K Number

Device Name

ILLUMIGENE GROUP B STREPTOCOCCUS CARROT BROTH CLAIM

Manufacturer

MERIDIAN BIOSCIENCE, INC.

Date Cleared

2012-05-01

(25 days)

Product Code

NJR

Regulation Number

866.3740

Intended Use

The illumigene Group B Streptococcus (GBS) assay, performed on the illumipro-10, is a qualitative in vitro diagnostic for the detection of Streptococcus agalactiae in enriched cultures obtained from vaginal/rectal swab specimens from antepartum women. Enriched cultures are obtained by 18-24 hour incubation of vaginal/rectal swab specimens in selective broth medium, Lim Broth, TransVag Broth or Carrot Broth. The illumigene GBS assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect Streptococcus agalactiae by targeting a segment of the Streptococcus agalactiae genome. Results from the illumigene GBS assay can be used as an aid in establishing the GBS colonization status of antepartum women. This assay does not diagnose or monitor treatment for GBS infections. The illumigene GBS assay does not provide susceptibility results. Culture isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women. illumigene Group B Streptococcus 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® Group B Streptococcus (GBS) DNA Amplification Test Kit, the illumigene Group B Streptococus (GBS) External Control Kit and the illumipro-10™ Automated Isothermal Amplification and Detection System. The illumigene Group B Streptococcus (GBS) DNA amplification assay utilizes loop-mediated isothermal amplification (LAMP) technology to detect the presence of Streptococcus agalactiae in enriched cultures obtained from vaginal/rectal swab specimens taken from antepartum women. Each illumigene GBS assay is completed using illumigene Control Reagent, illumigene Reaction Buffer, an illumigene GBS Test Device and an illumigene Heat Treatment Tube. Samples are diluted with the illumigene Control Reagent, target DNA is made available for isothermal amplification via heat-treatment in the illumigene Heat Treatment Tube and DNA amplification occurs in the illumigene GBS Test Device. The illumipro-10 heats each illumigene GBS Test Device containing prepared samples and Control Reagent, facilitating amplification of target DNA. When S. agalactiae is present in the enriched culture sample, a conserved sequence of the S. ggdractiae is amplified and magnesium pyrophosphate is formed. 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. Sample results are reported as Positive or Negative based on the detected change in light transmission. The illumigene Group B Streptococcus (GBS) External Control Kit consists of a Positive Control Reagent and a Negative 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. The illumigene Group B Streptococcus External Control Kit is required for routine Quality Control.

More Information

Contact

Type

Center

Panel

Date Received

Product Code

Subsequent Product Codes

Applicant Name (Manufacturer)

Device Name

Decision

Street 1

Street 2

City

State

Country Code

ZIP

Postal Code

Class Advise Committee

SSP Indicator

Third Party Reviewed

Expedited Review

Predicate Devices

K112125

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description focuses on LAMP technology and detection of light transmission changes, with no mention of AI or ML.

Therapeutic

No.
The device is an in vitro diagnostic for detecting Group B Streptococcus and explicitly states it "does not diagnose or monitor treatment for GBS infections," meaning it provides diagnostic information rather than directly treating a condition.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states that the device is a "qualitative in vitro diagnostic for the detection of Streptococcus agalactiae." It also mentions that the results "can be used as an aid in establishing the GBS colonization status of antepartum women," which is a diagnostic purpose.

SaMD (Software as a Medical Device)

The device description explicitly states the system is comprised of a test kit, external control kit, and an automated isothermal amplification and detection system (illumipro-10), which is a hardware component.

IVD (In Vitro Diagnostic)

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

The "Intended Use / Indications for Use" section explicitly states: "The illumigene Group B Streptococcus (GBS) assay, performed on the illumipro-10, is a qualitative in vitro diagnostic for the detection of Streptococcus agalactiae in enriched cultures obtained from vaginal/rectal swab specimens from antepartum women."

This statement clearly identifies the device as an in vitro diagnostic.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The illumigene GBS assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect Streptococcus agalactiae by targeting a segment of the Streptococcus agalactive genome. Results from the illumigene GBS assay can be used as an aid in establishing the GBS colonization status of antepartum women. This assay does not diagnose or monitor treatment for GBS infections. The illumigene GBS assay does not provide susceptibility results. Culture isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.

illumigene Group B Streptococcus 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)

NJR

Device Description

The illumigene Group B Streptococcus (GBS) DNA amplification assay utilizes loop-mediated isothermal amplification (LAMP) technology to detect the presence of Streptococcus agalactiae in enriched cultures obtained from vaginal/rectal swab specimens taken from antepartum women. Each illumigene GBS assay is completed using illumigene Control Reagent, illumigene Reaction Buffer, an illumigene GBS Test Device and an illumigene Heat Treatment Tube. Samples are diluted with the illumigene Control Reagent, target DNA is made available for isothermal amplification via heat-treatment in the illumigene Heat Treatment Tube and DNA amplification occurs in the illumigene GBS Test Device.

