(87 days)
K110203, CR240176
No
The description focuses on automated real-time PCR and the instrument system's hardware and software for running tests and viewing results. There is no mention of AI or ML algorithms for data analysis or interpretation.
No.
The device is an in vitro diagnostic test intended as an aid in the diagnosis of C. difficile infection by detecting specific gene sequences. It does not provide treatment or direct therapy.
Yes
The "Intended Use / Indications for Use" section explicitly states, "The Xpert® C. difficile/Epi test is an aid in the diagnosis of CDI." The "Device Description" also mentions it is an "automated in vitro diagnostic test."
No
The device is an in vitro diagnostic test that requires a specific hardware platform (GeneXpert® Instrument Systems) and single-use disposable cartridges to perform sample preparation, amplification, and detection. While it includes software for running tests and viewing results, it is fundamentally a hardware-dependent system, not a software-only medical device.
Based on the provided text, here's the analysis to determine if the device is an IVD:
Key indicators that this device is an IVD:
- Explicitly stated in the Intended Use/Indications for Use: The very first sentence states, "The Xpert® C. difficile/Epi test is a qualitative in vitro diagnostic test..."
- Explicitly stated in the Device Description: The first sentence of the Device Description also states, "The Xpert C. difficile/Epi test is an automated in vitro diagnostic test..."
- Intended Use: The test is intended "as an aid in the diagnosis of CDI." This is a clear diagnostic purpose.
- Specimen Type: The test is performed on "unformed (liquid or soft) stool specimens," which are biological specimens collected from the human body.
- Detection of Biomarkers: The test detects "toxin B gene sequences," "binary toxin (CDT) gene sequences," and a "single base pair deletion at nucleotide 117 in the tcdC gene," which are specific genetic markers associated with C. difficile.
- Performed on an Instrument System: The test is performed on the "GeneXpert® Instrument Systems," which are laboratory instruments designed for diagnostic testing.
- Utilizes Automated Real-Time PCR: PCR is a common technique used in in vitro diagnostic testing to amplify and detect specific DNA sequences.
- Includes Controls: The test includes an "internal sample processing control (SPC)" and a "Probe Check Control (PCC)," which are standard components of IVD tests to ensure proper performance and validity of results.
- Comparison to Predicate Device: A predicate device (K212427; cobas® Cdiff Nucleic acid test) is listed, which is also a nucleic acid test for C. difficile, further indicating the device's diagnostic nature.
Conclusion:
Yes, this device is an IVD (In Vitro Diagnostic). The text explicitly states this multiple times and provides numerous details about its intended use, specimen type, technology, and components that are characteristic of an in vitro diagnostic device.
N/A
Intended Use / Indications for Use
The Xpert® C. difficile/Epi test is a qualitative in vitro diagnostic test for detection of toxin B gene sequences and for presumptive identification of 027/NAP1/BI strains of toxigenic Clostridioides difficile from unformed (liquid or soft) stool specimens collected from patients suspected of having C. difficile infection (CDI). Presumptive identification of 027/NAP1/BI strains of C. difficile is by detection of binary toxin (CDT) gene sequences and the single base pair deletion at nucleotide 117 in the tcdC gene. The tcdC gene encodes for a negative regulator in C. difficile toxin production. The test is performed on the GeneXpert® Instrument Systems and utilizes automated real-time polymerase chain reaction (PCR) to detect toxin gene sequences associated with toxin producing C. difficile. The Xpert® C. difficile/Epi test is intended as an aid in the diagnosis of CDI. Detection of 027/NAP1/Bl strains of C. difficile by the Xpert® C. difficile/Evi test is presumptive and is solely for enidemiological purposes and is not intended to guide or monitor treatment for C. difficile infections. Concomitant culture is necessary only if further typing or organism recovery is required.
