(108 days)
Cytotoxic bacterial culture
No
The device description focuses on DNA amplification technology (LAMP) and detection based on light transmission changes due to chemical precipitation. There is no mention of AI or ML in the intended use, device description, or performance studies.
No
This device is a qualitative in vitro diagnostic test for the direct detection of toxigenic C. difficile, not a therapeutic device. It helps in diagnosing a disease, not treating it.
Yes
The "Intended Use / Indications for Use" section explicitly states that the illumigene C. difficile DNA amplification assay is a "qualitative in vitro diagnostic test for the direct detection of toxigenic C. difficile in human stool specimens suspected of having Clostridium difficile associated disease (CDAD)."
No
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 are hardware components.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "The illumigene C. difficile DNA amplification assay, performed on the illumipro-10, is a qualitative in vitro diagnostic test for the direct detection of toxigenic C. difficile in human stool specients suspected of having Clostridium difficile associated disease (CDAD)."
This statement clearly identifies the device as an in vitro diagnostic test.
N/A
Intended Use / Indications for Use
The illumigene C. difficile DNA amplification assay, performed on the illumipro-10, is a qualitative in vitro diagnostic test for the direct detection of toxigenic C. difficile in human stool specients suspected of having Clostridium difficile associated disease (CDAD).
The illumigene C. difficile assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect the pathogenicity locus (PaLoc) of toxigenic Clostridium difficile PaLoc is a gene segment present in all known toxigenic C. difficile strains. The C. difficile PaLoc codes for both the Toxin A gene (tcdA) and the Toxin B gene (tcdB), has conserved border regions, and is found at the same site on the C. difficile genome for all toxigenic strains. The illumigene C. difficile assay detects the PaLoc by targeting a partial DNA fragment on the Toxin A gene. The tcdA target region was selected as an intact region remaining in all known A+B+ and A-B+ toxinotypes.
illumigene C. difficile is intended for use in hospital, reference or state laboratory settings. The device is not intended for point-of-care use.
Product codes
OMN
Device Description
The illumigene Molecular Diagnostic Test System is comprised of the illuminene C. difficite DNA Ampification Test Kit. the illumigene C. difficile External Control Kit and the illumipro-10 Automated Isothermal Amplification and Detection System. The illumigene C. difficile DNA amplification assay utilizes loop-mediated isothermal ampification (LAMP) technology to detect the presence of toxigenic C. difficile in patients suspected of having C. difficile associated disease (CDAD). Each illumiaene C. difficile assay is combleted using an illuminene Sample Preparation Apparatus. Illumicene Reaction Buffer, illumigene C. difficile Test Device, Sample Collection Brush, and illumigene Extraction Tube. Samples are prepared using the Sample Collection Brush and the illumigene Sample Collection Apparatus, target DNA is heat extracted in the Extraction Tube and DNA amplification occurs in the illumigene C. difficile Test Device.
The illumipro-10 heats each illumigene C. difficile Test Device containing prepared samples, facilitation of target DNA. When toxigenic C. difficile is present in the patient specific sequence is amplified and Magnesium pyrophosphate is formed. Magnesium pyrophosphate in the reaction mixture. The Illumioro-10 detects the change in light transmission mixture created by the precipitating Magnesium pyrophosphate. Sample results are reported as Positive based on the detected change in transmission.
The illumigene C. difficile External Control Kit consists of a Positive Control Reagent. External Control reagents are provided to aid the user in deterioration, adverse environmental or test conditions, or variance in operator performance that may lead to test errors. The illumigene C. difficile 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
human stool
Indicated Patient Age Range
The age groups of patients range from 2 years of age to 96 years.
