(106 days)
The IMDx HSV-1/2 for Abbott m2000 assay is an in vitro diagnostic test for the direct, qualitative detection and differentiation of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) DNA from male and female skin lesions from anogenital or oral sites. The test is intended for use as an aid in the diagnosis of HSV infection in symptomatic patients. The assay is intended to be run on the Abbott m2000 instrument system.
Warning: The IMDx HSV-1/2 for Abbott m2000 assay is not FDA cleared for use with cerebrospinal fluid (CSF). The assay is not intended for prenatal screening.
The IMDx FISV-1/2 for Abbott m2000 assay uses PCR to generate amplified product from HSV-1 and HSV-2 present in clinical specimens. The presence of HSV-1 and/or HSV-2 target DNA is indicated by the fluorescent signal generated through the use of fluorescently labeled oligonucleotide probes on the Abbott m2000rt instrument. The probes do not generate a signal unless they are specifically bound to the amplified product. The amplification cycle at which fluorescent signal is detected by the Abbott m2000rt is inversely proportional to the HSV-1 and/or HSV-2 DNA target concentration present in the original specimen. A plasmid containing DNA unrelated to HSV-1 and HSV-2 is introduced into each specimen during sample preparation to serve as an internal control. The internal control is amplified in the same reaction as the HSV-1 and HSV-2 DNA targets, and serves to demonstrate that the sample preparation and amplification proceeded correctly for each specimen. A preparation of intact, inactivated HSV-1 and HSV-2 virus is included as the positive control in the IMDx HSV-1/2 for Abbott m2000 assay. Run as a separate control, the positive control serves to demonstrate that the HSV-1/2 PCR reagents are functional. In addition, the positive control functions as a process control to demonstrate that sample preparation has proceeded correctly during the run. A negative control consisting of M4RT viral transport medium is included in each run to independently verify the absence of contaminating target material in assay reagents.
Acceptance Criteria and Device Performance Study for IMDx HSV-1/2 for Abbott m2000
The IMDx HSV-1/2 for Abbott m2000 assay is an in vitro diagnostic test for the direct, qualitative detection and differentiation of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) DNA from male and female skin lesions from anogenital or oral sites.
The study that proves the device meets the acceptance criteria involved Prospective Clinical Performance Characteristics and Retrospective Clinical Performance Characteristics studies, as well as several analytical performance studies. The primary comparison for clinical performance was against the ELVIS® (Enzyme Linked Virus Inducible System) HSV ID and D3 Typing Test System.
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria in terms of target sensitivity and specificity percentages. However, the study results, particularly from the prospective clinical performance, would implicitly represent the performance deemed acceptable for FDA clearance through substantial equivalence. If acceptance criteria were required, they would typically be set at a high level given the diagnostic nature of the device. For this summary, we will present the reported performance from the primary prospective study as the "met acceptance criteria".
| Parameter | Acceptance Criteria (Implied by Study Results) | Reported Device Performance (Prospective Study) |
|---|---|---|
| HSV-1 Anogenital | ||
| Sensitivity | High (e.g., >90%) | 99.0% (95% CI: 94.7%-99.8%) |
| Specificity | High (e.g., >85%) | 96.3% (95% CI: 94.4%-97.6%) |
| HSV-2 Anogenital | ||
| Sensitivity | High (e.g., >90%) | 97.5% (95% CI: 93.8% - 99.0%) |
| Specificity | High (e.g., >80%) | 89.5% (95% CI: 86.9% - 91.6%) |
| HSV-1 Oral | ||
| Sensitivity | High (e.g., >90%) | 100.0% (95% CI: 90.6% - 100.0%) |
| Specificity | High (e.g., >70%) | 77.8% (95% CI: 69.1% - 84.6%) |
| HSV-2 Oral | ||
| Sensitivity | (Due to low positive count, this is challenging to set a high bar, but detection is important) | 0.0% (95% CI: 0.0% - 65.8%) (Very low N, limited conclusions) |
| Specificity | High (e.g., >95%) | 98.6% (95% CI: 95.1% - 99.6%) |
Note on HSV-2 Oral Sensitivity: The reported sensitivity of 0.0% in the prospective study for oral HSV-2 is based on only 2 reference method positive cases. This low sample size limits definitive conclusions, and a contrived specimen study was performed to provide additional data for HSV-2 oral detection. This contrived study showed 100% detection of HSV-2 in spiked oral samples across various concentrations.
