(100 days)
VIDAS® C. difficile GDH (GDH) is an automated test based on the Enzyme Linked Fluorescent Assay technique (ELFA), for use on the VIDAS family instruments. The VIDAS C. difficile GDH (glutamate dehydrogenase) assay is a qualitative test that detects the C. difficile antigen, glutamate dehydrogenase, as a screen for the presence of C. difficile in fecal specimens from persons suspected of having C. difficile infection (CDI). The test does not distinguish toxigenic from non-toxigenic strains of C. difficile. With the use of additional tests that detect C. difficile toxins, the test is to be used as an aid in the diagnosis of C. difficile infection. As with other C. difficile tests, results should be considered in conjunction with the patient history.
The VIDAS® C. difficile GDH assay principle combines a two-step enzyme immunoassay sandwich method with a final fluorescent detection (ELFA). The Solid Phase Receptacle (SPR®) serves as the solid phase as well as the pipetting device. Reagents for the assay are ready-to-use and are pre-dispensed in the sealed reagent strips. All of the assay steps are performed automatically by the instrument. The reaction medium is cycled in and out of the SPR several times. Each step is followed by a wash cycle which eliminates unbound components. Specific binding of GDH present in the sample with mouse monoclonal anti-GDH antibody coated on the interior of the SPR. Binding between GDH and mouse monoclonal anti-GDH antibody conjugated with alkaline phosphatase (ALP). Detection: alkaline phosphatase catalyzes the hydrolysis of the substrate (4-Methylumbellifery! phosphate) into a fluorescent product (4-Methy-umbelliferone) the fluorescence of which is measured at 450 nm. The intensity of the fluorescence increases according to the quantity of GDH in the sample. When the VIDAS C. difficile GDH test is completed, the results are analyzed automatically by the instrument, a test value is generated, and a result is printed for each sample.
The provided document describes the VIDAS® C. difficile GDH assay, intended for the detection of C. difficile antigen glutamate dehydrogenase in fecal specimens.
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria for clinical performance (sensitivity and specificity) in a pass/fail format. However, it presents the results of clinical studies against two different reference methods. The "Performance" rows in the tables below can be considered the reported device performance.
Against CCFA Bacterial Culture (Reference Standard)
| Performance Metric | Reported Device Performance (Total, All Sites combined) |
|---|---|
| Sensitivity | 95.6% (95% CI: 92.6 - 97.6%) |
| Specificity | 90.1% (95% CI: 88.5 - 91.5%) |
| Negative Predictive Value (NPV) | 99.1% (95% CI: 98.5 - 99.5%) |
Against C. difficile Chromogenic Media Bacterial Culture (Reference Standard)
| Performance Metric | Reported Device Performance (Total, All Sites combined) |
|---|---|
| Positive Percent Agreement (PPA) | 92.6% (95% CI: 89.3 - 95.2%) |
| Negative Percent Agreement (NPA) | 91.8% (95% CI: 90.3 - 93.1%) |
Against a Commercially Available C. difficile GDH Assay (Comparison Study)
| Performance Metric | Reported Device Performance (Total, All Sites combined) |
|---|---|
| Positive Percent Agreement | 97.3% (95% CI: 95.0 – 98.7%) |
| Negative Percent Agreement | 94.4% (95% CI: 93.1 – 95.5%) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 1904 stool samples (1891 prospective and 13 retrospective).
- Data Provenance: The samples were collected from patients suspected of having C. difficile infection (CDI) at three sites across the USA and Europe.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not specify the exact number of experts involved in establishing the ground truth or their specific qualifications (e.g., radiologist with X years of experience). The ground truth was established by bacterial culture tests (CCFA and C. difficile chromogenic media) performed "according to the instructions for use." This implies standard laboratory practices would have been followed, likely by trained laboratory personnel.
4. Adjudication Method for the Test Set
The document does not mention any adjudication method for resolving discordant results between the device and the ground truth. It presents the raw comparison data against the reference methods.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This study is for a diagnostic assay, and the studies described are evaluations of the assay's performance against reference methods and another commercially available assay.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, a standalone performance study was done. The VIDAS® C. difficile GDH assay is an automated test, and the reported clinical sensitivity, specificity, and agreement data reflect the performance of the algorithm only (the automated instrument) without additional human interpretation or intervention in the diagnostic decision once the test is run. The instrument generates a test value and prints a result for each sample automatically.
