(123 days)
The Focus Diagnostics Plexus™ HerpeSelect® HSV 1 and 2 IgG (with software) is intended for qualitatively detecting the presence or absence of human IgG antibodies to HSV-1 and HSV-2 in human sera. The test is indicated for pregnant women and sexually active adults, as an aid for presumptively diagnosing HSV-1 and HSV-2 infection. The predictive value of a positive or negative result depends on the population's prevalence and the pretest likelihood of HSV-1 and HSV-2 infection. The test is not intended for donor screening or for self-testing. The performance of this assay has not been established for use in a pediatric population, for neonatal screening, for testing of immunocompromised patients, for use by a point of care facility or for use with automated equipment.
The Focus Diagnostics Plexus™ HerpeSelect® HSV 1 and 2 IgG (with software) is a multiplexed immunoassay for qualitatively detecting and differentiating human IgG antibodies to HSV-2. Test principle is identical to the predicate device.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Device: Plexus™ HerpeSelect® HSV 1 and 2 IgG (with software)
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" in a quantitative manner for all performance aspects. However, the "Summary of Previous Studies for Plexus™ HerpeSelect® HSV 1 and 2 IgG (manual calculation)" table on page 2 provides clear performance metrics that can be interpreted as the device meeting expected performance for a similar predicate device.
For the purpose of this analysis, I will synthesize "acceptance criteria" from the described study results, assuming that the reported performance met the internal and regulatory expectations for market clearance.
| Acceptance Criteria (Inferred from Study Results) | Reported Device Performance (Plexus™ HerpeSelect® HSV 1 and 2 IgG) |
|---|---|
| Agreement with Plexus Software vs. Manual Calculation | |
| HSV-1 Index Agreement | 100% (95% CI: 0.977 - 1.00) for HSV-1 Positives (n=161)100% (95% CI: 0.398 - 1.00) for HSV-1 Equivocal (n=4)100% (95% CI: 0.973 - 1.00) for HSV-1 Negatives (n=134) |
| HSV-2 Index Agreement | 100% (95% CI: 0.974 - 1.00) for HSV-2 Positives (n=139)100% (95% CI: 0.590 - 1.00) for HSV-2 Equivocal (n=7)100% (95% CI: 0.976 - 1.00) for HSV-2 Negatives (n=153) |
| Performance in Indicated Populations | |
| Pregnant Women HSV-1 Specificity | 96.5% (95%CI 92.5-98.7%) |
| Pregnant Women HSV-1 Sensitivity | 92.2% (95%CI 86.1-96.2%) |
| Pregnant Women HSV-2 Specificity | 94.3% (95%CI 88.5-97.7%) |
| Pregnant Women HSV-2 Sensitivity | 95.5% (95%CI 91.2-98.0%) |
| Sexually Active Adults HSV-1 Specificity | 91.0% (95%CI 85.4-95.0%) |
| Sexually Active Adults HSV-1 Sensitivity | 96.5% (95%CI 92.0-98.9%) |
| Sexually Active Adults HSV-2 Specificity | 96.3% (95%CI 90.9-99.0%) |
| Sexually Active Adults HSV-2 Sensitivity | 97.4% (95%CI 93.9-99.1%) |
| Agreement with CDC HSV/CMV Panel | |
| Agreement with HSV-1 Positives | 100% (54/54), 95%CI 89.1-100% (for HSV-1 Positive only), 95%CI 84.6-100% (for Dual Positive) |
| Agreement with HSV-2 Positives | 100% (36/36), 95%CI 76.8-100% (for HSV-2 Positive only), 95%CI 84.6-100% (for Dual Positive) |
| Agreement with Negatives | 100% (32/32), 95%CI 89.1-100% (for Dual Negative) |
| Performance in Low Prevalence Population | |
| Low Prevalence HSV-1 Agreement with Negatives | 97.9% (46/47), 95%CI 88.7-99.9% |
| Low Prevalence HSV-2 Agreement with Negatives | 100% (71/71), 95%CI 94.9-100% |
| Cross-reactivity | |
| HSV-1 Cross-reactivity: CMV, EBV, VZV combined | 0-5% observed (e.g., 5.0% for CMV, 3.0% for VZV, 3.1% for EBV, for samples that were HSV-1 ELISA dual negative but positive for other viruses). Specifically, for dual negatives: One out of 37 samples was HSV-1 equivocal/positive, which was triple positive for CMV, VZV, EBV. |
| HSV-2 Cross-reactivity: CMV, EBV, VZV combined | 0-3% observed (e.g., 0.0% for CMV, 2.9% for VZV, 3.2% for EBV, for samples that were HSV-2 ELISA dual negative but positive for other viruses). Specifically, for dual negatives: One out of 37 samples was HSV-2 equivocal/positive, which was positive for VZV and EBV. |
| Reproducibility | |
| %CV of Positives (Inter/Intra-assay, Inter-Lab) | ≤10% for most positive samples, with some acceptable variations (e.g., Sample 9 HSV-1 Inter-assay %CV was 10.3%, Sample 3 HSV-1 Inter-assay %CV was 14.9%, HSV-2 Sample 3 Inter-assay %CV was 28.3%) |
| Inter-Lot %CV | Generally <15% for most positive samples, with higher CVs for very low index samples (e.g., Sample 3 HSV-1 Inter-Lot %CV was 17.0%, Sample 3 HSV-2 Inter-Lot %CV was 50.9%, Sample 10 HSV-1 Inter-Lot %CV was 50.6%) |
2. Sample Sizes and Data Provenance for Test Sets
-
Software Validation Test Set (Agreement between Plexus Software and Manual Calculation):
- Sample Size: n = 600 total (161 HSV-1 Pos, 4 HSV-1 Eqv, 134 HSV-1 Neg, 1 invalid; 139 HSV-2 Pos, 7 HSV-2 Eqv, 153 HSV-2 Neg, 1 invalid).
