(90 days)
The DiaSorin Molecular Simplexa™ HSV 1 & 2 Direct assay is intended for use on the LIAISON® MDX instrument for the qualitative detection and differentiation of herpes simplex virus (HSV-2) DNA present in mucocutaneous and cutaneous lesion swabs from patients with signs and symptoms of HSV-1 or HSV-2 infection. This test is an aid in the differential diagnosis of HSV-1 and HSV-2 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 MOL2160
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 cutaneous and mucocutaneous lesion swab specimens without nucleic acid extraction. The system consists of the Simplexa™ HSV 1 & 2 Direct assay, the LIAISON® MDX (with LIAISON® MDX 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.
Here's a breakdown of the acceptance criteria and study information for the Simplexa™ HSV 1 & 2 Direct device, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria (e.g., "PPA must be ≥ 95%"). Instead, it presents the "Clinical Agreement" results from validation studies and implies that these figures demonstrate acceptable performance for clearance. Therefore, the "acceptance criteria" listed below are inferred from the reported performance, representing the observed outcomes deemed sufficient for the device to be considered substantially equivalent.
| Metric (Target) | Acceptance Criteria (Implied from Performance) | HSV-1 Cutaneous Swabs Reported Performance | HSV-1 Mucocutaneous Swabs Reported Performance | HSV-2 Cutaneous Swabs Reported Performance | HSV-2 Mucocutaneous Swabs Reported Performance |
|---|---|---|---|---|---|
| Positive Percent Agreement (PPA) - Prospective | N/A (Observed: 97.0% - 100.0%) | 100.0% (30/30)(95% CI: 88.7%-100.0%) | 98.2% (162/165)(95% CI: 94.4%-99.6%) | 97.0% (32/33)(95% CI: 84.4%-99.5%) | 99.5% (193/194)(95% CI: 97.1%-100.0%) |
| Negative Percent Agreement (NPA) - Prospective | N/A (Observed: 96.3% - 97.9%) | 96.3% (182/189)(95% CI: 92.6%-98.5%) | 97.5% (703/721)(95% CI: 96.1%-98.4%) | 97.9% (182/186)(95% CI: 94.6%-99.2%) | 96.7% (669/692)(95% CI: 95.1%-97.8%) |
| Positive Percent Agreement (PPA) - Retrospective | N/A (Observed: 100.0%) | 100.0% (26/26)(95% CI: 87.1%-100.0%) | 100.0% (32/32)(95% CI: 89.3%-100.0%) | 100.0% (29/29)(95% CI: 88.3%-100.0%) | 100.0% (22/22)(95% CI: 85.1%-100.0%) |
| Negative Percent Agreement (NPA) - Retrospective | N/A (Observed: 98.9% - 100.0%) | 98.9% (91/92)(95% CI: 94.1%-99.8%) | 99.1% (113/114)(95% CI: 95.2%-100.0%) | 100.0% (89/89)(95% CI: 95.9%-100.0%) | 100.0% (124/124)(95% CI: 97.0%-100.0%) |
Note on "Acceptance Criteria": The document provides the study results directly. For diagnostics, these agreement percentages are typically compared against pre-specified acceptance criteria. The absence of explicit acceptance criteria in the provided text implies that the reported performance was considered adequate for FDA clearance.
2. Sample Size Used for the Test Set and Data Provenance
- Prospective Study 1 (K150962 data, re-used):
- Original Collected: 718 samples
- Evaluated: 696 samples (after removals for various reasons like not tested, invalid results, internal control failure, wrong sample type, insufficient volume, control issues, non-enrollable)
- Data Provenance: From 6 geographically diverse locations, prospectively collected from May 28, 2014, through December 4, 2014.
- Prospective Study 2 (K173798 data):
- Original Collected: 514 samples
- Evaluated:
- 511 samples for Simplexa™ HSV 1 & 2 Direct
- 512 samples for culture method
- 510 samples for bi-directional sequencing method (after removals for EC505 codes, insufficient volume, daily control issues, non-enrollable)
- Data Provenance: From 4 geographically diverse sites, prospectively collected from July 24, 2017, through October 11, 2017.
- Retrospective Study:
- Evaluated: 174 Cutaneous HSV-1 swabs, 174 Mucocutaneous HSV-2 swabs, and 17 samples from unknown locations.
- Data Provenance: Retrospectively collected from June 6, 2011, to May 17, 2014, and February 21, 2017, through July 17, 2017.
All clinical samples were cutaneous and mucocutaneous lesion swabs from patients with signs and symptoms of HSV-1 or HSV-2 infection.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the number or qualifications of experts for establishing ground truth. The ground truth was established using a "composite comparator algorithm" rather than expert opinion alone.
4. Adjudication Method for the Test Set
The ground truth was established using a composite comparator algorithm based on a "2 out of 3 rule":
- Components: Culture, bi-directional sequencing, and an FDA-cleared NAAT (Nucleic Acid Amplification Test).
- Method: Any sample yielding a positive result by either sequencing or culture was then tested on an FDA-cleared NAAT. A "2 out of 3 rule" (implying agreement between at least two of the three methods) was used to determine the final composite results.
- Note: For culture, HSV-2 was tested first. If positive for HSV-2, no further culture testing was done (meaning dual positives could not be identified by culture alone).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not explicitly done. The study focuses on evaluating the device's performance against a composite reference method, not on human reader performance with or without AI assistance. The device is a molecular diagnostic assay, not an AI-assisted diagnostic tool for human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies presented are for the standalone performance of the Simplexa™ HSV 1 & 2 Direct assay, which is a real-time PCR system. This system performs direct amplification, detection, and differentiation of HSV-1 and HSV-2 DNA from unprocessed swab specimens, without requiring human interpretation of results beyond reading the instrument's output. The "algorithm" here refers to the PCR assay's mechanics and the LIAISON® MDX instrument's software for detection.
7. The Type of Ground Truth Used
The ground truth for the clinical studies was a composite comparator algorithm consisting of:
- Cell culture
- Bi-directional sequencing
- An FDA-cleared NAAT
This is considered a robust method for establishing ground truth in molecular diagnostics, combining phenotypic (culture) and genotypic (sequencing, NAAT) evidence.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning, as this is a molecular diagnostic assay cleared through substantial equivalence, not an AI/ML-based device requiring separate training and test sets in that sense. The analytical studies (reproducibility, LoD, cross-reactivity, interference) use contrived samples and defined panels. The "clinical agreement" uses the prospective and retrospective patient samples as the validation/test sets to demonstrate performance against the composite reference standard.
9. How the Ground Truth for the Training Set Was Established
As stated above, no "training set" in the AI/ML context is described. For the analytical studies, the "ground truth" (e.g., presence/absence and concentration of a virus, presence of cross-reactants/interferents) was established by using:
- Quantified stocks of HSV-1 and HSV-2 (for Limit of Detection, Analytical Reactivity).
- Known concentrations of various microorganisms and substances (for Cross-Reactivity and Interference studies).
- Contrived sample pools with known viral loads (for Reproducibility and Competitive Interference).
{0}------------------------------------------------
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo in blue, with the words "U.S. FOOD & DRUG" stacked on top of the word "ADMINISTRATION".
March 14, 2018
DiaSorin Molecular LLC Sharon Young Senior Regulatory Affairs Specialist 11331 Valley View Street Cypress, California 90630
Re: K173798
Trade/Device Name: Simplexa HSV 1 & 2 Direct, Simplexa HSV 1 & 2 Positive Control Pack Regulation Number: 21 CFR 866.3309 Regulation Name: Herpes Virus Nucleic Acid-Based Cutaneous and Mucocutaneous Lesion Panel Regulatory Class: Class II Product Code: PGI Dated: December 12, 2017 Received: December 14, 2017
Dear Sharon 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 Part 801 and Part 809); medical device 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
{1}------------------------------------------------
Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Steven R. Gitterman -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
{2}------------------------------------------------
Indications for Use
510(k) Number (if known)
Device Name
Simplexa™ HSV 1 & 2 Direct MOL2150 and Simplexa™ HSV 1 & 2 Positive Control Pack MOL2160
Indications for Use (Describe)
Simplexa™ HSV 1 & 2 Direct MOL2150
The DiaSorin Molecular Simplexa™ HSV 1 & 2 Direct assay is intended for use on the LIAISON® MDX instrument for the qualitative detection and differentiation of herpes simplex virus (HSV-2) DNA present in mucocutaneous and cutaneous lesion swabs from patients with signs and symptoms of HSV-1 or HSV-2 infection. This test is an aid in the differential diagnosis of HSV-1 and HSV-2 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 MOL2160
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.
