(88 days)
Not Found
No
The device description details a fixed algorithm based on comparing absorbance ratios to established cut-off values, with no mention of AI or ML.
No
The device is described as a qualitative in vitro diagnostic test for the detection and differentiation of HSV-1 and HSV-2 DNA, used as an aid in diagnosis, not for treatment.
Yes
The "Intended Use / Indications for Use" section explicitly states that the illumigene HSV 1&2 DNA amplification assay is a "qualitative in vitro diagnostic test for the direct detection and differentiation of herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) DNA." It also mentions that "Results from illumigene HSV 1&2 are used as an aid in the diagnosis of HSV infection in symptomatic patients."
No
The device description explicitly states that the system is comprised of a test kit, external controls kit, and an automated isothermal amplification and detection system (illumipro-10™), which is a piece of hardware. While software is involved in the illumipro-10™ for calculations and reporting, the overall device is a system that includes hardware components.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "The illumigene HSV 1&2 DNA amplification assay, performed on the illumipro-10™, is a qualitative in vitro diagnostic test for the direct detection and differentiation of herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) DNA in cutaneous and mucocutaneous lesion specimens..."
This statement clearly identifies the device as an in vitro diagnostic test.
N/A
Intended Use / Indications for Use
The illumigene HSV 1&2 DNA amplification assay, performed on the illumipro-10™, is a qualitative in vitro diagnostic test for the direct detection and differentiation of herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) DNA in cutaneous and mucocutaneous lesion specimens from male and female patients suspected of Herpetic infections.
illumigene HSV 1&2 utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect HSV-1 and HSV-2 by targeting segments of the herpes simplex virus 1 and herpes simplex virus 2 genomes. Results from illumigene HSV 1&2 are used as an aid in the diagnosis of HSV infection in symptomatic patients.
The assay is intended for use in hospital, reference or state laboratory settings. This device is not intended for nonlaboratory point-of-care use.
WARNING: illumigene HSV 1&2 is not FDA cleared for use with cerebrospinal fluid (CSF) or to aid in the diagnosis of HSV infections of the central nervous system (CNS). The device is not intended for prenatal screening.
Product codes (comma separated list FDA assigned to the subject device)
PGI
Device Description
The illumigene Molecular Diagnostic Test System is comprised of the illumigene® HSV 1&2 DNA Amplification Assay Test Kit, the illumigene HSV 1&2 External Controls Kit, and the illumipro-10™ Automated Isothermal Amplification and Detection System.
The illumigene HSV 1&2 molecular assay utilizes loop-mediated amplification (LAMP) technology to detect herpes simplex virus in cutaneous and mucocutaneous lesion swab specimens. Each illumigene HSV 1&2 assay is completed using illumigene Sample Preparation Apparatus III (SMP PREP III), illumigene HSV 1 Test Devices, illumigene HSV 2 Test Devices, Mineral Oil, illumigene Heat Treatment Tubes, and transfer pipettes. Using a transfer pipette, specimens are added to SMP PREP III and dispensed into Heat Treatment Tubes. Samples are heat-treated to make target and control DNA available for amplification. Each heat-treated sample is added to one illumigene HSV 1 and one illumigene HSV 2 Test Device. Mineral oil is added to each illumigene Test Device to prevent evaporation.
The illumipro-10™ heats each illumigene HSV 1 and HSV 2 Test Device containing prepared sample and control material, facilitating amplification of target DNA. When HSV-1 or HSV-2 is present in the specimen, a 208 base pair (bp) sequence of the HSV-1 glycoprotein G (US4) gene or a 189 bp sequence of the HSV-2 glycoprotein G (US4) gene is amplified and magnesium pyrophosphate is generated. Magnesium pyrophosphate forms a precipitate in the reaction mixture.
The illumipro-10™ monitors the absorbance characteristics of the reaction solutions at the assay Run Start (Signalmita, S) and at the assay Run End (Signalina, S). The illumipro-10™ calculates the change in light transmission between Run End and Run Start (S; S; ) and compares the ratio to an established cut-off value. The illumipro-10™ performs this ratio calculation to both the TEST chamber and the CONTROL chamber.
Fixed cut-off values for the TEST chamber are used to report sample results. TEST chamber Sy:S, ratios less than 82% are reported as 'POSITIVE'; TEST chamber S;:S; ratios greater than or equal to 82% are reported as 'NEGATIVE'. Numerical values are not reported.
Fixed cut-off values for the CONTROL chamber are used to determine validity. CONTROL chamber Sy:S, ratios less than 90% are considered valid and allow for reporting of TEST chamber results (POSITIVE). CONTROL chamber S;S; ratios greater than or equal to 90% are considered invalid and prevent reporting of TEST chamber results. Invalid CONTROL chamber reactions are reported as "INVALID'. More stringent cut-off criteria are applied to the CONTROL chamber reaction is not inhibited, reagents are performing as intended and that sample processing was performed appropriately.
The illumigene HSV 1&2 External Controls Kit contains a combined HSV-1 and HSV-2 Positive Control and a Negative Control (Negative Control IV) for use in routine Quality Control testing. External Control reagents are provided to aid the user in detection of reagent deterioration, adverse environmental or test conditions, or variance in operator performance that may lead to test errors.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
cutaneous and mucocutaneous lesion specimens
Indicated Patient Age Range
The study population included specimens from pediatric, adult, and geriatric patients, with ages ranging from 1 day to 89 years.
Intended User / Care Setting
hospital, reference or state laboratory settings. This device is not intended for nonlaboratory point-of-care use.
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
Clinical trials for the illumigene® HSV 1&2 DNA Amplification Assay, including the illumipro-10™ Automated Isothermal Amplification and Detection System, were conducted between October 2014 and March 2015. Performance characteristics of the assay were established with cutaneous lesion swab specimens from patients suspected of herpes simplex virus type 1 (HSV-1) infection. Performance characteristics of the illumigene HSV 1&2 assay were established by comparison to the ELVIS® HSV ID and D3 Typing Test System.