Product codes
OZN, OOI
Device Description
The Xpert C. difficile/Epi test is an automated in vitro diagnostic test for qualitative detection of toxin producing Clostridioides difficile (formerly known as Clostridium difficile) directly from unformed (liquid or soft) stool specimens of patients suspected of having Clostridioides difficile infection (CDI). The test detects the toxin B gene (tcdB), the binary toxin (CDT) gene, and the single base pair deletion at nucleotide 117 (tcdCΔ117) within the gene encoding TcdC, a negative regulator of toxin production. The combined presence of the genes encoding toxin B and binary toxin and the tcdCA117 deletion has been associated with a hypervirulent C. difficile strain known as 027/NAP1/BI, which has been associated with severe disease outbreaks in healthcare facilities worldwide. The test is performed on the GeneXpert® Instrument Systems (comprised of the GeneXpert® Dx System. GeneXpert® System with Touchscreen, and GeneXpert® Infinity System). In the GeneXpert® Instrument Systems, sample preparation, amplification, and real-time detection are all fully automated and completely integrated. The single-use disposable Xpert C. difficile/Evi cartridge, required by the platform for use, holds the PCR reagents and hosts the PCR process. Because the cartridge is self-contained, cross-contamination between samples is minimized. The Xpert C. difficile/Epi test includes reagents for the detection of toxigenic C. difficile and the detection of sequences for presumptive identification of 027/NAP 1/BI strains. In addition, the test reagents include an internal sample processing control (SPC) to ensure adequate processing of the target bacteria and to monitor the presence of inhibitor(s) in the PCR Assay. The SPC also ensures that the PCR conditions (temperature and time) are appropriate for the amplification reaction and that the PCR reagents are functional. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability. The Xpert C. difficile/Evi test system performs sample preparation and real-time, multiplex polymerase chain reaction (PCR) for detection of target-specific DNA. A swab is inserted into the stool specimen and then placed in a tube containing Sample Reagent. Following brief vortexing, the content of the Sample Reagent is transferred to the Sample Chamber of the disposable fluidic cartridge (the Xpert C. difficile/Epi cartridge). The user initiates a test from the system user interface of the GeneXpert® Instrument Systems and places the cartridge with sample into a GeneXpert® instrument system which performs hands-off real-time PCR for detection of C. difficile DNA. Depending on the specific instrument, a GeneXpert® instrument system may contain 1-80 modules, each of which are randomly accessible and capable of performing separate sample preparation and real-time PCR tests for the detection of gene sequences for C. difficile toxin B and binary toxin and the tcdCA117 deletion in less than 45 minutes. Each module contains a syringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE® thermocycler for performing real-time PCR and detection. Each instrument in the GeneXpert® instrument family is equipped with a Windows OS-based personal computer that is preloaded with software applications for running the tests and viewing the results.
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
Not Found
Intended User / Care Setting
Trained users
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
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Prepared Cartridge Hold Time Study: Hold time refers to the duration between the preparation of the cartridge (i.e., addition of processed specimen to the cartridge) and the initiation of the Xpert C. difficile/Epi test. A prepared cartridge hold time study was conducted using contrived positive (C. difficile cells added to negative matrix) and negative (negative matrix only) samples held for various times under three (3) hold environments, i.e., at ambient (22°C), elevated (25°C) with high humidity, or high (35°C) temperatures. The maximum acceptable hold time for a prepared cartridge was verified as 4 hours under all environments.
Functional Testing: Functional testing was conducted using both contrived positive (C. difficile cells added to negative matrix) and negative (negative matrix only) samples to evaluate differences (if any) in the performance of the Xpert C. difficile/Epi test on the previously cleared GeneXpert® Dx System and the GeneXpert® Infinity System, running respectively under systems software GeneXpert® Dx (v6.5) and GeneXpert® Xpertise (v6.8 or v7.1). The study results showed 100% agreement with the expected results, with no statistically significant differences in Ct values observed among test runs in all instrument/software combinations. This study demonstrated equivalent performance of the Xpert C. difficile/Epi test when performed on any member of the GeneXpert® Instrument Systems family of instruments.
