(140 days)
The Focus Diagnostics Simplexa™ HSV 1 & 2 Direct assay is intended for use on the 3M Integrated Cycler instrument for the qualitative detection and differentiation of herpes simples virus (HSV-1 and HSV-2) DNA present in genital lesion swabs samples from patients with signs and symptoms of HSV-1 or HSV-2 infection of the genitalia. This test is an aid in the differential diagnosis of HSV-1 and HSV-2 genital infections.
The assay is not intended for use as a screening test for the presence of HSV-1 and HSV-2 in blood or blood products. The assay is for professional use only.
Simplexa™ HSV 1 & 2 Positive Control Pack
The Simplexa™ HSV 1 & 2 Positive Control Pack is intended to be used as a control with the Simplexa™ HSV 1 & 2 Direct kit. This control is not intended for use with other assays or systems.
The Simplexa™ HSV 1 & 2 Direct assay system is a real-time PCR that enables the direct amplification, detection and differentiation of HSV-1 and/or HSV-2 DNA from unprocessed genital swab specimens without nucleic acid extraction. The system consists of the Simplexa™ HSV 1 & 2 Direct assay, the 3M Integrated Cycler (with 3M Integrated Cycler Studio Software), the Direct Amplification Disc and associated accessories.
In the Simplexa™ HSV 1 & 2 Direct assay, bi-functional fluorescent probe-primers are used together with corresponding reverse primers to amplify HSV-1, HSV-2 and internal control targets. Well conserved regions of the HSV-1 and HSV-2 DNA polymerase genes are targeted to identify HSV-1 and HSV-2 DNA respectively in the specimen. An internal control is used to detect PCR failure and/or inhibition.
The provided document describes the Simplexa™ HSV 1 & 2 Direct assay and its performance evaluation. Here's a breakdown of the acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as distinct "acceptance criteria" but can be inferred from the reported performance results and the common thresholds for such diagnostic tests (e.g., typically ≥ 95% agreement/sensitivity/specificity). The document presents the performance in terms of percent agreement with expected results for reproducibility and sensitivity/specificity for clinical agreement.
Reproducibility (Inter-site, Inter-day, Inter/Intra-assay)
| Performance Metric | Acceptance Criteria (Inferred) | Reported Device Performance |
|---|---|---|
| HSV-1 Result - Total % Agreement with Expected Results (all sites combined) | High agreement (e.g., ≥95%) | HSV-1 Low Positive: 100.0% (90/90) HSV-1 Medium Positive: 100.0% (90/90) High Negative (for HSV-1): 93.3% (84/90) Positive Control (for HSV-1): 100.0% (89/89) Total Agreement (HSV-1): 98.5% (531/539) |
| HSV-2 Result - Total % Agreement with Expected Results (all sites combined) | High agreement (e.g., ≥95%) | HSV-1 Low Positive (for HSV-2): 98.9% (89/90) HSV-1 Medium Positive (for HSV-2): 100.0% (90/90) HSV-2 Low Positive: 94.4% (85/90) HSV-2 Medium Positive: 100.0% (90/90) High Negative (for HSV-2): 94.4% (85/90) Positive Control (for HSV-2): 100.0% (89/89) Total Agreement (HSV-2): 98.0% (528/539) |
| DNA IC Result - Total % Agreement with Expected Results (all sites combined) | High agreement (e.g., ≥95%) | 100.0% across all sample types (e.g., HSV-1 Low Positive: 100.0% (90/90), Positive Control: 100.0% (89/89)) Total Agreement (IC): 100.0% (539/539) |
Analytical Sensitivity/Limit of Detection (LoD)
| Performance Metric | Acceptance Criteria (Inferred) | Reported Device Performance |
|---|---|---|
| LoD for HSV-1 McIntyre | Detect positive ≥95% of the time | 32/32 (100%) at 4 TCID50/mL |
| LoD for HSV-1 HF | Detect positive ≥95% of the time | 32/32 (100%) at 160 TCID50/mL |
| LoD for HSV-2 G | Detect positive ≥95% of the time | 32/32 (100%) at 2 TCID50/mL |
| LoD for HSV-2 MS | Detect positive ≥95% of the time | 31/32 (~97%) at 10 TCID50/mL |
Clinical Agreement (Prospective Study vs. Composite Comparator)
| Performance Metric | Acceptance Criteria (Inferred) | Reported Device Performance (HSV-1) | Reported Device Performance (HSV-2) |
|---|---|---|---|
| Sensitivity | High sensitivity (e.g., ≥95%) | 97.4% (111/114) (95% CI: 92.5% to 99.1%) | 97.2% (175/180) (95% CI: 93.7% to 98.8%) |
| Specificity | High specificity (e.g., ≥95%) | 98.2% (560/570) (95% CI: 96.8% to 99.0%) | 97.8% (497/508) (95% CI: 96.2% to 98.8%) |
| Positive Predictive Value (PPV) | High predictive value (context-dependent) | 91.7% (111/121) (95% CI: 85.5% to 95.4%) | 94.1% (175/186) (95% CI: 89.7% to 96.7%) |
| Negative Predictive Value (NPV) | High predictive value (context-dependent) | 99.5% (560/563) (95% CI: 98.4% to 99.8%) | 99.0% (497/502) (95% CI: 97.7% to 99.6%) |
Clinical Agreement (Retrospective Study vs. Validated Bi-Directional Sequencing Assay)
| Performance Metric | Acceptance Criteria (Inferred) | Reported Device Performance (HSV-1) | Reported Device Performance (HSV-2) |
|---|---|---|---|
| Positive Percent Agreement (PPA) | High agreement (e.g., ≥95%) | 100.0% (14/14) (95% CI: 78.5% to 100.0%) | 100.0% (14/14) (95% CI: 78.5% to 100.0%) |
| Negative Percent Agreement (NPA) | High agreement (e.g., ≥95%) | 92.9% (13/14) (95% CI: 68.5% to 98.7%) | 100.0% (14/14) (95% CI: 78.5% to 100.0%) |
| Positive Predictive Value (PPV) | High predictive value (context-dependent) | 93.3% (14/15) (95% CI: 70.2% to 98.8%) | 100.0% (14/14) (95% CI: 78.5% to 100.0%) |
| Negative Predictive Value (NPV) | High predictive value (context-dependent) | 100.0% (13/13) (95% CI: 77.2% to 100.0%) | 100.0% (14/14) (95% CI: 78.5% to 100.0%) |
2. Sample Size Used for the Test Set and Data Provenance
-
Reproducibility Study:
- Test Set Size: For each of the six sample pools (HSV-1 Low Positive, HSV-1 Medium Positive, HSV-2 Low Positive, HSV-2 Medium Positive, High Negative, Positive Control), they were tested in triplicate on five different days by two operators at each of three sites. This amounts to: 6 samples * 3 replicates * 5 days * 2 operators * 3 sites = 540 data points (assuming complete datasets). The tables consolidate this, showing "Total Agreement" out of 539 samples for HSV-1, and 539 for HSV-2 and DNA IC across all categories (e.g., 531/539 for HSV-1 Total Agreement, 528/539 for HSV-2 Total Agreement, 539/539 for DNA IC Total Agreement).