7. The Type of Ground Truth Used
The primary ground truth used for the clinical performance evaluation was bacterial culture:
- CCFA bacterial culture test
- C. difficile chromogenic medium bacterial culture test
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" or its size. This is common for diagnostic assays where the development process typically involves internal optimization and validation, and then external clinical validation (the "test set" described) against a gold standard. The clinical study described served as the validation (test) set.
9. How the Ground Truth for the Training Set Was Established
As no specific training set is outlined in the document, there's no information on how its ground truth might have been established. However, for diagnostic assays, internal development and optimization would generally rely on well-characterized samples with confirmed positive and negative status, likely through similar gold standard methods like bacterial culture, to establish parameters like cut-off values.
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VIDAS®C. difficile GDH
510(k) SUMMARY
This 510(k) summary of safety and effectiveness information is being submitted in accordance with the requirement of Safe Medical Devices Act of 1990 and 21 CFR 807.92.
VIDAS® C. difficile GDH
A. Submitter Information
| Submitter's Name: | bioMérieux SA |
|---|---|
| Address: | Chemin de l'Orme69280 Marcy-l'Etoile - France |
| Contact Person: | Caroline KOCH-MATHIAN |
| Phone Number: | +33 4 78 87 70 32 |
| Fax Number: | +33 4 78 87 20 75 |
| Date of Preparation: | May 2013 |
OCT 0 9 2013
B. Device Name
| Trade Name: | VIDAS® C. difficile GDH |
|---|---|
| Common Name: | VIDAS C. difficile GDH Assay |
| Classification Name: | 21 CFR 866.2660 – Microorganism Differentiation and Identification Device |
| MCB - Antigen, Clostridium difficile |
C. Predicate Device Name
Trade Name: C. DIFF QUIK CHEK® (TECHLAB, INC.), K053572
D. Device Description
The VIDAS® C. difficile GDH assay principle combines a two-step enzyme immunoassay sandwich method with a final fluorescent detection (ELFA).
The Solid Phase Receptacle (SPR®) serves as the solid phase as well as the pipetting device. Reagents for the assay are ready-to-use and are pre-dispensed in the sealed reagent strips. All of the assay steps are performed automatically by the instrument. The reaction medium is cycled in and out of the SPR several times. Each step is followed by a wash cycle which eliminates unbound components.
- · Specific binding of GDH present in the sample with mouse monoclonal anti-GDH antibody coated on the interior of the SPR.
- · Binding between GDH and mouse monoclonal anti-GDH antibody conjugated with alkaline phosphatase (ALP).
- · Detection: alkaline phosphatase catalyzes the hydrolysis of the substrate (4-Methylumbellifery! phosphate) into a fluorescent product (4-Methy-umbelliferone) the fluorescence of which is measured at 450 nm.
The intensity of the fluorescence increases according to the quantity of GDH in the sample.
1
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When the VIDAS C. difficile GDH test is completed, the results are analyzed automatically by the instrument, a test value is generated, and a result is printed for each sample.
E. Intended Use
VIDAS® C. difficile GDH (GDH) is an automated test based on the Enzyme Linked Fluorescent Assay technique (ELFA), for use on the VIDAS family instruments. The VIDAS C. difficile GDH (glutamate dehydrogenase) assay is a qualitative test that
detects the C. difficile antigen, glutamate dehydrogenase, as a screen for the presence of C. difficile in fecal specimens from persons suspected of having C. difficile infection (CDI). The test does not distinguish toxigenic from non-toxigenic strains of C. difficile. With the use of additional tests that detect C. difficile toxins, the test is to be used as an aid in the diagnosis of C. difficile infection. As with other C. difficile tests, results should be considered in conjunction with the patient history.
F. Technological Characteristics Summary
A general comparison of the similarities and differences of the assays is presented in the table below.
