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.

Device Description

The cobas® Cdiff Nucleic Acid Test for use on the cobas® Liat® System (cobas® Cdiff) is a rapid, automated in vitro diagnostic test for qualitative detection and differentiation of C. difficile DNA in human stool specimens. The cobas® Liat® is for in vitro diagnostic use. The system is designed to identify and/or measure presence of genetic material in a biological sample. The system automates all nucleic acid amplification test (NAAT) processes, including reagent preparation, target enrichment, inhibitor removal, nucleic acid extraction, amplification, real-time detection, and result interpretation in a rapid manner. The cobas® Cdiff test uses silica magnetic particle-based nucleic acid extraction and TaqMan probe-based real-time PCR amplification and detection. The cobas® Liat® Analyzer automates and integrates sample purification, nucleic acid amplification and detection of the target sequence in biological samples. Other than adding the sample to the cobas® Cdiff assay tube, no reagent preparation or additional steps are required. The cobas® Cdiff assay tube that holds all of the sample purification and PCR reagents and hosts the sample preparation and PCR process specific for the Cdiff analyte. The test uses the assay tube as both the sample and reaction vessel. The assay tube comprises flexible tubing containing all required unit dose reagents pre-packed in tube segments, separated by pressure-sensitive seals, in the order of reagent use. During the testing process, multiple sample processing actuators of the analyzer compress the cobas® Cdiff assay tube to selectively release reagents from tube segments, move the sample from one segment to another, and control reaction conditions such as reaction volume, temperature, pressure, and incubation time. Precise control of all these parameters provides optimal conditions for assay reactions, allowing the test to achieve high performance similar to or better than that of currently available molecular assays. The cobas® Liat® Analyzer software controls and coordinated these actions to perform all required assay processes, including sample preparation, nucleic acid extraction, target enrichment, inhibitor removal, nucleic acid elution, and real-time PCR. All assay steps are performed within the closed and self-contained cobas® Cdiff assay tube, thereby eliminating the potential for cross-contamination between samples. The collected data are automatically analyzed and the result is displayed in the assay report on the integrated LCD touch screen of the cobas® Liat® Analyzer.

AI/ML Overview

The document provided does not contain the level of detail required to answer all aspects of your request. Specifically, it is a 510(k) summary for a change in shelf life for an existing device, the cobas® Cdiff Nucleic Acid Test. Therefore, it focuses on demonstrating that this change does not negatively impact performance, rather than providing all the original study details for the device's initial clearance.

Here's an analysis of the provided text in relation to your questions:

1. A table of acceptance criteria and the reported device performance.

The document does not explicitly state specific numerical acceptance criteria for the initial device performance. It focuses on demonstrating that the performance of the device with the new shelf life is equivalent to the currently cleared device.

However, it does mention a new stability study was performed with "modified stability testing approach and acceptance criteria." It then states the result:

Acceptance Criteria (Implied)	Reported Device Performance
Maintenance of overall cobas® Cdiff assay performance and claims, substantially equivalent to the currently cleared device.	Overall cobas® Cdiff assay performance and claims are substantially equivalent to the currently cleared device, with reagents up to ten (10) months after the date of manufacture, supporting a shelf life claim of 9 months.

2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective).

The document mentions a "new stability study" was performed to verify the shelf life. It does not provide:

Sample size: No explicit number of samples or runs for this stability study is provided.
Data Provenance: Not mentioned (e.g., country of origin).
Retrospective/Prospective: Implied to be prospective for the shelf-life stability study, as it's a "new stability study." However, for the original clearance of the device itself, this information is not provided.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience).

This device is an in vitro diagnostic (IVD) test for detecting a bacterial gene (Clostridioides difficile toxin B gene). The "ground truth" for such a test would typically be established by:

Reference methods: E.g., bacterial culture, toxigenic culture, or a highly sensitive and specific laboratory reference PCR assay.
Clinical diagnosis: Based on patient symptoms, other lab tests, and clinical assessment.

This document does not mention the use of human experts (like radiologists) for ground truth establishment. For an IVD, the "experts" are the laboratory and clinical staff following established protocols to provide the comparator data. The document does not specify details about these "experts" or their qualifications.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set.

Not applicable or not mentioned. Adjudication methods like 2+1 or 3+1 are typically used in image analysis studies where human readers interpret images. For an IVD, the comparison is usually against a pre-defined "gold standard" or reference method.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance.

Not applicable. This is an IVD test, not an AI-powered diagnostic imaging device that assists human readers.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done.

Yes, by its nature, an IVD test like the cobas® Cdiff Nucleic Acid Test on the cobas® Liat® System is a standalone device. The "algorithm" here refers to the pre-programmed steps of nucleic acid extraction, amplification, and real-time detection performed by the automated system, leading to a qualitative result (positive/negative). The document states: "The cobas® Liat® Analyzer automates and integrates sample purification, nucleic acid amplification and detection of the target sequence in biological samples... The collected data are automatically analyzed and the result is displayed in the assay report on the integrated LCD touch screen of the cobas® Liat® Analyzer." This indicates standalone performance.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc).

