K Number
K123423
Device Name
ILLUMIGENE MYCOPLASAMA DNA AMPLIFICATION ASSAY, AND ILLUMIGENE MYCOPLASMA EXTERNAL CONTROLS KIT
Date Cleared
2013-06-05

(211 days)

Product Code
Regulation Number
866.3980
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP Authorized
Intended Use
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. illumigene Mycoplasma is intended for use in hospital, reference or state laboratory settings. The device is not intended for point-of-care use.
Device Description
The illumigene Molecular Diagnostic Test System is comprised of the illumigene® Mycoplasma DNA Amplification Assay Test Kit, the illumigene® Mycoplasma External Control Kit and the illumipro-10™ Automated Isothermal Amplification and Detection System. The illumigene Mycoplasma assay utilizes loop-mediated isothermal amplification (LAMP) technology to detect the presence of Mycoplasma pneumoniae in human respiratory specimens (throat and nasopharyngeal swab specimens), Each illumigene Mvcoplasma assay is completed using an illumicene Assay Control Reagent containing Control material, an illumigene Reaction Buffer, an illumigene Mycoplasma Test Device and microcentrifuge tubes. Respiratory specimens are combined with the illumigene Assay Control Reagent. The Speciment is manually extracted and purfied using a commercially available extraction kit (Qiagen, QlAamp® DSP DNA Mini Kit). Extracted DNA is heat-treated. Target and Control DNA are made available for isothermal amplification via heattreatment. The heat-treated Specimen/Control sample is added to the illumigene Reaction Buffer. DNA amplification occurs in the illumigene 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 200 base pair sequence of the M. pneumoniae genome 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 (Signalinia) S) and at the assay Run End (Signalmar, S). 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 'INVALD': 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 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. The illumigene Mycoplasma External Controls Kit contains a Positive Control Reagent, 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. External Control reagents are provided for use in routine Quality Control testing. ## illumipro-10™ Automated Isothermal Amplification and Detection System: The illumipro-10™ heats each illumigene Mycoplasma Test Device containing prepared samples and Control Reagent, facilitating amplification of target DNA. When Mvcoplasma pneumoniae is present in the respiratory swab sample, a conserved sequence of the M. pneumoniae is amplified and magnesium pyrophosphate is generated. Magnesium pyrophosphate forms a precipitate in the reaction mixture. The illumipro-10 detects the change in light transmission through the reaction mixture created by the precipitating magnesium pyrophosphate. The illumipro-10 reports sample results as INVALID, POSITIVE or NEGATIVE based on the detected change in light transmission. The illumipro-10™ System Description was reviewed in previous submission. K10012. K112125. K121044 and K122019. No system or software changes were made for the illumigene Mycoplasma assay.
More Information

No
The device description details a fixed algorithm based on absorbance ratios and established cut-off values to determine results, with no mention of AI or ML.

No
This device is an in vitro diagnostic test designed to detect the DNA of Mycoplasma pneumoniae, aiding in the diagnosis of infection, rather than directly treating or preventing disease.

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" and the "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".

No

The device description explicitly states that the system is comprised of a test kit, an external control kit, and the illumipro-10™ Automated Isothermal Amplification and Detection System, which is a piece of hardware that heats and detects changes in the reaction mixture. This indicates the device is a combination of hardware and software, not software-only.

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

  • Intended Use: The "Intended Use / Indications for Use" section explicitly states that the illumigene Mycoplasma DNA amplification assay is a "qualitative in vitro diagnostic test".
  • Purpose: The assay is designed for the "direct detection of DNA from Mycoplasma pneumoniae in human throat and nasopharyngeal swabs obtained from patients suspected of having Mycoplasma pneumoniae infection." This is a diagnostic purpose performed outside of the body (in vitro).
  • Sample Type: It uses human biological specimens (throat and nasopharyngeal swabs).
  • Diagnostic Aid: The results are intended to be used "as an aid in the diagnosis of Mycoplasma infection".

All of these points align with the definition of an In Vitro Diagnostic device.

N/A

Intended Use / Indications for Use

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 ampification (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 coinfection 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.

illumigene Mycoplasma is intended for use in hospital, reference or state laboratory settings. The device is not intended for point-of-care use.

Product codes

OZX, OOI

Device Description

The illumigene Molecular Diagnostic Test System is comprised of the illumigene® Mycoplasma DNA Amplification Assay Test Kit, the illumigene® Mycoplasma External Control Kit and the illumipro-10™ Automated Isothermal Amplification and Detection System.

The illumigene Mycoplasma assay utilizes loop-mediated isothermal amplification (LAMP) technology to detect the presence of Mycoplasma pneumoniae in human respiratory specimens (throat and nasopharyngeal swab specimens). Each illumigene Mvcoplasma assay is completed using an illumicene Assay Control Reagent containing Control material, an illumigene Reaction Buffer, an illumigene Mycoplasma Test Device and microcentrifuge tubes. Respiratory specimens are combined with the illumigene Assay Control Reagent. The Speciment is manually extracted and purfied using a commercially available extraction kit (Qiagen, QlAamp® DSP DNA Mini Kit). Extracted DNA is heat-treated. Target and Control DNA are made available for isothermal amplification via heattreatment. The heat-treated Specimen/Control sample is added to the illumigene Reaction Buffer. DNA amplification occurs in the illumigene 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 200 base pair sequence of the M. pneumoniae genome 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 (Signalinia) S) and at the assay Run End (Signalmar, S). 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 'INVALD': 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 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.

