(268 days)
The Diagnostic Hybrids, Inc. D3 DFA Herpes Simplex Virus Identification and Typing Kit is intended for use in the qualitative detection and typing of human herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) in cell cultures by immunofluorescence using fluoresceinated monoclonal antibodies (MAbs). Negative results do not rule out an infection and should not be used as the sole basis for diagnosis, treatment or other management decisions. Performance using direct specimen testing has not been evaluated.
The Diagnostic Hybrids, Inc. D3 DFA Herpes Simplex Virus Identification and Typing Kit uses two separate blends of HSV Type-1 (HSV-1) and HSV Type-2 (HSV-2) antigen-specific murine MAbs that are directly labeled with fluorescein for the rapid detection and typing of HSV. The reagents can specifically detect and type either HSV-1 or HSV-2. The HSV-1 MAbs were developed using HSV-1(f) cell lysate as immunogen - one MAb has been determined to be directed against HSV-1 glycoprotein C1; the antigen to the other is undetermined. The HSV-2 MAbs were developed using a HSV-2 recombinant glycoprotein G as immunogen.
Kit Components:
• HSV-1 DFA Reagent - One dropper bottle containing a blend of two fluorescein labeled murine monoclonal antibodies directed against HSV-1 specific glycoproteins. The HSV-1 MAbs were developed using HSV-1(f) cell Ivsate as immunogen - one MAb has been determined to be directed against HSV-1 glycoprotein C1, the antigen to the other is undetermined. The buffered, stabilized, aqueous solution contains Evan's Blue as a counter-stain and 0.1% sodium azide as preservative.
• HSV-2 DFA Reagent - One dropper bottle containing a blend of two fluorescein labeled murine monoclonal antibodies directed against HSV-2 specific glycoproteins. The HSV-2 MAbs were developed using a HSV-2 recombinant glycoprotein G immunogen. The buffered, stabilized, aqueous solution contains Evan's Blue as a counter-stain and 0.1% sodium azide as preservative
• HSV-1/HSV-2 Antigen Control Slides - Individually packaged control slides containing wells with cell culture derived positive and negative control cells. Each slide consists of four wells containing acetone fixed cells; two wells of noninfected cells and one well each of HSV-1 infected cells and HSV-2 infected cells. Each slide is intended to be stained only one time.
• PBS Concentrate - A 40X concentrate consisting of 4% sodium azide in phosphate buffered saline (after dilution to 1X in water, the concentration of sodium azide in the solution is 0.1%).
• Mounting Fluid - an aqueous, buffered, stabilized solution of glycerol and 0.1% sodium azide.
The cells to be tested, on a slide prepared from a tube culture or on a monolayer of cells cultured in a multi-well plate or a coverslip in a shell vial, are fixed in acetone. The HSV-1 DFA Reagent or HSV-2 DFA Reagent is added to the cells to detect the presence of HSV specific viral antigens. After incubating for 15 to 30 minutes at 35° to 37°C, the stained cells are washed with the supplied Phosphate Buffered Saline (PBS). To prepare the slide for examination, a drop of the supplied Mounting Medium is added to the stained cells and a coverslip is placed on the slide. To prepare the centrifuge enhanced cell cultures for examination, a drop of Mounting Fluid is placed on a clean microscope slide. The coverslip is removed from the shell vial and placed on to the Mountina Fluid.
For multi-well plates, monolayers are fixed with an 80% aqueous acetone solution. The HSV DFA Reagent is added to the cells to detect the presence of any HSV specific viral antigens. After incubating for 15 to 30 minutes at 35° to 37°C, the stained cells are washed with the supplied Phosphate Buffered Saline (PBS). Mounting Fluid is added to each well to cover the monolayers.
The slides or wells are examined using a fluorescence microscope equipped with the correct filter combination for FITC at a magnification of 100-400X. Virus infected cells will be stained with bright apple-green fluorescence while uninfected cells will contain no apple-green fluorescence but will fluoresce red by the Evan's Blue counterstain which is included in the HSV DFA Reagent.
