(155 days)
Focus Diagnostics' Plexus™HerpeSelect®1 and 2 IgG is intended for qualitatively detecting the presence or absence of human IgG class antibodies to HSV-1 and HSV-2 in human sera. The test is indicated for testing sexually active adults or expectant mothers for aiding in the presumptive diagnosis of 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 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®1 and 2 IgG is a multiplexed immunoassay for qualitatively detecting and differentiating human IgG antibodies to HSV-1 and HSV-2. The Focus Diagnosics Plexus™HerpeSelect®1 and 2 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. The Focus Diagnostics Plexus 100 HerpeSelect®1 and 2 IgG is a three step procedure. Patient sera are diluted, and the diluted sera are incubated with Antibodies are present, then the 1 . antibodies bind to the corresponding antigen beads. Phycoerythrin-conjugated goat anti-human IgG, (Conjugate) is added, and the Conjugate binds to the bound HSV 2. antibody (if present), and forms a Conjugate-HSV antibody-antigen bead sandwich. Fluorescence from each distinct HSV antigen bead type is measured and compared against a Cut-off Calibrator. 3.
Here's a breakdown of the acceptance criteria and study details for the Plexus HerpeSelect 1 and 2 IgG device, based on the provided document:
Acceptance Criteria and Device Performance
| Study | Acceptance Criteria (Implicit from reported performance) | Reported Device Performance (Plexus HerpeSelect 1 IgG) | Reported Device Performance (Plexus HerpeSelect 2 IgG) |
|---|---|---|---|
| Expectant Mothers (Indicated population) | Agreement with positives: High (e.g., >90%) | 96.5% (164/170) | 94.3% (115/122) |
| Agreement with negatives: High (e.g., >90%) | 92.2% (118/128) | 95.5% (168/176) | |
| Sexually Active Adults (Indicated population) | Agreement with positives: High (e.g., >90%) | 91.0% (142/156) | 96.3% (105/109) |
| Agreement with negatives: High (e.g., >90%) | 96.5% (137/142) | 97.4% (184/189) | |
| CDC HSV/CMV Panel | Agreement with positives: 100% | 100% (54/54) | 100% (36/36) |
| Agreement with negatives: 100% | 100% (32/32) | 100% (32/32) | |
| Low Prevalence Population | Agreement with negatives: High (e.g., >95%) | 97.9% (46/47) | 100% (71/71) |
| Cross-reactivity with CMV, EBV and VZV. | Cross-reactivity: Low (e.g., <5%) | 0-5% | 0-3% |
| Reproducibility | %CV of positives: <= 10% | $\leq$ 10% (most samples) | $\leq$ 10% (most samples) |
Note: The document does not explicitly state the pre-defined "acceptance criteria" as numerical thresholds beyond what is simply reported for the CDC panel. The "acceptance criteria" column above infers a reasonable expectation based on the device's intended use and the reported performance.
Study Details
-
Sample sizes used for the test set and data provenance:
- Expectant Mothers: n=300 (150 from Focus Diagnostics, 150 from an external investigator at a University laboratory in Northern California). Sera were collected in the Pacific Northwestern United States. Retrospective (sequentially submitted, archived, and masked).
- Sexually Active Adults: n=300 (150 from Focus Diagnostics, 150 from an external investigator at a clinical laboratory in Southern California). Sera were collected in the Pacific Northwestern United States. Retrospective (sequentially submitted, archived, and masked).
- CDC HSV/CMV Panel: n=100 (contains duplicate samples of 50 test sera, effectively 50 unique sera for agreement, but 100 samples for reproducibility). Source: CDC.
- Low Prevalence Population: n=77 (from Focus Diagnostics). Sera from patients aged 18 and 19 years, submitted to a clinical laboratory in Southern California from states with a history of low STD prevalence. Sera indicating immunocompromised status or previous herpesvirus testing were excluded. Retrospective (sequentially selected, archived, and masked).
- Cross-reactivity: n=51 (37 "HSV ELISA dual negative" and 14 "HSV ELISA mixed sero-reactivity"). Source not explicitly stated, but likely laboratory archived samples tested by Focus.
