(80 days)
Not Found
No
The device description details a fixed cut-off value for determining results, which is a rule-based approach, not AI/ML. There is no mention of AI, ML, or training/test sets for model development.
No
The device is an in vitro diagnostic (IVD) test used to detect Mycoplasma pneumoniae DNA. It aids in diagnosis but does not provide any treatment or therapeutic function.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is a "qualitative in vitro diagnostic test for the direct detection of DNA from Mycoplasma pneumoniae." It also notes that results "should be used in conjunction with clinical presentation, other laboratory findings, and epidemiological risk factors as an aid in the diagnosis of Mycoplasma infection."
No
The device description explicitly states that the system is comprised of a test kit, external controls kit, and an automated instrument (illumipro-10™). This instrument is a hardware component that performs heating, monitors absorbance, and calculates results. Therefore, the device is not software-only.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The very first sentence explicitly states it is a "qualitative in vitro diagnostic test". It is intended for the direct detection of DNA from Mycoplasma pneumoniae in human throat swabs to aid in the diagnosis of Mycoplasma infection. This clearly aligns with the definition of an in vitro diagnostic device, which is used to examine specimens derived from the human body to provide information for diagnostic purposes.
- Device Description: The description details the components of the system, including test kits and an automated system, and explains how it processes human specimens (throat swabs) to detect the presence of Mycoplasma pneumoniae DNA. This process is performed in vitro (outside the body).
- Results and Interpretation: The device provides results (POSITIVE, NEGATIVE, INVALID) based on the analysis of the specimen, which are intended to be used in conjunction with other clinical information for diagnosis.
- Performance Studies: The document describes clinical studies where the device was used to test human specimens and its performance was compared to a reference molecular in vitro diagnostic method.
All these points strongly indicate that the illumigene Mycoplasma Direct DNA amplification assay is an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The illumigene Mycoplasma Direct DNA amplification assay, performed on the illumipro-10™, is a qualitative in vitro diagnostic test for the direct detection of DNA from Mycoplasma pneumoniae in human throat swabs obtained from patients suspected of having Mycoplasma pneumoniae infection.
The illumigene Mycoplasma Direct assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect Mycoplasma pneumoniae by targeting a segment of the Mycoplasma pneumoniae genome.
Results from the illumigene Mycoplasma Direct DNA amplification assay should be used in conjunction with clinical presentation, other laboratory findings, and epidemiological risk factors as an aid in the diagnosis of Mycoplasma infection and should not be used as the sole basis for treatment or other patient management. Positive results do not rule out co-infection with other organisms and negative results in persons with respiratory tract infections may be due to pathogens not detected by this assay. Lower respiratory tract infections due to M. pneumoniae may not be detected by this assay. If lower respiratory tract infection due to M. pneumoniae is suspected, additional laboratory testing using methods other than the illumigene Mycoplasma Direct DNA Amplification Assay may be necessary.
Product codes (comma separated list FDA assigned to the subject device)
OZX, OOI
Device Description
The illumigene Molecular Diagnostic Test System is comprised of the illumigene® Mycoplasma Direct DNA Amplification Assay Test Kit, the illumigene Mycoplasma Direct External Controls Kit, and the illumipro-10™ Automated Isothermal Amplification and Detection System.
The illumigene Mycoplasma Direct molecular assay utilizes loop-mediated amplification (LAMP) technology to detect Mycoplasma pneumoniae in throat swab specimens. The illumigene Mycoplasma Direct kit includes illumigene Sample Preparation Apparatus III (SMP PREP II), illumigene Mycoplasma Test Devices, and Heat Treatment Tubes. The throat swab is added directly to the SMP PREP II, which contains assay control buffer. Samples processed through SMP PREP II (sample/control mixture) are heat treated to make target and control DNA available for amplification. The heat-treated sample is added to the illumigene Mycoplasma Test Device.
The illumipro-10 heats each illumigene Mycoplasma Test Device containing prepared sample and control material, facilitating amplification of target DNA. When M. pneumoniae is present in the specimen, a 208 base pair (bp) sequence of the M. pneumoniae intracellular protease-like 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 (Signal initial, S;) and at the assay Run End (Signal final, S;). The illumipro-10 calculates the change in light transmission between Run End and Run Start (S, :S, ) and compares the ratio to a fixed cut-off value for disposition of results.
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 S; S, ratios less than 90% are considered valid and allow for reporting of TEST chamber results (POSITIVE, NEGATIVE). CONTROL chamber 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 to ensure amplification is not inhibited, reagents are performing as intended and that sample processing was performed appropriately.
The illumigene Mycoplasma Direct External Control Kit contains a Positive Control reagent for use in routine Quality Control testing; the illumigene Sample Preparation Apparatus III reagent provided with the Mycoplasma Direct Kit serves as the External Negative 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
human throat swabs
Indicated Patient Age Range
The eligible study population included throat swab specimens from pediatric patients ranging in age from 3 weeks to 97 years.