- Data Provenance: The study was conducted at "Three investigative sites," implying a multi-center study within the U.S. (typical for FDA submissions). It's a prospective design as samples were "contrived" (prepared specifically for the study) and tests were performed over different days.
-
Clinical Agreement (Prospective Study):
- Test Set Size:
- Initially, 718 genital swab samples were prospectively collected.
- 9 samples were removed (not tested or invalid results on 3 assays).
- 13 samples were removed (not tested on comparator method sufficiently).
- 696 samples were used for the primary analysis.
- Further exclusions for specific analyses: 6 samples excluded from discordant analysis due to insufficient volume for FDA cleared NAAT; 2 samples excluded for HSV-1/HSV-2 discrepancy due to insufficient volume for FDA cleared NAAT.
- Final analysis for HSV-1: 684 samples.
- Final analysis for HSV-2: 688 samples.
- Data Provenance: "Prospectively collected from patients with signs and symptoms of genital herpes simplex virus (HSV) infection from 6 geographically diverse locations." This indicates the data is from the U.S. and is prospective.
- Test Set Size:
-
Clinical Agreement (Retrospective Study):
- Test Set Size: 28 genital swab samples (14 positive HSV-1 and 14 positive HSV-2).
- Data Provenance: "Retrospectively collected from male patients with signs and symptoms of genital herpes simplex virus (HSV) infection." Specific country of origin is not stated but implies within the U.S. given the FDA submission.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
-
For the Reproducibility Study, the ground truth for contrived samples (low positive, medium positive, high negative, positive control) was established based on the known concentrations of HSV-1 and HSV-2 spiked into the matrix. This is an analytical study, not one requiring clinical experts for ground truth.
-
For the Clinical Agreement Studies (Prospective and Retrospective), the ground truth was established by a "composite comparator algorithm" and "validated bi-directional sequencing assay." This ground truth relies on laboratory results rather than expert interpretation of clinical data or images. Therefore, the document does not specify human experts for establishing ground truth, but rather relies on the interpretative methods of the comparator assays. Those interpreting the culture results, sequencing data, and FDA-cleared NAAT results would typically be trained laboratory personnel or clinical laboratorians.
4. Adjudication Method for the Test Set
-
Reproducibility Study: No explicit adjudication method is mentioned as the ground truth was "expected results" for contrived samples based on known concentrations. Adjudication wasn't necessary for these controlled samples.
-
Clinical Agreement (Prospective Study): An adjudication method was used for discordant results in the composite comparator algorithm:
- "A positive result for HSV-1 and/or HSV-2 was determined by a positive test result in either the culture or the bi-directional sequencing."
- "If both the culture and the bi-directional sequencing yielded positive results but disagreed in the differentiation of HSV-1 versus HSV-2, the results of the FDA cleared NAAT were used and a 2 out of 3 rule was followed to determine the type of the virus (e.g. if two of the methods were positive for HSV-1, the final comparator result was HSV-1 positive)." This is a form of 2-out-of-3 or majority rule adjudication.
-
Clinical Agreement (Retrospective Study): The ground truth was established by a "validated bi-directional sequencing assay." No specific adjudication process is described beyond the sequencing assay itself.
5. 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 Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study focuses on an in vitro diagnostic (IVD) PCR assay for the detection of viral DNA, not on image interpretation or other tasks typically performed by human readers that could be augmented by AI. Therefore, there's no mention of human readers or AI assistance.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done
- Yes, the performance presented for the Simplexa™ HSV 1 & 2 Direct assay is standalone performance. It describes the diagnostic accuracy of the assay itself (device only) against a comparator method. The device is an automated, real-time PCR system, and its output (qualitative detection and differentiation of HSV-1 and HSV-2 DNA) is directly compared. The assay operates without human "in-the-loop" interpretation for the final diagnostic call.
7. The Type of Ground Truth Used
- Reproducibility Study: Known concentrations of spiked viral material (contrived samples) were used as ground truth.
- Clinical Agreement (Prospective Study): A composite comparator algorithm was used as ground truth, consisting of:
- Culture
- Bi-directional sequencing
- An FDA cleared NAAT (used for discordant resolution)
- Clinical Agreement (Retrospective Study): A validated bi-directional sequencing assay was used as ground truth.
8. The Sample Size for the Training Set
- The document describes performance evaluation studies (reproducibility and clinical agreement) for the Simplexa™ HSV 1 & 2 Direct assay. It does not explicitly mention a "training set" or "validation set" in the context of machine learning model development. This is typical for IVD assays which are developed and then verified/validated rather than 'trained'. The data presented is for validation of the a priori defined assay.
