The cobas® Cdiff Nucleic acid test for use on the cobas® Liat® System is an automated, qualitative in vitro diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the detection of the toxin B (tcdB) gene of toxigenic Clostridium difficile in unformed (liquid or soft) stool specimens 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 the qualitative detection of C. difficile DNA in human stool specimens. The cobas® Liat® System is for in vitro diagnostic use. The system is designed to identify and/or measure the 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® Liat® System consists of an cobas® Liat® Analyzer with integrated software for running tests and analyzing the results, and a single-use disposable cobas® Cdiff assay tube that holds all of the sample purification and PCR reagents and hosts the sample preparation and PCR processes 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

Here's an analysis of the acceptance criteria and study details based on the provided text:

Acceptance Criteria and Device Performance for cobas® Cdiff Nucleic acid test for use on the cobas® Liat® System

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal "acceptance criteria" in a separate section with numerical targets like a typical clinical trial report for an AI device. Instead, the performance metrics are presented as the results of the studies conducted. I will infer the acceptance criteria from the reported performance, implying that the reported values met the internal standards set by the manufacturer for substantial equivalence.

Performance Metric	Acceptance Criteria (Inferred from Predicate/Study Goals)	Reported Device Performance (cobas® Cdiff Test)
Analytical Sensitivity (LOD)	To detect C. difficile at a concentration to yield a Hit Rate of at least 95%, where all higher concentrations also have a Hit Rate of ≥ 95%.	ATCC 43255: 90 CFU/swab R12087 (CD196): 45 CFU/swab
Inclusivity	To detect 100% of tested toxigenic strains at 3xLOD.	All 37 toxigenic strains detected with 100% hit rate.
Analytical Specificity (Cross-reactivity)	No cross-reactivity with non-toxigenic C. difficile strains, human genomic DNA, or other common stool microorganisms, and no interference with toxigenic C. difficile detection.	No cross-reactivity with 149 tested non-toxigenic Cdiff strains, human epithelial cells, or other microorganisms. No interference with detection of toxigenic Cdiff at 3x LOD.
Interference	No interference from common medications and fecal substances at specified concentrations.	Fecal Fat: No interference up to 39% (w/v) Whole blood: No interference up to 100% (v/v) Mucin: No interference up to 50% (w/v) Various other medications and substances tested and confirmed for no interference at specified concentrations (see Table 5).
Reproducibility (~1xLOD)	Overall percent agreement for low positive samples (~1xLOD) to demonstrate consistency across sites, operators, and lots.	98.5% (262/266) with a 95% CI of (96.2%, 99.4%)
Reproducibility (~3xLOD)	Overall percent agreement for moderate positive samples (~3xLOD) to demonstrate consistency across sites, operators, and lots.	99.3% (268/270) with a 95% CI of (97.3%, 99.8%)
Reproducibility (Negative)	Overall percent agreement for negative samples to demonstrate consistency across sites, operators, and lots.	100.0% (262/262) with a 95% CI of (98.6%, 100.0%)
Clinical Sensitivity (vs. Combined Culture)	High sensitivity for detecting toxigenic C. difficile in clinical samples.	87.2% (156/179; 95% CI: 81.5% to 91.3%)
Clinical Specificity (vs. Combined Culture)	High specificity for detecting toxigenic C. difficile in clinical samples.	98.1% (818/834; 95% CI: 96.9% to 98.8%)
Clinical PPV (vs. Combined Culture)	High Positive Predictive Value.	90.7% (156/172; 95% CI: 85.4% to 94.2%)
Clinical NPV (vs. Combined Culture)	High Negative Predictive Value.	97.3% (818/841; 95% CI: 95.9% to 98.2%)
Initial Invalid Rate	Low initial invalid rate.	1.4%
Initial Failed Rate	Low initial failed rate.	0.2%
Final Invalid Rate (after retest)	Very low final invalid rate.	0.1%
Final Failed Rate (after retest)	Zero final failed rate.	0%

2. Sample size used for the test set and the data provenance

Analytical Sensitivity (LOD): Not specified as a per-sample-size, but replicates of each 5-member test panel were tested with 2 different lots of assay tubes. Additional replicates were tested for confirmation.
Inclusivity: 3 replicates per strain (37 toxigenic strains) were tested.
Analytical Specificity (Cross-reactivity): Not specified as a per-sample-size, but 149 non-toxigenic organisms/cells were tested.
Interference: Not specified as a per-sample-size, but 38 commonly used medications, fecal fat, whole blood, and mucin were tested.
Reproducibility: 818 total tests were performed, with 798 valid for analysis across 3 panel members (Negative, ~1xLOD, ~3xLOD). 3 replicates per panel member, run on 5 nonconsecutive days by 2 operators at 3 sites for 3 reagent lots.
Clinical Performance: 1,013 evaluable fresh remnant stool specimens were prospectively collected.
- Data Provenance:
  - Country of Origin: Not explicitly stated, but "Nine (9) study sites from geographically diverse locations participated in this study." This suggests a multi-center study, likely within a single country (such as the US, given the FDA submission) or potentially across a few countries, but a specific list is not provided.
  - Retrospective/Prospective: The clinical performance study was prospective. "Evaluable fresh remnant specimens were prospectively collected from 1,013 patients."