Intended User / Care Setting
Not Found
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
The performance characteristics of the illumigene Mycoplasma Direct DNA Amplification Assay were established in clinical studies conducted in 2015-2016 at independent clinical test sites representing three geographically distinct regions throughout the United States. Performance characteristics of the assay were compared to a reference molecular in vitro diagnostic method, the illumigene Mycoplasma DNA Amplification Assay (Meridian Bioscience, Inc., Cincinnati, OH). A total of 458 prospective, deidentified, throat swab specimens collected under informed consent from symptomatic male and female patients were evaluated. Two samples (0.4%) were excluded from the clinical sample population due to an instrument error during testing (1) or an unacceptable sample type (1) for a total of 456 eligible samples for analysis.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
NON-CLINICAL PERFORMANCE DATA
Analytical Performance:
Precision/Reproducibility:
Blind-coded panels of 10 samples were supplied to three independent laboratories for reproducibility studies. Samples were randomly sorted within each panel to mask sample identities. The panels included contrived manufactured as low positive samples (near the limit of detect, n=3), moderate positive samples (n=3), and high negative samples (n=3). The panel also included one natural negative sample. 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 Mycoplasma Direct and eight illumipro-10 instruments were used in the study. Positive and Negative Controls were tested with each panel.
Results:
Site 1: High Negative 100.0% (30/30), Low Positive 100.0% (30/30), Moderate Positive 100.0% (30/30), Negative 90.0% (9/10), Negative Control 100.0% (10/10), Positive Control 100.0% (10/10).
Site 2: High Negative 100.0% (30/30), Low Positive 100.0% (30/30), Moderate Positive 100.0% (30/30), Negative 100.0% (10/10), Negative Control 100.0% (10/10), Positive Control 100.0% (10/10).
Site 3: High Negative 100.0% (30/30), Low Positive 96.7% (29/30), Moderate Positive 100.0% (30/30), Negative 100.0% (10/10), Negative Control 100.0% (10/10), Positive Control 100.0% (10/10).
Total: High Negative 100.0% (90/90), Low Positive 98.9% (89/90), Moderate Positive 100.0% (90/90), Negative 96.7% (29/30), Negative Control 100.0% (30/30), Positive Control 100.0% (30/30).
Detection Limit:
Analytical Sensitivity studies were designed to verify the analytical limit of detection (LoD) of Mycoplasma pneumoniae with the illumigene Mycoplasma Direct assay. The LoD is defined as the lowest concentration of analyte (CFU/mL) that can be distinguished from negative samples with a high degree of probability (95%). Two strains of M. pneumoniae (M129 and FH) diluted in a simulated negative throat swab matrix were used to establish the LoD with three kit lots of illumigene Mycoplasma Direct. A minimum of three dilutions near the expected LoD in twenty (20) individually prepared replicates were evaluated for each M. pneumoniae strain.
LoD Concentration (CFU/mL): M. pneumoniae FH (ATCC 15531) = 2350, M. pneumoniae M129 (ATCC 29342) = 200.
Analytical Specificity:
Interference Testing: Potentially interfering substances were tested with simulated negative and contrived low positive (M. pneumoniae strains M129 and FH) samples. The following substances, at the saturated solvent/diluent concentrations indicated, do not interfere with illumigene Mycoplasma Direct assay: Acetaminophen (18.1 mg/mL), Albuterol Sulfate (20 mg/mL), Azithromycin dehydrate (2.0 mg/mL), Cepacol® Mouthwash, Contac® Cold + Flu Tablets, Diphenhydramine HCI (2.6 mg/mL), Erythromycin (20.0 mg/mL), HALLS® Cough Drops, Ibuprofen (12.7 mg/mL), Prednisone (20.0 mg/mL), Robitussin® Cough+Chest Congestion Cough Syrup, Saline Nasal Spray, Mucus (5.0mg/mL), and White Blood Cells (0.5% v/v).
Whole blood was found to produce invalid results at concentrations greater than 2%.
Phenylephrine HCI at concentrations greater than 0.595 mg/mL may produce false negative results with low positive samples.
Cross-Reactivity Study: Crossreactivity studies were previously performed with the illumigene Mycoplasma DNA Amplification assay. Positive and negative specimens inoculated with potentially interfering bacterial or fungal organisms to minimum final concentrations of 1.0 x 10 CFU/mL. Viruses were tested at concentrations greater than 1.0 x 10 TClDgg/mL or 1.0 x 106 copies/mL. Human DNA was tested at 2.0 ng/test with no crossreactivity observed. Positive specimens contained M. pneumoniae concentrations near the limit of detection. None of the listed organisms or materials were identified as crossreactive or interfering. No crossreactivity is expected with the illumigene Mycoplasma Direct assay.