| Item | VIDAS® C. difficile GDH Assay | C. DIFF QUIK CHEK® Assay(K053572) |
|---|---|---|
| Intended Use | VIDAS® C. difficile GDH (GDH) is anautomated test based on the EnzymeLinked Fluorescent Assay technique(ELFA), for use on the VIDAS familyinstruments.The VIDAS C. difficile GDH(glutamate dehydrogenase) assay isa qualitative test that detects the C.difficile antigen, glutamatedehydrogenase, as a screen for thepresence of C. difficile in fecalspecimens from persons suspectedof having C. difficile infection (CDI).The test does not distinguishtoxigenic from non-toxigenic strainsof C. difficile. With the use ofadditional tests that detect C. difficiletoxins, the test is to be used as anaid in the diagnosis of C. difficileinfection. As with other C. difficiletests, results should be considered inconjunction with the patient history. | The C. DIFF QUIK CHEK® test is arapid membrane enzymeimmunoassay for use as ascreening test to detectClostridium difficile antigen,glutamate dehydrogenase, in fecalspecimens from personssuspected of having C. difficiledisease. The test does notdistinguish toxigenic from nontoxigenic strains of C. difficile. Withthe use of additional tests thatdetect C. difficile toxins, the test isto be used as an aid in thediagnosis of C. difficile disease. Aswith other C. difficile tests, resultsshould be considered inconjunction with the patienthistory. |
| Specimen | Fecal | Fecal |
| Analyte | Clostridium difficile glutamatedehydrogenase | Clostridium difficile glutamatedehydrogenase |
| Automated | Yes | No |
| AssayTechnique | Enzyme-linked fluorescent assay(ELFA) | Rapid Membrane Enzymeimmunoassay |
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All nonclinical and clinical tests were performed following the recommendations of the FDA draft guidance from November 29th 2010.
G. Nonclinical Tests
A summary of the non-clinical results is presented below.
Sample stability
Specimens storage after collection
Stool specimens may be stored at 2-8℃ for 3 days (from time of collection) prior to processing. If longer storage is required, freeze the specimens at -70°C+/- 10°C up to one month. Avoid repeated freezing and thawing cycles and storage at -19/-31℃
Specimens storage after pretreatment
Specimen supernatants may be stored up to 8 hours at 18-25°C or 48 hours at 2-8°C before being tested with the VIDAS C. difficile GDH assay. Specimen supernatants storage at -19/-31°C and -70°C +/-10°C was not validated and is therefore not recommended.
Precision
The within-laboratory precision was estimated at one site based on the recommendations of the CLSI® EP5-A2.
Three human samples, including 2 close to the clinical cut-off (1 high negative and 1 low positive) and 1 moderate positive, were tested in triplicate in 2 runs per day with 2 different operators, with 2 reagent lots for a total of 12 testing days (6 days of test per lot) on 1 VIDAS instrument (N=72 test values for each sample). Two calibrations were used for each reagent lot (3 days of test per calibration and lot) over the whole period of the study. Data from the study are summarized in the following table:
| Sample | N | Mean test value | Repeatability | Total within-laboratory precision(total within-instrument, between-lot, between-calibration) | ||
|---|---|---|---|---|---|---|
| Standarddeviation | CV (%) | Standarddeviation | CV (%) | |||
| Sample 1High negative | 72 | 0.07 | 0.00 | 6.0 | 0.01 | 14.1 |
| Sample 2Low positive | 72 | 0.12 | 0.01 | 5.2 | 0.01 | 11.9 |
| Sample 3Moderatepositive | 72 | 0.27 | 0.02 | 5.7 | 0.03 | 11.2 |
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The within-laboratory precision of each panel member was also analyzed by determining the percentage of agreement between the test interpretation and the expected outcome (negative/positive interpretation). There was no change of interpretation for the 3 panel samples tested: all replicates of each panel member resulted in the expected interpretation. Data from the qualitative analysis are summarized in the following table:
| Sample | Expected Result | N | Observed resultLot 1 | Observed resultLot 2 | TotalAgreement | [Cl95] % | ||
|---|---|---|---|---|---|---|---|---|
| Negative | Positive | Negative | Positive | |||||
| Sample 1Highnegative | Negative | 72 | 36 | 0 | 36 | 0 | 72/72(100.0%) | [95.0 -100.0]% |
| Sample 2Lowpositive | Positive | 72 | 0 | 36 | 0 | 36 | 72/72(100.0%) | [95.0 -100.0]% |
| Sample 3Moderatepositive | Positive | 72 | 0 | 36 | 0 | 36 | 72/72(100.0%) | [95.0 -100.0]% |
The reproducibility was estimated at three sites based on the recommendations of the CLSI® EP5-A2.