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 C. difficile assay, including the illumipro-10 Automated Isothermal amplification and detection system, were conducted in 2010. Performance characteristics of the illumigene C. difficile assay were determined by comparison to cytotoxic culture. Four independent clinical test sites located in the Midwestern and Southern recions of the United States and the manufacturer evaluated a total of 697 qualified patient samples. Samples were collected from 274 (39.3%) males and 419 (60.1%) females. In the case of 4 (0.6%) of the patients, sex was not known. The age groups of patients range from 2 years of age to 96 years. No differences in test performance were observed based on patient age, sex, or geographical location.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Interference Testing
Selected drugs and other non-microbial substances that might be present in stool samples from healthy persons or patients suspected of having C. difficile associated disease were added to a natural negative and a contrived positive sample. The natural negative and contrived positive samples were prepared from donor samples and were confirmed negative by cytotoxic bacterial culture. The contrive sample was prepared by spiking a confirmed negative sample with toxinogenic C. difficile strain VPI 10463 to 18 CFU/test, slightly above the 16 CFU assay limit of delection for this organism. Potentially interfering substances were added at final concentrations of 5% V/V or greater. Dilution Controls for each sample were prepared by adding a phosphate-buffered saline solution in place of the potentially interfering substance. Each sample was tested in triplicate.
The following substances, at the specified saturated solventrations, do not interfere with illumigene C. difficile test results in the final concentrations listed: Barium sulfate (5 mg/mL), fecal fat (equivalent to 2.65 mg stearic plus 1.3 mg palmitic acids per mL), hemoglobin) (3.2 mg/mL), IgA (5 mg/mL), Inodium AD® (0.00667 mg/mL), Kaopectate® (0.87 mg/mL), Metronidazole (12.5 mg/mL) Mylanta® (4.2 mg/mL), Pepto-Bismol® (0.87 mg/mL), Prilosec® (0.5 mg/mL), TUMS® (0.5 mg/mL), Vancomycin (12.5 mg/mL), white blood cells (5%V/V), whole blood (5% V/V).
Cross-reactivity Study
Potentially cross-reactive microorganisms that might be present in stool samples from healthy persons or patients suspected of having C, difficile associated disease were added to a natural negalive sample. The natural negative and contrived positive samples were prepared from donor samples and were confirmed negative by cytotoxic bacterial culture. The contrived positive sample was prepared by spiking a confirmed negative sample with toxinogenic C. difficile strain VPI 10463 to 18 CFU assay limit of detection for this organism. Potentially cross-reactive microorganisms were added at concentrations of 1.2 x 10 fmL (bacteria and fungi) or 1 x 10539mL TCIDgs/mL (viruses). Dilution Controls for each sample were prepared by adding a phosphate-buffered saline solution in place of the potentially cross-reactive microorganisms. Each sample was tested in triplicate.
The following microorganisms, at the indicated concentrations, do not interfere with illumigene C. difficile test results: Aeromonas hydrophila. Bacteroides fragilis. Campylobacter fetus. Campylobacter ieiuni, Candida albicans. Citrobacter frendi. Clostridium perfringens, Enterobacter cloacae, Enterococcus faccalis, Escherichia coli, Escherichia coli 0157:H7, Escherichia hermannii, Helicobacter pylori, Klebsiella pneumoniae, Lactococcus lactis, Listeria monocytogenes, anaerobius, Plesiomonas shigelloides, Proteus vulgaris, Pseudomonas aeruginosa, Pseudomonas fluorescens, Salmonella Groups B-E, Serratia liquefaciens, Serratia marcescens, Shigella flexneri, Shigella sonnei, Staphylococcus aureus, Staphylococus epidermidis. Vibrio parahaemolyticus, Yersinia enterocolliica, Adenovirus, Echovirus, Echovirus, Rotavirus.
Clinical Tests
697 patient samples.
Overall Sensitivity was determined to be 95.2% (95% Cl: 89.2% - 97.9%). Overall Specificity was determined to be 95.3% (95% Cl: 93.2% - 96.7%).
Correlation: 95.3% (95% Cl: 93.4% - 96.6%).
Invalid rate: 2.9% (20/697).