Inclusivity Study: A study to determine the Analytical Reactivity (Inclusivity) of the Xpert C. difficile/Epi test was previously conducted in support of K110203 with C. difficile strains selected to broadly represent the majority of C. difficile toxinotypes encountered in practice. This study utilized eighteen (18) toxigenic C. difficile strains representing toxinotype 0 and other variant toxinotypes, including 027/NAP1/BI toxinotype III isolates. With the current submission (K243730), to comply with the requirements of FDA's Class II Special Controls Guideline document "Toxin Gene Amplification Assays for the Detection of Clostridium difficile" (issued on August 27, 2015) as appropriate for this Class II device under regulation 21 CFR §866.3130, a supplemental inclusivity study was conducted with Xpert C. difficile/Epi test using another eight (8) C. difficile strains. Overall, the inclusivity study results showed that Xpert C. difficile/Epi test met the requirements of the Class II Special Controls and accurately identified all strains of toxigenic C. difficile tested, thereby demonstrating an inclusivity rate of 100% for the Xpert C. difficile/Epi test.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s)
Reference Device(s)
K110203, CR240176
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
N/A
0
February 28, 2025
Image /page/0/Picture/1 description: The image contains the logos of the Department of Health and Human Services and the U.S. Food and Drug Administration (FDA). The Department of Health and Human Services logo is on the left, and the FDA logo is on the right. The FDA logo includes the FDA acronym in a blue square, followed by the words "U.S. Food & Drug Administration" in blue text.
Cepheid Samir Ghevariya Regulatory Affairs Principal 904 Caribbean Drive Sunnyvale, California 94089
Re: K243730
| Trade/Device Name: | Xpert C. difficile/Epi |
|---|---|
| Regulation Number: | 21 CFR 866.3130 |
| Regulation Name: | Clostridium Difficile Toxin Gene Amplification Assay |
| Regulatory Class: | Class II |
| Product Code: | OZN, OOI |
| Dated: | December 3, 2024 |
| Received: | December 3, 2024 |
Dear Samir Ghevariva:
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 (the 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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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, §800-898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
Your device is also subject to, among other requirements, the Quality System (OS) regulation (21 CFR $820), which includes, but is not limited to, 21 CFR §820.30, Design controls; 21 CFR §820.90, Nonconforming product; and 21 CFR 8820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review
1
and approve changes to device design and production (21 CFR §820.70 and 21 CFR §820.70) and document changes and approvals in the device master record (21 CFR §820.181).
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 $801 and $809); medical device reporting (reporting of medical device-related adverse events) (21 CFR $803) for devices or postmarketing safety reporting (21 CFR §4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR §820) for devices or current good manufacturing practices (21 CFR Part A ) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR §801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR §801.18. The UDI Rule (21 CFR §830.300(a) and §830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR 8830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR $807.97). For questions regarding of adverse events under the MDR regulation (21 CFR $803), please go to https://www.fda.gov/medical-devices/medical-device-safety/medical-device-reporting-mdrhow-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Ribhi Shawar -S
Ribhi Shawar, PhD (ABMM) Branch Chief General Bacteriology and Antimicrobial Susceptibility Branch DMD: Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics OPEQ: Office of Product Evaluation and Quality CDRH: Center for Devices and Radiological Health
2
Indications for Use
510(k) Number (if known) K243730
Device Name
Xpert® C. difficile/Epi
Indications for Use (Describe)
The Xpert® C. difficile/Epi test is a qualitative in vitro diagnostic test for detection of toxin B gene sequences and for presumptive identification of 027/NAP1/BI strains of toxigenic Clostridioides difficile from unformed (liquid or soft) stool specimens collected from patients suspected of having C. difficile infection of 027/NAP 1/B1 strains of C. difficile is by detection of binary toxin (CDT) gene sequences and the single base par deletion at nucleotide 117 in the tedC gene. The tedC gene encodes for a negative regulator in C. difficile toxin production. The test is performed on the GeneXpert® Instrument Systems and utilizes automated real-time polymerase chain reaction (PCR) to detect toxin gene sequences associated with toxin producing C. difficile. The Xpert C. difficile/Evi test is intended as an aid in the diagnosis of CDI. Detection of C. difficile by the Xpert C. difficile/Epi test is presumptive and is solely for epidemiological purposes and is not intended to guide or monitor treatment for C. difficile infections. Concomitant culture is necessary only if further typing or organism recovery is required.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| X Prescription Use (Part 21 CFR 801 Subpart D) | ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
3
Image /page/3/Picture/0 description: The image shows the Cepheid logo. The logo consists of a blue graphic element resembling stylized wings or feathers on the left. To the right of the graphic is the word "Cepheid" in a sans-serif font, also in blue. A small circle is present to the right of the word.
