(72 days)
Not Found
No
The document describes a standard real-time PCR assay for detecting C. difficile genes and does not mention any AI or ML components in the device description, intended use, or performance studies.
No
This device is an in vitro diagnostic test intended for the detection of C. difficile toxin genes as an aid in diagnosis, not for treating or preventing disease.
Yes
The "Intended Use / Indications for Use" section states that the device is a "qualitative, multiplexed in vitro diagnostic test" for the detection of C. difficile and is "intended for use as an aid in the diagnosis of CDAD."
No
The device is an in vitro diagnostic test that includes reagents and is performed on specific hardware platforms (PCR instruments). It is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "The Quidel Molecular Direct C. difficile Assay is a qualitative, multiplexed in vitro diagnostic test..." This directly identifies the device as an IVD.
N/A
Intended Use / Indications for Use
The Quidel Molecular Direct C. difficile Assay is a qualitative, multiplexed in vitro diagnostic test for the direct detection of toxin A gene (tedA) or toxin B gene (tcdB) sequences of toxigenic strains of Clostridium difficile from unformed (liquid or soft) stool specimens collected from patients suspected of having Clostridium difficile-Associated Disease (CDAD).
The Quidel Molecular Direct C. difficile Assay is a real-time PCR test and utilizes proprietary sample preparation with fluorescently labeled primers and probes. The assay can be performed using either the Life Technologies QuantStudio® Dx; the Applied Biosystems 7500 Fast Dx, or the Cepheid SmartCycler II, to detect the toxin gene sequences associated with toxin-producing C. difficile strains.
The assay is intended to be performed directly on CDAD-suspected stool specimens, and is indicated for use as an aid in the diagnosis of CDAD.
Product codes (comma separated list FDA assigned to the subject device)
OZN
Device Description
The Quidel Molecular Direct C. difficile Assay detects nucleic acids that have been prepared from a patient sample using proprietary sample preparation. A multiplex real-time PCR reaction is performed under optimized conditions in a single well generating amplicons for each of the targets present in the sample. Identification occurs by the use of oligonucleotide primers and probes that are complementary to conserved regions in the tcdA and tcdB genes of the pathogenicity locus (PaLoc).
The Quidel Molecular Direct C. difficile Assay contains sufficient reagents to process 96 specimens or quality control samples. The kit contains the following:
| # | Component | Quantity |
|---|---|---|
| 1 | Rehydration Solution Part M5003 | 1 vial/kit 1.9 mL |
| 2 | Quidel Molecular C. difficile Master Mix Part M5043 | 12 vials/kit 8 reactions/vial |
SKU # M102
Assay Kit (96 Reactions) - Store at 2° to 8°C
SKU # M207
Rapid DNA Stool Sample Prep Kit (96 Specimens) - Store at 2º to 25ºC
| Component | Quantity |
|---|---|
| Process Buffer 1 Part M5032 | 96 tubes/kit 500 uL |
| 2 | Process Buffer 2 Part M5033 Contains Process Control |
| Neonatal flocked Swabs Part M5034 |
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
The test is for pediatric and adult patients.
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
A blinded four-member panel consisting of C. difficile positive and negative samples was tested by two operators, twice a day using a single assay lot of Quidel Molecular Direct C. difficile Assay for twelve (12) days on all three instruments for precision testing.
A blinded and randomized study panel containing Clostridium difficile negative and positive samples were tested at three (3) test sites, two of which were clinical sites. Each site tested a reproducibility panel and assay controls for five (5) days in triplicate on each instrument. The testing was done by two operators at each site. Each operator ran the panel once a day using one lot of Quidel Molecular Direct C. difficile Assay.
Performance of the Quidel Molecular Direct C. difficile Assay was evaluated with specimens collected at four geographically diverse locations within the United States between August 2012 and November 2012.
For the Applied Biosystems 7500 Fast Dx and Cepheid SmartCycler II studies, 665 specimens were tested. For the QuantStudio Dx study, 792 specimens were tested. These specimens were collected from patients suspected of having Clostridium difficile-associated disease (CDAD). Specimens were tested with the Quidel Assay at one of three (3) facilities.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Analytical performance:
Detection limit (LoD):
Applied Biosystems 7500 Fast Dx: ATCC BAA-1870 (IIIb) LoD was 8.4E+04 CFU/mL (4.2E-01 CFU/Assay), confirmed at 60/60. ATCC BAA-1872 (0) LoD was 2.4E+04 CFU/mL (1.2E-01 CFU/Assay), confirmed at 59/60.
Life Technologies QuantStudio: ATCC BAA-1870 (IIIb) LoD was 8.4E+04 CFU/mL (4.2E-01 CFU/Assay), confirmed at 20/20. ATCC BAA-1872 (0) LoD was 8.0E+03 CFU/mL (4.0E-02 CFU/Assay), confirmed at 20/20.
Cepheid SmartCycler II: ATCC BAA-1870 (IIIb) LoD was 8.4E+04 CFU/mL (4.2E-01 CFU/Assay), confirmed at 58/60. ATCC BAA-1872 (0) LoD was 2.4E+04 CFU/mL (1.2E-01 CFU/Assay), confirmed at 60/60.
The final assay LoD is 4.2E-01 CFU/assay.
Analytical Reactivity (Inclusivity): Twenty-four toxigenic strains of C. difficile were tested at 2 to 3x LoD using three assay lots. Broad range of toxigenic C. difficile strains detected at 2 to 3x LoD.
Analytical specificity (Cross-Reactivity): Panel of 66 bacterial, viral, yeast microorganisms, and human DNA tested. No cross-reactivity with medically relevant levels of viruses or bacteria. In silico analysis showed no predicted cross-reactivity for C. botulinum.