CLINICAL PERFORMANCE DATA
Clinical Studies:
The performance characteristics of the illumigene Mycoplasma Direct DNA Amplification Assay were established in clinical studies conducted in 2015-2016 at independent clinical test sites representing three geographically distinct regions throughout the United States. Performance characteristics of the assay were compared to a reference molecular in vitro diagnostic method, the illumigene Mycoplasma DNA Amplification Assay (Meridian Bioscience, Inc., Cincinnati, OH). A total of 458 prospective, deidentified, throat swab specimens collected under informed consent from symptomatic male and female patients were evaluated. Two samples (0.4%) were excluded from the clinical sample population due to an instrument error during testing (1) or an unacceptable sample type (1) for a total of 456 eligible samples for analysis. There were no invalid results generated by the illumigene Mycoplasma Direct assay during the clinical study (0.0%; 95% Cl: 0.0 - 0.8%).
Key results: Positive Percent Agreement 96.0% (24/25), Negative Percent Agreement 97.7% (421/431), Overall Percent Agreement 97.6% (445/456), Invalid Rate 0.0% (0/456).
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Positive Percent Agreement: 96.0% (24/25) (95% CI: 80.5 - 99.3%)
Negative Percent Agreement: 97.7% (421/431) (95% CI: 95.8 - 98.7%)
Overall Percent Agreement: 97.6% (445/456) (95% CI: 95.7 - 98.6%)
Invalid Rate: 0.0% (0/456) (95% CI: 0.0 - 0.8%)
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
§ 866.3980 Respiratory viral panel multiplex nucleic acid assay.
(a)
Identification. A respiratory viral panel multiplex nucleic acid assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or viral culture. The detection and identification of a specific viral nucleic acid from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection when used in conjunction with other clinical and laboratory findings. The device is intended for detection and identification of a combination of the following viruses:(1) Influenza A and Influenza B;
(2) Influenza A subtype H1 and Influenza A subtype H3;
(3) Respiratory Syncytial Virus subtype A and Respiratory Syncytial Virus subtype B;
(4) Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus;
(5) Human Metapneumovirus;
(6) Rhinovirus; and
(7) Adenovirus.
(b)
Classification. Class II (special controls). The special controls are:(1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid Assay;”
(2) For a device that detects and identifies Human Metapneumovirus, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Human Metapneumovirus (hMPV) Using Nucleic Acid Assays;” and
(3) For a device that detects and differentiates Influenza A subtype H1 and subtype H3, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Detection and Differentiation of Influenza A Virus Subtypes Using Multiplex Nucleic Acid Assays.” See § 866.1(e) for the availability of these guidance documents.
0
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an abstract symbol that resembles three stylized human profiles or a bird in flight, rendered in a dark color.
June 13, 2016
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
MERIDIAN BIOSCIENCE, INC. MICHELLE SMITH SR. DIRECTOR, REGULATORY AFFAIRS AND DESIGN ASSURANCE 3471 RIVER HILLS DRIVE CINCINNATI OH 45244
Re: K160829
Trade/Device Name: illumigene Mycoplasma Direct DNA Amplification Assay illumigene Mycoplasma Direct External Controls Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory Viral Panel Multiplex Nucleic Acid Assay Regulatory Class: II Product Code: OZX, OOI Dated: March 24, 2016 Received: March 25, 2016
Dear Ms. Smith:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
1
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Steven R. Gitterman -S
Steven Gitterman Deputy 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) K160829
Device Name illumigene Mycoplasma Direct DNA Amplification Assay
illumigene Mycoplasma Direct External Controls
Indications for Use (Describe)
The illumigene Mycoplasma Direct DNA amplification assay, performed on the illumipro-10™, is a qualitative in vitro diagnostic test for the direct detection of DNA from Mycoplasma pneumoniae in human throat swabs obtained from patients suspected of having Mycoplasma pneumoniae infection.
The illumigene Mycoplasma Direct assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect Mycoplasma pneumoniae by targeting a segment of the Mycoplasma pneumoniae genome.
Results from the illumigene Mycoplasma Direct DNA amplification assay should be used in conjunction with clinical presentation, other laboratory findings, and epidemiological risk factors as an aid in the diagnosis of Mycoplasma infection and should not be used as the sole basis for treatment or other patient management. Positive results do not rule out co-infection with other organisms and negative results in persons with respiratory tract infections may be due to pathogens not detected by this assay. Lower respiratory tract infections due to M. pneumoniae may not be detected by this assay. If lower respiratory tract infection due to M. pneumoniae is suspected, additional laboratory testing using methods other than the illumigene Mycoplasma Direct DNA Amplification Assay may be necessary.
| 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 contains the logo for Meridian Bioscience, Inc. The logo features a blue globe on the left, followed by the company name in a stylized blue font. Below the name is the tagline "Inspired Science. Trusted Solutions." also in blue.