510(k) Summary for Xpert® C. difficile/Epi
4
Image /page/4/Picture/0 description: The image shows the Cepheid logo. The logo consists of a blue graphic element on the left and the word "Cepheid" in black font on the right. The graphic element is a stylized representation of three curved lines, resembling a wing or a comet tail.
TABLE OF CONTENTS
| 1 | 510(K) SUMMARY | |
|---|---|---|
| 1.1 DEVICE DESCRIPTION | ||
| 1.2 DEVICE INTENDED USE | ||
| 1.3 TECHNICAL CHARACTERISTICS | ||
| 1.4 SUBSTANTIAL EQUIVALENCE……………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………… | ||
| 1.5 SUMMARY OF PERFORMANCE DATA | ||
| 1.6 CONCLUSION |
5
Image /page/5/Picture/0 description: The image shows the Cepheid logo. The logo consists of a blue graphic element resembling stylized wings or feathers on the left. To the right of the graphic is the word "Cepheid" in a dark blue, sans-serif font, with a small registration mark next to the 'd'.
1 510(k) Summary
As required by 21 CFR Section §807.92
| Submitted by: | Cepheid
904 Caribbean Drive
Sunnyvale, CA 90489
Phone number: (408) 541-4191 |
|--------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact:
Date of Preparation: | Samir Ghevariya, Regulatory Affairs Principal
February 5, 2025 |
| Device:
Trade name: | Xpert® C. difficile/Epi |
| Common name: | Xpert C. difficile/Epi test |
| Type of Test: | Qualitative Nucleic Acid Amplification Test for C. difficile toxin
B and binary toxin gene sequences and the single base pair
deletion at nucleotide 117 in tcdC from unformed stool
specimens. |
| Classification: | Class II |
| Classification name: | Clostridium difficile toxin gene amplification assay |
| Product code: | OZN, OOI |
| Regulation number: | 21 CFR §866.3130 |
| Classification | Microbiology |
| Advisory Panel:
Prescription Use: | Yes |
| Predicate Device: | cobas® Cdiff Nucleic acid test for use on the cobas® Liat® System
(K212427) |
1.1 Device Description
The Xpert C. difficile/Epi test is an automated in vitro diagnostic test for qualitative detection of toxin producing Clostridioides difficile (formerly known as Clostridium difficile) directly from unformed (liquid or soft) stool specimens of patients suspected of having Clostridioides difficile infection (CDI). The test detects the toxin B gene (tcdB), the binary toxin (CDT) gene, and the single base pair deletion at nucleotide 117 (tcdCΔ117) within the gene encoding TcdC, a negative regulator of toxin production. The combined presence of the genes encoding toxin B and binary toxin and the tcdCA117 deletion has been associated with a hypervirulent C. difficile
6
Image /page/6/Picture/0 description: The image shows the logo for Cepheid. The logo consists of a blue, stylized wing-like design on the left, followed by the word "Cepheid" in a simple, sans-serif font. A small circle is present to the right of the word.
strain known as 027/NAP1/BI, which has been associated with severe disease outbreaks in healthcare facilities worldwide.