The illumigene Mycoplasma External Controls Kit contains a Positive Control Reagent, 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. External Control reagents are provided for use in routine Quality Control testing.

illumipro-10™ Automated Isothermal Amplification and Detection System:

The illumipro-10™ heats each illumigene Mycoplasma Test Device containing prepared samples and Control Reagent, facilitating amplification of target DNA. When Mvcoplasma pneumoniae is present in the respiratory swab sample, a conserved sequence of the M. pneumoniae is amplified and magnesium pyrophosphate is generated. Magnesium pyrophosphate forms a precipitate in the reaction mixture. The illumipro-10 detects the change in light transmission through the reaction mixture created by the precipitating magnesium pyrophosphate. The illumipro-10 reports sample results as INVALID, POSITIVE or NEGATIVE based on the detected change in light transmission.

The illumipro-10™ System Description was reviewed in previous submission. K10012. K112125. K121044 and K122019. No system or software changes were made for the illumigene Mycoplasma assay.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

human throat and nasopharyngeal swabs

Indicated Patient Age Range

Age information was known for 83.5% (269/322) of the patients included in the performance analysis. Seven (2.6%) patients tested were between 0 - 28 days of age; 38 (14.1%) patients were between 29 days and up to 2 years of age; 139 (51.7%) palients were between 2 and up to 12 years of age; 61 (22.7%) patients were between 12 and up to 18 years of age; and 9 (3.3%) patients were between18 and up to 21 years of age. The remaining 15 (5.6%) study patients were 21 years or older. No performance differences were noted based on chronological age.

Intended User / Care Setting

hospital, reference or state laboratory settings. The device is not intended for 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

A total of 334 qualified throat and nasopharyngeal (NP) swab specimens, collected from patients.suspected of Mycoplasma pneumoniae infection were evaluated with the test device to establish performance characteristics. Specimens were leftover deidentified specimens submitted to the testing laboratories for routine M. pneumoniae testing. Specimens included in performance evaluation were prospective (never frozen) and retrospective (frozen prior to illumigene testing). The performance of illumigene was compared to a Composite Reference Method that included M. pneumoniae bacterial culture with identification and a validated real-time PCR assay followed by bi-directional sequencing for positive specimens producing positive Mycoplasma pneumoniae results from either the bacterial culture or real-time PCR and bi-directional sequencing were considered positive. Specimens negative for both culture and PCR were considered negative. A total of 12 specimens were excluded from the clinical sample population because culture results were inconclusive and PCR negative, making final disposition of patient status unavailable. A total of 103 (30.8%) prospective samples and 219 retrospective (65.6%) were tested with 1 initial invalid result (0.30%).

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Clinical Studies:
Clinical trials for the illumigene Mycoplasma DNA Amplification Assay, including the illumipro-10 Automated Isothermal amplification and detection system, were conducted from February to September 2012.

A total of 334 qualified throat and nasopharyngeal (NP) swab specimens, collected from patients.suspected of Mycoplasma pneumoniae infection were evaluated with the test device to establish performance characteristics. Specimens were leftover deidentified specimens submitted to the testing laboratories for routine M. pneumoniae testing. Specimens included in performance evaluation were prospective (never frozen) and retrospective (frozen prior to illumigene testing). The performance of illumigene was compared to a Composite Reference Method that included M. pneumoniae bacterial culture with identification and a validated real-time PCR assay followed by bi-directional sequencing for positive specimens producing positive Mycoplasma pneumoniae results from either the bacterial culture or real-time PCR and bi-directional sequencing were considered positive. Specimens negative for both culture and PCR were considered negative. A total of 12 specimens were excluded from the clinical sample population because culture results were inconclusive and PCR negative, making final disposition of patient status unavailable. A total of 103 (30.8%) prospective samples and 219 retrospective (65.6%) were tested with 1 initial invalid result (0.30%).

Data indicates performance is optimal when specimens are collected and tested prospectively.

Table 1. illumigene Mycoplasma Assay Performance: Nasopharyngeal Swab Specimens

Specimen Descriptionillumigene vs. Comparator (Composite Reference Method)% Sensitivity or PPA95% CIillumigene vs. Comparator (Composite Reference Method)% Specificity or NPA95% CIInvalid Results
Prospective4/4100.0%51.0 - 100.0%48/48100%92.6 - 100.0%0
Retrospective34/3694.4%81.9 - 98.5%86/9095.6%89.1 - 98.3%0
Specimen Descriptionillumigene vs. Comparator (PCR with Bi-Directional Sequencing)% Sensitivity or PPA95% CIillumigene vs. Comparator (PCR with Bi-Directional Sequencing)% Specificity or NPA95% CIInvalid Results
Prospective4/4100.0%51.0 - 100.0%48/48100%92.6 - 100.0%0
Retrospective34/3694.4%81.9 - 98.5%86/9095.6%89.1 - 98.3%0

Table 2. illumigene Mycoplasma Assay Performance: Throat Swab Specimens

Specimen Descriptionillumigene vs. Comparator (Composite Reference Method)% Sensitivity or PPA95% CIillumigene vs. Comparator (Composite Reference Method)% Specificity or NPA95% CIInvalid Results
Prospective8/8100.0%67.6 - 100.0%43/43100.0%91.8 - 100.0%0
Retrospective22/26a84.6%66.5 - 93.9%66/6798.5%92.0 - 99.7%1
Specimen Descriptionillumigene vs. Comparator (PCR with Bi-Directional Sequencing)% Sensitivity or PPA95% CIillumigene vs. Comparator (PCR with Bi-Directional Sequencing)% Specificity or NPA95% CIInvalid Results
Prospective8/8100.0%67.6 - 100.0%43/43100.0%91.8 - 100.0%0
Retrospective21/21b100.0%84.5 - 100.0%70/7297.2%90.4 - 99.2%1

a. Four specimens originally identified by culture as positived by either the illumigene assay or the independent PCR method. Results suggest sample degradation during storage.
b. One specimen onginally identified by the illure as positive was negative by the independent PCR method. This specimen is classified as a false positive relative to PCR.