- Data Provenance: Not explicitly stated regarding country of origin, but described as "Testing was done at two external sites and one internal site." This suggests multiple US-based labs. The study describes it as confirming internal and external consistency rather than a primary clinical validation. It is retrospective since it compares software calculations to existing manual calculations.
-
Clinical Studies Test Sets (Sensitivity and Specificity):
- Sexually Active Adults: n = 300 (150 from Focus Diagnostics, 150 from an external investigator). Sera were "sequentially submitted to the laboratory, archived, and masked."
- Data Provenance: Sera were collected in the Pacific Northwestern United States. One external site was a clinical laboratory in Southern California. Retrospective (archived).
- Pregnant Women: n = 300 (150 from Focus Diagnostics, 150 from an external investigator). Sera were "sequentially submitted to the laboratory, archived, and masked."
- Data Provenance: Sera were collected in the Pacific Northwestern United States. The external investigator was a University laboratory in Northern California. Retrospective (archived).
- CDC HSV/CMV Panel: n = 100 samples (consisting of 50 unique sera with duplicates).
- Data Provenance: Obtained from the CDC. This is a characterized, masked reference panel. Retrospective.
- Low Prevalence Population: n = 77. Sera were "sequentially selected, archived and masked."
- Data Provenance: Sera from patients aged 18-19, submitted to a clinical laboratory in Southern California from states "having a history of low sexually transmitted disease prevalence." Retrospective (archived).
- Cross-reactivity: n = 51 (37 HSV ELISA dual negative, 14 HSV ELISA mixed sero-reactivity).
- Data Provenance: Not explicitly stated, likely internal/archived samples. Retrospective.
- Reproducibility (Inter-laboratory, Inter/Intra-assay, Inter-Lot): Not specified sample provenance for the 11 tested samples, likely contrived or well-characterized internal samples.
- Sexually Active Adults: n = 300 (150 from Focus Diagnostics, 150 from an external investigator). Sera were "sequentially submitted to the laboratory, archived, and masked."
3. Number of Experts and Qualifications for Ground Truth
The document does not describe the use of "experts" to establish ground truth in the traditional sense of medical image interpretation (e.g., radiologists reviewing images). Instead, the ground truth for the serological assays is established by a reference method.
- Reference Method: The primary "gold-standard reference method" used for calculating sensitivity and specificity was the Focus Diagnostics HerpeSelect 1 and 2 Immunoblot IgG. This is a laboratory-based serological test, not one that relies on human expert interpretation of an image or clinical case.
- CDC Panel: The CDC panel itself is a "masked, characterized serum panel" where results (HSV-1, HSV-2, dual positive/negative) are pre-determined by CDC using their own established methods.
Therefore, the concept of "number of experts" and their "qualifications" as typically applied to devices requiring human interpretation (e.g., radiology AI) is not directly applicable here. The ground truth relies on the established accuracy and reliability of the predicate immunoblot assay and the CDC's characterization of their panel.
4. Adjudication Method for the Test Set
Adjudication, in the context of resolving discrepancies between multiple readers or between a device and a reader, is not applicable in this study design.
- The ground truth is established by a single reference method (Immunoblot IgG or CDC's characterization). The new device's results are compared directly to this established ground truth.
- For the "Agreement between Index Calculated with Plexus Software and Index Calculated Manually" study, it's a direct comparison of numerical results. Deviations would be identified as non-agreement, not adjudicated by experts.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study
No, a Multi Reader Multi Case (MRMC) comparative effectiveness study was not performed. This type of study typically assesses how a device (often AI) influences the diagnostic performance of human readers by comparing their performance with and without device assistance. The Plexus™ HerpeSelect® HSV 1 and 2 IgG (with software) is an in vitro diagnostic device, and its performance is evaluated against a predicate serological test, not as an aid for human interpretation.
6. Standalone (Algorithm Only) Performance Study
Yes, a standalone performance study was done. The entire set of performance characteristics presented (sensitivity, specificity, agreement with CDC panel, cross-reactivity, reproducibility) are measures of the algorithm's (device software's) direct performance in interpreting the multiplex immunoassay fluorescent signals to determine HSV-1 and HSV-2 IgG status.
- The study "Agreement between Index Calculated with Plexus Software and Index Calculated Manually" directly validates the software's ability to process raw data and generate results.
- All subsequent clinical performance studies compare the device's output (as determined by the software) directly against a reference method. Therefore, all reported performance metrics relate to the standalone performance of the Plexus™ HerpeSelect® HSV 1 and 2 IgG (with software).
7. Type of Ground Truth Used
The primary type of ground truth used was expert consensus (through an established reference method):
- Established Reference Method: The Focus Diagnostics HerpeSelect 1 and 2 Immunoblot IgG served as the "gold-standard reference method" for sensitivity and specificity calculations in the pregnant women and sexually active adults cohorts, as well as the low prevalence population. Immunoblot assays are considered highly accurate and specific for HSV typing.
