sec05_510k-Summary printed.doc
ª 50% tissue culture infectivity dose
6 Microsoft Office Excel, Microsoft Corporation
9
Clinical Performance:
Direct fresh specimens:
A study was performed prospectively at three sites with 1203 fresh specimens that were received for respiratory virus testing. Each specimen was evaluated by the D3 Duet DFA Influenza A/Respiratory Virus Screening Kit and a cleared DSFA device for the presence of influenza A, influenza B, respiratory syncytial virus, adenovirus, parainfluenza 1, parainfluenza 2 and parainfluenza 3 in cells derived from clinical specimens. A total of nineteen specimens were excluded from analysis due to a site deviations, duplicate specimen, insufficient cell numbers, or high background. These exclusions left 1184 specimen results for analysis.
The following tables detail the summary of the comparison of the D3 Duet and the cleared DSFA comparator assay, combined for study sites 1, 2, and 3:
| D3 Duet R-PE identification of influenza A virus positive specimens | |||
|---|---|---|---|
| Direct Specimen (1184 Specimens) | D3 Ultra Final Identification | ||
| (influenza A virus) | |||
| Pos | Neg | ||
| D3 Duet R-PE | |||
| (influenza A virus) | Pos | 99 | 0 |
| Neg | 1 | 1084 | |
| Positive Percent Agreement (PPA) | 99% (99/100) | ||
| 95% CI- PPA | 94.5, 99.8% | ||
| Negative Percent Agreement (NPA) | 100% | ||
| (1084/1084) | |||
| 95% CI- NPA | 99.7, 100% |
| D3 Duet FITC detection of influenza B virus, respiratory syncytial virus, adenovirus, and parainfluenza virus types 1, 2, and 3 viruses | |||
|---|---|---|---|
| Direct Specimen (1184 Specimens) | D3 Ultra Final Identification | ||
| Pos | Neg | ||
| D3 Duel FITC Screen | Pos | 386 | 0 |
| Neg | 0 | 798* | |
| Positive Percent Agreement (PPA) | 100% (386/386) | ||
| 95% CI- PPA | 99.0,100% | ||
| Negative Percent Agreement (NPA) | 100% (798/798) | ||
| 95% CI- NPA | 99.5,100% |
10
| Virus Follow-up Identification of 386 D³ Duet FITC Positive Specimens for influenza B
virus, respiratory syncytial virus, adenovirus, and parainfluenza virus types 1, 2, and 3
| viruses, using D³ Ultra Identification Reagents | ||||||
|---|---|---|---|---|---|---|
| Sensitivity | Specificity | 95% CI | ||||
| Virus | TP / | |||||
| (TP+FN) | percent | for | ||||
| Sensitivity | TN/ | |||||
| (TN+FP) | percent | for | ||||
| Specificity | ||||||
| Influenza B | ||||||
| virus | 11/11 | 100% | 74.12, 100 | 1173/1173 | 100% | 99.7, 100 |
| Adenovirus | 52/52 | 100% | 93.1, 100 | 1132/1132 | 100% | 99.7, 100 |
| Parainfluenza | ||||||
| type 1 | 4/4 | 100% | 51.0, 100 | 1180/1180 | 100% | 99.7, 100 |
| Parainfluenza | ||||||
| type 2 | 1/1 | 100% | 20.1, 100 | 1183/1183 | 100% | 99.7, 100 |
| Parainfluenza | ||||||
| type 3 | 19/19 | 100% | 83.2, 100 | 1165/1165 | 100% | 99.7, 100 |
| Respiratory | ||||||
| Syncytial Virus | 299/299 | 100% | 98.7, 100 | 885/885 | 100% | 99.6, 100 |
D³ DUET DFA INFLUENZA A/RESPIRATORY VIRUS SCREENING KIT Page 11 of 13
The D2 Duet's ability to identify influenza A virus using phycoerythrin in direct specimens was compared to the D3 Ultra's ability using fluorescein. The positive percent agreement was 99% (95% CI range of 94.5% to 99.8%). The negative percent agreement was 100% (95% CI range of 99.7% to 100%). When the ability of the D3 Duet to detect the six other respiratory viruses using fluorescein in direct specimens was compared to the D3 Ultra's ability using fluorescein, the positive percent agreement was 100% (95% CI range of 99.0% to 100%). The negative percent agreement was 100% (95% CI range of 99.5% to 100%).
