The Roche Elecsys Anti-HAV immunoassay is used for the in vitro qualitative detection of total antibodies (IgM and IgG) to hepatitis A virus in human serum and plasma (K2-EDTA). The assay is intended for use as an aid in the laboratory diagnosis of past or acute/recent hepatitis A infection.

Assay results, in conjunction with other laboratory results and clinical information, may be used to provide presumptive evidence of infection with hepatitis A virus in persons with signs or symptoms of hepatitis and in persons at risk for hepatitis A infection, or used as an aid to determine the presence of antibody response to HAV in vaccine recipients.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on Elecsys and cobas e immunoassav analyzers.

Elecsys PreciControl Anti-HAV is used for the quality control of the Elecsys Anti-HAV immunoassay on the Elecsys and cobas e immunoassay analyzers.

Device Description

The Elecsys anti-HAV test is a qualitative assay based on electrochemiluminescence immunoassay "ECLIA" technology. The Elecsys anti-HAV test utilizes a competitive immunoassay format in which sample anti-HAV antibody competes with biotinylated and ruthenvlated anti-HAV monoclonal antibodies for a limited amount of cell culture-derived HAV antigen. The sample antibody and the HAV antigen react in the first incubation. The biotinylated antibodies and ruthenium complex® -labeled antibodies specific for HAV antigen are added in the second incubation together with streptavidin-coated magnetic microparticles. The unbound HAV antigen reacts with the modified antibodies and the resulting immune complexes are bound to the solid phase through a biotinstreptavidin interaction. If all HAV antigens are complexed by sample anti-HAV antibody during the first incubation, no modified/labeled immune complexes are formed and captured during the second incubation.

Following the second incubation, the reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are removed by elution with ProCell. Application of a voltage to the electrode induces chemiluminescent emission from the captured immune complexes which is measured by a photomultiplier. The level of signal detected by the system decreases as the concentration of the anti-HAV antibody target present in a patient sample increases.

Results are determined via a calibration curve which is generated by 2-point calibration on the instrument and a master curve provided via the reagent barcode. The calibration process converts the output so that low levels of sample anti-HAV antibodies are expressed by low output and high levels of antibody are expressed by high output. These outputs are finally interpreted on a qualitative basis around the established cut-off output.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Elecsys® Anti-HAV Assay, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally implied by the performance metrics reported, as the submission concludes that the information "supports a substantial equivalence decision." This means the reported performance met the FDA's expectations for equivalence to the predicate device.

Performance Metric	Acceptance Criteria (Implied/General)	Reported Device Performance
Analytical Performance
Precision	Acceptable %CV for repeatability and intermediate precision, typically within established guidelines (e.g., CLSI EP15-A2/EP5-A2).	Elecsys 2010: - PC Anti-HAV 1: Repeatability CV 1.8%, Int. Precision CV 3.1% - PC Anti-HAV 2: Repeatability CV 3.2%, Int. Precision CV 4.5% - HSP 1, 2, 3: Repeatability CVs 2.5-3.4%, Int. Precision CVs 3.0-4.6% MODULAR ANALYTICS E170: - PC Anti-HAV 1: Repeatability CV 1.5%, Int. Precision CV 5.5% - PC Anti-HAV 2: Repeatability CV 2.3%, Int. Precision CV 5.8% - HSP 1, 2, 3: Repeatability CVs 1.1-3.5%, Int. Precision CVs 4.3-5.6% Reproducibility (Overall within-site and between-site CVs also provided, e.g., Overall PPA/NPA > 90%)
Detection Limits (LoD)	Lowest amount of analyte detectable with 95% probability, set at 6.00 IU/L.	Elecsys 2010 / cobas e 411: LoD = 5.155 IU/L MODULAR ANALYTICS E170 / cobas e 601: LoD = 2.994 IU/L Reported in labeling: 6.00 IU/L for both types.
Analytical Specificity (Cross-reactivity)	Minimal false positives with common interfering conditions/diseases.	177 samples from 15 subgroups tested: 174 non-reactive, 3 discordant with predicate. No HAMA effect found.
Analytical Specificity (Interference)	Recovery of positive samples within ± 20 % of initial value.	Unaffected by icterus (< 50 mg/dL), hemolysis (< 1000 mg/dL), lipemia (< 1500 mg/dL), and biotin (< 50 ng/mL). No interference from 18 common pharmaceuticals and folic acid.
Assay Cut-off Calibration	Negative Calibrator < 20 IU/L; Positive Calibrator ≥ 40 IU/L. (WHO recommendation for vaccination set at 20IU/L)	Negative Calibrator (Cal1) < 20 IU/L; Positive Calibrator (Cal2) ≥ 40 IU/L.
Clinical Performance
Overall Positive Percent Agreement (PPA) with Predicate	High agreement (e.g., >90-95%) with a legally marketed predicate device.	Overall PPA: 98.12% (96.46% to 99.14% CI)
Overall Negative Percent Agreement (NPA) with Predicate	High agreement (e.g., >90-95%) with a legally marketed predicate device.	Overall NPA: 97.37% (95.70% to 98.52% CI)
Seroconversion Sensitivity	Agreement with predicate and vendor data for seroconversion panels.	Elecsys Anti-HAV assay showed similar performance to comparator (Abbott AxSym HAV AB-2.0) based on post bleed day of earliest reactive/last positive result for 3 panels.
Method Comparison (between platforms)	High PPA and NPA (e.g., >95%) between the Elecsys 2010 and MODULAR ANALYTICS E170.	PPA: 96.8% (91.0% to 99.3% CI) NPA: 98.0% (93.0% to 99.8% CI) Pearson's regression correlation: 0.9951 (slope 1.024, intercept -0.555).

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

Clinical Performance Study (Comparison with Predicate):
- Total Samples: 1050 samples (after excluding one concordantly equivocal sample).
- Cohort Breakdown:
  - Subjects for whom routine hepatitis A testing had been ordered.
  - Hospitalized patients.
  - Subjects at increased risk for hepatitis.
  - Subjects with signs and symptoms of hepatitis.
  - Subjects characterized with acute hepatitis A.
  - Subjects below the age of 21 years (pediatric/adolescents).
  - Specific numbers per cohort are detailed in the tables (e.g., 197 for Routine HAV Testing, 219 for Hospitalized, etc., summing to the overall total).
- Data Provenance: Multi-center study conducted in the U.S. (across 3 sites: BW, WU, JH). Samples were a mix of prospective and retrospective collections. All samples stored frozen before shipment.
Analytical Specificity (Cross-reactivity): 177 samples from 15 potentially cross-reactive subgroups.
Analytical Specificity (Interference): Native human serum pools, and 18 commonly used pharmaceuticals and folic acid.
Prevalence Study (Expected Values): 602 patients (300 from high prevalence region, Western U.S. (New Mexico); 302 from low prevalence region, Eastern U.S. (Indiana)). This was a prospective study.
Seroconversion Sensitivity: 3 seroconversion panels.
Method Comparison (between platforms): 202 samples (100 non-reactive from prevalence cohort, 53 reactive from clinical cohorts, 49 reactive from Roche R&D archive).

