(90 days)
Not Found
No
The device description and performance studies focus on real-time PCR technology and standard statistical analysis of clinical agreement, with no mention of AI or ML.
No
The device is intended for the qualitative detection and differentiation of herpes simplex virus (HSV-2) DNA as an aid in the differential diagnosis of HSV-1 and HSV-2 infections, not for treatment.
Yes
The "Intended Use / Indications for Use" section explicitly states that the assay "is an aid in the differential diagnosis of HSV-1 and HSV-2 infections."
No
The device description explicitly states that 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. This includes hardware components (LIAISON® MDX instrument, Direct Amplification Disc, accessories) in addition to the software (LIAISON® MDX Studio Software).
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it's 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 is a diagnostic purpose, aiming to identify the presence of a specific pathogen in a human sample.
- Sample Type: It uses "mucocutaneous and cutaneous lesion swabs," which are samples taken from the human body.
- Method: It employs a "real-time PCR" method, which is a common technique used in in vitro diagnostics to detect and quantify nucleic acids.
- Device Description: The description details the components of the "assay system," including the assay itself, the instrument, and accessories, all designed for performing the test on the collected samples.
- Professional Use: The assay is intended for "professional use only," indicating it's used in a clinical or laboratory setting by trained personnel for diagnostic purposes.
All these characteristics align with the definition of an In Vitro Diagnostic device, which is a medical device intended for use in vitro for the examination of specimens derived from the human body solely or principally for the purpose of providing information concerning a physiological or pathological state, or a congenital abnormality, or to determine the compatibility with potential recipients, or to monitor therapeutic measures.
N/A
Intended Use / Indications for Use
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.
Product codes (comma separated list FDA assigned to the subject device)
PGI
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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
mucocutaneous and cutaneous lesion swabs
Indicated Patient Age Range
Not Found
Intended User / Care Setting
professional use only
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
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 non-evaluable 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 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.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Reproducibility:
Study Type: Reproducibility
Sample Size: Three investigative sites, 2 operators per site, 5 contrived sample pools tested in triplicate on 5 different days.
Key Results:
Combined results for all sites:
- HSV-1 Result Total Agreement: 98.5% (531/539) with 95% CI: 97.1 to 99.2%
- HSV-2 Result Total Agreement: 98.0% (528/539) with 95% CI: 96.4 to 98.9%
- DNA IC Result Total Agreement: 100.0% (539/539) with 95% CI: 96.4 to 98.9% (Note: CI for DNA IC result might be a copy-paste error from HSV-2 result as it's identical).
Analytical Sensitivity/Limit of Detection (LoD):
Study Type: Limit of Detection
Sample Size: 32 replicates for each virus strain.
Key Results:
- HSV-1 McIntyre: 4 TCID50/mL, Detected 32/32, Mean Ct ± SD: 36.4 ± 1.16
- HSV-1 HF: 160 TCID50/mL, Detected 32/32, Mean Ct ± SD: 35.2 ± 1.03
- HSV-2 G: 2 TCID50/mL, Detected 32/32, Mean Ct ± SD: 37.5 ± 1.08
- HSV-2 MS: 10 TCID50/mL, Detected 31/32, Mean Ct ± SD: 37.9 ± 1.15
Analytical Reactivity:
Study Type: Analytical Reactivity
Sample Size: Each HSV Strain/Isolate tested in triplicate.
Key Results: The Simplexa™ HSV 1 & 2 Direct assay was able to detect other strains of HSV-1 and HSV-2 viruses.
Cross-Reactivity (Analytical Specificity):
Study Type: Cross-Reactivity
Sample Size: 71 microorganisms, each spiked into negative matrix and assayed in triplicate.
Key Results: No cross-reactivity was observed.
Interference:
Study Type: Interference
Sample Size: 24 potentially interfering substances, each tested in a low positive HSV-1 and HSV-2 sample (4 times LoD) in triplicate.
Key Results: No interference was observed.
Competitive Interference:
Study Type: Competitive Interference
Sample Size: Samples with low levels of one virus and high concentrations of a co-infecting virus tested in triplicate or quintuplicate.
