ANTI-HAV IGM

K093955 · Roche Diagnostics · LOL · Jun 22, 2010 · Microbiology

Device Facts

• Record ID: K093955
• Device Name: ANTI-HAV IGM
• Applicant: Roche Diagnostics
• Product Code: LOL · Microbiology
• Decision Date: Jun 22, 2010
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3310
• Device Class: Class 2
• Attributes: Pediatric

Intended Use

The Roche Elecsys Anti-HAV IgM immunoassay is used for the in vitro qualitative detection of IgM antibodies to hepatitis A virus (anti-HAV IgM) in human serum and plasma (potassium EDTA, lithium or sodium heparin, sodium citrate). The assay is intended for use as an aid in the laboratory diagnosis of an acute or recently acquired hepatitis A virus 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 and symptoms of hepatitis and in persons at risk for hepatitis A infection. The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. Elecsys PreciControl Anti-HAV IgM is used for quality control of the Elecsys Anti-HAV IgM immunoassay on the Elecsys and cobas e immunoassay analyzers. 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 user is 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.

Device Story

The Elecsys Anti-HAV IgM is an in vitro diagnostic immunoassay for detecting IgM antibodies to hepatitis A virus in human serum and plasma. It utilizes a μ-capture test principle: monoclonal h-IgM directed biotinylated antibody, cell culture-derived Hepatitis A Virus, and a ruthenylated monoclonal antibody directed to HAV. Immune complexes are captured via biotin-streptavidin binding to magnetic microparticles collected on a measuring cell electrode. Electrochemiluminescence (ECLIA) technology triggers signal generation upon voltage application; signal intensity correlates with IgM antibody concentration. The device is used in clinical laboratories on Elecsys and cobas e immunoassay analyzers. Healthcare providers interpret results alongside clinical information to diagnose acute or recent HAV infection. The system includes PreciControl Anti-HAV IgM for quality monitoring. Benefits include rapid, automated detection of acute HAV infection, aiding clinical decision-making for patients with hepatitis symptoms or risk factors.

Clinical Evidence

Multi-center U.S. study of 1087 samples (routine testing, hospitalized, high-risk, symptomatic, acute HAV, pediatric). Overall positive percent agreement 97.5% (95% CI: 92.9-99.5%) and negative percent agreement 99.3% (95% CI: 98.5-99.7%) compared to an FDA-cleared reference method. Discrepant analysis performed with a second reference assay. Analytical sensitivity evaluated using three HAV seroconversion panels. Precision/reproducibility tested per CLSI EP15-A2/EP5-A2, showing CVs < 6%. Cross-reactivity tested against 15 disease states (211 specimens) with no significant interference.

Technological Characteristics

μ-capture immunoassay; electrochemiluminescence (ECLIA) detection; biotin-streptavidin magnetic microparticle capture; ruthenylated monoclonal antibody label. Analyzers: Elecsys 2010, cobas e 411, cobas e 601, MODULAR ANALYTICS E170. Sample types: serum, plasma (K2-EDTA, Li-heparin, Na-heparin, Na-citrate). Calibration: lot-specific, periodic. Controls: human serum-based.

Indications for Use

Indicated for the qualitative detection of IgM antibodies to hepatitis A virus in human serum and plasma as an aid in the diagnosis of acute or recently acquired hepatitis A infection in symptomatic individuals or those at risk for infection. Not for blood/tissue donor screening. Performance not established for immunocompromised/immunosuppressed patients.

Regulatory Classification

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.

Special Controls

*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.

