(265 days)
Not Found
No
The description focuses on standard real-time PCR technology and automated sample preparation. There is no mention of AI or ML in the device description, intended use, or performance studies.
No
This device is an in vitro diagnostic test designed to aid in the diagnosis of C. difficile infection by detecting the tcdB gene in stool specimens. It provides information for diagnosis but does not directly treat or prevent a disease.
Yes
Explanation: The "Intended Use / Indications for Use" section explicitly states that the device is an "automated, qualitative in vitro diagnostic test" and is "intended for use as an aid in the diagnosis of CDI in humans."
No
The device is an in vitro diagnostic test that utilizes hardware components (cobas x 480 Instrument and cobas z 480 Analyzer) in addition to software (cobas® 4800 System Software) to perform real-time PCR for the detection of C. difficile DNA.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The very first sentence explicitly states: "The cobas® Cdiff Test on the cobas® 4800 system is an automated, qualitative in vitro diagnostic test..."
- Device Description: The description further clarifies that it "utilizes real-time polymerase chain reaction (PCR) for the detection of Clostridium difficile (C. difficile) DNA from unformed (liquid or soft) stool specimens to aid in the diagnosis of Clostridium difficile infections in humans." This describes a test performed on a biological sample (stool) outside of the body to provide diagnostic information.
- Performance Studies: The document details clinical and non-clinical performance evaluations, which are standard for IVD devices to demonstrate their accuracy and reliability for diagnostic purposes.
- Predicate Device(s): The mention of predicate devices (K130470; BD MAX™ Cdiff Assay, BD MAX™ Instrument) indicates that this device is being compared to other legally marketed IVD devices for the same intended use.
All of these points strongly confirm that the cobas® Cdiff Test is an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The cobas® Cdiff Test on the cobas® 4800 system is an automated, qualitative in vitro diagnostic test, that utilizes realtime polymerase chain reaction (PCR), for the direct detection of the toxin B (tcdB) gene of toxigenic Clostridium difficile (C. difficile) in unformed (liquid or soft) stool specimens obtained from patients suspected of having C. difficile infection (CDI). The cobas® Cdiff Test is intended for use as an aid in the diagnosis of CDI in humans in conjunction with clinical and epidemiological risk factors.
Product codes
OZN, OOI
Device Description
The Roche Molecular Systems (RMS) cobas® Cdiff Test utilizes real-time polymerase chain reaction (PCR) for the detection of Clostridium difficile (C. difficile) DNA from unformed (liquid or soft) stool specimens to aid in the diagnosis of Clostridium difficile infections in humans.
The cobas Cdiff Test contains two major processes: (1) automated sample preparation to extract nucleic acids from the unformed stool specimens; (2) PCR amplification of target DNA sequences using C. difficile specific primers, and real-time detection of cleaved fluorescentlabeled C. difficile specific oligonucleotide detection probes. An Internal Control (IC), containing unrelated randomized DNA sequence, is added to all samples prior to automated sample preparation and is amplified and detected simultaneously with each sample to monitor the entire process.
The cobas® Cdiff Test utilizes six reagent kits:
- cobas® 4800 Cdiff Amplification/Detection Kit
- cobas® 4800 Cdiff Controls and Cofactor Kit
- cobas® 4800 System Wash Buffer Kit
- cobas® 4800 System Lysis Kit 1
- cobas® 4800 System Internal Control Kit 1
- cobas 4800 System Sample Preparation Kit
Required but not provided:
cobas® PCR Media and Swab Sample Kit
Sealing mat or deep well plate cover
Caps, neutral color (for recapping post-run specimens)
The cobas® Cdiff Test utilizes real-time PCR technology to detect the conserved regions of toxin B (tcdB) gene. Fluorogenic target specific probes are used for the detection of the amplified C. difficile DNA as well as IC. Primer and probe oligonucleotide sequences were designed to select C. difficile conserved sequences without cross reacting with other organisms commonly found in stool specimens.
Sample preparation for the cobas Cdiff Test is automated with the use of the cobas x 480 instrument. Unformed stool specimens are transferred into cobas® PCR Media by using a swab. Organisms are lysed with chaotropic agent, proteinase K, and SDS reagents. Released nucleic acids, along with added Internal Control DNA, are bound by magnetic glass particles. They are washed and then eluted into a small volume of buffer. The instrument then takes an aliquot of the eluted material and sets up the PCR reaction with an activated Master Mix.