Type of Use (Select one or both, as applicable)
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) |
|---|
| ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
{3}------------------------------------------------
Image /page/3/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo features a stylized DNA double helix in shades of green and blue on the left. To the right of the helix are the words "DiaSorin" in a dark blue, sans-serif font, with the word "Molecular" underneath in a lighter green color. The overall design is clean and modern, suggesting a company focused on molecular diagnostics or related fields.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 March 9. 2018 Page 1 of 20
| Applicant | DiaSorin Molecular LLC.11331 Valley View StreetCypress, California 90630USA |
|---|---|
| Establishment Registration No. | 2023365 |
| Contact Person | Sharon Youngtel 562.240.6680fax 562.240.6529Sharon.Young@DiaSorin.com |
| Summary Date | March 9, 2018 |
| Proprietary Name | Simplexa™ HSV 1 & 2 Direct MOL2150 and Simplexa™ HSV 1 & 2Positive Control Pack MOL2160 |
| Generic Name | HSV 1 & 2 nucleic acid |
| Classification RegulationProduct Code | PGI |
| Regulation Number | 866.3309 |
| Regulation name | Herpes Virus (VZV, HSV1, HSV2), DNA Detection Assay forCutaneous and Mucocutaneous Lesion Samples |
| Predicate Devices | Lyra® Direct HSV 1 + 2/VZV Assay K133448 |
Intended Use
Simplexa™ HSV 1 & 2 Direct
The DiaSorin Molecular Simplexa™ HSV 1 & 2 Direct assay is intended for use on the LIAISON® MDX instrument for the qualitative detection and differentiation of herpes simplex virus (HSV-1 and HSV-2) DNA present in mucocutaneous and cutaneous lesion swabs from patients with signs and symptoms of HSV-1 or HSV-2 infection. This test is an aid in the differential diagnosis of HSV-1 and HSV-2 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 cutaneous and mucocutaneous lesion swab specimens without nucleic acid extraction. The system consists of the Simplexa™ HSV 1 & 2 Direct assay, the LIAISON® MDX (with LIAISON® MDX 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.
{4}------------------------------------------------
Image /page/4/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo consists of a green and blue DNA helix on the left, followed by the text "DiaSorin" in blue and "Molecular" in green. The text is aligned to the right of the DNA helix.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 March 9, 2018 Page 2 of 20
Simplexa™ HSV 1 & 2 Direct REF MOL2150
| Component Name | REF | EC SYMBOLON LABEL | AbbreviatedName | CapColor | Numberof Vials | ReactionsperVial/Kit | Volumeper Vial | |
|---|---|---|---|---|---|---|---|---|
| Simplexa™ HSV 1 & 2 DirectReaction Mix | MOL2151 | REAG | C | RM | Brown | 24 | 1/24 | 50 μL |
Component Description
| Kit Component | Contents | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Simplexa™ HSV 1& 2 Direct ReactionMix (RM) | DNA polymerase, buffer, dNTPs, template DNA (Internal Control) dye-labeled fluorescentprobe-primers specific for detection of HSV-1 and/or HSV-2 and for the DNA InternalControl. | ||||||||||||||||||||
| Target ProbeFluorophore(Dye) Excitation(nm) Emission(nm) Targeted Gene HSV-1 CFR610 590 610 HSV-1 DNApolymerase HSV-2 FAM 495 520 HSV-2 DNApolymerase DNA InternalControl Q670 644 670 NA | |||||||||||||||||||||
| Simplexa™ HSV 1& 2 Kit BarcodeCard | Assay specific parameters. |
Simplexa™ HSV 1 & 2 Positive Control Pack REF MOL2160
| Component Name | REF | Description | Cap Color | Numberof Vials | Reactions perVial/Kit | Volume perVial |
|---|---|---|---|---|---|---|
| Simplexa™ HSV 1 & 2Direct Positive Control | MOL2161 | Inactivated HSV1 and 2 viruses | Red | 10 | 1/10 | 100 µL |
Direct Amplification Disc kit REF MOL1455
| Component Name | REF | Description | Number ofDiscs | Reactionsper Disc/Kit |
|---|---|---|---|---|
| Direct Amplification Disc | MOL1452 | Direct Amplification Disc for theprocessing of up to 8 individual controlsor specimens | 3 | 8/24 |
{5}------------------------------------------------
Image /page/5/Picture/0 description: The image contains the logo for DiaSorin Molecular. The logo consists of a green and blue DNA helix graphic on the left, followed by the text "DiaSorin" in dark blue. Below "DiaSorin" is the word "Molecular" in green.
510(k) Summary
March 9, 2018 Page 3 of 20
Predicate Device Information
| Table of Similarities | ||
|---|---|---|
| Predicate | Device | |
| Name | Lyra® Direct HSV 1 + 2/VZV AssayK133448 | Simplexa™ HSV1 & 2 Direct |
| IntendedUse | The Lyra® Direct HSV 1 + 2/VZV Assay is anin vitro multiplex Real-Time PCR test forqualitative detection and differentiation ofherpes simplex virus type 1, herpes simplexvirus type 2, and varicella-zoster virus DNAisolated and purified from cutaneous ormucocutaneous lesion samples obtained fromsymptomatic patients suspected of activeherpes simplex virus 1, herpes simplex virus 2and/or varicella-zoster infection. The Lyra®Direct HSV 1 + 2/VZV Assay is intended to aidin the diagnosis of herpes simplex virus 1,herpes simplex virus 2 and varicella-zostervirus active cutaneous or mucocutaneousinfections. Negative results do not precludeherpes simplex virus 1, herpes simplex virus 2and varicella-zoster virus infections and shouldnot be used as the sole basis for diagnosis,treatment or other management decisions. TheLyra® Direct HSV 1 + 2/VZV Assay is notintended for use with cerebrospinal fluid or toaid in the diagnosis of HSV or VZV infectionsof the central nervous system (CNS). TheLyra® Direct HSV 1 + 2/VZV Assay is notintended for use in prenatal screening. Thedevice is not intended for point-of-care use. | The DiaSorin Molecular Simplexa™ HSV 1 & 2Direct assay is intended for use on the LIAISON®MDX instrument for the qualitative detection anddifferentiation of herpes simplex virus (HSV-1 andHSV-2) DNA present in mucocutaneous andcutaneous lesion swabs from patients with signsand symptoms of HSV-1 or HSV-2 infection. Thistest is an aid in the differential diagnosis of HSV-1and HSV-2 infections.The assay is not intended for use as a screeningtest for the presence of HSV-1 and HSV-2 inblood or blood products. The assay is forprofessional use onlySimplexa™ HSV 1 & 2 Positive Control PackThe Simplexa™ HSV 1 & 2 Positive Control Packis intended to be used as a control with theSimplexa™ HSV 1 & 2 Direct kit.This control is not intended for use with otherassays or systems. |
| SampleTypes | Cutaneous or mucocutaneous lesion samples | Same |
| ExtractionMethods | None | Same |
| AssayMethodology | PCR-based system for detecting the presenceor absence of viral DNA in clinical specimens. | Same |
| DetectionTechniques | Multiplex assay using different reporter dyesfor each target. | Same |
| Table of Differences | ||
| Name | Predicate | Candidate |
| Lyra® Direct HSV 1 + 2/VZV AssayK133448 | Simplexa™ HSV1 & 2 Direct | |
| AssayTargets | HSV-1: glycoprotein G, HSV-2: glycoprotein G,VZV: ORF6: DNA-helicase primase. | Well conserved region of the polymerase genesfor HSV-1 and HSV-2. |
{6}------------------------------------------------
Image /page/6/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo consists of a green and blue DNA helix on the left, with the words "DiaSorin" in dark blue on the top right. Below "DiaSorin" is the word "Molecular" in green.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 March 9. 2018 Page 4 of 20
ANALYTICAL STUDIES
Results of the analytical studies performed were combined with analytical results from K150962.