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

This information is not explicitly provided in the summary. The "ground truth" for clinical performance is established by comparing the Elecsys Anti-HAV assay results against an "FDA-cleared reference method" (the predicate device, Abbott AxSym HAVAB® 2.0). However, the summary does not specify if or how many human experts were involved in interpreting results from either the new device or the predicate to establish a "ground truth" in cases of discordance, or to confirm clinical status. The study relies on the predicate device's established performance and classification of samples.

4. Adjudication Method for the Test Set

The summary does not explicitly describe an adjudication method involving human experts for the test set. The clinical performance section states that the assay's performance was determined by agreement with the predicate device, which indicates a direct comparison rather than a human adjudication process to "resolve" discordant results. For "borderline" results from the Elecsys Anti-HAV assay (18.0 < IU/L < 22.0), the protocol involves retesting in duplicate and interpreting based on the majority of the three results (initial + 2 retests). This is an internal retesting protocol, not an external expert adjudication.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, an MRMC comparative effectiveness study was not done. This document describes the performance of an in vitro diagnostic (IVD) assay, not the performance of human readers using an AI device. Therefore, the effect size of human readers improving with AI vs without AI assistance is not applicable.

6. Standalone Performance

Yes, standalone performance was done. The entire submission details the performance of the Elecsys Anti-HAV assay (the algorithm/device) as a standalone diagnostic tool for detecting total antibodies to hepatitis A virus. All performance metrics reported (precision, detection limits, analytical specificity, and clinical agreement with the predicate device) reflect the device's performance without human interpretation or intervention in the diagnostic output itself (though a human ultimately uses the result for clinical decision-making).

7. The Type of Ground Truth Used

The primary "ground truth" used for evaluating the clinical performance of the Elecsys Anti-HAV assay was the results from an FDA-cleared reference method: the Abbott AxSym HAVAB® 2.0 assay. The submission explicitly states: "The performance of the Elecsys anti-HAV assay was determined by percent agreement among negative samples and percent agreement among positive samples, against a consensus comparator method. The main predicate (Abbott AxSym HAV AB- 2.0) was used as sole comparator/reference."
For seroconversion, vendor data from the predicate device was also used.

8. The Sample Size for the Training Set

The summary does not explicitly specify a "training set" sample size in the context of an AI/machine learning model. This is an immunoassay, which typically relies on established chemical and biological reactions and calibration curves rather than an iterative learning process with a "training set" in the modern AI sense. The assay uses a master curve provided via a reagent barcode and 2-point instrument calibration. The master standard curve is established by diluting an anti-HAV positive human serum with an analyte free human serum matrix, with concentration values assigned by reading from a reference calibrator curve using multiple instruments and replicates. The "training" in this context would be the development and optimization of the assay itself and its reagents.

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

As noted above, there isn't a "training set" in the AI sense for this immunoassay. However, the calibration process (which is analogous to establishing the basis for decision-making) works as follows:

The device is standardized against the "Second International Standard for Anti-Hepatitis A, Immunoglobulin, Human, NIBSC code: 97/646" of the NIBSC.
Calibrators: Two calibrators are used: Calibrator 1 (anti-HAV negative serum) and Calibrator 2 (anti-HAV positive serum with approx. 46 IU/L).
Master Standard Curve: A reagent lot-specific master standard curve is provided on the barcode. This curve is established by diluting an anti-HAV positive human serum with an analyte free human serum matrix. The concentration value is assigned by reading the concentration from the reference calibrator curve using four Elecsys 2010 and four MODULAR ANALYTICS E170 instruments with 2 runs and 2 replicates per run and per instrument.
The calibration data ensures the assay's output signal can be accurately converted into a quantitative reading (IU/L) and then interpreted qualitatively (Reactive, Equivocal, Non-Reactive) based on the established cut-off.

Summary

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number: K100903
B. Purpose for Submission: Clearance of New Device
C. Measurand: Total Antibody to Hepatitis A Virus in serum and heparinized plasma
D. Type of Test: Electrochemiluminescence immunoassay (ECLIA)
E. Applicant: Roche Diagnostics
F. Proprietary and Established Names: Elecsys® Anti-HAV Assay Elecsys® PreciControl anti-HAV Assay

G. Regulatory Information:

1. Regulation section:	21 CFR §866.3310, Hepatitis A virus Serological Assays21 CFR §862.1660, Quality Control Material
2. Classification:	Class II
3. Product code:	LOL (Hepatitis A Test – antibody and IgM Antibody)JJX (Quality control material, assayed and unassayed)
4. Panel:	Microbiology (83)

H. Intended Use:

1. Intended use(s):
  The Roche Elecsys Anti-HAV immunoassay is used for the in vitro qualitative detection of total antibodies (IgM and IgG) to hepatitis A virus in human serum and plasma (K2-EDTA). The assay is intended for use as an aid in the laboratory diagnosis of past or acute/recent hepatitis A infection.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on Elecsys and cobas e immunoassav analyzers.

Elecsys PreciControl Anti-HAV is used for the quality control of the Elecsys Anti-HAV immunoassay on the Elecsys and cobas e immunoassay analyzers.

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This assay is not intended for screening blood or solid or soft tissue donors. Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients. The users are responsible for establishing their own assay performance characteristics in these populations.

Caution: U.S. Federal Law restricts this device to sale by or on the order of a physician.

1. Indication(s) for use:
  Same as Intended Use
1. Special conditions for use statement(s):
  For prescription use only
1. Special instrument requirements:
  Elecsys 2010 and cobas e 411 analyzers; MODULAR ANALYTICS E170 and cobas e 601 analyzers

I. Device Description:

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a) Tris(2,2'-bipyridyl)ruthenium(II)-complex (Ru(bpy)) 3 2+