| illumigene® Mycoplasma Direct DNA Amplification Assay | |
|---|---|
| Application Reference: | Section 1: General Information |
| Attachment Description: | Attachment 007: 510(k) Summary |
| Application Date: | June 7, 2016 |
510(k) Summary
| 510(k) number: | K160829 | Date of Preparation: | June 7, 2016 |
|---|---|---|---|
| Owner: | Meridian Bioscience, Inc. | ||
| 3471 River Hills Drive | |||
| Cincinnati, Ohio 45244 USA | |||
| Phone: (513) 271-3700 | |||
| Fax: (513) 272-5213 | Contact: | Primary Contact: | |
| Michelle L. Smith | |||
| Senior Director, Regulatory Affairs & Design Assurance |
Secondary Contact:
Susan D. Rolih
Executive Vice President, Regulatory and Quality Systems |
| Trade Name: | illumigene® Mycoplasma Direct DNA Amplification Assay
illumigene® Mycoplasma Direct External Controls | | |
| Common Name: | Mycoplasma pneumoniae DNA Assay System | | |
| Classification Name: | Respiratory viral panel multiplex nucleic acid assay
(21 CFR 866.3980, Product Code OZX, OOI) | | |
| Predicate Device: | illumigene Mycoplasma DNA Amplification Assay; Catalog 280550
K123423, K152800 | | |
4
Image /page/4/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 a bold, blue font. Below the company name is the tagline "Inspired Science. Trusted Solutions."
| Application Reference: | Section 1: General Information |
|---|---|
| Attachment Description: | Attachment 007: 510(k) Summary |
Device Description:
The illumigene Molecular Diagnostic Test System is comprised of the illumigene® Mycoplasma Direct DNA Amplification Assay Test Kit, the illumigene Mycoplasma Direct External Controls Kit, and the illumipro-10™ Automated Isothermal Amplification and Detection System.
The illumigene Mycoplasma Direct molecular assay utilizes loop-mediated amplification (LAMP) technology to detect Mycoplasma pneumoniae in throat swab specimens. The illumigene Mycoplasma Direct kit includes illumigene Sample Preparation Apparatus III (SMP PREP II), illumigene Mycoplasma Test Devices, and Heat Treatment Tubes. The throat swab is added directly to the SMP PREP II, which contains assay control buffer. Samples processed through SMP PREP II (sample/control mixture) are heat treated to make target and control DNA available for amplification. The heat-treated sample is added to the illumigene Mvcoplasma Test Device.
The illumipro-10 heats each illumigene Mycoplasma Test Device containing prepared sample and control material, facilitating amplification of target DNA. When M. pneumoniae is present in the specimen, a 208 base pair (bp) sequence of the M. pneumoniae intracellular protease-like 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 (Signal initial, S;) and at the assay Run End (Signal final, S;). The illumipro-10 calculates the change in light transmission between Run End and Run Start (S, :S, ) and compares the ratio to a fixed cut-off value for disposition of results.
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 S; S, ratios less than 90% are considered valid and allow for reporting of TEST chamber results (POSITIVE, NEGATIVE). CONTROL chamber 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 to ensure amplification is not inhibited, reagents are performing as intended and that sample processing was performed appropriately.
The illumigene Mycoplasma Direct External Control Kit contains a Positive Control reagent for use in routine Quality Control testing; the illumigene Sample Preparation Apparatus III reagent provided with the Mycoplasma Direct Kit serves as the External Negative 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/5/Picture/0 description: The image contains 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 above "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 ® Mycoplasma Direct DNA Amplification Assay | |
|---|---|
| Application Reference: | Section 1: General Information |
| Attachment Description: | Attachment 007: 510(k) Summary |
Intended Use:
The illumigene Mycoplasma Direct DNA amplification assay, performed on the illumipro-10™, is a qualitative in vitro diagnostic test for the direction of DNA from Mycoplasma pneumoniae in human throat swabs obtained from patients suspected of having Mycoplasma pneumoniae infection.
The illumigene Mycoplasma Direct assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect Mycoplasma pneumoniae by targeting a segment of the Mycoplasma pneumoniae genome.
Results from the illumigene Mycoplasma Direct DNA amplification assay should be used in conjunction with clinical presentation, other laboratory findings, and epidemiological risk factors as an aid in the diagnosis of Mycoplasma infection and should not be used as the sole basis for treatment or other patient management. Positive results do not rule out co-infection with other organisms and negative results in persons with respiratory tract infections may be due to pathogens not detected by this assay. Lower respiratory tract infections due to M. pneumoniae may not be detected by this assay. If lower respiratory tract infection due to M. pneumoniae is suspected, additional laboratory testing using methods other than the illumigene Mycoplasma Direct DNA Amplification Assay may be necessary.