NON-CLINICAL PERFORMANCE DATA:

Precision/Reproducibility:
Blind-coded panels of 10 samples were supplied to three independent laboratories. Samples were randomly sorted within each panel to mask sample identities. The panels included contrived samples manufactured as low positive samples (i.e. limit of detection, n = 3) and high negative samples (n = 3). The panels also included contrived positive (n = 3) samples and natural negative samples (n = 1). 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 and five illumipro-10 instruments were used in this study. Positive and Neqative Controls were tested each day of testing.

Sample TypeSite 1 Percent agreementSite 2 Percent agreementSite 3 Percent agreementTotal Percent agreement
Negative10/10 100%10/10 100%10/10 100%30/30 100%
High Negative30/30 100%30/30 100%30/30 100%90/90 100%
Low Positive30/30 100%30/30 100%30/30 100%90/90 100%
Positive29/30 96.7%30/30 100%29/30 96.7%88/90 97.8%
Negative Control10/10 100%10/10 100%10/10 100%30/30 100%
Positive Control10/10 100%10/10 100%10/10 100%30/30 100%

Detection Limit:
Analytical Sensitivity studies were designed to determine, within 95% confidence intervals, the analytical limit of detection (LoD) of Mycoplasma pneumoniae. The LoD is the lowest number of colony-forming units (CFUs) per test aliquot that can be distinguished from negative samples with a high degree of probability (95%). Two M. pneumoniae strains, FH (ATCC 15531) and M129, were evaluated for analytical Limit of Detection. Culture confirmed stock concentrations were serially diluted into negative matrix (rayon swabs inoculated with normal nasal flora screened negative for M. pneumoniae and M4 non-nutritive Transport Medium) and tested in the illumigene Mycoplasma assay. Meridian utilized a simulated negative matrix for analytical studies. Each dilution evaluated in the illuminene Mycoolasma assay was done so using individually prepared replicates. Not all prepared dilutions were tested in the illumigene Mycoplasma assay; testing for select dilutions was discontinued when replicate testing did not meet criteria established for limit of detection (e.g. more than 1 negative replicate obtained). The lowest dilution producing positive results in at least 19 of 20 replicates was identified as the assay limit of detection.

Testing was performed using three lots of illumigene Mycoplasma and six illumipro-10 instruments. External Positive and Negative Controls were tested each day throughout the study. The Limit of Delection for the assay was reported as 88 CFU/Test (2350 CFU/mL) for FH (ATCC 15531) and 7.5 CFU/Test (200 CFU/mL) for M129.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Nasopharyngeal Swabs (Composite Reference Method):

  • Prospective Sensitivity: 100.0% (95% CI: 51.0 - 100.0%)
  • Prospective Specificity: 100% (95% CI: 92.6 - 100.0%)
  • Retrospective PPA: 94.4% (95% CI: 81.9 - 98.5%)
  • Retrospective NPA: 95.6% (95% CI: 89.1 - 98.3%)

Nasopharyngeal Swabs (PCR with Bi-Directional Sequencing):

  • Prospective Sensitivity: 100.0% (95% CI: 51.0 - 100.0%)
  • Prospective Specificity: 100% (95% CI: 92.6 - 100.0%)
  • Retrospective PPA: 94.4% (95% CI: 81.9 - 98.5%)
  • Retrospective NPA: 95.6% (95% CI: 89.1 - 98.3%)

Throat Swabs (Composite Reference Method):

  • Prospective Sensitivity: 100.0% (95% CI: 67.6 - 100.0%)
  • Prospective Specificity: 100.0% (95% CI: 91.8 - 100.0%)
  • Retrospective PPA: 84.6% (95% CI: 66.5 - 93.9%)
  • Retrospective NPA: 98.5% (95% CI: 92.0 - 99.7%)

Throat Swabs (PCR with Bi-Directional Sequencing):

  • Prospective Sensitivity: 100.0% (95% CI: 67.6 - 100.0%)
  • Prospective Specificity: 100.0% (95% CI: 91.8 - 100.0%)
  • Retrospective PPA: 100.0% (95% CI: 84.5 - 100.0%)
  • Retrospective NPA: 97.2% (95% CI: 90.4 - 99.2%)

Precision/Reproducibility (Total Percent Agreement):

  • Negative: 100%
  • High Negative: 100%
  • Low Positive: 100%
  • Positive: 97.8%
  • Negative Control: 100%
  • Positive Control: 100%

Predicate Device(s)

K120267, FilmArray® Respiratory Panel (RP)

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

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

JUN 0 5 2013

OZX)

| Image: Meridian Bioscience Logo
Meridian
Bioscience, Inc.
Inspired Science. Trusted Solutions." | illumigene® Mycoplasma DNA Amplification Assay
Request for Additional Information |
|------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------|
| Application Reference: | Section 2 |
| Attachment Description: | 510(k) Summary |
| Application Date: | May 30, 2013 [1] |