Predicate Devices

• Abbott Axsym HAVAB-M 2.0 Assay (P790019/S011)

Submission Summary (Full Text)

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K043905

# JUN 2 2 2010

#### SUBMITTED BY:

Kelly French Regulatory Affairs Consultant Roche Diagnostics 9115 Hague Road Indianapolis, IN 46250 Phone: [phone] Fax: [phone] Email: [e-mail]

#### NAME OF DEVICE:

Trade Name:

Common Name:

Elecsys® Anti-HAV IgM Elecsys® PreciControl anti-HAV IgM

> Anti-HAV IgM Test System PreciControl anti-HAV IgM

Classification Name:

Anti-HAV IgM Test System Quality Control Material (Assayed and Unassayed)

Product Code:

LOL, JJX

Abbott Axsym HAVAB-M 2.0 Assay (P790019/S011)

DEVICE DESCRIPTION:

Predicate Device:

Intended Use: The Roche Elecsys Anti-HAV IgM immunoassay is used for the in vitro qualitative detection of IgM antibodies to hepatitis A virus (anti-HAV IgM) in human serum and plasma (potassium EDTA, lithium or sodium heparin, sodium citrate). The assay is intended for use as an aid in the laboratory diagnosis of an acute or recently acquired hepatitis A virus infection.

Assay results, in coniunction with other laboratory results and clinical information, may be used to provide presumptive evidence of infection with hepatitis A virus in persons with signs and symptoms of hepatitis and in persons at risk for hepatitis A infection.

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

Kit Description: The Elecsys Anti-HAV IgM immunoassay utilizes a u-capture test concept based on a monoclonal h-IgM directed biotinylated antibody, cell culture derived Hepatitis A Virus and a ruthenylated monoclonal antibody directed to HAV. Capture of formed immune complexes from the reaction mixture is based on biotin 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 increases as the concentration of the IgM antibody target present in a patient sample increases.

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The Elecsys PreciControl Anti-HAV IgM contains control serum based on human serum in the negative and positive concentration range. The controls are used for monitoring the accuracy of the Elecsys Anti-HAV IgM immunoassays.

| Table 1. Anti-HAV IgM Immunoassay Comparison | | |
|----------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Feature | Elecsys Anti-HAV IgM Assay | Predicate Device<br>Abbott Axsym HAVAB-M 2.0<br>Assay (P790019/S011 |
| Assay Protocol | μ-Capture test principle | Direct Binding principle |
| Detection Protocol | Electrochemiluminescence<br>immunoassay (ECLIA) | MEIA |
| Traceability/<br>Standardization | Roche Internal Standard | Not Given |
| Sample Type | Human serum and plasma | Same |
| Instrument<br>Platform | Elecsys 2010<br>(Request for CLIA categorization<br>has been made to add the<br>MODULAR ANALYTICS E170,<br>cobas e 411, and cobas e 601<br>analyzers according to the<br>Replacement Reagent and<br>Instrument Policy). | AxSYM System |
| Interpretation of<br>Results | $\ge$ 1.10 Reactive<br>$\ge$ 0.90 - $<$ 1.10 Grayzone<br>$<$ 0.9 Negative | $>$ 1.20 Reactive<br>0.80 -1.20 Grayzone<br>$<$ 0.80 Nonreactive |
| Calibration<br>Interval | Once per reagent lot and<br>• After 1 month (28 days) when<br>using the same reagent lot<br>• After 7 days (when using the<br>same reagent kit on the analyzer)<br>• As required: e.g. quality control<br>findings outside the specified<br>limits | A single sample of both the<br>Negative and Positive Controls<br>must be tested as a means of<br>evaluating the assay calibration.<br>Once the calibration is accepted and<br>stored, all subsequent samples may<br>be tested without further calibration<br>unless one or more of the following<br>occur:<br>• A reagent pack with a new lot<br>number is used<br>• Either of the AxSYM HAVAB-M<br>2.0 Control values is out of its<br>specified range<br>• The MEIA Optics Verification<br>Update has been performed |
| Controls | Elecsys PreciControl Anti-HAV<br>IgM | Abbott AxSYM HAVAB-M 2.0<br>Controls |

2

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### PERFORMANCE DATA:

## COMPARATIVE TESTING:

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

A total of 1087 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).