Interfering Substances: Thirty-five substances found in stool specimens were tested against two toxigenic C. difficile strains (ATCC BAA-1870 and ATCC BAA-1872). No interference found.
Precision/Reproducibility:
Precision:
Applied Biosystems 7500 Fast Dx: 5X LoD (100% detection, Avg Ct 18.2, STDEV 1.0, %CV 5.2%), 2X LoD (100% detection, Avg Ct 20.5, STDEV 1.3, %CV 6.2%), 0.3X LoD (71% detection, Avg Ct 25.8, STDEV 2.4, %CV 9.4%), Negative (0% detection).
Life Technologies QuantStudio™ Dx: 5X LoD (100% detection, Avg Ct 16.51, STDEV 0.42, %CV 2.6%), 2X LoD (100% detection, Avg Ct 17.70, STDEV 0.76, %CV 4.3%), 0.3X LoD (88% detection, Avg Ct 21.13, STDEV 1.37, %CV 6.5%), Negative (0% detection).
Cepheid SmartCycler II: 5X LoD (100% detection, Avg Ct 18.3, STDEV 1.1, %CV 6.0%), 2X LoD (96% detection, Avg Ct 20.6, STDEV 1.3, %CV 6.4%), 0.3X LoD (27% detection, Avg Ct 23.6, STDEV 1.1, %CV 4.7%), Negative (0% detection).
Reproducibility (3 sites, 2 operators):
Applied Biosystems 7500 Fast Dx
High Negative 0.3x LoD: Total Results 32/89 (36%)
Low Positive 2x LoD: Total Results 88/90 (97.8%)
Med Positive 5x LoD: Total Results 90/90 (100%)
Negative Specimen: Total Results 0/89 (0%)
Negative Control: Total Results 0/90 (0%)
Positive Control: Total Results 90/90 (100%)
Life Technologies QuantStudio Dx
High Negative 0.3x LoD: Total Results 38/90 (42.2%)
Low Positive 2x LoD: Total Results 90/90 (100%)
Med Positive 5x LoD: Total Results 90/90 (100%)
Negative Specimen: Total Results 0/90 (0%)
Negative Control: Total Results 0/90 (0%)
Positive Control: Total Results 90/90 (100%)
Cepheid SmartCycler II
High Negative 0.3x LoD: Total Results 65/90 (72.2%)
Low Positive 2x LoD: Total Results 88/89 (98.9%)
Med Positive 5x LoD: Total Results 90/90 (100%)
Negative Specimen: Total Results 0/89 (0%)
Negative Control: Total Results 0/89 (0%)
Positive Control: Total Results 90/90 (100%)
Clinical performance:
Comparison to Cytotoxic Tissue Culture:
Applied Biosystems 7500 Fast Dx (653 specimens analyzed)
Sensitivity: 94.3% (95% CI: 87.4% - 97.5%)
Specificity: 94.2% (95% CI: 91.9% - 95.8%)
Life Technologies QuantStudio Dx (788 specimens analyzed)
Sensitivity: 93.3% (95% CI: 86.9% - 96.7%)
Specificity: 93.4% (95% CI: 91.3% - 95.0%)
Cepheid SmartCycler II (657 specimens analyzed)
Sensitivity: 89.7% (95% CI: 81.5% - 94.5%)
Specificity: 93.3% (95% CI: 91.0% - 95.1%)
Comparison to Enriched Toxigenic Culture:
Applied Biosystems 7500 Fast Dx (656 specimens analyzed)
Sensitivity: 88.9% (95% CI: 82.2% - 93.3%)
Specificity: 98.9% (95% CI: 97.6% - 99.5%)
Life Technologies QuantStudio Dx (791 specimens analyzed)
Sensitivity: 87.3% (95% CI: 81.1% - 91.6%)
Specificity: 98.7% (95% CI: 97.5% - 99.4%)
Cepheid SmartCycler II (660 specimens analyzed)
Sensitivity: 82.4% (95% CI: 74.8% - 88.1%)
Specificity: 97.9% (95% CI: 95.4%) (Lower CI not provided)
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
See "Summary of Performance Studies" for detailed metrics.
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.
Portrait Toxigenic C. difficile Assay (K113358)
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 866.3130 Clostridium difficile toxin gene amplification assay.
(a)
Identification. AClostridium difficile toxin gene amplification assay is a device that consists of reagents for the amplification and detection of target sequences inClostridium difficile toxin genes in fecal specimens from patients suspected of havingClostridium difficile infection (CDI). The detection of clostridial toxin genes, in conjunction with other laboratory tests, aids in the clinical laboratory diagnosis of CDI caused byClostridium difficile. (b)
Classification. Class II (special controls). The special controls are set forth in FDA's guideline document entitled: “Class II Special Controls Guideline: Toxin Gene Amplification Assays for the Detection ofClostridium difficile; Guideline for Industry and Food and Drug Administration Staff.” See § 866.1(e) for information on obtaining this document.
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Image /page/0/Picture/0 description: The image shows the logo for Quidel Corporation. The logo is in black and white and features the word "QUIDEL" in large, bold letters. Below the word "QUIDEL" is the word "CORPORATION" in smaller letters. There is a registered trademark symbol to the right of the word "QUIDEL".
