(65 days)
Not Found
No
The device description details a fixed cut-off value for determining positive/negative results based on absorbance ratios, which is a deterministic algorithm, not AI/ML. There is no mention of AI, ML, or training/test sets for such technologies.
No
This device is an in vitro diagnostic test used for the detection of Streptococcus pyogenes, aiding in diagnosis. It does not provide therapy or treatment.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is a "qualitative in vitro diagnostic test for the detection of Streptococcus pyogenes (Group A ß-hemolytic Streptococcus) in throat swab specimens." It also notes that "Results from the illumigene Group A Strep assay can be used as an aid in the diagnosis of Group A Streptococcal pharyngitis."
No
The device description clearly states that the system is comprised of a test kit, an external control kit, and an automated isothermal amplification and detection system (illumipro-10™), which is a hardware component.
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® Group A Streptococcus assay is a "qualitative in vitro diagnostic test for the detection of Streptococcus pyogenes (Group A ß-hemolytic Streptococcus) in throat swab specimens." The term "in vitro diagnostic" is clearly used.
- Device Description: The description details how the test is performed on biological samples (throat swab specimens) outside of the body ("in vitro") to diagnose a condition (Group A Streptococcal pharyngitis).
- Purpose: The assay is used as an "aid in the diagnosis of Group A Streptococcal pharyngitis," which is a diagnostic purpose.
- Regulatory Context: The inclusion of a "Predicate Device(s)" section with a K number (K924715) indicates that this device has gone through a regulatory process for medical devices, specifically IVDs, in the United States (K numbers are associated with FDA 510(k) submissions).
N/A
Intended Use / Indications for Use
The illumigene® Group A Streptoccus (Group A Strep) assay, performed on the illumipro-10™, is a qualitative in vitro diagnostic test for the detection of Streptococcus pyogenes (Group A ß-hemolytic Streptococcus) in throat swab specimens.
The illumigene Group A Strep assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect Streptococcus pyogenes by targeting a segment of the Streptococcus pyogenes genome. Results from the illumigene Group A Strep assay can be used as an aid in the diagnosis of Group A Streptococcal pharyngitis. The assay is not intended to monitor treatment for Group A Streptococcus infections.
illumigene Group A Strep is intended for use in hospital, reference or state laboratory settings. The device is not intended for point-of-care use.
Product codes (comma separated list FDA assigned to the subject device)
OYZ, OOI
Device Description
The illumigene Molecular Diagnostic Test System is comprised of the illumigene® Group A Strep DNA Amplification Test Kit, the illumigene® Group A Strep External Control Kit and the illumipro-10™ Automated Isothermal Amplification and Detection System.
The illumigene Group A Strep assay utilizes loop-mediated isothermal amplification (LAMP) technology to detect the presence of Streptococcus pyogenes (Group A beta-hemolytic Streptococus) in throat swab specimens. Each illumigene Group A Strep assay is completed using an illumigene Sample Preparation Apparatus II/Negative Control III containing Control material, an illumigene Group A Streptococcus Test Device and an illumigene Heat Treatment Tube. Samples are diluted in the illumigene Sample Preparation Apparatus II and dispensed into an illumigene Heat Treatment Tube. Target and Control DNA is made available for isothermal amplification via heat-treatment. DNA amplification occurs in the illumigene Test Device.
The illumipro- 10heats each illumigene Group A Strep Test Device containing prepared sample and Control material, facilitating amplification of target DNA. When S. pyogenes is present in the throat swab specimen, a 206 base pair sequence of the S. pyogenes genome is amplified and magnesium pyrophosphate is generated. Magnesium pyrophosphate forms a precipitate in the reaction mixture. The absorbance characteristics of the reaction solutions at the assay Run Start (Signalwikal, S) and at the assay Run End (Signalman) S). The illumipro-10 calculates the change in light transmission between Run End and Run Start (S;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 volues ore 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 SyS, ratios greater than or equal to 90% are considered invalid and prevent reporting of TEST chamber results. Invalid CONTROL chamber reactions are reported as 'NVALID'. Numerical values 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.
The illumigene Group A Strep External Control Kit contains a Positive Control Reagent. The External Positive control Reagent is used in conjunction with the illumigene Sample Preparation Apparatus II/Negative Control III reagent included in the illumigene Group A Strep Kit as part of routine Quality Control testing. External Control reagents are provided to aid the user in detection of reagent deterioration, adverse environmental or test conditions, or variance in operator performance that may lead to test errors.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
throat swab specimens
Indicated Patient Age Range
Not Found
Intended User / Care Setting
hospital, reference or state laboratory settings.
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
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Analytical Performance:
- Precision/Reproducibility: Blind-coded panels of 10 samples (low positive, high negative, positive, natural negative) were supplied to three independent laboratories. Testing was performed by different operators at each site on the same day for five days. Three lots of illumigene Group A Strep and five illumipro-10 instruments were used.