The illumipro-10 heats each illumigene GBS Test Device containing prepared samples and Control Reagent, facilitating amplification of target DNA. When S. agalactiae is present in the enriched culture sample, a conserved sequence of the S. ggdractiae is amplified and magnesium pyrophosphate is formed. 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. Sample results are reported as Positive or Negative based on the detected change in light transmission.

The illumigene Group B Streptococcus (GBS) External Control Kit consists of a Positive Control Reagent and a Negative 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. The illumigene Group B Streptococcus External Control Kit is required for routine Quality Control.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Vaginal/rectal swab specimens

Indicated Patient Age Range

Antepartum women

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

Clinical trials for the illumigene Group B Streptococcus (GBS) assay, including the illumipro-10 Automated Isothermal amplification and detection system, were conducted in 2012. Performance characteristics of the illumigene GBS assay were determined by comparison to GBS bacterial culture in two separate studies: (1) Lim and TransVag Broth Enrichment, reference K112125; and (2) Carrot Broth Enrichment.

(1) Lim and TransVag Broth Enrichment: illumigene GBS assay performance using Lim Broth and TransVag Broth enriched specimens was evaluated in 2011 by four independent clinical test sites located in the Midwestern and Southern regions of the United States. A total of 826 qualified patient samples were evaluated. Samples were obtained according to established guidelines for the collection of clinical specimens for culture of Group B Streptococcus and enriched for 18-24 hours in either Lim Broth or TransVag Broth prior to illumigene testing. Four hundred three (403, 48.8%) specimens were enriched with Lim Broth and 423 (51.2%) specimens were enriched with TransVag Broth prior to testing. The age groups of patients tested ranged from 15 years of age to 44 years of age, with age unknown for 3 (0.4%) of the patient population.

(2) Carrot Broth Enrichment: Performance characteristics specific to Carrot Broth Enrichment were established by studies involving three independent clinical test sites located in the Midwestern and Southern regions of the United States. Independent clinical test sites located in the Midwestern and Southern regions of the United States evaluated a total of 600 qualified patient samples were obtained according to established guidelines for the collection of clinical specimens for culture of Group B Streptococcus and enriched in Carrot Broth prior to illumigene testing. The age groups of patients tested ranged from 15 years of age to 48 years of age.

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

Clinical Studies:
Clinical trials for the illumigene Group B Streptococcus (GBS) assay, including the illumipro-10 Automated Isothermal amplification and detection system, were conducted in 2012. Performance characteristics of the illumigene GBS assay were determined by comparison to GBS bacterial culture in two separate studies: (1) Lim and TransVag Broth Enrichment, reference K112125; and (2) Carrot Broth Enrichment.

Combined Performance Data (all studies and all enrichment broth types):

Sensitivity: 98.6% (285/289), 95% CI: 96.5% - 99.5%
Specificity: 93.2% (1045/1121), 95% CI: 91.6% - 94.5%

Lim and TransVag Broth Enrichment Study (2011):

Study Type: Clinical evaluation comparing illumigene GBS assay to GBS bacterial culture.
Sample Size: 826 qualified patient samples (403 Lim Broth, 423 TransVag Broth).
Key Results:
- Overall assay Sensitivity: 97.4% (150/154), 95% CI: 91.9% - 99.0%
- Overall assay Specificity: 92.3% (610/661), 95% CI: 90.0% - 94.1%
- Invalid results: 11/826 samples (1.3%).
- Discrepant results: 48 of 51 false positive results were positive by another molecular method (Lim Broth: 16 of 19, TransVag Broth: 32 of 32).
- Combined correlation between molecular methods for concordant samples: 97.7%.

Carrot Broth Enrichment Study (2012):

Study Type: Clinical evaluation comparing illumigene GBS assay to GBS bacterial culture.
Sample Size: 600 qualified patient samples.
Key Results:
- Overall assay Sensitivity: 100.0% (135/135), 95% CI: 97.2% - 100.0%
- Overall assay Specificity: 94.6% (435/460), 95% CI: 92.1% - 96.3%
- Invalid results: 5/600 (0.8%).
- Discrepant results: 16 of 24 illumigene Positive: GBS Culture Negative specimens were positive by an alternate molecular amplification assay.