REPRODUCIBILITY
Reproducibility studies were not conducted again for the purposes of this submission and the results from original submission K150962 are shown below.
Reproducibility for the Simplexa™ HSV 1 & 2 Direct assay was evaluated. Three investigative sites assessed the device's inter-site, inter-day and interlintra-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 negative approximately 95% of the time. The assays were performed in triplicate on 5 different days. Each site had 2 operators; each operator assayed the entire sample panel and positive control once per day, for a total of 2 sets of data per day. Combined results for all sites are presented in the tables below.
| Site - 1 | Site - 2 | Site - 3 | Total % Agreement With Expected Results | 95% CI | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | ||||
| HSV-1 Low Positive | 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 to 100.0% | ||
| HSV-1 Medium Positive | 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 to 100.0% | ||
| HSV-1Result | HSV-2 Low Positive | 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 to 99.8% | |
| HSV-2 Medium Positive | 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 to 99.8% | ||
| High Negative | 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 to 96.9% | ||
| Positive Control | 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 to 100.0% | ||
| Total Agreement | 99.4% (179/180) | 98.3% (177/180) | 97.8% (175/179) | 98.5% (531/539) | 97.1 to 99.2% | ||||||||
| a) Expected Results of HSV-2 Low Positive, HSV-2 Medium Positive and High Negative samples are "Negative" for HSV-1. | |||||||||||||
| 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 | ||
| HSV-2Result | HSV-1 LowPositive | 100.0%(30/30) | NA | NA | 100.0%(30/30) | 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) | NA | NA | 100.0%(30/30) | NA | NA | 100.0%(30/30)b | NA | NA | 100.0%(90/90) | 95.9 to100.0% | ||
| HSV-2 LowPositive | 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% | ||
| High Negative | 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. | |||||||||||||
| 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% |
{7}------------------------------------------------
Image /page/7/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo features a green and blue DNA helix graphic on the left. To the right of the graphic is the text "DiaSorin" in blue, with the word "Molecular" underneath in green.
510(k) Summary
March 9, 2018
Page 5 of 20
{8}------------------------------------------------
Image /page/8/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo consists of a stylized DNA double helix on the left, with the words "DiaSorin" in a dark blue sans-serif font to the right of the helix. Below "DiaSorin" is the word "Molecular" in a green sans-serif font. The DNA helix is colored with a gradient that transitions from green at the top to blue at the bottom.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 March 9. 2018 Page 6 of 20
ANALYTICAL SENSITIVITY/LIMIT OF DETECTION
Analytical Sensitivity/Limit of Detection studies were not conducted again for the purposes of this submission and the results from original submission K150962 are shown below.
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 cutaneous and mucocutaneous swab matrix. LoD was determined to be the lowest concentration that could be detected positive > 95% of the time.
| Virus Strain | LoD Concentration(TCID50/mL) | Qualitative Results(#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 |
ANALYTICAL REACTIVITY / CROSS REACTIVITY
Analytical Reactivity Cutaneous and Mucocutaneous Swab Sample Type
Analytical Reactivity studies were not conducted again for the purposes of this submission and the results from original submission K150962 are shown below.
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 cutaneous swab matrix containing male and female cutaneous and mucocutaneous 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.
| HSV Strain/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) Cutaneous and Mucocutaneous 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 cutaneous or mucocutaneous swabs. A total of 71 potential cross-reactants were spiked into negative cutaneous and mucocutaneous swab matrix and assayed in triplicate. No cross-reactivity was observed.
{9}------------------------------------------------
Image /page/9/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo features a stylized DNA double helix in shades of green and blue on the left. To the right of the helix are the words "DiaSorin" in a dark blue, sans-serif font, with the word "Molecular" underneath in a lighter green color.
510(k) Summary
March 9, 2018
Page 7 of 20
| No. | Microorganism | Tested Concentration | Qualitative Result(#Detected/#Total) | |
|---|---|---|---|---|
| HSV-1 | HSV-2 | |||
| 1 | Baseline | N/A | 35/35 | 35/35 |
| 2 | Acinetobacter calcoaceticus | 1.00 X 106 CFU/mL | 0/3 | 0/3 |
| 3 | Acinetobacter Iwoffii | 1.00 X 106 CFU/mL | 0/3 | 0/3 |
| 4 | Bacteroides fragilis | 1.00 X 106 CFU/mL | 0/3 | 0/3 |
| 5 | Bacteroides ureolyticus** | N/A | N/A | N/A |
| 6 | Bordetella bronchiseptica | 1.00 X 106 CFU/mL | 0/3 | 0/3 |
| 7 | Bordetella pertussis | 1.00 X 106 CFU/mL | 0/3 | 0/3 |
| 8 | Candida albicans | 1.00 X 106 CFU/mL | 0/3 | 0/3 |
| 9 | Candida glabrata | 1.00 X 106 CFU/mL | 0/3 | 0/3 |
| 10 | Candida guilliermondii | 1.00 x 106 CFU/mL | 0/3 | 0/3 |
| 11 | Candida krusei | 1.00 x 106 CFU/mL | 0/3 | 0/3 |
| 12 | Candida lusitaniae | 1.00 x 106 CFU/mL | 0/3 | 0/3 |
| 13 | Candida parapsilosis | 1.00 x 106 CFU/mL | 0/3 | 0/3 |
| 14 | Candida tropicalis | 1.00 x 106 CFU/mL | 0/3 | 0/3 |
| 15 | Chlamydophila pneumoniae | 1.00 x 106 IFU/mL | 0/3 | 0/3 |
| 16 | Chlamydia trachomatis | 1.00 X 106 IFU/mL | 0/3 | 0/3 |
| 17 | Clostridium sordellii | 1.00 X 106 CFU/mL | 0/3 | 0/3 |
| 18 | Clostridium perfringens | 1.00 x 106 CFU/mL | 0/3 | 0/3 |
| 19 | Corynebacterium genitalium | 1.00 X 106 CFU/mL | 0/3 | 0/3 |
| 20 | Coronavirus (HCoV OC43) | 1.00 x 105 TCID50/mL | 0/3 | 0/3 |
| 21 | Corynebacterium diphtheriae | 1.00 x 106 CFU/mL | 0/3 | 0/3 |
| 22 | Coxsackievirus B (CVB-1) | 1.00 x 105 TCID50/mL | 0/3 | 0/3 |
| 23 | Cytomegalovirus | 1.00 X 105 TCID50/mL | 0/3 | 0/3 |
| 24 | Enterobacter cloacae | 1.00 x 106 CFU/mL | 0/3 | 0/3 |
| 25 | Enterococcus faecium | 1.00 x 106 CFU/mL | 0/3 | 0/3 |
| 26 | Enterococcus faecalis vanB | 1.00 X 106 CFU/mL | 0/3 | 0/3 |
| 27 | Enterovirus 70 | 1.00 x 105 TCID50/mL | 0/3 | 0/3 |
| 28 | Enterovirus 71 | 1.00 X 105 TCID50/mL | 0/3 | 0/3 |