Key Results: No competitive interference was observed.
Inhibition by Other Microorganisms:
Study Type: Inhibition
Sample Size: 71 potentially inhibitory organisms, each individually spiked into a pool with HSV-1 and HSV-2 (4 times LoD) and initially tested in triplicate (with 5 additional replicates if any "Not Detected" results).
Key Results: None of the microorganisms caused >4/8 of the replicates to be "Not Detected", indicating no significant inhibitory effect. In silico NCBI BLAST analysis confirmed no inhibition for 7 organisms where physical testing was not possible.
Clinical Agreement - Prospective Study 1 (K150962) and Prospective Study 2 (K173798) and Retrospective Study:
Study Type: Clinical Agreement
Sample Size:
- Prospective Study 1: 696 evaluable samples
- Prospective Study 2: 511 evaluable samples on Simplexa, 512 by culture, 510 by sequencing
- Retrospective Study: 174 Cutaneous HSV-1, 174 Mucocutaneous HSV-2, 17 Unknown location samples.
Key Results: (Combined with data from second sample set)
Prospective Results - HSV-1 Cutaneous Swabs: - %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 - HSV-1 Mucocutaneous Swabs:
- %PPA: 98.2% (162/165), 95% CI: 94.4% to 99.6%
- %NPA: 97.5% (703/721), 95% CI: 96.1% to 98.4%
Prospective Results - HSV-2 Cutaneous Swabs:
- %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 - HSV-2 Mucocutaneous Swabs:
- %PPA: 99.5% (193/194), 95% CI: 97.1% to 100.0%
- %NPA: 96.7% (669/692), 95% CI: 95.1% to 97.8%
Retrospective Results - HSV-1 Cutaneous Swabs:
- %PPA: 100.0% (26/26), 95% CI: 87.1% to 100.0%
- %NPA: 98.9% (91/92), 95% CI: 94.1% to 99.8%
Retrospective Results - HSV-1 Mucocutaneous Swabs:
- %PPA: 100.0% (32/32), 95% CI: 89.3% to 100.0%
- %NPA: 99.1% (113/114), 95% CI: 95.2% to 100.0%
Retrospective Results - HSV-2 Cutaneous Swabs:
- %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 - HSV-2 Mucocutaneous Swabs:
- %PPA: 100.0% (22/22), 95% CI: 85.1% to 100.0%
- %NPA: 100.0% (124/124), 95% CI: 97.0% to 100.0%
Retrospective Results - HSV-1 Unknown Locations Cutaneous Swabs:
- %PPA: 100.0% (3/3), 95% CI: 43.9% to 100.0%
- %NPA: 100.0% (12/12), 95% CI: 75.8% to 100.0%
Retrospective Results - HSV-2 Unknown Locations Cutaneous Swabs:
- %PPA: 100.0% (3/3), 95% CI: 43.9% to 100.0%
- %NPA: 100.0% (12/12), 95% CI: 75.8% to 100.0%
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Positive Percent Agreement (PPA)
- Negative Percent Agreement (NPA)
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Lyra® Direct HSV 1 + 2/VZV Assay K133448
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
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) |
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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 Street
Cypress, California 90630
USA |
|-------------------------------------------|-------------------------------------------------------------------------------------------------------|
| Establishment Registration No. | 2023365 |
| Contact Person | Sharon Young
tel 562.240.6680
fax 562.240.6529
Sharon.Young@DiaSorin.com |
| Summary Date | March 9, 2018 |
| Proprietary Name | Simplexa™ HSV 1 & 2 Direct MOL2150 and Simplexa™ HSV 1 & 2
Positive Control Pack MOL2160 |
| Generic Name | HSV 1 & 2 nucleic acid |
| Classification Regulation
Product Code | PGI |
| Regulation Number | 866.3309 |
| Regulation name | Herpes Virus (VZV, HSV1, HSV2), DNA Detection Assay for
Cutaneous 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 SYMBOL
ON LABEL | Abbreviated
Name | Cap
Color | Number
of Vials | Reactions
per
Vial/Kit | Volume
per Vial | |
|--------------------------------------------|---------|-----------------------|---------------------|--------------|--------------------|------------------------------|--------------------|-------|
| Simplexa™ HSV 1 & 2 Direct
Reaction Mix | MOL2151 | REAG | C | RM | Brown | 24 | 1/24 | 50 μL |
Component Description
| Kit Component | Contents | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Simplexa™ HSV 1 | |||||||||||||||||||||