-
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document implies that the Focus HerpeSelect 1 and 2 Immunoblot IgG was the reference method used to establish ground truth for the Expectant Mothers, Sexually Active Adults, and Low Prevalence Population studies. For the CDC panel, it states "CDC Result" as the ground truth.
- The document does not specify the number of experts or their qualifications for interpreting the Immunoblot results or for establishing the CDC results.
-
Adjudication method for the test set:
- The document does not explicitly state an adjudication method for ambiguous or discordant results between the reference method (Immunoblot/CDC Result) and the Plexus device. The data shows samples categorized as "Eqv" (equivocal) for the Plexus device, but no details on how these were handled in the agreement calculations or if an adjudication process was in place.
-
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No, a MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) assay, specifically a multiplexed immunoassay for detecting antibodies. It does not involve human readers interpreting images or data that an AI might assist with. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable.
-
If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, this is effectively a standalone performance study. The device itself is an automated assay that produces a qualitative result (positive, negative, or equivocal) for HSV-1 and HSV-2 IgG antibodies. Its performance is evaluated against a reference standard without human interpretation being a variable in the device's output.
-
The type of ground truth used:
- Serological Reference Method / Consensus Standard:
- For Expectant Mothers, Sexually Active Adults, and Low Prevalence Population studies, the Focus HerpeSelect 1 and 2 Immunoblot IgG was used as the reference method. This is a commonly accepted confirmatory test for HSV serology.
- For the CDC panel, the "CDC Result" served as the ground truth, implying a characterized and validated reference panel.
- Serological Reference Method / Consensus Standard:
-
The sample size for the training set:
- The document does not specify distinct "training set" sizes. For IVD assays like this, the development process usually involves internal validation and optimization, but a formal "training set" like in machine learning algorithms is not typically detailed or distinguished in regulatory summaries. The studies described are primarily for performance validation.
-
How the ground truth for the training set was established:
- As no specific "training set" is detailed, the method for establishing ground truth for any internal development or optimization (which would be analogous to training) is not provided. However, it can be inferred that similar validated reference methods (like Immunoblot or well-characterized panels) would have been used during the development phase.
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Image /page/0/Picture/1 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, thinner font underneath. A curved, swooping line extends from the left side of the word "FOCUS", creating a visual element that emphasizes the brand name.
510(k) Summary of Safety and Effectiveness Plexus "HerpeSelect®1 and 2 IgG Catalog No. MP0900G Prepared January 29, 2007 Page 1 of 10
| Applicant | Focus Diagnostics, Inc.10703 Progress WayCypress, California 90630USA |
|---|---|
| Establishment Registration No. | 2023365 |
FEB - 1 2007
| Contact Person | Michael J. Wagner, Esq.tel 714.220.1900fax 714.995.6921mwagner@focusdx.com |
|---|---|
| Summary Date | January 29, 2007 |
| Proprietary Name | Plexus™HerpeSelect®1 and 2 IgG |
| Generic Name | Herpes Simplex Virus Types 1 and 2 Serological Assays |
| Classification | Class II |
| Predicate Devices | HerpeSelect 1 and 2 Immunoblot IgGHerpeSelect-1 ELISA IgGHerpeSelect-2 ELISA IgG |
Device Description
The Focus Diagnostics Plexus™HerpeSelect®1 and 2 IgG is a multiplexed immunoassay for qualitatively detecting and differentiating human IgG antibodies to HSV-1 and HSV-2.
Intended Use
Focus Diagnostics' Plexus™HerpeSelect®1 and 2 IgG is intended for qualitatively detecting the presence of human IgG class antibodies to HSV-1 and HSV-2 in human sera. The test is indicated for testing sexually active adults or expectant mothers for aiding in the presumptive diagnosis of HSV-1 infection. The predictive value of a positive or negative result depends on the population's prevalence and the pretest likelihood of HSV-2 infection. The performance of this assay has not been established for use in a pediative population, for testing of immunocompromised patients, for use by a point of care facility or for use with automated equipment.