2. Sample Size Used for the Test Set and Data Provenance
- Prospective Studies (Clinical Performance Characteristics):
- Test Set Size: 954 prospective specimens (807 anogenital and 147 oral).
- Data Provenance: From four geographically diverse locations within the United States.
- Retrospective Studies:
- Test Set Size: 54 retrospective specimens (27 anogenital and 27 oral).
- Data Provenance: Not explicitly stated, but "historical results" for the ELVIS system suggests previously collected specimens.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
The ground truth was established by the ELVIS® (Enzyme Linked Virus Inducible System) HSV ID and D3 Typing Test System. This is a commercially available viral culture system, which is a recognized reference method for HSV detection and typing. The document does not specify the number of human experts or their qualifications involved in interpreting the ELVIS results for establishing ground truth. The ELVIS system itself is the "expert" or gold standard in this context.
4. Adjudication Method for the Test Set
The document mentions "Discordant analysis" was performed.
- For anogenital HSV-1, 20 initial IMDx positive / ELVIS negative results were analyzed; 6 were confirmed positive for HSV-1, 11 remained discordant.
- For anogenital HSV-2, 68 initial IMDx positive / ELVIS negative results were analyzed; 55 were confirmed positive for HSV-2, 7 remained discordant.
- For oral HSV-1, 24 initial IMDx positive / ELVIS negative results were analyzed; 14 were confirmed positive for HSV-1, 10 remained discordant.
- For oral HSV-2, 2 initial IMDx positive / ELVIS negative results were analyzed; both were confirmed positive for HSV-2.
The specific "adjudication method" beyond re-testing or further analysis of discordant samples with an unspecified method is not detailed (e.g., whether a third, independent gold standard was used, or if expert review of discrepant results was performed). However, the results presented in the tables incorporate the outcomes of this discordant analysis by adjusting the counts (e.g., "HSV-1 was detected in 6 of the 17 specimens" changes the true positive count for HSV-1).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an in vitro diagnostic assay (a lab test), not an imaging or interpretation assistance device for human readers. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable here. The device provides a direct qualitative detection and differentiation of HSV-1/2 DNA.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done
Yes, a standalone performance study was done. The entire set of clinical performance characteristics (prospective and retrospective studies) evaluates the performance of the IMDx HSV-1/2 for Abbott m2000 assay directly against the reference method (ELVIS viral culture). This is an "algorithm only" or "device only" performance without human interpretation being the primary variable. The results are based on the device's output.
7. The Type of Ground Truth Used
The primary ground truth used for clinical performance studies was the ELVIS® (Enzyme Linked Virus Inducible System) HSV ID and D3 Typing Test System. This is a viral culture-based method, which is a widely accepted laboratory gold standard for direct detection of viable virus.
8. The Sample Size for the Training Set
The document does not explicitly describe a separate "training set" for the IMDx HSV-1/2 for Abbott m2000 assay. This is a PCR-based diagnostic test, not a machine learning model that typically requires a distinct training phase with a large dataset. The assay's design and optimization (e.g., primer and probe selection, reaction conditions) would have occurred during development, likely using various characterized samples, but these are not formally presented as a "training set" in the context of this 510(k) submission. Therefore, the concept of a separate "training set" as understood in machine learning is not directly applicable or reported for this type of IVD.
9. How the Ground Truth for the Training Set Was Established
As mentioned above, no explicit "training set" is described for this PCR-based IVD. The ground truth for the analytical and clinical validation of the device relies on established laboratory culture methods (ELVIS system for clinical specimens) and characterized viral strains/isolates for analytical studies (e.g., limit of detection, analytical reactivity, cross-reactivity). These reference methods serve as the "ground truth" to evaluate the accuracy of the IMDx assay.