MAR
8 2013
510(k) SUMMARY
510(k) Number: K123998 - Quidel Molecular Direct C. difficile Assay
Date of Preparation: December 20, 2012
Submitted by:
Quidel Corp. 10165 McKellar Court San Diego, CA, 92121 Phone: 848-552.110 Fax: 848-552-6451
Contact:
Ronald H. Lollar Senior Director, Clinical and Quality Affairs
Proprietary and Established Names:
Quidel Molecular Direct C. difficile Assay
Common Name:
Clostridium difficile Nucleic Acid Test C. difficile assay C. diff test
Regulatory Information:
Regulation section: 21 CFR 866.3130 - C. difficile Nucleic Acid Amplification Test Assay Classification: II Product code: OZN - Amplification assay for the detection of Clostridium difficile toxin genes from stool specimens of symptomatic patients Panel: Microbiology (83)
Predicate Devices: Portrait Toxigenic C. difficile Assay (K113358) (Great Basin Scientific)
10165 McKellar Court • San Diego • California 92121 858.552.1100 · Fax 858.453.4338 www.quidel.com
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Intended Use:
The Quidel Molecular Direct C. difficile Assay is a qualitative, multiplexed in vitro diagnostic test for the direct detection of toxin A gene (tedA) or toxin B gene (tcdB) sequences of toxigenic strains of Clostridium difficile from unformed (liquid or soft) stool specimens collected from patients suspected of having Clostridium difficile-Associated Disease (CDAD).
The Quidel Molecular Direct C. difficile Assay is a real-time PCR test and utilizes proprietary sample preparation with fluorescently labeled primers and probes. The assay can be performed using either the Life Technologies QuantStudio® Dx; the Applied Biosystems 7500 Fast Dx, or the Cepheid SmartCycler II, to detect the toxin gene sequences associated with toxin-producing C. difficile strains.
The assay is intended to be performed directly on CDAD-suspected stool specimens, and is indicated for use as an aid in the diagnosis of CDAD.
Special instrument requirements:
Life Technologies QuantStudio® Dx software version 1, or Applied Biosystems 7500 Fast Dx software version 1.4, or Cepheid SmartCycler II software version 3.0b
Device Description:
The Quidel Molecular Direct C. difficile Assay detects nucleic acids that have been prepared from a patient sample using proprietary sample preparation. A multiplex real-time PCR reaction is performed under optimized conditions in a single well generating amplicons for each of the targets present in the sample. Identification occurs by the use of oligonucleotide primers and probes that are complementary to conserved regions in the tcdA and tcdB genes of the pathogenicity locus (PaLoc).
The Quidel Molecular Direct C. difficile Assay contains sufficient reagents to process 96 specimens or quality control samples. The kit contains the following:
| # | Component | Quantity |
|---|---|---|
| 1 | Rehydration Solution Part M5003 | 1 vial/kit 1.9 mL |
| 2 | Quidel Molecular C. difficile Master Mix Part M5043 | 12 vials/kit |
| 8 reactions/vial |
SKU # M102
Assay Kit (96 Reactions) - Store at 2° to 8°C
SKU # M207
Rapid DNA Stool Sample Prep Kit (96 Specimens) - Store at 2º to 25ºC
| Component | Quantity |
|---|---|
| Process Buffer 1 Part M5032 | 96 tubes/kit 500 uL |
2
| # | Component | Quantity |
|---|---|---|
| 2 | Process Buffer 2 Part M5033 | |
| Contains Process Control | 96 tubes/kit 570 $ $\mu$ $ L | |
| Neonatal flocked Swabs Part M5034 | 96 swabs |
Test Principle:
The Quidel Molecular Direct C. difficile Assay detects nucleic acids that have been prepared from a patient sample using proprietary sample preparation. A multiplex real-time PCR reaction is performed under optimized conditions in a single well generating amplicons for each of the targets present in the sample. Identification occurs by the use of oligonucleotide primers and probes that are complementary to conserved regions in the tedA and tedB genes of the pathogenicity locus (PaLoc).
The following is a summary of the procedure:
-
- Sample Collection: Dip a neonatal flocked swab into the liquid or soft stool specimen using standard techniques from pediatric and adult patients suspected of having Clostridium difficile-Associated Disease (CDAD). Note: Remove mucus from the specimen prior to sampling the fecal material.
-
- Sample Preparation: Twirl the neonatal flocked swab in the first process buffer then add 30 µL of the sample into the second process buffer tube which contains the process control (PRC).
-
- Rehydration of Master Mix: Rehydrate the lyophilized Master Mix using the Rehydration Solution. The Master Mix contains oligonucleotide primers, fluorophore and quencher-labeled probes targeting conserved regions of the tcdA and tcdB as well as the process control sequence.
-
- Nucleic Acid Amplification and Detection: Add 15 uL of the rehydrated Master Mix to each reaction tube or plate well. Then add 5 uL of prepared specimen with PRC) to the plate well or appropriately labeled reaction tube. Place the plate or tube into the Life Technologies QuantStudio® Dx, Applied Biosystems 7500 Fast Dx instrument · or Cepheid® SmartCycler® II instruments.
Once the reaction tube or plate is added to the instrument, the Quidel Molecular Direct C. difficile Assay protocol is initiated. This assay is based on Tagman® chemistry, and uses an enzyme with DNA polymerase, and 5 -3' exonuclease activities. During DNA amplification, this enzyme cleaves the probe bound to the complementary DNA sequence, separating the quencher
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dye from the reporter dye. This step generates an increase in fluorescent signal upon excitation by a light source of the appropriate wavelength. With each cycle, additional dye molecules are separated from their quenchers resulting in an increase in the fluorescent signal. If sufficient fluorescence is achieved, the sample is reported as positive for the detected nucleic acid.
Performance Characteristics
Analytical performance:
Detection limit: The analytical sensitivity (limit of detection or LoD) of the Quidel Molecular Direct C. difficile Assay was determined on each instrument using quantified (CFU/mL) cultures of two C. difficile strains (ATCC BAA-1870 and ATCC BAA-1872) serially diluted in a negative fecal matrix. Analytical sensitivity (LoD) is defined as the lowest concentration at which 95% of all replicates tested positive.