Analytical Sensitivity
The analytical sensitivity of this assay for C. difficile was based on 20 replicates for each measurand and with a stated probability (e.g., 95% or 19/20 positive replicates) of obtaining positive responses at the following levels of the measurands:
Strain ID | Toxinotype | Phenotype | LoD/Test
VPI 10463 | 0 | A+/B+ | 4 CFU/test
2007431 | III (NAP1) | A+/B+ | 32 CFU/test
CF1 | VIII | A-/B+ | 64 CFU/test
2006240 | V (NAP7) | A+/B+ | 32 CFU/test
BI8 | III | A+/B+ | 64 CFU/test
2007858 | IX/XXIII | A+/B+ | 32 CFU/test
8864 | X | A-/B+ | 64 CFU/test
Additional C. difficile stock cultures from different sources were tested and produced positive reactions at 64 CFU/test with illumicene C. difficile. Strains and toxinotypes tested were as follows: Type 0 Strains: 10463, 2004111, 2004205, 2005070, 2005257, 2008029, 2008162, 2008341, 2008351, 2009066, 2009099, B1, G1, J7, K12, Y1; Type III Strains: 2004052, 2004118, 2007431, Bl17, Bl8; Type V Strains: 2005325, 2006240, 2008188, 2009018, 2009065, BK6; Type VIII Strains: 43598, 2008016, CF1; Type XII Strains: 2007435; Type IX/XIII Strains: 2007858; Unknown Strains: 2009132, 2009155, 2009277.
Reproducibility
Blind coded panels of 10 samples were supplied to three independent laboratories for precision studies. Panels included contrived samples at the assay limit of detection (n = 3) and just below the limit of blank (i.e., high negative sample, n = 3), and uncharacterized positive (n = 2) and negative (n = 2) samples. 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 C difficile were used.
Sample Type | Site 1 Percent agreement | Site 2 Percent agreement | Site 3 Percent agreement | Total Percent agreement
Negative | 20/20 (100%) | 20/20 (100%) | 19/19 (100%) | 59/59 (100%)
High Negative | 25/30 (83%) | 29/30 (97%) | 28/30 (93%) | 82/90 (91%)
Low Positive | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%)
Positive | 20/20 (100%) | 20/20 (100%) | 20/20 (100%) | 60/60 (100%)
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Sensitivity: 95.2% (95% Cl: 89.2% - 97.9%)
Specificity: 95.3% (95% Cl: 93.2% - 96.7%)
Correlation: 95.3% (95% Cl: 93.4% - 96.6%)
Predicate Device(s)
Reference Device(s)
Cytotoxic bacterial culture
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 866.2660 Microorganism differentiation and identification device.
(a)
Identification. A microorganism differentiation and identification device is a device intended for medical purposes that consists of one or more components, such as differential culture media, biochemical reagents, and paper discs or paper strips impregnated with test reagents, that are usually contained in individual compartments and used to differentiate and identify selected microorganisms. The device aids in the diagnosis of 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.
0
Image /page/0/Picture/0 description: The image shows the logo for Meridian Bioscience, Inc. The logo consists of a stylized globe on the left, followed by the word "Meridian" in a bold, sans-serif font. A horizontal line underlines the word "Meridian", and below the line is the text "Bioscience, Inc." in a smaller, bold, sans-serif font.
| 510(k) Application illumigene C. difficile | |
|---|---|
| Description: | 510(k) Summary illumigene C. difficile |
| Identification: | Attachment 003. Revision 002 |
| Date: | June 21, 2010 |
JUL 0 9 2010
| 510(k) number: | K100818 |
|---|---|
| Date of preparation: | June 21, 2010 |
| Submitter: | Meridian Bioscience, Inc. |
| Submitter's address: | 3471 River Hills Drive |
| Cincinnati, Ohio 45244 | |
| Contact: | Michelle Smith |
| Contact number: | (513) 271-3700 |
| Device name: | illumigene™ C. difficile |
| illumipro-10™ Automated Isothermal Amplification and Detection System | |
| illumigene™ C. difficile External Control Kit | |
| Common name: | C. difficile DNA Amplification Assay |
| Classification name: | C. difficile Nucleic Acids |
| OMN, CFR Section 866.2660 | |
| Predicate device: | K091109: Cepheid® Xpert® C. difficile |
| Model GXVDIFFICILE-10,900-0423, 900-0065, 900-0144, 900-0145, 900-0146, | |
| 900-0381, 900-0391, 900-0392, 900-393, 950-0151 | |
| Reference comparator: | Cytotoxic bacterial culture |
Description of the device: 1
The illumigene Molecular Diagnostic Test System is comprised of the illuminene C. difficite DNA Ampification Test Kit. the illumigene C. difficile External Control Kit and the illumipro-10 Automated Isothermal Amplification and Detection System. The illumigene C. difficile DNA amplification assay utilizes loop-mediated isothermal ampification (LAMP) technology to detect the presence of toxigenic C. difficile in patients suspected of having C. difficile associated disease (CDAD). Each illumiaene C. difficile assay is combleted using an illuminene Sample Preparation Apparatus. Illumicene Reaction Buffer, illumigene C. difficile Test Device, Sample Collection Brush, and illumigene Extraction Tube. Samples are prepared using the Sample Collection Brush and the illumigene Sample Collection Apparatus, target DNA is heat extracted in the Extraction Tube and DNA amplification occurs in the illumigene C. difficile Test Device.