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

Analytical (LOD, Inclusivity, Specificity, Interference): Not applicable for these studies as the "ground truth" is based on engineered samples (known concentrations of specific strains, or presence/absence of interfering substances).
Reproducibility: Not applicable, as this assessed the consistency of the device's own results, not against an external ground truth.
Clinical Performance:
- Number of experts: Not explicitly stated.
- Qualifications of experts: Not explicitly stated. The "ground truth" was established by "combined results of direct and enriched toxigenic culture using leftover, deidentified, unformed stool samples" performed at a "reference laboratory." The document mentions "Nineteen (19) operators distributed across these study sites performed testing with the cobas® Cdiff test," but these are operators, not necessarily the adjudicating experts for the ground truth. For microbiological culture, laboratory personnel with specific training in microbiology would establish the ground truth.

4. Adjudication method for the test set

Analytical, Reproducibility: Not applicable.
Clinical Performance:
- Initial Ground Truth: "Combined results of direct and enriched toxigenic culture" served as the primary comparative method.
- Discrepant Analysis: "All evaluable discordant specimens and an equal number of randomly selected and representative concordant samples were used for discrepant testing by an FDA-cleared comparator NAAT. Testing was performed at an external lab that was preselected and qualified by RMS." This implies a form of 2-method consensus with a third method for discrepancies. If direct and enrichment culture disagreed, or if the cobas test disagreed with the combined culture, a third (comparator NAAT) test was used for "discrepant analysis." However, the final clinical performance tables still directly compare the cobas test to the combined culture results, with the discrepant analysis results discussed qualitatively ("Of the 23 specimens with false-negative cobas® Cdiff test results relative to combined direct culture and enrichment culture, 19 were negative. 3 were positive and 1 was invalid by the second NAAT method.").

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done

No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) test, not an imaging AI device that relies on human-in-the-loop interpretation. The clinical study compares the device's output to laboratory culture results, not to human readers' interpretations with or without AI assistance.

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

Yes, the performance presented is purely standalone (algorithm/device only). The cobas® Cdiff Nucleic acid test is an automated, qualitative in vitro diagnostic test. The device provides "result interpretation" directly on its integrated LCD touch screen (page 5). The clinical performance data reflects the device's ability to detect the target gene independently, compared against culture methods.

7. The type of ground truth used

Analytical Studies (LOD, Inclusivity, Specificity, Interference): Lab-prepared spiked samples with known concentrations/compositions.
Clinical Performance: Microbiological culture results. Specifically, "combined results of direct and enriched toxigenic culture." A "second NAAT method" was used for discrepant analysis.

8. The sample size for the training set

Not applicable / Not explicitly stated. This is a molecular diagnostic test for Clostridium difficile, not a machine learning or AI algorithm in the typical sense that requires explicit "training data" for a model to learn from. The assay uses predefined primers and probes for real-time PCR detection (page 4). While the assay design and optimization would involve extensive internal development and testing, this is not characterized as a "training set" in the context of typical AI algorithm development.

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

Not applicable / Not explicitly stated. As mentioned above, this is not an AI/ML device that uses a "training set" in the conventional sense. The "ground truth" for developing the test was based on well-characterized isolates of C. difficile and other microorganisms to design and validate the specificity and sensitivity of the primers and probes.

Summary

{0}------------------------------------------------

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

September 12, 2017

Roche Molecular Systems, Inc. Clare Santulli Senior Manager 4300 Hacienda Drive Pleasanton, California 94588-2722

Re: K171770

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: June 13, 2017 Received: June 14, 2017

Dear Clare Santulli:

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. Isting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements

{1}------------------------------------------------

as set forth in the quality systems (OS) 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 vou desire specific advice for your device on our labeling regulation (21 CFR Part 801 and Part 809), please contact the Division of Industry and Consumer Education (DICE) 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 (DICE) 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,

Ribhi Shawar -S For

Uwe Scherf, M.Sc., Ph.D. 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) K171770

Device Name

cobas® Cdiff Nucleic acid test for use on the cobas® Liat® System

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)

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}------------------------------------------------

510(k) Summary

Submitter Name	Roche Molecular Systems, Inc.
Address	4300 Hacienda DrivePleasanton, CA 94588-2722
Contact	Clare SantulliPhone: (925) 730-8886FAX: (925) 225-0207Email: clare.santulli@roche.com
Date Prepared	September 11, 2017
Proprietary Name	cobas® Cdiff Nucleic acid test for use on the cobas® Liat® System
Common Name	Clostridium difficile Test
Classification Name	21 CFR 866.3130 - Clostridium difficile toxin gene amplification assay21 CFR 862.2570 - Real Time Nucleic Acid Amplification System
Product Codes	OZN, OOI
Predicate Devices	cobas® Cdiff Test on the cobas® 4800 system
Establishment Registration	Branchburg: 2243471Pleasanton: 3004141078Indianapolis: 1823260

{4}------------------------------------------------

1. DEVICE DESCRIPTION

The cobas® Liat® System is for in vitro diagnostic use. The system is designed to identify and/or measure the 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.

1.1. Target Selection

The cobas® Cdiff test detects the tcdB target-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. Primers and probe oligonucleotide sequences were designed to detect C. difficile conserved sequences without cross-reacting with other Clostridium genus organisms, as well as with organisms commonly found in normal gut flora.

1.2. Test Principle

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® Liat® System consists of an cobas® Liat® Analyzer with integrated software for running tests and analyzing the results, and a single-use disposable cobas® Cdiff assay tube that holds all of the sample purification and PCR reagents and hosts the sample preparation and PCR processes 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.