- Site 1: Negative (10/10, 100%), High Negative (29/30), Low Positive (30/30, 100%), Positive (30/30, 100%)
- Site 2: Negative (10/10, 100%), High Negative (30/30, 100%), Low Positive (30/30, 100%), Positive (30/30, 100%)
- Site 3: Negative (10/10, 100%), High Negative (28/30, 93.3%), Low Positive (30/30, 100%), Positive (30/30, 100%)
- Total: Negative (30/30, 100%), High Negative (87/90, 96.7%), Low Positive (90/90, 100%), Positive (90/90, 100%)
- Detection limit: Analytical limit of detection of S. pyogenes in throat swab specimens. Two common strains of S. pyogenes, ATCC 12344 and ATCC 19615, were evaluated. Each strain was spiked into sterile saline and serially diluted, then combined with negative matrix. A minimum of twenty replicates for each dilution were individually processed and tested. Three production lots of illumigene Group A Strep and six illumipro-70 instruments used.
- Limit of Detection: 400 CFU/Test for ATCC 12344 and 430 CFU/Test for ATCC 19615.
- Analytical specificity / Interference Testing: Potentially interfering substances (biological and chemical) were tested with negative and contrived positive samples (ATCC 12344, ATCC 19615) near the LOD. Each inoculated sample was tested in triplicate.
- No interference from: Mucus (5.0mg/mL), Human saliva (10% v/v), and Whole Blood (2.5% v/v), Acetaminophen (19.5 mg/mL), Aspirin (12.3 mg/mL), Cepacol® Mouthwash, Cepacol® Sore Throat Lozenges, Chloraseptic® Oral Anesthetic/Analgesic, Contac® Cold + Flu Tablets, Crest® Complete Toothpaste, Diphenhydramine HCl (2.7 mg/mL), HALLS® Cough Drops, Ibuprofen (15.6 mg/mL), Listerine® Antiseptic Mouthwash, Robitussin® Cough/Chest Congestion Cough Syrup.
- Interference from: Whole Blood at concentrations greater than 2.5% v/v. Zicam® Oral Mist produced invalid results in all replicates tested.
- Cross-Reactivity Study: Potentially cross-reacting microorganisms and Human DNA were added to negative and contrived positive samples (ATCC 12344 at ~400 CFU/Test). Each sample was tested in triplicate.
- No microorganism tested met the definition of interferent or cross-reactive.
Clinical Studies:
- Clinical Sensitivity: Clinical trials conducted from April to June 2012. Performance characteristics determined by comparison to composite bacterial culture method for Group A Streptococcus.
- Sample Size: 798 qualified specimens.
- Key Results:
- Overall assay Sensitivity: 98.0% [95% Cl: 93.1 -99.5%]
- Overall assay Specificity: 97.7% [95% Cl: 96.3 - 98.6%]
- Overall assay Invalid Rate: 0.3% (95% Cl: 0.1 - 0.9%)
- Performance Data Summary (illumigene Group A Strep vs. Composite Culture):
- Positive: 100/102
- Negative: 680/696
- Site Performance by Composite Culture Method:
- Site 1: Sensitivity 100.0% (47/47), Specificity 98.6% (287/291), Invalid 0.0% (0/338)
- Site 2: Sensitivity 93.3% (28/30), Specificity 96.2% (204/212), Invalid 0.4% (1/243)
- Site 3: Sensitivity 100.0% (25/25), Specificity 97.9% (189/193), Invalid 0.5% (1/219)
- Site Performance by Clinical Site Culture Method:
- Total: Sensitivity 100.0% (74/74), Specificity 94.2% (682/724), Invalid 0.3% (2/800)
- Site 1: Sensitivity 100.0% (40/40), Specificity 96.3% (287/298), Invalid 0.0% (0/338)
- Site 2: Sensitivity 100.0% (18/18), Specificity 92.0% (206/224), Invalid 0.4% (1/243)
- Site 3: Sensitivity 100.0% (16/16), Specificity 93.6% (189/202), Invalid 0.5% (1/219)
- Two specimens produced initial invalid results (one Control Chamber failure, one suspect Test Chamber reaction); retest produced valid, negative results.
- No performance differences noted based on chronological age or gender within the study population.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Overall assay Sensitivity: 98.0% [95% Cl: 93.1 -99.5%]
Overall assay Specificity: 97.7% [95% Cl: 96.3 - 98.6%]
Overall assay Invalid Rate: 0.3% (95% Cl: 0.1 - 0.9%)
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
§ 866.3740
Streptococcus spp. serological reagents.(a)
Identification. Streptococcus spp. serological reagents are devices that consist of antigens and antisera (excluding streptococcal exoenzyme reagents made from enzymes secreted by streptococci) used in serological tests to identifyStreptococcus spp. from cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by bacteria belonging to the genusStreptococcus and provides epidemiological information on these diseases. Pathogenic streptococci are associated with infections, such as sore throat, impetigo (an infection characterized by small pustules on the skin), urinary tract infections, rheumatic fever, and kidney disease.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.
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Image /page/0/Picture/0 description: The image shows a document with the title "Illumigene® Group A Streptococcus (Group A Strep) DNA Amplification Assay". The document has an application reference of Section 2 and an attachment description of 510(k) Substantial Equivalence Determination Decision Summary. The document is dated September 10, 2012, and has a reference number of K122019.
510(k) Substantial Equivalence Determination Decision Summary
A. 510(k) number: K122019
SEP 13 2012
B. Purpose for Submission:
To determine substantial equivale of the illumigene® Group A Streptoccus (Group A Strep) DNA Amplification Assay used for the qualitative detection of Streptococcus pyogenes.