The PCR cycling steps and detection of target signal occurs in the cobas z 480 Analyzer. The Master Mix reagent contains primer pairs and probes for two targets: the C. difficile toxin B gene and Internal Control. If the target nucleic acid sequences are present, amplification with the corresponding primers will occur by a thermostable DNA polymerase, generating PCR products (amplicons). These products are detected by specific TagMan probes containing a fluorescent dye and a quencher. Normally, the quencher suppresses the fluorescence of the dye. However, if the PCR product is present, the probe hybridizes to the product and gets cleaved by the 5' to 3' nuclease activity of the polymerase. This reaction allows the fluorescence to be emitted from the dye, and the signal is recorded in real time during each PCR cycle by the cobas z 480 analyzer. The signal is interpreted by the cobas 4800 System Software and reported as final results.
The cobas 4800 System uses the cobas x 480 Instrument for sample preparation, and the cobas z 480 Analyzer for amplification and detection. Both the cobas x 480 Instrument and the cobas z 480 Analyzer are controlled by a computer workstation running the cobas® 4800 System Software.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
stool specimens
Indicated Patient Age Range
The clinical study involved subjects with a mean age of 56 years (range 3 to 99).
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
Analytical Sensitivity (Limit of Detection or LOD) Study:
- Sample Size: Not explicitly stated as a single number (multiple dilutions and strains). Each level was analyzed using 3 unique lots of C. difficile specific reagents. For inclusivity, 40 replicates were tested for each concentration level.
- Data Source: 7 toxigenic C. difficile strains (ATCC 43255 (VPI 10463), ATCC BAA-1382 (630), CDC 204118, R12087 (CD196), 2748-06, ATCC 43598 (1470), and F15) and 28 additional toxigenic strains. Quantified cultures were diluted into pooled negative stool specimen matrix.
- Annotation Protocol: LOD determined as the lowest concentration exhibiting at least 95% positive rate for which all higher concentrations were greater than or equal to 95% positive rate.
In-house precision study:
- Sample Size: 72 tests per panel member. Total of 72 positive panel members at LOD and above LOD concentrations.
- Data Source: C. difficile concentrations below LOD, near LOD and above LOD of the cobas® Cdiff Test including pooled negative stool specimen matrix.
- Annotation Protocol: Not explicitly described, but involved analyzing Ct values and percent positive rates.
Analytical Specificity Study:
- Sample Size: 131 organisms and human DNA tested.
- Data Source: Non-toxigenic C. difficile, other Clostridium genus species, human DNA, and other organisms commonly found in the digestive tract.
- Annotation Protocol: Compared cobas® Cdiff Test results for negative prediction. Also, computer based in-silico analysis for C. botulinum.
Interference Study:
- Sample Size: 29 substances tested.
- Data Source: Twenty six commonly used OTC products and antibiotic medicines, whole blood, mucin, and fecal fat.
- Annotation Protocol: C. difficile was spiked to ~3xLOD. Absence or presence of interference was observed for each substance.
Cross Contamination Study:
- Sample Size: 1 out of 423 negative samples exhibited a positive result in checkerboard runs; 282 negative samples in last run.
- Data Source: High titer C. difficile and negative samples.
- Annotation Protocol: High titer samples were prepared to generate a Ct of the 95 percentile of the clinical specimen population. Negative and positive samples were processed in a checkerboard configuration.
Reproducibility Study:
- Sample Size: 4 specimens, with 3 replicates each, for a total of 720 tests per panel member (4 specimens x 3 replicates x 3 sites x 2 operators/site x 5 days/lot x 2 lots).
- Data Source: Simulated clinical samples prepared by seeding pooled, C. difficile-negative, unformed stool in cobas PCR Media with varying concentrations of C. difficile strain ATCC 43255 (Negative, Below LOD, 1 x LOD, and 3 x LOD).
- Annotation Protocol: Not explicitly detailed but results included Ct values and percent agreement.
Clinical Performance Study:
- Sample Size: Specimens from 683 subjects. 682 specimens included in the statistical analysis for comparison with combined direct and enrichment culture.