{5}------------------------------------------------

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.

2. INDICATIONS FOR USE

The cobas® Cdiff Nucleic acid test for use on the cobas® Liat® System is an automated, qualitative in vitro diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the 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 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.

TECHNOLOGICAL CHARACTERISTICS 3.

The primary technological characteristics and intended use of the RMS cobas® Cdiff Nucleic acid test for use on the cobas Liate System are substantially equivalent to other legally marketed nucleic acid amplification tests intended for the qualitative detection of Clostridium difficile. As indicated in Table 1, the RMS cobas® Cdiff Nucleic acid test for use on the cobas® Liat® System is substantially equivalent to significant characteristics of the identified predicate device, the currently cleared cobas® Cdiff Test for use on the cobas® 4800 System, 510(k) 142422. The predicate device and the submitted device both utilize the cobas® PCR Media Uni Swab Sample Kit for specimen transfer into cobas PCR Media.

{6}------------------------------------------------

	Submitted Device:cobas® Cdiff Nucleic acid test for useon the cobas® Liat® System	Predicate Device:cobas® Cdiff Test for use on the cobas®4800 System , K142422
Intended Use	The cobas® Cdiff Nucleic acid test for useon the cobas® Liat® System is anautomated, qualitative in vitro diagnostictest, that utilizes real-time polymerasechain reaction (PCR), for the detection ofthe toxin B (tcdB) gene of toxigenicClostridium difficile in unformed (liquid orsoft) stool specimens obtained frompatients suspected of having C. difficileinfection (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 conjunctionwith clinical and epidemiological riskfactors.	The cobas® Cdiff Test on thecobas® 4800 system is an automated,qualitative in vitro diagnostic test, thatutilizes real-time polymerase chainreaction (PCR), for the direct detection ofthe toxin B (tcdB) gene of toxigenicClostridium difficile in unformed (liquid orsoft) stool specimens obtained frompatients suspected of having C. difficileinfection (CDI). The cobas® Cdiff Test isintended for use as an aid in the diagnosisof CDI in humans in conjunction withclinical and epidemiological risk factors.
Conditions for use	For prescription use	Same
Regulation Number,Classification andSubsequent ProductCodes	21 CFR 866.2660: Microorganismdifferentiation and identification device.OMN: C. difficile Nucleic AcidAmplification Test Assay.OOI: Real Time Nucleic AcidAmplification System.	Same
Sample Types	Unformed soft stool specimens	Same
Amplification Technology	Real-time PCR	Same
Detection Technology	TaqMan probes with fluorescent dyes	Same
Internal Control	A gram-positive Bacillus thuringiensis israelensis bacterial organism to monitorthe full process on the cobas® Liat®Analyzer. Native sequence in the bacteriais used as the Internal Control target.	Lambda phage with encapsulated internalcontrol sequence
Positive Control	Plasmid in buffer	Same
Negative Control	Buffer only	Same
Analyte Targets	Toxin B ( tcdB ) gene	Same
Sample Transfer Devices	cobas® PCR Media Uni Swab Sample Kit	Same
Sample Preparation	Magnetic bead-based nucleic acidextraction automated bycobas® Liat® Analyzer	Magnetic bead-based nucleic acidextraction automated bycobas® 4800 System
Result Analysis	Based on PCR cycle threshold analysis	Same
Subject Status	Symptomatic	Same

Similarities and Differences between the cobas® Cdiff Nucleic acid test for use Table 1: on the cobas® Liat® System and the Predicate Device

{7}------------------------------------------------

NON-CLINICAL PERFORMANCE EVALUATION 4.

4.1. Analytical Sensitivity

The analytical sensitivity (Limit of Detection or LOD) for the cobas® Cdiff test was determined by analyzing 2 toxigenic C. difficile strains ATCC 43255(VPI 10463) and R12087 (CDI 196). Five-member test panels were prepared with the two different strains of Cdiff at concentrations that bracketed the expected Limit of Detection (LOD). Replicates of each test panel member were then tested with two different lots of cobas® Liat® Cdiff assay tubes to determine the Limit of Detection, or the lowest Cdiff concentration to yield a Hit Rate of at least 95%, where all higher concentrations also have a Hit Rate of ≥ 95%. Additional replicates were tested to confirm the LOD.

Negative stool background samples were also run to verify the Limit of Blank (LoB).

The LOD results among 2 reagent lots are shown in Table 2.

LOD cobas® Cdiff Nucleic acid test for use on the cobas® Liat® System Table 2:

Strain ID	Toxinotype	REA*Type	PFG†Type	Ribotype	Phenotype	LOD(CFU/swab)
ATCC 43255(VPI 10463)	0	N/A	N/A	87	A+B+CDT-	90
R12087 (CD196)	III	BI	NAP1	27	A+B+CDT+	45

*Restriction endonuclease analysis; *Pulse Field Gel

4.2. Inclusivity

The limit of detection of cobas Cdiff test on 37 toxigenic strains representing additional toxinotypes was verified by testing three replicates per strain at three times the LOD level (~60 CFU/ml equivalent to 270 CFU/swab) of ATCC 43255.

All 37 toxigenic strains were detected with a 100% hit rate for each toxigenic strain in this study, confirming that the cobas Cdiff test can detect these C. difficile toxinotypes. Results are shown in Table 3.