| Similarities | ||||
|---|---|---|---|---|
| MODIFIED DEVICE | ||||
| illumigene® Mycoplasma Direct | ||||
| DNA Amplification Assay | PREDICATE DEVICE | |||
| illumigene® Mycoplasma DNA | ||||
| Amplification Assay | ||||
| K123423, K152800 | ||||
| Organism | ||||
| Detected | Mycoplasma pneumoniae | Mycoplasma pneumoniae | ||
| Target | ||||
| Sequence | ||||
| Detected | The assay targets a 208 base pair (bp) | |||
| sequence of the Mycoplasma pneumoniae | ||||
| genome. The target DNA sequence is | ||||
| found in the intracellular protease-like | ||||
| protein gene. | The assay targets a 208 base pair (bp) | |||
| sequence of the Mycoplasma pneumoniae | ||||
| genome. The target DNA sequence is found in | ||||
| the intracellular protease-like protein gene. | ||||
| Instrumentation | illumipro-10™ Automated Isothermal | |||
| Amplification and Detection System | illumipro-10™ Automated Isothermal | |||
| Amplification and Detection System | ||||
| Amplification | ||||
| and Detection | Self-contained and automated | Self-contained and automated | ||
| Amplification | ||||
| Methodology | Loop-Mediated Isothermal Amplification | |||
| (LAMP) | Loop-Mediated Isothermal Amplification (LAMP) | |||
| Reading | ||||
| Method | Visible Light Transmission | Visible Light Transmission | ||
| Results | ||||
| Interpretation | Automated; Qualitative | Automated; Qualitative | ||
| Testing Time | Less than 60 minutes | Less than 60 minutes | ||
| Indications for | ||||
| Use | Professional Use | Professional Use |
Predicate Device Comparison:
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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." Below the company name is the tagline "Inspired Science. Trusted Solutions." in a smaller font size, also in blue. The overall design is clean and professional, conveying a sense of global reach and reliability.
| illumigene® Mycoplasma Direct DNA Amplification Assay | |
|---|---|
| Application Reference: | Section 1: General Information |
| Attachment Description: | Attachment 007: 510(k) Summary |
| Application Date: | June 7, 2016 |
| Similarities | ||
|---|---|---|
| MODIFIED DEVICE | ||
| illumigene® Mycoplasma Direct | ||
| DNA Amplification Assay | PREDICATE DEVICE | |
| illumigene® Mycoplasma DNA | ||
| Amplification Assay | ||
| K123423, K152800 | ||
| Analytical | ||
| Sensitivity | M. pneumoniae M129 strain: 200 CFU/mL | |
| M. pneumoniae FH strain: 2350 CFU/mL | M. pneumoniae M129 strain: 200 CFU/mL | |
| M. pneumoniae FH strain: 2350 CFU/mL | ||
| Packaging | Supplied as a kit; 50 tests per kit | Supplied as a kit; 50 tests per kit. |
| Differences | ||
|---|---|---|
| MODIFIED DEVICE | ||
| illumigene® Mycoplasma Direct | ||
| DNA Amplification Assay | PREDICATE DEVICE | |
| illumigene® Mycoplasma | ||
| DNA Amplification Assay | ||
| K123423, K152800 | ||
| Intended Use | The illumigene Mycoplasma Direct DNA | |
| amplification assay, performed on the | ||
| illumipro-10™, is a qualitative in vitro | ||
| diagnostic test for the direct detection of DNA | ||
| from Mycoplasma pneumoniae in human | ||
| throat swabs obtained from patients | ||
| suspected of having Mycoplasma | ||
| pneumoniae infection. | ||
| The illumigene Mycoplasma Direct assay | ||
| utilizes loop-mediated isothermal | ||
| DNA | ||
| amplification (LAMP) technology to detect | ||
| Mycoplasma pneumoniae by targeting a | ||
| segment of the Mycoplasma pneumoniae | ||
| genome. | ||
| Results from the illumigene Mycoplasma | ||
| Direct DNA amplification assay should be | ||
| used in conjunction with clinical presentation, | ||
| other laboratory findings, and epidemiological | ||
| risk factors as an aid in the diagnosis of | ||
| Mycoplasma infection and should not be | ||
| used as the sole basis for treatment or other | ||
| patient management. Positive results do not | ||
| rule out co-infection with other organisms and | ||
| negative results in persons with respiratory | ||
| tract infections may be due to pathogens not | ||
| detected by this assay. Lower respiratory | ||
| tract infections due to M. pneumoniae may | ||
| not be detected by this assay. If lower | ||
| respiratory | ||
| tract | ||
| infection | ||
| due | ||
| to | ||
| M. | The illumigene Mycoplasma DNA amplification | |
| assay, performed on the illumipro-10™, is a | ||
| qualitative in vitro diagnostic test for the direct | ||
| detection of DNA from Mycoplasma pneumoniae | ||
| in human throat and nasopharyngeal swabs | ||
| obtained from patients suspected of having | ||
| Mycoplasma pneumoniae infection. | ||
| The illumigene Mycoplasma assay utilizes loop- | ||
| mediated isothermal DNA amplification (LAMP) | ||
| technology to detect Mycoplasma pneumoniae | ||
| by targeting a segment of the Mycoplasma | ||
| pneumoniae genome. | ||
| Results from the illumigene Mycoplasma DNA | ||
| amplification | ||
| assay should be used | ||
| in | ||
| conjunction with clinical presentation, other | ||
| laboratory findings, and epidemiological risk | ||
| factors as an aid in the diagnosis of Mycoplasma | ||
| infection and should not be used as the sole | ||
| basis for treatment or other patient management. | ||
| Positive results do not rule out co-infection with | ||
| other organisms and negative results in persons | ||
| with respiratory tract infections may be due to | ||
| pathogens not detected by this assay. Lower | ||
| respiratory tract infections due to M. pneumoniae | ||
| may not be detected by this assay. If lower | ||
| respiratory tract infection due to M. pneumoniae | ||
| is suspected, additional laboratory testing using | ||
| methods other than the illumigene Mycoplasma | ||
| DNA Amplification Assay may be necessary. |
7
Image /page/7/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." Below the company name is the tagline "Inspired Science. Trusted Solutions." in a smaller font size, also in blue.