The test is performed on the GeneXpert® Instrument Systems (comprised of the GeneXpert® Dx System. GeneXpert® System with Touchscreen, and GeneXpert® Infinity System). In the GeneXpert® Instrument Systems, sample preparation, amplification, and real-time detection are all fully automated and completely integrated. The single-use disposable Xpert C. difficile/Evi cartridge, required by the platform for use, holds the PCR reagents and hosts the PCR process. Because the cartridge is self-contained, cross-contamination between samples is minimized.
The Xpert C. difficile/Epi test includes reagents for the detection of toxigenic C. difficile and the detection of sequences for presumptive identification of 027/NAP 1/BI strains. In addition, the test reagents include an internal sample processing control (SPC) to ensure adequate processing of the target bacteria and to monitor the presence of inhibitor(s) in the PCR Assay. The SPC also ensures that the PCR conditions (temperature and time) are appropriate for the amplification reaction and that the PCR reagents are functional. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.
The Xpert C. difficile/Evi test system performs sample preparation and real-time, multiplex polymerase chain reaction (PCR) for detection of target-specific DNA. A swab is inserted into the stool specimen and then placed in a tube containing Sample Reagent. Following brief vortexing, the content of the Sample Reagent is transferred to the Sample Chamber of the disposable fluidic cartridge (the Xpert C. difficile/Epi cartridge). The user initiates a test from the system user interface of the GeneXpert® Instrument Systems and places the cartridge with sample into a GeneXpert® instrument system which performs hands-off real-time PCR for detection of C. difficile DNA.
Depending on the specific instrument, a GeneXpert® instrument system may contain 1-80 modules, each of which are randomly accessible and capable of performing separate sample preparation and real-time PCR tests for the detection of gene sequences for C. difficile toxin B and binary toxin and the tcdCA117 deletion in less than 45 minutes. Each module contains a syringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE® thermocycler for performing real-time PCR and detection.
Each instrument in the GeneXpert® instrument family is equipped with a Windows OS-based personal computer that is preloaded with software applications for running the tests and viewing the results, as described in Table 1.
7
Image /page/7/Picture/0 description: The image shows the Cepheid logo. The logo consists of a stylized blue wing-like graphic on the left, followed by the word "Cepheid" in black, lowercase letters. A small trademark symbol is located to the right of the word.
| Instrument Family | Instrument Family
Members | System Software | GeneXpert Instruments |
|----------------------------------|---------------------------------------|-----------------------|----------------------------------------------|
| GeneXpert®
Instrument Systems | GeneXpert® Dx
System | GeneXpert Dx | GX-I† GX-II GX-IV GX-XVI |
| | GeneXpert® System
with Touchscreen | Cepheid OS | GX-II GX-IV GX-XVI |
| | GeneXpert® Infinity
System | GeneXpert
Xpertise | GeneXpert Infinity-48s GeneXpert Infinity-80 |
Table 1: Instrument Systems and Software in the GeneXpert® Instrument Family Members
- No longer manufactured but is in circulation in the market.
1.2 Intended Use
The Xpert® C. difficile/Epi test is a qualitative in vitro diagnostic test for detection of toxin B gene sequences and for presumptive identification of 027/NAP1/BI strains of toxigenic Clostridioides difficile from unformed (liguid or soft) stool specimens collected from patients suspected of having C. difficile infection (CDI). Presumptive identification of 027/NAP1/BI strains of C. difficile is by detection of binary toxin (CDT) gene sequences and the single base pair deletion at nucleotide 117 in the tcdC gene. The tcdC gene encodes for a negative regulator in C. difficile toxin production. The test is performed on the GeneXpert® Instrument Systems and utilizes automated real-time polymerase chain reaction (PCR) to detect toxin gene sequences associated with toxin producing C. difficile. The Xpert® C. difficile/Epi test is intended as an aid in the diagnosis of CDI. Detection of 027/NAP1/Bl strains of C. difficile by the Xpert® C. difficile/Evi test is presumptive and is solely for enidemiological purposes and is not intended to guide or monitor treatment for C. difficile infections. Concomitant culture is necessary only if further typing or organism recovery is required.