| & 2 Direct Reaction | |||||||||||||||||||||
| Mix (RM) | DNA polymerase, buffer, dNTPs, template DNA (Internal Control) dye-labeled fluorescent | ||||||||||||||||||||
| probe-primers specific for detection of HSV-1 and/or HSV-2 and for the DNA Internal | |||||||||||||||||||||
| Control. | |||||||||||||||||||||
| Target Probe | |||||||||||||||||||||
| Fluorophore | |||||||||||||||||||||
| (Dye) Excitation | |||||||||||||||||||||
| (nm) Emission | |||||||||||||||||||||
| (nm) Targeted Gene HSV-1 CFR610 590 610 HSV-1 DNA | |||||||||||||||||||||
| polymerase HSV-2 FAM 495 520 HSV-2 DNA | |||||||||||||||||||||
| polymerase DNA Internal | |||||||||||||||||||||
| Control Q670 644 670 NA | |||||||||||||||||||||
| Simplexa™ HSV 1 | |||||||||||||||||||||
| & 2 Kit Barcode | |||||||||||||||||||||
| Card | Assay specific parameters. |
Simplexa™ HSV 1 & 2 Positive Control Pack REF MOL2160
| Component Name | REF | Description | Cap Color | Number
of Vials | Reactions per
Vial/Kit | Volume per
Vial |
|------------------------------------------------|---------|------------------------------------|-----------|--------------------|---------------------------|--------------------|
| Simplexa™ HSV 1 & 2
Direct Positive Control | MOL2161 | Inactivated HSV
1 and 2 viruses | Red | 10 | 1/10 | 100 µL |
Direct Amplification Disc kit REF MOL1455
| Component Name | REF | Description | Number of
Discs | Reactions
per Disc/Kit |
|---------------------------|---------|------------------------------------------------------------------------------------------------|--------------------|---------------------------|
| Direct Amplification Disc | MOL1452 | Direct Amplification Disc for the
processing of up to 8 individual controls
or specimens | 3 | 8/24 |
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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 Assay | |
| K133448 | Simplexa™ HSV | |
| 1 & 2 Direct | ||
| Intended | ||
| Use | The Lyra® Direct HSV 1 + 2/VZV Assay is an | |
| in vitro multiplex Real-Time PCR test for | ||
| qualitative detection and differentiation of | ||
| herpes simplex virus type 1, herpes simplex | ||
| virus type 2, and varicella-zoster virus DNA | ||
| isolated and purified from cutaneous or | ||
| mucocutaneous lesion samples obtained from | ||
| symptomatic patients suspected of active | ||
| herpes simplex virus 1, herpes simplex virus 2 | ||
| and/or varicella-zoster infection. The Lyra® | ||
| Direct HSV 1 + 2/VZV Assay is intended to aid | ||
| in the diagnosis of herpes simplex virus 1, | ||
| herpes simplex virus 2 and varicella-zoster | ||
| virus active cutaneous or mucocutaneous | ||
| infections. Negative results do not preclude | ||
| herpes simplex virus 1, herpes simplex virus 2 | ||
| and varicella-zoster virus infections and should | ||
| not be used as the sole basis for diagnosis, | ||
| treatment or other management decisions. The | ||
| Lyra® Direct HSV 1 + 2/VZV Assay 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). The | ||
| Lyra® Direct HSV 1 + 2/VZV Assay is not | ||
| intended for use in prenatal screening. The | ||
| device is not intended for point-of-care use. | 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. |
| Sample
Types | Cutaneous or mucocutaneous lesion samples | Same |
| Extraction
Methods | None | Same |
| Assay
Methodology | PCR-based system for detecting the presence
or absence of viral DNA in clinical specimens. | Same |
| Detection
Techniques | Multiplex assay using different reporter dyes
for each target. | Same |
| Table of Differences | | |
| Name | Predicate | Candidate |
| | Lyra® Direct HSV 1 + 2/VZV Assay
K133448 | Simplexa™ HSV
1 & 2 Direct |
| Assay
Targets | HSV-1: glycoprotein G, HSV-2: glycoprotein G,
VZV: ORF6: DNA-helicase primase. | Well conserved region of the polymerase genes
for 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- | |||||||||||||
| 1 | |||||||||||||
| Result | 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- | |||||||||||||
| 2 | |||||||||||||