Analytical Performance - Precision/Reproducibility:

Study Type: Reproducibility study using blind coded panels.
Sample Size: 10 samples per panel, supplied to three independent laboratories.
Data Source: Contrived samples (low positive, high negative, positive), and natural negative samples.
Key Results: 100% agreement for Negative, High Negative, Low Positive, and Positive sample types across all three sites.

Analytical Performance - Detection limit:

Study Type: Sensitivity studies to determine the analytical limit of detection (LoD).
Data Source: Six common strains of S. agalactiae (representing six serotypes) spiked into negative Lim Broth and serially diluted.
Key Results: The LoD of the assay ranged from 60 CFU/Test to 1280 CFU/Test. Lowest positive concentration for each serotype was determined with 95% of replicates tested.

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

Combined Performance Data:

Sensitivity: 98.6%
Specificity: 93.2%

Lim and TransVag Broth Enrichment Study:

Sensitivity: 97.4%
Specificity: 92.3%

Carrot Broth Enrichment Study:

Sensitivity: 100.0%
Specificity: 94.6%

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K112125

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

Regulation Number and Section

§ 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.

Summary

Image: Meridian Bioscience, Inc. logo	illumigene® Group B Streptococcus (GBS) DNA Amplification Assay
	Application Number:	K121044
	Application Section 2:	510(k) Summary

510(k) Substantial Equivalence Determination Decision Summary

MAY - 1 2002

A. 510(k) number: K121044

B. Purpose for Submission:
To determine substantial equivalence for the illumigene® Group B Streptococcus (GBS) DNA Amplification Assay used for the qualitative detection of Streptococcus agalactiae.

C. Measurand:

Segment of the Streptococcus agalactiae genome

D. Type of Test:

Qualitative in vitro diagnostic using Loop-mediated isothermal DNA amplification (LAMP) technology

ﻧﻨﺎ Applicant:

Meridian Bioscience, Inc.

F. Propriety and Established Names:

illumigene® Group B Streptococcus (GBS) DNA Amplification Assay

G. Regulatory Information:

Product Code	Classification	Regulation Section	Panel
NJR, Nucleic acid amplification assay system,
Streptococcus spp., serological reagents	Class I	21 CFR § 866.3740	Microbiology (83)

H. Intended Use:

1. Intended use(s):

| Image: Meridian

Bioscience, Inc.	illumigene® Group B Streptococcus (GBS) DNA Amplification Assay
Application Number:	K121044
Application Section 2:	510(k) Summary

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

2. Indication(s) for use:

The illumiaene Group B Streptococcus (GBS) assay, performed on the illumipro-10, is a qualitative in vitro diagnostic for the detection of Streptococcus agalactiae in enriched cultures obtained from vaginal/rectal swab specimens from antepartum women. Enriched cultures are obtained by 18-24 hour incubation of vaginal/rectal swab specimens in selective broth medium, Lim Broth, TransVag Broth or Carrot Broth.

The illumigene GBS assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect Streptococcus agalactioe by targeting a segment of the Streptococcus agalactiae genome. Results from the illumigene GBS assay can be used as an aid in establishing the GBS colonization status of antepartum women. This assay does not diagnose or monitor treatment for GBS infections. The illumigene GBS assay does not provide susceptibility results. Culture isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.

illumigene Group B Streptococcus 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 ●

4. Special instrument requirements:

illumioro-10™ Automated Isothermal Amplification and Detection System

l. Device Description:

Image: Meridian Bioscience, Inc. logo	illumigene ® Group B Streptococcus (GBS) DNA Amplification Assay
	Application Number: K121044
	Application Section 2: 510(k) Summary

J. Substantial Equivalence Information:

1. Predicate device name(s): illumigene Group B Streptococcus (GBS) Assay
1. Predicate 510(k) numbers: K112125
1. Comparison with predicates:

Similarities
Item	DEVICE
illumigene ® GBS
K121044	PREDICATE
illumigene ® GBS
K112125
Intended Use	Qualitative	Same
Test Principle	DNA Amplification Assay	Same
DNA Amplification
Technology	Loop-Mediated Isothermal Amplification (LAMP)	Same
Target Sequences
Detected	213 base pair (bp) sequence residing in the 593-805
bp region of S. agalactiae genome Segment 3	Same
Specimen Types	Vaginal/Rectal Swab Specimen Enriched in Lim Broth Vaginal/Rectal Swab Specimen Enriched in TransVag Broth	Same
Reagents/Components	illumigene Control Reagent illumigene Reaction Buffer illumigene GBS Test Device illumigene Heat Treatment Tubes	Same
Amplification	Self contained and automated	Same
Detection	Self contained and automated	Same
Testing Time	60 minutes	Same
Instrumentation	illumipro-10™ Automated Isothermal Amplification
and Detection System	Same
Reading Method	Visible Light Transmission	Same
Calibration	Not required	Same