A total of 1158 leftover, de-identified lesion swab specimens from symptomatic male and female patients were evaluated. One sample was HSV positive by ELVIS, however, could not be identified as HSV-1 or HSV-2 (indeterminate) and another sample was tested with contaminated ELVIS cells and could not produce a result (indeterminate). Both samples were excluded from the performance analysis. . One invalid result for HSV-1 and one invalid result for HSV-2, which could not be repeated by the illumigene® HSV 1&2 DNA Amplification Assay, were also excluded from only the HSV-1 and the HSV-2 performance analysis, respectively. In addition, the ELVIS HSV ID and D Typing Test System is unable to detect HSV-1 if HSV-2 has been identified first in coinfected specimens. Therefore, if a specimen was HSV-2 positive by ELVIS it was removed from the calculation of the HSV-1 performance analysis. One hundred and eighty one (181) specimens were identified as HSV-2 positive by ELVIS and were removed from the HSV-1 data analysis, including two specimens identified as illumigene positive for both HSV-2. The swab specimens were categorized as cutaneous (skin lesion, genital - penis) or mucocutaneous (anorectal, genital-vaginal/cervical, nasal, ocular, oral, and urethral).
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Test Type: Clinical Studies
Sample Size: 1158 leftover, de-identified lesion swab specimens
Standalone Performance/Key Results (Combined Sites: HSV-1 Cutaneous N=264):
- Sensitivity: 48/51 = 94.1% (95% CI: 84.1-98.0%)
- Specificity: 207/213 = 97.2% (95% CI: 94.0-98.7%)
Standalone Performance/Key Results (Combined Sites: HSV-1 Mucocutaneous N=710):
- Sensitivity: 152/160 = 95.0% (95% CI: 90.5-97.5%)
- Specificity: 522/550 = 94.9% (95% CI: 92.7-96.5%)
Standalone Performance/Key Results (Combined Sites: HSV-2 Cutaneous N=306):
- Sensitivity: 42/42 = 100% (95% CI: 91.6-100.0%)
- Specificity: 251/264 = 95.1% (95% CI: 91.8-97.1%)
Standalone Performance/Key Results (Combined Sites: HSV-2 Mucocutaneous N=849):
- Sensitivity: 137/139 = 98.6% (95% CI: 94.9-99.6%)
- Specificity: 679/710 = 95.6% (95% CI: 93.9-96.9%)
Test Type: Precision/Reproducibility
Sample Size: 18 blind-coded samples supplied to 3 independent laboratories
Data Source: Contrived HSV-1 (strain HF) and HSV-2 (strain MS) positive and negative samples manufactured using simulated negative matrix (cheek swab matrix in MicroTest™ M4° viral transport medium).
Key Results (Reproducibility Study Summary for HSV-1 - Total % Agreement):
- HSV-1 Moderate Positive: 100.0% (90/90)
- HSV-1 Low Positive: 100.0% (90/90)
- HSV-1 & HSV-2 Near Cut-Off: 73.3% (66/90)
- HSV-1 & HSV-2 High Negative: 97.8% (88/90)
- HSV-1 Negative: 100.0% (180/180)
- Negative Control: 100.0% (30/30)
- Positive Control: 100.0% (30/30)
Key Results (Reproducibility Study Summary for HSV-2 - Total % Agreement):
- HSV-2 Moderate Positive: 100.0% (90/90)
- HSV-2 Low Positive: 100.0% (90/90)
- HSV-1 & HSV-2 Near Cut-Off: 87.8% (79/90)
- HSV-1 & HSV-2 High Negative: 97.8% (88/90)
- HSV-2 Negative: 100.0% (180/180)
- Negative Control: 100.0% (30/30)
- Positive Control: 100.0% (30/30)
Test Type: Detection Limit (Analytical Sensitivity)
Data Source: Two strains of HSV-1 (HF and Maclntyre) and two strains of HSV-2 (G and MS) diluted in a simulated negative cheek swab matrix. Confirmed through testing of 20 HSV-1 and 20 HSV-2 confirmed positive clinical samples from various anatomical locations at the assay LoD.
Key Results:
- Final assigned LoD: 9.89 x 10^4 TCID50/mL for HSV-1
- Final assigned LoD: 1.60 x 10^3 TCID50/mL for HSV-2
- All clinical samples detected at LoD or lower, except one HSV-1 clinical sample detected at 7.20 x 10^3 TCID50/mL.
Test Type: Analytical Specificity (Interference Testing)
Data Source: Contrived HSV-1 (strains HF and MacIntyre) and HSV-2 (strains G and MS) positive and negative samples with various non-microbial contaminants.
Key Results: No interference observed with listed substances, except Casein at concentrations greater than 5 mg/mL and Cold-EEZE® Cold Remedy plus Sore Throat (zincum gluconicum 2X) which produced invalid results.
Test Type: Cross-Reactivity Study
Data Source: Contrived positive (HSV-1 strain HF and HSV-2 strain MS) and negative specimens inoculated with bacterial or fungal organisms or virus.
Key Results: None of the listed organisms or their genetic material reacted with illumigene HSV 1&2. Human genomic DNA was nonreactive. No competitive inhibition observed from listed organisms with HSV-1 or HSV-2.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Combined Sites: HSV-1 Cutaneous (N=264)
- Sensitivity: 94.1%
- Specificity: 97.2%
Combined Sites: HSV-1 Mucocutaneous (N=710)
- Sensitivity: 95.0%
- Specificity: 94.9%
Combined Sites: HSV-2 Cutaneous (N=306)
- Sensitivity: 100%
- Specificity: 95.1%
Combined Sites: HSV-2 Mucocutaneous (N=849)
- Sensitivity: 98.6%
- Specificity: 95.6%
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.
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/1 description: The image shows the seal of the Department of Health & Human Services - USA. The seal is circular and contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the seal are three stylized human profiles facing to the right, stacked on top of each other.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
September 9, 2015
MERIDIAN BIOSCIENCE, INC. STEFANIE JOHNS, PH.D. REGULATORY AFFAIRS AND DESIGN ASSURANCE ASSOCIATE 3471 RIVER HILLS DRIVE CINCINNATI, OH 45244
Re: K151046 Trade/Device Name: illumigene® HSV 1&2 DNA Amplification Assay, illumigene® HSV 1&2 External Control Kit 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: April 16, 2015 Received: April 20, 2015
Dear Dr. Johns:
This letter corrects our substantially equivalent letter of July 17, 2015.
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
1
comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerelv vours.