9. How the Ground Truth for the Training Set Was Established
- As no "training set" in the machine learning sense is described, this question is not applicable based on the provided document. The ground truth for the validation and reproducibility sets is detailed in point 7.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
August 28, 2015
FOCUS DIAGNOSTICS, INC. SHARON YOUNG SENIOR REGULATORY AFFAIRS SPECIALIST 11331 VALLEY VIEW STREET CYPRESS, CA 90630
Re: K150962
Trade/Device Name: Simplexa HSV 1 & 2 Direct, Simplexa HSV1 & 2 Positive Control Pack
Regulation Number: 21 CFR 866.3305 Regulation Name: Herpes simplex virus serological assays Regulatory Class: II Product Code: OQO Dated: August 25, 2015 Received: August 26, 2015
Dear Ms. Young:
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. 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 (OS) 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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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/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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/ReportaProblem/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
Uwe Scherf, 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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Indications for Use
510(k) Number (if known) K150962
Device Name
Simplexa™ HSV 1 & 2 Direct and Simplexa™ HSV 1 & 2 Positive Control Pack
Indications for Use (Describe)
Simplexa™ HSV 1 & 2 Direct
The Focus Diagnostics Simplexa™ HSV 1 & 2 Direct assay is intended for use on the 3M Integrated Cycler instrument for the qualitative detection and differentiation of herpes simples virus (HSV-2) DNA present in genital lesion swabs samples from patients with signs and symptoms of HSV-2 infection of the genitalia. This test is an aid in the differential diagnosis of HSV-1 and HSV-2 genital infections.
The assay is not intended for use as a screening test for the presence of HSV-2 in blood or blood products. The assay is for professional use only.
Simplexa™ HSV 1 & 2 Positive Control Pack
The Simplexa™ HSV 1 & 2 Positive Control Pack is intended to be used as a control with the Simplexa™ HSV 1 & 2 Direct kit. This control is not intended for use with other assays or systems.
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
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Image /page/3/Picture/0 description: The image shows the logo for Focus Diagnostics. The word "FOCUS" is in large, bold, sans-serif font. A curved, black shape is to the left of the word, resembling a stylized check mark or swoosh. Below "FOCUS" is the word "Diagnostics" in a smaller, sans-serif font, underlined with a thin black line.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 August 20, 2015 Page 1 of 12
| Applicant | Focus Diagnostics, Inc.11331 Valley View StreetCypress, California 90630USA |
|---|---|
| Establishment Registration No. | 2023365 |
| Contact Person | Sharon Youngtel 562.240.6680fax 562.240.6529syoung@focusdx.com |
| Summary Date | August 20, 2015 |
| Proprietary Name | Simplexa™ HSV 1 & 2 DirectSimplexa™ HSV 1 & 2 Positive Control Pack |
| Generic Name | Herpes Simplex Virus serological assays |
| Classification | OQO |
| Regulation | |
| Product Code | |
| Predicate Device | OQO - artus® HSV-1/2 QS-RGQ MDx Kit (K142738) |
Intended Use
Simplexa™ HSV 1 & 2 Direct
The Focus Diagnostics Simplexa™ HSV 1 & 2 Direct assay is intended for use on the 3M Integrated Cycler instrument for the qualitative detection and differentiation of herpes simples virus (HSV-1 and HSV-2) DNA present in genital lesion swabs samples from patients with signs and symptoms of HSV-1 or HSV-2 infection of the genitalia. This test is an aid in the differential diagnosis of HSV-1 and HSV-2 genital infections.
The assay is not intended for use as a screening test for the presence of HSV-1 and HSV-2 in blood or blood products. The assay is for professional use only.
Simplexa™ HSV 1 & 2 Positive Control Pack
The Simplexa™ HSV 1 & 2 Positive Control Pack is intended to be used as a control with the Simplexa™ HSV 1 & 2 Direct kit. This control is not intended for use with other assays or systems.
Device Description
The Simplexa™ HSV 1 & 2 Direct assay system is a real-time PCR that enables the direct amplification, detection and differentiation of HSV-1 and/or HSV-2 DNA from unprocessed genital swab specimens without nucleic acid extraction. The system consists of the Simplexa™ HSV 1 & 2 Direct assay, the 3M Integrated Cycler (with 3M Integrated Cycler Studio Software), the Direct Amplification Disc and associated accessories.
In the Simplexa™ HSV 1 & 2 Direct assay, bi-functional fluorescent probe-primers are used together with corresponding reverse primers to amplify HSV-1, HSV-2 and internal control targets. Well conserved regions of the HSV-1 and HSV-2 DNA polymerase genes are targeted to identify HSV-1 and HSV-2 DNA respectively in the specimen. An internal control is used to detect PCR failure and/or inhibition.
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Image /page/4/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo consists of a stylized swoosh shape on the left, followed by the word "FOCUS" in a bold, sans-serif font. Below "FOCUS" is the word "Diagnostics" in a smaller, sans-serif font, underlined with a thin line. The entire logo is in black and white.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 August 20, 2015 Page 2 of 12
Predicate Device Information
Similarities
| Name | Simplexa™ HSV1 & 2 Direct | artus® HSV-1/2 QS-RGQ MDx KitK142738 |
|---|---|---|
| Intended Use | Simplexa™ HSV 1 & 2 DirectThe Focus Diagnostics Simplexa™ HSV 1 &2 Direct assay is intended for use on the 3MIntegrated Cycler instrument for thequalitative detection and differentiation ofherpes simplex virus (HSV-1 and HSV-2)DNA present in genital lesion swabs samplesfrom patients with signs and symptoms ofHSV-1 or HSV-2 infection of the genitalia.This test is an aid in the differential diagnosisof HSV-1 and HSV-2 genital infections.The assay is not intended for use as ascreening test for the presence of HSV-1 andHSV-2 in blood or blood products. The assayis for professional use only.Simplexa™ HSV 1 & 2 Positive Control PackThe Simplexa™ HSV 1 & 2 Positive ControlPack is intended to be used as a control withthe Simplexa™ HSV 1 & 2 Direct kit.This control is not intended for use with otherassays or systems. | The artus HSV-1/2 QS-RGQ MDx Kit is an in vitroreal-time PCR DNA amplification assay performedon the QIAsymphony RGQ MDx system for thedirect qualitative detection and differentiation ofherpes simplex virus (HSV-1 and HSV-2) DNA ingenital or oral vesicular lesions from male andfemale patients suspected of HSV infection.The assay is intended for use as an aid in diagnosisof HSV infection in symptomatic patients.Warning: The artus HSV-1/2 QS-RGQ MDx Kit isnot FDA-cleared for use with cerebrospinal fluid(CSF) or for prenatal screening. |
| AssayTargets | HSV-1 and HSV-2 DNA | HSV-1 and HSV-2 DNA |
| DetectionTechniques | Multiplex assay using different reporter dyesfor each target. | Multiplex assay using different reporter dyes foreach target. |
Differences
| Name | Simplexa™ HSV1 & 2 Direct | artus® HSV-1/2 QS-RGQ MDx KitK142738 |
|---|---|---|
| Sample Types | Genital herpetic lesion swab samples | Male and female genital or oral herpetic lesions. |
| Assay Methodology | PCR-based system for detecting thepresence / absence of viral DNA in clinicalspecimens | Amplification and detection are carried out using theartus HSV-1/2 QS-RGQ MDx Kit with the Rotor-Gene Q MDx (RGQ MDx) and Rotor-Gene AssayManager software. |
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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 a curved, swooping line above it. Below "FOCUS" is the word "Diagnostics" in a smaller, sans-serif font, underlined with a thin line.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 August 20, 2015 Page 3 of 12
REPRODUCIBILITY - Genital Swab Sample Type
Reproducibility for the Simplexa™ HSV 1 & 2 Direct assay was evaluated. Three investigative sites assessed the device's inter-site, inter-day and inter/intra-assay reproducibility. Each of the laboratories tested the positive control and a panel of five contrived sample pools including a low (approximately 1-2 times LoD) and medium positive (approximately 2-4 times LoD) for each analyte and a high negative. The high negative sample contained a small amount of HSV-1 and it was designed to be neqative approximately 95% of the time. The assays were performed in triplicate on five different days. Each site had two operators; each operator assayed the entire sample panel and positive control once per day, for a total of two sets of data per day. Combined results for all sites are presented in the tables below.