Three human samples, including 2 close to the clinical cut-off (1 high negative and 1 low positive) and 1 moderate positive, were tested in triplicate in 2 runs per day with 2 different operators, using 2 reagent lots for a total of 6 testing days (3 days of test for each lot) on 3 VIDAS instruments at 3 different sites (N=108 test values for each sample). One calibration was used for each reagent lot over the whole period of the study. Data from the study are summarized in the following table:
| Sample | N | Mean test value | Reproducibility(total between samplepreparation/operator/run/day/lotinstrument) | |
|---|---|---|---|---|
| Standard deviation | CV (%) | |||
| Sample 1High negative | 108 | 0.06 | 0.01 | 19.1 |
| Sample 2Low positive | 108 | 0.12 | 0.02 | 12.9 |
| Sample 3Moderatepositive | 108 | 0.26 | 0.03 | 13.0 |
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The reproducibility of each panel member was also analyzed by determining the percentage of agreement between the test interpretation and the expected outcome (negative/positive interpretation). Data from the qualitative analysis for all sites combined are summarized in the following table:
| PanolSample | ExpectedResult | N | Observed resultSite 1 | Observed resultSite 2 | Observed resultSite 3 | TotalAgreement | [CI₉₅] % | |||
|---|---|---|---|---|---|---|---|---|---|---|
| Negative | Positive | Negative | Positive | Negative | Positive | |||||
| Sample 1Highnegative | Negative | 108 | 36 | 0 | 36 | 0 | 35 | 1 | 107/108(99.1%) | [94.9 -99.9]% |
| Sample 2Lowpositive | Positive | 108 | 0 | 36 | 1 | 35 | 3 | 33 | 104/108(96.3%) | [90.8 -99.0]% |
| Sample 3Moderatepositive | Positive | 108 | 0 | 36 | 0 | 36 | 0 | 36 | 108/108(100.0%) | [96.6 -100.0]% |
Out of the 108 results obtained for each precision sample, there were:
- 1 change of interpretation (0.9%) for the high negative sample (Sample 1), -
- 4 changes of interpretation (3.7%) for the low positive sample (Sample 2), "
- 0 change of interpretation (0%) for the moderate positive sample (Sample 3). -
The percentages of change of interpretation observed for Sample 1 and Sample 2 were less than 5%, which was considered as normal and expected for these types of samples very close to the assay decision threshold (average test value for Sample 1 = 0.06 and average test value for Sample 2 = 0.12 for a decision threshold at 0.10.
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Strain reactivity
The VIDAS C. difficile GDH assay was evaluated using several strains of C. difficile. Strains were grown on Columbia agar + 5% sheep blood (bioMérieux ref. 43041).
The VIDAS C. difficile GDH detects the following C.difficile strains at the tested concentrations of 9x10° CFU/mL (3 McFarland) and 3x10° CFU/mL:
| Toxinogenic C.difficile strains: | Non toxinogenic C.difficile strains: | ||||
|---|---|---|---|---|---|
| ATCC® 43255TM | ATCC® 43600TM | ATCC® 700057TM | |||
| ATCC® 9689TM | ATCC® 43599TM | ATCC® 43593TM | |||
| ATCC® 700792TM | ATCC® 43596TM | X1a IS58 | |||
| ATCC® 17858TM | ATCC® 43594TM | X1b R1 1402 | |||
| ATCC® BAA-1805TM | ATCC® 17857TM | ATCC® 43601TM (3x108 CFU/mL only) | |||
| ATCC® BAA-1382TM | ATCC® 43598TM | ||||
| ATCC® 51695TM | CCUG 20309 |
The VIDAS C. difficile GDH detects the following C.difficile strains at the tested concentration of 9x108 CFU/mL (3 McFarland):
| Cardiff ECDC collectionincluding the followingribotypes | 001 (7 strains); 002; 003; 012; 014; 015; 017; 020; 023; 027;029; 046; 053; 056; 070; 075; 077; 078; 081; 087; 095; 106;126; 131; VPI 10463; 005; 010; 045; 048; 156; 174. |
|---|---|
| bioMerieux collectionincluding the followingribotypes | 001 (6 strains); 002 (9 strains); 005 (2 strains); 010 (1 strain);012 (4 strains); 014 (10 strains); 015 (1 strain); 017 (20 strains);020 (5 strains); 023 (1 strain); 027 (24 strains); 047 (1 strain);050 (1 strain); 053 (4 strains); 054 (2 strains); 056 (2 strains);057 (1 strain); 058 (1 strain); 075 (1 strain); 078 (3 strains); 096(1 strain); 097 (1 strain); 103 (2 strains); 106 (16 strains); 110 (2strains); 118 (1 strain); 153 (1 strain); 177 (1 strain). |
Analytical sensitivity
Limit of detection
The limit of detection was evaluated using a range of dilutions of purified native C.difficile GDH and recombinant C. difficile GDH in a pool of C. difficile-negative stool samples based on the recommendations of the CLSI EP17-A.