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

| Elecsys Anti-HAV IgM results versus 1st reference anti-HAV IgM assayp | | | | |
|-----------------------------------------------------------------------|---------------------------------------|-----------------------------|------------------------------------------|-----------------------------|
| Cohort | Positive percent<br>agreement % (x/n) | 95 % confidence<br>interval | Negative percent<br>agreement %<br>(x/n) | 95 % confidence<br>interval |
| Routine HAV<br>testing | 50.0 (1/2) | 1.26 - 98.7 | 99.0 (207/209) | 96.6 - 99.9 |
| Hospitalized | 0.00 (0/0) | 0.00 - 100 | 100 (216/216) | 98.3 - 100 |
| High risk for<br>hepatitis | 0.00 (0/0) | 0.00 - 100 | 100 (215/215) | 98.3 - 100 |
| Signs and<br>symptoms | 0.00 (0/0) | 0.00 - 100 | 99.5 (211/212) | 97.4 - 99.99 |
| Characterized<br>acute HAV | 98.3 (117/119) | 94.1 - 99.8 | 73.3 (11/15) | 44.9 - 92.2 |
| Pediatric/<br>adolescent | 0.00 (0/0) | 0.00 - 100 | 100 (99/99) | 96.3 - 100 |
| Overall | 97.5 (118/121) | 92.9 - 99.5 | 99.3 (959/966) | 98.5 - 99.7 |

Summary of percent agreements for the various specimen cohorts:

p) Additional testing was performed for the discrepant and several concordant specimens with a second FDA cleared anti-HAV IgM assay. The second predicate agreed with the Elecsys outcome in 7 of the 10 discrepant samples and with the first predicate in 2 of the 10 specimens. No consensus was obtained in the remaining specimen. Complete concordance was obtained among the three assays in the fifteen nonreactive and reactive concordant specimens also tested.

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## ANALYTICAL SENSITIVITY:

Three commercially available HAV seroconversion panels were tested using Elecsys Anti-HAV IgM immunoassay and the FDA approved comparator assay to determine the sensitivity of the assay. Results were also compared with the data supplied by the vendor. The comparator assay and vendor assay are based on the Abbott HAVAB-M. The results are summarized in the following table:

| Panel ID | Elecsys 2010 assay | Comparator anti-HAV IgM assay c | | Comparator anti-HAV IgM assay d | | |
|-------------------------------------------------------------------------------------------------|--------------------------------------------|----------------------------------------|--------------------------------------------|----------------------------------------|--------------------------------------------|----------------------------------------|
| | Post bleed day of earliest reactive result | Post bleed day of last positive result | Post bleed day of earliest reactive result | Post bleed day of last positive result | Post bleed day of earliest reactive result | Post bleed day of last positive result |
| HAV-01 | 0 | 21 | 0 | 34 | 0 | 28 |
| PHT 902The panel was not tested with the reference assay due to the limited sample size tested. | 16 | 21 | not tested | not tested | 16 | 21 |
| RP013 | 9 | 162 | 51 | 85 | 51 | 85 |

c) The comparator results were shown by Roche using the Abbott AxSym HAVAB-M 2.0 assay.

d) The comparator results were provided by Vendor using the Abbott HAVAB-M assay.

## EXPECTED VALUES:

The Elecsys Anti-HAV IgM assay was used to evaluate the prevalence of HAV IgM antibodies in an apparently healthy population (normal, healthy individuals without symptoms). 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 comprised of 208 (34.6 %) males and 394 (65.4 %) females including 493 (81.9 %) Caucasians, 32 (5.3 %) African Americans, 6 (1.0 %) Asians, 69 (11.5 %) American Indians and 2 (0.3 %) unknown. The data has been summarized according to age groups in decades, gender, geographical area and the number of reactive, non-reactive and equivocal results.