C. Measurand:
Segment of the Streptococcus pyogenes genome
D. Type of Test:
Qualitative in vitro diagnostic using Loop-mediated isothermal DNA amplification (LAMP) technology
E. Applicant:
Meridian Bioscience, Inc. 3471 River Hills Drive, Cincinnati, OH 45244 USA
Propriety and Established Names: ﻨﺎ
illumiqene® Group A Streptococcus (Group A Strep) DNA Amplification Assay illumigene® Group A Streptococcus (Group A Strep) External Control Kit
G. Regulatory Information:
Product Code | Classification | Regulation Section | Panel |
---|---|---|---|
OYZ, Group A Streptococcus Nucleic Acid | |||
Amplification Assay System | Class I | 21 CFR § 866.3740 | Microbiology (83) |
H. Intended Use:
1. Intended use(s):
The illumigene® Group A Streptoccus (Group A Strep) assay, performed on the illumipro-10™, is a qualitative in vitro diagnostic test for the detection of Streptococcus (Group A ß-hemolytic Streptococcus) in throat swab specimens.
The illumigene Group A Strep assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect Streptococcus pyogenes by targeting a segment of the Streptococcus pyogenes genome. Results from the illumigene Group A Strep assay can be used as an aid in the diagnosis of Group A Streptococcal pharyngitis. The assay is not intended to monitor treatment for Group A Streptococcus infections.
illumigene Group A Strep is intended for use in hospital, reference or state laboratory settings. The device is not intended for point-of-care use.
CONFIDENTIAL 02_i_IG_Grp A Strep
1
| Image: Meridian Bioscience, Inc. logo | K122019
Illumigene® Group A Streptococcus (Group A Strep) DNA Amplification Assay | |
|---------------------------------------|--------------------------------------------------------------------------------------|---------------------------------------------------------------|
| | Application Reference: | Section 2 |
| | Attachment Description: | 510(k) Substantial Equivalence Determination Decision Summary |
| | Date: | September 10, 2012 |
2. Indication(s) for use:
The illumigene® Group A Streptoccus (Group A Strep) assay, performed on the illumipro-10™, is a qualitative in vitro diagnostic test for the detection of Streptococcus pyogenes (Group A ß-hemolytic Streptococcus) in throat swab specimens.
The illumigene Group A Strep assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect Streptococcus pyogenes by targeting a segment of the Streptococcus pyogenes genome. Results from the illumigene Group A Strep assay can be used as an aid in the diagnosis of Group A Streptococcal pharyngitis. The assay is not intended to monitor treatment for Group A Streptococcus infections.
illumigene Group A Strep is intended for use in hospital, reference or state laboratory settings. The device is not intended for point-of-care use.
3. Special Conditions for use statement(s):
- . For Prescription Use Only
- The device is not intended for point-of-care use .
Special instrument requirements:
illumipro- 10™ Automated Isothermal Amplification and Detection System
Device Description: l.
The illumigene Molecular Diagnostic Test System is comprised of the illumigene® Group A Strep DNA Amplification Test Kit, the illumigene® Group A Strep External Control Kit and the illumipro-10™ Automated Isothermal Amplification and Detection System.
The illumigene Group A Strep assay utilizes loop-mediated isothermal amplification (LAMP) technology to detect the presence of Streptococcus pyogenes (Group A beta-hemolytic Streptococus) in throat swab specimens. Each illumigene Group A Strep assay is completed using an illumigene Sample Preparation Apparatus II/Negative Control III containing Control material, an illumigene Group A Streptococcus Test Device and an illumigene Heat Treatment Tube. Samples are diluted in the illumigene Sample Preparation Apparatus II and dispensed into an illumigene Heat Treatment Tube. Target and Control DNA is made available for isothermal amplification via heat-treatment. DNA amplification occurs in the illumigene Test Device.
The illumipro- 10heats each illumigene Group A Strep Test Device containing prepared sample and Control material, facilitating amplification of target DNA. When S. pyogenes is present in the throat swab specimen, a 206 base pair sequence of the S. pyogenes genome is amplified and magnesium pyrophosphate is generated. Magnesium pyrophosphate forms a precipitate in the reaction mixture. The absorbance characteristics of the reaction solutions at the assay Run Start (Signalwikal, S) and at the assay Run End (Signalman) S). The illumipro-10 calculates the change in light transmission between Run End and Run Start (S;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 volues ore 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
2
| Image: Meridian Bioscience, Inc. logo | K122019
Illumigene ® Group A Streptococcus (Group A Strep) DNA Amplification Assay |
|---------------------------------------|-----------------------------------------------------------------------------------------------------|
| | Application Reference: Section 2 |
| | Attachment Description: 510(k) Substantial Equivalence Determination Decision Summary |
| | Date: September 10, 2012 |
(POSITIVE, NEGATIVE). CONTROL chamber SyS, ratios greater than or equal to 90% are considered invalid and prevent reporting of TEST chamber results. Invalid CONTROL chamber reactions are reported as 'NVALID'. Numerical values 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.