The limit of detection of the VIDAS C. difficile GDH assay (95% detection rate for positive samples) is 3.0 ng/mL for purified native GDH.
Hook effect
No hook effect was observed up to purified native GDH concentrations of 2 µg/Ml.
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Interferences
Study of drug interferences and other potentially interfering substances
Potential interferences by commonly used drugs and other substances was determined based on the recommendations of the CLSI® EP7-A2, at 2 levels of GDH (a low positive close to the clinical cut-off and a high positive).
| Tested compound | Highestconcentrationtested | Result |
|---|---|---|
| Hemoglobin | 3.2 mg/mL | No significant interference observed |
| Lipids | 20 mg/mL | No significant interference observed |
| Mucin | 3.33 mg/mL | No significant interference observed |
| Amoxicillin | 206 µmol/L | No significant interference observed |
| Bismuth salicylate | 8.2 mg/mL | No significant interference observed |
| Calcium carbonate | 13.06 mg/mL | Potential interference* |
| Ceftriaxone | 1.46 mmol/L | No significant interference observed |
| Benzalkonium chloride | 2 µg/mL | No significant interference observed |
| Ciprofloxacin | 30.2 µmol/L | No significant interference observed |
| Erythromycin | 81.6 µmol/L | No significant interference observed |
| Ethanol | 86.8 mmol/L | No significant interference observed |
| Fidaxomicin | 4 mg/mL | No significant interference observed |
| Gentamicin | 21 µmol/L | No significant interference observed |
| Mineral oil | 0.27 v/v | Potential interference* |
| Hydrocortisone | 0.6 mg/mL | No significant interference observed |
| Aluminium hydroxide | 15.3 mg/mL | No significant interference observed |
| Magnesium hydroxide | 6.2 mg/mL | No significant interference observed |
| Lidocaine | 0.12 mg/mL | No significant interference observed |
| Loperamide | 0.08 mg/mL | No significant interference observed |
| Mesalazine | 19.2 mg/mL | No significant interference observed |
| Metronidazole | 2 mg/mL | No significant interference observed |
| Naproxen | 2170 µmol/L | No significant interference observed |
| Nystatin | 600 UI/mL | No significant interference observed |
| Phenylephrine | 0.225 mg/mL | No significant interference observed |
| Sennosides | 0.24 mg/mL | No significant interference observed |
| Tergitol (nonoxynol-9) | 0.5 v/v | Potential interference* |
| Tetracycline | 34 µmol/L | No significant interference observed |
| Vancomycin | 5 mg/mL | No significant interference observed |
*Calcium carbonate at 9.80 mg/mL, Mineral oil at 0.20 v/v and Tergitol at 0.125 v/v did not cause interference.
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Cross-reactivity and microbial interference:
To test for cross-reactivity, each micro-organism was diluted in a pool of C. difficile-negative stool samples, pretreated and a single replicate was tested using the VIDAS C. difficile GDH assav.
To test for microbial interference, each micro-organism was diluted in a pool of C. difficilepositive stool samples, pretreated and a single replicate was tested using the VIDAS C. difficile GDH assay.
For both cross-reactivity and microbial interference studies, the micro-organisms were tested at a concentration of 3x108 CFU/mL (1 McFarland) for bacteria and 1x10 PFU/mL for viruses.