| 29 | Epstein Barr Virus (B95-8) | 1.00 X 105 copies/mL | 0/3 | 0/3 |
| 30 | Escherichia coli O157H7 | 1.00 X 106 CFU/mL | 0/3 | 0/3 |
| 31 | Fusobacterium nucleatum | 1.00 x 106 CFU/mL | 0/3 | 0/3 |
| 32 | Gardnerella vaginalis | 1.00 X 106 CFU/mL | 0/3 | 0/3 |
| 33 | Haemophilus ducreyi** | N/A | N/A | N/A |
| 34 | Haemophilus influenzae (Type A) | 1.00 x 106 CFU/mL | 0/3 | 0/3 |
| 35 | Hepatitis B | 1.00 X 105 IU/mL | 0/3 | 0/3 |
| 36 | Hepatitis C | 1.00 X 105 IU/mL | 0/3 | 0/3 |
| 37 | HHV-6 (Z29 Strain) | 1.00 X 105 TCID50/mL | 0/3 | 0/3 |
| 38 | HHV-7 SB | 1.00 X 105 TCID50/mL | 0/3 | 0/3 |
| No. | Microorganism | Tested Concentration | Qualitative Result(#Detected/#Total) | |
| HSV-1 | HSV-2 | |||
| 39 | HIV-1 IIIB | $1.00 X 10^5$ copies/mL | 0/3 | 0/3 |
| 40 | HIV-2 NIHZ* | Not Available | 0/3 | 0/3 |
| 41 | HPV18 Recombinant | $1.00 X 10^5$ PFU/mL | 0/3 | 0/3 |
| 42 | Human metapneumovirus | $1.00 X 10^5$ TCID50/mL | 0/3 | 0/3 |
| 43 | Lactobacillus acidophilus | $1.00 X 10^6$ CFU/mL | 0/3 | 0/3 |
| 44 | Legionella pneumophila | $1.00 X 10^6$ CFU/mL | 0/3 | 0/3 |
| 45 | Mobiluncus mulieris | $1.00 X 10^6$ CFU/mL | 0/3 | 0/3 |
| 46 | Moraxella catarrhalis | $1.00 X 10^6$ CFU/mL | 0/3 | 0/3 |
| 47 | Mycoplasma genitalium** | N/A | N/A | N/A |
| 48 | Mycoplasma hominis | $1.00 X 10^6$ CCU/mL | 0/3 | 0/3 |
| 49 | Mycoplasma orale** | N/A | N/A | N/A |
| 50 | Mycoplasma pneumoniae | $1.00 X 10^6$ CCU/mL | 0/3 | 0/3 |
| 51 | Mycoplasma salivarium** | N/A | N/A | N/A |
| 52 | Neisseria gonorrhoeae | $1.00 X 10^6$ CFU/mL | 0/3 | 0/3 |
| 53 | Neisseria meningitides | $1.00 X 10^6$ CFU/mL | 0/3 | 0/3 |
| 54 | Prevotella melaninogenica | $1.00 X 10^6$ CFU/mL | 0/3 | 0/3 |
| 55 | Proteus vulgaris | $1.00 X 10^6$ CFU/mL | 0/3 | 0/3 |
| 56 | Respiratory syncytial virus A | $1.00 X 10^5$ TCID50/mL | 0/3 | 0/3 |
| 57 | Respiratory syncytial virus B | $1.00 X 10^5$ TCID50/mL | 0/3 | 0/3 |
| 58 | Rubella | $1.00 X 10^5$ TCID50/mL | 0/3 | 0/3 |
| 59 | Salmonella enteritidis** | N/A | N/A | N/A |
| 60 | Salmonella typhimurium | $1.00 X 10^6$ CFU/mL | 0/3 | 0/3 |
| 61 | Staphylococcus aureus (MRSA), ATCC700699 | $1.00 X 10^6$ CFU/mL | 0/3 | 0/3 |
| 62 | Staphylococcus epidermidis (MRSE),ATCC 29887 | $1.00 X 10^6$ CFU/mL | 0/3 | 0/3 |
| 63 | Streptococcus mutans | $1.00 X 10^6$ CFU/mL | 0/3 | 0/3 |
| 64 | Streptococcus salivarius | $1.00 X 10^6$ CFU/mL | 0/3 | 0/3 |
| 65 | Staphylococcus saprophyticus | $1.00 X 10^6$ CFU/mL | 0/3 | 0/3 |
| 66 | Streptococcus mitis | $1.00 X 10^6$ CFU/mL | 0/3 | 0/3 |
| 67 | Streptococcus pyogenes, M1 | $1.00 X 10^6$ CFU/mL | 0/3 | 0/3 |
| 68 | Toxoplasma gondii | $1.00 X 10^6$ tachyzooites/mL | 0/3 | 0/3 |
| 69 | Treponema pallidum** | N/A | N/A | N/A |
| 70 | Trichomonas vaginalis | $1.00 X 10^6$ trophozoites/ml | 0/3 | 0/3 |
| 71 | Ureaplasma urealyticum | $1.00 X 10^6$ CCU/mL | 0/3 | 0/3 |
| 72 | VZV | $1.00 X 10^5$ copies/mL | 0/3 | 0/3 |
{10}------------------------------------------------
Image /page/10/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo features a stylized DNA double helix in shades of green and blue on the left. To the right of the DNA helix are the words "DiaSorin" in a dark blue, sans-serif font, stacked above the word "Molecular" in a lighter green, sans-serif font.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 March 9, 2018
Page 8 of 20
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.
** Microorganism was not available for testing therefore in silico NCBI BLAST analysis was performed and found no cross reactivity.
N/A = Not applicable
{11}------------------------------------------------
Image /page/11/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo consists of a green and blue DNA helix on the left, followed by the text "DiaSorin" in dark blue and "Molecular" in green. The text is aligned to the right of the DNA helix.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 March 9. 2018 Page 9 of 20
INTERFERENCE
Cutaneous and Mucocutaneous Swab Sample Type
The performance of the Simplexa™ HSV 1 & 2 Direct assay was evaluated with potentially interfering substances that may be present on cutaneous and mucocutaneous swabs at the concentrations indicated in the table below. A total of 24 potentially interfering substances were tested in a low positive HSV-1 and HSV-2 sample (4 times LoD) in negative cutaneous and mucocutaneous swab matrix containing male and female cutaneous and mucocutaneous swabs and assayed in triplicate. No interference was observed.
| Potential Interferent | InterferentConcentration | # Detected/# Total | |
|---|---|---|---|
| HSV-1 | HSV-2 | ||
| Acetaminophen | 7% w/v | 3/3 | 3/3 |
| Albumin | 10 mg/mL | 3/3 | 3/3 |
| Buffy coat | 7% v/v | 3/3 | 3/3 |
| Carmex® Original Lip Balm (Camphor,1.7%; Menthol, 0.7%) | 10% v/v | 3/3 | 3/3 |
| Casein | 10 mg/mL | 3/3 | 3/3 |
| Chlorpheniramine maleate | 5 mg/mL | 3/3 | 3/3 |
| Cold-EEZE® Cold Remedy plus Throat(Zincum Gluconicum 2X) | 10% v/v | 3/3 | 3/3 |
| Cornstarch | 1.25 mg/mL | 3/3 | 3/3 |
| Desitin (Zinc Oxide, 40%) | 7% w/v | 3/3 | 3/3 |
| Dextromethorphan hydrobromide | 10 mg/mL | 3/3 | 3/3 |
| Foscarnet | 1.25 mg/mL | 3/3 | 3/3 |
| Ganciclovir | 2.5 mg/mL | 3/3 | 3/3 |
| Lanacane Benzethonium chloride, 0.2%;Benzocaine, 20%) | 7% v/v | 3/3 | 3/3 |
| Lip Clear® Lysine (Zinc Oxide, 1.2%) | 7% w/v | 3/3 | 3/3 |
| Listerine (Eucalyptol, 0.092%; Menthol,0.042%; Methyl salicylate, 0.060%;Thymol, 0.064%) | 7% v/v | 3/3 | 3/3 |
| Miconazole 3 (Miconazole nitrate, 2%) | 7% w/v | 3/3 | 3/3 |
| Seminal fluid | 7% w/v | 3/3 | 3/3 |
| Spermicide | 7% w/v | 3/3 | 3/3 |
| Tioconazole | 7% w/v | 3/3 | 3/3 |
| Toothpaste | 7% w/v | 3/3 | 3/3 |
| Valganciclovir | 2.5 mg/mL | 3/3 | 3/3 |
| Whole Blood | 10% v/v | 3/3 | 3/3 |
| Urine | 10% v/v | 3/3 | 3/3 |
| KY Jelly | 5% v/v | 3/3 | 3/3 |
{12}------------------------------------------------
Image /page/12/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo features a stylized DNA double helix in shades of green and blue on the left. To the right of the helix are the words "DiaSorin" in a bold, dark blue font, with the word "Molecular" underneath in a lighter green color. The overall design is clean and professional, suggesting a company focused on molecular diagnostics or related fields.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 March 9. 2018 Page 10 of 20
COMPETITIVE INTERFERENCE Cutaneous and Mucocutaneous Swab Sample Type
Competitive interference studies were not conducted again for the purposes of this submission and the results from original submission K150962 are shown below.