J. Substantial Equivalence Information:

1. Predicate device name(s): Abbott AxSym HAVAB® 2.0
Predicate Numbers (s): 2.
1. Comparison with predicate:

Similarities
Anti-HAV Immunoassay Comparison
Feature	Elecsys Anti-HAV Assay	Predicate DeviceAbbott Axsym HAVAB 2.0Assay (P780012/S009)
Intended Use	The Roche Elecsys Anti-HAVimmunoassay is used for the in vitroqualitative detection of total antibodies(IgM and IgG) to hepatitis A virus inhuman serum and plasma (K2-EDTA).The assay is intended for use as an aid inthe laboratory diagnosis of past oracute/recent hepatitis A infection.Assay results, in conjunction with otherlaboratory results and clinical information,may be used to provide presumptiveevidence of infection with hepatitis Avirus in persons with signs or symptomsof hepatitis and in persons at risk forhepatitis A infection, or used as an aid todetermine the presence of antibodyresponse to HAV in vaccine recipients.The electrochemiluminescenceimmunoassay “ECLIA” is intended foruse on Elecsys and cobas e immunoassayanalyzers.	Immunoassay for the qualitativedetection of total antibody tohepatitis A virus (anti-HAV) inhuman serum or plasma(potassium EDTA, sodiumheparin, sodium citrate, orlithium heparin). A test for anti-HAV is indicated as an aid in thelaboratory diagnosis of previousor ongoing hepatitis A viralinfection or in the identificationof HAV-susceptible individualsfor vaccination.Assay results, in conjunctionwith other laboratory results andclinical information, may beused to provide presumptiveevidence of infection withhepatitis A virus in persons withsigns or symptoms of hepatitisand in persons at risk forhepatitis A infection.
Indications forUse	Same	Same
Sample Type	Human serum and plasma	Same
Anti-HAV Immunoassay Comparison
Features	Elecsys Anti-HAV Assay	Predicate DeviceAbbott Axsym HAVAB 2.0 Assay(P780012/S009)
DetectionProtocol	Electrochemiluminescenceimmunoassay (ECLIA)	Microparticle Enzyme Immunoassay(MEIA)
Traceability/Standardization	Standardized against the "SecondInternational Standard for Anti-Hepatitis A, Immunoglobulin,Human, NIBSC code: 97/646" ofthe NIBSC (National Institute forBiological Standards and Control).	Not Given
Interpretation ofResults	≥ 22.0 IU/L Reactive18.0 ≤ IU/L< 22.0 Equivocal<18.0 IU/L Negative	0.000 to 1.000 Reactive1.001 to 1.200 Grayzone1.201 to 3.000 Nonreactive>3.000 Not applicable
CalibrationInterval	Once per reagent lot and• After 1 month (28 days) whenusing the same reagent lot• After 7 days (when using thesame reagent kit on the analyzer)• As required: e.g., quality controlfindings outside the specifiedlimits	A minimum of two replicates of theAxSYM HAFVAB 2.0 Index Calibratormust be tested. A single sample of boththe Negative and Positive Controls mustbe tested as a means of evaluating theassay calibration. Once the calibration isaccepted and stored, all subsequentsamples may be tested without furthercalibration unless one or more of thefollowing occur:• A reagent pack with a new lot numberis used• Either of the AxSYM HAVAB 2.0Control values is out of its specifiedrange• The MEIA Optics Verification Updatehas been performed
Controls	Elecsys PreciControl Anti-HAV	Abbott AxSYM HAVAB 2.0 Controls

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Differences

K. Standard/Guidance Document referenced (if applicable):

CLSI EP5-A2, "Evaluation of Precision Performance of Quantitative Measurement Methods"

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CLSI EP17-A, "Protocols for Determination of Limits of Detection" Class II Special Controls Guidance Document: Hepatitis A Virus Serological Assays http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/Guidan ceDocuments/ucm071055.pdf

L. Test Principle:

The Elecsys Anti-HAV immunoassay utilizes a competitive immunoassay format employing cell culture derived HAV antigen and a monoclonal antibody (modified by biotinylation or ruthenylation) in competition to the polyclonal sample antibody. Capture of formed immune complexes from the reaction mixture is based on biotin in the immune complex binding to streptavidin-coated magnetic microparticles which are collected on a measuring cell electrode. Signal generation is triggered by the application of a voltage to the electrode (electrochemiluminescence technology). The level of signal count detected by the system decreases as the concentration of the anti-HAV total antibody target present in a patient sample increases. Results are determined via a calibration curve which is instrument-specifically generated by 2-point calibration and a master curve provided via the reagent barcode

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Precision and Reproducibility of the Elecsys Anti-HAV assay was evaluated on Elecsys 2010 analyzer and MODULAR ANALYTICS E170 analyzer using Elecsys reagents, three human sera and controls, according to the CLSI EP15-A2/EP5-A2.

For precision study, three human sera (high negative, low positive and moderately positive) and controls (PreciControl Anti-HAV 1 and PreciControl Anti-HAV 2) were tested in replicates of 2 in 2 runs per day for 20 days with one reagent lot spanning at least two cycles of calibration using one Elecsys 2010 analyzer and one Modular Analytics E170 analyzer. Results are presented below.

Sample	Mean(IU/L)	Repeatability		Intermediate Precision(within-laboratoryprecision)		n
		SD(IU/L)	CV (%)(UCL 95%)	SD(IU/L)	CV (%)(UCL 95%)
PC Anti-HAV 1	12.3	0.221	1.8 (2.2)	0.378	3.1 (3.7)	80
PC Anti-HAV 2	29.2	0.947	3.2 (4.0)	1.325	4.5 (5.3)	80
HSP 1	17.6	0.534	3.0 (3.7)	0.586	3.3 (3.8)	80
HSP 2	21.9	0.538	2.5 (3.0)	0.667	3.0 (3.6)	80
HSP3	49.3	1.655	3.4 (4.1)	2.261	4.6 (5.4)	80

Precision on Elecsys® 2010 ●

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Sample	Mean(IU/L)	Repeatability		Intermediate Precision(within-laboratoryprecision)
		SD(IU/L)	CV (%)(UCL 95%)	SD(IU/L)	CV (%)(UCL 95%)	n
PC Anti-HAV 1	12.54	0.188	1.5 (1.8)	0.688	5.5 (7.1)	80
PC Anti-HAV 2	32.12	0.724	2.3 (2.8)	1.849	5.8 (7.4)	80
HSP 1	18.2	0.459	2.5 (3.1)	0.816	4.5 (5.6)	80
HSP 2	23	0.254	1.1 (1.4)	1.016	4.4 (5.9)	80
HSP3	55.37	1.088	2.0 (2.4)	2.374	4.3 (5.3)	80

Precision on MODULAR® ANALYTICS E170 .

PC = PreControl

UCL = Upper Confidence Limit

For reproducibility study, three human sera (high negative, low positive and moderately positive) and controls (PreciControl Anti-HAV 1 and PreciControl Anti-HAV 2) were tested in replicates of 3 in 2 runs per day for 5 days with three Elecsys 2010 analyzers and three Modular Analytics E170 analyzers. Results are presented below.

Clinical	Sample	N	MeanIU/L	Repeatability		Between Run		Between Day		Within SiteReproducibility
Site				SD	% CV	SD	% CV	SD	% CV	SD	% CV
Site 1	HSP 01	30	22.629	0.523	2.3	0.275	1.2	0.176	0.8	0.616	2.7
	HSP 02	30	49.903	2.469	4.9	0.000	0.0	0.123	0.2	2.472	5.0
	HSP 03	30	18.287	0.527	2.9	0.052	0.3	0.264	1.4	0.592	3.2
	PC A-HAV1	30	12.678	0.321	2.5	0.000	0.0	0.201	1.6	0.379	3.0
	PC A-HAV2	30	29.198	0.707	2.4	0.516	1.8	0.505	1.7	1.011	3.5
Site 2	HSP 01	30	23.196	0.302	1.3	0.452	2.0	0.000	0.0	0.544	2.3
	HSP 02	30	50.965	0.688	1.4	0.55	1.1	0.000	0.0	0.881	1.7
	HSP 03	30	18.499	0.417	2.3	0.336	1.8	0.000	0.0	0.535	2.9
	PC A-HAV1	30	12.942	0.278	2.2	0.309	2.4	0.000	0.0	0.416	3.2
	PC A-HAV2	30	30.814	0.376	1.2	0.441	1.4	0.000	0.0	0.58	1.9
Site 3	HSP 01	30	22.634	0.371	1.6	0.000	0.0	0.266	1.2	0.456	2.0
	HSP 02	30	48.03	1.356	2.8	1.451	3	0.000	0.0	1.985	4.1
	HSP 03	30	17.892	0.398	2.2	0.268	1.5	0.292	1.6	0.561	3.1
	PC A-HAV1	30	12.515	0.248	2.0	0.106	0.9	0.372	3.0	0.459	3.7
	PC A-HAV2	30	29.46	1.144	3.9	0.962	3.3	0.503	1.7	1.578	5.4