None of the following micro-organisms, present in the stool samples, reacted with the VIDAS C. difficile GDH assay:
Abiotrophia defectiva, Acinetobacter baumannii, Acinetobacter Iwoffii, Aeromonas hydrophila ssp hydrophila, Alcaligenes faecalis, Anaerococcus tetradius, Bacillus cereus, Bacteroides caccae, Bacteroides merdae, Bacteroides stercoris, Bifidobacterium adolescentis, Bifidobacterium longum, Campylobacter ieiuni, Candida albicans, Candida catenulata, Cedecea davisae, Chlamydia trachomatis, Citrobacter amalonaticus, Citrobacter freundii. Citrobacter koseri. Citrobacter sedlakii. Clostridium nexile. Clostridium beijerinckii, Clostridium bifermentans, Clostridium bolteae, Clostridium butyricum, Clostridium chauvoei, Clostridium fallax, Clostridium haemolyticum, Clostridium histolyticum, Clostridium innocuum, Clostridium novyi, Clostridium paraputrificum, Clostridium perfringens, Clostridium ramosum, Clostridium scindens, Clostridium septicum, Clostridium sordellii. Clostridium sphenoides, Clostridium spiroforme, Clostridium sporogenes, Clostridium symbosum, Clostridium tertium, Clostridium tetani, Collinsella aerofaciens, Corynebacterium genitalium, Desulfovibrio piger, Edwardsiella tarda, Eggerthella lenta, Enterobacter aerogenes, Enterobacter cloacae, Enteroccus casseliflavus, Enterococcus cecorum, Enterococcus dispar. Enterococcus faecalis, Enterococcus faecium, Enterococcus gallinarum, Enterococcus hirae, Enterococus raffinosus, Escherichia coli, Escherichia fergusonii, Escherichia hermannii, Flavonifractor plautii, Fusobacterium varium, Gardnerella vaginalis, Gemella morbillorum, Hafnia alvei, Helicobacter fenneliae, Helicobacter pylori, Klebsiella oxytoca, Klebsiella pneumoniae, Lactobacillus acidophilus, Lactobacillus reuteri, Lactoccus lactis, Leminorella grimontii, Listeria grayi, Listeria innocua, Listeria monocytogenes, Peptoniphilus asaccharolyticus, Peptostreptococcus anaerobius, Plesiomonas shigelloides, Porphyromonas asaccharolytica, Prevotella melaninogenica, Proteus mirabilis, Proteus penneri, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Pseudomonas aeruginosa, Pseudomonas putida, Salmonella enterica ssp arizonae, Salmonella ser.Choleraesuis, Salmonella ser.Typhimurium Serratia liquefaciens, Serratia marcescens, Shigella boydii, Shigella dysenteriae, Shigella sonnei, Staphylococcus aureus ssp aureus, Staphylococcus epidermidis, Stenotrophomonas maltophilia, Streptococcus ---------------------------------------------------------------------------------------------------------------------------------------------------------------agalactiae, Streptococcus dysgalactiae SSD dysgalactiae, Streptococcus intermedius, Streptococcus uberis, Trabulsiella quamensis, Veillonella parvula, Vibrio cholerae, Vibrio parahaemolyticus, Yersinia bercovieri. Yersinia rohdei, Adenovirus 40 et 41, Rotavirus RF, Norovirus, Enterovirus 70, Echovirus 12, Coxsackie virus, Cytomegalovirus AD169.
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H. Clinical Testing
Clinical sensitivity and specificity
1904 (1891 prospective and 13 retrospective) stool samples collected from patients suspected of having C. difficile infection (CDI) were tested at three sites (USA and Europe). The age groups of the patients range from 1 year to 100 years. A single replicate of each sample was tested using VIDAS C. difficile GDH on a VIDAS instrument. A bacterial culture test was performed for each sample on a CCFA medium according to the instructions for use. Data from the study are summarized in the following tables:
| CCFA bacterial culture test | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Site 1 (EU) | Site 2 (US) | Site 3 (US) | Total (All Sites) | ||||||
| Positive | Negative | Positive | Negative | Positive | Negative | Positive | Negative | ||
| VIDASC. difficileGDH | Positive | 42 | 24 | 78 | 21 | 163 | 113 | 283 | 158* |
| Negative | 7 | 451 | 4 | 363 | 2 | 623 | 13** | 1437 | |
| Total | 49 | 475 | 82 | 384 | 165 | 736 | 296 | 1595 | |
| Performance | % | [CI95%] | % | [CI95%] | % | [CI95%] | % | [CI95%] | |
| Sensitivity | 85.7% | [72.8 -94.1]% | 95.1% | [88.0 -98.7]% | 98.8% | [95.7 -99.9]% | 95.6% | [92.6 -97.6]% | |
| Specificity | 94.9% | [92.6 -96.7]% | 94.5% | [91.8 -96.6]% | 84.6% | [81.8 -87.2]% | 90.1% | [88.5 -91.5]% | |
| NegativePredictive Value(NPV) | 98.5% | [96.9 -99.4]% | 98.9% | [97.2 -99.7]% | 99.7% | [98.8 -99.9]% | 99.1% | [98.5 -99.5]% |
Performance of the VIDAS C. difficile GDH assay versus CCFA bacterial culture on prospective samnles
- 158 samples were found positive with the VIDAS C. difficile GDH assay and negative with the CCFA bacterial culture test, 73 of which were found positive and 85 negative with the commercially available C. difficile GDH assay.