Stephen J. Lovell -S for
Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known)
Device Name
illumigene® HSV 1&2 DNA Amplification Assay, illumigene® HSV 1&2 External Control Kit
Indications for Use (Describe)
illumigene® HSV 1&2 DNA Amplification Assay:
The illumigene HSV 1&2 DNA amplification assay, performed on the illumipro-10™, is a qualitative in vitro diagnostic test for the direct detection and differentiation of herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) DNA in cutaneous and mucocutaneous lesion specimens from male and female patients suspected of Herpetic infections.
illumigene HSV 1&2 utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect HSV-1 and HSV-2 by targeting segments of the herpes simplex virus 1 and herpes simplex virus 2 genomes. Results from illumigene HSV 1&2 are used as an aid in the diagnosis of HSV infection in symptomatic patients.
The assay is intended for use in hospital, reference or state laboratory settings. This device is not intended for nonlaboratory point-of-care use.
WARNING: illumigene HSV 1&2 is not FDA cleared for use with cerebrospinal fluid (CSF) or to aid in the diagnosis of HSV infections of the central nervous system (CNS). The device is not intended for prenatal screening.
illumigene® HSV 1&2 External Control Kit:
The illumigene HSV 1&2 External Control Kit contains Positive Control Reagents for use with the illumigene HSV 1&2 DNA Amplification Assay. External controls are used as part of a routine quality control program to aid the user in detection of unexpected conditions that may lead to test errors.
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)
PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.
FOR FDA USE ONLY
Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)
3
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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:
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Image /page/4/Picture/0 description: The image contains the logo for Meridian Bioscience, Inc. The logo features a blue globe on the left side, followed by the company name in a bold, blue font. Below the company name is the tagline "Inspired Science. Trusted Solutions." in a smaller font.
| illumigene® HSV 1&2 DNA Amplification Assay | |
|---|---|
| Application Reference: | Section 1: General Information |
| Attachment Description: | Attachment 007: 510(k) Summary |
| Application Date: | April 16, 2015 |
510(k) Summary
| 510(k) number: | K151046 | Date of Preparation: 17 July 2015 |
|---|---|---|
| Owner: | Meridian Bioscience, Inc. | |
| 3471 River Hills Drive | ||
| Cincinnati, Ohio 45244 USA | ||
| Phone: (513) 271-3700 | ||
| Fax: (513) 272-5213 | ||
| Contact: | Primary Contact: | |
| Stefanie Johns, PhD | ||
| Regulatory Affairs & Design Assurance Associate | ||
| Secondary Contact: | ||
| Susan D. Rolih | ||
| Executive Vice President, Regulatory and Quality Systems | ||
| Trade Name: | illumigene® HSV 1&2 DNA Amplification Assay | |
| illumigene® HSV 1&2 External Controls | ||
| Common Name: | Herpes simplex virus nucleic acid amplification assay | |
| Classification Name: | Herpes virus nucleic acid-based cutaneous and mucocutaneous lesion panel | |
| (21 CFR 866.3309, Product Code PGI) | ||
| Predicate Device: | Quidel Corporation Lyra™ Direct HSV 1 + 2/VZV Assay | |
| K133448 |
5
Image /page/5/Picture/0 description: The image shows the logo for Meridian Bioscience, Inc. The logo features a blue globe on the left, followed by the company name in blue, with "Meridian" on the top line and "Bioscience, Inc." on the second line. Below the company name is the slogan "Inspired Science. Trusted Solutions."
| illumigene® HSV 1&2 DNA Amplification Assay | |
|---|---|
| Application Reference: | Section 1: General Information |
| Attachment Description: | Attachment 007: 510(k) Summary |
| Application Date: | April 16, 2015 |
Device Description:
The illumigene Molecular Diagnostic Test System is comprised of the illumigene® HSV 1&2 DNA Amplification Assay Test Kit, the illumigene HSV 1&2 External Controls Kit, and the illumipro-10™ Automated Isothermal Amplification and Detection System.
The illumigene HSV 1&2 molecular assay utilizes loop-mediated amplification (LAMP) technology to detect herpes simplex virus in cutaneous and mucocutaneous lesion swab specimens. Each illumigene HSV 1&2 assay is completed using illumigene Sample Preparation Apparatus III (SMP PREP III), illumigene HSV 1 Test Devices, illumigene HSV 2 Test Devices, Mineral Oil, illumigene Heat Treatment Tubes, and transfer pipettes. Using a transfer pipette, specimens are added to SMP PREP III and dispensed into Heat Treatment Tubes. Samples are heat-treated to make target and control DNA available for amplification. Each heat-treated sample is added to one illumigene HSV 1 and one illumigene HSV 2 Test Device. Mineral oil is added to each illumigene Test Device to prevent evaporation.
The illumipro-10™ heats each illumigene HSV 1 and HSV 2 Test Device containing prepared sample and control material, facilitating amplification of target DNA. When HSV-1 or HSV-2 is present in the specimen, a 208 base pair (bp) sequence of the HSV-1 glycoprotein G (US4) gene or a 189 bp sequence of the HSV-2 glycoprotein G (US4) gene is amplified and magnesium pyrophosphate is generated. Magnesium pyrophosphate forms a precipitate in the reaction mixture.
The illumipro-10™ monitors the absorbance characteristics of the reaction solutions at the assay Run Start (Signalmita, S) and at the assay Run End (Signalina, S). The illumipro-10™ calculates the change in light transmission between Run End and Run Start (S; S; ) and compares the ratio to an established cut-off value. The illumipro-10™ performs this ratio calculation to both the TEST chamber and the CONTROL chamber.
Fixed cut-off values for the TEST chamber are used to report sample results. TEST chamber Sy:S, ratios less than 82% are reported as 'POSITIVE'; TEST chamber S;:S; ratios greater than or equal to 82% are reported as 'NEGATIVE'. Numerical values are not reported.
Fixed cut-off values for the CONTROL chamber are used to determine validity. CONTROL chamber Sy:S, ratios less than 90% are considered valid and allow for reporting of TEST chamber results (POSITIVE). CONTROL chamber S;S; ratios greater than or equal to 90% are considered invalid and prevent reporting of TEST chamber results. Invalid CONTROL chamber reactions are reported as "INVALID'. More stringent cut-off criteria are applied to the CONTROL chamber reaction is not inhibited, reagents are performing as intended and that sample processing was performed appropriately.