Applied Biosystems 7500 Fast Dx
| Strain Designation | Toxinotype | Calculated
CFU/mL at LoD | CFU per Assay at
LoD | LoD Confirmation
Results |
|--------------------|------------|-----------------------------|-------------------------|-----------------------------|
| ATCC BAA-
1870 | IIIb | 8.4E+04 | 4.2E-01 | 60/60 |
| ATCC BAA-
1872 | 0 | 2.4E+04 | 1.2E-01 | 59/60 |
Life Technologies QuantStudio
| Strain Designation | Toxinotype | Calculated | CFU per Assay at | LoD Confirmation |
|---|---|---|---|---|
| CFU/mL at LoD | LoD | Results | ||
| ATCC BAA- | ||||
| 1870 | IIIb | 8.4E+04 | 4.2E-01 | 20/20 |
| ATCC BAA- | ||||
| 1872 | 0 | 8.0E+03 | 4.0E-02 | 20/20 |
Cepheid SmartCycler II .
| Strain Designation | Toxinotype | Calculated
CFU/mL at LoD | CFU per Assay at
LoD | LoD Confirmation
Results |
|--------------------|------------|-----------------------------|-------------------------|-----------------------------|
| ATCC BAA-
1870 | IIIb | 8.4E+04 | 4.2E-01 | 58/60 |
| ATCC BAA-
1872 | 0 | 2.4E+04 | 1.2E-01 | 60/60 |
The final assay LoD is defined as the higher of the two strain concentrations where 95% positivity was observed. The final assay LoD is 4.2E-01 CFU/assay.
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Analytical Reactivity (Inclusivity): Twenty-four toxigenic strains for C. difficile were tested at 2 to 3x LoD in negative specimen matrix using three (3) Quidel Molecular Direct C. difficile Assay lots. Strains were reported to originate from at least five states and four countries (USA, Belgium, France and Sweden), Seven (7) toxinotypes were represented: 0, IIIb, IIIc, IV, V, VIII and XXIII. The analytical reactivity (inclusivity) testing conducted demonstrated that the Quidel Molecular Direct C. difficile Assay can detect a broad range of toxigenic Clostridium difficile strains at 2 to 3x LoD.
Analytical specificity:
Cross-Reactivity
The analytical specificity of the Quidel Molecular Direct C. difficile Assay was evaluated by testing a panel consisting of 66 bacterial, viral and yeast microorganisms and human DNA representing common enteric pathogens, flora or nucleic acid commonly present in the intestine. Microorganisms or nucleic acid was mixed with pooled negative matrix and tested directly or in the presence of 2 to 3x LoD level of C. difficile for cross reactivity and microbial interference, respectively. Bacteria were tested at concentrations greater than 1.0E+06 CFU/mL and viruses at greater than 1.0E+05 PFU/mL. In addition, in silico analysis showed that the Quidel Molecular Direct C. difficile Assay had no predicted cross-reactivity for C. botulinum. The results of this study demonstrate that the Ouidel Molecular Direct C. difficile Assay does not cross-react with medically relevant levels of viruses or bacteria found in stool specimens.
Interfering Substances
Two toxigenic strains of C. difficile (ATCC BAA-1870 and ATCC BAA-1872) were evaluated against a test panel consisting of thirty-five substances found in stool specimens. Substances were introduced into the assay dilution tubes at concentrations which were medically relevant. Each of the strains was tested for each substance. None of the substances tested were found to interfere with the Quidel Molecular Direct C. difficile Assay.
Precision/Reproducibility:
Precision:
For the Precision/Within Laboratory Repeatability study, a blinded four-member panel consisting of C. difficile positive and negative sample was tested by two operators, twice a day using a single assay lot of Quidel Molecular Direct C. difficile Assay for twelve (12) days on all three instruments.
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| Applied Biosystems 7500 Fast Dx | ||||
|---|---|---|---|---|
| C. difficile | 5X LoD | 2X LoD | 0.3X LoD | Negative |
| % Detection | 100% | 100% | 71% | 0% |
| Average Ct | 18.2 | 20.5 | 25.8 | N/A |
| STDEV | 1.0 | 1.3 | 2.4 | N/A |
| %CV | 5.2% | 6.2% | 9.4% | N/A |
| Life Technologies QuantStudio™ Dx Real-Time PCR
| Instrument | ||||
|---|---|---|---|---|
| C. difficile | 5X LoD | 2X LoD | 0.3X LoD | Negative |
| % Detection | 100% | 100% | 88% | 0% |
| Average Ct | 16.51 | 17.70 | 21.13 | N/A |
| STDEV | 0.42 | 0.76 | 1.37 | N/A |
| %CV | 2.6% | 4.3% | 6.5% | N/A |
| Cepheid SmartCycler II | ||||
|---|---|---|---|---|
| C. difficile | 5X LoD | 2X LoD ' | 0.3X LoD | Negative |
| % Detection | 100% | 96% | 27% | 0% |
| Average Ct | 18.3 | 20.6 | 23.6 | N/A |
| STDEV | 1.1 | 1.3 | 1.1 | N/A |
| %CV | 6.0% | 6.4% | 4.7% | N/A |
Reproducibility:
In order to confirm the reproducibility of the Quidel Molecular Direct C. difficile Assay a blinded and randomized study panel containing Clostridium difficile negative and positive samples were tested at three (3) test sites, two of which were clinical sites. Each site tested a reproducibility panel and assay controls for five (5) days in triplicate on each instrument. The testing was done by two operators at each site. Each operator ran the panel once a day using one lot of Quidel Molecular Direct C. difficile Assay.