If no fluorescent cells are found, report result as, "No herpes simplex virus detected."
If fluorescent cells are found in the HSV-1 DFA Reagent stained monolayer, report result as "Herpes simplex virus type 1 isolated by cell culture". If fluorescent cells are found in the HSV-2 DFA Reagent stained monolaver, report result as "Herpes simplex virus type 2 isolated by cell culture." If fluorescent cells are found in both the HSV-1 and HSV-2 stained wells, the results should be reported as "Herpes simplex virus types 1 and 2 isolated by cell culture".
Included in the kit are HSV-1/HSV-2 Antigen Control Slides. A Control Slide is intended to function as an indicator that the kit reagents are working properly in the test. [The slides are prepared with wells of HSV-1 infected cells, HSV-2 infected cells, and uninfected cells.] Positive and negative controls must demonstrate appropriate staining characteristics for specimen results to be valid. Controls may also aid in the interpretation of test results.
It is recommended that cell culture positive (infected with known HSV isolate) and negative (uninfected cells) controls be run with each assay to provide a means to ensure adequate performance of the cell culture system used. If control cultures fail to perform correctly, results are considered invalid.
Here's a breakdown of the acceptance criteria and study details for the DIAGNOSTIC HYBRIDS, INC. D3 DFA HERPES SIMPLEX VIRUS IDENTIFICATION KIT, based on the provided 510(k) summary:
Acceptance Criteria and Reported Device Performance
The acceptance criteria for this device are implied by the reported performance metrics, specifically the Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) with comparison devices. While explicit thresholds for "acceptance" are not stated, the high agreement percentages achieved indicate sufficient performance for regulatory clearance.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (HSV-1) | Reported Device Performance (HSV-2) |
|---|---|---|---|
| Positive Percent Agreement (PPA) | High agreement with predicate | 98.6% (92.7% - 100% CI) | 100% (95.3% - 100% CI) |
| Negative Percent Agreement (NPA) | High agreement with predicate | 100% (98.9% - 100% CI) | 99.7% (98.3% - 100% CI) |
| Analytical Specificity (Cross-Reactivity) | No cross-reactivity with non-HSV microorganisms | No cross-reactivity observed for 59 virus strains, 17 host cell types, 27 bacterial cultures, 1 yeast, and 1 protozoan (except S. aureus with distinguishable punctate staining). | No cross-reactivity observed for 59 virus strains, 17 host cell types, 27 bacterial cultures, 1 yeast, and 1 protozoan (except S. aureus with distinguishable punctate staining). |
Study Details
2. Sample Size and Data Provenance
- Test Set Sample Size: 398 specimens (out of 401 prospectively collected, 3 were excluded due to bacterial contamination).
- Data Provenance: Prospectively collected specimens at three different laboratories. The country of origin is not explicitly stated but implied to be the US given the submission to the FDA.
3. Number of Experts and Qualifications for Ground Truth
The document does not explicitly state the number of experts used to establish the ground truth or their specific qualifications (e.g., radiologist with X years of experience). Instead, the "ground truth" for the clinical study was established by "currently marketed HSV identification kits ('Comparison Devices')". This implies that these comparison devices, which are already cleared and established in clinical practice, served as the reference standard.
4. Adjudication Method
The document does not describe an adjudication method for the test set. The comparison was directly between the D3 DFA HSV ID & Typing Kit and the "Comparison Devices." Discrepancies are simply reported as either the D3 DFA kit being positive and the comparison negative, or vice versa, contributing to the PPA and NPA calculations.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
There is no mention of a Multi-Reader Multi-Case (MRMC) comparative effectiveness study being performed. The study focuses on comparing the new device's performance against existing, marketed identification kits, not on the improvement of human readers with AI assistance. The device is a diagnostic kit, not an AI-assisted interpretation tool for human readers.
6. Standalone Performance Study
Yes, a standalone performance study was done. The entire clinical performance section evaluates the algorithm (kit) only, without human-in-the-loop performance being a variable. The results are reported based on the kit's ability to detect and type HSV-1 and HSV-2 compared to predicate devices.