- Characterized Panel: For the CDC panel, the ground truth was based on the CDC's characterization of the serum samples. This implies a rigorous, multi-method approach by a recognized authority to establish the true serostatus of the samples.
8. Sample Size for the Training Set
The document does not explicitly state the sample size for the training set. The provided information focuses entirely on validation/test sets to demonstrate the performance characteristics of the finalized device and its associated software. For in vitro diagnostic devices like this, training data might implicitly refer to samples used during the development and optimization phases of the assay and software, which are not typically detailed in 510(k) summaries.
9. How the Ground Truth for the Training Set Was Established
Since no explicit training set is described, information on how its ground truth was established is not provided in this document. During the development of such an assay, the ground truth for any internal training or optimization samples would typically be established using similar or earlier versions of highly accurate reference methods, potentially including culture confirmation, Western blot, or other established serological tests.
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Image /page/0/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo features the word "FOCUS" in bold, sans-serif font, with a curved, swooping graphic element to the left of the word. Below "FOCUS" is the word "Diagnostics" in a smaller, non-bold font, underlined with a thin line. The overall design is simple and professional.
07151
of Safety and Effectiveness
V 1 and 2 IgG (with software) Catalog Number: MP0900G Prepared: September 24, 2007 Page 1 of 8
| Applicant | Focus Diagnostics, Inc.10703 Progress WayCypress, California 90630USA |
|---|---|
| Establishment Registration No. | 2023365 |
| Contact Person | Constance BridgesSid Mathur (Alternate Contact)tel 714.220.1900fax 714.995.6921cbridges@focusdx.comsmathur@focusdx.com |
| Summary Date | September 24, 2007 |
OCT 5 2007
| Proprietary Name | Plexus™ HerpeSelect® HSV 1 and 2 IgG (with software) |
|---|---|
| Generic Name | Herpes Simplex Virus Types 1 and 2 Serological Assays |
| Classification | Class II |
| Predicate Device | HerpeSelect 1 and 2 Immunoblot IgG |
Device Description
The Focus Diagnostics Plexus™ HerpeSelect® HSV 1 and 2 IgG (with software) is a multiplexed immunoassay for qualitatively detecting and differentiating human IgG antibodies to HSV-2. Test principle is identical to the predicate device.
Intended Use
The Focus Diagnostics Plexus™ HerpeSelect® HSV 1 and 2 IgG (with software) is intended for qualitatively detecting the presence or absence of human IgG antibodies to HSV-1 and HSV-2 in human sera. The test is indicated for pregnant women and sexually as an aid for presumptively diagnosing HSV-1 and HSV-2 infection. The predictive value of a positive or negative result depends on the population's prevalence and the pretest likelihood of HSV-1 and HSV-2 infection. The test is not intended for donor screening or for self-testing. The performance of this assay has not been established for use in a pediation, for neonatal screening, for testing of immunocompromised patients, for use by a point of care facility or for use with automated equipment.
Test Principle
The Focus Diagnostics HerpeSelect 1 and 2 Plexus IgG uses an Antigen Bead suspension that contains two distinct HSV antigen bead types that fluoresce at different wavelengths and/or intensities: gG-1 beads and gG-2 beads. The Focus Diagnostics HerpeSelect® 1 and 2 Multiplex IgG is a three step procedure.
- Patient sera are diluted, and the diluted sera are incubated with Antibodies are present, l . then the antibodies bind to the corresponding antigen beads.
- Phycoerythrin-conjugated goat anti-human IgG, (Conjugate) is added, and the Conjugate binds to the bound 2. HSV antibody (if present), and forms a Conjugate-HSV antibody-antigen bead sandwich.
-
- Fluorescence from each distinct HSV antigen bead type is measured against a Cut-off Calibrator.
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Image /page/1/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo features the word "FOCUS" in bold, sans-serif font. Above and to the left of the word "FOCUS" is a curved, crescent-shaped graphic. Below the word "FOCUS" is the word "Diagnostics" in a smaller, non-bold font, underlined with a thin line.
K071511 510(k) Summary of Safety and Effectiveness Plexus The HerpeSelect® HSV 1 and 2 IgG (with software) Catalog Number: MP0900G Prepared: September 24, 2007
Page 2 of 8
Performance Characteristics
Studies to Validate Plexus™ HerpeSelect® HSV 1 and 2 IgG (with software)
Testing was done at two external sites and one internal site to confirm that assay results obtained using Plexus Software are identical to results calculated manually using the instrument (Luminex) raw data.
| Agreement between Index Calculated with Plexus Software and Index Calculated Manually (n = 600) | ||
|---|---|---|
| Sample Type | n | % Agreement; 95% Confidence Interval |
| HSV-1 Pos | 161/161 | 100%; 95% CI: 0.977 - 1.00 |
| HSV-1 Eqv | 4/4 | 100%; 95% CI: 0.398 - 1.00 |
| HSV-1 Neg | 134/134 | 100%; 95% CI: 0.973 - 1.00 |
| HSV-1 Invalid | 1/1 | - |
| HSV-2 Pos | 139/139 | 100%; 95% CI: 0.974 - 1.00 |
| HSV-2 Eqv | 7/7 | 100%; 95% CI: 0.590 - 1.00 |
| HSV-2 Neg | 153/153 | 100%; 95% CI: 0.976 - 1.00 |
| HSV-1 Invalid | 1/1 | - |
100% of HSV-1 indexes and 100% of HSV-2 indexes calculated using the Plexus software mached the indexes calculated manually.