1.3 Technical Characteristics
The Xpert C. difficile/Epi test has similar technological characteristics to those of the predicate device. Briefly, Xpert C. difficile/Epi test is an in vitro qualitative nucleic acid (DNA) amplification test using real time polymerase chain reaction (PCR) that utilizes primers and TaqMan probes specific for toxigenic C. difficile toxin genes with fluorogenic target-specific hybridization.
1.4 Substantial Equivalence
The purpose of this 510(k) submission is to obtain a substantial equivalence determination for Cepheid's Xpert C. difficile/Epi test for use with Cepheid-manufactured GeneXpert® Instrument Systems family of instruments (see Table 1 above) and to update device labeling to reflect the inclusion of a member of the GeneXpert® Instrument Systems family-mamely, the GeneXpert® Infinity System, along with systems software (GeneXpert Xpertise)-in addition to other instrument members of the same family, which were previously cleared for use with or added to
8
Image /page/8/Picture/0 description: The image shows the logo for Cepheid. The logo consists of a stylized blue wing-like design above the word "Cepheid" in black font. There is a period after the word Cepheid.
the Xpert C. difficile/Epi test, namely, the GeneXpert® Dx System (K110203) and the GeneXpert® System with Touchscreen (CR240176).
For the determination of substantial equivalence with the legally marketed predicate device, cobas® Cdiff nucleic acid test for use on the cobas® Liat® System (K212427), the similarities and differences between the Xpert C. difficile/Epi test and predicate are noted, respectively, in Table 2 and Table 3. The Intended Use and the technological characteristics of the Xpert C. difficile/Epi test and the predicate device are equivalent, and the noted differences between the candidate and predicate devices do not raise new or different questions of safety and effectiveness.
| Similarities | ||
|---|---|---|
| Candidate Device (K243730) | Predicate (K212427) | |
| Attribute | Xpert® C. difficile/Epi | cobas® Cdiff Nucleic Acid Test for |
| use on the cobas® Liat® System | ||
| Device class | Same | Class II |
| Product code | Same | OZN ( C. difficile toxin gene |
| amplification assay) | ||
| OOI (Real Time Nucleic Acid | ||
| Amplification System) | ||
| Regulation | Same | 21 CFR §866.3130 |
| (Clostridium difficile toxin gene | ||
| amplification assay) | ||
| Intended Use | The Xpert® C. difficile/Epi test is a qualitative in vitro | |
| diagnostic test for detection of toxin B gene sequences | ||
| and for presumptive identification of 027/NAP1/BI | ||
| strains of toxigenic Clostridioides difficile from | ||
| unformed (liquid or soft) stool specimens collected | ||
| from patients suspected of having C. difficile infection | ||
| (CDI). Presumptive identification of 027/NAP1/BI | ||
| strains of C. difficile is by detection of binary toxin | ||
| (CDT) gene sequences and the single base pair | ||
| deletion at nucleotide 117 in the tcdC gene. The tcdC | ||
| gene encodes for a negative regulator in C. difficile | ||
| toxin production. The test is performed on the | ||
| GeneXpert® Instrument Systems and utilizes | ||
| automated real-time polymerase chain reaction (PCR) | ||
| to detect toxin gene sequences associated with toxin | ||
| producing C. difficile . The Xpert® C. difficile/Epi test | ||
| is intended as an aid in the diagnosis of CDI. | ||
| Detection of 027/NAP1/BI strains of C. difficile by | ||
| the Xpert® C. difficile/Epi test is presumptive and is | ||
| solely for epidemiological purposes and is not | ||
| intended to guide or monitor treatment for C. difficile | ||
| infections. Concomitant culture is necessary only if | ||