7. Type of Ground Truth Used
The ground truth used for the clinical performance study was based on diagnostic results from "currently marketed HSV identification kits ('Comparison Devices')". This can be considered a form of reference standard test result.
8. Sample Size for the Training Set
The document does not specify a separate training set or its sample size. The focus is on the performance evaluation of the final device against a clinical test set. The "development" of the monoclonal antibodies involved using HSV-1(f) cell lysate andHSV-2 recombinant glycoprotein G as immunogens, which would be part of the initial development and optimization phase, but not a distinct "training set" in the context of an AI/algorithm.
9. How the Ground Truth for the Training Set was Established
As no specific training set is mentioned in the context of machine learning, the concept of ground truth for a training set is not directly applicable here. The development of the reagents involved using specific antigens (HSV-1(f) cell lysate and HSV-2 recombinant glycoprotein G) to generate type-specific monoclonal antibodies. The analytical specificity (cross-reactivity) was evaluated using known ATCC reference strains, various other microorganisms, and cell types, which served to confirm the expected reactivity and non-reactivity of the reagents during development and validation.
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DIAGNOSTIC HYBRIDS, INC 350 West State Street Athens, OHIO 45701
510(k) SUMMARY
TM
K070265
| Applicant | DIAGNOSTIC HYBRIDS, INC.350 West State StreetAthens, OHIO 45701 |
|---|---|
| Contact Information | Gail R. GoodrumVice President, Regulatory and Quality AffairsE-mail: goodrum@dhiusa.comTelephone: 740.593.1784Desk Extension: 740.593.1787FAX: 740.597.1546 |
| Ronald Lollar, Senior Director of Clinical Development - secondary contact350 W. State StreetAthens, OH 45701740.593.1784 - Phone740.593.0980 - Faxlollar@dhiusa.com | |
| Date of preparation of510(k) summary: | September 27, 2007 |
| Device Name | Trade name - DIAGNOSTIC HYBRIDS, INC. D 3 HERPES SIMPLEX VIRUSIDENTIFICATION KITCommon name - Fluorescent antibody test for ID and typing HSV-1 and HSV-2Classification name - ANTISERA, FLUORESCENT, HERPESVIRUS HOMINIS 1,2 (21CFR 866.3305, product code GQL) |
| Legally marketed devicesto which equivalence isclaimed: | K880157 MicroTrak® HSV 1/HSV 2 Culture Identification and Typing Test |
| K904167 Pathodx® Herpes Typing Kit | |
| Device Description | The Diagnostic Hybrids, Inc. D 3 DFA Herpes Simplex Virus Identification andTyping Kit uses two separate blends of HSV Type-1 (HSV-1) and HSV Type-2 (HSV-2)antigen-specific murine MAbs that are directly labeled with fluorescein for the rapiddetection and typing of HSV. The reagents can specifically detect and type either HSV-1 or HSV-2. The HSV-1 MAbs were developed using HSV-1(f) cell lysate asimmunogen - one MAb has been determined to be directed against HSV-1 glycoproteinC1; the antigen to the other is undetermined. The HSV-2 MAbs were developed using aHSV-2 recombinant glycoprotein G as immunogen.Kit Components:• HSV-1 DFA Reagent - One dropper bottle containing a blend of twofluorescein labeled murine monoclonal antibodies directed against HSV-1 specificglycoproteins. The HSV-1 MAbs were developed using HSV-1(f) cell Ivsate asimmunogen - one MAb has been determined to be directed against HSV-1 glycoproteinC1, the antigen to the other is undetermined. The buffered, stabilized, aqueous solutioncontains Evan's Blue as a counter-stain and 0.1% sodium azide as preservative.• HSV-2 DFA Reagent - One dropper bottle containing a blend of twofluorescein labeled murine monoclonal antibodies directed against HSV-2 specificglycoproteins. The HSV-2 MAbs were developed using a HSV-2 recombinantglycoprotein G immunogen. The buffered, stabilized, aqueous solution contains Evan'sBlue as a counter-stain and 0.1% sodium azide as preservative |
Section 5-1 of 5-5
·
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· HSV-1/HSV-2 Antigen Control Slides - Individually packaged control slides containing wells with cell culture derived positive and negative control cells. Each slide consists of four wells containing acetone fixed cells; two wells of noninfected cells and one well each of HSV-1 infected cells and HSV-2 infected cells. Each slide is intended to be stained only one time.