510(k) Summary

510(k) number:K123423Date of Preparation:May 30, 2013
Owner:Meridian Bioscience, Inc.
3471 River Hills Drive
Cincinnati, Ohio 45244 USA
Phone: (513) 271-3700
Fax: (513) 272-5213
Contact:Primary Contact:
Jackie Godbey
Regulatory Affairs & Design Assurance Associate

Secondary Contact:
Michelle Smith
Sr. Director, Regulatory Affairs & Design Assurance | | |
| Trade Name: | illumigene® Mycoplasma DNA Amplification Assay
illumigene® Mycoplasma External Controls | | |
| Classification Name: | Respiratory viral panel multiplex nucleic acid assay (21 CFR 866.3980, Product Code) | | |
| Predicate Device: | K120267, FilmArray® Respiratory Panel (RP); Catalog RFIT-ASY-0001 | | |
| Device Description: | | | |

The illumigene Molecular Diagnostic Test System is comprised of the illumigene® Mycoplasma DNA Amplification Assay Test Kit, the illumigene® Mycoplasma External Control Kit and the illumipro-10™ Automated Isothermal Amplification and Detection System.

The illumigene Mycoplasma assay utilizes loop-mediated isothermal amplification (LAMP) technology to detect the presence of Mycoplasma pneumoniae in human respiratory specimens (throat and nasopharyngeal swab specimens), Each illumigene Mvcoplasma assay is completed using an illumicene Assay Control Reagent containing Control material, an illumigene Reaction Buffer, an illumigene Mycoplasma Test Device and microcentrifuge tubes. Respiratory specimens are combined with the illumigene Assay Control Reagent. The Speciment is manually extracted and purfied using a commercially available extraction kit (Qiagen, QlAamp® DSP DNA Mini Kit). Extracted DNA is heat-treated. Target and Control DNA are made available for isothermal amplification via heattreatment. The heat-treated Specimen/Control sample is added to the illumigene Reaction Buffer. DNA amplification occurs in the illumigene 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 200 base pair sequence of the M. pneumoniae genome 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 (Signalinia) S) and at the assay Run End (Signalmar, S). 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.

1

| Image: Meridian Bioscience, Inc. logo
Meridian
Bioscience, Inc.
Inspired Science. Trusted Solutions." | K123423: illumigene® Mycoplasma DNA Amplification Assay
Request for Additional Information | | |
|----------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------|----------------|-----|
| | Application Reference: | Section 2 | |
| | Attachment Description: | 510(k) Summary | |
| | Application Date: | May 30, 2013 | [2] |

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 'INVALD': 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 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.

The illumigene Mycoplasma External Controls Kit contains a Positive Control Reagent, 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. External Control reagents are provided for use in routine Quality Control testing.

illumipro-10™ Automated Isothermal Amplification and Detection System:

The illumipro-10™ heats each illumigene Mycoplasma Test Device containing prepared samples and Control Reagent, facilitating amplification of target DNA. When Mvcoplasma pneumoniae is present in the respiratory swab sample, a conserved sequence of the M. pneumoniae is amplified and magnesium pyrophosphate is generated. Magnesium pyrophosphate forms a precipitate in the reaction mixture. The illumipro-10 detects the change in light transmission through the reaction mixture created by the precipitating magnesium pyrophosphate. The illumipro-10 reports sample results as INVALID, POSITIVE or NEGATIVE based on the detected change in light transmission.

The illumipro-10™ System Description was reviewed in previous submission. K10012. K112125. K121044 and K122019. No system or software changes were made for the illumigene Mycoplasma assay.

Intended Use:

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 Mycopiasma 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. preumoniae is suspected, additional laboratory testing using methods other than the illumigene Mycoplasma 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.

2

Image /page/2/Picture/0 description: The image shows the logo for Meridian Bioscience, Inc. The logo features a globe graphic on the left, followed by the company name in bold, black font. Below the company name is the tagline "Inspired Science. Trusted Solutions."

K123423: illumigene® Mycoplasma DNA Amplification Assay
Request for Additional Information

Application Reference:Section 2
Attachment Description:510(k) Summary
Application Date:May 30, 2013[3]

Predicate Device Comparison:

Similarities
ItemDEVICE
illumigene® MycoplasmaPREDICATE
FilmArray® Respiratory Panel (RP) System
K120267
Intended UseQualitativeQualitative
Indications for UseProfessional UseProfessional Use
Assay TargetMycoplasma pneumoniae genomeMycoplasma pneumoniae DNA, Toxin Gene
Specimen TypesNasopharyngeal SwabNasopharyngeal Swab
DetectionSelf contained and automatedSelf contained and automated
Differences
ItemDEVICE
illumigene® MycoplasmaPREDICATE
FilmArray® Respiratory Panel (RP) System
K120267
Specimen TypeNasopharyngeal Swab
Throat SwabNasopharyngeal Swab
Test FormatDNA Amplification Assay; Loop-Mediated Isothermal
Amplification (LAMP)Multiplex PCR Amplification Assay
Reagents/ComponentsThe illumigene Mycoplasma DNA Amplification
Assay Kit contains illumigene Assay Control II,
illumigene Reaction Buffer II, illumigene
Mycoplasma Test Device and Screw-top Tubes.
External Control materials are provided separately in
the illumigene Mycoplasma External Control Kit.
The illumipro-10 is provided separately.The FilmArray Respiratory Panel (RP) Assay Kit contains
FilmArray RP pouch, Sample Buffer, Hydration Solution,
transfer pipettes and Sample Loading Syringes (with
attached cannula). The FilmArray Instrument with Loading
Station is provided separately.
External ControlsExternal Positive and Negative Controls for the
illumigene Mycoplasma Assay are provided in the
illumigene Mycoplasma External Control Kit.
The External Positive Control Reagent contains tris
buffered solution containing non-infectious Plasmid
DNA ( M. pneumoniae and S. aureus inserts) with
azide (0.09%) as a preservative.
The External Negative Control Reagent contains tris
buffered solution containing non-infectious Plasmid
DNA ( S. aureus insert) with azide (0.09%) as a
preservativeThe FilmArray Respiratory Panel (RP) Assay does not
require external controls. External Controls are not
indicated or available for the FilmArray Respiratory Panel
(RP) Assay.