| Sample | Site - 1 | Site - 2 | Site - 3 | Total %AgreementwithExpectedResults | 95% CI | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| %AgreementwithExpectedResults | Avg.Ct | Total%CV | %AgreementwithExpectedResults | Avg.Ct | Total%CV | %AgreementwithExpectedResults | Avg.Ct | Total%CV | ||||
| HSV-1 LowPositive | 100.0%(30/30) | 36.0 | 2.2 | 100.0%(30/30) | 36.1 | 2.6 | 100.0%(30/30) | 36.3 | 2.7 | 100.0%(90/90) | 95.9 to100.0% | |
| HSV-1Result | HSV-1MediumPositive | 100.0%(30/30) | 34.4 | 1.7 | 100.0%(30/30) | 34.8 | 1.2 | 100.0%(30/30) | 34.6 | 1.9 | 100.0%(90/90) | 95.9 to100.0% |
| HSV-2 LowPositive | 100.0%(30/30)a | NA | NA | 100.0%(30/30)a | NA | NA | 96.7%(29/30)a | NA | NA | 98.9%(89/90)a | 94.0 to99.8% | |
| HSV-2MediumPositive | 100.0%(30/30)a | NA | NA | 96.7%(29/30)a | NA | NA | 100.0%(30/30)a | NA | NA | 98.9%(89/90)a | 94.0 to99.8% | |
| HighNegative | 96.7%(29/30)a | 38.8 | 0.0 | 93.3%(28/30)a | 38.7 | 0.5 | 90.0%(27/30)a | 38.0 | 4.1 | 93.3%(84/90)a | 86.2 to96.9% | |
| PositiveControl | 100.0%(30/30) | 29.9 | 0.8 | 100.0%(30/30) | 30.4 | 1.3 | 100.0%(29/29) | 29.9 | 2.8 | 100.0%(89/89) | 95.9 to100.0% | |
| TotalAgreement | 99.4% (179/180) | 98.3% (177/180) | 97.8% (175/179) | 98.5%(531/539) | 97.1 to99.2% | |||||||
| a) Expected Results of HSV-2 Low Positive, HSV-2 Medium Positive and High Negative samples are "Negative" for HSV-1. |
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Image /page/6/Picture/0 description: The image shows the logo for Focus Diagnostics. The word "FOCUS" is in large, bold, black letters. Above and to the left of the word "FOCUS" is a black swoosh design. Below the word "FOCUS" is the word "Diagnostics" in smaller, black letters with a line above it.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 August 20, 2015 Page 4 of 12
| Sample | Site - 1 | Site - 2 | Site - 3 | Total %AgreementwithExpectedResults | 95% CI | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| %AgreementwithExpectedResults | Avg.Ct | Total%CV | %AgreementwithExpectedResults | Avg.Ct | Total%CV | %AgreementwithExpectedResults | Avg.Ct | Total%CV | ||||
| HSV-2Result | HSV-1LowPositive | 100.0%(30/30)b | NA | NA | 100.0%(30/30)b | NA | NA | 96.7%(29/30)b | 41.1 | 0.0 | 98.9%(89/90)b | 94.0 to99.8% |
| HSV-1MediumPositive | 100.0%(30/30)b | NA | NA | 100.0%(30/30)b | NA | NA | 100.0%(30/30)b | NA | NA | 100.0%(90/90)b | 95.9 to100.0% | |
| HSV-2LowPositive | 100.0%(30/30) | 37.4 | 2.9 | 90.0%(27/30) | 37.5 | 3.5 | 93.3%(28/30) | 37.1 | 2.8 | 94.4%(85/90) | 87.6 to97.6% | |
| HSV-2MediumPositive | 100.0%(30/30) | 35.5 | 1.9 | 100.0%(30/30) | 35.6 | 2.0 | 100.0%(30/30) | 35.3 | 1.6 | 100.0%(90/90) | 95.9 to100.0% | |
| HighNegative | 96.7%(29/30)b | 39.5 | 0.0 | 86.7%(26/30)b | 38.6 | 2.9 | 100.0%(30/30)b | NA | NA | 94.4%(85/90)b | 87.6 to97.6% | |
| PositiveControl | 100.0%(30/30) | 30.2 | 1.3 | 100.0%(30/30) | 30.1 | 0.6 | 100.0%(29/29) | 29.9 | 1.2 | 100.0%(89/89) | 95.9 to100.0% | |
| TotalAgreement | 99.4% (179/180) | 96.1% (173/180) | 98.9% (176/179) | 98.0%(528/539) | 96.4 to98.9% | |||||||
| b) Expected Results of HSV-1 Low Positive, HSV-1 Medium Positive and High Negative samples are "Negative" for HSV-2. |
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Image /page/7/Picture/0 description: The image shows the logo for Focus Diagnostics. The word "FOCUS" is in large, bold, black letters. A curved black line extends from the top left of the "F" and curves over the word. Below "FOCUS" is the word "Diagnostics" in smaller, black letters with a line above it.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 August 20, 2015 Page 5 of 12
