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 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 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 provided text is a 510(k) summary for the cobas® Cdiff Nucleic Acid Test for use on the cobas® Liat® System. The purpose of this submission is to demonstrate substantial equivalence to a previously cleared device (K171770), specifically addressing a software update (Liat® Analyzer Software 3.3).

Therefore, the primary study discussed is a performance evaluation to demonstrate that the software update does not negatively impact the device's performance, thereby maintaining substantial equivalence to the predicate device.

Here's a breakdown of the requested information based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a table of "acceptance criteria" with numerically reported performance metrics for sensitivity, specificity, accuracy, etc., as typically seen in initial device clearance studies. Instead, it states that the performance of the modified device was evaluated and that the overall cobas® Cdiff assay performance and claims were not impacted by the software changes. This implies that the acceptance criterion was essentially "no significant change in performance" compared to the predicate device, which had already met its own performance criteria.

Acceptance Criterion (Implied)	Reported Device Performance
No significant impact on overall cobas® Cdiff assay performance	"The result of this evaluation determined that the overall cobas® Cdiff assay performance and claims were not impacted by changes implemented in cobas® Liat® Analyzer Software 3.3, when compared to the current commercially available core software version."
Continued substantial equivalence to predicate device (K171770)	"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."

2. Sample Size Used for the Test Set and Data Provenance

The document does not provide details on the sample size or data provenance (e.g., country of origin, retrospective/prospective) for the performance evaluation related to the software update. It only discusses the evaluation of the software's impact on the assay. The original predicate device clearance (K171770) would contain this information for the initial performance claims.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This information is not provided in the context of this software update evaluation. The ground truth for the test set of the original device was likely established during its initial clearance (K171770), and this document focuses on confirming that the software change doesn't alter that established performance.

4. Adjudication Method for the Test Set

This information is not provided in this document.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

No, an MRMC comparative effectiveness study is not applicable here. This device is an automated in vitro diagnostic test (nucleic acid amplification test), not an imaging device or a system that involves human readers interpreting results in a comparative effectiveness study setting. The device is designed to provide a qualitative result (detection of the toxin B gene).

6. If a Standalone Study (i.e., algorithm only without human-in-the-loop performance) was Done

Yes, implicitly. The evaluation focuses on the performance of the cobas® Cdiff assay with the updated software on the cobas® Liat® System. This is a standalone performance assessment of the automated diagnostic device (algorithm and hardware combined) without human interpretation impacting the primary result itself. The result is "automatically analyzed and...displayed" (page 5).

7. The Type of Ground Truth Used

The document does not explicitly state the type of ground truth used for this specific software update evaluation. For the initial clearance of a diagnostic test like this, ground truth for clinical performance studies would typically involve:

Culture confirmation (e.g., toxigenic C. difficile culture)
An FDA-cleared reference method or composite reference method (CRM) utilizing multiple tests and/or expert clinical judgment.

This document assumes that the established ground truth methodology for the predicate device remains valid and that the software update does not affect the device's ability to correlate with that ground truth.

8. The Sample Size for the Training Set

The document does not provide information on the sample size for the training set for the software (algorithm) itself. Given that this is a software update for an already cleared diagnostic system, "training set" in the context of machine learning (if applicable for some internal functions) is not detailed. The test uses established PCR principles and validated oligonucleotide sequences.

9. How the Ground Truth for the Training Set was Established

This information is not provided and is likely not relevant as this is an update to an analytical testing platform rather than a de novo AI/ML algorithm requiring a specific "training set" with ground truth in the traditional sense. The assay's core principles (oligonucleotide sequences, PCR) are described as unchanged from the predicate, which would have undergone its own rigorous analytical and clinical validation.

Summary

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September 9, 2021

Roche Molecular Systems, Inc. Gaila Balniene Senior Regulatory Affairs Specialist 4300 Hacienda Drive Pleasanton, California 94588-2722

Re: K210385

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: February 8, 2021 Received: February 9, 2021

Dear Gaila Balniene:

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	Gaila BalnienePhone: (510) 305-6980FAX: (925) 225-0207Email: gaila.balniene@roche.com
Date Prepared	February 9, 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	OZN, OOI
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

1. DEVICE DESCRIPTION

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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, when used with cobas®Liat® Analyzer Software 3.3 are substantially equivalent to the legally marketed device, which was most recently cleared with cobas® Liat® Analyzer Software 3.0. 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 w/ cobas® Liat® System Software 3.3	Predicate Device: K171770cobas® Cdiff w/ cobas® Liat® System Software 3.0
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 from patientssuspected of having C. difficile infection (CDI). The cobas® Cdiff Nucleic acid test foruse on the cobas® Liat® System is intended for use as an aid in the diagnosis of CDIin humans in conjunction with clinical and epidemiological risk factors.
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 w/ cobas® Liat® System Software 3.3	Predicate Device: K171770cobas® Cdiff w/ cobas® Liat® System Software 3.0
SamplePreparation	Same	Magnetic bead-based nucleic acid extraction automated by cobas® Liat® Analyzer
Result Analysis	Same	Based on PCR cycle threshold analysis
Subject Status	Same	Symptomatic
Assay Instrument	Same	cobas® Liat® Analyzer
Software	cobas® Liat® Analyzer Core Software 3.3 cobas® Cdiff Assay Script CDFA 1.1	cobas® Liat® Analyzer Core Software 3.0 cobas® Cdiff Assay Script CDFA 1.0

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4. DESCRIPTION OF CHANGE: CORE SOFTWARE

cobas® Liat® Analyzer Software 3.3 incorporates the following changes:

Operating System Migration to LINUX OS .
Patient Verification .
Translations (not applicable to US customers) .
Enhanced Data Encryption .
. Thermal Printer Support
Generic Calculation Engine (not applicable to cleared assays) .
Assay Masking .
Integration of Advanced Tools .
Correction of defects (bug fixes) .

5. DESIGN AND DEVELOPMENT ACTIVITY SUMMARY

Roche Molecular Diagnostics (RMD), Pleasanton, CA designed and developed the core software component of the cobas® Liat® System. The cobas® Liat® Analyzer core software was designed and developed by Roche Molecular Diagnostics in Rotkreuz, Switzerland.

RMD in Pleasanton and Rotkreuz coordinated the development and verification of cobas® Liat® Analyzer Software 3.3 at the Product Requirements, Technical Requirements and Technical Requirement Specifications (Unit Specifications) level. These activities included risk management, requirements management, configuration management, verification testing, and regression analysis.

6. ASSAY PERFORMANCE

Performance of the cobas® Cdiff assay with cobas® Liat® Analyzer Software 3.3 was evaluated. The result of this evaluation determined that the overall cobas® Cdiff assay performance and claims were not impacted by changes implemented in cobas® Liat® Analyzer Software 3.3, when compared to the current commercially available core software version.

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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.