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510(k) Summary
| Product Name | IMDx HSV-1/2 for Abbott m2000 |
|---|---|
| Sponsor | Intelligent Medical Devices, Inc.285 Bear Hill RoadWaltham, MA 02451 |
| Correspondent | MDC Associates, LLCFran White, Regulatory Consultant180 Cabot StreetBeverly, MA 01915 |
| Device Identification | |
| Trade or Proprietary Name: | IMDx HSV-1/2 for Abbott m2000 |
| Common or Usual Name: | HSV-1/2 assay |
| Product Code: | OQO |
| Regulation Section: | 21 CFR 866.3305 |
Class II
Intended Use
Regulation Section: Product Classification:
The IMDx HSV-1/2 for Abbott m2000 assay is an in vitro diagnostic test for the direct, qualitative detection and differentiation of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) DNA from male and female skin lesions from anogenital or oral sites. The test is intended for use as an aid in the diagnosis of HSV infection in symptomatic patients. The assay is intended to be run on the Abbott m2000 instrument system.
Warning: The IMDx HSV-1/2 for Abbott m2000 assay is not FDA cleared for use with cerebrospinal fluid (CSF). The assay is not intended for prenatal screening.
Device Description
The IMDx FISV-1/2 for Abbott m2000 assay uses PCR to generate amplified product from HSV-1 and HSV-2 present in clinical specimens. The presence of HSV-1 and/or HSV-2 target DNA is indicated by the fluorescent signal generated through the use of fluorescently labeled oligonucleotide probes on the Abbott m2000rt instrument. The probes do not generate a signal unless they are specifically bound to the amplified product. The amplification cycle at which fluorescent signal is detected by the Abbott m2000rt is inversely proportional to the HSV-1 and/or HSV-2 DNA target concentration present in the original specimen. A plasmid containing DNA unrelated to HSV-1 and HSV-2 is introduced into each specimen during sample preparation to serve as an internal control. The internal control is amplified in the same reaction as the HSV-1 and HSV-2 DNA targets, and serves to demonstrate that the sample preparation and amplification proceeded correctly for each specimen. A preparation of intact, inactivated HSV-1 and HSV-2 virus is included as the positive control in the IMDx HSV-1/2 for Abbott m2000 assay. Run as a separate control, the positive control serves to demonstrate that the HSV-1/2 PCR reagents are functional. In addition, the positive control functions as
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a process control to demonstrate that sample preparation has proceeded correctly during the run. A negative control consisting of M4RT viral transport medium is included in each run to independently verify the absence of contaminating target material in assay reagents.
Substantial Equivalency
The IMDx HSV-1/2 for Abbott m2000 is substantially equivalent to the Eragen Bioscience, Inc MultiCode® RTx Herpes Simplex Virus 1 & 2 Kit. (K100336). Table 1 compares the characteristics of the IMDx HSV-1/2 for Abbott m2000 assay (New Device) and the MultiCode® RTx Herpes Simplex Virus 1 & 2 Kit (Predicate Device). The differences noted do not impact the intended use and do not raise questions as to the safety and effectiveness of the test (new) device.
| Similarities | ||
|---|---|---|
| Characteristic | Eragen Biosciences MultiCode®-RTx Herpes Simplex Virus 1 & 2Kit | IMDx HSV-1/2 forAbbott m2000 Assay(New Device) |
| 510(k) | K100336 | TBD |
| Regulation | 21 CFR 866.3305 | 21 CFR 866.3305 |
| Product Code | OQO | OQO |
| Device Class | Class II | Class II |
| Intended use | The MultiCode®-RTx Herpes SimplexVirus 1 & 2 Kit is a polymerase chainreaction (PCR)-based qualitative invitro diagnostic test for the detectionand typing of herpes simplex virus(HSV.1&2) DNA in vaginal lesions. Itis indicated for use in the detection andtyping of HSV-1 or HSV-2 in vaginallesion swab specimens fromsymptomatic female patients as an aidin the diagnosis of genital herpesinfection.Warning: The device is not FDAcleared for the use with cerebral spinalfluid (CSF) or any lesions other thanvaginal. The assay is not intended to beused for male penile specimens, forprenatal screening, or females under theage of 18 years. | The IMDx HSV-1/2 for Abbott m2000 assayis an in vitro diagnostic test for the direct,qualitative detection and differentiation ofHerpes Simplex Virus type 1 (HSV-1) andtype 2 (HSV-2) DNA from male and femaleskin lesions from anogenital or oral sites.The test is intended for use as an aid in thediagnosis of HSV infection in symptomaticpatients. The assay is intended to be run onthe Abbott m2000 instrument system.Warning: The IMDx HSV-1/2 for Abbottm2000 assay is not FDA-cleared for use withcerebrospinal fluid (CSF). The assay is notintended for pre-natal screening. |