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510(k) Summary: Quidel Molecular Direct C. difficile Assay
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| Reproducibility Results - Applied Biosystems 7500 Fast Dx | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Panel | ||||||||||
| Member ID | Site 1 | |||||||||
| Results | Site 1 | |||||||||
| AVE Ct | Site 1 | |||||||||
| %CV | Site 2 | |||||||||
| Results | Site 2 | |||||||||
| AVE Ct | Site 2 | |||||||||
| %CV | Site 3 | |||||||||
| Results | Site 3 | |||||||||
| AVE Ct | Site 3 | |||||||||
| %CV | Total | |||||||||
| Results | ||||||||||
| High | ||||||||||
| Negative | ||||||||||
| 0.3x LoD | 5/29 | 28.8 | 15.0 | 11/30 | 27.1 | 9.0 | 16/30 | 27.6 | 2.8 | 32/89 |
| Low | ||||||||||
| Positive | ||||||||||
| 2x LoD | 29/30 | 23.2 | 8.4 | 30/30 | 22.7 | 7.5 | 29/30 | 23.1 | 6.5 | 88/90 |
| Med | ||||||||||
| Positive 5x | ||||||||||
| LoD | 30/30 | 20.5 | 5.7 | 30/30 | 20.2 | 5.0 | 30/30 | 20.4 | 5.0 | 90/90 |
| Negative | ||||||||||
| Specimen | 0/29 | N/A | N/A | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/89 |
| Negative | ||||||||||
| Control | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/90 |
| Positive | ||||||||||
| Control | 30/30 | 15.8 | 2.9 | 30/30 | 16.2 | 2.6 | 30/30 | 15.7 | 2.9 | 90/90 |
| Reproducibility Results – Life Technologies QuantStudio Dx | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Panel | ||||||||||
| Member ID | Site 1 | |||||||||
| Results | AVE | |||||||||
| Ct | %CV | Site 2 | ||||||||
| Results | AVE | |||||||||
| Ct | %CV | Site 3 | ||||||||
| Results | AVE | |||||||||
| Ct | %CV | Total | ||||||||
| Results | ||||||||||
| High | ||||||||||
| Negative | ||||||||||
| 0.3x LoD | 8/30 | 22.9 | 5.0 | 15/30 | 22.5 | 5.7 | 15/30 | 22.5 | 1.5 | 38/90 |
| Low | ||||||||||
| Positive | ||||||||||
| 2x LoD | 30/30 | 20.4 | 5.9 | 30/30 | 19.0 | 5.1 | 30/30 | 19.2 | 0.8 | 90/90 |
| Med | ||||||||||
| Positive 5x | ||||||||||
| LoD | 30/30 | 18.4 | 4.2 | 30/30 | 17.5 | 2.2 | 30/30 | 17.9 | 0.7 | 90/90 |
| Negative | ||||||||||
| Specimen | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/90 |
| Negative | ||||||||||
| Control | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/90 |
| Positive | ||||||||||
| Control | 30/30 | 15.7 | 0.6 | 30/30 | 15.7 | 0.1 | 30/30 | 15.5 | 0.1 | 90/90 |
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| 510(k) Summary: Quidel Molecular Direct C. difficile Assay |
|---|
| ------------------------------------------------------------ |
| Reproducibility Results – Cepheid SmartCycler II | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Panel | ||||||||||
| Member ID | Site 1 | Site 2 | Site 3 | Total | ||||||
| Results | ||||||||||
| Results | AVE | |||||||||
| Ct | %CV | Results | AVE | |||||||
| Ct | %CV | Results | AVE | |||||||
| Ct | %CV | |||||||||
| High | ||||||||||
| Negative | ||||||||||
| 0.3x LoD | 17/30 | 23.4 | 6.6 | 22/30 | 25.3 | 13.4 | 26/30 | 23.4 | 9.3 | 65/90 |
| Low | ||||||||||
| Positive | ||||||||||
| 2x LoD | 29/30 | 20.1 | 4.6 | 29/29 | 20.1 | 5.1 | 30/30 | 19.9 | 6.4 | 88/89 |
| Med | ||||||||||
| Positive 5x | ||||||||||
| LoD | 30/30 | 18.4 | 9.5 | 30/30 | 18.5 | 3.1 | 30/30 | 18.3 | 6.4 | 90/90 |
| Negative | ||||||||||
| Specimen | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/29 | N/A | N/A | 0/89 |
| Negative | ||||||||||
| Control | 0/30 | N/A | N/A | 0/30 | N/A | N/A | 0/29 | N/A | N/A | 0/89 |
| Positive | ||||||||||
| Control | 30/30 | 15.1 | 3.8 | 30/30 | 14.8 | 2.2 | 30/30 | 14.5 | 3.4 | 90/90 |
Clinical performance:
The performance of the Quidel Molecular Direct C. difficile Assay was evaluated with specimens collected at four geographically diverse locations within the United States between August 2012 and November 2012. In two studies (one study for the ABI 7500 Fast Dx and Cepheid SmartCycler II (665 specimens) and a second study for the QuantStudio Dx (792 specimens)), the Quidel Molecular Direct C. difficile Assay was compared to cytotoxic tissue culture and an enriched toxigenic C. difficile culture. The tables below present the data from these studies.
Applied Biosystems 7500 Fast Dx
Performance characteristics of the Ouidel Molecular Direct C. difficile Assay were established during a prospective study conducted August to November 2012. Six hundred sixty-five (665) specimens used for this study were collected from patients suspected of having Clostridium difficile-associated disease (CDAD) at four distinct geographical sites across the United States. These specimens were tested with the Quidel Assay on the 7500 Fast Dx at one of three (3) facilities.
