The LIAISON® H. pylori IgG assay uses chemiluminescent immunoassay (CLIA) technology for the qualitative determination of IgG antibodies to Helicobacter pylori in human serum from symptomatic adults as an aid in the diagnosis of Helicobacter pylori infection. Assay results should be used in conjunction with other clinical or laboratory data to assist the clinician in making individual patient management decisions. The test has to be performed on the LIAISON® XL Analyzer.

The LIAISON® H. pylori IgG Control Set is intended for use as assayed quality control samples to monitor the performance of the LIAISON® H. pylori IgG assay.

Device Description

The method for qualitative determination of IgG antibodies to Helicobacter pylori (H.pv/ori IgG) is a two-step, indirect chemiluminescence immunoassay (CLIA). The principal components of the test are magnetic particles (solid phase) coated with Helicobacter pylori antigen and a conjugate of anti-human IgG monoclonal antibodies to linked to an isoluminol derivative (isoluminol-antibody conjugate). During the first incubation, H. pylori antibodies present in calibrators, samples or controls bind to the solid phase. During the second incubation, the monoclonal antibody conjugate reacts with H. pylori lgG that is already bound to the solid phase. After each incubation, unbound material is removed with a wash cycle.

Subsequently, the starter reagents are added and a flash chemiluminescence reaction is thus induced. The light signal, and therefore, the amount of isoluminol-antibody conjugate, is measured by a photomultiplier as relative light units (RLU) and is indicative of the presence of H. pylori IgG in calibrators, samples or controls.

All assay steps and incubations are performed by the LIAISON® XL Analyzer.

AI/ML Overview

The provided text describes a 510(k) premarket notification for the "LIAISON® H. pylori IgG" assay, an in vitro diagnostic device. This document focuses on demonstrating the substantial equivalence of the new device to a legally marketed predicate device (Siemens IMMULITE 2000 H. pylori IgG Assay).

Here's an analysis of the acceptance criteria and study data based on the provided text, using the requested framework:

Acceptance Criteria and Device Performance

The document doesn't explicitly state "acceptance criteria" in a table format with specific numerical targets. Instead, it presents performance data for comparison against a predicate device. The implied acceptance criteria are that the new device's performance (specifically, accuracy as measured by percent agreement) is comparable to that of the predicate device within acceptable statistical variation.

Here's a table summarizing the reported device performance, which serves as evidence of meeting the implied acceptance criteria for equivalence:

Table 1: Device Performance (Comparative Clinical Study)

Performance Metric	Acceptance Criteria (Implied: Comparable to Predicate)	Reported Device Performance (LIAISON® H. pylori IgG)
Negative Percent Agreement	High agreement with predicate device (e.g., >90-95%)	99.2% (95% CI: 97.9 – 99.8%)
Positive Percent Agreement	High agreement with predicate device (e.g., >90-95%)	95.5% (95% CI: 90.4 – 98.4%)

Note: The document also includes extensive precision/reproducibility data (Within-Laboratory Precision and Reproducibility at multiple sites), which are crucial for establishing the reliability and consistency of the assay. While not direct "acceptance criteria" in terms of accuracy against a true disease state, these data demonstrate the device's analytical performance meets expected standards for an in vitro diagnostic.

Study Details

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

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

Sample Size: 504 samples
Data Provenance:
- Country of Origin: Multiple geographical locations in the U.S.
- Retrospective or Prospective: Prospective study. Samples were collected from non-selected adult subjects sent to the laboratory for H. pylori IgG serological testing.

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

Not Applicable / Not Provided: For this type of in vitro diagnostic device (immunoassay for antibodies), the "ground truth" for the comparative clinical study is established by the results of a legally marketed predicate device, not by expert interpretation of images or other clinical data. Hence, there is no mention of experts establishing a ground truth in the context of radiologists or similar clinical reviewers.

4. Adjudication Method for the Test Set:

Not Applicable / Not Provided: Adjudication methods (e.g., 2+1, 3+1) are typically used in studies involving human interpretation (e.g., image reading) where there might be disagreement. In this comparative study with a predicate device, the comparison is directly between the new device's results and the predicate device's results, with no mention of human adjudication of results. The "ground truth" is effectively the predicate device's result.