Summary of Previous Studies for Plexus™ HerpeSelect® HSV 1 and 2 IgG (manual calculation)
| Study | PlexusHerpeSelect 1Results | PlexusHerpeSelect 2Results | |
|---|---|---|---|
| Pregnant Women (Indicated population) | Specificity | 96.5% | 94.3% |
| Sensitivity | 92.2% | 95.5% | |
| Sexually Active Adults (Indicated population) | Specificity | 91.0% | 96.3% |
| Sensitivity | 96.5% | 97.4% | |
| CDC HSV/CMV Panel | Agreement with positives | 100% | 100% |
| Agreement with negatives | 100% | 100% | |
| Low Prevalence Population | Agreement with negatives | 97.9% | 100% |
| Cross-reactivity with CMV, EBV and VZV. | Cross-reactivity | 0-5% | 0-3% |
| Reproducibility | %CV of positives | ≤10% | ≤10% |
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Image /page/2/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo consists of the word "FOCUS" in large, bold, sans-serif font, with the word "Diagnostics" in a smaller font size underneath. To the left of the word "FOCUS" is a curved, black shape that resembles a stylized check mark or a swoosh.
K071511 510(k) Summary of Safety and Effectiveness
Plexus 131 HerpeSelect® HSV 1 and 2 IgG (with software) Catalog Number: MP0900G Prepared: September 24, 2007 Page 3 of 8
Sensitivity and Specificity with Pregnant Women (n = 300)
Focus (n = 150) and an external investigator (n = 150) assessed the device's reactivity with sera from pregnant women. The sera were sequentially submitted to the laboratory, archived, and masked. The external investigator was a University laboratory located in Northern California, and the sera were collected in the Pacific Northwestern United States. The gold-standard reference method was the Focus Diagnostics HerpeSelect 1 and 2 Immunoblot IgG for calculation of sensitivity and specificity. The device was also evaluated with the HerpeSelect2 ELISA IgG a cleared predicate device which is not required for regulatory clearance for typing assay.
HSV-1 Sensitivity and Specificity The Focus HerpeSelect 1 Immunoblot IgG was: HSV-1 positive for 170 samples, HSV-1 negative with 128 samples, and HSV Common Antigen band positive for two samples.
The Plexus HerpeSelect 1 agreed with: 96.5% (164/170) of Immunoblot positives, and 92.2% (118/128) of Immunoblot negatives. The two Immunoblot HSV Common Antigen band positives were both negative in the Plexus.
HSV-2 Sensitivity and Specificity The Focus HerpeSelect 2 Immunoblot IgG was: HSV-2 positive for 122 samples, HSV-2 negative with 176 samples, and HSV Common Antigen band positive for two samples.
The Plexus HerpeSelect 2 agreed with: 94.3% (115/122) of Immunoblot positives, and 95.5% (168/176) of Immunoblot negatives. The two Immunoblot HSV Common Antigen band positives were both negative in the Plexus.
| Lab | Herpe-SelectImmunoblot | n | Neg | Eqv | Pos | Sensitivity andSpecificity | n | Neg | Eqv | Pos | % Agreement |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Focus andSite 1 | Pos | 170 | 6 | 0 | 164 | 96.5% (164/170)95%CI 92.5-98.7% | 170 | 5 | 1 | 164 | 96.5% (164/170)95%CI 92.5-98.7% |
| Focus andSite 1 | Neg | 128 | 118 | 3 | 7 | 92.2% (118/128)95%CI 86.1-96.2% | 128 | 118 | 3 | 7 | 92.2% (118/128)95%CI 86.1-96.2% |
| Focus andSite 1 | Com | 2 | 2 | 0 | 0 | Na | 2 | 2 | 0 | 0 | Na |
Plexus HerpeSelect 1 IgG Reactivity with Expectant Mothers (n = 300)
Plexus HerpeSelect 2 IgG Reactivity with Expectant Mothers (n = 300)
| Lab | Herpe-SelectImmunoblot | Plexus HerpeSelect-2 | HerpeSelect-2 ELISA | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| n | Neg | Eqv | Pos | Sensitivity andSpecificity | n | Neg | Eqv | Pos | % Agreement | ||
| Focus andSite 1 | Pos | 122 | 5 | 2 | 115 | 94.3% (115/122)95%CI 88.5-97.7% | 122 | 3 | 0 | 119 | 97.5%(119/122)95%CI 93.0-99.5% |
| Focus andSite 1 | Neg | 176 | 168 | 3 | 5 | 95.5% (168/176)95%CI 91.2-98.0% | 176 | 166 | 1 | 9 | 94.3% (166/176)95%CI 89.8-97.2% |
| Focus andSite 1 | Com | 2 | 2 | 0 | 0 | Na | 2 | 2 | 0 | 0 | Na |
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Image /page/3/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo consists of the word "FOCUS" in large, bold, sans-serif font, with the word "Diagnostics" in a smaller font size underneath. A curved, black swoosh is positioned to the left of the word "FOCUS", adding a dynamic element to the design. The overall design is simple, clean, and professional.
07151 510(k) Summary of Safety and Effectiveness Plexus TM HerpeSelect® HSV 1 and 2 IgG (with software) Catalog Number: MP0900G Prepared: September 24, 2007 Page 4 of 8
Reactivity with Sexually Active Adults (n = 300)
Focus (n = 150) and an external investigator (n = 150) assessed the device's reactivity with sera from sexually active adults. The sera were sequentially submitted to the laboratory, archived, and masked. The external investigator was a clinical laboratory located in Southern California, and the sera were collected in the Pacific Northwestern United States. The gold-standard reference method was the Focus Diagnostics HerpeSelect 1 and 2 Immunoblot IgG for calculation of sensitivity and specificity. The device was also evaluated with the HerpeSelect2 ELISA IgG a cleared predicate device which is not required for regulatory clearance for typing assay.