Competitive interference was studied to evaluate the effects of clinically relevant co-infections with each of the analytes detected by the Simplexa™ HSV 1 & 2 Direct assay. The study assessed whether a high concentration of one virus in the sample could potentially affect the Simplexa™ HSV 1 & 2 Direct assay performance for another target present at low levels. A low sample was contrived at approximately 4 times LoD for each target (HSV-1 McIntryre strain and HSV-2 G strain), and a baseline Ct was determined for each sample. Each potential concomitant infecting virus was spiked into the low level sample and assayed in triplicate. Baseline sample results are also shown below. No competitive interference was observed.
| Baseline (Low Level) | Competitive Interferent(High Concentration) | Qualitative Results(#Detected/#Total) | |||
|---|---|---|---|---|---|
| Strain | Concentration(TCID50/mL) | Strain | Concentration(TCID50/mL) | HSV-1 | HSV-2 |
| HSV-1 McIntyre | 16 | HSV-2 G | 0 | 5/5 | 0/5 |
| HSV-1 McIntyre | 16 | HSV-2 G | 1.00 X 106 | 3/3 | 3/3 |
| HSV-2 G | 8 | HSV-1 McIntyre | 0 | 0/5 | 5/5 |
| HSV-2 G | 8 | HSV-1 McIntyre | 1.71 X 103 | 3/3 | 3/3 |
INHIBITION BY OTHER MICROORGANISMS - Cutaneous and Mucocutaneous Swab Sample Type
The Simplexa™ HSV 1 & 2 Direct assay was evaluated by testing the ability to identify HSV-1 and HSV-2 viruses when other potentially inhibitory organisms are present. The panel of 71 potentially inhibitory organisms was individually spiked into a pool with a low concentration (approximately 4 times LoD) of HSV-1 and HSV-2 in cutaneous and mucocutaneous swab matrix. Each microorganism sample was initially tested in triplicate and if any one of the replicates was "Not Detected" for either the HSV-1 or the HSV-2 targets then five additional replicates would be tested to confirm if any inhibition was caused by the microorganism. If the majority (>4/8) replicates were "Not Detected" then an inhibitory effect would be determined. None of the microorganisms caused >4/8 of the replicates to be "Not Detected". In silico NCBI BLAST analysis was performed for 7 potential inhibitory organisms.
| No. | Microorganism | Tested Concentration | Qualitative Result(#Detected/#Total) | |
|---|---|---|---|---|
| HSV-1 | HSV-2 | |||
| 1 | Baseline | Not Applicable | 35/35 | 35/35 |
| 2 | Acinetobacter calcoaceticus | 1.00 x 106 CFU/mL | 3/3 | 3/3 |
| 3 | Acinetobacter Iwoffii | 1.00 x 106 CFU/mL | 3/3 | 3/3 |
| 4 | Bacteroides fragilis | 1.00 X 106 CFU/mL | 3/3 | 3/3 |
| 5 | Bacteroides ureolyticus** | N/A | N/A | N/A |
| 6 | Bordetella bronchiseptica | 1.00 x 106 CFU/mL | 3/3 | 3/3 |
| 7 | Bordetella pertussis | 1.00 x 106 CFU/mL | 3/3 | 3/3 |
| 8 | Candida albicans | 1.00 X 106 CFU/mL | 3/3 | 3/3 |
| 9 | Candida glabrata | 1.00 x 106 CFU/mL | 3/3 | 3/3 |
| 10 | Candida guilliermondii | 1.00 x 106 CFU/mL | 3/3 | 3/3 |
| 11 | Candida krusei | 1.00 x 106 CFU/mL | 3/3 | 3/3 |
| No. | Microorganism | Tested Concentration | Qualitative Result(#Detected/#Total) | |
| HSV-1 | HSV-2 | |||
| 12 | Candida lusitaniae | $1.00 x 10^6$ CFU/mL | 3/3 | 3/3 |
| 13 | Candida parapsilosis | $1.00 x 10^6$ CFU/mL | 3/3 | 3/3 |
| 14 | Candida tropicalis | $1.00 x 10^6$ CFU/mL | 3/3 | 3/3 |
| 15 | Chlamydophila pneumoniae | $1.00 x 10^6$ IFU/mL | 3/3 | 3/3 |
| 16 | Chlamydia trachomatis | $1.00 X 10^6$ IFU/mL | 3/3 | 3/3 |
| 17 | Clostridium sordellii | $1.00 X 10^6$ CFU/mL | 3/3 | 3/3 |
| 18 | Clostridium perfringens | $1.00 x 10^6$ CFU/mL | 3/3 | 3/3 |
| 19 | Corynebacterium genitalium | $1.00 X 10^6$ CFU/mL | 3/3 | 3/3 |
| 20 | Coronavirus (HCOV OC43) | $1.00 x 10^5$ TCID50/mL | 3/3 | 3/3 |
| 21 | Corynebacterium diphtheriae | $1.00 x 10^6$ CFU/mL | 3/3 | 3/3 |
| 22 | Coxsackievirus B (CVB-1) | $1.00 x 10^5$ TCID50/mL | 3/3 | 3/3 |
| 23 | Cytomegalovirus | $1.00 X 10^5$ TCID50/mL | 3/3 | 3/3 |
| 24 | Enterobacter cloacae | $1.00 x 10^6$ CFU/mL | 3/3 | 3/3 |
| 25 | Enterococcus faecium | $1.00 x 10^6$ CFU/mL | 3/3 | 3/3 |
| 26 | Enterococcus faecalis vanB | $1.00 X 10^6$ CFU/mL | 3/3 | 3/3 |
| 27 | Enterovirus 70 | $1.00 x 10^5$ TCID50/mL | 3/3 | 3/3 |
| 28 | Enterovirus 71 | $1.00 X 10^5$ TCID50/mL | 3/3 | 3/3 |
| 29 | Epstein Barr Virus (B95-8) | $1.00 X 10^5$ copies/mL | 3/3 | 3/3 |
| 30 | Escherichia coli O157H7 | $1.00 X 10^6$ CFU/mL | 3/3 | 3/3 |
| 31 | Fusobacterium nucleatum | $1.00 x 10^6$ CFU/mL | 3/3 | 3/3 |
| 32 | Gardnerella vaginalis | $1.00 X 10^6$ CFU/mL | 3/3 | 3/3 |
| 33 | Haemophilus ducreyi** | N/A | N/A | N/A |
| 34 | Haemophilus influenzae (Type A) | $1.00 x 10^6$ CFU/mL | 3/3 | 3/3 |
| 35 | Hepatitis B | $1.00 X 10^5$ IU/mL | 3/3 | 3/3 |
| 36 | Hepatitis C | $1.00 X 10^5$ IU/mL | 3/3 | 3/3 |
| 37 | HHV-6 (Z29 Strain) | $1.00 X 10^5$ TCID50/mL | 3/3 | 3/3 |
| 38 | HHV-7 SB | $1.00 X 10^5$ TCID50/mL | 3/3 | 3/3 |
| 39 | HIV-1 IIIB | $1.00 X 10^5$ copies/mL | 3/3 | 3/3 |
| 40 | HIV-2 NIHZ* | N/A | 3/3 | 3/3 |
| 41 | HPV18 Recombinant | $1.00 X 10^5$ PFU/mL | 3/3 | 3/3 |
| 42 | Human metapneumovirus | $1.00 x 10^5$ TCID50/mL | 3/3 | 3/3 |
| 43 | Lactobacillus acidophilus | $1.00 X 10^6$ CFU/mL | 3/3 | 3/3 |
| 44 | Legionella pneumophila | $1.00 x 10^6$ CFU/mL | 3/3 | 3/3 |
| 45 | Mobiluncus mulieris | $1.00 X 10^6$ CFU/mL | 3/3 | 3/3 |
| 46 | Moraxella catarrhalis | $1.00 x 10^6$ CFU/mL | 3/3 | 3/3 |
| 47 | Mycoplasma genitalium** | N/A | N/A | N/A |
| 48 | Mycoplasma hominis | $1.00 X 10^6$ CCU/mL | 3/3 | 3/3 |
| 49 | Mycoplasma orale** | Not Applicable | N/A | N/A |
| 50 | Mycoplasma pneumoniae | $1.00 x 10^6$ CCU/mL | 4/8 | 5/8 |
| No. | Microorganism | Tested Concentration | Qualitative Result(#Detected/#Total) | |
| HSV-1 | HSV-2 | |||
| 51 | Mycoplasma salivarium ** | N/A | N/A | N/A |
| 52 | Neisseria gonorrhoeae | 1.00 X 106 CFU/mL | 3/3 | 3/3 |
| 53 | Neisseria meningitides | 1.00 x 106 CFU/mL | 3/3 | 3/3 |
| 54 | Prevotella melaninogenica | 1.00 x 106 CFU/mL | 3/3 | 3/3 |
| 55 | Proteus vulgaris | 1.00 X 106 CFU/mL | 3/3 | 3/3 |
| 56 | Respiratory syncytial virus A | 1.00 x 105 TCID50/mL | 3/3 | 3/3 |
| 57 | Respiratory syncytial virus B | 1.00 x 105 TCID50/mL | 3/3 | 3/3 |
| 58 | Rubella | 1.00 X 105 TCID50/mL | 3/3 | 3/3 |
| 59 | Salmonella enteritidis ** | N/A | N/A | N/A |
| 60 | Salmonella typhimurium | 1.00 x 106 CFU/mL | 3/3 | 3/3 |