· PBS Concentrate - A 40X concentrate consisting of 4% sodium azide in phosphate buffered saline (after dilution to 1X in water, the concentration of sodium azide in the solution is 0.1%).
· Mounting Fluid - an aqueous, buffered, stabilized solution of glycerol and 0.1% sodium azide.
The cells to be tested, on a slide prepared from a tube culture or on a monolayer of cells cultured in a multi-well plate or a coverslip in a shell vial, are fixed in acetone. The HSV-1 DFA Reagent or HSV-2 DFA Reagent is added to the cells to detect the presence of HSV specific viral antigens. After incubating for 15 to 30 minutes at 35° to 37°C, the stained cells are washed with the supplied Phosphate Buffered Saline (PBS). To prepare the slide for examination, a drop of the supplied Mounting Medium is added to the stained cells and a coverslip is placed on the slide. To prepare the centrifuge enhanced cell cultures for examination, a drop of Mounting Fluid is placed on a clean microscope slide. The coverslip is removed from the shell vial and placed on to the Mountina Fluid.
For multi-well plates, monolayers are fixed with an 80% aqueous acetone solution. The HSV DFA Reagent is added to the cells to detect the presence of any HSV specific viral antigens. After incubating for 15 to 30 minutes at 35° to 37°C, the stained cells are washed with the supplied Phosphate Buffered Saline (PBS). Mounting Fluid is added to each well to cover the monolayers.
The slides or wells are examined using a fluorescence microscope equipped with the correct filter combination for FITC at a magnification of 100-400X. Virus infected cells will be stained with bright apple-green fluorescence while uninfected cells will contain no apple-green fluorescence but will fluoresce red by the Evan's Blue counterstain which is included in the HSV DFA Reagent.
If no fluorescent cells are found, report result as, "No herpes simplex virus detected."
If fluorescent cells are found in the HSV-1 DFA Reagent stained monolayer, report result as "Herpes simplex virus type 1 isolated by cell culture". If fluorescent cells are found in the HSV-2 DFA Reagent stained monolaver, report result as "Herpes simplex virus type 2 isolated by cell culture." If fluorescent cells are found in both the HSV-1 and HSV-2 stained wells, the results should be reported as "Herpes simplex virus types 1 and 2 isolated by cell culture".
Included in the kit are HSV-1/HSV-2 Antigen Control Slides. A Control Slide is intended to function as an indicator that the kit reagents are working properly in the test. [The slides are prepared with wells of HSV-1 infected cells, HSV-2 infected cells, and uninfected cells.] Positive and negative controls must demonstrate appropriate staining characteristics for specimen results to be valid. Controls may also aid in the interpretation of test results.
It is recommended that cell culture positive (infected with known HSV isolate) and negative (uninfected cells) controls be run with each assay to provide a means to ensure adequate performance of the cell culture system used. If control cultures fail to perform correctly, results are considered invalid.
Intended Use
The Diagnostic Hybrids, Inc. D DFA Herpes Simplex Virus Identification and Typing Kit is intended for use in the qualitative detection and typing of human herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) in cell cultures by immunofluorescence using fluoresceinated monoclonal antibodies (MAbs). Neqative results do not rule out an infection and should not be used as the sole basis for diagnosis, treatment or other management decisions.
Performance using direct specimen testing has not been evaluated.
Explanation
HSV infections in humans can cause lesions at a variety of sites, e.g., oral-facial,
510(k) summary
350 West State Street
hens, Ohio 45701
350 West State Street · · Athens, Ohio 45701 · 1-800-344-5847 · Fax 740-593-0980 · www.chiusa.com
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genital, eye, and cutaneous sites.