HSV-1 Sensitivity and Specificity
The Focus HerpeSelect 1 Immunoblot IgG was: HSV-1 positive for 157 samples, HSV-1 negative with 142 samples, and HSV Common Antigen band positive for one sample.
The Plexus HerpeSelect 1 agreed with: 91.0% (142/156) of Immunoblot positives (one sample was not run on the Plexus device), and 96.5% (137/142) of Immunoblot negatives.
HSV-2 Sensitivity and Specificity The Focus HerpeSelect 2 Immunoblot IgG was: HSV-2 positive for 109 samples, HSV-2 negative with 190 samples, and HSV Common Antigen band positive for one sample.
The Plexus HerpeSelect 2 agreed with: 96.3% (105/109) of Immunoblot positives, and 97.4% (184/189) of Immunoblot negatives (one sample was not run on the Plexus device).
Plexus HerpeSelect 1 IgG Reactivity with Sexually Active Adults (n = 300)
| Lab | Herpe-SelectImmunoblot | Plexus HerpeSelect-1 | HerpeSelect-1 ELISA | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| n | Neg | Eqv | Pos | Sensitivity andSpecificity | n | Neg | Eqv | Pos | % Agreement | |||
| Focus andSite 2 | Pos | 156 | 9 | 5 | 142 | 91.0% (142/156)95%CI 85.4-95.0% | 157 | 7 | 2 | 147 | 93.6% (147/157)95%CI 88.6-96.9% | |
| Focus andSite 2 | Neg | 142 | 137 | 3 | 2 | 96.5% (137/142)95%CI 92.0-98.9% | 142 | 137 | 1 | 4 | 96.5% (137/142)95%CI 92.0-98.9% | |
| Focus andSite 2 | Com | 1 | 1 | 0 | 0 | na | 1 | 1 | 0 | 0 | na |
*One of 300 samples was not run in the Plexus HerpSelect, and that one sample was HSV-1 negative/HSV-2 positive in the Immunoblot.
Plexus HerpeSelect 2 IgG Reactivity with Sexually Active Adults (n = 300)
| Lab | Herpe-SelectImmunoblot | Plexus HerpeSelect-2 | HerpeSelect-2 ELISA | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| n | Neg | Eqv | Pos | % Agreement | n | Neg | Eqv | Pos | % Agreement | ||
| Focus andSite 2 | Pos | 109 | 3 | 1 | 105 | 96.3% (105/109)95%CI 90.9-99.0% | 109 | 1 | 1 | 107 | 98.2% (107/109)95%CI 93.5-99.8% |
| Focus andSite 2 | Neg | 189 | 184 | 1 | 4 | 97.4% (184/189)95%CI 93.9-99.1% | 190 | 186 | 1 | 3 | 97.9% (186/190)95%CI 94.7-99.4% |
| Focus andSite 2 | Com | 1 | 1 | 0 | 0 | na | 1 | 1 | 0 | 0 | na |
*One of 300 samples was not run in the Plexus HerpeSelect, and that one sample was HSV-1 negative in the Immunible.
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Image /page/4/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo features the word "FOCUS" in bold, sans-serif font, with a curved, black shape resembling a swoosh or checkmark to the left of the word. Below "FOCUS" is the word "Diagnostics" in a smaller, sans-serif font, underlined with a thin black line.
K071511
510(k) Summary of Safety and Effectiveness Plexus The HerpeSelect® HSV 1 and 2 IgG (with software) Catalog Number: MP0900G Prepared: September 24, 2007 Page 5 of 8
Agreement with CDC Panel (n = 100)
The following information is from a serum panel obtained from the CDC and tested by Focus Diagnostics. The results are presented as a means to convey further information on the performance of this assay with a masked, characterized serum panel. This does not imply an endorsement of the assay by the CDC.
The test panel consists of 100 samples. This panel contains duplicate samples of 50 test sera. The duplicates serve to test for reproducibility. There are 16 HSV-1 positive, 11 double-positive and 16 doublenegative sera resulting in 54 HSV-1 positive and 36 HSV-2 positive specimens.
Determination of positive and negative samples
Of the 54 HSV-1 positive samples, the HerpeSelect® Plexus IgG correctly identified 100% (54/54). Of the 36 HSV-2 positive samples, the HerpeSelect® Plexus IgG correctly identified 100% (36/36). Of the 22 double positive samples, the HerpeSelect® Plexus IgG correctly identified 100% (22/22). Of the 32 double negative samples, the HerpeSelect® Plexus IgG correctly identified 100% (32/32).