| 61 | Staphylococcus aureus (MRSA), ATCC 700699 | 1.00 X 106 CFU/mL | 3/3 | 3/3 |
| 62 | Staphylococcus epidermidis (MRSE), ATCC 29887 | 1.00 X 106 CFU/mL | 3/3 | 3/3 |
| 63 | Streptococcus mutans | 1.00 x 106 CFU/mL | 3/3 | 3/3 |
| 64 | Streptococcus salivarius | 1.00 x 106 CFU/mL | 3/3 | 3/3 |
| 65 | Staphylococcus saprophyticus | 1.00 X 106 CFU/mL | 3/3 | 3/3 |
| 66 | Streptococcus mitis | 1.00 X 106 CFU/mL | 3/3 | 3/3 |
| 67 | Streptococcus pyogenes , M1 | 1.00 X 106 CFU/mL | 3/3 | 3/3 |
| 68 | Toxoplasma gondii | 1.00 X 106 tachyzooites/mL | 3/3 | 3/3 |
| 69 | Treponema pallidum ** | N/A | N/A | N/A |
| 70 | Trichomonas vaginalis | 1.00 X 106 trophozoites/ml | 3/3 | 3/3 |
| 71 | Ureaplasma urealyticum | 1.00 X 106 CFU/mL | 3/3 | 3/3 |
| 72 | VZV | 1.00 X 105 copies/mL | 3/3 | 3/3 |
{13}------------------------------------------------
Image /page/13/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo features a stylized DNA double helix in shades of green and blue on the left. To the right of the helix are the words "DiaSorin" in dark blue, with the word "Molecular" underneath in green. The logo is clean and modern, suggesting a focus on biotechnology and molecular diagnostics.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150
Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2150 March 9, 2018
Page 11 of 20
{14}------------------------------------------------
Image /page/14/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo consists of a stylized DNA double helix in shades of green and blue on the left. To the right of the helix are the words "DiaSorin" in dark blue, with "Molecular" underneath in a lighter green color. The logo is clean and professional, suggesting a company focused on molecular diagnostics or related fields.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 March 9, 2018
Page 12 of 20
- 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.
**Microorganism was not available for testing therefore in silico NCBI BLAST analysis was performed and found no inhibition.
N/A = Not applicable.
{15}------------------------------------------------
Image /page/15/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo consists of a stylized DNA double helix in shades of green and blue on the left. To the right of the helix are the words "DiaSorin" in dark blue, with "Molecular" underneath in green. The logo is clean and modern, suggesting a company focused on molecular diagnostics or related fields.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 March 9, 2018 Page 13 of 20
CLINICAL AGREEMENT
Prospective Study 1 – Cutaneous and Mucocutaneous Swab Sample Type K150962
A total of 718 cutaneous and mucocutaneous lesion swab samples were prospectively collected May 28. 2014 through December 4, 2014 from patients with signs and symptoms of 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 were removed from the analysis because they were not tested on the tests included in the composite comparator method sufficient to generate a final comparator result. A total of 696 samples were used for the analysis. Samples were tested on Simplexa™ HSV 1 & 2 Direct at the collection sites, culture samples were sent to a central lab, and the sequencing samples were sent to DiaSorin Molecular. All samples were either tested fresh or frozen within 72 hours of sample collection. Aliquots were made from each sample; 1 aliquot was tested on Simplexa™ HSV 1 & 2 Direct at the collection site, and the remainder was sent to DiaSorin Molecular. One aliguot was sent for culture testing at an external site. 1 aliguot was used for bi-directional sequencing, and the last aliquot was held as a retain. Any sample that was not collected and frozen within 72 hours was disqualified.
The testing included 332 total runs with 638 evaluable controls, and 5 invalid control pairs. There were 718 patient samples of which 2 were not evaluable due to internal control failure, 5 not evaluable due to invalid runs. 1 was not evaluable due to wrong sample type. 1 not evaluable due to testing on a commercial instrument, 5 Insufficient Volume Errors, 3 not evaluable because of daily control issues, and 5 non-enrollable patient samples not meeting acceptance criteria (tested >72hrs post collection).
Prospective Study 2 – Cutaneous and Mucocutaneous Swab Sample Type K173798
A total of 514 cutaneous and mucocutaneous lesion swab samples were prospectively collected July 24, 2017 through October 11. 2017. These samples were collected from patients with signs and symptoms of herpes simplex virus (HSV) infection from 4 geographically diverse sites. Of the 514 samples, 511 samples were evaluable on Simplexa™ HSV 1 & 2 Direct, 512 were evaluable by the culture method, and 510 were evaluable by the bi-directional sequencing method. Samples were tested on Simplexa™ HSV 1 & 2 Direct at the collection sites, culture samples were sent to a central lab, and the sequencing samples were sent to DiaSorin Molecular. All samples were either tested fresh or frozen within 72 hours of sample collection. Aliquots were made from each sample; 1 aliquot was tested on Simplexa™ HSV 1 & 2 Direct at the collection site, and the remainder was sent to DiaSorin Molecular. One aliquot was sent for culture testing at an external site, 1 aliquot was used for bi-directional sequencing, and the last aliquot was held as a retain. Any sample that was not collected and frozen within 72 hours was disqualified.
The testing included 153 total Runs with 250 evaluable controls, and 3 invalid control pairs. There were 514 patient samples of which 2 were not evaluable due to EC505 codes from both the HSV-1 (FAM) & HSV-2 (CFR610) channel, 2 Insufficient Volume errors, 18 samples not evaluable because of daily control issues (7 samples were non-evaluable due to invalid PC control runs and 11 samples were nonevaluable due to no daily control runs) and 1 was a non-enrollable patient sample that did not meet the acceptance criteria (tested >72hrs post collection).
Retrospective Study - Cutaneous and Mucocutaneous Swab Sample Type
A total of 174 Cutaneous HSV-1 swabs, 174 Mucocutaneous HSV-2 swabs and 17 samples from unknown locations, were retrospectively collected June 6, 2011 to May 17, 2014 and February 21, 2017 through July 17, 2017. All samples were tested using the composite comparator method.