Test Principle
The Focus Diagnosics Plexus™HerpeSelect®1 and 2 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. The Focus Diagnostics Plexus 100 HerpeSelect®1 and 2 IgG is a three step procedure.
- Patient sera are diluted, and the diluted sera are incubated with Antibodies are present, then the 1 . antibodies bind to the corresponding antigen beads.
- Phycoerythrin-conjugated goat anti-human IgG, (Conjugate) is added, and the Conjugate binds to the bound HSV 2. antibody (if present), and forms a Conjugate-HSV antibody-antigen bead sandwich.
- Fluorescence from each distinct HSV antigen bead type is measured and compared against a Cut-off Calibrator. 3.
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Image /page/1/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo consists of a stylized crescent shape on the left, followed by the word "FOCUS" in bold, sans-serif font. Below "FOCUS" is the word "Diagnostics" in a smaller, less bold font, underlined with a thin line.
K062543 510(k) Summary of Safety and Effectiveness Plexus™HerpeSelect®1 and 2 IgG Catalog No. MP0900G Prepared January 29, 2007 Page 2 of 10 ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
.
Performance Characteristics
Summary of Studies (details below)
| Study | PlexusHerpeSelect 1 IgGResults | PlexusHerpeSelect 2 IgGResults | |
|---|---|---|---|
| Expectant Mothers (Indicated population) | Agreement with positives | 96.5% | 94.3% |
| Agreement with negatives | 92.2% | 95.5% | |
| Sexually Active Adults (Indicated population) | Agreement with positives | 91.0% | 96.3% |
| Agreement with negatives | 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 | $\leq$ 10% | $\leq$ 10% |
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Image /page/2/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo consists of a stylized black swoosh above the word "FOCUS" in a bold, sans-serif font. Below "FOCUS" is the word "Diagnostics" in a smaller, less bold font, underlined with a thin black line. The overall design is simple and professional.
Reactivity with Expectant Mothers (n = 300)
Focus (n = 150) and an external investigator (n = 150) assessed the device's reactivity with sera from Expectant Mothers. The sera were sequentially submitted to the laboratory, archived, and masked. The external investigator was an University laboratory located in Northern California, and the sera were collected in the Pacific Northwestern United States. The HerpeSelect Plexus results were compared to the HerpeSelect 1 ELISA IgG and the HerpeSelect 2 ELISA IgG, using the Focus HerpeSelect 1 and 2 Immunoblot IgG as the reference method.
HSV-1 Reactivity
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 Reactivity
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.
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Image /page/3/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo features the word "FOCUS" in bold, uppercase letters, with a curved 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.
K062543
510(k) Summary of Safety and Effectiveness Plexus™HerpeSelect®1 and 2 IgG Catalog No. MP0900G
Prepared January 29, 2007
Page 4 of 10
Plexus HerpeSelect 1 IgG Reactivity with Expectant Mothers (n = 300)
| Lab | HerpeSelectImmunoblot | n | Neg | Eqv | Pos | % Agreement | n | Neg | Eqv | Pos | % Agreement |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Site 1 | Pos | 84 | 6 | 0 | 78 | 92.9% (78/84)95%CI 85.1-97.3% | 84 | 5 | 1 | 78 | 92.9% (78/84)95%CI 85.1-97.3% |
| Focus | Pos | 86 | 0 | 0 | 86 | 100% (86/86)95%CI 95.8-100% | 86 | 0 | 0 | 86 | 100% (86/86)95%CI 95.8-100% |
| Combined Labs | 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% |
| Site 1 | Neg | 66 | 61 | 1 | 4 | 92.4% (61/66)95%CI 83.2-97.5% | 66 | 59 | 2 | 5 | 89.4% (59/66)95%CI 79.4-95.6% |