| HerpeSelect-1 Plexus Results | HerpeSelect-2 Plexus Results | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Sample Type | CDC Result | n | Neg | Eqv | Pos | % Agreement | Neg | Eqv | Pos | % Agreement | |
| HSV1 | HSV2 | ||||||||||
| HSV-1Positive | Pos | Neg | 32 | 0 | 0 | 32 | 100% (32/32)95%CI 89.1-100% | 32 | 0 | 0 | 100% (32/32)95%CI 89.1-100% |
| HSV-2Positive | Neg | Pos | 14 | 14 | 0 | 0 | 100% (14/14)95%CI 76.8-100% | 0 | 0 | 14 | 100% (14/14)95%CI 76.8-100% |
| DualPositive | Pos | Pos | 22 | 0 | 0 | 22 | 100% (22/22)95%CI 84.6-100% | 0 | 0 | 22 | 100% (22/22)95%CI 84.6-100% |
| DualNegative | Neg | Neg | 32 | 32 | 0 | 0 | 100% (32/32)95%CI 89.1-100% | 32 | 0 | 0 | 100% (32/32)95%CI 89.1-100% |
Agreement with CDC Panel (n = 100)
CDC Panel Reproducibility
All paired sera were correctly identified: The Focus Diagnostics HerpeSelect® 1 and 2 Plexus IgG identified 16 out of 16 paired HSV-1 positive and HSV-2 negative (100%), 7 out of 7 paired HSV-2 positive and HSV-1 negative (100%), 11 out of 11 paired double-positive (100%) and 16 out of 16 paired double-negative (100%) samples.
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Image /page/5/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo consists of a stylized black swoosh above the word "FOCUS" in bold, sans-serif font. Below "FOCUS" is the word "Diagnostics" in a smaller, non-bold, sans-serif font, underlined with a thin black line. The overall design is simple and professional.
K071511
510(k) Summary of Safety and Effectiveness Plexus 11 HerpeSelect® HSV 1 and 2 IgG (with software) Catalog Number: MP0900G Prepared: September 24, 2007 Page 6 of 8
Specificity with a Low Prevalence Population (n = 77)
Focus (n = 77) assessed the device's reactivity with sera from a low prevalence population. Focus selected sera from patients aged 18 and 19 years, and that had been submitted to a clinical laboratory in Southern California from states having a history of low sexually transmitted disease prevalence. Focus excluded sera that were submitted for sexually transmitted diseases, herpesvirus testing, and tests indicating the patient may be immunocompromised. The sera were sequentially selected, archived and masked. The HerpeSelect Plexus results were compared to the Focus HerpeSelect 1 and 2 Immunoblot IgG.
HSV-1 Reactivity
The Focus HerpeSelect 1 Immunoblot IgG was: HSV-1 positive for 28 samples, HSV-1 negative with 47 samples, and HSV Common Antigen band positive for two samples.
The Plexus HerpeSelect 1 agreed with: 96.4% (27/28) of Immunoblot positives (one HSV-1 Immunoblot positive was equivocal in the Plexus device), and 97.9% (46/47) of Immunoblot negatives (one HSV-1 Immunoblot negative was positive in the Plexus device).
One Immunoblot HSV Common Antigen band positive was equivocal in the Plexus, and the other sample was Plexus negative.
HSV-2 Reactivity
The Focus HerpeSelect 2 Immunoblot IgG was: HSV-2 positive for four samples, HSV-2 negative with 71 samples, and HSV Common Antigen band positive for two samples.
The Plexus HerpeSelect 2 agreed with: 75.0% (3/4) of Immunoblot positives (one HSV-1 Immunoblot positive was equivocal in the Plexus device), and 100% (71/71) of Immunoblot negatives (one HSV-1 Immunoblot negative was positive in the Plexus device). Both Immunoblot HSV Common Antigen band positives were negative in the Plexus.
| HerpeSelectImmunoblot | Plexus HerpeSelect-1 | Plexus HerpeSelect-2 | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| n | Neg | Eqv | Pos | Sensitivity andSpecificity | n | Neg | Eqv | Pos | Sensitivity andSpecificity | |
| Positive | 28 | 0 | 1 | 27 | 96.4% (27/28)95%CI 81.6-99.9% | 4 | 0 | 1 | 3 | 75.0% (3/4)95%CI 19.4-99.4% |
| Negative | 47 | 46 | 0 | 1 | 97.9% (46/47)95%CI 88.7-99.9% | 71 | 71 | 0 | 0 | 100% (71/71)95%CI 94.9-100% |
| Common | 2 | 1 | 1 | 0 | NA | 2 | 2 | 0 | 0 | NA |
Specificity with Low Prevalence Population (n = 77)
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Image /page/6/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo features the word "FOCUS" in bold, sans-serif font, with the word "Diagnostics" in a smaller font size underneath. A curved, black shape is positioned to the left of the word "FOCUS", resembling a stylized check mark or a swoosh. The overall design is simple and professional, suggesting a focus on precision and accuracy in diagnostics.
0715
510(k) Summary of Safety and Effectiveness
Plexus HerpeSelect® HSV 1 and 2 IgG (with software) Catalog Number: MP0900G Prepared: September 24, 2007 Page 7 of 8
Cross-reactivity (n = 51)
Focus assessed cross-reactivity with two groups of samples: a "HSV ELISA dual negative" group (n=37), and a "HSV ELISA mixed sero-reactivity" group (n=14).
The HSV ELISA dual negative group (n=37) included samples that were sero-negative with both the HerpeSelect-1 ELISA IgG and HerpeSelect 2 ELISA IgG, and were sero-positive by at least one of
a FDA cleared CMV ELISA IgG (n = 18),
a home brerw VZV ACIF (n=32),
a FDA cleared EBV VCA IgG (n=31).
The HerpeSelect 1 and 2 Plexus IgG was HSV-1 negative with all but one of the HSV ELISA dual negatives, and equivocal with one sample (the one sample was CMV+ VZV+ and EBV+).