3

| Image: Meridian Bioscience, Inc. logo | K123423: illumigene® Mycoplasma DNA Amplification Assay
Request for Additional Information | |
|---------------------------------------|-----------------------------------------------------------------------------------------------|-----|
| Application Reference: | Section 2 | |
| Attachment Description: | 510(k) Summary | |
| Application Date: | May 30, 2013 | [4] |

Differences (continued)
ItemDEVICE
Illumigene® MycoplasmaPREDICATE
FilmArray® Respiratory Panel (RP) System
K120267
Amplification
Technology and Target
Sequence DetectedAssay performed with the illumipro-10™ instrument,
utilizes loop-mediated isothermal amplification
(LAMP) technology for the detection of 208 base pair
(bp) sequence of the Mycoplasma pneumoniae
genome. The illumipro-10™ detects changes in
reaction solution absorbance by visible light
transmission.Assay performed with the FilmArray Instrument, utilizes
freeze-dried reagents to perform nucleic acid purification,
reverse transcription, and nested multiplex PCR with DNA
melt analysis for the detection of multiple respiratory
pathogens including detection of a specific Mycoplasma
pneumoniae toxin gene sequence.
Instrumentationillumipro-10™ Automated Isothermal Amplification
and Detection SystemFilmArray® Instrument
Reading MethodVisible Light TransmissionFluorescence Emissions
Interpretation of ResultsResults of the illumigene Mycoplasma Assay are
interpreted by the illumipro-10 and reported as
INVALID, POSITIVE and NEGATIVE based on
change in light transmission of the reaction mixtures.
EMPTY WELL is reported when an illumigene Test
Device is not detected by the illumipro-10 or when
questionable Signal Initial (S) transmission is
detected.Results of the FilmArray Respiratory Panel (RP) Assay
report are interpreted by the FilmArray Instrument for M.
pneumoniae and reported as Detected, Not Detected or
Invalid.
Performance
CharacteristicsProspective Specimens
Nasopharyngeal Swabs
Sensitivity: 100.0% [95% CI: 51.0% - 100.0%]
Specificity: 100.0% [95% CI: 92.6% - 100.0%]
Throat Swabs
Sensitivity: 100.0% [95% CI: 67.6% - 100.0%]
Specificity: 100.0% [95% CI: 91.8% - 100.0%]
Retrospective Specimens
Nasopharyngeal Swabs
PPA: 94.4% [95% CI: 81.9% - 98.5%]
NPA: 95.6% [95% CI: 89.1% - 98.3%]
Throat Swabs
PPA: 84.6% [95% CI: 66.5% - 93.9%]
NPA: 98.5% [95% CI: 92.0% - 99.7%]Prospective Samples
Nasopharyngeal Swabs
Sensitivity: 100.0% [95% CI:39.8 – 100%]
Specificity: 100.0% [95% CI: 99.7 - 100%]
Throat Swab - Not Evaluated
Retrospective Samples
Nasopharyngeal Swabs
PPA: 84.4% [95% CI: 73.1 - 92.2%]
NPA: 89.2% [95% CI: 79.1 - 95.6%]
Throat Swab - Not Evaluated

:

.

4

| Image: Meridian Bioscience, Inc. logo | K123423: illumigene ® Mycoplasma DNA Amplification Assay
Request for Additional Information | | |
|---------------------------------------|-------------------------------------------------------------------------------------------------------|----------------|-----|
| | Application Reference: | Section 2 | |
| | Attachment Description: | 510(k) Summary | |
| | Application Date: | May 30, 2013 | [5] |

NON-CLINICAL PERFORMANCE DATA:

Analytical Performance:

Precision/Reproducibility:

Blind-coded panels of 10 samples were supplied to three independent laboratories. Samples were randomly sorted within each panel to mask sample identities. The panels included contrived samples manufactured as low positive samples (i.e. limit of detection, n = 3) and high negative samples (n = 3). The panels also included contrived positive (n = 3) samples and natural negative samples (n = 1). 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 and five illumipro-10 instruments were used in this study. Positive and Neqative Controls were tested each day of testing. The results are given in the table below:

| Sample Type | Site 1
Percent agreement | Site 2
Percent agreement | Site 3
Percent agreement | Total
Percent agreement |
|------------------|-----------------------------|-----------------------------|-----------------------------|----------------------------|
| Negative | 10/10 100% | 10/10 100% | 10/10 100% | 30/30 100% |
| High Negative | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% |
| Low Positive | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% |
| Positive | 29/30 96.7% | 30/30 100% | 29/30 96.7% | 88/90 97.8% |
| Negative Control | 10/10 100% | 10/10 100% | 10/10 100% | 30/30 100% |
| Positive Control | 10/10 100% | 10/10 100% | 10/10 100% | 30/30 100% |