{8}------------------------------------------------

Sample ID	Cdiff Strain	Toxinotype	Ribotype
1	RMSCC 11251(ATCC#BAA-1382; 630)	0	012
2	EX 623	I	102
3	AC 008	II	103
4	RMSCC 12827 [2004118; CDC-204118 (NAP-1)]	III	027
5	SE 844	IIIa	080
6	CH6230	IIIc	N/A
7	RMSCC 11298 (P43)	IV	N/A
8	55767	IV	023
9	RMSCC 11300 (2748-06)	V	078
10	SE 881	V	045
11	RMSCC 11302 (SE 1203)	VI	033
12	57267	VII	063
13	RMSCC 12472(ATCC# 43598; 1470)	VIII	017
14	RMSCC 11299 (51680)	IX	019
15	RMSCC 11304 (CCUG 8864/STCC20309)	X	036
16	RMSCC 11308 (F15)	XII	N/A
17	IS 25	XII	056
18	R 9367	XIII	070
19	R 10870	XIV(New-XIVa)	111
20	R 9385	XV(New XIVb)	122
21	SUC36	XVI	078
22	RMSCC 11309 (No 1313)	XVII	232
23	K095	XVIII	014
24	TR13	XIX	N/A
25	TR14	XX	N/A
26	CH6223	XXI	N/A
27	CD07-468	XXII	N/A
28	8785	XXIII(New-IXc)	N/A
29	597B	XXIV	131
30	7325	XXV	027
31	7459	XXVI	N/A
32	KK2443/2006	XXVII	N/A
33	CD08-070	XXVIII	126
34	CD07-140	XXIX	056
35	ES 130	XXX	N/A
36	WA 151	XXXI	N/A
37	173070	XXXII	N/A

Table 3: Results of Testing Three Replicates of 40 Cdiff Strains at 60CFU/mL (~3x LOD)

{9}------------------------------------------------

Analytical Specificity (Cross-reactivity) 4.3.

The cobas Liat Cdiff test was examined for analytical specificity by testing 146 non-toxigenic strains (toxinotype XI) of Clostridium difficile, human genomic DNA, and other microorganisms which could be present in clinical stool specimens at ~3xLOD concentration.

Test panels were prepared that contained each of these microorganisms, and each test panel was tested with the cobas Liat® Cdiff assay tubes. The microorganism concentrations that were tested correspond to approximately 1E+06 units (CFU, IFU, cells) per mL of stool specimen for bacteria and human epithelial cells (as a source for human genomic DNA) and 1E+05 TCID50and/or PFU per mL of stool specimen for viruses.

Three non-toxigenic Cdiff strains (toxinotype XI) tested during inclusivity study [RMSCC # 11305 (ES 1103), 11306 (6035/06) and 12414 (F14)] were not detected by the cobas® Cdiff test are included in this section.

The cobas® Liat Cdiff Test did not cross react with Cdiff non-toxigenic (toxinotype XI) strains, human epithelial cells (tested as a source of human genomic DNA) or other microorganisms which could be present in clinical stool specimens and that were tested in the study. Further, the presence of any of these potential cross reactants tested did not interfere with detection of toxigenic Cdiff strains tested at approximately 3x LOD level.

All 149 non-toxigenic strains (toxinotype XI) of Clostridium difficile, human genomic DNA, and other microorganisms are listed in Table 4.