The document implies the ground truth for establishing initial performance would have been comparison to a reference method, likely a combination of toxigenic C. difficile culture and a highly reliable molecular method, or clinical diagnosis supported by confirmatory lab tests in the original clearance (K171770). For the current shelf-life stability study, the ground truth appears to be the expectation that the device continues to perform according to its established analytical specifications when tested at different time points after manufacturing. It refers to "assay performance and claims."

8. The sample size for the training set.

Not applicable/Not mentioned. As an IVD test, there isn't a "training set" in the machine learning sense. The device's performance is established through analytical and clinical validation studies with defined sample sizes. The document doesn't provide these sizes for the original device, nor for any "training" in the context of this specific 510(k) which is for a shelf-life change.

9. How the ground truth for the training set was established.

Not applicable/Not mentioned for the same reasons as #8. For an IVD, the "ground truth" for validation studies (analogous to a test set in ML) would be established by reference methods or clinical diagnosis.

Summary

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October 20, 2021

Roche Molecular Systems, Inc. Kaitlyn Hameister Senior Regulatory Affairs Specialist I 4300 Hacienda Drive Pleasanton, California 94588-2722

Re: K212427

Trade/Device Name: cobas Cdiff nucleic acid test for use on the cobas Liat System Regulation Number: 21 CFR 866.3130 Regulation Name: Clostridium Difficile Toxin Gene Amplification Assay Regulatory Class: Class II Product Code: OZN, OOI Dated: August 3, 2021 Received: August 4, 2021

Dear Kaitlyn Hameister:

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. 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 located 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, 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

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801 and Part 809); medical device 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 Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-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, Ph.D. (ABMM) Chief General Bacteriology and Antimicrobial Susceptibility Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

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Indications for Use

510(k) Number (if known)

Device Name

Indications for Use (Describe)

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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cobas® Cdiff Nucleic Acid Test for Use on the cobas® Liat® System 510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.

Submitter Name	Roche Molecular Systems, Inc.
Address	4300 Hacienda DrivePleasanton, CA 94588-2722
Contact	Kaitlyn HameisterPhone: (925) 368-0589FAX: (925) 225-0207Email: kaitlyn.hameister@roche.com
Date Prepared	July 29, 2021
Proprietary Name	cobas® Cdiff Nucleic acid test for use on the cobas® Liat® System
Common Name	Clostridioides difficile Test
Classification Name	Clostridioides difficile Toxin Gene AmplificationAssay Real Time Nucleic Acid AmplificationSystem
Product Codes	OZNOOI
Regulation Number	21 CFR 866.3130
Predicate Devices	cobas® Cdiff Nucleic Acid Test for use on the cobas® Liat® System
Establishment Registration	Roche Molecular Systems, Inc. Branchburg, NJEstablishment Number: 2243471Roche Molecular Systems, Inc. Pleasanton, CAEstablishment Number: 3004141078

DEVICE DESCRIPTION 1.

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The cobas® Liat® is for in vitro diagnostic use. The system is designed to identify and/or measure presence of genetic material in a biological sample. The system automates all nucleic acid amplification test (NAAT) processes, including reagent preparation, target enrichment, inhibitor removal, nucleic acid extraction, amplification, real-time detection, and result interpretation in a rapid manner.

Target Selection 1.1.

The cobas® Cdiff test detects tcdB target-specific and Internal Control specific oligonucleotide sequences. Toxin B (or tcdB) is a major toxin that is implicated in C. difficile pathogenesis and allows the differentiation between toxigenic and non-toxigenic C. difficile strains. The same Internal Control as in the predicate assay (Bacillus thuringiensis israelensis) is used. Primers and probe oligonucleotide sequences were designed to detect C. difficile genus organisms, as well as with organisms commonly found in normal gut flora. All oligonucleotide sequences remain unchanged from the predicate assay.

Test Principle 1.2.

The cobas® Cdiff test uses silica magnetic particle-based nucleic acid extraction and TaqMan probe-based real-time PCR amplification and detection. The cobas® Liat® Analyzer automates and integrates sample purification, nucleic acid amplification and detection of the target sequence in biological samples. Other than adding the sample to the cobas® Cdiff assay tube, no reagent preparation or additional steps are required. The cobas® Cdiff assay tube that holds all of the sample purification and PCR reagents and hosts the sample preparation and PCR process specific for the Cdiff analyte. The test uses the assay tube as both the sample and reaction vessel. The assay tube comprises flexible tubing containing all required unit dose reagents pre-packed in tube segments, separated by pressure-sensitive seals, in the order of reagent use.