Nine specimens (1.35%) were invalid in the Quidel Molecular Direct C. difficile Assay when initially tested. We calculated the age and gender distribution based on the initial test result obtained for each specimen. Therefore, the patient age and gender data below is for the remaining six hundred fifty-six (656) specimens.
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| Combined Sites - Age and Gender Distribution | ||||
|---|---|---|---|---|
| Age | Gender | Total | Prevalence by age of C. difficile positives with the Quidel Molecular Direct C. difficile Assay on the Applied Biosystems 7500 Fast Dx | |
| Male | Female | |||
| Unknown Gender | 3 | 33.3% (1/3) | ||
| Infant (21 to 59 years) | 132 | 146 | 278 | 19.1% (53/278) |
| Sr. Adult (≥ 60 years) | 127 | 169 | 296 | 15.9% (47/296) |
| Total | 297 | 356 | 656 | 18.0% (118/656) |
Direct Culture Cytotoxicity Assay Comparison
Six hundred sixty-five specimens were tested by both the Quidel Molecular Direct C. difficile Assay and the tissue culture cytotoxin assay. Three specimens (0.5%) were indeterminate in the cytotoxin assay due to toxicity in the antitoxin well. Nine specimens (1.35%) were invalid in the Quidel Molecular Direct C. difficile Assay when initially tested. Eight specimens yielded a valid result when retested according to the Quidel Molecular Direct C. difficile Assay draft package insert (7 were negative, 1 was positive). One specimen remained invalid upon repeat testing. We calculated clinical performance based on the initial test result obtained for each specimen. Therefore, the data below is for the remaining six hundred fifty-three (653) specimens.
| Combined Sites – Combined Ages | Direct Culture | 95% CI | ||||||
|---|---|---|---|---|---|---|---|---|
| Quidel | ||||||||
| Molecular Real-Time PCR Direct | ||||||||
| C. difficile Assay | ||||||||
| on | ||||||||
| ABI 7500 | POS | NEG | Total | Sensitivity | ||||
| POS | 83 | 33* | 116 | 94.3% | 87.4% | 97.5% | ||
| NEG | 5** | 532 | 537 | Specificity | 94.2% | 91.9% | 95.8% | |
| Total | 88 | 565 | 653 |
9
-
- Of the thirty-three (33) discordant specimens (Quidel Molecular Positive/Direct Culture ) reported, thirty-two (32) were tested with a FDA-cleared molecular device. All thirty-two of these specimens were positive for C. difficile. The remaining specimen was unavailable for testing.
- ** Five (5) discordant specimens (Quidel Negative/Tissue Culture Cytotoxin Positive) reported were tested with the FDA-cleared molecular device. All five (5) of these specimens were found to be negative for C. difficile.
Enriched Toxigenic Culture Comparison
Six hundred sixty-five (665) specimens were tested by both the Quidel Molecular Direct C. difficile Assay and enriched toxigenic culture. Nine specimens (1.35%) were invalid in the Quidel Molecular Direct C. difficile Assay when initially tested. Eight specimens yielded a valid result (7 were negative, 1 was positive) when retested according to the Quidel Molecular Direct C. difficile Assay draft package insert. One specimen remained invalid upon repeat testing. We calculated clinical performance based on the initial test result obtained for each specimen. Therefore, the data below is for the remaining six hundred fifty-six (656) specimens.
| Combined Sites – Combined Ages | ||||||||
|---|---|---|---|---|---|---|---|---|
| Enhanced Toxigenic Culture | 95% CI | |||||||
| POS | NEG | Total | Sensitivity | 88.9% | 82.2% | 93.3% | ||
| Quidel | ||||||||
| Molecular Direct | ||||||||
| C. difficile Assay | ||||||||
| on | ||||||||
| ABI 7500 | POS | 112 | 6* | 118 | Specificity | 98.9% | 97.6% | 99.5% |
| NEG | 14** | 524 | 538 | |||||
| Total | 126 | 530 | 656 |
- Six (6) discordant specimens (Quidel Molecular Positive/Enriched Toxigenic Culture Negative) reported were tested with a FDA-cleared molecular device. All of these specimens were positive for C. difficile.
** T welve ( 12) discordant specimens (Quidel Negative/ Enriched Toxigenic Culture Positive) reported in Table 20.15, were tested with a FDA-cleared molecular device. Two (2) specimens were unavailable for testing. Nine (9) of these specimens were found negative for C. difficile, and three (3) were positive.
Life Technologies QuantStudio Dx Real-Time PCR Instrument System
Performance characteristics of the Quidel Molecular Direct C. difficile Assay were established during a prospective study conducted August to November 2012. Seven hundred ninety-two (792) samples used for this study were collected from patients suspected of having Clostridium difficile-associated disease (CDAD) at four (4) distinct geographical sites across the United States. These specimens were tested with the Quidel Assay on the QuantStudio Dx Instrument at one of three (3) facilities.