The HerpeSelect 1 and 2 Plexus IgG was HSV-2 negative with all but one of the HSV ELISA dual negatives, and equivocal with one sample (the one sample was CMV- VZV+ and EBV+).
The HSV ELISA mixed reactivity group (n=14) included samples that were sero-positive with either the HerpeSelect-1 ELISA IgG or HerpeSelect 2 ELISA IgG, and were sero-positive by at least one of
a FDA cleared CMV ELISA IgG (HSV-1 neg n = 2, HSV-2 neg n = 9),
a home brew VZV ACIF (HSV-1 neg n = 1, HSV-2 neg n = 2),
a FDA cleared EBV VCA IgG (HSV-1 neg n = 1, HSV-2 neg n = 0).
The HerpeSelect 1 and 2 Plexus IgG was HSV-1 negative with all of the HSV-1 ELISA negatives in the mixed reactivity group.
The HerpeSelect 1 and 2 Plexus IgG was HSV-2 negative with all of the HSV-2 ELISA negatives in the mixed reactivity group.
| Cross-reactivity (n = 51) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Cross-reactant | HSVELISAs | n | Neg | Eqv* | Pos | %Pos | n | Neg | Eqv† | Pos | %Pos |
| CMV IgG + | Dual Neg | 18 | 17 | 1 | 0 | 5.6% (1/18)95%CI 0.1-27.3% | 18 | 18 | 0 | 0 | 0.0% (0/18)95%CI 0.0-18.5% |
| +/- or -/+ | 2 | 2 | 0 | 0 | 0.0% (0/2)95%CI 0.0-84.2% | 9 | 9 | 0 | 0 | 0.0% (0/9)95%CI 0.0-33.6% | |
| Total | 20 | 19 | 1 | 0 | 5.0% (1/20)95%CI 0.1-24.9% | 27 | 27 | 0 | 0 | 0.0% (0/27)95%CI 0.0-12.8% | |
| VZV IgG + | Dual Neg | 32 | 31 | 1 | 0 | 3.1% (1/32)95%CI 0.1-16.2% | 32 | 31 | 1 | 0 | 3.1% (1/32)95%CI 0.1-16.2% |
| +/- or -/+ | 1 | 1 | 0 | 0 | 0.0% (0/1)NA | 2 | 2 | 0 | 0 | 0.0% (0/2)95%CI 0.0-84.2% | |
| Total | 33 | 32 | 1 | 0 | 3.0% (1/33)95%CI 0.1-15.8% | 34 | 33 | 1 | 0 | 2.9% (1/34)95%CI 0.1-15.3% | |
| EBV IgG + | Dual Neg | 31 | 30 | 1 | 0 | 3.2% (1/31)95%CI 0.1-16.7% | 31 | 30 | 1 | 0 | 3.2% (1/31)95%CI 0.1-16.7% |
| +/- or -/+ | 1 | 1 | 0 | 0 | 0.0% (0/1)NA | 0 | 0 | 0 | 0 | NA | |
| Total | 32 | 31 | 1 | 0 | 3.1% (1/32)95%CI 0.1-16.2% | 31 | 30 | 1 | 0 | 3.2% (1/31)95%CI 0.1-16.7% |
- The HerpeSelect-1 Plexus was equivocal with one sample, and the sample was IgG positive for CMV, VZV and EBV.
- The HerpeSelect -2 Plexus was equivocal with one sample was IgG positive for VZV and EBV.
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Image /page/7/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo features the word "FOCUS" in bold, sans-serif font, with a curved, swooping graphic element to the left of the word. Below "FOCUS" is the word "Diagnostics" in a smaller, sans-serif font, underlined with a thin line.
10(k) Summary of Safety and Effectiveness TM HerpeSelect® HSV 1 and 2 IgG (with software) Catalog Number: MP0900G Prepared: September 24, 2007
Page 8 of 8
Inter-laboratory Reproducibility and Inter/Intra-assay Reproducibility
Focus, a clinical laboratory located in Southern California, and a university laboratory located in Northern California assessed the device's inter-laboratory reproducibility and inter/intra-assay reproducibility. Each of the three laboratories tested eleven samples in triplicate on five different days.