Specimen type distribution:
Tables below show the study results by the claimed specimen type. Results from sites 1, 2, and 3 have been combined.
| Influenza A virus by specimen type | ||||||
|---|---|---|---|---|---|---|
| Specimen | ||||||
| type | PPA | NPA | ||||
| TP / | ||||||
| (TP+FN) | percent | 95%CI for | ||||
| PPA | TN/ | |||||
| (TN + FP) | percent | 95% CI for | ||||
| NPA | ||||||
| NPA | 61/62 | 98.4% | 91.4, 99.7 | 525/525 | 100% | 99.3, 100 |
| NPS | 38/38 | 100% | 90.8, 100 | 501/501 | 100% | 99.2, 100 |
| D³ Duet FITC detection of influenza B virus, respiratory syncytial virus, adenovirus, | ||||||
| and parainfluenza virus types 1, 2, and 3 viruses by specimen type | ||||||
| Specimen | ||||||
| type | PPA | NPA | ||||
| TP / | ||||||
| (TP+FN) | percent | 95%CI for | ||||
| PPA | TN/ | |||||
| (TN+FP) | percent | 95% CI for | ||||
| NPA |
Influenza A virus by specimen type
11
D³ DUFT DFA INFLUENZA A/RESPIRATORY VIRUS SCREENING KIT Page 12 of 13
| NPA | 196/196 | 100% | 98.1, 100 | 391/391 | 100% | 99.0, 100 |
|---|---|---|---|---|---|---|
| NPS | 173/173 | 100% | 97.8, 100 | 366/366 | 100% | 99.0, 100 |
Cultured specimens:
To evaluate the performance of this device using cultured clinical specimens, a fourth study was performed with 298 frozen specimens to compare performance of the D' Duet DFA Influenza A/Respiratory Virus Screening Kit with that of the predicate for the presence of Influenza A, Influenza B, Respiratory Syncytial Virus, Adenovirus, Parainfluenza 1, Parainfluenza 2 and Parainfluenza 3 (Para 3) from cultured clinical specimens. At Study Site 4, 298 frozen specimens were processed for cell culture testing in accordance with the procedure in the Comparator product insert (same procedure for both Subject and Comparator devices) using R-Mix Too™ FreshCells™ in 48/24-fill multi-well plates. All specimens at study site 4 were derived from nasopharyngeal specimens. The results of this study are presented below. The table below shows the age distribution for individuals studied at site 4:
| Site 4 (culture) – Age Distribution | |
|---|---|
| 0 - 1 month | 5 |
| >1 month - 2 years | 130 |
| >2 - 12 years | 44 |
| >12 - 21 years | 28 |
| 22- 30 years | 19 |
| 31- 40 years | 20 |
| 41- 50 years | 10 |
| 51 - 60 years | 9 |
| 61-70 years | 8 |
| 71 - 80 years | 6 |
| 81-90 years | 8 |
| >90 years | 5 |
| Unknown age | 6 |
| Total | 298 |
The following tables detail the results of the cell culture study's comparison of D3 Duet's phycoerythrin-labeled MAbs identification of influenza A virus positive specimens, and D2 Duet's fluorescein-labeled MAbs detection of influenza B virus, respiratory syncytial virus, adenovirus, and parainfluenza virus types 1, 2, and 3 positive specimens.