The illumigene Group A Strep External Control Kit contains a Positive Control Reagent. The External Positive control Reagent is used in conjunction with the illumigene Sample Preparation Apparatus II/Negative Control III reagent included in the illumigene Group A Strep Kit as part of routine Quality Control testing. External Control reagents are provided to aid the user in detection of reagent deterioration, adverse environmental or test conditions, or variance in operator performance that may lead to test errors.
Substantial Equivalence Information: J.
-
- Predicate device name(s): GEN-PROBE® Group A Streptococcus Direct Test; Catalog 103890
-
- Predicate 510(k) numbers: K924715
-
- Comparison with predicates:
Similarities | ||
---|---|---|
Item | DEVICE illumigene® Group A Streptococcus | PREDICATE GEN-PROBE® Group A Streptococcus Direct K924715 |
Intended Use | Qualitative | Qualitative |
Test Format | Molecular-based Amplification Assay | Molecular-based Direct Assay |
Target | Streptococcus pyogenes | Streptococcus pyogenes |
Specimen Types | Throat Swab | Throat Swab |
Detection | Self contained and automated | Self contained and automated |
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Image /page/3/Picture/0 description: The image is a logo for Meridian Bioscience, Inc. The logo features a globe on the left side, followed by the word "Meridian" in bold, sans-serif font. Below "Meridian" is the text "Bioscience, Inc." in a smaller, sans-serif font. The tagline "Inspired Science. Trusted Solutions." is located below the company name.
K122019 illumigene® Group A Streptococcus (Group A Strep) DNA Amplification Assay Application Reference: Section 2 Attachment Description: 510(k) Substantial Equivalence Determination Decision Summary Date: September 10, 2012
Differences | ||
---|---|---|
Item | DEVICE | |
illumigene® Group A Streptococcus | PREDICATE | |
GEN-PROBE® Group A Streptococcus Direct | ||
K924715 | ||
Test Format | DNA Amplification Assay; Loop-Mediated | |
Isothermal Amplification (LAMP) | Nucleic Acid Hybridization | |
Target Sequences | ||
Detected | 206 base pair (bp) sequence S. pyogenes genome, | |
resident in the pyrogenic exotoxin B (speB) gene | Streptococcus pyogenes ribosomal RNA | |
Reagents/Components | illumigene Sample Preparation Apparatus | |
II/Negative Control III illumigene Group A Streptococcus Test Device illumigene Heat Treatment Tubes | Lysis Reagent Probe Reagent Hybridization Buffer Selection Reagent Positive Control Negative Control Sealing Cards Polypropylene Tubes | |
Amplification | Self contained and automated | Not Appliable |
Testing Time | Less than 60 minutes | Less than 90 minutes |
Instrumentation | illumipro-10™ Automated Isothermal Amplification | |
and Detection System | GEN-PROBE® LEADER® Luminometer | |
Reading Method | Visible Light Transmission | Chemiluminescent Emissions |
Performance | ||
Characteristics | Sensitivity: 98.0% [95% CI: 93.1% - 99.5%] | |
Specificity: 97.7% [95% CI: 96.3% - 98.6%] | Sensitivity: 94.1% | |
Specificity: 98.3% |
K. Standard/Guidance Document Referenced (if applicable):
- Clinical and Laboratory Standards Institute. 2008. User Protocol for Evaluation of Qualitative Test Performance; . Approved Guideline- Second Edition (EP12-A)
- Clinical and Laboratory Standards Institute. 2005. User Verification of Performance for Precision and Trueness; . Approved Guideline- Second Edition (EP15-A2)
- Clinical and Laboratory Standards Institute. 2005. Interference Testing in Clinical Chemistry; Approved Guideline-. Second Edition (EP7-A2)
L. Test Principle:
The illumigene Group A Strep assay is based on loop-mediated isothermal amplification technology (LAMP). Loopmediated amplification of DNA is accomplished by the use of specially designed primers that provide specific and continuous isothermal amplification. Magnesium-pyrophosphate is produced as a by-product of LAMP amplification. The magnesium-pyrophosphate forms a white precipitate in the reaction solution, giving the reaction solution a turbid appearance. Change in sample absorbance created by precipitation of magnesium pyrophosphate indicates the presence of target DNA and is considered a positive reaction. The absence of target DNA results in no significant change in sample absorbance and is considered a negative reaction.
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Image /page/4/Picture/0 description: This image contains the logo for Meridian Bioscience, Inc. and information about the Illumigene Group A Streptococcus DNA Amplification Assay. The application reference is Section 2, and the attachment description is 510(k) Substantial Equivalence Determination Decision Summary. The date on the document is September 10, 2012, and the document number is K122019.
M. Performance Characteristics (if/when applicable):
1. Analytical Performance:
- a. 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 Group A Strep and five illumipro- 10 instruments were used in this study. The results are given in the table below:
Site 1 | Site 2 | Site 3 | Total | |||||
---|---|---|---|---|---|---|---|---|
Sample Type | Percent agreement | Percent agreement | Percent agreement | Percent agreement | ||||
Negative | 10/10 | 10/10 | 100% | 10/10 | 100% | 30/30 | 100% | |
High Negative | 29/30 | 30/30 | 100% | 28/30 | 93.3% | 87/90 | 96.7% | |
Low Positive | 30/30 | 30/30 | 100% | 30/30 | 100% | 90/90 | 100% | |
Positive | 30/30 | 30/30 | 100% | 30/30 | 100% | 90/90 | 100% |
- Linearity/assay reportable range: b.