Elecsys anti-HAV: Within Site Reproducibility: Elecsys® 2010 Analyzer

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ClinicalSite	Sample	N	MeanIU/L	Repeatability		Between Run		Between Day		Within SiteReproducibility
				SD	% CV	SD	% CV	SD	% CV	SD	% CV
Site 1	HSP 01	30	23.433	0.237	1.0	0.419	1.8	0.000	0.0	0.481	2.1
	HSP 02	30	51.725	0.454	0.9	0.707	1.4	0.000	0.0	0.84	1.6
	HSP 03	30	18.918	0.158	0.8	0.167	0.9	0.135	0.7	0.266	1.4
	PC A-HAV1	30	13.205	0.197	1.5	0.211	1.6	0.132	1.0	0.317	2.4
	PC A-HAV2	30	31.477	0.339	1.1	0.787	2.5	0.000	0.0	0.857	2.7
Site 2	HSP 01	30	22.541	0.705	3.1	0.090	0.4	0.231	1.0	0.747	3.3
	HSP 02	30	51.871	1.344	2.6	0.000	0.0	0.302	0.6	1.378	2.7
	HSP 03	30	18.455	0.642	3.5	0.000	0.0	0.355	1.9	0.733	4
	PC A-HAV1	30	12.676	0.695	5.5	0.000	0.0	0.627	4.9	0.936	7.4
	PC A-HAV2	30	31.438	0.733	2.3	0.231	0.7	0.000	0.0	0.769	2.4
Site 3	HSP 01	30	23.946	0.288	1.2	0.22	0.9	0.000	0.0	0.363	1.5
	HSP 02	30	52.166	0.299	0.6	0.829	1.6	0.000	0.0	0.881	1.7
	HSP 03	30	19.426	0.203	1.0	0.336	1.7	0.000	0.0	0.392	2.0
	PC A-HAV1	30	12.974	0.205	1.6	0.225	1.7	0.000	0.0	0.304	2.3
	PC A-HAV2	30	31.236	0.241	0.8	1.038	3.3	0.000	0.0	1.066	3.4

Elecsys anti-HAV: Within Site Reproducibility: MODULAR® ANALYTICS E170

Elecsys anti-HAV: Between Site Reproducibility: Elecsys® 2010 Analyzer

	N	MeanIU/L	Repeatability		Between Run		Between Day		Between Site		Reproducibility
Sample			SD	% CV	SD	% CV	SD	% CV	SD	% CV	SD	% CV
HSP 01	90	22.819	0.409	1.8	0.3	1.3	0.000	0.0	0.304	1.3	0.591	2.6
HSP 02	90	49.633	1.674	3.4	0.697	1.4	0.000	0.0	1.462	2.9	2.33	4.7
HSP 03	90	18.226	0.451	2.5	0.25	1.4	0.166	0.9	0.276	1.5	0.608	3.3
PC A-HAV1	90	12.712	0.284	2.2	0.179	1.4	0.22	1.7	0.176	1.4	0.438	3.4
PC A-HAV2	90	29.824	0.807	2.7	0.68	2.3	0.394	1.3	0.808	2.7	1.386	4.6

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Sample	N	MeanIU/L	Repeatability		Between Run		Between Day		Between Site		Reproducibility
			SD	% CV	SD	% CV	SD	% CV	SD	% CV	SD	% CV
HSP 01	90	23.307	0.46	2	0.278	1.2	0.000c	0.0	0.7	3	0.883	3.8
HSP 02	90	51.921	0.837	1.6	0.542	1	0.000c	0.0	0.168	0.3	1.011	1.9
HSP 03	90	18.933	0.399	2.1	0.148	0.8	0.17	0.9	0.472	2.5	0.658	3.5
PC A-HAV1	90	12.952	0.433	3.3	0.000c	0	0.368	2.8	0.193	1.5	0.6	4.6
PC A-HAV2	90	31.384	0.487	1.6	0.764	2.4	0.000c	0	0.000c	0	0.906	2.9

Elecsys anti-HAV: Between Site Reproducibility: MODULAR® ANALYTICS E170

b. Linearity/assay reportable range:

The qualitative assay has a quantitative measurement. The detectable range is from 6 IU/L to 60 IU/L.

Traceability, Stability, Expected values (controls, calibrators, or methods): C.
Traceability: This method has been standardized against the "Second International Standard for Anti-Hepatitis A, Immunoglobulin, Human, NIBSC code: 97/646" of the NIBSC (National Institute for Biological Standards and Control).

Controls:

PC A-HAV 1: anti-HAV antibodies (human), with approximately 12 IU/L

PC A-HAV 2: anti-HAV antibodies (human), with approximately 30 IU/L

Calibrators:

Calibration of the Elecsys anti-HAV is performed by using the 2 calibrators provided with the reagent kit. Calibrator 1 is an anti-HAV negative serum; Calibrator 2 is an anti-HAV positive serum with approx. 46 IU/L.

A reagent lot specific master standard curve is provided on the barcode of each reagent kit. The calibrator master standard curve is established by diluting an anti-HAV positive human serum with an analyte free human serum matrix. The concentration value was assigned to it by reading the concentration from the reference calibrator curve using four E2010 and four E170 instruments with 2 runs and 2 replicates per run and per instrument. The master curve is stored in the barcode and is automatically read in by the instrument when the barcode is scanned for the new reagent.

The calibration must be performed once per reagent lot. Acceptance criteria for the assigned values are < 20 IU/L for Cal 1 and > 40 IU/L for Cal 2. Recalibration is recommended if the same reagent lot was used more than 1 month (28 days), or if the same reagent kit has been left on the analyzer for 7 days.

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

Stability:

Reagents:
-----------

unopened at 2-8 °C	up to the stated expiration date
M, R1, R2 after opening at 2-8 °C	8 weeks
on Elecsys® 2010 and cobas e® 411at20-25 °C	8 weeks
	on MODULAR® ANALYTICS E170 and cobas e® 601 at 20-25 °C
Reconstituted calibrators at -20 °C	12 weeks
Reconstituted calibrators at 2-8 °C	2 weeks
Reconstituted calibrators onElecsys® 2010 and cobas e® 411 at20-25 °C	up to 6 hours
	Reconstituted calibrators onMODULAR® ANALYTICS E170and cobas e® 601 at 32°C

PreciControls:

unopened at 2-8 °C	up to the stated expiration date
after opening at 2-8 °C	8 weeks
After opening at -20 °C	3 months (freeze only once)
on Elecsys® 2010 and cobas e® 411at 20-25 °C	up to 7 hours
on MODULAR® ANALYTICSE170 and cobas e® 601 at 20-25 °C	up to 7 hours

Samples:

Sample stability was determined using different sample materials e.g. Serum, Serum with separating gel, K2-EDTA Plasma. Four negative samples, one sample around cutoff, and three low positive samples were tested and compared with fresh reference materials.