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| Expected results for the Elecsys Anti-HAV IgM assay in subjects from low prevalence areas for Hepatitis A | | | | | | | | | |
|------------------------------------------------------------------------------------------------------------|--------|------------------------------|---------|-----------|-----------|--------------|--------------|---------|-------|
| Age range | Gender | Reactive | | Equivocal | | Non-reactive | | Total | |
| | | N | Percent | N | Percent | N | Percent | | |
| | | 11 - 20 | Female | 0 | 0.00 | 0 | 0.00 | | 1 |
| 11 - 20 | Male | 0 | 0.00 | 0 | 0.00 | 1 | 100 | 1 | |
| 21 - 30 | Female | 0 | 0.00 | 0 | 0.00 | 7 | 100 | 7 | |
| 21 - 30 | Male | 0 | 0.00 | 0 | 0.00 | 6 | 100 | 6 | |
| 31 - 40 | Female | 0 | 0.00 | 0 | 0.00 | 21 | 100 | 21 | |
| 31 - 40 | Male | 0 | 0.00 | 0 | 0.00 | 2 | 100 | 2 | |
| 41 - 50 | Female | 0 | 0.00 | 0 | 0.00 | 22 | 100 | 22 | |
| 41 - 50 | Male | 0 | 0.00 | 0 | 0.00 | 13 | 100 | 13 | |
| 51 - 60 | Female | 0 | 0.00 | 0 | 0.00 | 42 | 100 | 42 | |
| 51 - 60 | Male | 0 | 0.00 | 0 | 0.00 | 19 | 100 | 19 | |
| 61 - 70 | Female | 0 | 0.00 | 0 | 0.00 | 51 | 100 | 51 | |
| 61 - 70 | Male | 0 | 0.00 | 0 | 0.00 | 28 | 100 | 28 | |
| 71 - 80 | Female | 0 | 0.00 | 0 | 0.00 | 48 | 100 | 48 | |
| Expected results for the Elecsys Anti-HAV IgM assay in subjects from high prevalence areas for Hepatitis A | | | | | | | | | |
| Age range | Gender | Elecsys Anti-HAV IgM results | | | | | | | Total |
| | | Reactive | | | Equivocal | | Non-reactive | | |
| | | N | Percent | | N | Percent | N | Percent | |
| 11 - 20 | Female | 0 | 0.00 | | 0 | 0.00 | 8 | 100 | 8 |
| | Male | 0 | 0.00 | | 0 | 0.00 | 5 | 100 | 5 |
| 21 - 30 | Female | 0 | 0.00 | | 0 | 0.00 | 17 | 100 | 17 |
| | Male | 0 | 0.00 | | 0 | 0.00 | 11 | 100 | 11 |
| 31 - 40 | Female | 0 | 0.00 | | 0 | 0.00 | 27 | 100 | 27 |
| | Male | 0 | 0.00 | | 0 | 0.00 | 13 | 100 | 13 |
| 41 - 50 | Female | 0 | 0.00 | | 0 | 0.00 | 52 | 100 | 52 |
| | Male | 0 | 0.00 | | 0 | 0.00 | 18 | 100 | 18 |
| 51 - 60 | Female | 0 | 0.00 | | 0 | 0.00 | 54 | 100 | 54 |
| | Male | 0 | 0.00 | | 0 | 0.00 | 24 | 100 | 24 |
| 61 - 70 | Female | 0 | 0.00 | | 0 | 0.00 | 25 | 100 | 25 |
| | Male | 1 | 4.00 | | 0 | 0.00 | 24 | 96.0 | 25 |
| 71 - 80 | Female | 0 | 0.00 | | 0 | 0.00 | 12 | 100 | 12 |
| | Male | 0 | 0.00 | | 0 | 0.00 | 7 | 100 | 7 |
| > 80 | Female | 0 | 0.00 | | 0 | 0.00 | 1 | 100 | 1 |
| | Male | 0 | 0.00 | | 0 | 0.00 | 0 | 0.00 | 0 |
| un- | Female | 0 | 0.00 | | 0 | 0.00 | 1 | 100 | 1 |
| known | Male | 0 | 0.00 | | 0 | 0.00 | 0 | 0.00 | 0 |
| All ages | Female | 0 | 0.00 | | 0 | 0.00 | 197 | 100 | 197 |

T

The prevalence rate for reactive anti-HAV IgM antibody in specimens collected in a low
prevalence region, Eastern states of the U.S. (Indiana), was 0.00 %.