| Sample | Site - 1 | Site - 2 | Site - 3 | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sample | % Agreement with Expected Results | Avg.Ct | Total%CV | % Agreement with Expected Results | Avg.Ct | Total%CV | % Agreement with Expected Results | Avg.Ct | Total%CV | Total % Agreement with Expected Results | 95% CI | |
| DNAICResult | HSV-1 LowPositive | 100.0%(30/30) | 29.6 | 0.7 | 100.0%(30/30) | 29.8 | 1.2 | 100.0%(30/30) | 29.7 | 1.0 | 100.0%(90/90) | 95.9 to100.0% |
| HSV-1MediumPositive | 100.0%(30/30) | 29.6 | 0.8 | 100.0%(30/30) | 29.8 | 1.4 | 100.0%(30/30) | 29.7 | 0.9 | 100.0%(90/90) | 95.9 to100.0% | |
| HSV-2 LowPositive | 100.0%(30/30) | 29.6 | 0.8 | 100.0%(30/30) | 29.8 | 1.2 | 100.0%(30/30) | 29.7 | 1.0 | 100.0%(90/90) | 95.9 to100.0% | |
| HSV-2MediumPositive | 100.0%(30/30) | 29.5 | 0.6 | 100.0%(30/30) | 29.7 | 1.4 | 100.0%(30/30) | 29.8 | 1.4 | 100.0%(90/90) | 95.9 to100.0% | |
| HighNegative | 100.0%(30/30) | 29.6 | 0.6 | 100.0%(30/30) | 29.8 | 1.2 | 100.0%(30/30) | 29.7 | 1.0 | 100.0%(90/90) | 95.9 to100.0% | |
| PositiveControl | 100.0%(30/30) | 29.5 | 0.5 | 100.0%(30/30) | 29.7 | 1.4 | 100.0%(29/29) | 29.7 | 0.9 | 100.0%(89/89) | 95.9 to100.0% | |
| TotalAgreement | 100.0% (180/180) | 100.0% (180/180) | 100.0% (179/179) | 100.0%(539/539) | 96.4 to98.9% |
ANALYTICAL SENSITIVITY/LIMIT OF DETECTION - Genital Swab Sample Type
The Limit of Detection (LoD) was determined for the Simplexa™ HSV 1 & 2 Direct assay using quantified
stocks of HSV-1 and HSV-2 serially diluted into negative genital swab ma genital swabs. LoD was determined to be the lowest concentration that could be detected positive > 95% of the time.
| Virus Strain | LoD Concentration(TCID50/mL) | QualitativeResults(#Detected/#Total) | Mean Ct ± SD(from DetectedReplicates only) |
|---|---|---|---|
| HSV-1 McIntyre | 4 | 32/32 | 36.4 ± 1.16 |
| HSV-1 HF | 160 | 32/32 | 35.2 ± 1.03 |
| HSV-2 G | 2 | 32/32 | 37.5 ± 1.08 |
| HSV-2 MS | 10 | 31/32 | 37.9 ± 1.15 |
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Image /page/8/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 font size underneath. To the left of the word "FOCUS" is a curved, black shape that resembles a swoosh or a stylized checkmark.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 August 20, 2015 Page 6 of 12
ANALYTICAL REACTIVITY/ CROSS REACTIVITY
Analytical Reactivity -Genital Swab Sample Type
The analytical reactivity of the Simplexa™ HSV 1 & 2 Direct assay was evaluated using different strains of HSV-1 and HSV-2 that were not used in the determination of the limit of detection (LoD) for the assay. Quantified viral material was spiked into negative genital swab matrix containing male and female genital swabs using a single dilution and assayed in triplicate. The Simplexa™ HSV 1 & 2 Direct assay was able to detect other strains of HSV-1 and HSV-2 viruses.
| HSVStrain/Isolate | Spiked Concentration[TCID50/mL] | Qualitative Result(#Detected/#Total) | |
|---|---|---|---|
| HSV-1 | HSV-2 | ||
| HSV-1 KOS | 16 | 3/3 | 0/3 |
| HSV-1 F | 32 | 3/3 | 0/3 |
| HSV-2 Isolate 1 | 8 | 0/3 | 3/3 |
| HSV-2 Isolate 2 | 8 | 0/3 | 3/3 |
| HSV-2 Isolate 3 | 8 | 0/3 | 3/3 |
Cross-Reactivity (Analytical Specificity) - Genital Swab Sample Type
The Simplexa™ HSV 1 & 2 Direct assay's analytical specificity was evaluated by testing the ability to exclusively identify HSV-1 and HSV-2 viruses with no cross-reactivity to organisms that are closely related, or cause similar clinical symptoms or may be present on swabs of the genital region. Thirty six (36) potential cross-reactants were spiked into negative genital swab matrix containing male and female genital swabs and assayed in triplicate. No cross-reactivity was observed.