The clinical performance of the Simplexa HSV 1 & 2 Direct assay was evaluated by comparing the positive and negative percent agreement to a composite comparator algorithm consisting of culture, bidirectional sequencing and a FDA cleared NAAT. All samples yielding a positive result by either sequencing or culture were tested on an FDA cleared NAAT and a 2 out of 3 rule was used to determine the final composite results. All sites collected and tested the 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
{16}------------------------------------------------
Image /page/16/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo features a green and blue DNA helix on the left side. To the right of the helix is the company name, "DiaSorin", in blue, with the word "Molecular" underneath in green.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 March 9. 2018 Page 14 of 20
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 DiaSorin Molecular and tested in a validated bi-directional sequencing assay. Results for Simplexa™ HSV 1 & 2 Direct compared to the composite comparator algorithm are presented in the tables that follow when combined with the data from the second sample set.
Prospective Results Composite Reference Method HSV-1 Cutaneous Swabs
The table below shows HSV-1 positive and negative percent (PPA and NPA) vs. Composite Reference Method based on the observed prevalence in the study population for HSV-1 for cutaneous swabs.
| Clinical Agreement - (Cutaneous for HSV-1) | |||
|---|---|---|---|
| Simplexa™ HSV 1 & 2 DirectResults | Composite Reference Method | ||
| Detected | Not Detected | Total | |
| Detected | 30 | 7 | 37 |
| Not Detected | 0 | 182 | 182 |
| Total | 30 | 189 | 219 |
| %PPA | 100.0%(30/30)95% CI: 88.7% to 100.0% | %NPA | 96.3%(182/189)95% CI: 92.6% to 98.5% |
Prospective Results Composite Reference Method HSV-1 Mucocutaneous Swabs
The table below shows HSV-1 positive and negative percent (PPA and NPA) vs. Composite Reference Method based on the observed prevalence in the study population for HSV-1 for Mucocutaneous swabs.
| Clinical Agreement - (Mucocutaneous for HSV-1) | |||
|---|---|---|---|
| Simplexa™ HSV 1 & 2 DirectResults | Composite Reference Method | ||
| Detected | Not Detected | Total | |
| Detected | 162 | 18 | 180 |
| Not Detected | 3 | 703 | 706 |
| Total | 165 | 721 | 887 |
| %PPA | 98.2%(162/165)95% CI: 94.4% to 99.6% | %NPA | 97.5%(703/721)95% CI: 96.1% to 98.4% |
{17}------------------------------------------------
Image /page/17/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo consists of a stylized DNA double helix in shades of green and blue on the left. To the right of the helix are the words "DiaSorin" in dark blue, with the word "Molecular" underneath in green. The logo is clean and modern, suggesting a focus on biotechnology and molecular diagnostics.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 March 9, 2018 Page 15 of 20
Prospective Results Composite Reference Method HSV-2 Cutaneous Swabs
The table below shows HSV-2 positive and negative percent (PPA and NPA) vs. Composite Reference Method based on the observed prevalence in the study population for HSV-2 for cutaneous swabs.
| Clinical Agreement - (Cutaneous for HSV-2) | |||
|---|---|---|---|
| Simplexa™ HSV 1 & 2 DirectResults | Composite Reference Method | ||
| Detected | Not Detected | Total | |
| Detected | 32 | 4 | 36 |
| Not Detected | 1 | 182 | 183 |
| Total | 33 | 186 | 219 |
| %PPA | 97.0%(32/33)95% CI: 84.4% to 99.5% | %NPA | 97.9%(182/186)95% CI: 94.6% to 99.2% |
Prospective Results Composite Reference Method HSV-2 Mucocutaneous Swabs
The table below shows HSV-2 positive and negative percent (PPA and NPA) vs. Composite Reference Method based on the observed prevalence in the study population for HSV-2 for mucocutaneous swabs.
| Clinical Agreement - (Mucocutaneous for HSV-2) | |||
|---|---|---|---|
| Simplexa™ HSV 1 & 2 DirectResults | Composite Reference Method | ||
| Detected | Not Detected | Total | |
| Detected | 193 | 23 | 216 |
| Not Detected | 1 | 669 | 670 |
| Total | 194 | 692 | 886 |
| %PPA | 99.5%(193/194)95% CI: 97.1% to 100.0% | %NPA | 96.7%(669/692)95% CI: 95.1% to 97.8% |
{18}------------------------------------------------
Image /page/18/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo features a stylized DNA double helix in shades of green and blue on the left. To the right of the helix are the words "DiaSorin" in a dark blue, sans-serif font, with the word "Molecular" underneath in a lighter green color. The overall design is clean and modern, suggesting a focus on biotechnology and molecular diagnostics.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 March 9, 2018 Page 16 of 20
Retrospective Results Composite Reference Method HSV-1 Cutaneous Swabs
The table below shows HSV-1 positive and negative percent (PPA and NPA) vs. Composite Reference Method for retrospectively collected HSV-1 for cutaneous swabs.
| Clinical Agreement - (Cutaneous for HSV-1) | |||
|---|---|---|---|
| Simplexa™ HSV 1 & 2 DirectResults | Composite Reference Method | ||
| Detected | Not Detected | Total | |
| Detected | 26 | 1 | 27 |
| Not Detected | 0 | 91 | 91 |
| Total | 26 | 92 | 118 |
| %PPA | 100.0%(26/26)95% CI: 87.1% to 100.0% | %NPA | 98.9%(91/92)95% CI: 94.1% to99.8% |
Retrospective Results Composite Reference Method HSV-1 Mucocutaneous Swabs
The table below shows HSV-1 positive and negative percent (PPA and NPA) vs. Composite Reference Method for retrospectively collected HSV-1 for mucocutaneous swabs.
| Clinical Agreement - (Mucocutaneous for HSV-1) | |||
|---|---|---|---|
| Simplexa™ HSV 1 & 2 DirectResults | Composite Reference Method | ||
| Detected | Not Detected | Total | |
| Detected | 32 | 1 | 33 |
| Not Detected | 0 | 113 | 113 |
| Total | 32 | 114 | 146 |
| %PPA | 100.0%(32/32)95% CI: 89.3% to 100.0% | %NPA99.1%(113/114)95% CI: 95.2% to100.0% |
{19}------------------------------------------------
Image /page/19/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo consists of a stylized DNA helix in green and blue on the left, with the words "DiaSorin" in dark blue on the top right and "Molecular" in green below it. The logo is clean and modern, with a focus on the company's expertise in molecular diagnostics.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 March 9, 2018 Page 17 of 20
Retrospective Results Composite Reference Method HSV-2 Cutaneous Swabs
The table below shows HSV-2 positive and negative percent agreement (PPA and NPA) vs. Composite Reference Method for retrospectively collected HSV-2 for cutaneous swabs.
| Clinical Agreement - (Cutaneous for HSV-2) | |||
|---|---|---|---|
| Simplexa™ HSV 1 & 2 DirectResults | Composite Reference Method | ||
| Detected | Not Detected | Total | |
| Detected | 29 | 0 | 29 |
| Not Detected | 0 | 89 | 89 |
| Total | 29 | 89 | 118 |
| %PPA | 100.0%(29/29)95% CI: 88.3% to 100.0% | %NPA | 100.0%(89/89)95% CI: 95.9% to 100.0% |
Retrospective Results Composite Reference Method HSV-2 Mucocutaneous Swabs
The table below shows HSV-2 positive and negative percent (PPA and NPA) vs. Composite Reference Method for retrospectively collected HSV-2 for mucocutaneous swabs.
| Clinical Agreement - (Mucocutaneous for HSV-2) | |||
|---|---|---|---|
| Simplexa™ HSV 1 & 2 DirectResults | Composite Reference Method | Total | |
| Detected | Not Detected | ||
| Detected | 22 | 0 | 22 |
| Not Detected | 0 | 124 | 124 |
| Total | 22 | 124 | 146 |
| %PPA | 100.0%(22/22)95% CI: 85.1% to 100.0% | %NPA | 100.0%(124/124)95% CI: 97.0% to100.0% |
{20}------------------------------------------------
Image /page/20/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo features a stylized DNA double helix in shades of green and blue on the left. To the right of the helix, the text "DiaSorin" is written in a dark blue, sans-serif font. Below "DiaSorin", the word "Molecular" is written in a lighter green, sans-serif font.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 March 9, 2018 Page 18 of 20
Retrospective Results Composite Reference Method HSV-1 Unknown Locations Cutaneous Swabs The table below shows HSV-1 positive and negative percent (PPA and NPA) vs. Composite Reference Method for retrospectively collected HSV-1 for cutaneous swabs from unknown locations.