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Prevalence rate for reactive anti-HAV IgM antibody in specimens collected in a high prevalence region, Western states of the U.S. (New Mexico), was 0.33 %.

#### PRECISION/REPRODUCIBILITY:

Precision and Reproducibility were determined using Elecsys reagents, human sera, and controls. Precision results were collected on three Elecsys 2010 analyzers using a single lot of reagent. PreciControl Anti-HAV IgM 1 and 2 (PC1 and PC2) materials and three human serum pools (high negative HSP1, low positive HSP2 and moderately positive HSP3) were tested in replicates of 2 in 2 runs/day for 20 days according to the CLSI EP15-A2/EP5-A2.

| Precision on Elecsys 2010 analyzer | | | | | | |
|------------------------------------|-------|----------------|-----|-------|-------------------------|--|
| | | Repeatabilityf | | | Intermediate precisiong | |
| Sample | Mean | SD | CV | SD | CV | |
| | COI | COI | % | COI | % | |
| HSP1 | 0.884 | 0.018 | 2.1 | 0.035 | 4.0 | |
| HSP2 | 1.14 | 0.030 | 2.6 | 0.051 | 4.5 | |
| HSP3 | 2.23 | 0.060 | 2.7 | 0.094 | 4.2 | |
| PC A-HAVIGM1 | 0.230 | 0.004 | 1.5 | 0.009 | 4.1 | |
| PC A-HAVIGM2 | 2.04 | 0.050 | 2.5 | 0.098 | 4.8 | |

1) Repeatability = within-run precision

8) Intermediate precision = between-run and between-day variation

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| Precision on MODULAR ANALYTICS E170 analyzers | | | | | |
|-----------------------------------------------|-------|----------------|-----|-------------------------|-----|
| | | Repeatabilityh | | Intermediate precisioni | |
| Sample | Mean | SD | CV | SD | CV |
| | COI | COI | % | COI | % |
| HSP1 | 0.929 | 0.018 | 1.9 | 0.040 | 4.4 |
| HSP2 | 1.22 | 0.024 | 2.0 | 0.060 | 4.9 |
| HSP3 | 2.36 | 0.052 | 2.2 | 0.110 | 4.7 |
| PC A-HAVIGM1 | 0.217 | 0.005 | 2.3 | 0.010 | 4.5 |
| PC A-HAVIGM2 | 2.13 | 0.043 | 2.0 | 0.110 | 5.1 |

h) Repeatability = within-run precision

1) Intermediate precision = between-run and between-day variation

Reproducibility was performed on three external sites on three different Elecsys 2010 and cobas e 411 analyzers. Three human serum pools (high negative HSP3, low positive HSP1 and moderately positive HSP2) were tested in replicates of 3 in 2 runs/day for 5 days according to the CLSI EP15-A2/EP5-A2.

| Reproducibility on Elecsys 2010 analyzer | | | | | | | | | | | |
|------------------------------------------|-------|---------------------|-----|---------------------------------|-----|-----------------|-----|------------------|-----|------------------------------|-----|
| | | Repeat-<br>abilityj | | Inter-<br>mediate<br>precisionk | | Between-<br>day | | Between-<br>site | | Repro-<br>ducibility (total) | |
| Sample | Mean | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV |
| | COIm | COI | % | COI | % | COI | % | COI | % | COI | % |
| HSP1 | 0.917 | 0.031 | 3.4 | 0.007 | 0.8 | 0.003 | 0.3 | 0.023 | 2.5 | 0.039 | 4.3 |
| HSP2 | 1.12 | 0.034 | 3.0 | 0.024 | 2.1 | 0.000 | 0.0 | 0.025 | 2.2 | 0.048 | 4.3 |
| HSP3 | 2.24 | 0.086 | 3.8 | 0.050 | 2.2 | 0.000 | 0.0 | 0.029 | 1.3 | 0.104 | 4.6 |
| PCll 1 | 0.239 | 0.006 | 2.6 | 0.000 | 0.0 | 0.004 | 1.9 | 0.010 | 4.4 | 0.013 | 5.4 |
| PC 2 | 1.65 | 0.049 | 3.0 | 0.021 | 1.3 | 0.058 | 3.5 | 0.027 | 1.6 | 0.083 | 5.1 |