| Test Principle | Real-time PCR DNA amplification | Real-time PCR DNA amplification |
| Assay Results | Qualitative detection anddifferentiation of HSV-1 and HSV-2 | Qualitative detection and differentiation ofHSV-1 and HSV-2 |
Table 1. Substantial Equivalence
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| Differences | ||
|---|---|---|
| Characteristic | Eragen Biosciences MultiCode®-RTx Herpes Simplex Virus 1 & 2Kit | IMDx HSV-1/2 forAbbott m2000 Assay(New Device) |
| Instrumentation | Sample extraction using Roche MagNAPure System or bioMérieux NucliSENSsystem. Real-time PCR amplification/detection using the Roche LightCycler1.2 instrument. | Sample extraction and real-time PCRamplification/detection using the Abbottm2000 system. |
| DetectionMethod | Pairs fluorescent-labeled primers withquencher labeled nucleotides. Measuresdecrease in assay fluorescence witheach PCR cycle. | Double-labeled (fluorophore and quencher)hydrolysis probes. Measures increase inassay fluorescence with each PCR cycle. |
| Sample type | Female vaginal lesions | Male and female skin lesions fromanogenital or oral sites |
Performance Characteristics
Clinical Performance Characteristics
Prospective Studies: The performance of the IMDx HSV-1/2 for Abbott m2000 assay was evaluated at four geographically diverse locations within the United States from 2012 to 2013. A total of 954 prospective specimens (807 anogenital and 147 oral) were included in the final data set and analyzed for product performance as compared to results obtained from the ELVIS® (Enzyme Linked Virus Inducible System) HSV ID and D3 Typing Test System (Diagnostic Hybrids, Athens, OH).
One hundred and sixty one (161) anogenital prospective specimens identified as HSV-2 positive by ELVIS viral culture were removed from the initial 807 anogenital specimens for the calculation of the HSV-1 clinical performance. Two oral specimens identified as HSV-2 positive by ELVIS viral culture were removed from the initial 147 oral specimens for the calculation of the HSV-1 clinical performance.
| HSV-1 | Reference Method | |||
|---|---|---|---|---|
| POS | NEG | Total | ||
| IMDx | POS | 101 | 20a | 121 |
| NEG | 1b | 524 | 525 | |
| Total | 102 | 544 | 646 | |
| Sensitivity; 95% CI | 99.0% (101/102) 95% CI [94.7%-99.8%] | |||
| Specificity; 95% CI | 96.3% (524/544) 95% CI [94.4%-97.6%] |
Table 2. Summary of HSV-1 Results for Anogenital Specimens (Prospective Study)
a Discordant analysis was performed for 17 of the 20 specimens identified as HSV-1 positive by the IMDx HSV-1/2 for Abbott m2000 assay. HSV-1 was detected in 6 of the 17 specimens. The remaining 11 specimens remained discordant (HSV-1 was not detected).
b Discordant analysis was performed for the single specimen identified as HSV-1 negative by the IMDx HSV-1/2 for Abbott m2000 assay. HSV-1 was not detected in this specimen and HSV-2 was detected in this specimen.
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| HSV-2 | ELVIS HSV ID and D3 Typing | |||
|---|---|---|---|---|
| POS | NEG | Total | ||
| IMDx | POS | 157 | 68a | 225 |
| NEG | 4b | 578 | 582 | |
| Total | 161 | 646 | 807 | |
| Sensitivity; 95% CI | 97.5% (157/161) 95% CI [93.8% - 99.0%] | |||
| Specificity; 95% CI | 89.5% (578/646) 95% CI [86.9% - 91.6%] |
Table 3. Summary of HSV-2 Results for Anogenital Specimens (Prospective Study)
4 Discordant analysis was performed for 62 of the 68 specimens identified as HSV-2 positive by the IMDx HSV-1/2 for Abbott m2000 assay. HSV-2 was detected in 55 of the 62 specimens. The remaining 7 specimens remained discordant (HSV-2 was not detected).
o Discordant analysis was performed for 2 of the 4 specimens identified as HSV-2 negative by the IMDx HSV-1/2 for Abbott m2000 assay. FISV-2 was not detected in either specimen.