| illumigene® Mycoplasma Direct DNA Amplification Assay | |
|---|---|
| Application Reference: | Section 1: General Information |
| Attachment Description: | Attachment 007: 510(k) Summary |
| Application Date: | June 7, 2016 |
| Differences | ||
|---|---|---|
| MODIFIED DEVICE | ||
| illumigene® Mycoplasma Direct | ||
| DNA Amplification Assay | PREDICATE DEVICE | |
| illumigene® Mycoplasma | ||
| DNA Amplification Assay | ||
| K123423, K152800 | ||
| pneumoniae is suspected, additional | ||
| laboratory testing using methods other than | ||
| the illumigene Mycoplasma Direct DNA | ||
| Amplification Assay may be necessary. | illumigene Mycoplasma is intended for use in | |
| hospital, reference or state laboratory settings. | ||
| The device is not intended for point-of-care use. | ||
| Specimen | ||
| Type | Human throat swab specimens | Human throat swab and nasopharyngeal swab |
| specimens | ||
| Swab Types | Rayon, Flocked Nylon, or Polyester | Cotton, Foam, Flocked Nylon, Polyester or |
| Rayon | ||
| Transport | ||
| Media | Transport medium on pledget: Liquid Amies | |
| without charcoal or Liquid Stuart | 0.85% saline, M4, M4-RT, M5, UTM-RT, or | |
| Liquid Amies without charcoal | ||
| Sample | ||
| Preparation | All reagents for sample processing included | |
| within the kit. | Manual purification/extraction using Qiagen® | |
| DSP DNA Minikit, Catalog Number 61304, | ||
| required. | ||
| Reagents/ | ||
| Components | illumigene Mycoplasma Test Device illumigene Sample Preparation | |
| Apparatus II/ Negative Control III illumigene Heat Treatment Tubes | illumigene Mycoplasma Test Device illumigene Assay Control II illumigene Reaction Buffer II Screw-top Microcentrifuge Tubes | |
| Kit Storage | 2-27 C | 2-8 C |
8
Image /page/8/Picture/0 description: The image shows the logo for Meridian Bioscience, Inc. The logo features a blue globe on the left, followed by the word "Meridian" in a large, blue font. Below "Meridian" is "Bioscience, Inc." in a smaller, blue font. Underneath that is the text "Inspired Science. Trusted Solutions." also in blue.
| illumigene® Mycoplasma Direct DNA Amplification Assay | |
|---|---|
| Application Reference: | Section 1: General Information |
| Attachment Description: | Attachment 007: 510(k) Summary |
| Application Date: | June 7, 2016 |
NON-CLINICAL PERFORMANCE DATA
Analytical Performance:
Precision/Reproducibility:
Blind-coded panels of 10 samples were supplied to three independent laboratories for reproducibility studies. Samples were randomly sorted within each panel to mask sample identities. The panels included contrived manufactured as low positive samples (near the limit of detect, n=3), moderate positive samples (n=3), and high negative samples (n=3). The panel also included one natural negative sample. 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 Mycoplasma Direct and eight illumipro-10 instruments were used in the study. Positive and Negative Controls were tested with each panel. The results are provided in the table below:
| Site 1 | Site 2 | Site 3 | Total | |||||
|---|---|---|---|---|---|---|---|---|
| Sample Type | Percent Agreement | Percent Agreement | Percent Agreement | Percent Agreement | ||||
| High Negative | 30/30 | 100.0% | 30/30 | 100.0% | 30/30 | 100.0% | 90/90 | 100.0% |
| Low Positive | 30/30 | 100.0% | 30/30 | 100.0% | 29/30 | 96.7% | 89/90 | 98.9% |
| Moderate Positive | 30/30 | 100.0% | 30/30 | 100.0% | 30/30 | 100.0% | 90/90 | 100.0% |
| Negative | 9/10 | 90.0% | 10/10 | 100.0% | 10/10 | 100.0% | 29/30 | 96.7% |
| 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% |
Detection Limit:
Analytical Sensitivity studies were designed to verify the analytical limit of detection (LoD) of Mycoplasma pneumoniae with the illumigene Mycoplasma Direct assay. The LoD is defined as the lowest concentration of analyte (CFU/mL) that can be distinguished from negative samples with a high degree of probability (95%). Two strains of M. pneumoniae (M129 and FH) diluted in a simulated negative throat swab matrix were used to establish the LoD with three kit lots of illumigene Mycoplasma Direct. A minimum of three dilutions near the expected LoD in twenty (20) individually prepared replicates were evaluated for each M. pneumoniae strain. The overall confirmed analytical LoD by M. pneumoniae strain for illumigene Mycoplasma Direct is summarized below:
| M. pneumoniae Strain | LoD Concentration
(CFU/mL) |
|------------------------------------|-------------------------------|
| M. pneumoniae FH
(ATCC 15531) | 2350 |
| M. pneumoniae M129
(ATCC 29342) | 200 |
The following M. pneumoniae strains were tested with illumigene Mycoplasma and produced positive reactions at or below stated assay limit of detect of 2350 CFU/mL:Pl 1428 (ATCC 29085), MAC (ATCC 15492), M52 (ATCC 15293), Bru (ATCC 15377), M129-B170 (ATCC 29343), Mutant 22 (ATCC 39505) UAB 55612, UAB 56317, UMTB-10G (ATCC 49899). Testing demonstrated that both Type 1 and Type 2 strains are detected with the assay. The same reactivity is expected with the illumigene Mycoplasma Direct assay.