| Inter-laboratory Reproducibility and Inter/Intra-assay Reproducibility" | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| HerpeSelect 1 Plexus IgG Results | HerpeSelect 2 Plexus IgG Results | |||||||||
| Intra- and Inter-assay | Inter-Lab | Intra- and Inter-assay | Inter-Lab | |||||||
| Sample | Mean Index | Intra-assay % CV | Inter-assay % CV | Mean Index | % CV | Mean Index | Intra-assay % CV | Inter-assay % CV | Mean Index | % CV |
| 9 | 4.93 | 3.6 | 10.3 | 4.94 | 3.7 | 3.88 | 3.4 | 10.0 | 3.87 | 2.5 |
| 6 | 4.24 | 3.8 | 8.7 | 4.22 | 3.3 | 4.90 | 2.6 | 8.5 | 4.89 | 2.1 |
| 2 | 3.87 | 4.8 | 7.9 | 3.86 | 1.3 | 3.36 | 4.3 | 7.7 | 3.35 | 2.0 |
| 8 | 3.27 | 4.9 | 9.1 | 3.25 | 3.0 | 4.56 | 3.1 | 8.3 | 4.55 | 1.5 |
| 4 | 3.24 | 4.9 | 7.4 | 3.22 | 2.1 | 2.55 | 4.5 | 8.9 | 2.54 | 5.8 |
| 1 | 3.04 | 4.3 | 8.9 | 3.02 | 2.3 | 2.71 | 3.8 | 9.3 | 2.70 | 2.1 |
| 12b | 2.13 | 7.9 | 8.7 | 2.13 | 4.1 | 1.87 | 7.2 | 8.8 | 1.87 | 3.4 |
| 3 | 0.34 | 9.1 | 14.9 | 0.34 | 6.8 | 0.06 | 8.7 | 28.3 | 0.06 | 22.6 |
| 10c | 0.19 | 9.9 | 213.1 | 0.19 | 59.0 | 0.12 | 11.4 | 334.2 | 0.40 | 103.8 |
| 10d | 0.13 | 10.0 | 15.8 | 0.12 | 1.9 | 0.06 | 11.5 | 41.7 | 0.06 | 38.3 |
| 7 | 0.18 | 8.3 | 16.3 | 0.17 | 9.4 | 0.06 | 8.1 | 23.7 | 0.06 | 17.3 |
| 5 | 0.14 | 9.0 | 16.0 | 0.14 | 2.7 | 0.06 | 8.3 | 39.8 | 0.06 | 38.1 |
Inter-laboratory Reproducibility and Inter/Intra-assay Reproducibility"
a. Excludes two runs at one site that were invalide Control index was beyond the accoptable QC criteria (it appears that the Positive Control was run in those wells since the indices were about 1.9 for both gG1 and gG2)
b. Samples 12 (inter-lab reproducibility) and 14 (inter-lot reproducibility below) were scparate samples with the same sera Samples 11 did not have sufficient volume to be sent to investigators.
c. This line includes all data for Sample 10, including one run at Lab 2, where it appears that Sample 1 may have the indices were about 2.7 for both gG1 and gG2.
d. This line includes all data for Sample 10, except for one at Lab 2, where it appears that Sample 1 may have been run instead since the indices were about 2.7 for both gG1 and gG2.
Inter-Lot Reproducibility
Focus assessed the device's Inter-lot Reproducibility by testing eleven samples with three separate lots. The samples were run in triplicate. Each lot had a different set of gG-1 and gG2 beads, a different lot of conjugate (made from 2 different stock conjugates), and a different lot of calibrator (made from 2 different combinations of positive and negative sera). The results of the studies are summarized in the tables below:
| Inter-lot Reproducibility | ||||
|---|---|---|---|---|
| Sample | HSV-1 | HSV-2 | ||
| Mean Index | Inter-Lot %CV | Mean Index | Inter-Lot %CV | |
| 9 | 5.20 | 7.4 | 3.90 | 12.8 |
| 6 | 4.36 | 8.5 | 4.76 | 9.2 |
| 2 | 3.60 | 7.3 | 3.19 | 9.3 |
| 4 | 3.29 | 7.9 | 2.54 | 6.4 |
| 8 | 3.23 | 11.3 | 4.45 | 9.4 |
| 1 | 3.14 | 5.8 | 2.73 | 4.8 |
| 12/14* | 2.22 | 10.5 | 1.86 | 7.8 |
| 3 | 0.31 | 17.0 | 0.11 | 50.9 |
| 7 | 0.15 | 31.3 | 0.08 | 21.8 |
| 5 | 0.10 | 45.6 | 0.06 | 24.9 |
| 10 | 0.09 | 50.6 | 0.06 | 26.9 |
Inter-lot Reproducibility
- Samples 12 (inter-lab reproducibility above) and 14 (inter-lot reproducibility) were scparate samples, but the same sera. Samples 11 and 13 did not have sufficient volume to be sent to investigators.
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Image /page/8/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized depiction of an eagle or bird-like figure with three curved lines representing its wings or body. The logo is surrounded by text that reads "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" in a circular arrangement.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Constance Bridges, MBA, RAC, ASQ-CBA Director, Regulatory and Compliance Focus Diagnostics, Inc. 10703 Progress Way Cypress, California 90630
0CT 5 " 2007
Re: K071511
Trade/Device Name: Plexus™ HerpeSelect® HSV 1 and 2 IgG (with software) Regulation Number: 21CFR 866.3305 Regulation Name: Herpes simplex virus serological reagents Regulatory Class: Class II Product Code: MXJ, MYF Dated: September 5, 2007 Received: September 10, 2007
Dear Ms. Bridges:
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 device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); 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 - Michael J. Wagner
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 Compliance at (240) 276- 0100. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Sayar
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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510(k) Number (if known):
Device Name:
Indications for Use:
Plexus™ HerpeSelect® HSV 1 and 2 IgG (with software)
The Focus Diagnostics Plexus™ HerpeSelect® HSV 1 and 2 IgG (with software) is intended for qualitatively detecting the presence or absence of human IgG antibodies to HSV-1 and HSV-2 in human sera. The test is indicated for pregnant women and sexually active adults, as an aid for presumptively diagnosing HSV-1 and HSV-2 infection. The predictive value of a positive or negative result depends on the population's prevalence and the pretest likelihood of HSV-1 and HSV-2 infection. The test is not intended for donor screening or for self-testing. The performance of this assay has not been established for use in a pediatric population, for neonatal screening, for testing of immunocompromised patients, for use by a point of care facility or for use with automated equipment.
Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR
Over-the-Counter Use (21 CFR 807 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Saezarz
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety Page 1 of 1
5300 k07151
§ 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).