Image: Meridian Bioscience, Inc. logo	illumigene® Group B Streptococcus (GBS) DNA Amplification Assay
	Application Number: K121044
	Application Section 2: 510(k) Summary

Differences
Item	DEVICE
illumigene ® GBS
K121044	PREDICATE
illumigene ® GBS
K112125
Specimen Types	Vaginal/Rectal Swab Specimen Enriched in Carrot
Broth	N/A
Performance
Sensitivity Specificity	98.6% [95% CI: 96.5% - 99.5%]
93.2% [95% CI: 91.6% - 94.5%]	97.4% [95% CI: 91.9% - 99.0%]
92.3% [95% CI: 90.0% - 94.1%]

Standard/Guidance Document Referenced (if applicable): K.

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 B Streptococcus assay is based on loop-mediated isothermal amplification technology (LAMP). Loop-mediated amplification of DNA is accomplished by the use of specially designed primers that provide specific and continuous isothermal amplification. Magnesium-pyrophosphate is a by-product of LAMP amplification. The magnesium-pyrophosphate forms a white precion 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 detectable change in sample absorbance and is considered a negative reaction.

M. Performance Characteristics (if/when applicable):

1. Analytical Performance:
- a. Precision/Reproducibility:

Reproducibility studies were completed with K12225. 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 (interassay variability). Three lots of illumipro-10 instruments were used in this study. The results are given in the table below:

Image /page/4/Picture/0 description: The image shows the logo for Meridian Bioscience, Inc. The logo consists of a globe-like graphic on the left, followed by the word "Meridian" in a bold, stylized font. Below "Meridian" is the text "Bioscience, Inc." in a smaller, also bold font. The overall design is simple and professional.

illumigene® Group B Streptococcus (GBS) DNA Amplification Assay
Application Number:	K121044
Application Section 2:	510(k) Summary

	Site 1		Site 2		Site 4		Total
Sample Type		Percent agreement		Percent agreement		Percent agreement		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	30/30	100%	30/30	100%	30/30	100%	90/90	100%

Linearity/assay reportable range: b.

Not applicable as this assay is qualitative

Traceability, Stability, Expected values (controls, calibrators, or methods): ﻥ

Stability:

Stability studies were completed with K112125 and supplemented for K121044. Sample storage and hold time studies were performed to characterize illumiqene® Group B Streptococcus (GBS) assay ranges. Validation studies performed at Meridian indicated that Lim Broth represented the worst-case matrix; therefore studies were completed using Lim Broth. Assay ranges were confirmed for the remaining TransVag Broth and Carrot Broth by testing one high negative and one LoD positive sample prepared from each broth.

Study results demonstrated that undiluted samples can be held at 19 -27 C for up to 6 hours or at 2-8 C for up to 7 days after culture enrichment and prior to testing. Samples diluted with illumigene® Control Reagent can be held at 21 -27 C for up to 15 minutes prior to heat-treated samples may be held at 19-29 C for up to 45 minutes prior to further processing.

Sample freeze/thaw studies were also performed. Samples were enriched 18-24 hours and frozen prior to initiation of testing. Samples were subject to multiple freeze/thaw cycles. Study results showed that samples should not be freeze/thawed.

Final testing demonstrated that Lim Broth, in combination with Dacron/polyester, flocked nylon and foam swab types perform acceptably with the illumigene® GBS assay. Amies Clear and Calcium Alginate Swabs produced invalid results and are not considered validated for use with illumigene® GBS. Swab types with demonstrated performance in the illumigene® GBS assay appear in the Package Insert.

d. Detection limit:

Detection limit studies were completed with K12225. Sensitivity studies were designed to determine the analytical limit of detection of S. agalactiae in Lim Broth. Six common strains of S.agalactiae, representing six serotypes, were evaluated with the illumigene® GBS assay. Each strain was spiked into negative Lim Broth and diluted serially. A minimum of twenty replicates for each dilution were individually processed and tested to establish LoD. Testing was performed using three production lots of illumigene® GBS assay and six illumipro-10™ instruments. External Positive and Negative Controls were tested each day throughout the study.

The LoD of the assay ranged from 60 CFU/Test to 1280 CFU/Test. The table below shows the lowest concentration for each serotype that produced positive results for 95% of the replicates tested.