- Data Source: Leftover, de-identified, unformed stool samples from subjects suspected of having CDI, collected at five geographically diverse sites across the US.
- Annotation Protocol: Toxigenic culture (direct, repeat direct, and enrichment culture followed by cytotoxicity testing) was used as the reference standard. Suspected colonies were identified by Gram stain, aerotolerance test, and Pro Disk test. Cytotoxicity testing performed using C. DIFFICILE TOX-B TEST, TECHLAB®. Discrepant analysis was performed using a second FDA-cleared nucleic acid amplification test (NAAT).
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Analytical Sensitivity (Limit of Detection or LOD)
- Study Type: Analytical study
- Sample Size: Not explicitly stated as a single number (multiple dilutions and strains were tested with 40 replicates each for inclusivity).
- Key Results: The claimed LOD among the seven initial strains tested was 225 CFU/swab based on 95% positive rate. The LOD for the 28 inclusivity strains varied, ranging from 77.9 to 460.
Precision
- Study Type: In-house precision study
- Sample Size: 72 tests per panel member for Level 0, Level 1, Level 2, and Level 3.
- Key Results: Overall CV (%) at LOD (Level 2) and above LOD (Level 3) were 1.5% and 1.1%, respectively. For concentration level at or around LOD, most variability of target Ct values is attributed to within run (random) and lot to lot factors (60.0% and 25.3%, respectively). For concentration level above LOD, most of the Ct value variability is attributed to within run (random) and instrument to instrument factors (72.5% and 24.7%, respectively).
Analytical Specificity
- Study Type: Analytical study (wet lab testing and in-silico analysis)
- Sample Size: 131 organisms and human DNA.
- Key Results: The cobas® Cdiff Test gave expected negative results in the presence of 131 organisms and human DNA. Computer based in-silico analysis indicated that any cross reactivity against C. botulinum is highly unlikely.
Interference
- Study Type: Analytical study
- Sample Size: 29 substances.
- Key Results: No interference was observed for OTC products and fecal fat. For whole blood and mucin, no interference was observed at 25% (w/v) and 25% (w/v) respectively, but 50% (v/v) of mucin exhibited interference.
Cross Contamination
- Study Type: Analytical study
- Sample Size: 423 negative samples (checkerboard runs), 282 negative samples (last runs).
- Key Results: 1 out of 423 negative samples exhibited a positive result (0.24% cross contamination rate). No carry-over run-to-run contamination observed (0.00%).
Reproducibility
- Study Type: Multi-site investigation with simulated clinical samples.
- Sample Size: 720 tests per panel member (4 specimens x 3 replicates x 3 sites x 2 operators/site x 5 days/lot x 2 lots). 712 valid results out of 720 performed.
- Key Results: The SD and CV (%) for Ct values across positive panel members ranged from 0.64 to 0.71 and 1.7 to 1.9%, respectively. The positive percent agreement for "Below LOD," "1 x LOD," and "3 x LOD" were 66.1% (95% CI: 58.7% to 73.0%), 100.0% (95% CI: 98.0% to 100.0%), and 100.0% (95% CI: 97.9% to 100.0%), respectively. The negative percent agreement for negative panel members was 100.0% (95% CI: 97.9% to 100.0%).
Clinical Performance
- Study Type: IRB-approved, prospective, multi-site investigation.
- Sample Size: 683 subjects; 682 specimens for statistical analysis (one sample lacked sufficient volume).