10
One (1) specimen (0.1%) was invalid in the Quidel Molecular Direct C. difficile Assay when initially tested. We calculated age and gender distribution based on the initial test result obtained for each specimen. Therefore, the patient age and gender data below is for the remaining seven hundred ninety-one (791) specimens.
| Combined Sites – Age and Gender Distribution | ||||
|---|---|---|---|---|
| Age | Gender | Total | Prevalence by age of | |
| C. difficile positives | ||||
| with the Quidel | ||||
| Molecular Direct C. difficile Assay on the | ||||
| QuantStudio | ||||
| Male | Female | |||
| Unknown Gender | 2 | 50.0% (1/2) | ||
| Infant (21 to 59 years) | 158 | 170 | 328 | 18.3% (60/328) |
| Sr. Adult (≥ 60 years) | 163 | 202 | 365 | 17.8% (65/365) |
| Total | 370 | 419 | 791 | 18.3% (145/791) |
Direct Culture Assay Comparison
Seven hundred and ninety-two samples were tested by both the Quidel Molecular Direct C. difficile Assay and the direct culture assay. Three (3) specimens (0.4%) were indeterminate in the cytotoxin assay due to toxicity in the antitoxin well. One (1) specimen (0.1%) was invalid in the Quidel Molecular Direct C. difficile Assay when initially tested. The specimen yielded a valid result when retested according to the Quidel Molecular Direct C. difficile Assay draft package insert (it was negative). We calculated clinical performance based on the initial test result obtained for each specimen. Therefore, the data below is for the remaining seven hundred eighty-eight (788) specimens.
11
| Combined Sites – Combined Ages | ||||||||
|---|---|---|---|---|---|---|---|---|
| Tissue Culture Cytotoxin | 95% CI | |||||||
| POS | NEG | Total | Sensitivity | 93.3% | 86.9% | 96.7% | ||
| Quidel | ||||||||
| Molecular Direct | POS | 98 | 45* | 143 | Specificity | 93.4% | 91.3% | 95.0% |
| C. difficile Assay | ||||||||
| on | ||||||||
| LTI QuantStudio | NEG | 7** | 638 | 645 | ||||
| Total | 105 | 683 | 788 |
Of the forty-five (45) discordant specimens (Quidel Molecular Positive/Direct Culture Negative) reported, forty-four (44) were tested with a FDA-cleared molecular device. Thirty-five (35) of these specimens were positive for C. difficile, and nine (9) were negative. The remaining specimen was unavailable for testing.
** Seven (7) discordant specimens (Quidel Negative/Direct Culture Positive) reported were tested with a FDA-cleared molecular device. Two (2) of these specimens were found positive for C. difficile, and five ' (5) were negative.
Enriched Toxigenic Culture Comparison
- Seven hundred ninety-two (792) samples were tested by both the Quidel Molecular Direct C. difficile Assay and enhanced toxigenic culture. One (1) specimen (0.1%) was invalid in the Quidel Molecular Direct C. difficile Assay when initially tested. The specimen yielded a valid result (it was negative) when retested according to the Quidel Molecular Direct C. difficile Assay draft package insert. We elected to calculate clinical performance based on the initial test result obtained for each specimen. Therefore, the data below is for the remaining seven hundred ninety-one (791) specimens.
| Combined Sites - Combined Ages | ||||||||
|---|---|---|---|---|---|---|---|---|
| Enriched Toxigenic Culture | 95% CI | |||||||
| Quidel | POS | NEG | Total | Sensitivity | 87.3% | 81.1% | 91.6% | |
| Molecular Direct | ||||||||
| C. difficile Assay | ||||||||
| on | ||||||||
| LTI QuantStudio | POS | 137 | 8* | 145 | Specificity | 98.7% | 97.5% | 99.4% |
| NEG | 20** | 626 | 646 | |||||
| Total | 157 | 634 | 791 |
关 Eight (8) discordant specimens (Quidel Molecular Positive/Enriched Toxigenic Culture Negative) reported were tested with a FDA-cleared molecular device. Two (2) of these specimens were positive for C. difficile, and six (6) were negative.
12
- ** Seventeen (17) out of twenty (20) discordant specimens (Quidel Negative/ Enriched Toxigenic Culture Positive) reported, were tested with a FDA-cleared molecular device. Three (3) specimens were unavailable for testing. Eleven (11) of these specimens were found negative for C. difficile, and six (6) were positive.
Cepheid SmartCycler II
Performance characteristics of the Quidel Molecular Direct C. difficile Assay were established during a prospective study conducted August to November 2012. Six hundred sixty-five (665) specimens used for this study were collected from patients suspected of having Clostridium difficile-associated disease (CDAD) at four distinct geographical sites across the United States. These specimens were tested with the Quidel Assay on the SmartCycler II at one of three (3) facilities.
Five (5) specimens (0.75%) were invalid in the Quidel Molecular Direct C. difficile Assay when initially tested. We calculated the age and gender distribution based on the initial test result obtained for each specimen. Therefore, the patient age and gender data below is for the remaining six hundred sixty (660) specimens.
| Combined Sites - Age and Gender Distribution | |||||
|---|---|---|---|---|---|
| Age | Gender | Total | Prevalence by age of | ||
| C. difficile positives | |||||
| with the Quidel | |||||
| Molecular Direct C. difficile Assay on the | |||||
| Cepheid SmartCycler II | |||||
| M | F | ||||
| Unknown Gender | 3 | 33.3% (1/3) | |||
| Infant (21 to 59 years) | 133 | 147 | 280 | 18.6% (52/280) | |
| Sr. Adult (≥ 60 years) | 129 | 169 | 298 | 17.1% (51/298) | |
| Total | 300 | 357 | 660 | 17.9% (118/660) |
13
Direct Culture Assay Comparison
Six hundred sixty-five specimens were tested by both the Quidel Molecular Direct C. difficile Assay and the direct culture assay. Three (3) specimens (0.5%) were indeterminate in the cytotoxin assay due to toxicity in the antitoxin well. Five (5) specimens (0.75%) were invalid in the Quidel Molecular Direct C. difficile Assay when initially tested. All five (5) specimens yielded a valid when retested according to the Quidel Molecular Direct C. difficile Assay draft package insert result (3 were negative, 2 were positive). We calculated clinical performance based on the initial test result obtained for each specimen. Therefore, the data below is for the remaining six hundred fifty-seven (657) specimens.