Image /page/5/Picture/0 description: The image shows the logo for Meridian Bioscience, Inc. The logo features a globe-like icon on the left, followed by the word "Meridian" in a bold, italicized font. Below "Meridian" is the text "Bioscience, Inc." in a smaller, bold font. A horizontal line separates "Meridian" from "Bioscience, Inc."

illumigene® Group B Streptococcus (GBS) DNA Amplification Assay
Application Number:	K121044
Application Section 2:	510(k) Summary

| Serotype | Streptococcus agalactiae Strain
Description | CFU/Test |
|----------|------------------------------------------------|----------|
| Ia | NCTC 11248 | 60 |
| Ib | ATCC 12401 | 80 |
| Ic | NCTC 11253 | 640 |
| II | II/2 | 320 |
| III | ATCC 12403 | 160 |
| V | ATCC BAA-611 | 1280 |

Additional S. agoloctioe strains were tested and produced positive reactions at 1280 CFU/test with Strains and serotypes were tested as follows: Serotype IV: NCTC 11930, hemolytic; illumiaene GBS. Serotype VIa: NCTC 08188, non-hemolytic; Serotype VII: VII/2, hemolytic; Serotype VIII: VIII/2, hemolytic; Serotype X: NCTC 11249, hemolytic; Unknown Serotype: ATCC 13813, non-hemolytic; and ATCC12386, hemolytic.

Limit of Detection studies are acceptable.

e. Analytical specificity:

Interference Testing:

Interference testing was completed with K112125. Selected substances that might be expected to be present in vaginal/rectal swab samples taken from antepartum women were added to a negative Lim broth sample and two contrived positive Lim broth sample was prepared by pooling confirmed negative Lim Broth samples while the contrived positive samples were prepared by spiking a pooled, confirmed negative Lim sample with either Streptococcus agalactiae, strain 11248 Serotype la (123 CFU/test) or Streptococcus agalactiae, strain 12401 Serotype Ib (80 CFU/test). Potentially interfering substances were added to Lim broth samples at final concentrations of 2.5% v/v or greater when the substances could be pipetted. Substances that could not be pipetted were coated onto cotton swabs, immersed in the negative/positive Lim broth samples and tested. Dilution Controls were prepared by adding a phosphate buffered saline solution in place of the potentially cross-reactive organisms. Each inoculated sample was tested in triplicate.

The following substances, at the specified saturated solvent/diluents concentrations, do not interfere with illumigene Group B Streptococcus test results: Amniotic fluid (10% v/v), Human DNA (100 ng/Test), Urine (30%v/v), Whole Blood (2.5% v/v). The following substances do not interfere with test results: Meconium, Stool, Hemorrhoidal cream (30.65 mg/100mg), Miconazole (fungicide), Mucin (0.5-1.5%), Spermicidal gel (nonoxynol 9) (4 mg/100mg). Lubricating gel produced False Negative Results in 1 of 11 replicates tested. Body Powder produced False Negative Results in 1 of 10 replicates tested. Whole Blood at concentrations greater than 2.5% v/v interferes with the illumigene GBS assay.

Interference studies are acceptable.

Cross-Reactivity Study:

Cross-reactivity studies were completed with K12125. Potentially cross-reacting microorganisms expected to be present in vaginal/rectal swab specimens were added to negative and contrived positive Lim Broth The negative sample was prepared by pooling confirmed negative Lim Broth samples. The samples. contrived positive sample was prepared by spiking a confirmed negative matrix with Streptococcus

Image: Meridian Bioscience, Inc. logo	illumigene® Group B Streptococcus (GBS) DNA Amplification Assay
	Application Number: K121044
	Application Section 2: 510(k) Summary

agoloctioe, strain 12401, at 122 CFU/test, near the limit of detection for this strain. Potentially crossreactive microorganisms were added at concentrations of 1.2 x 10° CFU/mL (bacteria and fungi) or virus at a minimum of 1 x 10 TCIDso/mL (viruses). 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. Cross-reactivity with Enterococcus dispar was observed in one of seven replicates tested.