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:

No: An MRMC comparative effectiveness study is not applicable as this is an in vitro diagnostic assay, not an AI-assisted diagnostic tool for human readers. The device performs the test autonomously.

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

Yes: This device (LIAISON® H. pylori IgG assay) is inherently a standalone diagnostic test. Its performance is evaluated based on its ability to detect antibodies independently. The clinical study compares its standalone performance against another standalone device (the predicate).

7. The Type of Ground Truth Used:

Predicate Device Results: For the comparative clinical study, the "ground truth" against which the LIAISON® H. pylori IgG assay was evaluated was the results from the FDA-cleared predicate device (Siemens IMMULITE 2000 H. pylori IgG Assay).

8. The Sample Size for the Training Set:

Not Applicable / Not Provided: This is an immunoassay, not an AI/machine learning algorithm that requires a "training set" in the conventional sense. The development of reagents and assay parameters is based on biochemical and analytical principles, not on training data in the way an AI model would be.

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

Not Applicable / Not Provided: As noted above, there is no "training set" in this context. The assay's performance characteristics (e.g., cutoff values) are established through analytical validation and optimization, often against known positive and negative samples, but not through a "ground truth" establishment process for a training set as would be done for an AI algorithm.

Summary

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Public Health Service

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

July 26, 2016

DIASORIN, INC. KELLY R. SAUER REGULATORY AFFAIRS SPECIALIST 1951 NORTHWESTERN AVE. STILLWATER, MN 55082-0285

Re:K161139

Trade/Device Name: Liaison H. pylori IgG, Liaison H. pylori IgG Control Set Regulation Number: 21 CFR 866.3110 Regulation Name: Campylobacter fetus serological reagents Regulatory Class: I Product Code: LYR, JJX, JJQ Dated: April 15, 2016 Received: April 22, 2016

Dear Ms. Sauer:

This letter corrects our substantially equivalent letter of July 22, 2016.

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration. listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

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

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21

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CFR Part 807); labeling (21 CFR Parts 801 and 809 ); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely.

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

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Indications for Use

510(k) Number (if known) K161139

Device Name LIAISON® H. pylori IgG LIAISON® H.pylori IgG Control Set

Indications for Use (Describe)

The LIAISON® H. pylori IgG Control Set is intended for use as assayed quality control samples to monitor the performance of the LIAISON® H. pylori IgG assay.

Type of Use (Select one or both, as applicable)
-------------------------------------------------

X Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

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5.0 510(k) SUMMARY

SUBMITTED BY:	Kelly R. SauerRegulatory Affairs SpecialistDiaSorin Inc.1951 Northwestern AvenueP.O. Box 285Stillwater, MN 55082-0285Phone (651) 351-5884Fax (651) 351-5669Email: kelly.sauer@diasorin.com
DATE PREPARED:	April 15, 2016
NAME OF DEVICE:
Trade Name:	LIAISON® H. pylori IgGLIAISON® H. pylori IgG Control Set
Common Names/Descriptions:	Helicobacter pylori IgG assay andHelicobacter pylori IgG controls
Classification Names:	Campylobacter fetus serological reagents:Class I, 21 CFR: 866.3110; Microbiology (83)
Product Code:	LYR - Campylobacter fetus serological reagentsJJX - Single (Specified) analyte controls(assayed and unassayed)JJQ - Colorimeter, photometer,spectrophotometer for clinical use
PREDICATE DEVICES :	IMMULITE® 2000 H. pylori IgGReference K000463 (assay)DiaSorin LIAISON® Control Toxo IgG II(K132234)

DEVICE DESCRIPTION:

INTENDED USE:

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The LIAISON® H. pylori IgG Control Set is intended for use as assayed quality control samples to monitor the performance of the LIAISON® H. pylori IgG assay.

KIT DESCRIPTION:

All assay steps and incubations are performed by the LIAISON® XL Analyzer.

COMPARISON TO PREDICATE DEVICE:

The DiaSorin LIAISON H. pylori IgG assay is substantially equivalent in principle and performance to Siemens IMMULITE 2000 H. pylori IgG Assay (K000463) which was FDA cleared June 1, 2000.