| No. | Potential Cross-Reactants | Tested Concentration | Qualitative Result(#Detected/#Total) | |
|---|---|---|---|---|
| HSV-1 | HSV-2 | |||
| 1 | None (Baseline) | Not Applicable | 0/15 | 0/15 |
| 2 | Bacteroides fragilis | 1.00 X 106 cfu/mL | 0/3 | 0/3 |
| 3 | Bacteroides ureolyticus* | Not Applicable | Not Applicable | Not Applicable |
| 4 | Candida albicans | 1.00 X 106 cfu/mL | 0/3 | 0/3 |
| 5 | Chlamydia trachomatis | 1.00 X 106 IFU/mL | 0/3 | 0/3 |
| 6 | Clostridium sordellii | 1.00 X 106 cfu/mL | 0/3 | 0/3 |
| 7 | Corynebacterium genitalium | 1.00 X 106 cfu/mL | 0/3 | 0/3 |
| 8 | Cytomegalovirus AD169 strain | 1.00 X 105 TCID50/mL | 0/3 | 0/3 |
| 9 | Enterococcus faecalis vanB | 1.00 X 106 cfu/mL | 0/3 | 0/3 |
| 10 | Enterovirus 71 | 1.00 X 105 TCID50/mL | 0/8 | 1/8 |
| 11 | Epstein Barr Virus (B95-8) | 1.00 X 105 copies/mL | 0/3 | 0/3 |
| 12 | Escherichia coli O157H7 | 1.00 X 106 cfu/mL | 0/3 | 0/3 |
| 13 | Gardnerella vaginalis | 1.00 X 106 cfu/mL | 0/3 | 0/3 |
| 14 | Hepatitis B | 1.00 X 105 IU/mL | 0/3 | 0/3 |
| 15 | Hepatitis C | 1.00 X 105 IU/mL | 0/3 | 0/3 |
| 16 | HHV-6 (Z29 Strain) | 1.00 X 105 TCID50/mL | 0/3 | 0/3 |
| 17 | HHV-7 SB | 1.00 X 105 TCID50/mL | 0/3 | 0/3 |
| 18 | HIV-1 IIIB | 1.00 X 105 copies/mL | 0/3 | 0/3 |
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Image /page/9/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo consists of the word "FOCUS" in large, bold, black letters. To the left of the word is a curved, black shape that resembles a stylized check mark or swoosh. Below the word "FOCUS" is the word "Diagnostics" in a smaller font, underlined with a thin black line.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 August 20, 2015 Page 7 of 12
| No. | Potential Cross-Reactants | Tested Concentration | Qualitative Result(#Detected/#Total) | |
|---|---|---|---|---|
| HSV-1 | HSV-2 | |||
| 19 | HIV-2 NIHZ** | Not Available | 0/3 | 0/3 |
| 20 | HPV18 Recombinant | 1.00 X 105 pfu/mL | 0/3 | 0/3 |
| 21 | Lactobacillus acidophilus | 1.00 X 106 cfu/mL | 0/3 | 0/3 |
| 22 | Mobiluncus mulieris | 1.00 X 106 cfu/mL | 0/3 | 0/3 |
| 23 | Mycoplasma genitalium** | Not Applicable | Not Applicable | Not Applicable |
| 24 | Mycoplasma hominis | 1.00 X 106 CCU/mL | 0/3 | 0/3 |
| 25 | Neisseria gonorrhoeae | 1.00 X 106 cfu/mL | 0/3 | 0/3 |
| 26 | Proteus vulgaris | 1.00 X 106 cfu/mL | 0/3 | 0/3 |
| 27 | Rubella | 1.00 X 105 TCID50/mL | 0/3 | 0/3 |
| 28 | Staphylococcus aureus (MRSA),ATCC 700699 | 1.00 X 106 cfu/mL | 0/3 | 0/3 |
| 29 | Staphylococcus epidermidis (MRSE),ATCC 29887 | 1.00 X 106 cfu/mL | 0/3 | 0/3 |
| 30 | Staphylococcus saprophyticus | 1.00 X 106 cfu/mL | 0/3 | 0/3 |
| 31 | Streptococcus mitis | 1.00 X 106 cfu/mL | 0/3 | 0/3 |
| 32 | Streptococcus pyogenes, M1 | 1.00 X 106 cfu/mL | 0/3 | 0/3 |
| 33 | Toxoplasma gondii | 1.00 X 106 tachyzooites/mL | 0/3 | 0/3 |
| 34 | Treponema pallidum** | Not Applicable | Not Applicable | Not Applicable |
| 35 | Trichomonas vaginalis | 1.00 X 106 trophozoites/ml | 0/3 | 0/3 |
| 36 | Ureaplasma urealyticum | 1.00 X 106 CCU/mL | 0/3 | 0/3 |
| 37 | VZV | 1.00 X 105 copies/mL | 0/3 | 0/3 |
" Microorganism was not available for testing therefore in-silico NCBI BLAST analysis was performed and found no predicted cross reactivity. ** Quantified material was not available to test; instead the vendor provided a culture fluid with a known Ct value. The site was directed to dilute the stock to a relevant Ct value; 1:50 dilution factor.
INTERFERENCE - Genital Swab Sample Type
The performance of the Simplexa™ HSV 1 & 2 Direct assay was evaluated with potentially interfering substances that may be present on swabs of the genital region at the concentrations indicated in the table below. A total of five (26) potentially interfering substances were tested in a low positive HSV-1 and HSV-2 sample (4 times LoD) in negative genital swab matrix containing male and female genital swabs and assayed in triplicate. No interference was observed.