During the testing process, multiple sample processing actuators of the analyzer compress the cobas® Cdiff assay tube to selectively release reagents from tube segments, move the sample from one segment to another, and control reaction conditions such as reaction volume, temperature, pressure, and incubation time. Precise control of all these parameters provides optimal conditions for assay reactions, allowing the test to achieve high performance similar to or better than that of currently available molecular assays. The cobas® Liat® Analyzer software controls and coordinates these actions to perform all required assay processes, including sample preparation, nucleic acid extraction, target enrichment, inhibitor removal, nucleic acid elution, and real-time PCR. All assay steps are performed within the closed and self-contained cobas® Cdiff assay tube, thereby eliminating the potential for cross-contamination between

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samples. The collected data are automatically analyzed and the result is displayed in the assay report on the integrated LCD touch screen of the cobas® Liat® Analyzer.

2. INDICATIONS FOR USE

3. TECHNOLOGICAL CHARACTERISTICS

The primary technological characteristics and intended use of cobas® Cdiff for use on the cobas® Liat® System are substantially equivalent to the legally marketed device. Table 1 provides a comparison of the modified device to the predicate device, as cleared through K171770.

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Item Name	Submitted Device:cobas® Cdiff	Predicate Device: K171770cobas® Cdiff
Intended Use	Same	The cobas® Cdiff Nucleic acid test for use on the cobas® Liat® System is anautomated, qualitative in vitro diagnostic test, that uses real-time polymerase chainreaction (PCR), for the detection of the toxin B ( tcdB ) gene of toxigenic Clostridioidesdifficile ( C. difficile ) in unformed (liquid or soft) stool specimens obtained frompatients suspected of having C. difficile Infection (CDI). The cobas® Cdiff Nucleicacid test for use on the cobas® Liat® System is intended for use as an aid in thediagnosis of CDI in humans in conjunction with clinical and epidemiological riskfactors.
Conditions for Use	Same	For prescription use
RegulationNumber	Same	21 CFR 866.3130
Classification	Same	Clostridioides difficile Toxin Gene Amplification AssayReal Time Nucleic Acid Amplification System
Product Code	Same	OZN, OOI
Sample Type	Same	Unformed soft stool specimens
AmplificationTechnology	Same	Real-time PCR
DetectionTechnique	Same	Multiplex assay using different reporter dyes for each target
ErrorDiagnosticSystem	Same	Yes, monitors and records system parameters for error recover or abort ifunrecoverable
Internal Control	Same	A gram-positive Bacillus thuringiensis israelensis bacterial organism to monitor thefull process of cobas® Liat® Analyzer. Native sequence in the bacteria is used as theInternal Control Target.
Positive Control	Same	Plasmid in buffer
Negative Control	Same	Buffer only
Analyte Targets	Same	Toxin B ( tcdB ) gene
Sample CollectionDevices	Same	cobas® PCR Media Swab Sample Kit
Item Name	Submitted Device:cobas® Cdiff	Predicate Device: K171770cobas® Cdiff
SamplePreparation	Same	Magnetic bead-based nucleic acid extraction automated by cobas® Liat® Analyzer
Subject Status	Same	Symptomatic
Assay Instrument	Same	cobas® Liat® Analyzer
Software	cobas® Liat® Analyzer Core Software 3.3*CDFA 1.1	cobas® Liat® Analyzer Core Software 3.0 (K171770)CDFA 1.0
Shelf Life StabilityMethod	Statistical Sampling with Adapted Acceptance Criteria	Small Batch Sampling

Comparison of the cobas® Cdiff Assay for use on the cobas® Liat® System to the Predicate Device Table 1:

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cobas® Liat® Analyzer Software 3.3 is currently cleared by FDA as part of K210385.

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4. DESCRIPTION OF CHANGE: SHELF LIFE

The modified cobas® Cdiff incorporates changes to shelf life (from 12 months to 9 months).

5. DESIGN AND DEVELOPMENT ACTIVITY SUMMARY

Roche Molecular Diagnostics (RMD), Pleasanton, CA designed and developed the cobas® Cdiff nucleic acid test for use on the cobas® Liat® System, and coordinated stability testing activities related to shelf life verification. These activities included risk management, requirements management, configuration management, verification testing, and regression analysis.

6. ASSAY PERFORMANCE

A new stability study with modified stability testing approach and acceptance criteria has been performed to evaluate and verify the shelf life of the cobas® Cdiff assay. The result of this evaluation determined that the overall cobas® Cdiff assay performance and claims are substantially equivalent to the currently cleared device, with reagents up to ten (10) months after the date of manufacture, supporting a shelf life claim of 9 months, as supported by stability testing data.

CONCLUSION 7.

Equivalent performance of the modified device and the current commercial device has been demonstrated, and analytical or clinical performance has not changed. The modified device is substantially equivalent to the predicate device, as cleared through K171770.

Regulation Number and Section

§ 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.