The following microorganisms at the indicated concentrations do not interfere with illumigene GBS: Aeromonas hydrophila, Alcaligenes faecalis, Bacillus subtilis, Bacteroides fragilis, Campylobacter coli, Campylobacter fetus, Campylobacter jejuni, Candida albicans, Candida glabrata, Candida krusei, Candida parapsilosis, Citrobacter freundii, Clostridium bifermentans, Clostridium butyricum, Clostridium difficile, Clostridium histolyticum, Clostridium novyi, Clostridium perfringens, Clostridium septicum, Clostridium sordelli, Clostridium sporogenes, Clostridium tetani, Corynebacterium genitalium, Corynebacterium urealyticum, Corynebacterium xerosis, Enterobacter aerogenes, Enterobacter cloocae, Enterococcus avium, Enterococcus durans, Enterococcus faccalis, Enterococus faecium, Escherichia coli, Escherichia coli 0157:H7, Escherichia fergusonii, Escherichia hermannii, Gardnerella vagindiis ducreyi, Helicobacter pylori, Klebsiella pneumoniae, Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus delbruekii subspecies Iactis, Lactobacillus jensenii, Lactococcus lactis, Legionella pneumophila, Listeria monocytogenes, Moraxella osloensis, Morganella morganii, Neisseria gonorrhoeae, Peptostreptococcus anaerobius, Plesiomonas shigelloides, Porphyromonas asaccharolytica, Prevotella melaninogenica, Propionibacterium acnes, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Pseudomonus fluorescens, Salmonella Group B, Salmonella Group C, Salmonella Group D, Salmonella Group E, Serratia marcescens, Shigella boydii. Shigella flexneri. Staphylococcus aureus, Staphylococcus aureus (Cowan), Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococus anginosus, Streptococcus bovis, Streptococcus dysgalactiae equisimilis, Streptococcus intermedius, Streptococcus mitis, Streptococcus ordis, Streptococcus pneumoniae, Streptocacus pyogenes, Streptococcus salivarius, Streptococcus sanguinis, Vibrio parahaemolyticus, Yersinia enterocolitica, Adenovirus 41, BK virus, Coxsackievirus, Echovirus, Epstein Barr virus, Herpes Simplex Virus-1, Herpes Simplex Virus-2, Rotavirus.

Mycoplasma genitalium, Mycoplasma hominis and Ureaplasma urealyticum were tested at final concentrations ranging between 1.6 x 10 and 9.9 x 10 CFU/mL with no reaction with the illumigene GBS assay.

Cross-reactivity studies are acceptable.

f. Assay cut-off:
The illumigene Group B Streptococcus 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 (Signalmon) and at the end of the Assay Run (Signalma). The illumipro-10 calculates that change in transmission between the Signalmar and compares the result to a fixed cut-off value. Test results are reported as Positive based on comparison to the assay cut-off. Fixed cut-off values were based on well characterized clinical specimens.

Image /page/7/Picture/0 description: The image shows the logo for Meridian Bioscience, Inc. The logo consists of a globe-like graphic on the left, followed by the word "Meridian" in a bold, sans-serif font. Below "Meridian" is the phrase "Bioscience, Inc." in a smaller, also bolded, sans-serif font. A horizontal line underlines the word "Meridian".

illumigene® Group B Streptococcus (GBS) DNA Amplification Assay

Application Number:	K121044
Application Section 2:	510(k) Summary

2. Comparison Studies:

Method comparison with predicate device: 0.
Not applicable

b. Matrix comparison:

Not applicable

3. Clinical Studies:

Clinical Sensitivity: a.
Clinical trials for the illumigene Group B Streptococcus (GBS) assay, including the illumipro-10 Automated Isothermal amplification and detection system, were conducted in 2012. Performance characteristics of the illumigene GBS assay were determined by comparison to GBS bacterial culture in two separate studies: (1) Lim and TransVag Broth Enrichment, reference K112125; and (2) Carrot Broth Enrichment. Combined performance data for all studies and all enrichment broth types is shown in Table 1.

Sample Type	Positive Samples			Negative Samples
	illumigene /
GBS Culture	Sensitivity %	95% CI	illumigene /
GBS Culture	Specificity %	95% CI
Total	285/289	98.6%	96.5 - 99.5%	1045/1121	93.2%	91.6 - 94.5%
Lim Broth	82/84	97.6%	91.7 - 99.3%	296/315	94.0%	90.8 - 96.1%
TransVag Broth	68/70	97.1%	90.2 - 99.2%	314/346	90.8%	87.2 - 93.4%
Carrot Broth	135/135	100%	97.2 - 100.0%	435/460	94.6%	92.1 - 96.3%

Table 1: illumigene Group B Streptococcus assay performance characteristics

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illumigene® Group B Streptococcus (GBS) DNA Amplification Assay
Application Number:	K121044
Application Section 2:	510(k) Summary

Group B Streptococcus	illumigene Group B Streptococcus (GBS)
Culture	Positive	ా Negative	Total
Positive	150 ·	য	154
Negative	51	eio	661
Total	201	614	845
			વેટી વિદર્ભ
Sensitivity	150/154	97.4%	91.9 - 99.0%
Specificity	610/661	92.3%	90.0 - 94.1%
Correlation	760/815	93.3%	91.3 - 94.8%

I im and TransVas enrichment performance data

Forty-eight of the 51 false positive results were positive by another molecular method. Invalid results were obtained for 11/826 samples tested or 1.3%. Two of the 11 samples remained invalid after repeat testing of the original sample.

