The LIAISON® Helicobacter Antigen assay is a chemiluminescent immunoassay (CLIA) intended for the qualitative determination of Helicobacter pylori (H. pylori) antigen in human stool. The test is an aid in the diagnosis of patients suspected of H. pylori infection and to measure post therapy response from patients who have discontinued therapy for at least 4 weeks. Assay results should be used in conjunction with other clinical and laboratory data to assist the clinician in making individual patient management decisions.

The test must be performed on the LIAISON® XL Analyzer.

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

The performance characteristics of the LIAISON® Helicobacter Antigen Control Set have not been established for any other assay or instrument platforms different from the LIAISON® XL.

Device Description

The LIAISON® Helicobacter Antigen assay is a delayed one-step sandwich assay for detection of H. pylori stool antigen. H. pylori antigen is first extracted from human stool samples with sample diluent using the LIAISON® Stool Extraction Device.

The assay uses a monoclonal antibody for detection of H. pylori stool antigen. The assay uses 200 µL of sample consisting of a mixture of extraction buffer and stool extracted H. pylori stool antigen which is incubated with paramagnetic particles coated with a capture antibody for H. pylori stool antigen. Following incubation, an isoluminol conjugated antibody for H. pylori stool antigen is added to the reaction and incubated. After the second incubation, the unbound material is removed with a wash cycle. The starter reagents are then added and a flash chemiluminescent reaction is initiated. The light signal is measured by a photomultiplier as relative light units (RLU) and is proportional to the concentration of H. pylori stool antigen present in the calibrators, controls or samples.

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

AI/ML Overview

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

Device Name: LIAISON® Helicobacter Antigen

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of numerical thresholds for sensitivity and specificity. Instead, it presents the achieved performance in clinical studies. We can infer the "accepted performance" to be the results obtained in these studies, which are then deemed sufficient for substantial equivalence.

Metric	Acceptance Criteria (Implied)	Reported Device Performance (Pre-Therapy Population)	Reported Device Performance (Post-Therapy Population)
Clinical Specificity	Not explicitly stated	98.6% (95.9 – 99.7% CI)	N/A (no 'not infected' cases in post-therapy study)
Clinical Sensitivity	Not explicitly stated	95.5% (87.5 – 99.1% CI)	100% (63.1 - 100% CI)

Further Performance Data (Precision/Reproducibility):

The precision studies (12-Day and 5-Day) show low percent coefficients of variation (%CV) for various samples and controls, indicating good reproducibility. This data supports the reliability of the device but doesn't have a direct "acceptance criteria" table in the manner of specificity/sensitivity.

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

Pre-Therapy Population Test Set: 277 subjects (specimens)
Post-Therapy Population Test Set: 8 subjects (specimens)
Data Provenance:
- Country of Origin: Both within the US and outside the US (OUS). The specific countries OUS are not detailed.
- Retrospective or Prospective: Prospective study. Samples were collected from subjects undergoing evaluation for H. pylori infection.

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

The ground truth was established using a "Composite Reference Method (CRM)" which comprised at least two of the three methods:

Histological Evaluation
Culture of the Organism
Urease Detection Test

The document does not specify:

The number of experts involved in performing or interpreting these CRM methods.
The qualifications of those experts (e.g., specific medical specialization, years of experience).

4. Adjudication Method for the Test Set

The document describes the ground truth as a "Composite Reference Method (CRM)" using at least two of three methods. It does not explicitly detail an adjudication method (e.g., 2+1, 3+1 consensus) if there were discrepancies between the CRM components. It implies that the CRM itself served as the definitive diagnosis.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of AI Improvement

No, an MRMC comparative effectiveness study involving human readers and AI assistance was not performed. This device is an in-vitro diagnostic (IVD) assay designed for standalone performance, not for aiding human interpretation of complex images or data in an MRMC setting.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study Was Done

Yes, the clinical performance study directly assesses the standalone performance of the LIAISON® Helicobacter Antigen assay. The results (sensitivity and specificity) are for the device itself, against the Composite Reference Method, without human interpretation as a variable or as an aid to the device. The device is a "chemiluminescent immunoassay (CLIA)" performed on an automated analyzer (LIAISON® XL Analyzer).

7. The Type of Ground Truth Used

The ground truth used was a Composite Reference Method (CRM), consisting of at least two of the following:

Histological Evaluation
Culture of the Organism
Urease Detection Test

This is a robust method often used in IVD studies to establish infection status. It directly assesses the presence of the pathogen by different laboratory techniques.