The illumipro-10 heats each illumigene C. difficile Test Device containing prepared samples, facilitation of target DNA. When toxigenic C. difficile is present in the patient specific sequence is amplified and Magnesium pyrophosphate is formed. Magnesium pyrophosphate in the reaction mixture. The Illumioro-10 detects the change in light transmission mixture created by the precipitating Magnesium pyrophosphate. Sample results are reported as Positive based on the detected change in transmission.
The illumigene C. difficile External Control Kit consists of a Positive Control Reagent. External Control reagents are provided to aid the user in deterioration, adverse environmental or test conditions, or variance in operator performance that may lead to test errors. The illumigene C. difficile External Control Kit is required for routine Quality Control.
1
| Meridian
| Bioscience, Inc. | 510(k) Application illumigene C. difficile |
|---|---|
| Description: 510(k) Summary illumigene C. difficile | |
| Identification: Attachment 003. Revision 002 | |
| Date: June 21, 2010 |
Intended Use:
The illumigene C. difficile DNA amplification assay, performed on the illumipro-10, is a qualitative in vitro direct detection of toxigenic C. difficile in human stool spected of having Clostridium difficile-associated disease (CDAD).
The illumicene C. difficile assay utilizes loop-mediated issthermal DNA amplification (LAMP) technology to detect the pathogenicity locus (PaLoc) of toxigenic Clostridium difficile Paloc is a gene segment present in all known toxigenic C. difficile strains. The C. difficile Paloc codes for both the Toxin B gene (tcdA) and the Toxin B gene (tcdB), has conserved border regions, and is found at the same site on the C. difficile genome for all toxigenic strains . The illumigene C. difficile assay detects the PaLoc by targeting a partial DNA fragment on the Toxin A gene. The tcdA target region was selected as an intact region remaining in all known A+B+ and A-B+ toxinotypes.
Illumigene C. difficile is intended for use in hospital, reference or state laboratory settings. The device is not intended for point-of-care use.
Comparison to predicated device:
| Characteristic | Illumigene™ C. difficile | Cepheid® Xpert® C. difficile |
|---|---|---|
| Test Format | DNA Amplification Assay | DNA Amplification Assay |
| Intended Use | ||
| DNA Amplification Technology | Loop-Mediated Isothermal Amplification (LAMP) | Real-Time Polymerase Chain Reaction (PCR) |
| Target Sequences Detected | Partial DNA fragment on the Toxin A gene of the | |
| pathogenicity locus (PaLoc) found in all known | ||
| strains for toxigenic C. difficile. | Toxin B sequences | |
| Qualitative/Quantitative | Qualitative | Qualitative |
| Screening, Diagnostic or | ||
| Identification Test | Diagnostic | Diagnostic |
| Specimen Types | ||
| Unformed Human Stool | Yes | Yes |
| Human Stool in Cary-Blair-based | ||
| Media | Yes | No |
| illumigene Sample Preparation Apparatus | Xpert C. difficile Assay cartridges | |
| illumigene Reaction Buffer | Sample Reagent | |
| Reagents/Components | illumigene C. difficile Assay Device | Reagent 1 |
| illumigene Extraction Tubes | Reagent 2 | |
| Sample Collection Brushes | ||
| Extraction | Manual | Self-contained and automated |
| Amplification | Self-contained and automated | Self-contained and automated |
| Detection | Self-contained and automated | Self-contained and automated |
| Testing Time | Approximately 60 minutes | Approximately 45 minutes |
2
Image /page/2/Picture/0 description: The image shows the logo for Meridian Bioscience, Inc. The logo consists of a globe graphic on the left, followed by the word "Meridian" in a bold, sans-serif font. Below "Meridian" is the text "Bioscience, Inc." in a smaller, also bolded, sans-serif font. A thin line is placed between the word "Meridian" and "Bioscience, Inc."