9
Image /page/9/Picture/0 description: The image shows the logo for Meridian Bioscience, Inc. The logo features a blue globe on the left, followed by the word "Meridian" in a bold, blue font. Below "Meridian" is the word "Bioscience, Inc." in a smaller, blue font. Underneath that is the text "Inspired Science. Trusted Solutions."
| illumigene® Mycoplasma Direct DNA Amplification Assay | |
|---|---|
| Application Reference: | Section 1: General Information |
| Attachment Description: | Attachment 007: 510(k) Summary |
| Application Date: | June 7, 2016 |
Analvtical Specificity:
Interference Testing:
Potentially interfering substances were tested with simulated negative and contrived low positive (M. pneumoniae strains M129 and FH) samples. The following substances, at the saturated solvent/diluent concentrations indicated, do not interfere with illumigene Mycoplasma Direct assay:
Acetaminophen (18.1 mg/mL), Albuterol Sulfate (20 mg/mL), Azithromycin dehydrate (2.0 mg/mL), Cepacol® Mouthwash [Alcohol (1.4% v/v), Cetylpyridinium chloride (0.005% v/v)], Contac® Cold + Flu Tablets [Acetaminophen (14.8 mq/mL), Chlorpheniramine maleate (0.06 mg/mL), Phenylephrine HCl (0.15 mg/mL)], Diphenhydramine HCI (2.6 mg/mL), Erythromycin (20.0 mg/mL), HALLS® Cough Drops [Menthol (0.06 mg/mL)], Ibuprofen (12.7 mg/mL), Phenylephrine HCl (0.595 mg/mL), Prednisone (20.0 mg/mL), Robitussin® Cough+Chest Congestion Cough Syrup (Dextromethorphan HBr (0.20 mq/mL), Guaifenesin (2.0 mg/mL)), Saline Nasal Spray [Sodium chloride (0.65 mg/mL)], Mucus (5.0mg/mL), and White Blood Cells (0.5% v/v).
Whole blood was found to produce invalid results at concentrations greater than 2%.
Phenylephrine HCI at concentrations greater than 0.595 mg/mL may produce false negative results with low positive samples.
Robitussin Cough+Congestion Cough Syrup initially produced 1/3 invalid results with Positive Sample P2 that produced acceptable results during repeat testing (1/1 positive). Robitussin® Cough Syrup is not considered an interferent.
Cross-Reactivity Study:
Crossreactivity studies were previously performed with the illumicene Mycoplasma DNA Amplification assay. P ositive and negative specimens inoculated with potentially interfering bacterial or fungal organisms to minimum final concentrations of 1.0 x 10 CFU/mL. Viruses were tested at concentrations greater than 1.0 x 10 TClDgg/mL or 1.0 x 106 copies/mL. Human DNA was tested at 2.0 ng/test with no crossreactivity observed. Positive specimens contained M. pneumoniae concentrations near the limit of detection. None of the following organisms or materials were identified as crossreactive or interfering in the illumigene Mycoplasma assay:
Acinetobacter baumannii, Acinetobacticus, Actinomyces odontolyticus, Bacillus subtilis, Bacteroides fragilis, Bordetella parapertussis, Bordetella pertussis, Burkholderia cepacia, Candida glabrata, Candida parapsilosis. Chlamvdia pneumoniae. Citrobacter freundii. Clostridium difficile. Corvnebacterium diphtheriae, Enterobacter cloacae, Enterococcus faecalis, Escherichia coli (ESBL), Fusobacterium nucleatum, Haemophilus influenzae, Haemophilus parainfluenzae, Helicobacter pvlori. Klebsiella pneumoniae (KPC). Legionella pneumophila. Listeria monocytogenes, Moraxella catarrhalis, Mycoplasma hominis, Neisseria cinerea, Neisseria gonorrhoeae, Neisseria meningitidis, Nocardia asteroides, Peptostreptococcus anaerobius, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella paratyphi (Group A), Salmonella typhimurium (Group B), Serratia liquefaciens, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus agalactiae (Group B), Streptococcus anginosus (Group F), Streptococus bovis (Group D), Streptococcus canis (Group G), Streptococcus equisimilis, Streptococcus mitis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus salivarius, Ureaplasma urealyticum, Adenovirus, Coxsackievirus, Cytomegalovirus, Epstein Barr virus. Herpes simplex virus 1. Herpes simplex virus 2. Human metapneumovirus. Influenza A. Influenza B, Parainfluenza virus 1, Parainfluenza virus 3, Respiratory syncytial virus A, Respiratory syncytial virus B, Rhinovirus, Human DNA.