{10}------------------------------------------------

Organism / CellNumber	Organism / Cell Name:	Source#
1	Abiotrophia defectiva	ATCC# 49176
2	Acinetobacter baumannii	ATCC# 19606
3	Acinetobacter Iwoffii	ATCC# 15309
4	Aeromonas hydrophila	ATCC# 7966
5	Alcaligenes faecalis	ATCC# 35655
6	Alcaligenes faecalis subsp. Faecalis	ATCC# 8750
7	Alcaligenes faecalis subsp. Faecalis	ATCC# 15554
8	Anaerococcus tetradius	ATCC# 35098
9	Bacillus cereus	ATCC# 13472
10	Bacillus cereus	ATCC# 11778 (also known as HER 1414)
11	Bacteroides caccae	ATCC# 43185
12	Bacteroides fragilis	ATCC# 25285
13	Bacteroides merdae	ATCC# 43184
14	Bacteroides stercoris	ATCC# 43183
15	Bifidobacterium adolescentis	ATCC# 15703
16	Bifidobacterium longum	ATCC# 15707
17	Campylobacter coli	ATCC# 33559
18	Campylobacter jejuni (f.k.a Campylobacter coli)	ATCC# 43479
19	Campylobacter jejuni Subsp. jejuni	ATCC# 33292
20	Candida albicans	ATCC# 10231
21	Candida catenulata	ATCC# 10565
22	Cedecea davisae	ATCC# 33431
23	Chlamydia Trachomatis Serovar L2	Zeptometrix # 0801776
24	Citrobacter amalonaticus	ATCC# 25405
25	Citrobacter freundii	ATCC# 8090
26	Citrobacter koseri	ATCC# 27028
27	Citrobacter sedlakii	ATCC# 51115
28	Clostridium beijerinckii	ATCC# 8260
29	Clostridium bifermentans	ATCC# 638
30	Clostridium bolteae	ATCC# BAA-613
31	Clostridium butyricum	ATCC# 19398
32	Clostridium chauvoei	ATCC# 11957
33	Clostridium difficile (Non-toxigenic, Serogroup B)	ATCC# 43593
34	Clostridium difficile (Non-toxigenic, Serogroup I)	ATCC# 43601
35	Clostridium fallax	ATCC# 19400
36	Clostridium haemolyticum	ATCC# 9650
37	Clostridium histolyticum	ATCC# 19401
38	Clostridium innocuum	ATCC# 14501
39	Clostridium methylpentosum	ATCC# 43829
40	Clostridium nexile	ATCC# 27757
41	Clostridium novyi	ATCC# 19402
42	Clostridium orbiscindens (re-namedFlavonifractor plautii)	ATCC# 49531
Organism / CellNumber	Organism / Cell Name:	Source#
43	Clostridium paraputrificum	ATCC# 17796
44	Clostridium perfringens	ATCC# 13124
45	Clostridium ramosum	ATCC# 25582
46	Clostridium scindens	ATCC# 35704
47	Clostridium septicum	ATCC# 12464
48	Clostridium sordellii	ATCC# 9714
49	Clostridium sphenoides	ATCC# 19403
50	Clostridium spiroforme	ATCC# 29899
51	Clostridium sporogenes	CCRI# 11128
52	Clostridium sporogenes	ATCC# 15579
53	Clostridium symbiosum	ATCC# 14940
54	Clostridium tertium	DSMZ# 662
55	Clostridium tetani	ATCC# 19406
56	Collinsella aerofaciens	ATCC# 25986
57	Corynebacterium genitalium	ATCC# 33030
58	Cytomegalovirus (AD-169)	ZeptoMetrix # 0810003CF
59	Desulfovibrio piger	ATCC# 29098
60	Edwardsiella tarda	ATCC# 15947
61	Eggerthella lenta	ATCC# 25559
62	Enterobacter aerogenes	ATCC# 13048
63	Enterobacter cloacae	ATCC# 13047
64	Enterococcus casseliflavus	ATCC# 25788
65	Enterococcus cecorum	ATCC# 43198
66	Enterococcus dispar	ATCC# 51266
67	Enterococcus faecalis Van B	ATCC# 51299
68	Enterococcus faecium Van A	ATCC# 35667
69	Enterococcus gallinarum Van C	ATCC# 49573
70	Enterococcus hirae	ATCC# 8043
71	Enterococcus raffinosus	ATCC# 49427
72	Escherichia coli	ATCC# 11775
73	Escherichia coli	ATCC# 25922
74	Escherichia coli O157:H7	ATCC# 700927
75	Escherichia fergusonii	ATCC# 35469
76	Escherichia hermannii	ATCC# 33650
77	Fusobacterium varium	ATCC# 8501
78	Gardnerella vaginalis	ATCC# 14018
79	Gemella morbillorum	ATCC# 27824
80	Hafnia alvei	CMCC# 147
81	HCT-15 Human Cells	ATCC# CCL-225
82	Helicobacter fennelliae	ATCC# 35683
83	Helicobacter pylori	ATCC# 43504
84	Human Adenovirus 41	ZeptoMetrix # 0810085CF
85	Human Coxsackievirus A4	ZeptoMetrix # 0810142CF
86	Human Coxsackievirus B4	ZeptoMetrix # 0810075CF
87	Human Echovirus 11	ZeptoMetrix # 0810023CF
Organism / CellNumber	Organism / Cell Name:	Source#
88	Human Enterovirus 71	ZeptoMetrix # 0810236CF
89	Human Rotavirus	ZeptoMetrix # 0810041CF
90	Klebsiella oxytoca	ATCC# 33496
91	Klebsiella pneumoniae subsp. Pneumoniae	ATCC# 13883
92	Lactobacillus acidophilus	ATCC# 4356
93	Lactobacillus reuteri	ATCC# 23272
94	Lactococcus lactis	ATCC# 19435
95	Leminorella grimontii	ATCC# 33999
96	Listeria grayi	ATCC# 19120
97	Listeria innocua	ATCC# 33090
98	Listeria monocytogenes	ATCC# 15313
99	Listeria monocytogenes	ATCC# BAA-839
100	Mitsuokella multacida	ATCC# 27723
101	Mobiluncus curtisii	ATCC# 35241
102	Molellerella wisonsensis	ATCC# 35017
103	Morganella morganii	ATCC# 25830
104	Neiserria gonorrhoeae	ATCC# 35201
105	Norovirus GII	ZeptoMetrix # 0810087CF
106	Peptoniphilus asaccharolyticus	ATCC# 14963
107	Peptostreptococcus anaerobius	ATCC# 27337
108	Plesiomonas shigelloides	ATCC# 14029
109	Porphyromonas asaccharolytica	ATCC# 25260
110	Prevotella melaninogenica	ATCC# 25845
111	Proteus mirabilis	ATCC# 29906
112	Proteus mirabilis	ATCC# 25933
113	Proteus penneri	ATCC# 35198
114	Providencia alcalifaciens	ATCC# 9886
115	Providencia rettgeri	ATCC# 9250
116	Providencia stuartii	ATCC# 29914
117	Pseudomonas aeroginosa	ATCC# 35554
118	Pseudomonas aeruginosa	ATCC# 33584
119	Pseudomonas putida	ATCC# 12633
120	Ruminococcus bromii	ATCC# 27255
121	Salmonella enterica subsp. arizonae (f.k.a.Salmonella choleraesuis ssp. arizonae)	ATCC# 13314
122	Salmonella enterica subsp. enterica	CMCC# 1975
123	Salmonella enterica subsp. enterica serovarCholeraesuis	ATCC# 7001
124(^)	Salmonella enterica subsp. enterica serovarTyphi	ATCC# 19430
125	Salmonella enterica subsp.enterica serovarTyphimurium	ATCC# 14028
126	Serratia liquefaciens	CMCC# 169
127	Serratia marcescens	ATCC# 8100
128	Serratia marcescens	ATCC# 13880
129	Serratia liquefaciens	ATCC# 27592
Organism / CellNumber	Organism / Cell Name:	Source#
130	Shigella boydii	ATCC# 9207
131	Shigella dysenteriae	ATCC# 11835
132	Shigella sonnei	ATCC# 29930
133	Staphylococcus aureus	ATCC# 43300
134	Staphylococcus epidermidis	ATCC# 14990
135	Stenotrophomonas maltophilia	ATCC# 13637
136	Streptococcus agalactiae	ATCC# 13813
137	Streptococcus dysgalactiae	ATCC# 43078
138	Streptococcus intermedius	ATCC# 27335
139	Streptococcus sp.; strain V8	ATCC# 12973
140	Streptococcus uberis	ATCC# 19436
141	Trabulsiella guamensis	ATCC# 49490
142	Veillonella parvula	ATCC# 10790
143	Vibrio cholerae	ATCC# 25870
144	Vibrio parahaemolyticus	ATCC# 17802
145	Yersinia bercovieri	ATCC# 43970
146	Yersinia rohdei	ATCC# 43380
147	Clostridium difficile (Non-toxigenic- Xla)(ES 1103)*	BMTU# 13799 (RMSCC 11305)
148	Clostridium difficile (Non-toxigenic- Xia)(6035/06)*	BMTU#9961 (RMSCC 11306)
149	Clostridium difficile (Non-toxigenic-Xlb) (F14)*	BMTU# 9962 (RMSCC 12414 and 11307)