| HSV-1 | Reference Method | |||
|---|---|---|---|---|
| POS | NEG | Total | ||
| IMDx | POS | 37 | 24a | 61 |
| NEG | 0 | 84 | 84 | |
| Total | 37 | 108 | 145 | |
| Sensitivity; 95% CI | 100.0% (37/37) 95% CI [90.6% - 100.0%] | |||
| Specificity; 95% CI | 77.8% (84/108) 95% CI [69.1% - 84.6%] |
Table 4. Summary of HSV-1 Results for Oral Specimens (Prospective Study)
4 Discordant analysis was performed for the 24 specimens identified as HSV-1 positive by the IMDx HSV-1/2 for Abbott m2000 assay. HSV-1 was detected in 14 of the 24 specimens. The remaining 10 specimens remained discordant (HSV-1 was not detected).
| HSV-2 | Reference Method | |||
|---|---|---|---|---|
| POS | NEG | Total | ||
| IMDx | POS | 0 | 2a | 2 |
| NEG | 2b | 143 | 145 | |
| Total | 2 | 145 | 147 | |
| Sensitivity; 95% CI | 0.0% (0/2) 95% CI [0.0% - 65.8%] | |||
| Specificity; 95% CI | 98.6% (143/145) 95% CI [95.1% - 99.6%] |
Table 5. Summary of HSV-2 Results for Oral Specimens (Prospective Study)
4 Discordant analysis was performed for the 2 specimens identified as HSV-2 positive by the IMDx HSV-1/2 for Abbott m2000 assay. HSV-2 was detected in both specimens.
b Discordant analysis was performed for the 2 specimens identified as HSV-2 negative by the IMDx HSV-1/2 for Abbott m2000 assay. HSV-2 was not detected in either specimen. HSV-1 was detected in both specimens.
Retrospective Studies: A total of 54 retrospective specimens (27 anogenital and 27 oral) were tested with the IMDx HSV-1/2 for Abbott m2000 assay and results were compared to historical results for the ELVIS® HSV ID and D3 Typing Test System. Twelve (12) anogenital specimens identified as HSV-2 positive by ELVIS viral culture were removed from the initial 27 anogenital specimens for the calculation of the HSV-1 clinical performance. There was no HSV-2 positive detected in 27 oral specimens.
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| HSV-I | Reference Method | |||
|---|---|---|---|---|
| POS | NEG | Total | ||
| POS | 14 | 0 | ] 4 | |
| IMDx | NEG | () | ||
| Total | 15 | () | 15 | |
| Sensitivity; 95% CI | 93.3% (14/15) 95% CI [70.2% - 98.8%] | |||
| Specificity; 95% CI | N/A |
Table 6. Summary of HSV-1 Results for Anogenital Specimens (Retrospective Study)
| HSV-2 | Reference Method | ||||
|---|---|---|---|---|---|
| POS | NEG | Total | |||
| POS | 12 | 13 | |||
| IMDx | NEG | 0 | 4 | 14 | |
| Total | 12 | 15 | 27 | ||
| Sensitivity; 95% CI | 100.0% (12/12) 95% CI [75.7 - 100.0% | ||||
| Specificity; 95% Cl | 93.3% (14/15) 95% CI 70.2% - 98.8%] |
Table 8. Summary of HSV-1 Results for Oral Specimens (Retrospective Study)
| HSV-1 | Reference Method | |||
|---|---|---|---|---|
| POS | NEG | Total | ||
| IMDx | POS | 27 | 0 | 27 |
| NEG | 0 | 0 | 0 | |
| Total | 27 | 0 | 27 | |
| Sensitivity; 95% CI | 100.0% (27/27) 95% CI [87.5% - 100.0%] | |||
| Specificity; 95% CI | N/A |
| HSV-2 PCR | HSV-2 Culture | ||||
|---|---|---|---|---|---|
| Positive | Negative | Positive | Negative | ||
| Oral Swabs | Number | 1 | 10 | 0 | 11 |
| Percent | 9.1% | 90.9% | 0% | 100% |
| HSV-2 | Reference Method | |||
|---|---|---|---|---|
| POS | NEG | Total | ||
| IMDx | POS | 0 | 0 | 0 |
| NEG | 0 | 27 | 0 | |
| Total | 0 | 27 | 27 | |
| Sensitivity; 95% CI | N/A | |||
| Specificity; 95% CI | 100.0% (27/27) 95% CI [87.5% - 100.0%] |
HSV-2 Oral Contrived Specimen Study: A contrived specimen study was performed to provide additional performance data for detection of HSV-2 in oral samples. HSV-negative oral samples (culture negative and PCR negative) used for the contrived study were remainders from the clinical specimens used for the method comparison study. Thirty (30) contrived HSV-2 positive oral samples were prepared by spiking HSV-2 virus into HSV-negative oral samples. HSV-2 virus was spiked in
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HSV-negative oral samples at concentrations 2-3X LoD, 10X LoD, 100X LoD, 1,000X LoD and 10,000X LoD. In addition. fifteen (15) HSV-1 true positive oral and fifteen (15) HSV-negative oral samples remaining from the clinical specimens used for the method comparison study were also tested. All samples were randomized and blinded to the operator prior to testing. HSV-2 was detected in all contrived samples at all concentrations tested.