The illumigene HSV 1&2 External Controls Kit contains a combined HSV-1 and HSV-2 Positive Control and a Negative Control (Negative Control IV) for use in routine Quality Control testing. External Control reagents are provided to aid the user in detection of reagent deterioration, adverse environmental or test conditions, or variance in operator performance that may lead to test errors.
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Image /page/6/Picture/0 description: The image shows the logo for Meridian Bioscience, Inc. The logo features a blue globe on the left, followed by the company name in blue, with "Meridian" in a larger font size than "Bioscience, Inc." A thin blue line separates the two parts of the name. Below the company name is the tagline "Inspired Science. Trusted Solutions."
| illumigene ® HSV 1&2 DNA Amplification Assay | ||
|---|---|---|
| Application Reference: | Section 1: General Information | |
| Attachment Description: | Attachment 007: 510(k) Summary |
Intended Use:
The illumigene HSV 1&2 DNA amplification assay, performed on the illumipro-10™, is a qualitative in vitro diagnostic test for the direct detection and differentiation of herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) DNA in cutaneous and mucocutaneous lesion specimens from male and female patients suspected of Herpetic infections.
illumigene HSV 1&2 utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect HSV-1 and HSV-2 by targeting segments of the herpes simplex virus 1 and herpes simplex virus 2 genomes. Results from illumigene HSV 1&2 are used as an aid in the diagnosis of HSV infection in symptomatic patients.
The assay is intended for use in hospital, reference or state laboratory settings. This device is not intended for nonlaboratory point-of-care use.
WARNING: illumigene HSV 1&2 is not FDA cleared for use with cerebrospinal fluid (CSF) or to aid in the diagnosis of HSV infections of the central nervous system (CNS). The device is not intended for prenatal screening.
| Similarities | ||
|---|---|---|
| DEVICE | ||
| illumigene® HSV 1&2 DNA Amplification | ||
| Assay | PREDICATE | |
| Quidel | ||
| Lyra™ Direct HSV 1 + 2/VZV assay | ||
| K133448 | ||
| Intended Use | Qualitative in vitro diagnostic test for the direct | |
| detection and differentiation of herpes simplex | ||
| virus type 1 (HSV-1) and herpes simplex virus | ||
| type 2 (HSV-2) DNA in cutaneous and | ||
| mucocutaneous lesion specimens from male and | ||
| female patients suspected of Herpetic infections. | 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. | ||
| Assay Results | Qualitative | Qualitative |
| Indications for Use | Professional Use | Professional Use |
| DNA Detected | Herpes simplex virus type 1 | |
| Herpes simplex virus type 2 | Herpes simplex virus type 1 | |
| Herpes simplex virus type 2 | ||
| Varicella-zoster virus | ||
| Typing of HSV-1 and | ||
| HSV-2? | Yes | Yes |
| Specimen Types | Male and female cutaneous and mucocutaneous | |
| lesion swab specimens | Male and female cutaneous and mucocutaneous | |
| lesion swab specimens | ||
| Method | DNA Amplification | DNA Amplification |
| Detection | Instrument | Instrument |
Predicate Device Comparison:
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Image /page/7/Picture/0 description: The image shows the logo for Meridian Bioscience, Inc. The logo features a blue globe on the left side, followed by the company name in blue, bold font. Below the company name is the tagline "Inspired Science. Trusted Solutions."
| illumigene® HSV 1&2 DNA Amplification Assay | |
|---|---|
| Application Reference: | Section 1: General Information |
| Attachment Description: | Attachment 007: 510(k) Summary |
| Application Date: | April 16, 2015 |
| Differences | ||
|---|---|---|
| DEVICE | ||
| illumigene ® HSV 1&2 DNA Amplification Assay | PREDICATE | |
| Quidel | ||
| Lyra™ Direct HSV 1 + 2/VZV assay | ||
| K133448 | ||
| Amplification | ||
| Methodology | Loop-Mediated Isothermal Amplification (LAMP) | Multiplex Real-Time PCR |
| Detection | ||
| Methodology | Loop-Mediated Isothermal Amplification (LAMP) | Target-specific fluorescent-labeled hybridization |
| probes. | ||
| Reagents/ | ||
| Components | The illumigene HSV 1&2 DNA Amplification Assay | |
| Kit contains illumigene Sample Preparation | ||
| Apparatus III, illumigene HSV 1 Test Devices, | ||
| illumigene HSV 2 Test Devices, Mineral Oil, | ||
| illumigene Heat Treatment Tubes, and Transfer | ||
| Pipettes. | The Lyra™ Direct HSV 1 + 2/VZV Assay kit | |
| consists of: |
- Rehydration Solution
- Process Buffer Part M5050 (contains the
PRC) - Lyra™ Direct HSV 1 + 2/VZV Master Mix
Part M5012
Lyophilized Contents:
◦ DNA polymerase enzyme
◦ Primers and probes
◦ dNTPs
◦ Stabilizers |
| Instrumentation | illumipro -10™ Automated Isothermal Amplification
and Detection System | Life Technologies QuantStudio™ Dx, the Applied
Biosystems® 7500 Fast Dx, or the Cepheid
SmartCycler® II System |
| Reading Method | Visible Light Transmission | Fluorescence detection of dual-labeled hydrolysis
probes, Ct values. |
| Packaging | Supplied as a kit; 25 tests per kit | Supplied as a kit; 96 tests per kit. |
| Kit Storage | 2-30°C | Reagents and Controls: 2-8°C |
| VZV detection? | No | Yes |
NON-CLINICAL PERFORMANCE DATA
Analytical Performance:
Precision/Reproducibility:
Reproducibility studies were carried out by three independent laboratories. Blind-coded panels of eighteen (18) samples were supplied to participating laboratories. Samples were randomly sorted within each panel to mask sample identities. Contrived HSV-1 (strain HF) and HSV-2 (strain MS) positive and negative samples were manufactured using simulated negative matrix (cheek swab matrix in MicroTest™ M4° viral transport medium). The panel included moderate positive samples (HSV-1: 2.16 x 10 TCID-2: 4.80 x 10 TCIDs(mL), low positive samples (HSV-1: 1.08 x 104 TCID %/mL or HSV-2: 2.40 x 103 TCIDs/mL), and two HSV-contrived negative samples (HSV-1 near cut-off: 308 TCIDsy/mL, HSV-1 high negative: 29.7 TCID50/mL; HSV-2 near cut-off:
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| Image: Meridian Bioscience, Inc. logo | illumigene® HSV 1&2 DNA Amplification Assay |
|---|---|
| Application Reference: | |
| Attachment Description: | |
| Application Date: | Section 1: General Information |
| Attachment 007: 510(k) Summary | |
| April 16, 2015 |
24 TCIDs«/mL, HSV-2 high negative: 2.2 TCIDs;/mL). The panel also included two HSV-1 and HSV-2 negative samples and a Positive and Negative Control. Testing was performed by different operators at each site on the same day (intra-assay variability) for five days (inter-assay variability). Three lots of illumigene HSV 1&2 and five illumipro-10 instruments were used in this study. Positive and Negative Controls were tested with each panel. Results are provided in the tables below:
| Reproducibility Study Summary for HSV-1 | ||||||||
|---|---|---|---|---|---|---|---|---|
| Site 1 | Site 2 | Site 3 | Total | |||||
| Sample Type | Percent Agreement | Percent Agreement | Percent Agreement | Percent Agreement | ||||
| HSV-1 Moderate Positive | 30/30 | 100.0% | 30/30 | 100.0% | 30/30 | 100.0% | 90/90 | 100.0% |
| HSV-1 Low Positive | 30/30 | 100.0% | 30/30 | 100.0% | 30/30 | 100.0% | 90/90 | 100.0% |
| HSV-1 & HSV-2 Near | ||||||||
| Cut-Off | 20/30 | 66.7% | 26/30 | 86.7% | 20/30 | 66.7% | 66/90 | 73.3% |
| HSV-1 & HSV-2 High | ||||||||
| Negative | 29/30 | 96.7% | 30/30 | 100.0% | 29/30 | 96.7% | 88/90 | 97.8% |
| HSV-1 Negative | 60/60 | 100.0% | 60/60 | 100.0% | 60/60 | 100.0% | 180/180 | 100.0% |
| Negative Control | 10/10 | 100.0% | 10/10 | 100.0% | 10/10 | 100.0% | 30/30 | 100.0% |
| Positive Control | 10/10 | 100.0% | 10/10 | 100.0% | 10/10 | 100.0% | 30/30 | 100.0% |
| Reproducibility Study Summary for HSV-2 | ||||
|---|---|---|---|---|
| Site 1 | ||||
| Percent Agreement | Site 2 | |||
| Percent Agreement | Site 3 | |||
| Percent Agreement | Total | |||
| Percent Agreement | ||||
| Sample Type | ||||
| HSV-2 Moderate Positive | 30/30 | |||
| 100.0% | 30/30 | |||
| 100.0% | 30/30 | |||
| 100.0% | 90/90 | |||
| 100.0% | ||||
| HSV-2 Low Positive | 30/30 | |||
| 100.0% | 30/30 | |||
| 100.0% | 30/30 | |||
| 100.0% | 90/90 | |||
| 100.0% | ||||
| HSV-1 & HSV-2 Near | ||||
| Cut-Off | 25/30 | |||
| 83.3% | 29/30 | |||
| 96.7% | 25/30 | |||
| 83.3% | 79/90 | |||
| 87.8% | ||||
| HSV-1 & HSV-2 High | ||||
| Negative | 29/30 | |||
| 96.7% | 30/30 | |||
| 100.0% | 29/30 | |||
| 96.7% | 88/90 | |||
| 97.8% | ||||
| HSV-2 Negative | 60/60 | |||
| 100.0% | 60/60 | |||
| 100.0% | 60/60 | |||
| 100.0% | 180/180 | |||
| 100.0% | ||||
| Negative Control | 10/10 | |||
| 100.0% | 10/10 | |||
| 100.0% | 10/10 | |||
| 100.0% | 30/30 | |||
| 100.0% | ||||
| Positive Control | 10/10 | |||
| 100.0% | 10/10 | |||
| 100.0% | 10/10 | |||
| 100.0% | 30/30 | |||
| 100.0% |
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Image /page/9/Picture/0 description: The image is a logo for Meridian Bioscience, Inc. The logo features a blue globe on the left side, followed by the company name in blue, with the word "Meridian" in a larger font size than "Bioscience, Inc." Underneath the company name is the tagline "Inspired Science. Trusted Solutions."
| illumigene ® HSV 1&2 DNA Amplification Assay | |
|---|---|
| Application Reference: | Section 1: General Information |
| Attachment Description: | Attachment 007: 510(k) Summary |
| Application Date: | April 16, 2015 |
Detection Limit:
Analytical sensitivity studies were designed to determine the analytical limit of detection (LoD) of herpes simplex virus type 1 and type 2. The LoD is defined as the lowest concentration of analyte (TCID35/mL) that can be distinguished from negative samples with a high degree of probability (95%). Two strains of HSV-1 (HF and Maclntyre) and two strains of HSV-2 (G and MS) diluted in a simulated negative cheek swab matrix were used to establish the LoD with three kit lots of illumigene HSV 1&2. A minimum of four dilutions near the expected LoD were evaluated for each HSV strain during preliminary testing of twenty (20) individually prepared replicates. The preliminary LoD was confirmed through testing of an additional sixty (60) individually prepared replicates with HSV concentration at the LoD. The overall confirmed analytical LoD by HSV strain for illumigene HSV 1&2 is summarized below:
| HSV Type | Strain Description | LoD Concentration
(TCID50/mL) |
|--------------------------------|---------------------------|----------------------------------|
| Herpes simplex virus
type 1 | HF Strain (VR-260) | $7.20 x 10^3$ |
| | MacIntyre Strain (VR-539) | $9.89 x 10^4$ |
| Herpes simplex virus
type 2 | G Strain (VR-734) | $1.20 x 10^3$ |
| | MS Strain (VR-540) | $1.60 x 10^3$ |
The final assigned LoD is 9.89 x 104 TCID56mL for HSV-1 and 1.60 x 103 TCID56mL for HSV-2.
Analytical sensitivity of illumigene HSV 1&2 was verified through testing of twenty (20) HSV-1 and twenty (20) HSV-2 confirmed positive clinical samples from a variety of anatomical locations (i.e. oral, genital, anorectal, etc.) at the assay LoD. Each clinical sample was quantified and diluted to 9.89 x 10° TCID=0mL or 1.60 x 10° TCIDs /mL for HSV-1 and HSV-2, respectively: samples quantified at concentrations less than the limit of detection were tested undiluted. All samples were detected by illumigene HSV 182 at LoD or lower, except one HSV-1 clinical sample, which was detected at 7.20 x 10' TCID50/mL.