| further typing or organism recovery is required. | The cobas® Cdiff Nucleic acid test for | |
| use on the cobas® Liat® System is an | ||
| automated, qualitative in vitro | ||
| diagnostic test that uses real-time | ||
| polymerase chain reaction (PCR) for | ||
| the detection of the toxin B ( tcdB ) | ||
| gene of toxigenic Clostridioides | ||
| difficile ( C. difficile ) in unformed | ||
| (liquid or soft) stool specimens | ||
| obtained from patients suspected of | ||
| having C. difficile infection (CDI). | ||
| The cobas® Cdiff Nucleic acid test for | ||
| use on the cobas® Liat® System is | ||
| intended for use as an aid in the | ||
| diagnosis of CDI in humans in | ||
| conjunction with clinical and | ||
| epidemiological risk factors. | ||
| Specimen | Same | Unformed (liquid or soft) stool |
Table 2. Similarities between Xpert C. difficile/Epi and Predicate
9
Image /page/9/Picture/0 description: The image shows the logo for Cepheid. The logo consists of a blue graphic on the left and the word "Cepheid." on the right. The graphic is a stylized representation of three curved lines, resembling a wing or a stylized letter C.
Traditional 510(k) Submission
| Similarities | ||
|---|---|---|
| Attribute | Candidate Device (K243730) | Predicate (K212427) |
| Xpert® C. difficile/Epi | cobas® Cdiff Nucleic Acid Test for use on the cobas® Liat® System | |
| Test Technology | Same | Real time PCR |
| Detection Technique | Same | Multiplex assay using different reporter dyes for each target |
| Test Automation | Same | Fully automated DNA extraction, detection, and results interpretation |
| Test Format | Same | Disposable single-use, multi-chambered, fluidic cartridge |
| Intended Use Environment | Same | Trained users |
| Test Access | Same | Prescription use only |
Table 3. Differences between Xpert C. difficile/Epi and Predicate
| Differences | ||
|---|---|---|
| Attribute | Candidate Device | Predicate (K212427) |
| Xpert® C. difficile/Epi | cobas® Cdiff Nucleic Acid Test for use on the | |
| cobas® Liat® System | ||
| Purpose of Use | Detection of toxin B gene sequences and | |
| presumptive identification of 027/NAP1/BI | ||
| strains of toxigenic Clostridioides difficile | Detection of toxin B gene sequences of | |
| toxigenic Clostridioides difficile | ||
| DNA Target | ||
| Sequence | toxin B gene | |
| ● binary toxin gene | ||
| ● tcdC gene by deletion of nucleotide 117 | ||
| (tcdC△117) | ● toxin B gene | |
| Internal | ||
| Controls | ● Sample Processing Control (SPC) | |
| ● Probe Check Control (PCC) | ● A gram-positive Bacillus thuringiensis | |
| israelensis bacterial organism to monitor | ||
| the full process of cobas® Liat® Analyzer. | ||
| Native sequence in the bacteria is used as | ||
| the Internal Control Target. | ||
| Instrument | ||
| Systems | ● GeneXpert® Dx System | |
| ● GeneXpert® System with Touchscreen | ||
| ● GeneXpert® Infinity System | ● cobas® Liat® System | |
| Collection | ||
| Device | Cepheid Sample Collection Device | cobas® PCR Media Swab Sample Kit |
| Time to | ||
| Results | Less than 45 minutes | ~20 minutes |
1.5 Performance Studies
There have been no changes to the analytical and clinical performance data for the Xpert C. difficile/Epi test since the device's original clearance in K110203. In accordance with Cepheid's design control process, additional analytical verification studies were performed with the Xpert C. difficile/Epi test for use on GeneXpert® Infinity System and to establish compliance with
10
Image /page/10/Picture/0 description: The image shows the Cepheid logo. The logo consists of a blue graphic element resembling stylized wings or feathers, positioned to the left of the company name. The word "Cepheid" is written in a modern, sans-serif font, with a period at the end.