- Key Results (Comparison with combined direct and enrichment culture):
- Sensitivity: 92.9% (131/141; 95% CI: 87.4% to 96.1%)
- Specificity: 98.7% (534/541; 95% CI: 97.4% to 99.4%)
- PPV: 94.9% (95% CI: 89.9% to 97.5%)
- NPV: 98.2% (95% CI: 96.6% to 99.0%)
- Key Results (Comparison with direct culture):
- Positive Percent Agreement: 97.3% (110/113; 95% CI = 92.5% to 99.1%)
- Negative Percent Agreement: 94.9% (541/570; 95% CI = 92.8% to 96.4%)
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Clinical Performance (Comparison with combined direct and enrichment culture):
- Sensitivity: 92.9% (131/141; 95% CI: 87.4% to 96.1%)
- Specificity: 98.7% (534/541; 95% CI: 97.4% to 99.4%)
- PPV: 94.9% (95% CI: 89.9% to 97.5%)
- NPV: 98.2% (95% CI: 96.6% to 99.0%)
Clinical Performance (Comparison with direct culture):
- Positive Percent Agreement: 97.3% (110/113; 95% CI = 92.5% to 99.1%)
- Negative Percent Agreement: 94.9% (541/570; 95% CI = 92.8% to 96.4%)
Reproducibility:
- Positive percent agreement: "Below LOD," were 66.1% (95% CI: 58.7% to 73.0%); "1 x LOD," 100.0% (95% CI: 98.0% to 100.0%); "3 x LOD," 100.0% (95% CI: 97.9% to 100.0%)
- Negative percent agreement: 100.0% (95% CI: 97.9% to 100.0%)
Predicate Device(s)
BD MAX™ Cdiff Assay, BD MAX™ Instrument, K130470
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
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/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features the department's emblem, which is a stylized representation of a human figure in profile, repeated three times to symbolize life and growth. The emblem is encircled by the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002 December 7, 2015
ROCHE MOLECULAR SYSTEMS, INC. DAVID W. GATES. PH.D. SENIOR DIRECTOR, REGULATORY AFFAIRS 4300 HACIENDA DRIVE PLEASANTON CA 94588-2722
Re: K142422
Trade/Device Name: cobas Cdiff Test Regulation Number: 21 CFR 866.3130 Regulation Name: Clostridium difficile Toxin Gene Amplification Assay Regulatory Class: II Product Code: OZN, OOI Dated: April 16, 2015 Received: April 17, 2015
Dear Dr. Gates:
This letter corrects our substantially equivalent letter of May 20, 2015.
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 Parts 801 and 809); medical device reporting (reporting of
1
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.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 8091 ), please contact the Division of Industry and Consumer Education 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. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/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 Industry and Consumer Education 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 yours,
Ribhi Shawar -S
Uwe Scherf, M.Sc., Ph.D. For Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K142422
Device Name cobas® Cdiff Test
Indications for Use (Describe)
The cobas® Cdiff Test on the cobas® 4800 system is an automated, qualitative in vitro diagnostic test, that utilizes realtime polymerase chain reaction (PCR), for the direct detection of the toxin B (tcdB) gene of toxigenic Clostridium difficile (C. difficile) in unformed (liquid or soft) stool specimens obtained from patients suspected of having C. difficile infection (CDI). The cobas® Cdiff Test is intended for use as an aid in the diagnosis of CDI in humans in conjunction with clinical and epidemiological risk factors.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
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3
510(k) Summary
| Submitter Name | Roche Molecular Systems, Inc. |
|---|---|
| Address | 4300 Hacienda Drive |
| Pleasanton, CA 94588-2722 | |
| Contact | David Gates |
| Phone: (925) 730-8237 | |
| FAX: (925) 225-0207 | |
| Date Prepared | April 16, 2015 |
| Proprietary Name | cobas® Cdiff Test |
| Common Name | Clostridium difficile Test |
| Classification Name | 21 CFR 866.3130 - Clostridium difficile toxin gene amplification assay |
| 21 CFR 862.2570 - Real Time Nucleic Acid Amplification System | |
| Product Codes | OZN, OOI |
| Predicate Devices | BD MAX™ Cdiff Assay, BD MAX™ Instrument, K130470 |
| Establishment Registration | Branchburg: 2243471 |
| Pleasanton: 3004141078 | |
| Indianapolis: 1823260 |
4
1. DEVICE DESCRIPTION
The Roche Molecular Systems (RMS) cobas® Cdiff Test utilizes real-time polymerase chain reaction (PCR) for the detection of Clostridium difficile (C. difficile) DNA from unformed (liquid or soft) stool specimens to aid in the diagnosis of Clostridium difficile infections in humans.
The cobas Cdiff Test contains two major processes: (1) automated sample preparation to extract nucleic acids from the unformed stool specimens; (2) PCR amplification of target DNA sequences using C. difficile specific primers, and real-time detection of cleaved fluorescentlabeled C. difficile specific oligonucleotide detection probes. An Internal Control (IC), containing unrelated randomized DNA sequence, is added to all samples prior to automated sample preparation and is amplified and detected simultaneously with each sample to monitor the entire process.