Analytical Specificity:
Interference Testing:
Non-microbial contaminants potentially found in cutaneous swab specimens were evaluated for the potential to interfere with the illumigene HSV 1&2 assay. Each potentially interfering substance was added to contrived HSV-1 (strains HF and MacIntyre) and HSV-2 (strains G and MS) positive and negative samples at final concentrations of 60 µg/mL, 7% v/v, 7% w/v, or greater.
No interference was observed with the following substances:
(1) At concentrations of 7% w/v or v/v: Abreve (10% Docosano), Balneol Hygienic Cleansing Loton,
Carmex Original Lip Balm (1.7% camphor, 0.7% menthol Pharmacy Disposable), Fluoride toothpaste (Crest, 0.243% sodium fluoride), K-Y Brand Jelly, Lanacane (0.2% benzethonium chloride, 20% benzocaine), Lip Clear" (1.2% zinc oxide), Miconazole 3 (CVST's
Yeast Infection Relief: 2% miconazole nitrate), Mouthwash (Listerine " Origin menthol, 0.060% methyl salicylate, 0.064% thymol), Preparation H® Hemorrhoidal Ointment (14% mineral oil, 74.9% petrolatum, 0.25% phenylephrine HCl), Releev® (0.13% benzalkonium chloride), Tioconazole, Vagisil Regular Strength (5% benzocaine, 2% resorcinol), Yeast Guard® Gel Treatment (Candida albicans, 27X HPUS: Candida parapsilosis, 27X HPUS: Pulsatilla, 27X HPUS). Feces, Seminal fluid, Urine, Whole blood, Buffy Coat.
(2) At concentrations of: 60 ug/mL - Mucus (Mucin, bovine submaxillary gland type I-S); 1.25 mg/mL -Cornstarch: 3.3 mg/mL - Albumin: 5 mg/mL - Acetaminophen, Casein, Chlorpheniramine maleate; 7 mg/mL - Acyclovir; 10 mg/mL - Acetylsalicylic acid, Dextromethorphan hydrobromide.
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| Image: Meridian Bioscience, Inc. logo | illumigene® HSV 1&2 DNA Amplification Assay | |
|---|---|---|
| Application Reference: | Section 1: General Information | |
| Attachment Description: | Attachment 007: 510(k) Summary | |
| Application Date: | April 16, 2015 |
Casein at concentrations greater than 5 mg/mL was found to interfere with the assay.
Cold-EEZE® Cold Remedy plus Sore Throat (zincum gluconicum 2X) was tested at 7% v/v and produced invalid results in all replicates.
Cross-Reactivity Study:
Crossreactivity studies employed contrived positive (HSV-1 strain HF and HSV-2 strain MS) and negative specimens inoculated with bacterial or fungal organisms to a minimum concentration of 1.0 x 10° CFU/mL (1.0 x 10° copies/mL where genomic DNA was used) or virus at a minimum of 1.0 x 10° TCID=ymL (1.0 x 10° copies/mL where genomic DNA or RNA was used). None of the following organisms or their genetic material reacted with illumigene HSV 1&2:
Acinetobacter calcoaceticus, Acinetobacter Iwoffii, Bacteroides fragilis, Bordetella bronchiseptica, Bordetella pertussis, Candida albicans, Candida quilliermondii, Candida krusei, Candida Iusitaniae, Candida parapsilosis, Candida tropicalis, Chlamydia trachomatis, Chlamydophila pneumoniae, Clostridium difficile, Clostridium perfringens, Corynebacterium diphtheriae, Enterococcus facalis, Enteroccus faecium, Escherichia coli (ESBL), Fusobacterium nucleatum, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (Type A), Klebsiella pneumoniae, Lactobacillus acidophilus, Legionella pneumophila, Mobiluncus curtisii, Mobiluncus mulieris, Moraxella catarrhalis, Mycoplasma orale, Mycoplasma pneumoniae, Mycoplasma salivarium, Neisseria meningitidis, Prevotella melaninoqenica. Proteus mirabilis, Pseudomonas aeruginosa. Salmonella typhimurium, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptoccus agalactiae, Streptococcus mitis, Streptococcus pneumoniae, Streptococus pyogenes, Streptococcus salivarius, Toxoplasma gondii, Treponema palladium, Trichomonas vaginalis, Ureaplasma urealyticum, Adenovirus, Coronavirus, Coxsackievirus, Cytomegalovirus, Enterovirus, Epstein Barr virus, Influenza A virus, Influenza B virus, Hepatitis C virus, Human herpes 6 virus, Human herpes 7 virus, Human herpes 8 virus, Human immunodeficiency virus type 1, Human metapneumovirus, Human papilloma virus, Measles virus, Parainfluenza virus, Respiratory syncytial virus, Rubella virus, Varicella zoster virus.
Human genomic DNA was nonreactive at 1.0 x 10 copies/mL. In addition, there was no competitive inhibition observed from the organisms listed above with HSV-1 or HSV-2 in the illumigene HSV 1&2 assay.
Assay cut-off:
The illumigene HSV 1&2 assay is manufactured with fixed cut-off values. The product is designed with a preselected cut-off value and amplification reagent concentrations are optimized to ensure appropriate reactions are obtained. Development optimization includes evaluation of characterized positive and negative clinical specimens. Amplification reagent concentrations are adjusted during design as needed to ensure illumigene results are aligned with clinical specimen reported results.
Cut-off values applied in the following manner:
The illumipro-10™ calculates the ratio of the Run End (Signal final or S) reads with the Run Start (Signal initial or S) reads and compares the ratio to an established cut-off value. The illumipro-10 performs this ratio calculation to both the TEST chamber and the CONTROL chamber.
Fixed cut-off values for the CONTROL chamber are used to determine validity. CONTROL chamber S;S, ratios less than 90% are considered valid and allow for reporting of TEST chamber results (POSITIVE). CONTROL chamber S;S, ratios greater than or equal to 90% are considered invalid. Results are reported as 'INVALID'; Test chamber results are not reported. More stringent cut-off criteria are applied to the Control chamber reaction to ensure amplification is not inhibited, reagents are performing as intended and that sample processing was performed appropriately.