| Combined Sites – Combined Ages | ||||||||
|---|---|---|---|---|---|---|---|---|
| Tissue Culture Cytotoxin | 95% CI | |||||||
| POS | NEG | Total | Sensitivity | 89.7% | 81.5% | 94.5% | ||
| Quidel | ||||||||
| Molecular Direct | ||||||||
| C. difficile Assay | ||||||||
| on | ||||||||
| Cepheid | ||||||||
| SmartCycler II | POS | 78 | 38* | 116 | Specificity | 93.3% | 91.0% | 95.1% |
| NEG | 9** | 532 | 541 | |||||
| Total | 87 | 570 | 657 |
- The thirty-three (38) discordant specimens (Quidel Molecular Positive/Direct Culture Negative) reported were tested with a FDA-cleared molecular device. Nine (9) of these specimens were negative for C. difficile, and twenty-nine (29) were positive for C. difficile.
** Eight (8) of the nine (9) discordant specimens (Ouidel Negative/Direct Culture Positive) reported were tested with a FDA-cleared molecular device. One (1) specimen was unavailable for testing. Five (5) of these specimens were found to be negative for C. difficile, and three (3) were found to be positive.
Enriched Toxigenic Culture Comparison
Six hundred sixty-five (665) specimens were tested by both the Quidel Molecular Direct C. difficile Assay and enriched toxigenic culture. Five (5) specimens (0.75%) were invalid in the Quidel Molecular Direct C. difficile Assay when initially tested. All five (5) specimens yielded a valid result when retested according to the Quidel Molecular Direct C. difficile (3 were negative, 2 were positive). We elected to calculate clinical performance based on the initial test result obtained for each specimen. Therefore, the data below is for the remaining six hundred sixty (660) specimens.
14
| Combined Sites - Combined Ages | |||||||
|---|---|---|---|---|---|---|---|
| Enhanced Toxigenic Culture | 95% CI | ||||||
| POS | NEG | Total | Sensitivity | ||||
| Quidel | |||||||
| Molecular Direct | |||||||
| C. difficile Assay | |||||||
| on | |||||||
| Cepheid | |||||||
| SmartCycler II | POS | 103 | 15* | 118 | 82.4% | 74.8% | 88.1% |
| NEG | 22** | 520 | 542 | Specificity | 97.9% | 95.4% | |
| Total | 125 | 535 | 660 |
- Fifteen (15) discordant specimens (Quidel Molecular Positive/Enriched Toxigenic Culture Negative) reported were tested with a FDA-cleared molecular device. Six (6) of these specimens were positive for, nine (9) of these specimens were negative.
- ** Nineteen (19) of the twenty-two (22) discordant specimens (Quidel Negative/ Enriched Toxigenic Culture Positive) reported were tested with a FDA-cleared molecular device. Three (3) specimens were unavailable for testing. Ten (10) of these specimens were found to be positive for C. difficile, and nine (9) were found to be negative.
Proposed Labeling:
The labeling is per the requirements of 21 CFR Part 809.10.
Conclusion:
Quidel has submitted this 510(k) in accordance with the requirements of SMDA 1990 and 21 CFR 807.92. This summary of 510(k) safety and effectiveness information provides the necessary detail for a determination of substantial equivalence for the Quidel Molecular Direct C. difficile Assay.
15
Image /page/15/Picture/0 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" arranged around the perimeter. Inside the circle is a stylized representation of an eagle or bird-like figure with flowing lines, symbolizing health and human services.
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
Quidel Corporation C/O Ronald H. Lollar 10165 McKellar Court San Diego, California 92121
March 8, 2013
Re: K123998
Trade/Device Name: Regulation Number: Regulation Name: Regulatory Class: Product Code: Dated: Received:
Quidel Molecular Direct C. difficile Assay 21 CFR 8866.3130 C. difficile Nucleic Acid Amplification Test Assay Class II OZN. OOI December 20, 2012 December 26, 2012
Dear Mr. Lollar:
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 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
16
Page 2 - Mr. Ron H. Lollar
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/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/ResourcesforYou/Industry/default.htm.
Sincerely vours.
Sally Aೃฟอjyat
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
17
510(k) NumberK123998
Device Name: Quidel Molecular Direct C. difficile Assay
Indication for Use:
The Quidel Molecular Direct C. difficile Assay is a qualitative, multiplexed in vitro diagnostic test for the direct detection of toxin A gene (tcdA) or toxin B gene (tcdB) sequences of toxigenic strains of Clostridium difficile from unformed (liquid or soft) stool specimens collected from patients suspected of having Clostridium difficile-Associated Disease (CDAD).
The Quidel Molecular Direct C. difficile Assay is a real-time PCR test and utilizes proprietary sample preparation with fluorescently labeled primers and probes. The assay can be performed using either the Life Technologies QuantStudio® Dx; the Applied Biosystems 7500 Fast Dx. or the Cepheid SmartCycler II. to detect the toxin gene sequences associated with toxin-producing C. difficile strains.
The assay is intended to be performed directly on CDAD-suspected stool specimens, and is indicated for use as an aid in the diagnosis of CDAD.
Prescription Use X (Part 21 CFR 801 Subpart D)
Over-The-Counter Use AND/OR (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELQW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED
Concurrence of CDRH, Office of Device Evaluation (ODE)
Raquel A. Peat -S 2013.03.06 18:18:43 -05'00'
Division Sign-Off CDRH, Center for Devices and Radiological Health 510 (k) K123998