The cobas® Cdiff Test utilizes six reagent kits:
-
- cobas® 4800 Cdiff Amplification/Detection Kit
-
- cobas® 4800 Cdiff Controls and Cofactor Kit
-
- cobas® 4800 System Wash Buffer Kit
-
- cobas® 4800 System Lysis Kit 1
-
- cobas® 4800 System Internal Control Kit 1
-
- cobas 4800 System Sample Preparation Kit
Required but not provided:
cobas® PCR Media and Swab Sample Kit
Sealing mat or deep well plate cover
Caps, neutral color (for recapping post-run specimens)
1.1. Target Selection
The cobas® Cdiff Test utilizes real-time PCR technology to detect the conserved regions of toxin B (tcdB) gene. Fluorogenic target specific probes are used for the detection of the amplified C.
5
difficile DNA as well as IC. Primer and probe oligonucleotide sequences were designed to select C. difficile conserved sequences without cross reacting with other organisms commonly found in stool specimens.
1.2. Test Principle
Sample Preparation 1.1.1.
Sample preparation for the cobas Cdiff Test is automated with the use of the cobas x 480 instrument. Unformed stool specimens are transferred into cobas® PCR Media by using a swab. Organisms are lysed with chaotropic agent, proteinase K, and SDS reagents. Released nucleic acids, along with added Internal Control DNA, are bound by magnetic glass particles. They are washed and then eluted into a small volume of buffer. The instrument then takes an aliquot of the eluted material and sets up the PCR reaction with an activated Master Mix.
Note: The cobas® Cdiff Test has been validated for use with the cobas® PCR Media and Swab Sample Kit. Do not use other devices or media types.
PCR Amplification and TaqMan® Detection 1.1.2.
The PCR cycling steps and detection of target signal occurs in the cobas z 480 Analyzer. The Master Mix reagent contains primer pairs and probes for two targets: the C. difficile toxin B gene and Internal Control. If the target nucleic acid sequences are present, amplification with the corresponding primers will occur by a thermostable DNA polymerase, generating PCR products (amplicons). These products are detected by specific TagMan probes containing a fluorescent dye and a quencher. Normally, the quencher suppresses the fluorescence of the dye. However, if the PCR product is present, the probe hybridizes to the product and gets cleaved by the 5' to 3' nuclease activity of the polymerase. This reaction allows the fluorescence to be emitted from the dye, and the signal is recorded in real time during each PCR cycle by the cobas z 480 analyzer. The signal is interpreted by the cobas 4800 System Software and reported as final results.
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cobas® 4800 System Description 1.3.
The cobas 4800 System uses the cobas x 480 Instrument for sample preparation, and the cobas z 480 Analyzer for amplification and detection. Both the cobas x 480 Instrument and the cobas z 480 Analyzer are controlled by a computer workstation running the cobas® 4800 System Software.
The system hardware is unchanged from that originally approved for IVD use in PMA P100020 (cobas® HPV Test, April 19, 2011). The software version has been updated to software release 2.1 in order to support the expanded test menu. The updated software was cleared for other currently available tests on the cobas 4800 System per Special 510(K) 140887.
2. INTENDED FOR USE
The cobas® Cdiff Test on the cobas® 4800 System is an automated, qualitative in vitro diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the direct detection of the toxin B (tcdB) gene of toxigenic Clostridium difficile (C. difficile) in unformed (liquid or soft) stool specimens obtained from patients suspected of having C. difficile infection (CDI). The cobas " Cdiff Test is intended for use as an aid in the diagnosis of CDI in humans in conjunction with clinical and epidemiological risk factors.
3. TECHNOLOGICAL CHARACTERISTICS
The primary technological characteristics and intended use of the RMS cobas® Cdiff Test are substantially equivalent to other legally marketed nucleic acid amplification tests intended for the qualitative detection of toxigenic Clostridium difficile.
As indicated in Table 1, the RMS cobas® Cdiff Test is substantially equivalent to technological characteristics of the predicate device. Both assays have the same intended use, and utilize nucleic acid amplification and detection technology for the detection of C. difficile DNA in patient specimens.