Detection Limit:

Analytical Sensitivity studies were designed to determine, within 95% confidence intervals, the analytical limit of detection (LoD) of Mycoplasma pneumoniae. The LoD is the lowest number of colony-forming units (CFUs) per test aliquot that can be distinguished from negative samples with a high degree of probability (95%). Two M. pneumoniae strains, FH (ATCC 15531) and M129, were evaluated for analytical Limit of Detection. Culture confirmed stock concentrations were serially diluted into negative matrix (rayon swabs inoculated with normal nasal flora screened negative for M. pneumoniae and M4 non-nutritive Transport Medium) and tested in the illumigene Mycoplasma assay. Meridian utilized a simulated negative matrix for analytical studies. Each dilution evaluated in the illuminene Mycoolasma assay was done so using individually prepared replicates. Not all prepared dilutions were tested in the illumigene Mycoplasma assay; testing for select dilutions was discontinued when replicate testing did not meet criteria established for limit of detection (e.g. more than 1 negative replicate obtained). The lowest dilution producing positive results in at least 19 of 20 replicates was identified as the assay limit of detection.

Testing was performed using three lots of illumigene Mycoplasma and six illumipro-10 instruments. External Positive and Negative Controls were tested each day throughout the study. The Limit of Delection for the assay was reported as 88 CFU/Test (2350 CFU/mL) for FH (ATCC 15531) and 7.5 CFU/Test (200 CFU/mL) for M129.

The following M. preumoniae strains were tested and produced positive reactions at or below stated assay limit of detection of 88 CFU/Test (2350 CFU/mL) with illumigene Mycoplasma: P11428, MAC (ATCC 15492), M52, Bru, M129-B170, Mutant 22, UAB 56317, UMTB-10G (M. pneumoniae and M. genitalium).

5

| Image: Meridian Bioscience, Inc. logo | K123423: illumigene® Mycoplasma DNA Amplification Assay
Request for Additional Information | |
|---------------------------------------|-----------------------------------------------------------------------------------------------|-----|
| Application Reference: | Section 2 | |
| Attachment Description: | 510(k) Summary | |
| Application Date: | May 30, 2013 | [6] |

Analytical Specificity:

Interference Testing:

Interfering substance testing was performed to assess the potential impact of non-microbial contaminants expected to be present in samples collected for Mycoplasma pneumoniae testing on illumigene Mycoplasma test results. Potentially interfering substances were tested with simulated negative (M. pneumoniae strains M129 and FH) samples. Potentially interfering substances were added to M4 medium with rayon swabs (Negative Sample) and to M4 medium with polyester swabs (Contrived Positive Sample) at final concentrations of 0.5% V/V or greater and tested.

The following biological substances, at the saturated solventrations indicated do not interfere with the illumigene Mycoplasma test results: Mucus (5.0 mg/mL), White blood cells (0.5% v/v), Whole blood (5% V/V).

The following chemical substances, at the saturated solventiations indicated do not interfere with test results: Acetaminophen (18.1 mg/mL), Albuterol Suffate (20 mg/mL), Aspirin (9.1 mg/mL), Azithromycin dehydrate (2.0 mg/mL), Cepacol® Mouthwash [Ethanol, denatured (1.4% v/v), Cetylpyridinium chloride (0.005% v/v)] Contac® Cold + Flu Tablets [Acetaminophen (14.8 mg/mL), Chlorpheniramine maleate (0.06 mg/mL), Phenylephrine HC! (0.15 mg/mL)], Diphenhydramine HCl (2.6 mg/mL), Erythromycin (20.0 mg/mL), HALLS® Cough (Menthol (0.06 mg/mL)), Ibuprofen (12.7 ma/mL), Phenylephrine HCl (0.595 mg/mL), Prednisone (20.0 mg/mL), Robitussin® Cough+Chest Congestion Cough Syrup [Dextromethorphan HBr (0.20 mg/mL), Guaifenesin (2.0 mg/mL)}, Saline Nasal Spray [Sodium chloride (0.65 mg/mL)],

Phenylephrine HCI found in nasal decongestants produced false negative results at concentrations above 0.595 mg/mL during M. pneumoniae strain M129 Limit of Detection replicate testing.

Cross-Reactivity Study:

Potentially cross-reacting microorganisms expected to be present in respiratory specimens (throat swab, nasopharyngeal swab or bronchoalveolar lavage specimens) were added to negative and contrived positive samples. Negative samples were prepared with M4 transport medium inoculated with nasal flora on rayon swabs. The contrived positive sample was prepared by spiking confirmed negative sample matrix (M4 transport medium inoculated with nasal flora on polyester swabs) with Mycoplasma pneumoniae, FH strain, at concentrations at or near the determined limit of detection for the strain. Dilution Controls were prepared by adding a sterile saline solution in place of the potentially cross-reactive organisms. Each inoculated sample was tested in triplicate.

Potentially cross-reactive (or interfering) microorganisms were at minimum concentrations of 1.0 x 10 CFU/mL for bacterialfungi or concentrations greater than 1.0 x 10 TC/Dg/mL or 1.0 x 10 copies/mL for viruses; Human DNA was tested at 2.0ng/test.