| Clinical Agreement - (Unknown Sample Locations for HSV-1) | |||
|---|---|---|---|
| Simplexa™ HSV 1 & 2 DirectResults | Composite Reference Method | ||
| Detected | Not Detected | Total | |
| Detected | 3 | 0 | 3 |
| Not Detected | 0 | 12 | 12 |
| Total | 3 | 12 | 15 |
| %PPA | 100.0%(3/3)95% CI: 43.9% to 100.0% | %NPA | 100.0%(12/12)95% CI: 75.8% to100.0% |
Retrospective Results Composite Reference Method HSV-2 Unknown Locations Cutaneous Swabs
The table below shows HSV-2 positive and negative percent (PPA and NPA) vs. Composite Reference Method for retrospectively collected HSV-2 for cutaneous swabs from unknown locations.
| Clinical Agreement - (Unknown Sample Locations for HSV-2) | |||
|---|---|---|---|
| Simplexa™ HSV 1 & 2 DirectResults | Composite Reference Method | ||
| Detected | Not Detected | Total | |
| Detected | 3 | 0 | 3 |
| Not Detected | 0 | 12 | 12 |
| Total | 3 | 12 | 15 |
| %PPA | 100.0%(3/3)95% CI: 43.9% to 100.0% | %NPA | 100.0%(12/12)95% CI: 75.8% to100.0% |
{21}------------------------------------------------
Image /page/21/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo consists of a stylized DNA double helix on the left, colored in shades of green and blue. To the right of the helix is the text "DiaSorin" in a dark blue, sans-serif font. Below "DiaSorin" is the word "Molecular" in a lighter green color, also in a sans-serif font.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 March 9, 2018 Page 19 of 20
EXPECTED VALUES – Cutaneous and Mucocutaneous Swabs
The observed expected values using the Simplexa™ HSV 1 & 2 Direct assay are presented below. The data is stratified by age, gender and lesion location.
Cutaneous and Mucocutaneous Lesion Swabs by Age and Gender
| Gender | Age Group | Total | Simplexa™ HSV 1& 2 DirectHSV-1 Results | Simplexa™ HSV 1& 2 DirectHSV-2 Results | ||
|---|---|---|---|---|---|---|
| Positive | Prevalence | Positive | Prevalence | |||
| Female | ≤18 years | 128 | 24 | 18.8% | 20 | 15.6% |
| >18 to 21 years | 96 | 34 | 35.4% | 24 | 25.0% | |
| >21 years | 779 | 141 | 18.1% | 204 | 26.2% | |
| All | 1003 | 199 | 19.8% | 248 | 24.7% | |
| Male | ≤18 years | 36 | 11 | 30.6% | 1 | 2.8% |
| >18 to 21 years | 31 | 14 | 45.2% | 7 | 22.6% | |
| >21 years | 142 | 19 | 13.4% | 28 | 19.7% | |
| All | 209 | 44 | 21.1% | 36 | 17.2% | |
| All | 1212 | 243 | 20.0% | 284 | 23.4% |
Cutaneous and Mucocutaneous Lesion Swabs by Lesion Location
| Skin Type | LesionLocation | TotalSpecimens | Simplexa™ HSV 1& 2 DirectHSV-1 Results | Simplexa™ HSV 1& 2 DirectHSV-2 Results | ||
|---|---|---|---|---|---|---|
| Positive | Prevalence | Positive | Prevalence | |||
| Cutaneous | Genital | 136 | 28 | 20.6% | 31 | 22.8% |
| Skin | 92 | 12 | 13.0% | 7 | 7.6% | |
| All | 228 | 40 | 17.5% | 38 | 16.7% | |
| Mucocutaneous | Anorectal | 16 | 6 | 37.5% | 2 | 12.5% |
| Genital | 854 | 167 | 19.6% | 232 | 27.2% | |
| Nasal | 3 | 1 | 33.3% | 0 | 0.0% | |
| Ocular | 11 | 2 | 18.2% | 0 | 0.0% | |
| Oral | 51 | 20 | 39.2% | 1 | 2.0% | |
| Unknown | 2 | 0 | 0.0% | 0 | 0.0% | |
| Urethra | 3 | 0 | 0.0% | 0 | 0.0% | |
| All | 940 | 196 | 20.9% | 235 | 25.0% | |
| Unknown | Unknown | 44 | 7 | 15.9% | 11 | 25.0% |
| All | 44 | 7 | 15.9% | 11 | 25.0% | |
| All | 1212 | 243 | 20.0% | 284 | 23.4% |
{22}------------------------------------------------
Image /page/22/Picture/0 description: The image shows the logo for DiaSorin Molecular. The logo features a stylized DNA helix in shades of green and blue on the left. To the right of the helix, the text "DiaSorin" is written in a dark blue, sans-serif font. Below "DiaSorin", the word "Molecular" is written in a lighter green color, also in a sans-serif font.
510(k) Summary
Simplexa™ HSV 1 & 2 Direct Catalog No. MOL2150 Simplexa™ HSV 1 & 2 Positive Control Pack Catalog No. MOL2160 March 9. 2018 Page 20 of 20
CARRY-OVER CONTAMINATION
The amplification carry-over for the Simplexa™ assays including the Simplexa™ HSV 1 & 2 Direct assay was assessed from the Simplexa™ Flu A/B & RSV Direct REF MOL2650 (K120413) viral assay, and can be found on the FDA website. The study can be applied to the Simplexa™ HSV 1 & 2 Direct assays as the study is not analyte specific. In the Simplexa™ Flu A/B & RSV Direct REF MOL2650 (K120413), the amplification carry-over study searched for the presence of contamination in negative samples adjacent to strong positive samples. The study was designed by alternately placing high positive and negative samples on each disc. No evidence of carry-over contamination was observed.
FRESH VS FROZEN
Fresh versus frozen studies were not performed for the subject 510K submission and data from the original submission K150962 was used (see below).
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. The validated storage for samples was found to be the following;
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.
§ 866.3309 Herpes virus nucleic acid-based cutaneous and mucocutaneous lesion panel.
(a)
Identification. A herpes virus nucleic acid-based cutaneous and mucocutaneous lesion panel is a qualitative in vitro diagnostic device intended for the simultaneous detection and differentiation of different herpes viruses in cutaneous and mucocutaneous lesion samples from symptomatic patients suspected of Herpetic infections. Negative results do not preclude infection and should not be used as the sole basis for treatment or other patient management decisions. The assay is not intended for use in cerebrospinal fluid samples.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include detailed documentation for the device description, including the device components, ancillary reagents required but not provided, and a detailed explanation of the methodology including primer design and selection.
(2) Premarket notification submissions must include detailed documentation from the following analytical and clinical performance studies: Analytical sensitivity (Limit of Detection), reactivity, inclusivity, precision, reproducibility, interference, cross reactivity, carry-over, and cross contamination.
(3) Premarket notification submissions must include detailed documentation of a clinical study using lesion samples in which Herpes Simplex Virus 1, Herpes Simplex Virus 2, or Varicella Zoster Virus DNA detection was requested. The study must compare the device performance to an appropriate well established reference method.
(4) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling.
(5) The device labeling must include a limitation statement that reads: “The device is not intended for use with cerebrospinal fluid or to aid in the diagnosis of HSV or VZV infections of the central nervous system (CNS).”
(6) Premarket notification submissions must include quality assurance protocols and a detailed documentation for device software, including, but not limited to, standalone software applications and hardware-based devices that incorporate software.
(7) The risk management activities performed as part of the manufacturer's 21 CFR 820.30 design controls must document an appropriate end user device training program that will be offered as part of efforts to mitigate the risk of failure to correctly operate the instrument.