Table 3: Performance characteristics summary: Lim and TransVag Broth Enrichment

| Site
Identification | Enrichment
Broth | Positive Samples | | | Negative Samples | | |
|------------------------|---------------------|-----------------------------------|------------------|--------------|-----------------------------------|------------------|--------------|
| | | illumigene
/GBS Culture | %
Sensitivity | 95% CI | illumigene
/GBS Culture | %
Specificity | 95% CI |
| Total | N/A | 150/154 | 97.4% | 91.9 - 99.0% | 610/661 | 92.3% | 90.0 - 94.1% |
| Site 1 | TransVag | 32/33 | 97.0% | 84.7 - 99.5% | 197/199 | 99.0% | 96.4 - 99.7% |
| Site 3 | TransVag | 36/37 | 97.3% | 86.2 - 99.5% | 117/147 | 79.6% | 72.4 - 85.3% |
| Site 2 | Lim | 38/39 | 97.4% | 86.8 - 99.5% | 162/168 | 96.4% | 92.4 - 98.4% |
| Site 4 | Lim | 44/45 | 97.8% | 88.4 - 99.6% | 134/147 | 97.8% | 85.5 - 94.8% |

Specimens that generated discrepant results were further evaluated by independent testing laboratories using FDA cleared or laboratory validated molecular assays. Sixteen of nineteen Lim Broth False Positive results were positive by an alternate molecular method. All thirty-two TransVag Broth False Positive results were positive by an alternate molecular method. In addition to discrepant sample analysis, a selection of concordant samples was tested with non-illumigene molecular methodologies. Concordant result testing showed a combined correlation between molecular methods of 97.7%.

illumigene® Group B Streptococcus (GBS) DNA Amplification Assay
Application Number:	K121044
Application Section 2:	510(k) Summary

Group B Streptococcus Culture	illumigene Group B Streptococcus (GBS)
	Positive	Negative	Total
Positive	135	0	135
Negative	25	435	460
Total	160	435	595
			95% CI
Sensitivity	135/135	100.0%	97.2 - 100.0%
Specificity	435/460	94.6%	92.1 - 96.3%
Correlation	570/595	95.8%	93.9 - 97.1%

Invalid results were obtained for 5/600 (0.8%) samples. One of the 5 samples remained invalid after repeat testing. Repeat test results are not included in assay performance calculations. Twenty four of the 25 illumigene Positive: GBS Culture Negative specimens were further analyzed by an independent laboratory developed GBS Molecular Assay. Sixteen of the 24 discrepant samples were positive by the alternate molecular amplification assay.

Table 5: illumigene Group B Streptococcus assay performance by Site

| Site

Identification	Positive Samples			Negative Samples			Invalid Samples
	illumigene /
GBS Culture	%
Sensitivity	95% CI	illumigene
/GBS Culture	%
Specificity	95% CI	Invalid
/Total	%
Invalid
Total	135/135	100.0%	97.2 - 100.0%	435/460	94.6%	92.1 - 96.3%	5/600	0.8%
Site 1	58/58	100.0%	93.8 - 100.0%	92/93	98.9%	94.2 - 99.8%	0/151	0.0%
Site 2	36/36	100.0%	90.4 - 100.0%	145/149	97.3%	93.3 - 99.0%	1/186	0.5%
Site 3	41/41	100.0%	91.4 - 100.0%	198/218	90.8%	86.3 - 94.0%	4/263	1.5%

Enriched carrot broth samples were visually inspected for color at the enrichment incubation and prior to initiation of illumigene testing. Table 3 summarizes performance data and observed broth color. Thirty four of the 135 (25.1%) illumigene/GBS Culture positive specimens were reported as showing no visual change in color at the end of enrichment incubation.

Table 6: Performance Characteristics by Carrot Broth Results

	Positive Samples			Negative Samples
Sample Type	illumigene /
GBS Culture	Sensitivity %	95% CI	illumigene /
GBS Culture	Specificity %	95% CI
Color Change	100/100	100.0%	96.3 - 100.0%	2/2	100.0%	34.2 - 100.0%
No Color Change	34/34	100.0%	89.8 - 100.0%	433/458	94.5%	92.1 - 96.3%
Unspecified	1/1	100.0%	20.7 - 100.0%	0/0	0.0	0.0 - 0.0%

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illumigene® Group B Streptococcus (GBS) DNA Amplification Assay
Application Number:	K121044
Application Section 2:	510(k) Summary

Clinical Specificity: b.
See Section 3a
Other Clinical Supportive Data C.
Not applicable
1. Clinical cut-off:
  Not applicable

5. Expected values/Reference range:

Approximately 10-30% of antepartum women are colonized with Group B Streptocccus in the vagina or rectum: Clinical performance of the illumigene GBS Assay was established during two clinical studies completed in 2011 (Lim Broth and TransVag Broth) and 2012 (Carrot Broth). The overall incidence of GBS colonization in antepartum women tested during the 2011 study was 24.3% (201 of 826). Incidence of GBS colonization for enrichment performed using Lim Broth was found to be 25.1% (101 of 403); while incidence for specimens enriched by TransVag Broth was found to be 23.6% (100 of 423). The overall incidence of GBS colonization in antepartum women tested during the 2012 Carrot Broth study was found to be 22.5% (135 of 600).