None of the following organisms reacted or interfered with illumigene Mycoplasma: Acinetobacter baumannii, Acinetobacter calcoaceticus, Actinomyces odontolyticus, Bacillus subtilis, Bacteroides fragilis, Bordella parapertussis. Bordetella pertussis. Burkholderia cepacia. Candida glabrata. Candida parapsilosis. Chlamydia pneumoniae, Citrobacter freundii, Clostridium difficile, Corynebacterium diphtheriae, Enterobacter cloacae, Enterococus faecalis, Escherichia coli (ESBL), Fusobacterium nucleatum. Haemophilus ducrevi, Haemophilus influenzae, Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella pneumoniae, Klebsiella pneumoniae (KPC), Legionella pneumophila, Listeria monocytogenes, Mycoplasma genitalium, Mycoplasma hominis, Neisseria gonorrhoeae, Neisseria meningitidis, Peptostreptococus anaerobius, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella paratyphi A (Group A), Salmonella typhimurium (Group B), Serratia liquefaciens, Staphylococus

6

| Image: Meridian Bioscience, Inc. logo | K123423: illumigene® Mycoplasma DNA Amplification Assay
Request for Additional Information | |
|---------------------------------------|-----------------------------------------------------------------------------------------------|----------------|
| | Application Reference: | Section 2 |
| | Attachment Description: | 510(k) Summary |
| | Application Date: | May 30, 2013 |

aureus, Staphylococcus epidemidis, Streptococus aqalactiae (Group B), Streptococcus anginosus (Group F), Streptococcus bovis (Group D), Streptococus canis (Group G), Streptococcus equisimilis, Streptococus mitis, Streptococcus pneumoniae, Streptococus pyogenes, Streptococcus salivarius, Ureaplasma urealyticum, Adenovirus, Coxsackievirus, Cytomegalovirus, Epstein Barr virus, Herpes simplex virus 1, Herpes simplex virus 2, Influenza B, Metapneumovirus, Parainfluenza virus 1, Parainfluenza virus 2, Parainfluenza virus 3, Respiratory syncytial virus A, Respiratory syncytial virus B, Rhinovirus, Human DNA.

Original replicate testing for Moraxella catarthalis, Nocardia asteroides and Coronavirus produced one of three false-negative results when tested with the Mycoplasma pneumoniae FH strain, Limit of Detection sample. Four additional replicates were tested for each organism with expected results oblained. In all cases, the original unexpected results were not confirmed through supplemental testing.

Assay Cut-Off:

The illumigene Mycoplasma is manufactured with fixed cut-off values. The product is designed around a preselected cut-off value and amplification reagent concentrations are optimized to ensure appropriate reactions are obtained. Development optimization includes evaluation of characterized positive 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 illumioro-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.

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 Sy.S ratios greater than or equal to 82% are reported as 'NEGATIVE'. Numerical values are not reported.

CLINICAL PERFORMANCE DATA:

Clinical Studies:

Clinical Sensitivity:

Clinical trials for the illumigene Mycoplasma DNA Amplification Assay, including the illumipro-10 Automated Isothermal amplification and detection system, were conducted from February to September 2012.

A total of 334 qualified throat and nasopharyngeal (NP) swab specimens, collected from patients.suspected of Mycoplasma pneumoniae infection were evaluated with the test device to establish performance characteristics. Specimens were leftover deidentified specimens submitted to the testing laboratories for routine M. pneumoniae testing. Specimens included in performance evaluation were prospective (never frozen) and retrospective (frozen prior to illumigene testing). The performance of illumigene was compared to a Composite Reference Method

7

| Meridian
Bioscience, Inc.
Inspired Science. Trusted Solutions." | K123423: illumigene® Mycoplasma DNA Amplification Assay
Request for Additional Information | |
|-----------------------------------------------------------------------|-----------------------------------------------------------------------------------------------|-----|
| Application Reference: | Section 2 | |
| Attachment Description: | 510(k) Summary | |
| Application Date: | May 30, 2013 | [8] |

that included M. pneumoniae bacterial culture with identification and a validated real-time PCR assay followed by bi-directional sequencing for positive specimens producing positive Mycoplasma pneumoniae results from either the bacterial culture or real-time PCR and bi-directional sequencing were considered positive. Specimens negative for both culture and PCR were considered negative. A total of 12 specimens were excluded from the clinical sample population because culture results were inconclusive and PCR negative, making final disposition of patient status unavailable. A total of 103 (30.8%) prospective samples and 219 retrospective (65.6%) were tested with 1 initial invalid result (0.30%).

Tables 1-2 summarize performance characteristics. Statistical analysis of Specimen Type performance data was performed with no significant difference between swab types identified.

Data indicates performance is optimal when specimens are collected and tested prospectively.