| 510(k) Application illumigene C. difficile | |
|---|---|
| Description: | 510(k) Summary illumigene C. difficile |
| Identification: | Attachment 003. Revision 002 |
| Date: | June 21, 2010 |
| Calibration | Not required | Not required |
|---|---|---|
| Comparison to predicated device: | ||
| Characteristic | Illumigene™ C. difficile | Cepheid® Xpert® C. difficile |
| Controls | ||
| Inhibition, Assay | Provided | |
| Illumigene Sample Preparation Apparatus: | ||
| Staphylococcus aureus | ||
| Illumigene C. difficile Assay Device: | ||
| Staphylococcus aureus LAMP Primers | ||
| Adjunct Reagents | Provided | |
| Sample Processing Control (SPC): Bacillus globigii | ||
| Probe Check Control (PCC): Fluorescence emitting probes | ||
| External | Illumigene C. difficile External Control Kit | |
| Catalog 279920 | User Supplied | |
| KWIK-STIK™ from MicroBioLogics catalog 0329 (toxigenic C. difficile) as positive control | ||
| KWIK-STIK™ from MicroBioLogics catalog 0331 ( C. sordelli ) as negative control | ||
| Extraction | User Supplied | User Supplied |
| Equipment | ||
| Instrumentation | illumipro-10™ Automated Isothermal Amplification and Detection System | |
| Micropipette 50 μL, 200 μL | GeneXpert® Dx System | |
| Vortex Mixer | ||
| General Laboratory Equipment | Dry-bath with 12mm heat block, 95 C | |
| Interval Timer | ||
| Vortex Mixer | ||
| Reading Method | Visible Light Transmission | Fluorescence |
| Results | ||
| C. difficile Toxinotypes Tested | 0 (A+/B+) | |
| III (A+/B+) | ||
| V (A+/B+) | ||
| VIII (A-/B+) | ||
| X (A-/B+) | ||
| XII (A+/B+) | ||
| IX/XXIII (A+/B+) | 0 (A+/B+) | |
| III (A+/B+) | ||
| V (A+/B+) | ||
| VIII (A-/B+) | ||
| XII (A+/B+) | ||
| Results Interpretation | INVALID | |
| POSITIVE | ||
| NEGATIVE | Toxigenic C. difficile POSITIVE | |
| Toxigenic C. difficile NEGATIVE | ||
| INVALID | ||
| ERROR | ||
| NO RESULT |
3
| Image: Meridian Bioscience, Inc. logo | 510(k) Application illumigene C. difficile |
|---|---|
| Description: 510(k) Summary illumigene C. difficile | |
| Identification: Attachment 003. Revision 002 | |
| Date: June 21, 2010 |
Performance Comparison, Non-clinical Tests:
Interference Testing
Selected drugs and other non-microbial substances that might be present in stool samples from healthy persons or patients suspected of having C. difficile associated disease were added to a natural negative and a contrived positive sample. The natural negative and contrived positive samples were prepared from donor samples and were confirmed negative by cytotoxic bacterial culture. The contrive sample was prepared by spiking a confirmed negative sample with toxinogenic C. difficile strain VPI 10463 to 18 CFU/test, slightly above the 16 CFU assay limit of delection for this organism. Potentially interfering substances were added at final concentrations of 5% V/V or greater. Dilution Controls for each sample were prepared by adding a phosphate-buffered saline solution in place of the potentially interfering substance. Each sample was tested in triplicate.