When an appropriately sensitive cell line is infected with HSV, a characteristic deterioration of cells, termed cytopathic effect (CPE), can be observed. Tube culture, a classic format for virus amplification, can take several days before CPE is evident. In the case of those specimens with low titers of virus, 7 days of culture may be required by the standard tube culture method before CPE can be observed2-3.4.5.6
The rate of isolation may be enhanced and the time required for HSV identification and typing may be decreased by centrifugation of specimens in shell vials or multi-well
plates containing appropriately sensitive cell lines (centrifuge enhanced technique) 18,9 Even so, CPE may be difficult to interpret due to, for instance, deterioration of cells, which can result from toxic components present in the clinical specimen making microscopic examination of the infected cells problematic. Further, determination of type cannot be done with CPE alone. Because of this, immunofluorescence
confirmation of cell culture is regarded as the standard for confirmation of a HSV
positive result. Fundamental technology and intended use of the device are the same as those of the predicate devices, which are based on a standard immunofluorescence assay technique using cells inoculated with patient specimens. They employ directly labeled
fluorescein monoclonal antibodies specific for HSV-1 and HSV-2 antigens enabling visualization of the infected cells. A summary is provided in the table below:
| HSV Systems | DFA | DirectSpecimens | CultureConfirmation | FITCLabel | MonoclonalAntibody | DistinguishesHSV-1 and HSV-2 |
|---|---|---|---|---|---|---|
| DiagnosticHybrids, Inc. | Yes | No | Yes | Yes | Yes | Yes |
| MicroTrak®(Trinity) | Yes | No | Yes | Yes | Yes | Yes |
| PathoDx®(Remel) | Yes | Yes | Yes | Yes | Yes | Yes |
Non-clinical Performance
Technological
Characteristics
Staining patterns of the conjugated monoclonal antibodies on HSV-1 and HSV-2 infected cells were similar to those of the predicate devices. Analytical specificity was evaluated by staining cultures infected with a number of ATCC reference HSV-1 and HSV-2 strains and found to react with all of them. The HSV-1 DFA Reagent and HSV-2 DFA Reagent were tested for cross-reactivity against a wide variety of other microorganisms and cells. No cross-reactivity was observed for 59 virus strains (cultured and processed for staining) or for 17 host culture cell types. Twenty-seven (27) bacterial cultures, one yeast and one protozoan culture were stained and examined for cross-reactivity, including Staphylococcus aureus, a protein-A-producing bacterium. Staining of S. aureus appeared as small points of fluorescence while all other cultures were negative. [Protein A will specifically bind to the Fc portions of conjugated antibodies. Such binding can be distinguished from viral antigen binding on the basis of morphology, i.e., S. aureus-bound fluorescence appears as small (~1 micron diameter). bright dots.] [Note: Results from cell cultures with bacterial contamination must, therefore, be interpreted with caution.]Stringent conditions for cross-reactivity testing were achieved by using a high concentration of the HSV-1 DFA Reagent or the HSV-2 DFA Reagent and high titers of microorganisms. The DFA Reagents were prepared at 1.5X the concentration that is provided in the kit. Depending on the particular virus, 500 to 715 TCIDso viruses were inoculated into shell vial or multi-well plate cultures and incubated for 24 to 48 hours to yield a 1+ to 3+ infection, processed and stained with the 1.5X DFAs according to the procedure detailed in the product insert. Stained cells were examined at 200x magnification. Cell cultures were stained as confluent monolayers. Bacteria and yeast were cultured, processed as suspensions, then spotted on microscope slides (at CFUs ranging from 6.4x104 to 2.93x10'/well in a 10 µL dot, depending on the bacterium), then stained with the 1.5X DFAs according to the procedure in the product insert. Stained slides were examined at 400X magnification. Some microorganisms were procured from an external source as prepared microscope slides, intended to be used as positive controls for assays.