Positive SpecimensNegative Specimens
Specimen Descriptionillumigene vs.
Comparator% Sensitivity
or
PPA95% CIillumigene vs.
Comparator% Specificity
or
NPA95% CIInvalid
Results
Composite Reference Method
Prospective4/4% Sensitivity
100.0%51.0 - 100.0%48/48% Specificity
100%92.6 - 100.0%0
Retrospective34/36PPA
94.4%81.9 - 98.5%86/90NPA
95.6%89.1 - 98.3%0
PCR with Bi-Directional Sequencing
Prospective4/4% Sensitivity
100.0%51.0 - 100.0%48/48% Specificity
100%92.6 - 100.0%0
Retrospective34/36PPA
94.4%81.9 - 98.5%86/90NPA
95.6%89.1 - 98.3%0

Table 1. illumigene Mycoplasma Assay Performance: Nasopharyngeal Swab Specimens

8

| Image: Meridian Bioscience, Inc. logo
Inspired Science. Trusted Solutions. | K123423: illumigene® Mycoplasma DNA Amplification Assay
Request for Additional Information |
|-------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------|
| | Application Reference: Section 2 |
| | Attachment Description: 510(k) Summary |
| | Application Date: May 30, 2013 [9] |

Table 2. illumigene Mycoplasma Assay Performance: Throat Swab Specimens

Positive SpecimensNegative Specimens
Specimen Descriptionillumigene
vs.
Comparator% Sensitivity
or
PPA95% CIillumigene
vs.
Comparator% Specificity
or
NPA95% CIInvalid
Results
Composite Reference Method
Prospective8/8% Sensitivity
100.0%67.6 - 100.0%43/43% Specificity
100.0%91.8 - 100.0%0
Retrospective22/26aPPA
84.6%66.5 - 93.9%66/67NPA
98.5%92.0 - 99.7%1
PCR with Bi-Directional Sequencing
Prospective8/8% Sensitivity
100.0%67.6 - 100.0%43/43% Specificity
100.0%91.8 - 100.0%0
Retrospective21/21bPPA
100.0%84.5 - 100.0%70/72NPA
97.2%90.4 - 99.2%1

a. Four specimens originally identified by culture as positived by either the illumigene assay or the independent PCR method. Results suggest sample degradation during storage.

b. One specimen onginally identified by the illure as positive was negative by the independent PCR method. This specimen is classified as a false positive relative to PCR.

Age information was known for 83.5% (269/322) of the patients included in the performance analysis. Seven (2.6%) patients tested were between 0 - 28 days of age; 38 (14.1%) patients were between 29 days and up to 2 years of age; 139 (51.7%) palients were between 2 and up to 12 years of age; 61 (22.7%) patients were between 12 and up to 18 years of age; and 9 (3.3%) patients were between18 and up to 21 years of age. The remaining 15 (5.6%) study patients were 21 years or older. No performance differences were noted based on chronological age.

The study population included 90 (27.9%) female patients and 91 (28.3%) male patients. Gender was unknown for 141 (43.8%) of the study participants. In the specimens for which patient gender was known, no performance differences were noted based on gender.

Clinical performance of the illumigene Mycoplasma DNA Ampification Assay was assessed by the testing of deidentified nasopharyngeal and throat swab specimens lacking clinical information; accordingly, the number of patients with M. oneumonia included in the clinical studies is unknown and performance for this group cannot be described separately.

Expected values/Reference range:

Overall incidence of Mycoplasma pneumoniae in prospectively collected and tested specimens during the 2012 clinical study was 11.7% (12/103).

9

| Image: Meridian Bioscience Logo
Meridian
Bioscience, Inc.
Inspired Science. Trusted Solutions. | K123423: illumigene® Mycoplasma DNA Amplification Assay
Request for Additional Information | |
|---------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------|----------------|
| | Application Reference: | Section 2 |
| | Attachment Description: | 510(k) Summary |
| | Application Date: | May 30, 2013 |

CONCLUSIONS

02_i_Rev 6_IG_Myco

The illumigene® Mycoplasma DNA amplification assay, performed on the illumipro-10™, can be used to detect Mycoplasma pneumoniae in human throat and nasopharyngeal swabs oblained from patients suspected of having Mycoplasma pneumoniae respiratory infection. ・

10

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/10/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized depiction of an eagle or bird-like figure with three curved lines representing its body and wings. The logo is surrounded by a circular border containing the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" in capital letters. The text is arranged around the circumference of the circle, with the logo positioned in the center.

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

June 5,2013

JACQUELINE C. GODBEY REGULATORY AFFAIRS AND DESIGN ASSURANCE ASSOCIATE MERIDIAN BIOSCIENCE, INC. 3471 RIVER HILLS DRIVE CINCINNATI OH 45244

Re: K123423

Trade/Device Name: illumigene® Mycoplasma DNA Amplification Assay Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory viral panel multiplex nucleic acid assay Regulatory Class: II Product Code: OZX, OOI Dated: May 22, 2013 Received: May 23, 2013

Dear Ms. Godbey:

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:-GDRH-does-not-evaluate-information-related to-contract-liabilitywarranties. 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 (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.

11

Page 2-Ms. Godbey

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance 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" (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 Small Manufacturers, International and Consumer Assistance 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.

Sincerely yours,

Sally A. Hojvat -S

Sally Hojvat Ph.D., M.Sc Director, Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

12

illumigene® Mycoplasma DNA Amplification Assay
Application Reference:Section 3
Attachment Description:Indications for Use Form
Inspired Science. Trusted Solutions."Application Date:May 30, 2012

Indication(s) for Use Form

510(k) Number: K123423

Device Name: illumigene® Mycoplasma DNA Amplification Assay

Indications for Use:

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 ampification (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 coinfection 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.

illumigene Mycoplasma is intended for use in hospital, reference or state laboratory settings. The device is not intended for point-of-care use.

Prescription Use X

Over-The-Counter Use

-(Part-2-1-CFR-801-Subpart-D)-AND/OR-(21-CFR-801-Subpart-G)-

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

John Hobson 2013.06.04 12:1

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

A.f. Hff
Division Sign-Off

of in Vitro Diagnostics and Radiological Health

510(k) K123423

510(k) K123423

01_ii_Rev 4 IG Myco