1) Repeatability = within-run precision

k) Intermediate precision = between-run

1) SD = standard deviation

m) COI = cutoff index

") PC = PreciControl A-HAVIGM

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| Reproducibility on MODULAR ANALYTICS E170 analyzer | | | | | | | | | | | |
|----------------------------------------------------|--------------|----------------------------------|---------|-----------------------------------------|---------|------------------------------|---------|-------------------------------|---------|-------------------------------------------|---------|
| Sample | Mean<br>COIm | Repeat-<br>abilityj<br>SD<br>COI | CV<br>% | Intermediate<br>precisionk<br>SD<br>COI | CV<br>% | Between-<br>day<br>SD<br>COI | CV<br>% | Between-<br>site<br>SD<br>COI | CV<br>% | Repro-<br>ducibility (total)<br>SD<br>COI | CV<br>% |
| HSP1 | 0.923 | 0.019 | 2.1 | 0.020 | 2.1 | 0.000o | 0.0 | 0.014 | 1.5 | 0.031 | 3.4 |
| HSP2 | 1.13 | 0.026 | 2.3 | 0.024 | 2.1 | 0.000o | 0.0 | 0.000o | 0.0 | 0.035 | 3.1 |
| HSP3 | 2.30 | 0.046 | 2.0 | 0.078 | 3.4 | 0.000o | 0.0 | 0.000o | 0.0 | 0.091 | 4.0 |
| PCn 1 | 0.213 | 0.004 | 1.9 | 0.000o | 0.0 | 0.001 | 0.4 | 0.016 | 7.7 | 0.017 | 8.0 |
| PC 2 | 1.67 | 0.048 | 2.9 | 0.047 | 2.8 | 0.000o | 0.0 | 0.018 | 1.1 | 0.069 | 4.2 |

] Repeatability = within-run precision

k) Intermediate precision = between-run

1) SD = standard deviation

™ COI = cutoff index

") PC = PreciControl A-HA VIGM

® SD of zero due to variance contributed by particular component was below stated significant figure.

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### CROSS-REACTIVITY:

The specificity of the Elecsys Anti-HAV IgM assay was evaluated by testing a total of 211 specimens representing a variety of disease states (ANA, CMV, EBV, HBV, HCV, HIV, HSV, Mumps/Rubeola, Parvo B19, Rubella, Toxoplasmosis, and VZV).

| Cross- reactant | No.<br>tested | Elecsys Anti-<br>HAV IgM/<br>Reference<br>Neg/Neg | Elecsys Anti-<br>HAV IgM/<br>Reference<br>Equivocal/ Neg | Elecsys Anti-<br>HAV IgM/<br>Reference Neg/<br>Equivocal | Elecsys Anti-<br>HAV IgM/<br>Reference<br>Pos/Pos |
|-------------------|---------------|---------------------------------------------------|----------------------------------------------------------|----------------------------------------------------------|---------------------------------------------------|
| ANA | 11 | 10 | 0 | 1 | 0 |
| CMV | 13 | 13 | 0 | 0 | 0 |
| EBV | 16 | 16 | 0 | 0 | 0 |
| Elevated IgG | 13 | 13 | 0 | 0 | 0 |
| Elevated IgM | 12 | 11 | 1 | 0 | 0 |
| HBV | 20 | 20 | 0 | 0 | 0 |
| HCV | 11 | 11 | 0 | 0 | 0 |
| HIV | 11 | 11 | 0 | 0 | 0 |
| HSV | 11 | 11 | 0 | 0 | 0 |
| Mumps/ Rubeola | 15 | 15 | 0 | 0 | 0 |
| Parvo B19 | 15 | 15 | 0 | 0 | 0 |
| Rheumatoid factor | 12 | 12 | 0 | 0 | 0 |
| Rubella | 20 | 20 | 0 | 0 | 0 |
| Toxoplasmosis | 16 | 16 | 0 | 0 | 0 |
| VZV | 15 | 15 | 0 | 0 | 0 |
| Total | 211 | 209 | 1 | 1 | 0 |

The testing results are summarized in the table below.