8. The Sample Size for the Training Set

The document does not mention a specific training set size or methodology. Given that this is an IVD assay, the development process would involve internal optimization and validation, but the reported performance data focuses on a distinct test set (prospective clinical study) to demonstrate performance against a reference standard. There isn't an "algorithm training set" in the sense of AI/machine learning models that typically require large, curated training datasets for model development.

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

As no specific "training set" with separate ground truth establishment is described for an algorithm, this question is not directly applicable in the context of this device's submission. The development and internal validation of the assay (e.g., establishing optimal antibody concentrations, reaction times, cutoff values) would have occurred prior to the clinical performance studies, likely using characterized samples, but details of this are not part of the regulatory submission description for a training set.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left, there is a symbol of the Department of Health & Human Services. To the right of the symbol, there is the FDA logo in blue, followed by the words "U.S. FOOD & DRUG" in a larger font and "ADMINISTRATION" in a smaller font below it, also in blue.

August 31, 2018

DiaSorin Inc. Sandra Zimniewicz Regulatory Affairs Specialist 1951 Northwestern Ave. Stillwater. Minnesota 55082-0285

Re: K181464

Trade/Device Name: LIAISON Helicobacter Antigen, LIAISON Helicobacter Antigen Control Set Regulation Number: 21 CFR 866.3110 Regulation Name: Campylobacter fetus serological reagents Regulatory Class: Class I Product Code: LYR, JJX, JJF Dated: June 5, 2018 Received: June 6, 2018

Dear Sandra Zimniewicz:

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/cdrl/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 801 and Part 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR

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for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (OS) 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Ribhi Shawar -S
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) K181464

Device Name

LIAISON® Helicobacter Antigen LIAISON® Helicobacter Antigen Control Set

Indications for Use (Describe)

The test must be performed on the LIAISON® XL Analyzer.

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

The performance characteristics of the LIAISON® Helicobacter Antigen Control Set have not been established for any other assay or instrument platforms different from the LIAISON® XL.

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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510(k) SUMMARY

SUBMITTED BY:	Sandra ZimniewiczRegulatory Affairs SpecialistDiaSorin Inc.1951 Northwestern AvenueP.O. Box 285Stillwater, MN 55082-0285Phone (651) 351-5711Fax (651) 351-5711Email: sandra.zimniewicz@diasorin.com
DATE PREPARED:	August 31, 2018
NAME OF DEVICE:
Trade Name:	LIAISON® Helicobacter AntigenLIAISON® Helicobacter Antigen Control Set
Common Names/Descriptions:	Helicobacter pylori Antigen assay andHelicobacter pylori Antigen controls
Classification Names:	Campylobacter fetus serological reagents:Class I, 21 CFR: 866.3110; Microbiology (83)
	Single (Specified) analyte controls (assayedand unassayed): Class I,21 CFR 862.1660; Clinical Chemistry (75)
Product Code:	LYR - Campylobacter fetus serological reagentsJJX - Single (Specified) analyte controls(assayed and unassayed)JJF – Analyzer, Chemistry, Micro,For Clinical Use
PREDICATE DEVICES :	Meridian Platinum Premier HpSA PLUSReference_K053335 assayLIAISON® H. pylori IgG Control Set (K161139)

DEVICE DESCRIPTION:

INTENDED USE:

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clinical and laboratory data to assist the clinician in making individual patient management decisions.

The test must be performed on the LIAISON® XL Analyzer.

The LIAISON® Helicobacter Antigen Control Set is intended for use as assayed quality control samples to monitor the performance of the LIAISON® Helicobacter Antigen assay. The performance characteristics of the LIAISON® Helicobacter Antigen Control Set have not been established for any other assay or instrument platforms different from the LIAISON® XL.

KIT DESCRIPTION:

controls or samples.