Table 4: All Cross Reactivity Panel Members

{11}------------------------------------------------

{12}------------------------------------------------

{13}------------------------------------------------

Non-toxigenic Clostridium difficile (#147,148,149) were tested during Inclusivity study.

{14}------------------------------------------------

Interference 4.4.

Thirty eight commonly used medications, as well as fecal fat, whole blood, and mucin, were tested for potential interference effects with the cobas Cdiff test. All substances were tested at levels above what could be reasonably expected to be collected by a swab in a stool specimen. The amount of interference substance is expressed as concentration in primary stool specimen. Two toxigenic C. difficile isolates were spiked to 3 x Limit of Detection (LOD) of the cobas Cdiff test and used as targets in the tests. Exogenous substances at the highest tolerable concentration with no interference on cobas Cdiff test are shown in Table 5. Exogenous substances concentrations higher than listed in Table 5 may generate false negative or invalid results.

For fecal fat, no interference was observed up to 39% (w/v), and for mucin, no interference was observed up to 50% (w/v). For whole blood, no interference was observed up to 100% (v/v), which is equivalent to 100% of the capacity of the transfer swab. These results are summarized in Table 5.

Substance	Primary StoolSpecimenConcentration
Fecal Fat	0.22% - 39% (w/v)
Whole blood	100% (v/v)
Mucin	50% (w/v)
Aleve	100% (w/v)
Mylanta	100% (w/v)
Anusol	100% (w/v)
Dulcolax	23% (w/v)*
Equate Laxative	50% (w/v)*
Equate Hydrocortisone	100% (w/v)
E-Z-HD Barium Sulfate	100% (w/v)
Fleet	100% (w/v)
Glycerin Suppositories	100% (w/v)
Gravol Suppositories	100% (w/v)
Gynol II Contraceptive	10% (w/v)*
Imodium	100% (w/v)
Kaopectate	100% (w/v)
K-Y Jelly	100% (w/v)
Metronidazole	100% (w/v)

Results from Interference Substances Testing Table 5:

{15}------------------------------------------------

Substance	Primary StoolSpecimenConcentration
Miconazole	100% (w/v)
Mineral Oil	100% (w/v)
Monistat Cream	100% (w/v)
Monistat Complete Care	100% (w/v)
Nystatin Ointment	100% (w/v)
Palmitic Acid	100% (w/v)
Pedia Lax	100% (w/v)
Pepto Bismol	25% (w/v)*
Witch Hazel	50% (w/v)*
Preparation H Hemorrhoidal Cream	100% (w/v)
Preparation H Hemorrhoidal ointment	100% (w/v)
Dramamine	12.5% (w/v)*
Steric Acid	100% (w/v)
Docusate Sodium	100% (w/v)
Tums	50% (w/v)*
Mesalamine Rectal Suspension	100% (w/v)
Vagisil Anti-itch Cream	12.5% (w/v)*
Vancomycin	100% (w/v)
Vaseline	100% (w/v)
Sun Screen	100% (w/v)
Monistat Vaginal Insert	100% (w/v)
Vaginal Contraceptive Film	1 film vortexed with20 ml of primary stoolsample
Spermicidal Condoms	1 Condom vortexedwith 20 mL of primarystool sample

5. CLINICAL PERFORMANCE EVALUATION

5.1. Reproducibility

The reproducibility of the cobas Cdiff test was established in a multi-site investigation (2 external sites, 1 internal site) using simulated clinical samples evaluated across reagent lot, site, operator, and testing day. Overall, 818 tests were performed in this study, out of which 798 were valid for the study and included in the final percent agreement analysis.