N. Other Supportive Device and Instrument Information:

Instrument: illumipro-10™

O. System Descriptions:

System Description was reviewed in previous submission, K100818, K110012 and K12225. No system or software changes were made.

1. Modes of Operation:

The illumipro-10™ heats each illumigene® GBS Test Device containing prepared samples and Control Reagent, facilitating amplification of target DNA. When S. agoloction is present in the enriched culture sample, a conserved sequence of the S. agalaction is amplified and magnesium pyrophosphate is formed. 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. Sample results are reported as Positive or Negative based on the detected change in light transmission.

1. Software:
  FDA has reviewed applicant's Hazard Analysis and software development processes for this line of product types:

Yes Yes No

1. Specimen Identification:
  The illumipro-10™ utilizes software to automate incubation of illumigene Molecular Diagnostic in vitro diagnostic test reactions. The illumipro-10™ reports sample results as INVALID, POSITIVE or NEGATIVE.

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illumigene® Group B Streptococcus (GBS) DNA Amplification Assay
Application Number:	K121044
Application Section 2:	510(k) Summary

4. Specimen Sampling and Handling:

Specimens are prepared manually. Incubation and detection are automated using the illumipro-10™.

5. Calibration:

Calibration of the illumipro-10™ is not required.

6. Quality Control:

The illumigene® Group B Streptococcus External Control Kit consists of a Positive Control Reagent and a Negative 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. The illumigene® Group B Streptococcus External Control Kit is required for routine Quality Control.

Statement for the Record, K 121044 Meridian BioScience, Inc. Illumigene Group B Streptococcus (GBS) DNA Amplification Assay

This 510(k) was reviewed under OIVD's Pilot Triage Program. This program represents an internal workload management tool intended to reduce internal FDA review resources for 510(k) applications that are of good quality upon receipt by FDA.

The information in the 510(k) is complete and supports a substantial equivalence (SE) determination. Please refer to the applicant's 510(k) summary for a summary of the information that supports this SE determination.

DEPARTMENT OF HEALTH & HUMAN SERVICES

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Food and Drug Administration

10903 New Hampshire Avenue Silver Spring, MD 20993

MAY - 1 2012

Meridian Bioscience, Inc. C/o Michelle L. Smith Senior Director, RA/DA 3471 River Hills Drive Cincinnati, Ohio 45244

Re: K121044

Trade/Device Name: illumigene® Group B Streptococcus (GBS) DNA Amplification Assay Regulation Number: 21 CFR 888.3740 Regulation Name: Streptococcus spp. serological reagents Regulatory Class: Class I Product Code: NJR Dated: April 5, 2012 Received: April 6, 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act that 1 Driveral statutes and regulations administered by other Federal agencies. You must of any I cural statutios and registanents, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical

Page 2 - Ms. Michelle L. Smith

device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. 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/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/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours.

Sall artgins

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

Enclosure

	illumigene® Group B Streptococcus (GBS) DNA Amplification Assay
OFFICE TO	Application Number:	K121044
cience. Inc.	Application Section 1:	Indication(s) for Use Form

Indication(s) for Use Form

510(k) Number: K121044

Device Name: illumigene Group B Streptococcus (GBS) DNA Amplification Assay

Indications for Use:

The illumigene Group B Streptococus (GBS) assay, performed on the illumipro-10™, is a qualitative in vitro diagnostic for the detection of Streptococcus agalactiae in enriched cultures obtained from vaginal/rectal swab specimens from antepartum women. Enriched cultures are obtained by 18-24 hour incubation of vaginal/rectal swab specimens in selective broth medium, either Lim Broth, TransVag Broth or Carrot Broth.

The illumigene GBS assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect Streptococus agalactiae by targeting a segment of the Streptococcus agalactiae genome. Results from the illumigene GBS assay can be used as an aid in establishing the GBS colonization status of antepartum women. This assay is not intended to diagnose or monitor treatment for GBS infections.

The illumigene GBS assay does not provide susceptibility results. Culture isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.

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

Prescription Use _ AND/OR (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (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)

Freddie Lee Pool, MS

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

510(k) K120044 (Sol)

K121044