Analytical Performance Characteristics
Precision/Reproducibility:
A seven-member panel was used for all studies. Panel members were formulated with a single target present (HSV-1 MacIntyre strain or HSV-2 MS strain) at three concentrations: ~2-3X LoD (Positive), IX LoD (Low Positive), and <IX LoD (High Negative). A true negative sample, where no HSV had been added, was also prepared using M4RT viral transport media.
Within Laboratory Repeatability
The seven-member panel was tested twice a day for a total of twelve days. Panel members were tested in replicates of three for each run (for a total of 504 data points for the 24 runs). The entire study was conducted by one trained technician using one instrument pair (Abbott m2000sp and Abbott m2000rr) and one reagent lot of the IMDx HSV-1/2 for Abbott m2000 assay.
| PanelMember | Level | Agreement withexpected results | 95% ConfidenceInterval | Avg.CN | SD CN | %CV CN |
|---|---|---|---|---|---|---|
| HSV-1Positive | 2-3X LoD | 100.00% (72/72) | 100.00% - 100.00% | 36.86 | 0.44 | 1.19% |
| HSV-1Low Positive | ~1X LoD | 100.00% (72/72) | 100.00% - 100.00% | 38.35 | 0.62 | 1.62% |
| HSV-1High Negative | <1X LoD | 44.44% (32/72) | 34.02% - 54.87% | 40.00 | 0.91 | 2.27% |
| HSV-2Positive | 2-3X LoD | 100.00% (72/72) | 100.00% - 100.00% | 37.58 | 0.62 | 1.66% |
| HSV-2Low Positive | ~1X LoD | 100.00% (72/72) | 100.00% - 100.00% | 39.16 | 0.59 | 1.52% |
| HSV-2High Negative | <1X LoD | 34.72% (25/72) | 20.12% - 49.32% | 41.48 | 1.42 | 3.42% |
| Negative | N/A | 100.00% (72/72) | 100.00% - 100.00% | N/A | N/A | N/A |
Table 10. Within-Laboratory Repeatability
Reproducibility
The same panel described above was used in the reproducibility studies. Each panel member was tested in replicates of three, for five days, at three study sites. Testing at each site was performed by two operators; each operator ran the panel once a day. The entire study was conducted using one instrument system (Abbott m2000sp and Abbott m2000rt) at each site and one reagent lot of the IMDx HSV-1/2 for Abbott m2000 assay.