** 13 samples were found negative with the VIDAS C. difficile GDH assay and positive with the CCFA bacterial culture test. 9 of which were found negative and 4 positive with the commercially available C. difficile GDH assay.
Out of 2038 patient samples tested with the VIDAS C. difficile GDH assay, 21 (1,0%) were reported as invalid.
Testing on retrospective samples
Thirteen (13) retrospectively collected samples from pediatric patients submitted for routine C. difficile testing (2-12 years) were assayed for C. difficile according to the same protocol. For these 13 retrospective samples alone, the VIDAS C. difficile GDH assay demonstrated a sensitivity of 100.0% (10/10) and a specificity of 33.3% (1/3).
Performance of the VIDAS C. difficile GDH assay versus CCFA bacterial culture on all prospective and retrospective samples
For all 1904 specimens and all sites combined, the VIDAS C. difficile GDH assay demonstrated a sensitivity of 95.8% (293/306) with 95%C1: 92.8 - 97.7%, a specificity of 90.0% (1438/1598) with 95%Cl: 88.4 – 91.4%, and a negative predictive value of 99.1% with 95%Cl: 98.5 - 99.5%.
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| Age Group | VIDAS Positive/CCFA Positive | Sensitivity [Cl95] % | VIDASNegative/CCFANegative | Specificity [Cl95] % |
|---|---|---|---|---|
| < 2 years | 1/1 | 100.0% [2.5 - 100.0]% | 2/2 | 100.0% [15.8 - 100.0]% |
| 2-12 years | 12/12 | 100.0% [73.5 - 100.0]% | 39/44 | 88.6% [75.4 - 96.2]% |
| 13-21 years | 13/13 | 100.0% [75.3 - 100.0]% | 40/45 | 88.9% [75.9 - 96.3]% |
| 22-59 years | 122/125 | 97.6% [93.1 - 99.5]% | 562/632 | 88.9% [86.2 - 91.3]% |
| ≥ 60 years | 135/145 | 93.1% [87.7 - 96.6]% | 794/872 | 91.1% [89.0 - 92.9]% |
Sensitivity and Specificity performances versus CCFA medium by age group on prospective samples
For all 69 (56 prospective and 13 retrospective) samples from the 2-12 years pediatric population, the VIDAS C. difficile GDH assay demonstrated a sensitivity of 100.0% (22/22) with 95%Cl: 84.6 - 100.0%, and a specificity 85.1% (40/47) with 95%CI: 71.7 - 93.8%.
Method comparison with a commercially available C. difficile GDH assay
1904 (1891 prospective and 13 retrospective) stool samples collected from patients suspected of having C. difficile infection (CDI) were tested at 3 sites (USA and Europe). A single replicate of each sample was tested using VIDAS C. difficile GDH on a VIDAS instrument and a commercially available C. difficile GDH assay. Data from the study are summarized in the following table:
| Commercially available C. difficile GDH assay | ||||||||
|---|---|---|---|---|---|---|---|---|
| Site 1 (EU) | Site 2 (US) | Site 3 (US) | Total (All Sites) | |||||
| Positive | Negative | Positive | Negative | Positive | Negative | Positive | Negative | |
| VIDASC.difficileGDH | 56 | 10 | 92 | 7 | 207 | 69 | 355 | 86 |
| 4 | 454 | 2 | 365 | 4 | 621 | 10 | 1440 | |
| Total | 60 | 464 | 94 | 372 | 211 | 690 | 365 | 1526 |
| Performance | % | [CI95%] | % | [CI95%] | % | [CI95%] | % | [CI95%] |
| Positive PercentAgreement | 93.3% | [83.8 –98.2]% | 97.9% | [92.5 –99.7]% | 98.1% | [95.2 –99.5]% | 97.3% | [95.0 –98.7]% |
| NegativePercentAgreement | 97.8% | [96.1 –99.0]% | 98.1% | [96.2 –99.2]% | 90.0% | [87.5 –92.1]% | 94.4% | [93.1 –95.5]% |
Method comparison between the VIDAS C. difficile GDH assay and the commercially available C. difficile GDH assay on prospective samples
In order to better estimate the performance of the VIDAS C. difficile GDH assay in specimens from pediatric patients (2-12 years), thirteen (13) C. difficile retrospectively collected samples were tested according to the same protocol.For all 1904 specimens and all sites combined, the VIDAS C. difficile GDH assay demonstrated a positive percent agreement of 97.3%
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(367/377) with 95%Cl: 95.2 - 98.7%, and a negative percent agreement of 94.4% (1441/1527) with 95%CI: 93.1 - 95.5%.