The following substances, at the specified saturated solventrations, do not interfere with illumigene C. difficile test results in the final concentrations listed: Barium sulfate (5 mg/mL), fecal fat (equivalent to 2.65 mg stearic plus 1.3 mg palmitic acids per mL), hemoglobin) (3.2 mg/mL), IgA (5 mg/mL), Inodium AD® (0.00667 mg/mL), Kaopectate® (0.87 mg/mL), Metronidazole (12.5 mg/mL) Mylanta® (4.2 mg/mL), Pepto-Bismol® (0.87 mg/mL), Prilosec® (0.5 mg/mL), TUMS® (0.5 mg/mL), Vancomycin (12.5 mg/mL), white blood cells (5%V/V), whole blood (5% V/V).
Cross-reactivity Study
Potentially cross-reactive microorganisms that might be present in stool samples from healthy persons or patients suspected of having C, difficile associated disease were added to a natural negalive sample. The natural negative and contrived positive samples were prepared from donor samples and were confirmed negative by cytotoxic bacterial culture. The contrived positive sample was prepared by spiking a confirmed negative sample with toxinogenic C. difficile strain VPI 10463 to 18 CFU assay limit of detection for this organism. Potentially cross-reactive microorganisms were added at concentrations of 1.2 x 10 fmL (bacteria and fungi) or 1 x 10539mL TCIDgs/mL (viruses). Dilution Controls for each sample were prepared by adding a phosphate-buffered saline solution in place of the potentially cross-reactive microorganisms. Each sample was tested in triplicate.
The following microorganisms, at the indicated concentrations, do not interfere with illumigene C. difficile test results: Aeromonas hydrophila. Bacteroides fragilis. Campylobacter fetus. Campylobacter ieiuni, Candida albicans. Citrobacter frendi. Clostridium perfringens, Enterobacter cloacae, Enterococcus faccalis, Escherichia coli, Escherichia coli 0157:H7, Escherichia hermannii, Helicobacter pylori, Klebsiella pneumoniae, Lactococcus lactis, Listeria monocytogenes, anaerobius, Plesiomonas shigelloides, Proteus vulgaris, Pseudomonas aeruginosa, Pseudomonas fluorescens, Salmonella Groups B-E, Serratia liquefaciens, Serratia marcescens, Shigella flexneri, Shigella sonnei, Staphylococcus aureus, Staphylococus epidermidis. Vibrio parahaemolyticus, Yersinia enterocolliica, Adenovirus, Echovirus, Echovirus, Rotavirus.
Performance Comparison, Clinical Tests:
Clinical trials for the illumigene C. difficile assay, including the illumipro-10 Automated Isothermal amplification and detection system, were conducted in 2010. Performance characteristics of the illumigene C. difficile assay were determined by comparison to cytotoxic culture. Four independent clinical test sites located in the Midwestern and Southern recions of the United States and the manufacturer evaluated a total of 697 qualified patient samples. Samples were collected from 274 (39.3%) males and 419 (60.1%) females. In the case of 4 (0.6%) of the patients, sex was not known. The age groups of patients range from 2 years of age to 96 years. No differences in test performance were observed based on patient age, sex, or geographical location. Overall Sensitivity was determined to be 95.2% (95% Cl: 89.2% - 97.9%). Overall Specificity was determined to be 95.3% - 96.7%). Subsequent tables show overall assay performance as well as performance by clinical site and patient age.
4
Image /page/4/Picture/0 description: The image shows the logo for Meridian Bioscience, Inc. The logo consists of a globe graphic on the left, followed by the company name in bold, black font. The word "Meridian" is on the top line, and "Bioscience, Inc." is on the bottom line.
| 510(k) Application illumigene C. difficile | |
|---|---|
| Description: | 510(k) Summary illumigene C. difficile |
| Identification: | Attachment 003. Revision 002 |
| Date: | June 21, 2010 |
Table 1. Overall performance data
| Cytotoxic bacterial
| culture | illumigene C. difficile | ||
|---|---|---|---|
| culture | Positive | Negative | Total |
| Positive | 99 | 5** | 104 |
| Negative | 27* | 546 | 573 |
| Total | 126 | 551 | 677 |
| 95% CI | |||
| Sensitivity | 99/104 | 95.2% | 89.2 - 97.9% |
| Specificity | 546/573 | 95.3% | 93.2 - 96.7% |
| Correlation | 645/677 | 95.3% | 93.4 - 96.6% |
15/27 false positive results were positive by and the remaining 12 false positive results, 8 were positive results, 8 were positive by an FDA cleared assay for the detection of GDH.