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

Similarities
Item	Device: LIAISON® HelicobacterAntigen (K181464)	Predicate: PremierPlatinum HpSA PLUS(K053335)
Product Code	LYR	Same
Intended Use	The LIAISON® Helicobacter Antigenassay is a chemiluminescentimmunoassay (CLIA) intended for thequalitative determination ofHelicobacter pylori (H. pylori) antigenin human stool. The test is an aid inthe diagnosis of patients suspected ofH. pylori infection and to measure posttherapy response from patients whohave discontinued therapy for at least4 weeks. Assay results should be usedin conjunction with other clinical and	The Premier PlatinumHpSA PLUS enzymeimmunoassay (EIA) is an invitro qualitative procedurefor the detection ofHelicobacter pyloriantigens in human stool.Test results are intended toaid in the diagnosis of H.pylori infection and tomonitor response duringand post-therapy in

COMPARISON TO FDA CLEARED METHOD

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Similarities
Item	Device: LIAISON® HelicobacterAntigen (K181464)	Predicate: PremierPlatinum HpSA PLUS(K053335)
	laboratory data to assist the clinician inmaking individual patient managementdecisions.The test must be performed on theLIAISON® XL Analyzer.The LIAISON® Helicobacter AntigenControl Set is intended for use asassayed quality control samples tomonitor the performance of theLIAISON® Helicobacter Antigen assay.The performance characteristics of theLIAISON® Helicobacter AntigenControl Set have not been establishedfor any other assay or instrumentplatforms different from the LIAISON®XL.	patients. Accepted medicalpractice recommends thattesting by any currentmethod, to confirmeradication, be done atleast four weeks followingcompletion of therapy.
Results	Qualitative	Same
Measurand	H. pylori antigen	Same
SpecimenRequired	Stool	Same

Differences
Item	Device: LIAISON Helicobacter Antigen(K181464)	Predicate: PremierPlatinum HpSA PLUS(K053335)
Limit ofDetection	4 ng/mL	$\ge$ 4.67 ng/mL in stool
Technology	Automated ChemiluminescentImmunoassay (CLIA)	Manual/SemiautomatedEnzyme Immunoassay(EIA)
Cutoff	1.1 Index (for positive)	0.100 at OD450/630
Interpretation	Negative <0.90 IndexEquivocal ( $\ge$ 0.90 Index and < 1.10 Index)Positive $\ge$ 1.10 Index	Negative <0.100 OD450/630Positive $\ge$ 0.100 OD450/630

PERFORMANCE DATA: COMPARATIVE CLINICAL STUDIES:

A prospective study was performed to compare the performance of the LIAISON®

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Helicobacter Antigen assay to at least two of the three methods which comprise the Composite Reference Method (CRM): Histological Evaluation, Culture of the Organism, and Urease Detection Test.

The prospective study consisted of 285 specimens collected from subjects undergoing evaluation for H. pylori infection to determine infection status both pre and post therapy. Prospective samples were collected at multiple sites, and regions, within the US and outside the US (OUS).

Pre-Therapy population

The pre-therapy study population consisted of 277 male or female adult subjects (≥ 22 years), undergoing evaluation to determine H. pylori infection status prior to any therapeutic intervention.

The results are summarized as sensitivity and specificity with 95% confidence intervals.

	Composite Reference Method Diagnosis
LIAISON® Helicobacter Antigen	Infected	Not Infected	Total
Positive	64	3	67
Equivocal	0	0	0
Negative	3	207	210
Total	67	210	277

H. pylori Pre-Therapy Population Comparison

			95% Confidence Interval
Clinical Specificity	207/210	98.6%	95.9 – 99.7%
Clinical Sensitivity	64/67	95.5%	87.5 – 99.1%

Post-Therapy population

The post-therapy study population consisted of 8 male or female adult subjects (≥ 22 years), undergoing evaluation to measure post therapy response for H. Pylori.

The results are summarized as sensitivity with 95% confidence intervals.

H. pylori Post-Therapy Population Comparison

	Composite Reference Method Diagnosis
LIAISON® Helicobacter Antigen	Infected	Not Infected	Total
Positive	8	0	8
Equivocal	0	0	0
Negative	0	0	0
Total	8	0	8

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			95% Confidence Interval
Clinical Sensitivity	8/8	100%	63.1 - 100%

Prevalence:

The observed prevalence of the LIAISON® Helicobacter Antigen assay was calculated from the 277 specimens obtained from eligible subjects of the pre-therapy population who underwent EGD with signs and symptoms of a Helicobacter pylori infection. The specimens were from 86 males (31%) and 191 females (69%), collected from multiple U.S. and OUS geographical locations. Known ages ranged from 22 to 87 years old.

The observed prevalence of the LIAISON® Helicobacter Antigen assay is 24.2%. 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 antigen samples containing high negative, low positive and moderate positive concentrations of H. pylori stool antigen and kit controls (negative and positive). All samples and controls were assayed in duplicate, two runs per day over twelve operating days with multiple technicians. The following within-laboratory precision results were obtained from samples tested internally at DiaSorin Inc. with one kit lot using one LIAISON® XL Analyzer.