Method comparison with bacterial culture (C. difficile chromogenic medium)
1904 (1891 prospective and 13 retrospective) stool samples collected from patients suspected of having C. difficile infection (CDI) were tested at 3 sites (USA and Europe). A single replicate of each sample was tested using VIDAS C. difficile GDH on a VIDAS instrument. A bacterial culture test was performed for each sample on a C. difficile chromogenic medium according to the instructions for use. Data from the study are summarized in the following table:
Performance of the VIDAS C. difficile GDH assay versus C. difficile chromogenic media bacterial culture on prospective samples
| C. difficile chromogenic bacterial culture test | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Site 1 (EU) | Site 2 (US) | Site 3 (US) | Total (All Sites) | ||||||
| Positive | Negative | Positive | Negative | Positive | Negative | Positive | Negative | ||
| VIDASC.difficileGDH | Positive | 42 | 24 | 85 | 14 | 187 | 89 | 314 | 127 |
| Negative | 8 | 450 | 3 | 364 | 14 | 611 | 25 | 1425 | |
| Total | 50 | 474 | 88 | 378 | 201 | 700 | 339 | 1552 | |
| Performance | % | [CI95%] | % | [CI95%] | % | [CI95%] | % | [CI95%] | |
| PositivePercentAgreement | 84.0 | [70.9 -92.8]% | 96.6% | [90.4 -99.3]% | 93.0% | [88.6 -96.1]% | 92.6% | [89.3 -95.2]% | |
| NegativePercentAgreement | 94.9% | [92.6 -96.7]% | 96.3% | [93.9 -98.0]% | 87.3% | [84.6 -89.7]% | 91.8% | [90.3 -93.1]% |
In order to better estimate the performance of the VIDAS C. difficile GDH assay in specimens from pediatric patients (2-12 years), thirteen (13) C. difficile retrospectively collected samples were tested according to the same protocol.For all 1904 specimens and all sites combined. the VIDAS C. difficile GDH assay demonstrated a positive percent agreement of 92.9% (325/350) with 95%Cl: 89.6 - 95.3%, and a negative percent agreement of 91.8% (1426/1554) with 95%CI: 90.3 - 93.1%.
I. Conclusion
The results from the non-clinical and clinical studies submitted in this premarket notification are complete and demonstrate that the VIDAS® C. difficile GDH assay is substantially equivalent to the predicate device identified in Item C of this summary.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
BIOMERIEUX SA CAROLINE KOCH-MATHIAN 5 RUE DES AQUEDUCS CRAPONNE 69290 FRANCE
October 9, 2013
Re: K132010 Trade/Device Name: VIDAS C. difficile GDH Regulation Number: 21 CFR § 866.2660 Regulation Name: Microorganism Differentiation and Identification Device Regulatory Class: 1 Product Code: MCB Dated: September 16, 2013 Received: September 17, 2013
Dear Ms. Koch-Mathian:
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 11 (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the
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Page 2-Ms. Koch-Mathian
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 regulations (2) CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resources/orYou/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Salety/ReportalProblem/delault.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/ResourcesforYou/Industry/default.htm.
Sincerely vours.
Sally A Hojvat -S
Sally A. Hojvat. M.Sc.. Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known): K132010
Device Name: VIDAS® C. difficile GDH
Indications For Use:
VIDAS® C. difficile GDH (GDH) is an automated test based on the Enzyme linked Fluorescent Assay technique (ELFA), for use on the VIDAS family instruments.
The VIDAS C. difficile GDH (glutamate dehydrogenase) assay is a qualitative test that detects the C. difficile antigen, glutamate dehydrogenase, as a screen for the presence of C. difficile in fecal specimens from persons suspected of having C. difficile infection (CDI). The test does not distinguish toxigenic from non-toxigenic strains of C. difficile. With the use of additional tests that detect C. difficile toxins, the test is to be used as an aid in the diagnosis of C. difficile infection. As with other C. difficile tests, results should be considered in conjunction with the patient history.
X ____________________________________________________________________________________________________________________________________________________________________________ Prescription Use (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR 807 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Ribhi Shawar -S 2013.10.09 13:46:27 -04'00'
Page 1 of 1 .
§ 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.