** 2/5 false negative results were negative by another FDA cleared molecular assay
Table 2. Performance characteristics by site
| Site | Positive Samples | Negative Samples | ||||
|---|---|---|---|---|---|---|
| illumigenel | ||||||
| Cytotoxic | ||||||
| bacterial | ||||||
| culture | Sensitivity % | 95% CI | illumigenel | |||
| Cytotoxic | ||||||
| bacterial | ||||||
| culture | Specificity % | 95% CI | ||||
| Total | 99/104 | 95.2% | 89.2 - 97.9% | 546/573 | 95.3% | 93.2 - 96.7% |
| Site 1 | 4/5 | 80.0% | 37.6 - 96.4% | 58/60 | 97.6% | 88.6 - 99.1% |
| Site 2 | 12/12 | 100% | 75.7 - 100% | 62/67 | 92.5% | 83.7 - 96.8% |
| Site 3 | 20/20 | 100% | 83.9 - 100% | 87/92 | 94.6% | 87.9 - 97.7% |
| Site 4 | 8/8 | 100% | 67.6 - 100% | 36/39 | 92.3% | 79.7 - 97.3% |
| Site 5 | 55/59 | 93.2% | 83.8 - 97.3% | 303/315 | 96.2% | 93.5 - 97.8% |
Table 3. Invalid rates by site
| Site | Clinical Site Evaluation | |||
|---|---|---|---|---|
| Total Invalids | Assay | |||
| Invalids | Instrument | |||
| Invalids | Invalid Rate | |||
| Site 1 | 3 | 3 | 0 | 3/68 (4.4%) |
| Site 2 | 1 | 0 | 1 | 1/80 (1.3%) |
| Site 3 | 8 | 1 | 7 | 8/120 (6.7%) |
| Site 4 | 1 | 1 | 0 | 1/48 (2.1%) |
| Site 5 | 7 | 6 | 1 | 7/381 (1.8%) |
| Total | 20 | 11/697 (1.6%)*** | 9/697 (1.3%) | 20/697 (2.9%) |
*** 1 Specimen remained invalid after repeat testing from the original sample.
Table 4. Results by patient age
| Positive Samples | Negative Samples | |||||
|---|---|---|---|---|---|---|
| Patient age | illumigenel | |||||
| Toxigenic | ||||||
| culture | Sensitivity % | 95% CI | illumigenel | |||
| Toxigenic | ||||||
| culture | Specificity % | 95% CI | ||||
| ≥ 2 - 12 years | 10/11 | 90.9% | 62.3 - 98.4% | 75/79 | 94.9% | 87.7 - 98.0% |
| > 12 to 21 years | 5/5 | 100% | 56.6 - 100% | 53/56 | 94.6% | 85.4 - 98.2% |
| > 21 years | 83/87 | 95.4% | 88.8 - 98.2% | 417/437 | 95.4% | 93.0 - 97.0% |
| Age Unknown | 1/1 | 100% | 20.7 - 100% | 1/1 | 100% | 20.7 - 100% |
5
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| . Be a series and the comments of the section of the section of the states of the section of the section of the states of the section of the section of the section of the sta |
| 510(k) Application illumigene C. difficile | |
|---|---|
| Description: | 510(k) Summary illumigene C. difficile |
| Identification: | Attachment 003. Revision 002 |
| Date: | June 21, 2010 |
Analytical Sensitivity
The analytical sensitivity of this assay for C. difficile was based on 20 replicates for each measurand and with a stated probability (e.g., 95% or 19/20 positive replicates) of obtaining positive responses at the following levels of the measurands:
| Strain ID | Toxinotype | Phenotype | LoD/Test |
|---|---|---|---|
| VPI 10463 | 0 | A+/B+ | 4 CFU/test |
| 2007431 | III (NAP1) | A+/B+ | 32 CFU/test |
| CF1 | VIII | A-/B+ | 64 CFU/test |
| 2006240 | V (NAP7) | A+/B+ | 32 CFU/test |
| BI8 | III | A+/B+ | 64 CFU/test |
| 2007858 | IX/XXIII | A+/B+ | 32 CFU/test |
| 8864 | X | A-/B+ | 64 CFU/test |
Additional C. difficile stock cultures from different sources were tested and produced positive reactions at 64 CFU/test with illumicene C. difficile. Strains and toxinotypes tested were as follows: Type 0 Strains: 10463, 2004111, 2004205, 2005070, 2005257, 2008029, 2008162, 2008341, 2008351, 2009066, 2009099, B1, G1, J7, K12, Y1; Type III Strains: 2004052, 2004118, 2007431, Bl17, Bl8; Type V Strains: 2005325, 2006240, 2008188, 2009018, 2009065, BK6; Type VIII Strains: 43598, 2008016, CF1; Type XII Strains: 2007435; Type IX/XIII Strains: 2007858; Unknown Strains: 2009132, 2009155, 2009277.