Samples stored at -20°C	up to 3 months
Samples stored at 2-8°C	Up to 7 days
Freeze and thaw cycles	Up to 5 cycles
on Elecsys® 2010 and cobas e® 411at 20-25 °C	up to 8 hours

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

d. Detection limits:

Limit of Blank (LoB) of the Elecsys® Anti-HAV assay was determined according to CLSI EP17-A. Limit of Blank determines the highest observed measurement values for samples free of analyte. The LoB was determined as the 95 percentile of measurements of blank samples. The distribution of values for five zero-level human serum has been determined on two Elecsys® 2010 / cobas e 411 Analyzers and on two MODULAR® ANALYTICS E170 / cobas e® 601 Immunoassay Analyzers over 3 days, 2 runs per day. The LoB for Elecsys® 2010 / cobas e 411 Analyzer is 3.03 IU/L and 2.099 IU/L for MODULAR® ANALYTICS E170 / cobas e® 601 Immunoassay Analyzers.

Limit of detection (LoD) of the Elecsys® Anti-HAV assay was determined according to CLSI EP17-A. The LoD was determined as the lowest amount of analyte in a sample that can be detected with 95% probability. The distribution of values for five low-level human serum samples has been determined on two Elecsys® 2010 / cobas e® 411 Analyzers and on two MODULAR® ANALYTICS E170 / cobas e 601 Immunoassay Analyzers over 3 days, 2 runs per day. Samples were measured in one-fold determination in each run. 30 measuring points were collected per instrument.

LOD = LOB + 1.6529 x SD total (of low analyte samples) The LoD for Elecsys® 2010 / cobas e® 411 Analyzer is 5.155 IU/L, and 2.994 IU/L for MODULAR® ANALYTICS E170 / cobas e® 601 Immunoassay Analyzers.

The LOD is set at 6.00 IU/L for both types of analyzers and is reported in the labeling.

Calibrators: Range for the electrochemiluminescence signals for the calibrators:

Negative calibrator (Call): < 20 IU/L (Elecsys® 2010, MODULAR® ANALYTICS E170 and cobas e® analyzers). Positive calibrator (Cal2): ≥ 40 IU/L (Elecsys® 2010, MODULAR® ANALYTICS E170 and cobas e® analyzers)

e. Analytical specificity:
Cross-reactivity: 177 samples from 15 potentially cross-reactive sub-groups were used for cross-reactivity study on the Elecsys 2010. 174 Samples were found to be nonreactive (negative) in both the Elecsys anti-HAV assay and the predicate AxSym HAVAB 2.0 assay; 3 samples were found to be discordant between the Elecsys anti-HAV assay and the AxSym HAVAB 2.0 assay. The testing results are summarized in the table below:

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

	HAVAB 2.0 Assay
		Reactive			Equivocal			Non-Reactive
Category	Elecsys 2010 HAV 2.1 Assay									Total
	RXa	EQb	NRc	RX	EQ	NR	RX	EQ	NR
Anti-nuclear Antibody (ANA)	0	0	0	0	0	0	0	0	13	13
Cytomegalovirus (anti-CMV)	0	0	0	0	0	0	0	0	13	13
Epstein-Barr Virus (anti-EBV)	0	0	0	0	0	0	0	0	14	14
Elevated IgG	0	0	0	0	0	0	0	0	13	13
Elevated IgM	0	0	0	0	0	0	0	0	13	12
Hepatitis B Virus(HBsAg or HBV-DNA)	0	0	0	0	0	0	1	0	10	11
Hepatitis C Virus (anti-HCV)	0	0	0	0	0	0	0	0	12	12
Human Immunodeficiency Virus(anti-HIV-1)	0	0	0	0	0	0	2	0	11	13
Herpes Simplex Virus (anti-HSV)	0	0	0	0	0	0	0	0	10	10
Mumps / Rubeola	0	0	0	0	0	0	0	0	12	12
Parvovirus B19 Infection	0	0	0	0	0	0	0	0	11	11
Rheumatoid factor	0	0	0	0	0	0	0	0	7	7
Rubella (anti-Rubella )	0	0	0	0	0	0	0	0	10	10
Toxoplasmosis (anti-Toxo)	0	0	0	0	0	0	0	0	13	13
Varicella Zoster (anti-VZV)	0	0	0	0	0	0	0	0	12	12
Total	0	0	0	0	0	0	3	0	174	177

a Number of Reactive specimens

b Number of Equivocal or Borderline specimens

° Number of Non-Reactive specimens

HAMA (human anti-mouse antibodies) effect was tested by comparing the recovery of 4 human serum samples spiked with different suitable HAMA serum samples versus 4 unspiked aliquots of samples. No HAMA effect was found.

Interference: The impact of endogenous interfering substances on the Elecsys Anti-HAV assay was determined testing native human serum pools on Elecsys® 2010 Immunoassay Analyzer.

The assay is unaffected by icterus (bilirubin < 50 mg/dL), hemolysis (Hb

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

< 1000 mg/dL), lipemia (Intralipid < 1500 mg/dL), and biotin < 50 ng/mL. Serum pools (high negative, low positive, and high positive) were used to spike with the intereferent. In patients receiving therapy with high biotin doses (i.e. > 5 mg/day), no sample should be taken until at least 8 hours after the last biotin administration. One aliquot of each serum sample was spiked with the interfering substance; another aliquot was spiked with the same volume of isotonic NaCl solution (dilution pool). The interfering pool was then diluted into the dilution pool in 10% increments. The % recovery was determined by dividing the mean value of the measured concentration by the expected concentration. Criterion: Recovery of positive samples within ± 20 % of initial value.

In vitro tests were performed on 18 commonly used pharmaceuticals (Acetylcysteine, Ampicillin-Na, Ascorbic acid. Ca-Dobesilate, Cyclosporine, Cefoxitin, Heparin, Intralipid, Levodopa, Methyldopa, Metronidazole, Phenylbutazone, Tetracycline, Acetylsalicylic acid, Rifampicin, Acetaminophen, Ibuprofen, and Theophylline) and in addition on folic acid. No interference with the assay was found.

f. Assay cut-off:
The cutoff was set at 20 IU/L according to the WHO recommendation for vaccination. It was established by histogram analysis of the predicate and was confirmed by measuring a total of 736 samples from 2 European centers including hospitalized patients, acute HAV infection patient, blood doors, pregnant women and the other samples that suspected for HAV infection. The 20 IU/L in the Elecsys anti-HAV assay corresponds to 1.0 of S/CO in the predicate.

Non-reactive: < 18 IU/L 18.0 < IU/L < 22.0 IU/L Border: Reactive: > 22.0 IU/L

Samples with a concentration < 18.0 IU/L are considered non-reactive in the Elecsys Anti-HAV test and no further testing is necessary.

Samples with a concentration ≥ 22.0 IU/L are considered reactive in the Elecsys Anti-HAV test.

Samples with a concentration between 18.0 and < 22.0 are considered border (borderline). The sample should be retested in duplicate.

. If 2 of the 3 results have a concentration < 18.0 IU/L, the result is interpreted as non-reactive and no further testing is necessary.
If 2 of the 3 results have a concentration between 18.0 and < 22.0 IU/L, the . result is interpreted as borderline. It is recommended that a specimen be drawn in two weeks and retested.

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

If 2 of the 3 results have a concentration ≥ 22.0 IU/L, the result is ● interpreted as reactive.