| Result | HSV-1 Low | ||||||||||||
| Positive | 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 to | ||||||||||||
| 99.8% | |||||||||||||
| HSV-1 | |||||||||||||
| Medium | |||||||||||||
| Positive | 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 to | ||||||||||||
| 100.0% | |||||||||||||
| HSV-2 Low | |||||||||||||
| Positive | 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 to | ||||||||||||
| 97.6% | |||||||||||||
| HSV-2 | |||||||||||||
| Medium | |||||||||||||
| Positive | 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 to | ||||||||||||
| 100.0% | |||||||||||||
| 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 to | ||||||||||||
| 97.6% | |||||||||||||
| Positive | |||||||||||||
| Control | 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 to | ||||||||||||
| 100.0% | |||||||||||||
| Total | |||||||||||||
| Agreement | 99.4% (179/180) | 96.1% (173/180) | 98.9% (176/179) | 98.0% | |||||||||
| (528/539) | 96.4 to | ||||||||||||
| 98.9% | |||||||||||||
| 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 | ||
| DNA | |||||||||||||
| IC | |||||||||||||
| Result | HSV-1 Low | ||||||||||||
| Positive | 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 to | ||||||||||||
| 100.0% | |||||||||||||
| HSV-1 | |||||||||||||
| Medium | |||||||||||||
| Positive | 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 to | ||||||||||||
| 100.0% | |||||||||||||
| HSV-2 Low | |||||||||||||
| Positive | 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 to | ||||||||||||
| 100.0% | |||||||||||||
| HSV-2 | |||||||||||||
| Medium | |||||||||||||
| Positive | 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 to | ||||||||||||
| 100.0% | |||||||||||||
| High | |||||||||||||
| Negative | 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 to | ||||||||||||
| 100.0% | |||||||||||||
| Positive | |||||||||||||
| Control | 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 to | ||||||||||||
| 100.0% | |||||||||||||
| Total | |||||||||||||
| Agreement | 100.0% (180/180) | 100.0% (180/180) | 100.0% (179/179) | 100.0% | |||||||||
| (539/539) | 96.4 to | ||||||||||||
| 98.9% |
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 Detected
Replicates 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), ATCC
700699 | $1.00 X 10^6$ 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 | Interferent
Concentration | # 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 Direct | |||
| Results | 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 Direct | |||
| Results | 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 Direct | |||
| Results | 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 Direct | |||
| Results | 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 Direct | |||
| Results | 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% to | |||
| 99.8% |
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 Direct | |||
| Results | 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% | %NPA | ||
| 99.1%(113/114) | |||
| 95% CI: 95.2% to | |||
| 100.0% |
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 Direct | |||
| Results | 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 Direct | |||
| Results | 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% to | |||
| 100.0% |
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 Direct | |||
| Results | 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% to | |||
| 100.0% |
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 Direct | |||
| Results | 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% to | |||
| 100.0% |
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 Direct
HSV-1 Results | | Simplexa™ HSV 1& 2 Direct
HSV-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 | Lesion
Location | Total
Specimens | Simplexa™ HSV 1& 2 Direct
HSV-1 Results | | Simplexa™ HSV 1& 2 Direct
HSV-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% |
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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.