| Focus | Neg | 62 | 57 | 2 | 3 | 91.9% (57/62)95%CI 82.2-97.3% | 62 | 59 | 1 | 2 | 95.2% (59/62)95%CI 86.5-99.0% |
| Combined Labs | 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% |
| Site 1 | Com | 0 | 0 | 0 | 0 | NA | 0 | 0 | 0 | 0 | NA |
| Focus | Com | 2 | 2 | 0 | 0 | NA | 2 | 2 | 0 | 0 | NA |
| Combined Labs | Com | 2 | 2 | 0 | 0 | NA | 2 | 2 | 0 | 0 | NA |
Plexus HerpeSelect 2 IgG Reactivity with Expectant Mothers (n = 300)
| Lab | Herpe-SelectImmunoblot | Plexus HerpeSelect-2 | HerpeSelect-2 ELISA | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| n | Neg | Eqv | Pos | % Agreement | n | Neg | Eqv | Pos | % Agreement | ||
| Site I | Pos | 60 | 3 | 1 | 56 | 93.3% (56/60)95%CI 83.8-98.2% | 60 | 2 | 0 | 58 | 96.7% (58/60)95%CI 88.5-99.6% |
| Focus | Pos | 62 | 2 | 1 | 59 | 95.2% (59/62)95%CI 86.5-99.0% | 62 | 1 | 0 | 61 | 98.4% (61/62)95%CI 91.3-100% |
| Combined Labs | 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% |
| Site 1 | Neg | 90 | 88 | 0 | 2 | 97.8% (88/90)95%CI 92.2-99.7% | 90 | 86 | 0 | 4 | 95.6% (86/90)95%CI 89.0-98.8% |
| Focus | Neg | 86 | 80 | 3 | 3 | 93.0% (80/86)95%CI 85.4-97.4% | 86 | 80 | 1 | 5 | 93.0% (80/86)95%CI 85.4-97.4% |
| Combined Labs | 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% |
| Site 1 | Com | 0 | 0 | 0 | 0 | NA | 0 | 0 | 0 | 0 | NA |
| Focus | Com | 2 | 2 | 0 | 0 | NA | 2 | 2 | 0 | 0 | NA |
| Combined Labs | Com | 2 | 2 | 0 | 0 | NA | 2 | 2 | 0 | 0 | NA |
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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 large, bold, sans-serif font. Below "FOCUS" is the word "Diagnostics" in a smaller, thinner font with a line above it. To the left of the word "FOCUS" is a curved, crescent-shaped graphic element.
Page 5 of 10
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 HerpeSelect Plexus results were compared to the HerpeSelect 1 ELISA IgG and the HerpeSelect 2 ELISA IgG, using the Focus HerpeSelect 1 and 2 Immunoblot IgG as the reference method.
HSV-1 Reactivity
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 Reactivity 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).
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Image /page/5/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo consists of the word "FOCUS" in bold, sans-serif font, with the word "Diagnostics" in a smaller, serif font underneath. A curved, black shape is positioned to the left of the word "FOCUS", creating a visual element that complements the text.
K062543 10(k) Summary of Safety and Effectiveness Plexus™HerpeSelect®1 and 2 IgG Catalog No. MP0900G Prepared January 29, 2007
Page 6 of 10
Plexus HerpeSelect 1 IgG Reactivity with Sexually Active Adults (n = 300)
| Lab | HerpeSelectImmunoblot | n | Neg | Eqv | Pos | % Agreement | n | Neg | Eqv | Pos | % Agreement |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Site 2 | Pos | 71 | 4 | 2 | 65 | 91.5% (65/71)95%CI 82.5-96.8% | 71 | 3 | 0 | 68 | 95.8% (68/71)95%CI 88.1-99.1% |
| Focus | Pos | 85* | 5 | 3 | 77 | 90.6% (77/85)95%CI 82.3-95.9% | 86 | 4 | 2 | 80 | 93.0% (80/86)95%CI 85.4-97.4% |
| Combined Labs | 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% |
| Site 2 | Neg | 79 | 78 | 1 | 0 | 98.7% (78/79)95%CI 93.1-100% | 79 | 77 | 1 | 1 | 97.5% (77/79)95%CI 91.2-99.7% |
| Focus | Neg | 63 | 59 | 2 | 2 | 93.7% (59/63)95%CI 84.5-98.2% | 63 | 60 | 0 | 3 | 95.2% (60/63)95%CI 86.7-99.0% |
| Combined Labs | 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% |
| Site 2 | Com | 0 | 0 | 0 | 0 | NA | 0 | 0 | 0 | 0 | NA |
| Focus | Com | 1 | 1 | 0 | 0 | NA | 1 | 1 | 0 | 0 | NA |
| Combined Labs | 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/HSV-2 positive in the Immunoble.