Class II Special Controls Guidelines appropriate for 21 CFR §866.3130. These verification studies are summarized below.
Verification Studies to Demonstrate Performance on GeneXpert Infinity System 1.5.1
The performance of the Xpert C. difficile/Epi test when used with the GeneXpert® Infinity System instruments was assessed through two (2) verification studies, namely, a prepared cartridge hold time study and a functional testing study. The study results support the use of the Xpert C. difficile/Epi test on the additional GeneXpert® Instrument Systems family member (i.e., GeneXpert® Infinity System).
Prepared Cartridge Hold Time Study
Hold time refers to the duration between the preparation of the cartridge (i.e., addition of processed specimen to the cartridge) and the initiation of the Xpert C. difficile/Epi test. A prepared cartridge hold time study was conducted using contrived positive (C. difficile cells added to negative matrix) and negative (negative matrix only) samples held for various times under three (3) hold environments, i.e., at ambient (22°C), elevated (25°C) with high humidity, or high (35°C) temperatures. The maximum acceptable hold time for a prepared cartridge was verified as 4 hours under all environments.
Functional Testing
Functional testing was conducted using both contrived positive (C. difficile cells added to negative matrix) and negative (negative matrix only) samples to evaluate differences (if any) in the performance of the Xpert C. difficile/Epi test on the previously cleared GeneXpert® Dx System and the GeneXpert® Infinity System, running respectively under systems software GeneXpert® Dx (v6.5) and GeneXpert® Xpertise (v6.8 or v7.1). The study results showed 100% agreement with the expected results, with no statistically significant differences in Ct values observed among test runs in all instrument/software combinations. This study demonstrated equivalent performance of the Xpert C. difficile/Epi test when performed on any member of the GeneXpert® Instrument Systems family of instruments.
1.5.2 Verification Studies to Establish Compliance with Special Controls Guidelines
Inclusivity Study
A study to determine the Analytical Reactivity (Inclusivity) of the Xpert C. difficile/Epi test was previously conducted in support of K110203 with C. difficile strains selected to broadly represent the majority of C. difficile toxinotypes encountered in practice. This study utilized eighteen (18) toxigenic C. difficile strains representing toxinotype 0 and other variant toxinotypes, including 027/NAP1/BI toxinotype III isolates. With the current submission (K243730), to comply with the requirements of FDA's Class II Special Controls Guideline document "Toxin Gene Amplification Assays for the Detection of Clostridium difficile" (issued on August 27, 2015) as appropriate for this Class II device under regulation 21 CFR §866.3130, a supplemental inclusivity study was conducted with Xpert C. difficile/Epi test using another eight (8) C. difficile strains. Overall, the inclusivity study results showed that Xpert C. difficile/Epi test met the requirements of the Class II Special Controls and accurately identified all strains of toxigenic C.
11
Image /page/11/Picture/0 description: The image shows the logo for Cepheid. The logo consists of a stylized blue wing-like design on the left, followed by the word "Cepheid." in a serif font. The logo is simple and modern.
difficile tested, thereby demonstrating an inclusivity rate of 100% for the Xpert C. difficile/Epi test.
1.6 Conclusion
Overall, analytical and clinical studies conducted with Xpert C. difficile/Epi
- . Demonstrate the safe and effective use of the Xpert C. difficile/Epi test, when performed on the members of the GeneXpert® Instrument Systems family (including the GeneXpert® Infinity System),
- Demonstrate compliance with the Class II Special Controls under regulation 21 CFR §866.3130, and
- Support the finding of Substantial Equivalence with the predicate.