2. Comparison studies:

a. Method comparison with predicate device:
The performance of the Elecsys anti-HAV assay was determined by percent agreement among negative samples and percent agreement among positive samples, against a consensus comparator method, in specific populations. The main predicate (Abbott AxSym HAV AB- 2.0) was used as sole comparator/reference. Detailed information can be found in clinical performance.
b. Matrix comparison:
The effect on quantitation of analyte in the presence of anticoagulants with the Elecsys® Anti-HAV Immunoassay was determined on Elecsys 2010 Immunoassay Analyzer by comparing values obtained from native samples (single donors) drawn into Serum, K2-EDTA-Plasma and Serum-Gel Separation primary tubes. The following tables summarize the results for the comparison between serum and plasma matrices.

Plasma matrix	Number of positive specimens showing recovery toserum within various ranges
	< 10%	10-15%	> 15%
K2-EDTA	24	1	0
Serum Gel	23	2	0

Plasma matrix	Number of borderline specimens showing recoveryto serum within various ranges
	< 10%	10-15%	> 15%
K2-EDTA	3	0	0
Serum Gel	3	0	0

Plasma matrix	Number of negative specimens showing recoveryto serum within various ranges
	< 1.0 IU/L	1.0 -2.0 IU/L	> 2.0 IU/L
K2-EDTA	29	1	0
Serum Gel	30	0	0

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

3. Clinical studies:

a. Clinical Sensitivity: N/A
b. Clinical specificity: N/A
c. Other clinical supportive data (when a. and b. are not applicable):

Clinical Performance

Clinical Study Cohorts:

A multi-center study was conducted in the U.S. to characterize the performance of the Elecsys Anti-HAV Immunoassay. All subjects were tested with the Elecsys Anti-HAV assay on the Elecsys 2010 analyzer and with an FDAcleared reference method in strict accordance with the manufacturer's package insert instructions.

A total of 1050 samples were obtained from multiple specimen sources, representing subjects for whom routine hepatitis A testing had been ordered. hospitalized patients, subjects at increased risk for hepatitis, subjects with signs and symptoms of hepatitis, subjects characterized with acute hepatitis A, and subjects below the age of 21 years (pediatric/adolescents). All samples (prospective and retrospective) are stored frozen before shipment to Roche and to the respective sites for testing. Among the 1050 samples, 487 were (46.38%) were from males and 563 (53.62%) were from females. 0.38% were from American Indian/Alaska Native, 2.76% were Asian, 15.90% were African American /Black, 65.14% were Caucasian/White, 14.95% unknown and 0.86% others.

Among all specimens tested, one specimen subjected to routine Hepatitis A testing was concordantly equivocal, and was excluded from the calculations.

The positive and negative percent agreement for prospectively collect samples is 98.13% (95.96% to 99.31%) and 97.37% (95.06% to 98.79%), respectively.

The positive and negative percent agreement for retrospectively collect samples is 98.11% (94.59% to 99.61%) and 97.37% (94.36% to 99.03%), respectively.

The positive percent agreement and the negative percent agreement results for the different clinical population are presented in the following table:

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

Elecsys2010 Result	Predicate Result
	Site 1 BW	Site 2 WU	Site 3 JH	All Sites
	RX	EQ	NR	RX	EQ	NR	RX	EQ	NR	RX	EQ	NR
Reactive	60	0	2	0	0	0	16	0	0	76	0	2
Equivocal	1	0	2	0	0	0	1	0	0	2	0	2
Negative	0	0	97	0	0	0	0	0	17	0	0	114
Total	61	0	101	0	0	0	17	0	17	78	0	118
PPA	98.36 (60/61)			0.00 (0/0)			94.12 (16/17)			97.44 (76/78)
95% CI	91.20 to 99.96			0.00 to 100.00			71.31 to 99.85			91.04 to 99.69
NPA	96.04 (97/101)			0.00 (0/0)			100.00 (17/17)			96.61 (114/118)
95% CI	90.17 to 98.91			0.00 to 100.00			80.49 to 100.00			91.55 to 99.07

Percent Agreement for Elecsys and Predicate anti-HAV Assay Results from Symptomatic Individuals

Percent Agreement for Elecsys and Predicate anti-HAV Assay Results from Specimens Subjected to Routine Hepatitis A Testing

	Predicate Result
Elecsys2010 Result	Site 1 BW			Site 2 WU			Site 3 JH			All Sites
	RX	EQ	NR	RX	EQ	NR	RX	EQ	NR	RX	EQ	NR
Reactive	90	0	2	0	0	0	36	0	1	126	0	3
Equivocal	0	0	1	0	0	0	0	1	1	0	1	2
Negative	2	0	54	0	0	0	0	0	21	2	0	75
Total	92	0	57	0	0	0	36	1	23	128	1	80
PPA		97.83 (90/92)		0.00 (0/0)			100.00 (36/36)			98.44 (126/128)
95% CI	92.37 to 99.74			0.00 to 100.00			90.26 to 100.00			94.47 to 99.81
NPA		94.74 (54/57)		0.00 (0/0)			91.30 (21/23)			93.57 (75/80)

Percent Agreement for Elecsys and Predicate anti-HAV Assay Results from
Hospitalized Patients (Retrospective and Prospective)

	Predicate Result
	Site 1 BW		Site 2 WU		Site 3 JH		All Sites
Elecsys2010 Result	RX	EQ	NR	RX	EQ	NR	RX	EQ	NR	RX	EQ	NR
Reactive	42	0	0	0	0	0	28	0	0	70	0	0
Equivocal	0	0	0	0	0	0	1	0	0	1	0	0
Negative	0	0	90	0	0	0	1	0	51	1	0	141

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

Total	42	0	0	0	72
PPA	100.00 (42/42)	0.00 (0/0)		93.33 (28/30)	97.22 (70/72)
95% CI	91.59 to 100.00		0.00 to 100.00	77.93 to 99.18	90.32 to 99.66
NPA	100.00 (90/90)		0.00 (0/0)	100.00 (51/51)	100.00 (141/141)
95% CI	95.98 to 100.00	0.00 to 100.00		93.02 to 100.00	97.42 to 100.00

Percent Agreement for Elecsys and Predicate anti-HAV Assay Results from Subjects Characterized as Acute Hepatitis A (Retrospective and Prospective)

	Predicate Result
	Site 1 BW			Site 2 WU			Site 3 JH			All Sites
Elecsys 2010 Result	RX	EQ	NR	RX	EQ	NR	RX	EQ	NR	RX	EQ	NR
Reactive	81	0	0	0	0	0	50	0	0	131	0	0
Equivocal	0	0	0	0	0	0	0	0	0	0	0	0
Negative	0	0	3	0	0	0	0	0	0	0	0	3
Total	81	0	3	0	0	0	50	0	0	131	0	3
PPA	100.00 (81/81)			0.00 (0/0)			100.00 (50/50)			100.00 (131/131)
95% CI	95.55 to 100.00			0.00 to 100.00			92.89 to 100.00			97.22 to 100.00
NPA	100.00 (3/3)			0.00 (0/0)			0.00 (0/0)			100.00 (3/3)
95% CI	29.24 to 100.00			0.00 to 100.00			0.00 to 100.00			29.24 to 100.00

Percent Agreement for Elecsys and Predicate anti-HAV Assay Results from Pediatric and Adolescent Subjects