| Study Site 4 (culture) - D3 Duet R-PE identification of influenza A virus positive specimens | |||
|---|---|---|---|
| Cell Culture (298 Specimens) | D3 Ultra Final Identification | ||
| (influenza A virus) | |||
| Pos | Neg | ||
| D3 Duet R-PE | |||
| (influenza A virus) | Pos | 67 | 0 |
| Neg | 0 | 231 | |
| Positive Percent Agreement (PPA) | 100% (67/67) |
DHI-Duct_FluARespi_Sec05 510k-Summary printed.doc
12
D² DUET DFA INFLUENZA A/RESPIRATORY VIRUS SCREENING KIT Page 13 of 13
| 050/21 | 94 6 100% | |
|---|---|---|
| Negative Percent Agreement (NPA) | 100% 1731/23 | |
| 95% CI- NPA | ||
| 100.014 | 100% | |
| ﺍﻟﻤﺴﺘﻘﻠﺔ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘ |
Study Site 4 (culture) - D3 Duet FITC detection of influenza B virus, respiratory syncytial virus, adenovirus, and parainfluenza virus types 1, 2, and 3 viruses Cell Culture (298 Specimens) D3 Ultra Final Identification Pos Neg Pos 72 0 D3 Duet FITC Screen Neg 0 226 100% (72/72) Positive Percent Agreement (PPA) 95% CI- PPA 95.0,100% Negative Percent Agreement (NPA) 100% (226/226) 95% CI- NPA 98.4,100%
A variety of viral respiratory pathogens were isolated. Virus identification of De Duet FITC Positive Specimens using D3 Ultra Identification Reagents yiclded the following isolates: influenza A virus [prevalence 22.5% (67/298)], influenza B virus [prevalence 6.7% (20/298)], respiratory syncytial virus [prevalence 11.1% (33/298)], adenovirus [prevalence 3.4% (10/298)], parainfluenza type 1 virus [prevalence 1.7% (5/298)], parainfluenza type 2 virus [prevalence 1.0% (3/298)], and parainfluenza type 3 virus [prevalence 3.0% (9/298)]. There were sixteen co-infections as follows: three influenza A virus + parainfluenza type 3 virus, one influenza A virus + parainfluenza type 1 virus, one influenza A virus + parainfluenza type 2 virus, two influenza A virus + respiratory syncytial virus, one influenza A virus + adenovirus, one influenza B virus + parainfluenza type 2 virus, one influenza B virus + parainfluenza type 3 virus, one influenza B virus + respiratory syncytial virus, one respiratory syncytial virus + parainfluenza type 1 virus, two respiratory syncytial virus + parainfluenza type 3 virus, one adenovirus + parainfluenza type 1 virus and one adenovirus + parainfluenza type 3 virus.
13
DFPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/13/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS). The seal is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the seal is an eagle with its wings spread.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Gail R. Goodrum Vice President of Regulatory Affairs Diagnostic Hybrids, Inc. 1055 East State Street Suite 100 Athens, Ohio 45701
DEC 2 3 2008
Re: K081746
Trade/Device Name: D3 Duet DFA Influenza A/Respiratory Virus Screening Kit Regulation Number: 21 CFR 866.3330 Regulation Name: Influenza virus serological reagents Regulatory Class: Class I Product Code: GNW Dated: November 26, 2008 Received: November 28, 2008
Dear Ms. Goodrum:
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 r ou may , the survisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter
ﻟﻤﺆﺳﺴﺎ
14
Page 2 -
This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at 240-276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. 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 (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Sally attayna
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
15
D3 DUET DFA INFLUENZA A/RESPIRATORY VIRUS SCREENING KIT
Page 1 of 1
SECTION 04 - INDICATIONS FOR USE
510(k) Number (if known): K081746
Device Name: D3 Duet DFA Influenza A/Respiratory Virus Screening Kit
Indication for Use: The Diagnostic Hybrids, Inc. device, D3 Duet DFA Influenza A/Respiratory Virus Screening Kit, is intended for the qualitative detection and identification of influenza A, while screening for influenza B virus, respiratory syncytial virus, adenovirus, and parainfluenza virus types 1, 2 and 3 viral antigens, in nasal and nasopharyngeal swabs and aspirates or in cell culture. The assay detects viral antigens by immunofluorescence using monoclonal antibodies (MAbs), from patients with signs and symptoms of respiratory infection.
It is recommended that specimens found to be negative after examination of the direct specimen result be confirmed by cell culture. Negative results do not preclude influenza virus infection and should not be used as the sole basis for diagnosis, treatment or other management decisions.
Performance characteristics for influenza A virus detection and identification were established when influenza A H3N2 and influenza A H1N1 were the predominant influenza A strains circulating in the United States. When other Influenza A viruses are emerging, performance characteristics may vary. If infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent Influenza viruses and sent to a state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
| Prescription Use | AND/OR | Over |
|---|---|---|
| X | ||
| (Part 21 CFR 801 Subpart D) | ( |
r-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED
Concurrence of CDRH, Office of Device Evaluation (ODE)
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
209 1746 510(k)