510(k) summary
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| Virus Strains Tested for Cross Reactivity with D³ HSV DFA Reagent | |||||
|---|---|---|---|---|---|
| Organism | Strain or Type | Inoculum(TCID50) | Organism | Strain or Type | Inoculum(TCID50) |
| Adenovirus | Type 1 | 715 | Influenza B | Hong Kong | 715 |
| Adenovirus | Type 3 | 715 | Influenza B | Maryland | 715 |
| Adenovirus | Type 5 | 715 | Influenza B | Mass | 715 |
| Adenovirus | Type 6 | 715 | Influenza B | Taiwan | 715 |
| Adenovirus | Type 7 | 715 | Influenza B | GL | 715 |
| Adenovirus | Type 8 | 715 | Influenza B | JH-001 isolate | 715 |
| Adenovirus | Type 10 | 715 | Influenza B | Russia | 715 |
| Adenovirus | Type 13 | 715 | RSV | Long | 715 |
| Adenovirus | Type 14 | 715 | RSV | Wash | 715 |
| Adenovirus | Type 18 | 715 | RSV | 9320 | 715 |
| Adenovirus | Type 31 | 715 | Parainfluenza 1 | C-35 | 715 |
| Adenovirus | Type 40 | 715 | Parainfluenza 2 | Greer | 715 |
| Adenovirus | Type 41 | 715 | Parainfluenza 3 | C 243 | 715 |
| Influenza A | Aichi | 715 | Parainfluenza 4a | M-25 | 715 |
| Influenza A | Mal | 715 | Parainfluenza 4b | CH19503 | 715 |
| Influenza A | Hong Kong | 715 | CMV | Towne | 700 |
| Influenza A | Denver | 715 | CMV | Davis | 700 |
| Influenza A | Port Chalmers | 715 | CMV | AD169 | 700 |
| Influenza A | Victoria | 715 | VZV | Webster | 500 |
| Influenza A | New Jersey | 715 | VZV | Allen | 500 |
| Influenza A | PR | 715 | Epstein-Barr | ||
| Influenza A | WS | 715 | Rubeola | Commercially available slides staine | |
| Mumps | |||||
| Echovirus | Types 4, 6, 9,11, 30, 34 | Commerciallyavailable slidesstained. | HPV | Types 6, 11 | Commerciallyavailable slidesstained. |
| Coxsackievirus | Types B1, B2,B3, B4, B5, B6 | Commerciallyavailable slidesstained. | Cell Lines Tested for Cross Reactivity with D³ HSV DFA Reagent | ||
| A549 | MRHF | RhMK II | |||
| BGMK | Mv1Lu | pRK | |||
| HEp-2 | NCI-H292 | RD | |||
| LLC-MK2 | pCMK | R-Mix | |||
| MDCK | pRhMK | Vero | |||
| MRC-5 | WI-38 | ||||
| Microorganisms Tested for Cross Reactivity with D³ HSV DFA Reagent | |||||
| BACTERIA | CFUTESTED | BACTERIA | CFU TESTED | ||
| Acinetobacter calcoaceticus | 9.7 x 10⁵ | Salmonella typhimurium | 1.7 x 10⁶ | ||
| Bordetella bronchiseptica | 1.7 x 10⁶ | Staphylococcus aureus | 1.0 x 10⁷ | ||
| Bordetella pertussis | 4.6 x 10⁶ | Streptococcus agalactiae | 9.6 x 10⁵ | ||
| Corynebacterium diphtheriae | 2.5 x 10⁶ | Streptococcus pneumoniae | 8.0 x 10⁵ | ||
| Escherichia coli | 2.6 x 10⁵ | Streptococcus pyogenes | 2.9 x 10⁷ | ||
| Gardnerella vaginalis | 5.0 x 10⁵ | Acholeplasma laidlawi | ~6 x 10⁴ | ||
| Haemophilis influenzae type A | 9.3 x 10⁵ | Mycoplasma hominis | ~6 x 10⁴ | ||
| Klebsiella pneumoniae | 6.4 x 10⁶ | Mycoplasma orale | ~6 x 10⁴ | ||
| Legionella pneumophila | 6.5 x 10⁴ | Mycoplasma pneumoniae | ~6 x 10⁴ | ||
| Moraxella cartarrhalis | 6.4 x 10⁴ | Mycoplasma salivarium | ~6 x 10⁷ | ||
| Neisseria gonorrhoeae | 1.3 x 10⁶ | Ureaplasma uralyticum | ~6 x 10⁴ | ||
| Proteus mirabilis | 2.1 x 10⁶ | Chlamydophila pneumoniae | Commercially availableslides stained. | ||
| Pseudomonas aeruginosa | 1.0 x 10⁷ | Chlamydia trachomatis | Commercially availableslides stained. | ||
| Salmonella enteriditis | 2.5 x 10⁶ | ||||
| YEAST | PROTOZOAN |
Clinical Performance
Clinical studies have been conducted at three different laboratories where they compared the Diagnostic Hybrids, Inc. D3 DFA Herpes simplex virus Identification and Typing Kit ("D3 DFA HSV ID & Typing Kit") performance to that of currently marketed
510(k) summary
a Test material is from commercially available prepared slides. Each positive well contained 10% to 50% reactive cells.