| Potential Interferent | Interferent Concentration | #Detected/#Total | ||
|---|---|---|---|---|
| HSV-1 | HSV-2 | IC | ||
| Abreva cold sore treatment | 7% w/v | 3/3 | 3/3 | 3/3 |
| Acyclovir | 2.5 mg/mL | 3/3 | 3/3 | 3/3 |
| Acyclovir Cream* | 7% w/v | 8/8 | 5/8 | 8/8 |
| Albumin | 10 mg/mL | 3/3 | 3/3 | 3/3 |
| Balneol Hygienic Cleansing lotion | 7% w/v | 3/3 | 3/3 | 3/3 |
| Casein | 10 mg/mL | 3/3 | 3/3 | 3/3 |
| Cidofovir | 2.5 mg/mL | 3/3 | 3/3 | 3/3 |
| Clotrimazole vaginal cream | 7% w/v | 3/3 | 3/3 | 3/3 |
| Denavir | 2.5 mg/mL | 3/3 | 3/3 | 3/3 |
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Image /page/10/Picture/0 description: The image shows the logo for Focus Diagnostics. The logo features the word "FOCUS" in bold, uppercase letters. A curved line extends from the left side of the "F", arching over the word. Below "FOCUS" is the word "Diagnostics" in a smaller, non-bold font, underlined with a thin line.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 August 20, 2015 Page 8 of 12
| #Detected/#Total | ||||
|---|---|---|---|---|
| Potential Interferent | Interferent Concentration | HSV-1 | HSV-2 | IC |
| Douche | 7% w/v | 3/3 | 3/3 | 3/3 |
| Famciclovir | 2.5 mg/mL | 3/3 | 3/3 | 3/3 |
| Feces | 2.5 mg/mL | 3/3 | 3/3 | 3/3 |
| Gynol II (Contraceptive jelly) | 7% w/v | 3/3 | 3/3 | 3/3 |
| KY Jelly | 5% v/v | 3/3 | 3/3 | 3/3 |
| Monistat 1 | 7% w/v | 3/3 | 3/3 | 3/3 |
| Monistat 3 | 7% w/v | 3/3 | 3/3 | 3/3 |
| Mucin | 7% w/v | 3/3 | 3/3 | 3/3 |
| Preparation H Hemorrhoid cream | 7% w/v | 3/3 | 3/3 | 3/3 |
| Releev cold sore treatment | 7% w/v | 3/3 | 3/3 | 3/3 |
| Urine | 10% v/v | 3/3 | 3/3 | 3/3 |
| Vagicaine Anti-Itch Cream | 7% w/v | 3/3 | 3/3 | 3/3 |
| Vagisil creme | 7% w/v | 3/3 | 3/3 | 3/3 |
| VagiStat 1 | 7% w/v | 3/3 | 3/3 | 3/3 |
| Valacyclovir | 2.5 mg/mL | 3/3 | 3/3 | 3/3 |
| Whole Blood | 10% v/v | 3/3 | 3/3 | 3/3 |
| YeastGard Suppositories | 7% w/v | 3/3 | 3/3 | 3/3 |
| * One out of three (1/3) initial replicates and two out of five (2/5) confirmation replicates were negative for HSV-2 |
CLINICAL AGREEMENT - Genital Swab Sample Type
Prospective Study
A total of 718 genital swab samples were prospectively collected from patients with signs and symptoms of genital herpes simplex virus (HSV) infection from 6 geographically diverse locations. Of the 718 samples collected. 9 samples were removed from the analysis because they were either not tested or had invalid results on the 3 assays (Simplexa™ HSV 1 & 2 Direct, Culture or bi-directional sequencing). Of the 709 remaining samples, 13 samples were removed from the analysis because they were not tested on the tests included in the comparator method sufficient to generate a final comparator result. A total of 696 samples were used for the analysis. The clinical performance of the Simplexa HSV 1 & HSV 2 assay was evaluated by comparing the positive and negative percent agreement to a composite comparator algorithm consisting of; culture, bi-directional sequencing and an FDA cleared NAAT. A positive result for HSV-1 and/or HSV-2 was determined by a positive test result in either the culture or the bi-directional sequencing. If both the culture and the bi-directional sequencing yielded positive results but disagreed in the differentiation of HSV-1 versus HSV-2, the results of the FDA cleared NAAT were used and a 2 out of 3 rule was followed to determine the type of the virus (e.g. if two of the methods were positive for HSV-1, the final comparator result was HSV-1 positive). All sites collected the genital swab samples on the Simplexa™ HSV-1 and HSV-2 Direct and sent samples to a central lab for culture testing. For culture, each sample was tested for HSV- 2 first and if positive for HSV-2 no further testing was performed. Samples that were HSV-2 culture negative were further tested for HSV-1 culture positivity. Dual positives could not be identified in the culture assay.
The available retained samples were sent to Focus Diagnostics and tested in a validated bi-directional sequencing assay. Of the 24 discordant samples that were positive for HSV-2 by the culture method but positive for HSV-1 by the bi-directional sequencing assay, 18 samples had valid results and 1 sample had an invalid result when tested on an FDA cleared NAAT. There were 5 samples that were not tested on the FDA cleared NAAT due to insufficient volume and therefore 6 out of 24 samples were excluded from the
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Image /page/11/Picture/0 description: The image shows the logo for Focus Diagnostics. The word "FOCUS" is in large, bold, sans-serif font. A curved, swooping shape is to the left of the word. Below the word "FOCUS" is the word "Diagnostics" in a smaller, sans-serif font, underlined with a thin line.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 August 20, 2015 Page 9 of 12
analysis. There were 2 samples that were positive for HSV-1 by the culture method but positive for HSV-2 by the bi-directional sequencing assay that were not tested on the FDA cleared NAAT for insufficient volume and therefore were excluded from analysis. Results for Simplexa™ HSV 1 & 2 Direct compared to the composite comparator algorithm are presented in the following tables.
Simplexa™ HSV 1 & 2 Direct Compared to Composite Comparator Result (HSV-1)
| Simplexa™ HSV 1 & 2 DirectResults HSV-1 | Composite Comparator Result (HSV-1) | ||
|---|---|---|---|
| Detected | Not Detected | Total | |
| Detected | 111 | 10 | 121 |
| Not Detected | 3 | 560 | 563 |
| Total | 114 | 570 | 684 |
| Sensitivity | 97.4%(111/114)95% CI: 92.5% to 99.1% | Specificity | 98.2%(560/570)95% CI: 96.8% to 99.0% |
| PPV | 91.7%(111/121)95% CI: 85.5% to 95.4% | NPV | 99.5%(560/563)95% CI: 98.4% to 99.8% |
Simplexa™ HSV 1 & 2 Direct Compared to Composite Comparator Result (HSV-2)
| Simplexa™ HSV 1 & 2 Direct | Composite Comparator Result (HSV-2) | ||
|---|---|---|---|
| Results HSV-2 | Detected | Not Detected | Total |
| Detected | 175 | 11 | 186 |
| Not Detected | 5 | 497 | 502 |
| Total | 180 | 508 | 688 |
| Sensitivity | 97.2%(175/180)95% Cl: 93.7% to 98.8% | Specificity | 97.8%(497/508)95% CI: 96.2% to 98.8% |
| PPV | 94.1%(175/186)95% Cl: 89.7% to 96.7% | NPV | 99.0%(497/502)95% CI: 97.7% to 99.6% |
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Image /page/12/Picture/0 description: The image shows the logo for Focus Diagnostics. The word "FOCUS" is in large, bold, black letters. Above and to the left of the word is a curved, black shape. Below the word "FOCUS" is a horizontal line, and below that line is the word "Diagnostics" in a smaller font.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 August 20, 2015 Page 10 of 12
Retrospective Study
A total of 28 genital swab samples (14 positive HSV-1 and 14 positive HSV-2) were retrospectively collected from male patients with signs and symptoms of genital herpes simplex virus (HSV) infection and contained preselected positive and negative samples were tested at Focus Diagnostics using the SimplexaTM HSV 1 & 2 Direct and a validated bi-directional sequencing assay.