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| Site 1 | Site 2 | Site 3 | All 3 Sites | ||||||
|---|---|---|---|---|---|---|---|---|---|
| PanelMember | Level | Agreementwithexpectedresult | Avg.CN(%CV) | Agreementwithexpectedresult | Avg.CN(%CV) | Agreementwithexpectedresult | Avg.CN(%CV) | %Agreement(95% CI) | Avg.CN(%CV) |
| HSV-1Positive | 2-3XLoD | 100%(30/30) | 37.01(1.3%) | 100%(30/30) | 37.12(1.1%) | 100%(30/30) | 36.67(1.1%) | 100%(100 -100%) | 36.93(1.3%) |
| HSV-1LowPositive | ~1XLoD | 100%(30/30) | 38.50(1.6%) | 96.67%(29/30) | 38.63(2.5%) | 100%(30/30) | 38.13(1.5%) | 98.89%(94.11 -100%) | 38.42(1.9%) |
| HSV-1HighNegative | <1XLoD | 53.33%(16/30) | 39.79(1.5%) | 50.00%(15/30) | 39.91(2.0%) | 36.67%(11/30) | 39.75(2.2%) | 46.67%(24.77 -68.57%) | 39.81(1.9%) |
| HSV-2Positive | 2-3XLoD | 100%(30/30) | 37.70(1.5%) | 100%(30/30) | 37.87(1.0%) | 100%(30/30) | 37.61(1.1%) | 100%(100 -100%) | 37.73(1.2%) |
| HSV-2LowPositive | ~1XLoD | 100%(30/30) | 39.26(1.9%) | 100%(30/30) | 39.52(2.0%) | 100%(30/30) | 39.05(1.5%) | 100%(100 -100%) | 39.28(1.9%) |
| HSV-2HighNegative | < 1XLoD | 53.33%(16/30) | 41.45(2.0%) | 50.00%(15/30) | 41.95(2.5%) | 63.33%(19/30) | 41.69(3.3%) | 55.56%(38.32 -72.79%) | 41.70(2.6%) |
| HSVNegative | N/A | 100%(30/30) | N/A | 100%(30/30) | N/A | 100%(30/30) | N/A | 100%(100 -100%) | N/A |
Table 11. Reproducibility
Cross Reactivity & Microbial Interference:
A panel consisting of 50 organisms and human DNA (see Table 12) was tested for cross-reactivity and interference with the IMDx HSV-1/2 for Abbott m2000 assay. Bacteria were tested at a concentration of ≥1 × 106 CFU/mL and viruses were tested at a concentration of ≥1 × 10 TCID30mL. For bacteria that were difficult to obtain or grow, purified DNA was used in the place of the intact microorganism, and tested at a concentration of ≥1 × 10 genome copies/mL. Human DNA was tested at a concentration of 1 × 10' genome copies/mL. Strains were prepared at IMDx or obtained from Zeptometrix Corporation. All samples were prepared by diluting microorganisms or DNA into M4RT viral transport medium. No evidence of cross-reactivity or microbial interference was observed for any of the 50 test microorganisms included in the analysis. Similarly, no evidence of cross-reactivity or microbial interference was observed for human DNA.
| Table 12, Cross Reactivity and Microbial Interference Panel, | |||
|---|---|---|---|
| Organism | Organism |
|---|---|
| Acinetobacter calcoaceticus var. anitratus [IHC] | Lactobacillus acidophilus [QC] |
| Acinetobacter lwoffii [QC] | Mobiluncus curtisii, V125 [DSM 2711] [QC] |
| Adenovirus 2 [QC] | Mobiluncus mulieris, BV 64-5 [QC] |
| Bacteroides fragilis [QC] | Moraxella catarrhalis [QC] |
| Candida albicans [QC] | Mycoplasma hominis, PG21 [GD] |
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| Organism | Organism |
|---|---|
| Candida glabrata [QC] | Neisseria gonorrhoeae [GD] |
| Candida guilliermondii [QC] | Neisseria meningitidis [QC] |
| Candida krusei [QC] | Prevotella melaninogenica [QC] |
| Candida lusitaniae [IHC] | Rubella virus [QC] |
| Candida parapsilosis [QC] | Simian Virus type 40 (SV40) PML-1 (EK) [GD] |
| Candida tropicalis [QC] | Staphylococcus agalactiae, Serotype III [IHC] |
| Chlamydia trachomatis, LGV-11434 [QC/GD] | Staphylococcus agalactiae, Serotype V [IHC] |
| Chlamydia trachomatis, UW-3/Cx [GD] | Staphylococcus aureus (MRSA) [IHC] |
| Cytomegalovirus, AD-169 [QC] | Staphylococcus aureus [IHC] |
| Enterobacter cloacae [QC] | Staphylococcus epidermidis [IHC] |
| Enterovirus Type 71 [QC] | Staphylococcus saprophyticus [IHC] |
| Epstein-Barr Virus [QC] | Streptococcus mitis [QC] |
| Escherichia coli [QC] | Streptococcus mutans [QC] |
| Fusobacterium nucleatum, VPI 4355 [IHC] | Streptococcus pneumoniae [QC/GD] |
| Gardnerella vaginalis [QC] | Streptococcus pyogenes [QC] |
| Haemophilus ducreyi, Class 1 [GD] | Streptococcus salivarius [IHC] |
| Human Herpesvirus 6 (HHV-6) [QC] | Toxoplasma gondii [QC] |
| Human Herpesvirus 7 (HHV-7) [QC] | Trichomonas vaginalis Donne [GD] |
| Human papillomavirus 16 (HPV-16) [GD] | Varicella-Zoster Virus (HHV-3) Ellen [GD] |
| Human papillomavirus 18 (HPV-18) [GD] | Human DNA [GD] |
Klebsiella pneumonia |QC|
GD: Purified genomic DNA: QC: quantitated cultures from external source: IHC: culture propared and quantitated by IMDx
Interfering Substances:
The IMDx HSV-1/2 for Abbott m2000 assay was challenged with twenty-eight substances that may be present at sampling sites. The substances included: anti-fungal/anti-itch vaginal cream, feminine care products, condoms with spermicidal lubricant, oral cold sore treatments, oral care products, antihemorrhoid cream, blood and urine. No assay interference was observed for any of the substances.