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HSV identification kits ("Comparison Devices") using four hundred and one (401) prospectively collected specimens submitted for Herpes simplex culture. A combination of fresh (154) and frozen (247) specimens were tested. Three specimens from sife 3 were not evaluated due to bacterial contamination of the monolayers, leaving 398 for analvsis.
Two study sites used tube cultures and one used multi-well plates. Specimens were processed and cultured according to each laboratory's established procedures and testing performed according to the respective tests' instructions for use. The resulting stained cells were microscopically evaluated and results reported as HSV-1 positive, HSV-2 positive, or negative for detection of HSV.
Positive and Negative Percent Agreement between the Subject and Comparison test results were calculated and reported at 95% confidence interval.
| Table of Combined Specimen Results from Three Study Sites | ||||||
|---|---|---|---|---|---|---|
| HSV-1 | ||||||
| Comparison Device | ||||||
| + | - | + | - | |||
| D3 DFA HSV ID &Typing Kit | + | 73 | 0 | + | 76 | 1 |
| - | 1 | 324 | - | 0 | 321 | |
| Agreed | 95% CIb | Agreed | 95% CI | |||
| Positive PercentAgreement c (PPA) = | 98.6% | 92.7% - 100% | 100% | 95.3% - 100% | ||
| Negative PercentAgreement d (NPA) = | 100% | 98.9% - 100% | 99.7% | 98.3% -100% |
Specter, S., Hodinka, R. L., and Young, S.A. 2000, Clinical Virology Manual, Washington D.C., ASM Press, 420-424.
2 Bryson, Y.J., M. Dillon, M. Lovett, G. Acura, S. Taylor, J.D. Cherry, L. Johnson, E. Weismeier, W. Growdeon, T. Creagh-Kirk and R. Keeney. 1983. "Treatment of first episodes of genital Herpes simplex virus infection with oral acyclovir: A randomized double-blind controlled trial in normal subjects". New Eng. J. Med., 308: 916-921.
4 Gleaves, C.A., D.J. Wilson, A.D. Wold and T.F. Smith. 1985. "Detection and Serotyping of Herpes simplex Virus in MRC-5 cells by use of centrifugation and monoclonal antibodies 16h post-inoculation". J. Clin. Micro., 21: 29-32.
5 Reeves, E.C., L. Corey, H.G. Adams. L.A. Vontver and K.K. Holmes. 1981. "Risk of recurrence after first episodes of genital herpes: relation to HSV type and antibody response". New Eng. J. Med., 305: 315-319.
® Moore, D.F. 1984. "Comparison of human fibroblast cells and primary rabbit kidney cells for isolation of Herpes simplex virus". J. Clin. Micro 19. 548-549
510(k) summary
3 Dulbecco, R. and H.S. Ginsberg, 1973. "Herpesviruses", Chapter 55 in Microbiology, Third Edition, D.D. Davis, et al. (eds.), Harper and Row, Hagerstown.