Plexus HerpeSelect 2 IgG Reactivity with Sexually Active Adults (n = 300)
| Lab | HerpeSelectImmunoblot | n | Neg | Eqv | Pos | % Agreement | n | Neg | Eqv | Pos | % Agreement |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Site 2 | Pos | 47 | 3 | 1 | 43 | 91.5% (43/47)95%CI 79.6-97.6% | 47 | 1 | 0 | 46 | 97.9% (46/47)95%CI 88.7-99.9% |
| Focus | Pos | 62 | 0 | 0 | 62 | 100%(62/62)95%CI 94.2-100% | 62 | 0 | 1 | 61 | 98.4%(61/62)95%CI 91.3-100% |
| Combined Labs | 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% |
| Site 2 | Neg | 103 | 100 | 1 | 2 | 97.1% (100/103)95%CI 91.7-99.4% | 103 | 102 | 0 | 1 | 99.0% (102/103)95%CI 94.7-100% |
| Focus | Neg | 86* | 84 | 0 | 2 | 97.7% (84/86)95%CI 91.8-99.7% | 87 | 84 | 1 | 2 | 96.6% (84/87)95%CI 90.3-99.3% |
| Combined Labs | 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% |
| Site 2 | Com | 0 | 0 | 0 | 0 | NA | 0 | 0 | 0 | 0 | NA |
| Focus | Com | 1 | 1 | 0 | 0 | NA | 1 | 1 | 0 | 0 | NA |
| Combined Labs | 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 Immunoblot.
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Image /page/6/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, crescent-shaped graphic is positioned to the left and above the word "FOCUS", adding a visual element to the logo. A horizontal line is placed above the word "Diagnostics".
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 double-negative 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).
| SampleType | CDC Result | n | HerpeSelect-1 Plexus Results | HerpeSelect-2 Plexus Results | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| HSV1 | HSV2 | Neg | Eqv | Pos | % Agreement | Neg | Eqv | Pos | % Agreement | ||
| 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-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/7/Picture/1 description: The image shows the logo for Focus Diagnostics. The logo consists of the word "FOCUS" in bold, sans-serif font, with a curved, black shape resembling a crescent moon or a stylized checkmark to the left of the word. Below the word "FOCUS" is the word "Diagnostics" in a smaller, non-bold font, underlined by a thin line.
Plexus "HerpeSelect®1 and 2 IgG Catalog No. MP0900G Prepared January 29, 2007
Page 8 of 10
Reactivity 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 diseases, herpesvirus testing, and tests indicating the patient may be immunocompromised. The sera were sequentially selected, archived and masked. The HereSelect 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 other sample was Plexus negative.
HSV-2 Reactivity
The Focus HerpeSclect 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 in the Plexus device). Both Immunoblot HSV Common Antigen band positives were negative in the Plexus.
| HerpeSelectImmunoblot | n | Plexus HerpeSelect-1 | % Agreement | Plexus HerpeSelect-2 | % Agreement | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Neg | Eqv | Pos | Neg | Eqv | Pos | |||||
| Pos | 28 | 0 | 1 | 27 | 96.4% (27/28)95%CI 81.6-99.9% | 0 | 1 | 3 | 75.0% (3/4)95%CI 19.4-99.4% | |
| Neg | 47 | 46 | 0 | 1 | 97.9% (46/47)95%CI 88.7-99.9% | 71 | 0 | 0 | 100% (71/71)95%CI 94.9-100% | |
| Com | 2 | 1 | 1 | 0 | NA | 2 | 0 | 0 | NA |
Reactivity with Low Prevalence Population (n = 77)
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Image /page/8/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo consists of a stylized black swoosh shape on the left, followed by the word "FOCUS" in bold, sans-serif font. Below "FOCUS" is a horizontal line, and below that line is the word "Diagnostics" in a smaller, sans-serif font.