Panels consisted of 3 members: 1 negative specimen and 2 specimens with different concentrations of 1 strain of toxigenic C. difficile – the first a low positive concentration at ~ 1 x limit of detection (LOD) and the second a moderate positive at ~3 x LOD. There were

{16}------------------------------------------------

3 replicates per panel member; testing of 1 replicate sample was 1 test. A run was defined as testing of 3 replicates of a panel member. For each of 3 lots, panels were run on 5 different nonconsecutive days by 2 different operators at each of the 3 sites. Table 6 shows the percent agreement results by panel member concentration, negative percent agreement for negative panel members and positive percent agreement for positive panel members. For the ~1 x LOD panel members (low positive), the overall percent agreement was 98.5% with a lower bound of the two-sided 95% Score CI of 96.2%. Overall percent agreement was 99.3% for the ~3 x LOD panel member (moderate positive) and 100% for the negative panel member.

Percent Agreement by Panel Member Compared to Acceptance Criteria Table 6:

		Percent Agreement
Panel Member	Number of ValidTest Results	Estimate	(95% CI)*	MetAcceptanceCriteria
Negative	262	100.0% (262/262)	(98.6%, 100.0%)	n/a
~1xLOD	266	98.5% (262/266)	(96.2%, 99.4%)	Yes
~3xLOD	270	99.3% (268/270)	(97.3%, 99.8%)	n/a

95% CI = two-sided 95% Score binomial confidence interval.

Results were in agreement when a positive panel member had a valid result of Positive (Cdiff Detected) for the analyte orwhen the negative panel member had a valid result of Negative (Cdiff Not Detected) for the analyte. n/a = not applicable

Table 7 presents the mean, total standard deviation (SD), and total percent coefficient of variation (CV %) of Ct values by panel member concentration.

Table 7 also presents percent agreement separately by lot, site, operator, and testing day.

{17}------------------------------------------------

Panel Member		Negative	~1x LOD	~3x LOD
Number of Valid Test Results		262	266	270
Overall Percent Agreement, % (n/N)*
	PercentAgreement	100.0(262/262)	98.5(262/266)	99.3(268/270)
Overall	95% Score CI	(98.6, 100.0)	(96.2, 99.4)	(97.3, 99.8)
Percent Agreement for Component Variables, % (n/N)*
Reagent Lot	1	100.0 (85/85)	100.0 (87/87)	100.0 (90/90)
	2	100.0 (88/88)	100.0 (90/90)	100.0 (90/90)
	3	100.0 (89/89)	95.5 (85/89)	97.8 (88/90)
Site	1	100.0 (85/85)	100.0 (88/88)	100.0 (90/90)
	2	100.0 (89/89)	97.8 (87/89)	98.9 (89/90)
	3	100.0 (88/88)	97.8 (87/89)	98.9 (89/90)
	1	100.0 (43/43)	100.0 (44/44)	100.0 (45/45)
	2	100.0 (42/42)	100.0 (44/44)	100.0 (45/45)
	3	100.0 (45/45)	97.7 (43/44)	100.0 (45/45)
Operator	4	100.0 (44/44)	97.8 (44/45)	97.8 (44/45)
	5	100.0 (44/44)	100.0 (44/44)	97.8 (44/45)
	6	100.0 (44/44)	95.6 (43/45)	100.0 (45/45)
Testing Day	1	100.0 (53/53)	100.0 (54/54)	100.0 (54/54)
	2	100.0 (54/54)	96.3 (52/54)	100.0 (54/54)
	3	100.0 (52/52)	96.0 (48/50)	98.1 (53/54)
	4	100.0 (52/52)	100.0 (54/54)	98.1 (53/54)
	5	100.0 (51/51)	100.0 (54/54)	100.0 (54/54)

Table 7: Percent Agreement by Panel Member for Lot, Site, Operator and Testing Day

Note: CI = confidence interval.

For the negative panel member: Percent agreement = (number of not detected results) x 100. For the positive panel members: Percent agreement = (number of detected results/total valid results) x 100.

Table 8 below presents the overall SD and percent CV (%) of Ct values for positive panel members at ~1 x LOD and ~3 x LOD concentrations, as well as the variance attributed to individual components (lot, site, operator, testing day, and within-run). Within-run variation refers to the variation within a 'study run' that consists of the 3 replicates for a given panel member processed by the same operator on the same analyzer on the same day.

Across all components, the total CV (%) was ≤ 1.9% with respect to the cycle threshold (Ct) value for all positive panel members. Within each component, the CV (%) was ≤ 1.6% across positive panel members.