	Predicate Result
	Site 1 BW			Site 2 WU			Site 3 JH			All Sites
Elecsys2010 Result	RX	EQ	NR	RX	EQ	NR	RX	EQ	NR	RX	EQ	NR
Reactive	0	0	0	0	0	0	19	0	2	19	0	2
Equivocal	0	0	0	0	0	0	0	0	0	0	0	0
Negative	0	0	0	0	0	0	0	0	65	0	0	65
Total	0	0	0	0	0	0	19	0	67	19	0	67
PPA	0.00 (0/0)			0.00 (0/0)			100.00 (19/19)			100.00 (19/19)
95% CI	0.00 to 100.00			0.00 to 100.00			82.35 to 100.00			82.35 to 100.00
NPA	0.00 (0/0)			0.00 (0/0)			97.01 (65/67)			97.01 (65/67)
95% CI	0.00 to 100.00			0.00 to 100.00			89.63 to 99.64			89.63 to 99.64

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

	Predicate Result
	Site 1 BW			Site 2 WU			Site 3 JH			All Sites
Elecsys2010 Result	RX	EQ	NR	RX	EQ	NR	RX	EQ	NR	RX	EQ	NR
Reactive	10	0	1	0	0	0	38	0	2	48	0	3
Equivocal	0	0	0	0	0	0	0	0	1	0	0	1
Negative	1	0	5	0	0	0	2	0	152	3	0	157
Total	11	0	6	0	0	0	40	0	155	51	0	161
PPA	90.91 (10/11)			0.00 (0/0)			95.00 (38/40)			94.12 (48/51)
95% CI	58.72 to 99.77			0.00 to 100.00			83.08 to 99.39			83.76 to 98.77
NPA	83.33 (5/6)			0.00 (0/0)			98.06 (152/155)			97.52 (157/161)
95% CI	35.88 to 99.58			0.00 to 100.00			94.45 to 99.60			93.76 to 99.32

Agreement for Elecsys and Predicate anti-HAV Assay Results from Subjects at Increased Risk for Hepatitis

RX - Reactive, positive, EQ - equivocal, borderline, NR - non-reactive, negative, PPA - positive percent agreement, NPA negative percent agreement, 95% CI - 95% Exact confidence interval

Cohort	Positive Percent Agreement	Negative Percent Agreement
	PPA (x/n)	95 % confidence interval	NPA (x/n)	95 % confidence interval
Routine HAV Testing	98.44 (126/128)	94.47 to 99.81	93.75 (75/80)	86.01 to 97.94
Hospitalized	97.22 (70/72)	90.32 to 99.66	100.00 (141/141)	97.42 to 100.00
Signs and Symptoms	97.44 (76/78)	91.04 to 99.69	96.61 (114/118)	91.55 to 99.07
Increased Risk for Hepatitis	94.12 (48/51)	83.76 to 98.77	97.52 (157/161)	93.76 to 99.32
Characterized Acute HAV	100.00 (131/131)	97.22 to 100.00	100.00 (3/3)	29.24 to 100.00
Pediatric/Adolescent	100.00 (19/19)	82.35 to 100.0	97.01 (65/67)	89.63 to 99.64
Overall	98.12 (470/479)	96.46 to 99.14	97.37 (555/570)	95.70 to 98.52

Summary of the Percent Agreements for the Various Specimen Cohorts

HAV Vaccination:

Fifty-four specimens that were collected both pre- and post-HAV vaccination was evaluated by the Elecsys anti-HAV assay and the predicate. The post-vaccination specimens were obtained at least four weeks but not more than 10 weeks after the completion of the vaccine regimen. Three HAV vaccines which are currently licensed in the US were used in this study: VAQTA (16), HAVRIX (20) and TWINRIX (18). Two vaccination studies are represented: one conducted in the Eastern region of the US and the other in Penzberg Germany. There was no antibody response observed in pre-vaccination specimens with the exception of two

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

specimens which were just above the equivocal/borderline (- 23.23 IU/L) and just reactive (30.34 IU/L), respectively.

	anti-HAV Assay Results
	Predicate Result
ElecsysResult	HAVRIX			TWINRIX			VAQTA			All Vaccines
	RX	EQ	NR	RX	EQ	NR	RX	EQ	NR	RX	EQ	NR
Reactive	0	0	0	0	0	1	0	0	0	0	0	1
Equivocal	0	0	0	0	0	0	0	0	0	0	0	0
Non-Reactive	0	0	20	0	0	17	0	0	16	0	0	53
Total	0	0	20	0	0	18	0	0	16	0	0	54
PPA	0.00 (0/0)			0.00 (0/0)			0.00 (0/0)			0.00 (0/0)
95% CI*	0.00 to 100.00			0.00 to 100.00			0.00 to 100.00			0.00 to 100.00
NPA	100.00 (20/20)			94.44 (17/18)			100.00 (16/16)			98.15 (53/54)
95% CI*	83.16 to 100.00			72.71 to 99.86			79.41 to 100.00			90.11 to 99.95

Percent Agreement for Elecsys and Predicate anti-HAV Assays Results from
Pre-HAV Vaccination Specimens

Percent Agreement for Elecsys and Predicate anti-HAV Assays Results from Post-HAV Vaccination Specimens

anti-HAV Assay Results
	Predicate Result
ElecsysResult	HAVRIX			TWINRIX			VAQTA			All Vaccines
	RX	EQ	NR	RX	EQ	NR	RX	EQ	NR	RX	EQ	NR
Reactive	20	0	0	17	0	1	16	0	0	53	0	1
Equivocal	0	0	0	0	0	0	0	0	0	0	0	0
Non-Reactive	0	0	0	0	0	0	0	0	0	0	0	0
Total	20	0	0	17	0	1	16	0	0	53	0	1
PPA	100.00 (20/20)			100.00 (17/17)			100.00 (16/16)			100.00 (53/53)
95% CI*	83.16 to 100.00			80.49 to 100.00			79.41 to 100.00			93.28 to 100.00
NPA	0.00 (0/0)			0.00 (0/1)			0.00 (0/0)			0.00 (0/1)
95% CI*	0.00 to 100.00			0.00 to 97.50			0.00 to 100.00			0.00 to 97.50

RX - Reactive, positive, EQ - equivocal, borderline, NR - non-reactive, negative, PPA - positive percent agreement, NPA negative percent agreement, 95% CI - 95% Exact confidence interval

Prevalence Studies:

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

The Elecsys Anti-HAV assay was used to evaluate the prevalence of HAV total antibodies in an apparently healthy population (normal, healthy individuals without symptoms). The prospective study population for the Elecsys Anti-HAV assay consisted of 602 patients. Of these 602 patients, 300 patients were from the high prevalence region, Western states of the U.S. (New Mexico) and 302 patients were from the low risk region Eastern states of the U.S. (Indiana). The prospective study population was 208 (34.6 %) males and 394 (65.4 %) females (total n = 602) including 493 (81.9 %) Caucasians, 32 (5.3 %) African Americans, 6 (1.0 %) Asians, 69 (11.5 %) American Indians and 2 (0.3 %) Others. The results of prevalence population are summarized according to age groups in decades, gender, geographical area and the number of reactive, non-reactive and equivocal results.