No crossreactivity is expected with the illumigene Mycoplasma Direct assay.
10
Image /page/10/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 horizontal line separates the two parts of the name. Below the company name is the tagline "Inspired Science. Trusted Solutions."
| illumigene® Mycoplasma Direct DNA Amplification Assay | |
|---|---|
| Application Reference: | Section 1: General Information |
| Attachment Description: | Attachment 007: 510(k) Summary |
| Application Date: | June 7, 2016 |
Assav cut-off:
The illumigene Mycoplasma Direct assay is manufactured with fixed cut-off values. The product is designed with a pre-selected cut-off value and amplification reagent concentrations are optimized to ensure appropriate reactions are obtained. Development optimization 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, NEGATIVE). 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.
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:
The performance characteristics of the illumigene Mycoplasma Direct DNA Amplification Assay were established in clinical studies conducted in 2015-2016 at independent clinical test sites representing three geographically distinct regions throughout the United States. Performance characteristics of the assay were compared to a reference molecular in vitro diagnostic method, the illumigene Mycoplasma DNA Amplification Assay (Meridian Bioscience, Inc., Cincinnati, OH). A total of 458 prospective, deidentified, throat swab specimens collected under informed consent from symptomatic male and female patients were evaluated. Two samples (0.4%) were excluded from the clinical sample population due to an instrument error during testing (1) or an unacceptable sample type (1) for a total of 456 eligible samples for analysis. There were no invalid results generated by the illumigene Mycoplasma Direct assay during the clinical study (0.0%; 95% Cl: 0.0 - 0.8%). Performance characteristics of the illumigene Mycoplasma Direct assay are summarized below.
| illumigene Mycoplasma | ||||
|---|---|---|---|---|
| illumigene Mycoplasma Direct | Positive | Negative | Invalid | Total |
| Positive | 24 | 10a | 0 | 34 |
| Negative | 1b | 421 | 0 | 422 |
| Invalid | 0 | 0 | 0 | 0 |
| Total | 25 | 431 | 0 | 456 |
| 95% CI | ||||
| Positive Percent Agreement | 24/25 | 96.0% | 80.5 - 99.3% | |
| Negative Percent Agreement | 421/431 | 97.7% | 95.8 - 98.7% | |
| Overall Percent Agreement | 445/456 | 97.6% | 95.7 - 98.6% | |
| Invalid Rate | 0/456 | 0.0% | 0.0 - 0.8% |
a 4/10 samples were identified positive by illumigene Mycoplasma after testing with an additional frozen sample.
PRepeat testing by illumigene Mycoplasma with the original patient sample produced negative results.
11
| Image: Meridian Bioscience, Inc. logo | illumigene® Mycoplasma Direct DNA Amplification Assay | |
|---|---|---|
| Application Reference: | Section 1: General Information | |
| Attachment Description: | Attachment 007: 510(k) Summary | |
| Application Date: | June 7, 2016 |
The eligible study population included throat swab specimens from pediatric patients ranging in age from 3 weeks to 97 years. There was no difference in assay performance based on patient age. The study population included 230 (50.4%) female and 226 (49.6%) male specimens. There was no difference in assay performance based on gender. Prevalence based on patient age is provided below:
| Patient Age | Total Positive | Total Samples | Prevalence (%) |
|---|---|---|---|
| 0 to 1 Month | 0 | 7 | 0.0% |
| 2 Months to 2 Years | 5 | 157 | 3.2% |
| 3 Years to 12 Years | 22 | 147 | 15.0% |
| 13 Years to 21 Years | 5 | 38 | 13.2% |
| 22 Years to 65 Years | 2 | 86 | 2.3% |
| >65 Years | 0 | 21 | 0.0% |
Expected Values:
The incidence of Mycoplasma pneumoniae was established during clinical studies conducted in 2015-2016. The overall prevalence of M. pneumoniae in prospective throat swab specimens was 7.5% (34/456).
CONCLUSION
The illumigene Mycoplasma Direct DNA amplification assay, performed on the illumipro-10™, can be used to detect Mycoplasma pneumoniae in human throat swab specimens and is substantially equivalent to the predicate device.