Table 1: Table of Similarities
Item	DeviceK161139	PredicateK000463
Intended Use	The LIAISON® H. pylori IgG assayuses chemiluminescent immunoassay(CLIA) technology for the qualitativedetermination of IgG antibodies toHelicobacter pylori in human serumfrom symptomatic adults as an aid in thediagnosis of Helicobacter pyloriinfection. Assay results should be usedin conjunction with other clinical orlaboratory data to assist the clinician inmaking individual patient managementdecisions. The test has to be performedon the LIAISON® XL Analyzer.The LIAISON® H. pylori IgG ControlSet is intended for use as assayedquality control samples to monitor theperformance of the LIAISON® H.pylori IgG assay.	For in vitro diagnostic use withthe IMMULITE® 2000 SystemsAnalyzers – for the qualitativedetection of IgG antibodies toHelicobacter pylori in humanserum from symptomatic adults,as an aid in the diagnosis ofHelicobacter pylori infection
Measured Analyte	IgG antibodies to H. pylori	Same

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Table 1: Table of Similarities
Item	DeviceK161139	PredicateK000463
Assay Type	Solid Phase Two StepChemiluminescent	Same
Sample Handling	Automated	Same
Reagent Storage	On-board or in refrigerator (@ 2-8°C	In refrigerator @, 2-8°C
Calibration	Two point verification of stored mastercurve	Same
Calibration	Qualitative assay	Same
Calculation of Result
Sample Matrix	Human Serum	Same
Sample SizeVolume	10 uL	Same
Controls	Provided separately	Same

Table 2 : Table of Differences
Item	DeviceK161139	PredicateK000463
Unit of Measure	Index	U/mL
Assay Time	30 minutes	60 minutes
Conjugate	Mouse monoclonal antibodies tohuman IgG linked to an isoluminolderivative	Monoclonal murine anti-humanIgG antibodies labeled withalkaline phosphatase in buffer
Measurement System	Photomultiplier (flashchemiluminescence reader)	Luminometer
Cutoff	0.85 Index	1.00 U/mL
Equivocal Zone	$0.80 - < 0.90$ Index	$0.90 - < 1.10$ U/mL
Controls	2 levels: negative and positive	3 levels: negative, low positive,positive
Control Stability	12 weeks	2 weeks
Open Use
Calibration Stability	4 weeks	1 week

PERFORMANCE DATA:

COMPARATIVE CLINICAL STUDIES:

A prospective study was performed to compare the performance of the LIAISON® H. pylori IgG assay to an FDA-cleared predicate device.

The prospective study consisted of 504 samples collected from non-selected adult subjects sent to the laboratory for H. pylori IqG serological testing.

A. Prospective:

The prospective population consisted of 504 adult subjects (Table 3) and collected from multiple locations geographical locations in the U.S.

The results are summarized as negative and positive percent agreement with 95% confidence intervals.

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LIAISON®H. pylori IgG	Comparator Assay			Total
	Positive	Equivocal	Negative
Positive	105	7	1	113
Equivocal	1	2	2	5
Negative	4	4	378	386
Total	110	13	381	504

Table 3: H. pylori IgG Prospective Population Comparison

		Percent Agreement	95% Confidence Interval
Negative	378/381	99.2%	97.9 – 99.8%
Positive	105/110	95.5%	90.4 – 98.4%

D. Prevalence:

The observed prevalence of the LIAISON® H. pylori IgG assay was calculated from the 504 samples collected from adult subjects sent to the lab for H. pylori lgG testing. The samples were from 151 males (30%) and 353 females (70%), and collected from multiple U.S. geographical locations. Known ages ranged from 18 to 91 years.

The observed prevalence of the LIAISON® H. pylori IgG is 22.4%. However, the prevalence may vary depending upon geographical location, age, gender, type of test employed, specimen collection and handling procedures as well as clinical history of the patient.

PRECISION/REPRODUCIBILITY:

12 Day Study

A within-laboratory precision study was performed consulting CLSI document EP5-A3 in the preparation of the testing protocol. Six contrived serum samples containing high negative, low positive and moderate positive concentrations of H. pylori IgG and kit controls (negative and positive) as duplicate samples were assaved in duplicate, in two runs per day over 12 operating days with multiple technicians. The following withinlaboratory precision results (Table 4) were obtained from samples tested internally at DiaSorin Inc. in one kit lot using one LIAISON® XL Analyzer.