HSV-1 Validated Bi-Directional Sequencing Assay Results
| Simplexa™ HSV 1 & 2 DirectResults | Composite Comparator Result (HSV-1) | ||
|---|---|---|---|
| Detected | Not Detected | Total | |
| Detected | 14 | 1 | 15 |
| Not Detected | 0 | 13 | 13 |
| Total | 14 | 14 | 28 |
| PPA | 100.0%(14/14) | NPA | 92.9%(13/14) |
| 95% CI: 78.5% to 100.0% | 95% CI: 68.5% to 98.7% | ||
| PPV | 93.3%(14/15) | NPV | 100.0%(13/13) |
| 95% CI: 70.2% to 98.8% | 95% CI: 77.2% to 100.0% |
HSV-2 Validated Bi-Directional Sequencing Assay Results
| Simplexa™ HSV 1 & 2 DirectResults | Composite Comparator Result (HSV-2) | ||
|---|---|---|---|
| Results | Detected | Not Detected | Total |
| Detected | 14 | 0 | 14 |
| Not Detected | 0 | 14 | 14 |
| Total | 14 | 14 | 28 |
| PPA | 100.0%(14/14)95% CI: 78.5% to 100.0% | NPA | 100.0%(14/14)95% CI: 78.5% to 100.0% |
| PPV | 100.0%(14/14)95% CI: 78.5% to 100.0% | NPV | 100.0%(14/14)95% CI: 78.5% to 100.0% |
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Image /page/13/Picture/0 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 below it. A curved, black shape is to the left of the word "FOCUS", which gives the logo a modern and professional look. The logo is simple, clean, and easy to read.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 August 20, 2015 Page 11 of 12
EXPECTED VALUES - Genital Swab Sample Type
The observed expected values using the Simplexa™ HSV 1 & 2 Direct assay are presented below for patients 17 years of age or older from the prospective study population. The data is stratified by age, and gender and collection sites.
| Sample Demographics by Simplexa™ HSV 1 & 2 Direct Assay | |||||||
|---|---|---|---|---|---|---|---|
| Gender | Age Group | Simplexa™ HSV 1 & 2 Direct Result | |||||
| All | HSV-1 &HSV-2 NotDetected | HSV-1 Detected& HSV-2 NotDetected | HSV-1 NotDetected & HSV-2Detected | HSV-1 & HSV-2Dual Positive | Not-Evaluable | ||
| Female | 17 Years ofage to 21Years of age | 98 | 41.8% (41/98) | 25.5% (25/98) | 30.6% (30/98) | 0.0% (0/98) | 2.0% (2/98) |
| More than 21Years of age | 503 | 54.3% (273/503) | 16.9% (85/503) | 25.8% (130/503) | 0.8% (4/503) | 2.2% (11/503) | |
| All | 601 | 52.2% (314/601) | 18.3% (110/601) | 26.6% (160/601) | 0.7% (4/601) | 2.2% (13/601) | |
| Male | 17 Years ofage to 21Years of age | 14 | 42.9% (6/14) | 21.4% (3/14) | 35.7% (5/14) | 0.0% (0/14) | 0.0% (0/14) |
| More than 21Years of age | 66 | 68.2% (45/66) | 10.6% (7/66) | 18.2% (12/66) | 1.5% (1/66) | 1.5% (1/66) | |
| All | 80 | 63.8% (51/80) | 12.5% (10/80) | 21.3% (17/80) | 1.3% (1/80) | 1.3% (1/80) | |
| All | 681 | 53.6% (365/681) | 17.6% (120/681) | 26.0% (177/681) | 0.7% (5/681) | 0.7% (5/681)** |
volume, daily PC/NTC failure,
** Excluded from this table are 35 samples from 17 years of age and 2 samples where the age of the patient was not t available.
| Hypothetical Prevalence | HSV-1 | HSV-2 | ||
|---|---|---|---|---|
| PPV* | NPV** | PPV* | NPV** | |
| 1.0% | 35.3% | 100.0% | 30.9% | 100.0% |
| 2.0% | 52.5% | 99.9% | 47.4% | 99.9% |
| 3.0% | 62.6% | 99.9% | 57.7% | 99.9% |
| 5.0% | 74.0% | 99.9% | 69.9% | 99.8% |
| 10.0% | 85.7% | 99.7% | 83.1% | 99.7% |
| 15.0% | 90.5% | 99.5% | 88.6% | 99.5% |
| 20.0% | 93.1% | 99.3% | 91.7% | 99.3% |
| 30.0% | 95.9% | 98.9% | 95.0% | 98.8% |
| 50.0% | 98.2% | 97.4% | 97.8% | 97.2% |
*Positive Predictive Value (PPV) was calculated using:
(Sensitivity x Prevalence)/(Sensitivity x Prevalence + [1 - Specificity] x [1 - Prevalence]).
**Negative Predictive Value (NPV ) was calculated using:
(Specificity x [1 - Prevalence])/([1 - Sensitivity] x Prevalence + Specificity x [1 - Prevalence]).
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Image /page/14/Picture/0 description: The image shows the logo for Focus Diagnostics. The word "FOCUS" is in large, bold, black letters. A curved black line extends from the top left of the "F" and curves around the word. Below "FOCUS" is the word "Diagnostics" in smaller, black letters, underlined with a thin black line.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 August 20, 2015 Page 12 of 12
FRESH VS FROZEN STUDY
Storage conditions were validated using the following transport media types BD VTM, M4, M4RT, M5, M6, and UTM by spiking media with organism at concentrations ranging from 3 times LoD to 50 times LoD and at different storage temperatures and durations.
Samples should be transported on ice and stored at 2 to 8°C for up to 7 days post collection. If there is a greater than 7 day delay before processing of the sample, store the sample at -70° C.
CONCLUSION
The conclusions drawn from the nonclinical tests demonstrate the device is as safe and effective as the legally marketed device identified above.
§ 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).