Not applicable as this assay is qualitative
C. Traceability, Stability, Expected values (controls, calibrators, or methods):
Stability:
Sample storage and hold time studies were performed to characterize illumigene Group A Strep assay ranges. Validation studies performed at Meridian were completed using rayon swabs in both Liquid Amies (without charcoal) and Liquid Stuart Transport Medium.
Study results demonstrated that throat swab samples can be held at 21-27 C for up to 48 hours or at 2-8 C for up to 7 days prior to testing. Samples diluted in the illumigene Sample Preparation Apparatus can be held at 2-29 C for up to 2 hours prior to heat treatment. Heattreated samples may be held at 21-29 C for up to one hour prior to testing.
Final testing demonstrated that rayon, polyester and flocked nylon swab types with either Liquid Amies (without charcoal) or Liquid Stuart Transport Medium perform acceptably with the illumigene Group A Strep assay. Swab and transport medium types with demonstrated performance in the illumigene Group A Strep assay appear in the Package Insert.
- Detection limit: d.
Sensitivity studies were designed to determine the analytical limit of detection of S. pyogenes in throat swab specimens. Two common strains of S. pyogenes, ATCC 12344 and ATCC 19615, were evaluated with the illumigene Group A Strep assay. Each strain was spiked into sterile saline and
5
| | K122019
illumigene® Group A Streptococcus (Group A Strep) DNA Amplification Assay | | | | |
|--------------------------------------|--------------------------------------------------------------------------------------|---------------------------------------------------------------|--|--|--|
| | Application Reference: | Section 2 | | | |
| Bioscience. Inc. | Attachment Description: | 510(k) Substantial Equivalence Determination Decision Summary | | | |
| Inspired Science. frusted Solutions. | Date: | September 10, 2012 | | | |
diluted serially. Dilutions were combined with negative matrix (rayon swabs inoculated with normal throat flora screened negative for S. pyogenes, and Liquid Amies (without charcoal) Transport Media) prior to testing. A minimum of twenty replicates for each dilution were individually processed and tested to establish limit of detect. Testing was performed using three production lots of illumigene Group A Strep and six illumipro-70 instruments. External Positive and Negative Controls were tested each day throughout the study. The Limit of Detection for the assay was reported as 400 CFU/Test for ATCC 12344 and 430 CFU/Test for ATCC 19615.
The following S. pyogenes strains were tested and produced positive reactions at or below stated assay limit of detect of 400 CFU/Test with illumigene Group A Strep: ATCC 12384, NCIMB 13285, CCUG 33061, CCUG 33409, CCUG 39158, ATCC 49399, CCUG 53553.
Limit of Detection studies are acceptable.
Analytical specificity: e.
Interference Testing:
Interfering substance testing was performed to assess the potential impact of non-microbial contaminants expected to be present in throat swab samples on illumigene Group A Strep test results. Potentially interfering substances were tested with negative and contrived positive (ATCC 12344, ATCC 19615) samples. Contrived positive samples were prepared near the reported limit of detection for each strain tested. Negative samples and contrived positive samples were added to the illumigene Sample Preparation Apparatus II and inoculated with throat swab matrix (rayon swab inoculated with normal throat flora, screened negative for Streptococcus pyogenes, and Liquid Amies Transport Medium). Each inoculated sample was tested in triplicate.
The following biological substances, at the saturated solvent/diluent concentrations indicated, do not interfere with test results: Mucus (5.0mg/mL), Human saliva (10% v/v), and Whole Blood (2.5% v/v). Whole Blood at concentrations greater than 2.5% v/v may interfere with the illumigene Group A Strep Assay.
The following chemical substances, at the saturated solvent/diluents concentrations indicated, do not interfere with test results: Acetaminophen (19.5 mg/mL), Aspirin (12.3 mg/mL), Cepacol® Mouthwash, [Cetyopridinium Chloride (0.005% v/v)}, Cepacol® Sore Throat Lozenges [Benzocaine (0.09 mg/mL), Menthol (0.02 mg/mL)}, Chloraseptic® Oral Anesthetic/Analgesic (Phenol (0.07% v/v)], Contac® Cold + Flu Tablets - [Acetaminophen (16.2 mg/mL), Chlorpheniramine maleate (0.06 mg/mL), Phenylephrine HCl (0.16 mg/mL)], Crest® Complete Toothpaste {Sodium fluoride (0.1 mg/mL}], Diphenhydramine HCl (2.7 mg/mL), HALLS® Cough Drops [Menthol (0.08 mg/mL)], Ibuprofen (15.6 mg/mL), Listerine® Antiseptic Mouthwash [Eucalvptol (0.0092% v/v), Menthol (0.0042% v/v), Methyl salicylate (0.0060% v/v), Thymol (0.0064% v/v)], Robitussin® Cough/Chest Congestion Cough Syrup [Dextromethorphan HBr (0.2 mg/mL), Guaifenesin (2.0 mg/mL)].
Zicam® Oral Mist [Zincum Aceticum 2X, Zincum Gluonicum 1X (0.625% v/v) produced invalid results in all replicates tested.