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SampleID	MeanIndex	Within Run		Within Day		Between Day		Total
		SD	%CV	SD	%CV	SD	%CV	SD	%CV
Neg Ctrl	1341*	115	8.6%	46.8	3.5%	145	10.8%	190	14.2%
Neg Ctrl	1320*	120	9.1%	52.6	4.0%	119	9.0%	177	13.4%
Pos Ctrl	2.77	0.145	5.2%	0.119	4.3%	0.112	4.1%	0.218	7.9%
Pos Ctrl	2.73	0.144	5.3%	0.176	6.5%	0.053	1.9%	0.234	8.6%
Sample#1	0.74	0.049	6.6%	0.043	5.7%	0.051	6.8%	0.082	11.1%
Sample#2	0.71	0.048	6.7%	0.000	0.0%	0.030	4.2%	0.055	7.7%
Sample#3	1.32	0.071	5.4%	0.040	3.1%	0.075	5.7%	0.111	8.4%
Sample#4	1.25	0.081	6.5%	0.015	1.2%	0.053	4.3%	0.098	7.9%
Sample#5	1.52	0.076	5.0%	0.074	4.9%	0.000	0.0%	0.106	7.0%
Sample#6	1.50	0.084	5.6%	0.042	2.8%	0.095	6.3%	0.133	8.9%

Table 4. Within-Laboratory Precision

Sample N=48

*Precision calculations are based on signal (RLU) for the two negative controls

5 Day Study

A reproducibility/precision study was performed at two external sites and internally at DiaSorin Inc. consulting CLSI document EP15-A3 in the preparation of the testing protocol. Six contrived serum samples containing high negative, low positive and moderate positive concentrations of H. pylori IgG and kit controls (negative and positive) as duplicate samples were assayed in replicates of three, in two runs per day over 5 operating days with two technicians at each site performing the test every day. The following reproducibility/precision results (Table 5) were obtained from samples tested at the three sites in one kit lot.

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Sample		Within Run		Run to RunWithin Day		Day to DayWithin Site		Site to Site		Total
ID	MeanIndex	SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Neg Ctrl	1013*	54.0	5.3%	25.4	2.5%	19.1	1.9%	50.4	5.0%	80.4	7.9%
Neg Ctrl	996*	43.7	4.4%	25.4	2.6%	0.900	0.1%	79.8	8.0%	94.5	9.5%
Pos Ctrl	3.34	0.111	3.3%	0.060	1.8%	0.013	0.4%	0.062	1.9%	0.141	4.2%
Pos Ctrl	3.36	0.103	3.1%	0.012	0.4%	0.068	2.0%	0.019	0.6%	0.126	3.7%
Sample#1	0.626	0.035	5.6%	0.010	1.6%	0.016	2.5%	0.061	9.8%	0.073	11.7%
Sample#2	0.628	0.025	4.0%	0.018	2.9%	0.005	0.7%	0.047	7.4%	0.056	9.0%
Sample#3	1.28	0.043	3.4%	0.004	0.3%	0.030	2.4%	0.064	5.0%	0.083	6.5%
Sample#4	1.27	0.050	3.9%	0.011	0.9%	0.035	2.7%	0.044	3.5%	0.076	6.0%
Sample#5	1.82	0.061	3.3%	0.049	2.7%	0.045	2.5%	0.067	3.7%	0.113	6.2%
Sample#6	1.74	0.060	3.4%	0.034	1.9%	0.041	2.4%	0.067	3.8%	0.104	6.0%

Table 5. Reproducibility

Sample N=90

*Precision calculations are based on signal (RLU) for the two negative controls

CONCLUSION:

The material submitted in this premarket notification is complete and supports a substantial equivalence decision. The labeling is sufficient and it satisfies the requirements of 21CFR 809.10.

Regulation Number and Section

§ 866.3110

Campylobacter fetus serological reagents.(a)
Identification. Campylobacter fetus serological reagents are devices that consist of antisera conjugated with a fluorescent dye used to identifyCampylobacter fetus from clinical specimens or cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by this bacterium and provides epidemiological information on these diseases.Campylobacter fetus is a frequent cause of abortion in sheep and cattle and is sometimes responsible for endocarditis (inflammation of certain membranes of the heart) and enteritis (inflammation of the intestines) in humans.(b)
Classification. Class I (general controls).