Reproducibility
Blind coded panels of 10 samples were supplied to three independent laboratories for precision studies. Samples were randomly sorted within each panels identities. The panels included contrived samples manufactured at the assay limit of detection (n = 3) and just below the limit of blank (i.e., high negative sample, n = 3). The panels also included uncharacterized positive (n = 2) and negative (n = 2) samples. 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 C difficile 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 | 20/20 | 100% | 20/20 | 100% | 19/19**** | 100% | 59/59 | 100% |
| High Negative | 25/30 | 83% | 29/30 | 97% | 28/30 | 93% | 82/90 | 91% |
| Low Positive | 30/30 | 100% | 30/30 | 100% | 30/30 | 100% | 90/90 | 100% |
| Positive | 20/20 | 100% | 20/20 | 100% | 20/20 | 100% | 60/60 | 100% |
*** 1 specimen generated an instrument invalid test result.
Conclusions
The illumigene C. difficile assay used in coniunction with the illumioro-10 can be used to defficile in human stool samples. The test is diagnostic for toxigenic C. difficile infection.
6
DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized graphic of three overlapping human profiles facing to the right, with the profiles gradually decreasing in size from front to back. The profiles are rendered in black, and the text is also in black against a white background.
Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center -- WO66-0609 Silver Spring, MD 20993-0002
Meridian Bioscience, Inc. c/o Michelle L. Smith Senior Director, Quality Systems 3471 River Hills Dr. Cincinnati, OH 45244
JUL 9 2010
Re: K100818
| Trade/Device Name: | Illumigene C. difficile Assay |
|---|---|
| Regulation Number: | 21 CFR §866.2660 |
| Regulation Name: | Microorganism differentiation and identification device |
| Regulatory Class: | Class I |
| Product Code: | OMN |
| Dated: | June 21, 2010 |
| Received: | June 22, 2010 |
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 either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
7
Page 2 - Michelle L. Smith
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please 115809.html 1580.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/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.
Sincerely yours,
Sal, aAr
Sally A. Hojvat, M.Sc., Ph.I Director
Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
8
Indication(s) for Use Form
510(k) Number (if known): K100818
Device Name: illumigene Molecular Diagnostic Test System (illumigene C. difficile DNA Amplification Assay, illumipro-10)
Indications for Use:
The illumigene C. difficile DNA amplification assay, performed on the illumipro-10, is a qualitative in vitro diagnostic test for the direct detection of toxigenic C. difficile in human stool specients suspected of having Clostridium difficile associated disease (CDAD).
The illumigene C. difficile assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect the pathogenicity locus (PaLoc) of toxigenic Clostridium difficile PaLoc is a gene segment present in all known toxigenic C. difficile strains. The C. difficile PaLoc codes for both the Toxin A gene (tcdA) and the Toxin B gene (tcdB), has conserved border regions, and is found at the same site on the C. difficile genome for all toxigenic strains . The illumigene C. difficile assay detects the PaLoc by targeting a partial DNA fragment on the Toxin A gene. The tcdA target region was selected as an intact region remaining in all known A+B+ and A-B+ toxinotypes.
illumigene C. difficile is intended for use in hospital, reference or state laboratory settings. The device is not intended for point-of-care use.
Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use 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)
Kurdalin M. Fode
ion Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K10 0817