Interference studies are acceptable.
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| Image: Meridian
Bioscience, Inc.
Inspired Science. Trusted Solutions. | K122019
Illumigene® Group A Streptococcus (Group A Strep) DNA Amplification Assay | Application Reference: | Section 2 |
|-----------------------------------------------------------------------------|--------------------------------------------------------------------------------------|-------------------------|-----------------------------------------------------------|
| | | Attachment Description: | 510(k) Substantial Equivalence Determination Decision Sum |
| | | Date: | September 10, 2012 |
marv
Cross-Reactivity Study:
Potentially cross-reacting microorganisms expected to be present in throat swab specimens were added to negative and contrived positive samples. The negative sample was prepared from S. pyogenes negative clinical throat swab sample in Liquid Amies (without charcoal) Transport Medium. The contrived positive sample was prepared by spiking sterile saline with Streptococcus pyogenes, strain ATCC 12344 at approximately 400 CFU/Test, the reported limit of detection for the strain.
Potentially cross-reactive microorganisms were added at concentrations of 1.2 x 10° CFU/mL (bacteria and fungi); Human DNA was tested at 0.02 mg/mL. Dilution controls for each sample were prepared by adding sterile saline solution in place of the potentially cross-reactive microorganisms. Each sample was tested in triplicate. No microorganism tested met the definition of interferent or cross-reactive.
None of the following organisms reacted with illumigene Group A Strep: Acinetobacter baumannii, Acinetobacter Iwoffii, Aeromonas hydrophila, Arcanobacterium haemolyticum, Bordetella bronchiseptica, Bordetella holmesii, Bordetella parapertussis, Bordetella pertussis, Burkholderia cepacia, Campylobacter jejuni, Candida albicans, Citrobacter freundii, Corynebacterium diphtheria, Corynebacterium pseudodiphtheriticum, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Haemophilus influenza, Klebsiella pneumoniae, Lactococcus lactis, Legionella jordanis, Legionella micdadei, Legionella pneumophila, Listeria monocytogenes, Moraxella catarrhalis, Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitidis, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Pseudomonas fluorescens, Staphylococcus aureus, Staphylococcus epidermidis, Stenotrophomonas anginosus, Streptococcus bovis, Streptococcus canis, Streptococcus dysgalactiae (subspecies equisimilis), Streptococcus equinus, Streptococcus intermedius, Streptococcus mitis, Streptococcus mutans, Streptococcus pneumoniae, Streptococcus salivarius, Streptococcus suis, Streptococcus uberis, Streptococcus sp. Viridans type.
Mycoplasma pneumoniae was tested at 1.5 x 10° CFU/mL with no reaction with the illumigene Group A Strep assay.
Cross-reactivity studies are acceptable.
- f. Assay cut-off:
The illumigene Group A Strep assay has a fixed cut-off based on the measured change in light transmission at the assay endpoint. The illumipro- 10 measures transmission of light through the Test and the Control reactions at the start of the Assay Run (Signalinia) and at the end of the Assay Run (Signalma). The illumipro-10 calculates the change in transmission between the Signalmai:Signalinital and compares the result to a fixed cut-off value. Test results are reported as Positive or Negative based on comparison to the assay cut-off. Fixed cut-off values were based on well characterized clinical specimens.
7
| Image: Meridian Logo
Meridian
Bioscience, Inc.
Inspired Science. Trusted Solutions. | K122019
Illumigene® Group A Streptococcus (Group A Strep) DNA Amplification Assay | Application Reference: | Section 2 |
|----------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------|-------------------------|---------------------------------------------------------------|
| | | Attachment Description: | 510(k) Substantial Equivalence Determination Decision Summary |
| | | Date: | September 10, 2012 |
2. Comparison Studies:
-
a. Method comparison with predicate device:
Not applicable -
Matrix comparison: b.
Not applicable
3. Clinical Studies:
- a. Clinical Sensitivity:
Clinical trials for the illumigene Group A Streptococcus (Group A Strep) DNA Amplification Assay, including the illumipro-10 Automated Isothermal amplification and detection system, were conducted from April to June 2012. Performance characteristics of the assay were determined by comparison to composite bacterial culture method for Group A Streptococcus. A total of 798 qualified specimens were evaluated with the test; two specimens produced initial invalid results which were negative upon retest. Overall assay Sensitivity was reported as 98.0% [95% Cl: 93.1 -99.5%); overall assay Specificity was reported as 97.7% [95% Cl: 96.3 - 98.6%]; overall assay Invalid Rate was 0.3% (95% Cl: 0.1 - 0.9%). Compiled clinical study information is described below:
| Group A Streptococcus
Composite Culture | illumigene Group A Strep | ||
---|---|---|---|
Positive | Negative | Total | |
Positive | 100 | 2 | 102 |
Negative | 16 | 680* | 696 |
Total | 116 | 682 | 798 |
95% CI | |||
Sensitivity | 100/102 | 98.0% | 93.1 - 99.5% |
Specificity | 680/696 | 97.7% | 96.3 - 98.6% |
Invalid Rate | 2/800 | 0.3% | 0.1 - 0.9% |
Table 1: illumigene Group A Strep Performance Data Summary
- Two specimens produced initial invalid results that were negative upon re-test. A total of 798 qualified specimens were evaluated with the test device and composite bacterial culture methods.