6 Ashley, R.L., L. Corey, and W. E. Rawls. 1989. "Herpes simplex Viruses", Chapter 11 in Diagnostic Procedures for Viral, Rickettsial and Chlamydial Infections. Sixth Edition, N.J. Schmidt and R.W. Emmons, (eds), American Public Health Association, Inc., Washington, D.C.
' Gleaves, C.A., D.J. Wilson, A.D. Wold and T.F. Smith. 1985. "Detection and Serotyping of Herpes simplex Virus in MRC-5 cells by use of centrifugation and monoclonal antibodies 16h post-inoculation". J. Clin. Micro., 21: 29-32.
° Ashley, R.L., L. Corey, and W. E. Rawls. 1989. "Herpes simplex Viruses", Chapter 11 in Diagnostic Procedures for Viral, Rickettsial and Chlamydial Infections. Sixth Edition, N.J. Schmidt and R.W. Emmons, (eds), American Public Health Association, Inc., Washington, D.C.
9 "95% Cl" refers to 95% Confidence Intervals, which were calculated according to Exact method (Clopper, C. and S. Pearson, Biometrika 26:404-413, 1934).
6 "Positive Percent Agreement", or "PPA", values were calculated according to {{Total Number of Positive Results in Agreement by both Subject and Predicate Tests) divided by {{Total Number of Positive Results in Agreement by both Subject and Predicate Tests) plus (Number of Results Positive by Predicate but Negative by Subject)}} multiplied by 100%.
9 "Negative Percent Agreement", or "NPA", values were calculated according to {[Total Number of Negative Results in Agreement by both Subject and Predicate Tests) divided by [(Total Number of Negative Results in Agreement by both Subject and Predicate Tests) plus (Number of Results Negative by Predicate but Positive by Subject)]} multiplied by 100%.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
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Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Gail R. Goodrum Vice President, Regulatory and Quality Affairs Diagnostic Hybrids, Inc. 350 West State Street Athens, OH 45701
OCT 2 4 2007
Re: K070265
Trade/Device Name: Diagnostic Hybrids D3 DFA Herpes Simplex Virus Identification and Typing Kit Regulation Number: 21 CFR § 866.3305 Regulation Name: Herpes simplex virus serological reagents Regulatory Class: II Product Code: GON Dated: October 12, 2007 Received: October 15, 2007
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 general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your 11 vice 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 af 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).
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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 attyma
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
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Indications for Use
510(k) Number (if known): K070265
Device Name: Diagnostic Hybrids, Inc. D3 DFA Herpes Simplex Virus Identification and Typing Kit
Indications for Use: The Diagnostic Hybrids, Inc. D3 DFA Herpes Simplex Virus Identification and Typing Kit is intended for use in the qualitative detection and typing of human herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) in cell cultures by immunofluorescence using fluoresceinated monoclonal antibodies (MAbs). Negative results do not rule out an infection and should not be used as the sole basis for diagnosis, treatment or other management decisions. Performance using direct specimen testing has not been evaluated.
Prescription Use X (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)
| Concurrence of CDRH, Office of Device Evaluation (ODE) |
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Ule Schuf
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K070265
§ 866.3305 Herpes simplex virus serological assays.
(a)
Identification. Herpes simplex virus serological assays are devices that consist of antigens and antisera used in various serological tests to identify antibodies to herpes simplex virus in serum. Additionally, some of the assays consist of herpes simplex virus antisera conjugated with a fluorescent dye (immunofluorescent assays) used to identify herpes simplex virus directly from clinical specimens or tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by herpes simplex viruses and provides epidemiological information on these diseases. Herpes simplex viral infections range from common and mild lesions of the skin and mucous membranes to a severe form of encephalitis (inflammation of the brain). Neonatal herpes virus infections range from a mild infection to a severe generalized disease with a fatal outcome.(b)
Classification. Class II (special controls). The device is classified as class II (special controls). The special control for the device is FDA's revised guidance document entitled “Class II Special Controls Guidance Document: Herpes Simplex Virus Types 1 and 2 Serological Assays.” For availability of the guidance revised document, see § 866.1(e).