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| Image: Meridian Bioscience Logo | illumigene® HSV 1&2 DNA Amplification Assay | |
|---|---|---|
| Image: Meridian Bioscience, Inc. Inspired Science. Trusted Solutions. | Application Reference: | Section 1: General Information |
| Attachment Description: | Attachment 007: 510(k) Summary | |
| Application Date: | April 16, 2015 |
Fixed cut-off values for the TEST chamber are used to report sample results. TEST chamber S.S. ratios less than 82% are reported as 'POSITIVE'; TEST chamber S;.S; ratios greater than or equal to 82% are reported as 'NEGATIVE'. Numerical values are not reported.
CLINICAL PERFORMANCE DATA
Clinical Studies:
Clinical trials for the illumigene® HSV 1&2 DNA Amplification Assay, including the illumipro-10™ Automated Isothermal Amplification and Detection System, were conducted between October 2014 and March 2015. Performance characteristics of the assay were established with cutaneous lesion swab specimens from patients suspected of herpes simplex virus type 1 (HSV-1) infection. Performance characteristics of the illumigene HSV 1&2 assay were established by comparison to the ELVIS® HSV ID and D3 Typing Test System.
A total of 1158 leftover, de-identified lesion swab specimens from symptomatic male and female patients were evaluated. One sample was HSV positive by ELVIS, however, could not be identified as HSV-1 or HSV-2 (indeterminate) and another sample was tested with contaminated ELVIS cells and could not produce a result (indeterminate). Both samples were excluded from the performance analysis. . One invalid result for HSV-1 and one invalid result for HSV-2, which could not be repeated by the illumigene® HSV 1&2 DNA Amplification Assay, were also excluded from only the HSV-1 and the HSV-2 performance analysis, respectively. In addition, the ELVIS HSV ID and D Typing Test System is unable to detect HSV-1 if HSV-2 has been identified first in coinfected specimens. Therefore, if a specimen was HSV-2 positive by ELVIS it was removed from the calculation of the HSV-1 performance analysis. One hundred and eighty one (181) specimens were identified as HSV-2 positive by ELVIS and were removed from the HSV-1 data analysis, including two specimens identified as illumigene positive for both HSV-2. The swab specimens were categorized as cutaneous (skin lesion, genital - penis) or mucocutaneous (anorectal, genital-vaginal/cervical, nasal, ocular, oral, and urethral). The tables below include performance of the remaining 974 specimens tested for HSV-1 and 1155 specimens tested for HSV-2 for all sites combined.
| Reference Method | illumigene | Performance | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Pos | Neg | Total | INVc | 95% CI | |||||
| Pos | 48 | 6a | 54 | 0 (0) | Sensitivity | 48/51 | 94.1% | 84.1-98.0% | |
| illumigene | |||||||||
| HSV 1&2 | Neg | 3b | 207 | 210 | 0 (0) | Specificity | 207/213 | 97.2% | 94.0-98.7% |
| Total | 51 | 213 | 264 | 0 (0) |
Combined Sites: HSV-1 Cutaneous (N=264)
6/6 samples identified as HSV-1 positive by an alternative, FDA-cleared molecular assay.
1/3 samples identified as HSV-1 negative by an alternative, FDA-cleared molecular assay.
f Initial invalid results are reported within the parentheses. The final number of invalid samples remaining after repeat testing are shown before the parenthesis.
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Image /page/12/Picture/0 description: The image shows the logo for Meridian Bioscience, Inc. The logo features a blue globe on the left side, followed by the company name in blue, bold font. Below the company name is the tagline "Inspired Science. Trusted Solutions."
| illumigene ® HSV 1&2 DNA Amplification Assay | |
|---|---|
| Application Reference: | Section 1: General Information |
| Attachment Description: | Attachment 007: 510(k) Summary |
| Application Date: | April 16, 2015 |
Combined Sites: HSV-1 Mucocutaneous (N=710)
| Reference Method | illumigene | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Pos | Neg | Total | INVd | Performance | 95% CI | ||||
| illumigene | |||||||||
| HSV 1&2 | Pos | 152 | 28b | 180 | 0 (1) | Sensitivity | 152/160 | 95.0% | 90.5-97.5% |
| Neg | 8c | 522 | 530 | 0 (5) | Specificity | 522/550 | 94.9% | 92.7-96.5% | |
| Total | 160 | 550 | 710 | 0 (6)a |
4 There were six initial INV samples by illumigene negative (ELVIS negative (ELVIS negative); one repeated as illumigene HSV 1 positive (ELVIS HSV 1 positive).
8 19/28 samples identified as HSV-1 positive by an alternative, FDA-cleared molecular assay; 3 samples could not be tested.
6 7/8 samples were identified as HSV-1 negative by an alternative, FDA-cleared molecular assay: 1 sample could not be tested.
9 Initial invalid results are reported within the parentheses. The final number of invalid samples remaining after repeat testing are shown before the parenthesis.
Combined Sites: HSV-2 Cutaneous (N=306)
| Reference Method | illumigene | Performance | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Pos | Neg | Total | INVc | 95% CI | |||||
| Pos | 42 | 13b | 55 | 0 (0) | Sensitivity | 42/42 | 100% | 91.6-100.0% | |
| illumigene | |||||||||
| HSV 1&2 | Neg | 0 | 251 | 251 | 0 (1) | Specificity | 251/264 | 95.1% | 91.8-97.1% |
| Total | 42 | 264 | 306 | 0 (1)a |
18 There was one initial INV sample by illumigene. The sample repeated as illumigene negative (ELVIS) negative).
6 8/13 samples were identified as HSV-2 positive by an alternative, FDA-cleared molecular assay; 1 sample could not be tested.
S hitial invalid results are reported within the parentheses. The final number of invalid samples remaining after repeat testing are shown before the parenthesis.
Combined Sites: HSV-2 Mucocutaneous (N=849)
| Reference Method | illumigene | Performance | |||||
|---|---|---|---|---|---|---|---|
| Pos | Neg | Total | INVd | 95% CI | |||
| illumigene | |||||||
| HSV 1&2 | Pos | 137 | 31b | 168 | 0 (0) | Sensitivity 137/139 98.6% | 94.9-99.6% |
| Neg | 2c | 679 | 681 | 0 (1) | Specificity 679/710 95.6% | 93.9-96.9% | |
| Total | 139 | 710 | 849 | 0 (1)a |
4 There was one initial INV sample by illumigene. The sample repeated illumigene negative (ELVIS negative). 6 24/31 samples were identified as HSV-2 positive by an alternative, FDA-cleared molecular assay; 4 samples could not be tested.