Three independent clinical test sites located in the Midwestern and Southern regions of the United States participated in the device evaluation. All samples utilized in the study were leftover human specimens, not individually identifiable. All samples included in the study were submitted to the testing laboratory by an ordering physician for Group A Streptoccus testing and were presumed from symptomatic patients. No restrictions were placed on age, gender, medications or known pharmaceutical therapies.
Composite culture methods were employed to accommodate reports that Group A Streptococcus culture is considered 90 - 95% sensitive when correct sampling and plating techniques are used. 32 The Composite Culture Method consisted of the Clinical Site Culture Method as performed in standard of care testing and a Reference Culture Method performed by
8
Image /page/8/Picture/0 description: The image shows a document with the title "illumigene® Group A Streptococcus (Group A Strep) DNA Amplification Assay". The document includes the application reference, which is Section 2, and the attachment description, which is 510(k) Substantial Equivalence Determination Decision Summary. The document date is September 10, 2012, and the document number is K122019.
Meridian Bioscience. Site culture testing was performed by direct plating of the throat swab specimen while reference culture testing was performed by plating the swab transport media. Specimens producing positive Group A Streptococcus results from either the Site Culture Method or the Reference Culture Method were considered positive.
Specimens that generated invalid results were further evaluated. Data review for the two initial invalid samples revealed one Control Chamber failure and one suspect Test Chamber reaction. Repeat testing for both specimens produced valid, negative results. Site performance information was analyzed by Composite Culture Reference Testing and Site Culture Methods. Site performance as compared to Composite Culture Method, is summarized in Table 2. Site performance as compared to Site Culture Methods is presented in Table 3.
Table 2: illumigene Group A Strep Assay Performance by Site; Composite Culture Method
Positive Specimens | Negative Specimens | Invalid Specimens | ||||||
---|---|---|---|---|---|---|---|---|
Site | ||||||||
Identification | illumigene | |||||||
/Composite | ||||||||
Culture | % | |||||||
Sensitivity | 95% CI | illumigene | ||||||
/Composite | ||||||||
Culture | % | |||||||
Specificity | 95% CI | Invalid | ||||||
/Total | % | |||||||
Invalid | ||||||||
Total | 100/102 | 98.0% | 93.1 - 99.5% | 680/696 | 97.7% | 96.3 - 98.6% | 2/800 | 0.3% |
Site 1 | 47/47 | 100.0% | 92.4 - 100.0% | 287/291 | 98.6% | 96.5 - 99.5% | 0/338 | 0.0% |
Site 2 | 28/30 | 93.3% | 78.7 - 98.2% | 204/212 | 96.2% | 92.7 - 98.1% | 1/243 | 0.4% |
Site 3 | 25/25 | 100.0% | 86.7 - 100.0% | 189/193 | 97.9% | 94.8 - 99.2% | 1/219 | 0.5% |
Table 3: illumigene Group A Strep Assay Performance by Site; Clinical Site Culture Method
Positive Specimens | Negative Specimens | Invalid Specimens | ||||||
---|---|---|---|---|---|---|---|---|
Site | ||||||||
Identification | illumigene | |||||||
/Composite | ||||||||
Culture | % | |||||||
Sensitivity | 95% CI | illumigene | ||||||
/Composite | ||||||||
Culture | % | |||||||
Specificity | 95% CI | Invalid | ||||||
/Total | % | |||||||
Invalid | ||||||||
Total | 74/74 | 100.0% | 95.1 - 100.0% | 682/724 | 94.2% | 92.3 - 95.7% | 2/800 | 0.3% |
Site 1 | 40/40 | 100.0% | 91.2 - 100.0% | 287/298 | 96.3% | 93.5 - 97.9% | 0/338 | 0.0% |
Site 2 | 18/18 | 100.0% | 82.4 - 100.0% | 206/224 | 92.0% | 87.7 - 94.9% | 1/243 | 0.4% |
Site 3 | 16/16 | 100.0% | 80.6 - 100.0% | 189/202 | 93.6% | 89.3 - 96.2% | 1/219 | 0.5% |
Seven of the 102 Composite Culture-positive specimens were positive by Site Culture methods only; 26 of the 102 Composite Culture-positive specimens were positive only by the Reference Culture method; the two illumigene false-negative results were positive only by the Reference Culture performed by Meridian Bioscience. Statistical analysis of Site performance data was performed with no significant difference among Sites identified.
Clinical performance data was evaluated by patient age and gender. Seventy two (9.0%) patients tested were two years of age or younger; 385 (48.2%) patients were between two and 12 years of age; while 259 (32.5%) patients were greater than 12 and less than 21 years of age. The remaining 82 (10.3%) study patients were greater than 21 years old. Age information was known for all patients included in the performance analysis. No performance differences were noted based on chronological age. The study population included 410 (51.4%) female patients and 386
9
| Meridian
Bioscience, Inc.