{18}------------------------------------------------

Standard Deviation and Percent Coefficient of Variation
			Lot		Site		Operator		Day		Within-Run		Total
Panel Member	N	Mean Ct	SD	CV	SD	CV	SD	CV	SD	CV	SD	CV	SD	CV
~1xLOD	262	31.4	0.13	0.4%	0.26	0.8%	0.00	0.0%	0.13	0.4%	0.51	1.6%	0.60	1.9%
~3xLOD	268	30.0	0.23	0.8%	0.25	0.8%	0.08	0.3%	0.00	0.0%	0.38	1.3%	0.51	1.7%

Table 8: Overall Mean, Standard Deviation (SD) and Percent Coefficients of Variation (CV) for Ct Values from Valid Results for Positive Panel Members

5.2. Clinical Performance

The clinical performance of the cobas® Cdiff test was established in a prospective, multi-site investigation designed to evaluate the sensitivity and specificity of the cobas Cdiff test compared to the combined results of direct and enriched toxigenic culture using leftover, deidentified, unformed stool samples from patients suspected of having C. difficile infection.

Nine (9) study sites from geographically diverse locations participated in this study. Nineteen (19) operators distributed across these study sites performed testing with the cobas® Cdiff test. Reference culture (combined direct and enriched toxigenic culture) was performed at a reference laboratory. The remnant sample was stored frozen for discrepant analyses or possible additional testing, as determined by Roche Molecular Solution (RMS).

All evaluable discordant specimens and an equal number of randomly selected and representative concordant samples were used for discrepant testing by an FDA-cleared comparator NAAT. Testing was performed at an external lab that was preselected and qualified by RMS.

Evaluable fresh remnant specimens were prospectively collected from 1,013 patients; 483 males (47.7%) and 530 females (52.3%) with a median age of 59 years (range 5 to 98). All 1,013 specimens had valid results for both combined direct and enrichment culture and the cobas Cdiff test. Of the 1,013 specimens, 179 were positive for toxigenic C. difficile using the combined results from direct and enrichment toxigenic culture, for a prevalence rate of 17.7% for the study.

{19}------------------------------------------------

Comparison with Combined Direct and Broth Enrichment Culture 5.3.

The clinical performance of the cobas® Cdiff test compared with the combined results of direct and broth enrichment toxigenic culture are shown in Table 9. The sensitivity and specificity of the cobas® Cdiff test were 87.2% (156/179; 95% CI: 81.5% to 91.3%) and 98.1% (818/834; 95% CI: 96.9% to 98.8%), respectively; and the PPV and NPV were 90.7% (95% CI: 85.4% to 94.2%) and 97.3% (95% CI: 95.9% to 98.2%), respectively. Of the 23 specimens with falsenegative cobas® Cdiff test results relative to combined direct culture and enrichment culture, 19 were negative. 3 were positive and 1 was invalid by the second NAAT method. Of the 16 specimens with false-positive cobas Cdiff test results relative to combined direct and enrichment culture, 14 were positive and 2 were negative by the second NAAT method.

Table 9: Comparison of cobas Ciat® Cdiff Test with Combine Direct and Enrichment
Culture Results

	Combined Direct and Enrichment Culture Result
cobas® Liat Cdiff TestResult	Positive	Negative	Total
Detected	156	16	172
Not Detected	23	818	841
Total	179	834	1013

Sensitivity (95% CI)	87.2% (156/179; 95% CI = 81.5% to 91.3%)
Specificity (95% CI)	98.1% (818/834; 95% CI = 96.9% to 98.8%)
PPV (95% CI)	90.7% (156/172; 95% CI = 85.4% to 94.2%)
NPV (95% CI)	97.3% (818/841; 95% CI = 95.9% to 98.2%)

Note: Specimens with both combined direct and enrichment culture and valid cobas Liat Cdiff test results are considered evaluable and included in this summary table.

Note: Cl = (score) confidence interval, PPV = positive predictive value, NPV = negative predictive value, OPA = overall percent agreement.

Of the 1,016 specimens tested with the cobas® Cdiff test, 1.4% were initially invalid and 0.2% initially had failed results. Following 1 retest per invalid or failed result, the final invalid rate was 0.1% and the final failed rate was 0%.

{20}------------------------------------------------

Comparison with Direct Culture 5.4.

The performance of the cobas® Cdiff test compared to direct culture is shown in Table 10. The positive percent agreement (PPA) and negative percent agreement (NPA) of the cobas® Cdiff test compared to the direct culture for all 1.013 specimens were 94.6% (139/147) and 96.2% (833/866). respectively. Of the 8 specimens with false-negative cobas® Cdiff test results relative to direct culture, 7 were negative and 1 was positive by a second NAAT method. Of the 33 specimens with false-positive cobas 9 Cdiff test results relative to direct culture, only 17 were tested with the second NAAT method: 14 were positive and 3 were negative by that second NAAT method. The remaining 16/33 specimens were positive by enrichment culture and hence not tested with the second NAAT method per the discrepant analysis protocol.

Table 10: Comparison of cobas Liat® Cdiff Test with Direct Culture Results

	Direct Culture Result
cobas Liat Cdiff Test Result	Positive	Negative	Total
Detected	139	33	172
Not Detected	8	833	841
Total	147	866	1013
PPA	94.6% (139/147; 95% CI = 89.6% to97.2%)
NPA	96.2% (833/866; 95% CI = 94.7% to97.3%)

Note: Specimens with both direct culture and valid cobas Liat Cdiff test results are considered evaluable and included in this summary table.

Note: CI = (score) confidence interval.

CONCLUSIONS 6.

A comparison of the intended use, technological characteristics, and the results of non-clinical analytical and clinical performance studies demonstrate that the cobas® Cdiff Nucleic acid test for use on the cobas "Liat" System is substantially equivalent to the predicate device.

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.