8 1/2 samples were identified as HSV-2 negative by an alternative, FDA-cleared molecular assay.
9 Initial invalid results are reported within the parentheses. The final number of invalid samples remaining after repeat testing are shown before the parenthesis.
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Image /page/13/Picture/0 description: The image shows a document with the title "illumigene® HSV 1&2 DNA Amplification Assay". It includes the Meridian Bioscience, Inc. logo. The document provides information such as the application reference, which is Section 1: General Information, the attachment description, which is Attachment 007: 510(k) Summary, and the application date, which is April 16, 2015.
Prevalence of HSV-1 and HSV-2 in cutaneous and mucocutaneous lesion specimens was estimated for the 1158 specimens producing valid results with the illumigene HSV 1&2 assay. One sample generated invalid results by illumigene HSV 1 and HSV 2 and it was therefore excluded; this sample is also ELVIS indeterminate due to cell contamination. Two samples tested for HSV-1 and one sample tested for HSV-2 generated invalid results by illumigene that were not repeated due to processing errors were also excluded. One sample unable to be typed by ELVIS and two HSV-1/HSV-2 coinfected specimens were included in the prevalence calculation as they produced valid illumigene results. ELVIS HSV-2 positive samples, excluded from the HSV-1 performance calculation, were included in the prevalence calculation. Of the remaining eligible samples producing valid results. 306 were from cutaneous lesions; there were 849 specimens tested for HSV-1 and 850 specimens tested for HSV-2 from mucocutaneous lesions. The study population included specimens from pediatric, adult, and geriatric patients, with ages ranging from 1 day to 89 years. There were three samples tested for HSV-1 and two tested for HSV-2 mucocutaneous from patients with unknown age.
The prevalence of HSV-1 and HSV-2 by the illumigene HSV 1&2 assay by anatomical location and patient age is provided in the tables below.
| HSV-1 | HSV-2 | |||||
|---|---|---|---|---|---|---|
| Location | Total # | Total Positive | Prevalence | Total # | Total Positive | Prevalence |
| Genital - Penis | 92 | 7 | 7.6% | 92 | 28 | 30.4% |
| Skin Lesion | 214 | 47 | 22.0% | 214 | 27 | 12.6% |
Prevalence by Anatomical Location (All Sites) - Cutaneous (N=306)
Prevalence by Anatomical Location (All Sites) - Mucocutaneous
| Location | HSV-1 (N=849) | HSV-2 (N=850) | ||||
|---|---|---|---|---|---|---|
| Total # | Total Positive | Prevalence | Total # | Total Positive | Prevalence | |
| Anorectal | 47 (1*) | 7 | 14.9% | 46 (2*) | 9 | 19.6% |
| Genital - Vaginal/Cervical | 624 (2*) | 112 | 17.9% | 626 | 158 | 25.2% |
| Nasal | 18 | 9 | 50.0% | 18 | 0 | 0.0% |
| Ocular | 20 | 0 | 0.0% | 20 | 0 | 0.0% |
| Oral Lesion | 135 | 54 | 40.0% | 135 | 2 | 1.5% |
| Urethral | 5 | 1 | 20.0% | 5 | 0 | 0.0% |
- Number of samples producing invalid illumigene results, which could not be resolved and therefore, were excluded from the analysis.
Prevalence by Age (All Sites) - Cutaneous (N=306)
| HSV-1 | HSV-2 | |||||
|---|---|---|---|---|---|---|
| Age | Total # | Total Positive | Prevalence | Total # | Total Positive | Prevalence |
| ≤ 5 years | 38 | 12 | 31.6% | 38 | 1 | 2.6% |
| 6 to 11 years | 14 | 7 | 50.0% | 14 | 1 | 7.1% |
| 12 to 21 years | 51 | 14 | 27.5% | 51 | 4 | 7.8% |
| 22 to 59 years | 166 | 18 | 10.8% | 166 | 36 | 21.7% |
| ≥60 years | 37 | 3 | 8.1% | 37 | 13 | 35.1% |
| Not Provided | 0 | 0 | 0.0% | 0 | 0 | 0.0% |
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Image /page/14/Picture/0 description: The image shows the logo for Meridian Bioscience, Inc. The logo features a blue globe on the left side, followed by the company name in blue, bold font. Below the company name is the tagline "Inspired Science. Trusted Solutions." also in blue.
| illumigene® HSV 1&2 DNA Amplification Assay | |
|---|---|
| Application Reference: | Section 1: General Information |
| Attachment Description: | Attachment 007: 510(k) Summary |
| Application Date: | April 16, 2015 |
Prevalence by Age (All Sites) – Mucocutaneous
| Age | Total # | Total Positive | Prevalence | Total # | Total Positive | Prevalence |
|---|---|---|---|---|---|---|
| ≤ 5 years | 47 | 8 | 17.0% | 47 | 0 | 0.0% |
| 6 to 11 years | 12 | 0 | 0.0% | 12 | 0 | 0.0% |
| 12 to 21 years | 174 (1*) | 46 | 26.4% | 175 | 42 | 24.0% |
| 22 to 59 years | 550 (1*) | 111 | 20.2% | 551 | 116 | 21.1% |
| ≥60 years | 63 (1*) | 18 | 28.6% | 63 (1*) | 11 | 17.5% |
| Not Provided | 3 | 0 | 0.0% | 2 (1*) | 0 | 0.0% |
- Number of samples producing invalid illumigene results, which could not be resolved and therefore, were excluded from the analysis.
Expected Values:
The observed expected values in the clinical study are calculated using all eligible cutaneous and mucoutaneous lesion samples submitted for HSV testing. The overall incidence of HSV infection by the illumigene HSV 1&2 assay during the clinical study is 20.5% (237/1155) for HSV-1 and 19.4% (224/1156) for HSV-2. Three HSV-1 and two HSV-2 samples producing invalid illumigene results that could not be resolved were excluded from the total eligible sample population.
CONCLUSION
The illumigene® HSV 1&2 DNA amplification assay, performed on the illumipro-10™, can be used to detect HSV-1 and HSV-2 in cutaneous and mucocutaneous lesion specimens and is substantially equivalent to the predicate device.