Formatted: Font color: Blue Deleted: Table 1
7
| | Submitted Device:
RMS cobas® Cdiff Test | Predicate Device:
BD MAX™ Cdiff Assay, K130470 |
|------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The cobas® Cdiff Test on the cobas®
4800 system is an automated, qualitative
in vitro diagnostic test, that utilizes real-
time polymerase chain reaction (PCR), for
the direct detection of the toxin B (tcdB)
gene of toxigenic Clostridium difficile in
unformed (liquid or soft) stool specimens
obtained from patients suspected of
having C. difficile infection (CDI). The
cobas® Cdiff Test is intended for use as
an aid in the diagnosis of CDI in humans
in conjunction with clinical and
epidemiological risk factors. | The BD MAX™ Cdiff Assay performed on
the BD MAX™ System is an automated in
vitro diagnostic test for the direct,
qualitative detection of the Clostridium
difficile toxin B gene (tcdB) in human liquid
or soft stool specimens from patients
suspected of having C. difficile infection
(CDI). The test, performed directly on the
specimen, utilizes real-time polymerase
chain reaction (PCR) for the amplification
of C. difficile toxin B gene DNA and
fluorogenic target-specific hybridization
probes for the detection of the amplified
DNA. The BD MAX™ Cdiff Assay is
intended to aid in the diagnosis of CDI. |
| Conditions for use | For prescription use | Same |
| Sample Types | Liquid and soft stool specimens | Same |
| Subject Status | Symptomatic | Same |
| Sample Collection Devices | cobas® PCR Media and Swab Sample Kit | BD MAX™ Cdiff Sample Buffer |
| Analyte Targets | Toxin B (tcdB) gene | Same |
| Sample Preparation Procedure | Automated by cobas® x480 | Automated by BD MAX™ System |
| Amplification Technology | Real-time PCR | Same |
| Detection Chemistry | Paired reporter and quencher
fluorescence labeled probes (TaqMan
Technology) using fluorescence
resonance energy transfer (FRET) | Same |
| Controls used | Sample processing control (IC)
Positive and negative control | Sample processing control
Positive and negative control (optional) |
| Result Analysis | Based on PCR cycle threshold analysis | Same |
Similarities and Differences between the cobas® Cdiff Test Table 1: and the Predicate Device
In summary, the intended use, technology, and characteristics of the cobas® Cdiff Test as compared to the predicate device do not raise any new types of safety or effectiveness questions and are substantially equivalent.
8
NON-CLINICAL PERFORMANCE EVALUATION 4.
Analytical Sensitivity 4.1.
The analytical sensitivity (Limit of Detection or LOD) for the cobas® Cdiff Test was determined by analyzing 7 toxigenic C. difficile strains ATCC 43255 (VPI 10463), ATCC BAA-1382 (630), CDC 204118, R12087 (CD196), 2748-06, ATCC 43598 (1470), and F15. CDC 204118 and R12087 (CD196) are BI/ NAP1/027 hyper-virulent epidemic strains. Quantified cultures were diluted into pooled negative stool specimen matrix to determine the LOD. All levels were analyzed using cobas® Cdiff Test with 3 unique lots of C. difficile specific reagents. The LOD of the test was determined as the lowest concentration exhibiting at least 95% positive rate for which all higher concentrations were greater than or equal to 95% positive rate.
The highest LOD among 3 reagent lots are shown in Table 2. The claimed LOD among the seven strains tested was 225 CFU/swab based on 95% positive rate.
Formatted: Font color: Blue Deleted: Table 3
Deleted: 3
| | Strain ID | Toxinotype | REA*
Type | PFG†
Type | Ribotype | Phenotype | LOD (CFU/swab) | |
|--|---------------------------|------------|--------------|--------------|----------|-----------|------------------------|-----------------------------------|
| | | | | | | | By
Positive
Rate | By Probit
Analysis
(95% CI) |
| | ATCC 43255 (VPI
10463) | 0 | N/A | N/A | 087 | A+B+CDT- | 113 | 90 (66 – 311) |
| | ATCC BAA-1382 (630) | 0 | R 23 | N/A | 012 | A+B+CDT- | 81 | 83 (62 – 145) |
NAP1
NAP1
N/A
N/A
N/A
027
027
078
017
N/A
A+B+CDT+
A+B+CDT+
N/A
A-B+
N/A
54
54
54
225
54
BI 8
Bl
N/A
N/A
N/A
- Restriction endonuclease analysis; 1 Pulse Field Gel
=
111