HAMA effect was tested by comparing the recovery of 10 human serum samples spiked with HAMA versus 10 unspiked aliquots of samples. No HAMA effect was found.

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# POTENTIALLY INTERFERING SUBSTANCES:

The assay is unaffected by icterus (bilirubin < 855 umol/L or < 50 mg/dL), hemolysis (Hb < 0.623 mmol/L or < 1.0 g/dL), lipemia (Intralipid < 2000 mg/dL), and biotin < 205 nmol/L or < 50 ng/mL. There is no high-dose hook effect up to 16 COI.

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

# SERUM AND PLASMA COMPARISON:

The following tables summarize the results for the comparison between serum and 4 plasma matrices.

| Plasma matrix | Number of positive specimens showing recovery to serum within<br>various ranges | | |
|----------------|---------------------------------------------------------------------------------|-----------|--------|
| | < 10 % | 10 - 15 % | > 15 % |
| Li-heparin | 9 | 1 | 0 |
| Na-heparin | 9 | 1 | 0 |
| K2-EDTA | 10 | 0 | 0 |
| Sodium citrate | 9 | 1 | 0 |

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| Plasma matrix | Number of borderline specimens showing recovery to serum within various ranges | | |
|----------------|--------------------------------------------------------------------------------|-----------|--------|
| | < 10 % | 10 - 15 % | > 15 % |
| Li-heparin | 15 | 0 | 0 |
| Na-heparin | 15 | 0 | 0 |
| K2-EDTA | 15 | 0 | 0 |
| Sodium citrate | 12 | 3 | 0 |

| Plasma matrix | Number of negative specimens showing recovery to serum within<br>various ranges | | |
|----------------|---------------------------------------------------------------------------------|---------------|-----------|
| | < 0.1 COI | 0.1 - 0.3 COI | > 0.3 COI |
| Li-heparin | 20 | 0 | 0 |
| Na-heparin | 20 | 0 | 0 |
| K2-EDTA | 20 | 0 | 0 |
| Sodium citrate | 20 | 0 | 0 |

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Image /page/12/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States. The seal features a stylized eagle with three stripes forming its body, symbolizing health and human services. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.

#### Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center -- WO66-0609 Silver Spring, MD 20993-0002

Ms. Kelly French, RN, BSN, RAC Regulatory Affairs Consultant Roche Diagnostics Roche Professional Diagnostics 9115 Hague Road Indianapolis, IN 46250-0416

JUN 2 2 2010

Re: K093955

| Trade/Device Name: | Elecsys® Anti-HAV IgM<br>Elecsys® PreciControl Anti-HAV IgM |
|--------------------|------------------------------------------------------------------|
| Regulation Number: | 21 CFR §866.3310<br>21 CFR §862.1660 |
| Regulation Name: | Hepatitis A Virus Serological Assays<br>Quality Control Material |
| Regulatory Class: | Class II |
| Product Code: | LOL<br>JJX |
| Dated: | March 23, 2010 |
| Received: | March 24, 2010 |

Dear Ms. French:

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. Iisting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

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 Part 801); 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), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. 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/ReportalProblem/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 Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Uue Scif Ar

Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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# Indication for Use

510(k) Number: K093955

Device Name: Elecsys Anti-HAV IgM Assay

Indication For Use:

The Roche Elecsys Anti-HAV IgM immunoassay is used for the in vitro qualitative detection of IgM antibodies to hepatitis A virus (anti-HAV IgM) in human serum and plasma (potassium EDTA, lithium or sodium heparin, sodium citrate). The assay is intended for use as an aid in the laboratory diagnosis of an acute or recently acquired hepatitis A virus 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 and symptoms of hepatitis and in persons at risk for hepatitis A infection.

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

Device Name: Elecsys Anti-HAV IgM PreciControl

Indication For Use:

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

Prescription Use X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Uve Schly

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) k093955