Inspired Science. Trusted Solutions." | K122019
Illumigene® Group A Streptococcus (Group A Strep) DNA Amplification Assay |
|-----------------------------------------------------------------------|--------------------------------------------------------------------------------------|
| Application Reference: | Section 2 |
| Attachment Description: | 510(k) Substantial Equivalence Determination Decision Summary |
| Date: | September 10, 2012 |
(48.4%) male patients. Gender was unknown for two (0.2%) of the study participants. No performance differences were noted based on gender.
References:
-
Diagnosis and Tretament of Streptococcal Phayrngitis. Beth A. Choby, MD. Volume 79, Number 5. March 1, 2009, American Family Physician, pp. 383-390.
-
Pediatrics, American Academy of. Group A Streptococcal Infections. Pickering LK. Red Book: 2012 Report of the Committee on Infectious Diseases. Elk Grove Village, IL : American Academy of Pediatrics, 29th ed., 2012, pp. 669-680.
b. Clinical Specificity:
See Section 3a
-
Other Clinical Supportive Data ﻥ
Not applicable -
- Clinical cut-off:
Not applicable
- Clinical cut-off:
5. Expected values/Reference range:
Overall incidence of Streptococcus pyogenes in patients tested during the 2012 clinical study was 14.6% (116/796).
N. Other Supportive Device and Instrument Information:
Instrument: illumipro- 10™
O. System Descriptions:
System Description was reviewed in previous submission, K100818, K112125 and K121044. No system or software changes were made for the illumigene Group A Streptococcus assay.
1.
The illumipro-10m heats each illumiqene Group A Strep Test Device containing prepared samples and Control Reagent, facilitating amplification of target DNA. When S. pyogenes is present in the throat swab sample, a conserved sequence of the S. pyogenes is amplified and magnesium pyrophosphate is generated. Magnesium pyrophosphate forms a precipitate in the reaction mixture. The illumipro- 10detects the change in light transmission through the reaction mixture created by the precipitating magnesium pyrophosphate. Sample results are reported as Positive or Negative based on the detected change in light transmission.
10
| | K122019
illumigene® Group A Streptococcus (Group A Strep) DNA Amplification Assay | |
|---------------------------------------|--------------------------------------------------------------------------------------|---------------------------------------------------------------|
| | Application Reference: | Section 2 |
| Bioscience. Inc. | Attachment Description: | 510(k) Substantial Equivalence Determination Decision Summary |
| Inspired Science. Trusted Solutions." | Date: | September 10, 2012 |
2. Software: . . . . .
FDA has reviewed applicant's Hazard Analysis and software development processes for this line of product types:
Yes___________________________________________________________________________________________________________________________________________________________________________ No
3. Specimen Identification:
The illumipro- 10utilizes software to automate incubation and detection of illumigene Molecular Diagnostic in vitro diagnostic test reactions. The illumipro- 10reports sample results as INVALID, POSITIVE or NEGATIVE.
4. Specimen Sampling and Handling:
Specimens are prepared manually. Incubation and detection are automated using the illumipro-10.
-
- Calibration:
Calibration of the illumipro- 10is not required.
- Calibration:
6. Quality Control:
The illumigene Group A Strep External Control Kit includes a Positive Control Reagent. The External Positive Control is used in conjunction with the illumigene Sample Preparation Apparatus II/Negative Control III provided in the illumigene Group A Strep DNA Amplification Assay. 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. The illumigene® Group A Strep External Control Kit is required for routine Quality Control.
11
Image /page/11/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States. The seal features a stylized caduceus, a symbol often associated with medicine and healthcare, with three intertwined snakes around a staff. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the caduceus. The seal is black and white.
Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993
Meridian Biosciences, Inc. c/o Michelle L. Smith 3471 River Hills Drive Cincinnati, OH, 45244, US
SEP 13 2012
Re: K122019
Trade Name: illumigene® Group A Streptococcus (Group A Strep) DNA Amplification Assav illumigene® Group A Streptococcus (Group A Strep) External Control Kit Regulation Number: 21 CFR §866.3740 Regulation Name: Group A Streptococcus spp. Nucleic Acid Amplification Assay Regulatory Class: Class I
Product Codes: OYZ, OOI Dated: September 10, 2012
Received: September 11, 2012
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.
If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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
12
Page 2 - Michelle L. Smith
medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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/ReportalProblem/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/cdrh/industry/support/index.html.
Sincerely yours.
Salgado
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
13
Indication(s) for Use Form
510(k) Number: K122019
Device Name: illumigene® Group A Streptococcus (Group A Strep) DNA Amplification Assay
Indications for Use:
The illumigene® Group A Streptococcus (Group A Strep) assay, performed on the illumipro-10™, is a qualitative in vitro diagnostic test for the detection of Streptococcus pyogenes (Group A ß-hemolytic Streptococcus) in throat swab specimens.
The illumigene Group A Strep assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect Streptococcus pyogenes by targeting a segment of the Streptococcus pyogenes genome. Results from the illumigene Group A Strep assay can be used as an aid in the diagnosis of Group A Streptococcal pharyngitis. The assay is not intended to monitor treatment for Group A Streptococcus infections.
illumigene Group A Strep is intended for use in hospital, reference or state laboratory settings. The device is not intended for point of-care use.
× Over-The-Counter Use Prescription Use (Part 21 CFR 801 Subpart D) AND/OR (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Leslie Lu-Paolo
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) k12 2019