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 Plexus HerpeSelect®1 and 2 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 Plexus HerpeSelect®1 and 2 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 Plexus HerpeSelect®1 and 2 IgG was HSV-1 negative with all of the HSV-1 ELISA negatives in the mixed reactivity group.
The Plexus HerpeSelect®1 and 2 1gG was HSV-2 negative with all of the HSV-2 ELISA negatives in the mixed reactivity group.
| Cross-reactant | HSVELISAs | n | HerpeSelect-1 Plexus | n | HerpeSelect-2 Plexus | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Neg | Eqv* | Pos | %Pos | 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% |
Cross-reactivity (n = 51)
-
The HerpeSelect-1 Plexus was equivocal with one 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/9/Picture/1 description: The image shows the logo for Focus Diagnostics. The logo consists of the word "FOCUS" in a bold, sans-serif font, with the word "Diagnostics" in a smaller font underneath. A curved, black shape is to the left of the word "FOCUS", which appears to be a stylized eye or lens.
510(k) Summary of Safety and Effectiveness
Plexus THerpeSelect®1 and 2 IgG Catalog No. MP0900G
Prepared January 29, 2007
Page 10 of 10
Inter-laboratory Reproducibility and Inter/Intra-assay Reproducibility
Focus, a clinical laboratory located in Southern California, and a university located in Northern California assessed the device's inter-laboratory reproducibility and interlintra-assay reproducibility. Each of the three laboratories tested eleven samples in triplicate on five different days.
| Inter-laboratory Reproducibility and Inter/Intra-assay Reproducibilitya | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 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 |
d Inter/Intro ossov Reproducibility"
a. Excludes two runs at one site that were invalide Control index was beyond the acceptable 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 reporters, but they were made with the same sera Samples 11 did not have sufficient volume to be sent to investigators.
c. This includes all cata for Sample 10, including one run 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.
d. This line includes all dual for Sample 10, except for one run at Lab 2, where it appears that Sample 1 may have 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 |
- Sumples 12 (inter-lab reproducibility) were separate sumples, but they were made with the same ser. Samples 11 and 13 did not have sufficient volume to be sent to investigators.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/10/Picture/1 description: The image shows a logo with a stylized bird figure on the right and text on the left. The bird figure is composed of three curved lines that suggest wings and a head. The text on the left is arranged in a circular fashion, following the curve of the logo. The logo appears to be a symbol of a government or public health organization.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Michael J. Wagner, Esq. Regulatory Counsel Focus Diagnostics, Inc. 10703 Progress Way Cypress, CA 90630
FEB - 1 2007
Re: K062543
Trade/Device Name: HerpeSelect 1 and 2 Plexus IgG Regulation Number: 21 CFR 866.3305 Regulation Name: Herpes simplex virus serological reagents Regulatory Class: Class II Product Code: MXJ. MYF Dated: January 15, 2007 Received: January 17, 2007
Dear Mr. Wagner:
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 indicetions 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, Ilsting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820),
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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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, 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). Other general information on your responsibilities under the Act may be obtained 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/dsma/dsmamain.html.
Sincerely yours,
Sally, axtom
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): K062543
Device Name:
Plexus™HerpeSelect®1 and 2 IgG
Focus Diagnostics' Plexus "HerpeSelect®1 and 2 IgG is intended Indications for Use: for qualitatively detecting the presence or absence of human IgG class antibodies to HSV-1 and HSV-2 in human sera. The test is indicated for testing sexually active adults or expectant mothers for aiding in the presumptive diagnosis of 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 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)
Nallard
Division Sign-Off
Office of In Vitro Diagnostic
Device Evaluation and Safety
Page 1 of 1
510(k) K062543
§ 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).