Sample ID	Mean	Within Run		Within Day		Between Day		Total
N=48	Index	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Neg Ctrl	0.06	0.00	7.8%	0.00	0.0%	0.00	4.6%	0.00	7.8%
Neg Ctrl	0.06	0.00	7.6%	0.00	0.0%	0.00	5.6%	0.01	8.8%
Pos Ctrl	2.72	0.05	1.9%	0.04	1.5%	0.03	1.2%	0.07	2.6%
Pos Ctrl	2.70	0.06	2.4%	0.03	1.2%	0.01	0.2%	0.07	2.7%
Sample #1	0.80	0.02	2.6%	0.02	2.3%	0.03	3.1%	0.04	4.7%
Sample #2	0.84	0.02	2.9%	0.01	1.0%	0.03	3.8%	0.04	4.9%
Sample #3	1.84	0.06	3.1%	0.02	1.2%	0.04	2.4%	0.08	4.1%
Sample #4	1.99	0.04	2.1%	0.07	3.5%	0.02	1.0%	0.08	4.2%
Sample #5	3.03	0.08	2.7%	0.00	0.0%	0.07	2.2%	0.10	3.3%
Sample #6	3.00	0.08	2.6%	0.06	2.1%	0.06	2.0%	0.12	3.9%

Within-Laboratory Precision

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 antigen samples containing high negative, low positive and

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moderate positive concentrations of H. pylori stool antigen 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 were obtained from samples tested at the three sites using one kit lot.

Sample ID	MeanIndex	Within Run		Run to RunWithin Day		Day to DayWithin Site		Site to Site		Total
	Value	SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Neg Ctrl	0.07	0.004	5.1%	0.002	2.4%	0.002	2.1%	0.009	12.5%	0.010	13.9%
Neg Ctrl	0.07	0.003	4.0%	0.003	4.0%	0.001	1.4%	0.007	10.0	0.009	11.5%
Pos Ctrl	4.80	0.076	1.6%	0.050	1.0%	0.063	1.3%	0.105	2.2%	0.153	3.1%
Pos Ctrl	4.78	0.070	1.5%	0.050	1.0%	0.068	1.4%	0.113	2.4%	0.157	3.3%
Sample #1	2.12	0.034	1.6%	0.038	1.8%	0.108	5.1%	0.119	5.6%	0.168	8.0%
Sample #2	2.37	0.049	2.1%	0.046	1.9%	0.156	6.6%	0.226	9.5%	0.283	11.9%
Sample #3	0.69	0.024	3.5%	0.021	3.0%	0.037	5.4%	0.065	9.4%	0.081	11.8%
Sample #4	0.69	0.023	3.3%	0.026	3.8%	0.019	2.7%	0.065	9.4%	0.077	11.0%
Sample #5	1.21	0.031	2.5%	0.037	3.1%	0.029	2.4%	0.093	7.7%	0.109	9.0%
Sample #6	1.20	0.021	1.7%	0.030	2.5%	0.056	4.7%	0.120	10.1%	0.138	11.5%

Reproducibility

REAGENT STABILITY

LIAISON® Helicobacter Antigen
Study	Stability
Calibration Curve	4 weeks
Reagent Integral Open Use storage On-board Analyzer	8 weeks
Reagent Integral Open Use storage at 2-8°C	8 weeks
Calibrator Freeze/Thaw cycles	3 cycles
Reconstituted Calibrator open use at room temperature(18-25°C)	8 hours
Reconstituted Calibrator open use at 2 - 8°C	28 days
Reconstituted Calibrator open use at -20°C	16 weeks

LIAISON® Helicobacter Antigen Control Set
Study	Stability
Reconstituted Positive Control Open Use at -20°C	16 weeks
Reconstituted Positive Control Freeze/Thaw cycles	3 cycles
Negative and Reconstituted Positive Control Open Use storage at 2-8°C	28 days

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SPECIMEN STABILITY

Studies were performed to determine the stability of sample at different storage conditions. The results are provided in the tables below.

Stool Sample
Study	Stability
Refrigerated at 2- 8°C	72 hours
Store samples frozen at -20°C if not tested within 72 hours.

Sample Extract
Study	Stability
Room temperature (18 - 25°C)	8 hours
Refrigerated at 2- 8°C	72 hours
Frozen at -20°C	12 weeks
Freeze/Thaw cycles	3 cycles

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).