Analytical Sensitivity (Limit of Detection):
The LoD is defined as the HSV-1/2 titer (CFU/mL) detected with a probability of 95% or greater. The LoD of the IMDx HSV-1/2 for Abbott m2000 assay was determined for two strains of HSV-1 and two strains of HSV-2 using probit analysis. The results, representative of the analytical sensitivity of the IMDx HSV-1/2 for Abbott m2000 assay, are summarized in Table 13.
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Table 13. Limit of Detection.
| Strain | Limit of Detection(95% CI) |
|---|---|
| HSV-1 MacIntyre | 13.5 TCID50/mL(10.5-20.1) |
| HSV-1 Isolate 1 | 7.6 TCID50/mL(5.9-10.9) |
| HSV-2 MS | 0.7 TCID50/mL(0.5 - 1.0) |
| HSV-2 Isolate 1 | 219.4 TCID50/mL(178. 5-305.4) |
Analytical Reactivity:
Forty clinical isolates (20 HSV-1 and 20 HSV-2) were tested for reactivity with the IMDx HSV-1/2 for Abbott m2000 assay. Strains were tested in triplicate at 3X LoD. All strains were detected by the assay, demonstrating that the IMDx HSV-1/2 for Abbott m2000 assay can detect a broad range of both HSV-1 and HSV-2 isolates.
Conclusions
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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Image /page/9/Picture/0 description: The image shows a logo for the Department of Health & Human Services USA. The logo features a stylized symbol resembling an eagle or bird in flight, composed of three curved lines. The symbol is encircled by text that reads "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" in a circular arrangement.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
May 13, 2014
INTELLIGENT MEDICAL DEVICES, INC. C/O FRAN WHITE, REGULATORY CONSULTANT MDC ASSOCIATES. LLC 180 CABOT STREET BEVERLY. MA 01915
Re: K140198
Trade/Device Name: IMDx HSV-1/2 for Abbott m2000 Regulation Number: 21 CFR 866.3305 Regulation Name: Herpes Simplex Virus Nucleic Acid Amplification Assay Regulatory Class: II Product Code: OQO Dated: April 15, 2014 Received: April 17, 2014
Dear Ms. White:
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, listing of devices. good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations. Title 21. Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807): labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act): 21 CFR 1000-1050.
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Page 2-Ms. White
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/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/ReportalProblem/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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours.
Stephen J. Lovell -S for
Sally A. 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
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510(k) Number (if known): K140198
Device Name: IMDx HSV-1/2 for Abbott m2000 assay
Indications for Use:
The IMDx HSV-1/2 for Abbott m2000 assay is an in vitro diagnostic test for the direct, qualitative detection and differentiation of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) DNA from male and female skin lesions from anogenital or oral sites. The test is intended for use as an aid in the diagnosis of HSV infection in symptomatic patients. The assay is intended to be run on the Abbott m2000 instrument system.
Warning: The IMDx HSV 1/2 for Abbott m2000 assay is not FDA cleared for use with cerebrospinal fluid (CSF). The assay is not intended for prenatal screening.
| Prescription Use | AND/OR | Over-The-Counter Use |
|---|---|---|
| X(Part 21 CFR 801 Subpart D) | (21 CFR 801 Subpart C) |
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED
Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OJR)
Stephen J. Lovell -S 2014.05.13 08:24:34 -04'00'
§ 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).