Prevalence rate for reactive anti-HAV assay in specimens collected in a low prevalence region, Eastern states of the US (Indiana), was 35.10 %. Prevalence rate for reactive anti-HAV assay in specimens collected in a high prevalence region, Western states of the US (New Mexico), was 37.33%. The results of prevalence study are summarized according to age groups and gender.

Expected results for the Elecsys Anti-HAV assay in subjects from low prevalence
areas for Hepatitis A

Agerange(years)	Gender	Elecsys Anti-HAV result
		Reactive		Equivocal		Non-reactive
		N	Percent	N	Percent	N	Percent	Total
11 - 20	Female	0	0.0	0	0.0	1	100.0	1
11 - 20	Male	0	0.0	0	0.0	1	100.0	1
21-30	Female	1	14.3	0	0.0	6	85.7	7
21-30	Male	0	0.0	0	0.0	6	100.0	6
31-40	Female	2	9.5	1	4.8	18	85.7	21
31-40	Male	0	0.0	0	0.0	2	100.0	2
41-50	Female	3	13.6	1	4.6	18	81.8	22
41-50	Male	1	7.7	0	0.0	12	92.3	13
51-60	Female	7	16.7	1	2.4	34	81.0	42
51-60	Male	9	47.4	0	0.0	10	52.6	19
61-70	Female	23	45.1	0	0.0	28	54.9	51
61-70	Male	12	42.9	0	0.0	16	57.1	28
71-80	Female	24	50.0	0	0.0	24	50.0	48
71-80	Male	14	46.7	0	0.0	16	53.3	30
> 80	Female	4	80.0	0	0.0	1	20.0	5
> 80	Male	6	100.0	0	0.0	0	0.0	6
Allages	Female	64	32.5	3	1.5	130	66.0	197
Allages	Male	42	40.0	0	0.0	63	60.0	105
Total		106	35.1	3	1.0	193	63.9	302

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

Age range (years)	Gender	N	Percent	Percent	N	Percent	Total
11-20	Female	4	50.0	0	4	50.0	8
11-20	Male	2	40.0	0.0	3	60.0	5
21-30	Female	4	23.5	0.0	13	76.5	17
21-30	Male	2	18.2	0.0	9	81.8	11
31-40	Female	3	11.1	0.0	24	88.9	27
31-40	Male	3	23.1	0.0	10	76.9	13
41-50	Female	14	26.9	0.0	38	73.1	52
41-50	Male	6	33.3	0.0	12	66.7	18
51-60	Female	21	38.9	0.0	33	61.1	54
51-60	Male	11	45.8	0.0	13	54.2	24
61-70	Female	18	72.0	0.0	7	28.0	25
61-70	Male	9	36.0	0.0	16	64.0	25
71-80	Female	9	75.0	0.0	3	25.0	12
71-80	Male	5	71.4	0.0	2	28.6	7
> 80	Female	0	0.0	0.0	1	100.0	1
> 80	Male	0	0.0	0.0	0	0.0	0
Unknown	Female	1	100.0	0.0	0	0.0	1
Unknown	Male	0	0.0	0.0	0	0.0	0
All ages	Female	74	37.6	0.0	123	62.4	197
All ages	Male	38	36.9	0.0	65	63.1	103
Total		112	37.3	0.0	188	62.7	300

Expected results for the Elecsys Anti-HAV assay in subjects from high prevalence areas for Hepatitis A

Seroconversion Sensitivity:

Seroconversion sensitivity of the Elecsys anti-HAV assay was shown by testing 3 seroconversion panels in comparison to that of the comparator assay (Abbott AxSym HAV AB- 2.0). Seroconversion panel results were also compared with the data provided by the vendor for the Abbott AxSym HAV AB 2.0 assay. The comparator assay and vendor assay are based on the Abbott AxSym HAV AB-2.0. The results are summarized in the following table:

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Panel ID	Elecsys 2010 assay	1Comparator anti-HAV assay		2Comparator anti-HAV assay
	Post bleed day of earliest reactive result	Post bleed day of last positive result	Non-Reactive	Reactive	Non-Reactive	Reactive
HAV-01	0	91	0	91	0	91
3PHT 902	16	163	Not tested	Not tested	16	163
RP013	6	190	Not tested	Not tested	9	190

Elecsys anti-HAV assay Seroconversion Panel Results

The comparator results were shown by Roche using the Abbott AxSym HAV AB-2.0.

َ The comparator results were provided by Vendor i.e. Abbott AxSym HAV AB-2.0

3 The panel was not tested with the reference assay due to the limited sample size tested.

Method Comparison studies on two instruments:

The method comparison for the Elecsys anti-HAV assay between the two platforms E2010 and E170 was demonstrated by testing the prevalence and other clinical cohort specimens on MODULAR Analytics E170 and Elecsys 2010 analyzers. 100 non-reactive specimens were obtained from the Prevalence cohort. 53 reactive specimens were collected in the US from various clinical cohorts and another 49 reactive samples were provided by Roche R & D from sample archive. Among those samples, 96 were low negatives; 6 were high negatives; 12 were low reactive and 88 were high reactive samples. The regression analyses for the comparisons using the prevalence cohort and the combined clinical cohorts were carried out using the least squares and Passing-Bablok regression methods. The Pearson's regression correlation for the 202 data pairs was 0.9951, with slope at 1.024 and intercept at -0.555. Positive percent agreement was 91/94 = 96.8 % (95 % exact confidence limits of 91.0 to 99.3). Negative percent agreement was 98/100 = 98.0 % (95 % exact confidence limits of 93.0 to 99.8). 8 specimens were concordantly equivocal.

4. Clinical cut-off:

Refer to assay cutoff section above for additional details.

5. Expected values/Reference range:

The Elecsys anti-HAV assay was used to evaluate the prevalence of HAV antibodies in an apparently healthy population (normal, healthy Individuals without symptoms). A statistically significant number of subjects were prospectively collected in a "high prevalence" region, the Western states, and a "low prevalence" region, the Eastern states, and were tested using only the Elecsys anti-HAV assay and were not compared with the predicate device.

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Expected Results from low and high Prevalence based on the test device are presented under the prevalence study section. Prevalence rate for reactive anti-HAV total antibody in specimens collected in a high prevalence region, Western states of the US (New Mexico), was 37.33 %. Prevalence rate for reactive anti-HAV total antibody in specimens collected in a low prevalence region, Eastern states of the US (Indiana), was 35.10 %.

N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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Regulation Number and Section

§ 866.3310 Hepatitis A virus (HAV) serological assays.

(a)
Identification. HAV serological assays are devices that consist of antigens and antisera for the detection of hepatitis A virus-specific IgM, IgG, or total antibodies (IgM and IgG), in human serum or plasma. These devices are used for testing specimens from individuals who have signs and symptoms consistent with acute hepatitis to determine if an individual has been previously infected with HAV, or as an aid to identify HAV-susceptible individuals. The detection of these antibodies aids in the clinical laboratory diagnosis of an acute or past infection by HAV in conjunction with other clinical laboratory findings. These devices are not intended for screening blood or solid or soft tissue donors.(b)
Classification. Class II (special controls). The special control is “Guidance for Industry and FDA Staff: Class II Special Controls Guidance Document: Hepatitis A Virus Serological Assays.” See § 866.1(e) for the availability of this guidance document.