(181 days)
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.
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.
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.
The Elecsys® Anti-HAV IgM immunoassay is intended for the in vitro qualitative detection of IgM antibodies to hepatitis A virus (anti-HAV IgM) in human serum and plasma. The assay is meant to aid in the laboratory diagnosis of an acute or recently acquired hepatitis A virus infection.
Here's an analysis of the acceptance criteria and the supporting study:
1. Table of Acceptance Criteria and Reported Device Performance
The submission does not explicitly state pre-defined acceptance criteria in terms of numerical thresholds for sensitivity, specificity, or agreement. However, the study aims to demonstrate the performance of the Elecsys Anti-HAV IgM immunoassay by comparing it to an FDA-cleared reference method. The implicit acceptance criterion is a high level of agreement with the predicate device across various sample cohorts.
| Performance Metric | Implicit Acceptance Criterion (High Agreement) | Reported Device Performance (Overall Cohort) |
|---|---|---|
| Positive Percent Agreement (PPA) | High PPA | 97.5% (118/121) with 95% CI (92.9% - 99.5%) |
| Negative Percent Agreement (NPA) | High NPA | 99.3% (959/966) with 95% CI (98.5% - 99.7%) |
| Analytical Sensitivity: | ||
| Earliest reactive result vs. predicate | Similar or earlier | Matches or earlier on HAV-01 and PHT 902 |
| Last positive result vs. predicate | Similar or later | Varies, generally similar or earlier |
| Precision (CV%) | Low CV% | |
| Elecsys 2010 (Repeatability) | Low (e.g., < 5%) | 1.5% - 3.8% |
| Elecsys 2010 (Intermediate Precision) | Low (e.g., < 5%) | 4.0% - 4.8% |
| MODULAR ANALYTICS E170 (Repeatability) | Low (e.g., < 5%) | 1.9% - 2.3% |
| MODULAR ANALYTICS E170 (Intermediate Precision) | Low (e.g., < 5%) | 4.4% - 5.1% |
| Reproducibility (Total CV%) | Low CV% | |
| Elecsys 2010 | Low (e.g., < 5%) | 4.3% - 5.4% |
| MODULAR ANALYTICS E170 | Low (e.g., < 5%) | 3.1% - 8.0% |
| Cross-reactivity | No significant cross-reactivity | 209/211 specimens showed no cross-reactivity |
| Interfering Substances | No interference | None found for tested substances and levels |
| Serum and Plasma Comparison | Consistent results across matrices | High recovery within various ranges |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- Comparative Testing (Clinical Performance): 1087 total samples.
- Analytical Sensitivity: 3 commercially available HAV seroconversion panels.
- Expected Values (Prevalence): 602 subjects (208 males, 394 females) from two US regions.
- Cross-reactivity: 211 specimens representing various disease states.
- Potentially Interfering Substances: Not explicitly stated, implied to be sufficient for 18 pharmaceuticals and other substances.
- Serum and Plasma Comparison: 10 positive, 15 borderline, and 20 negative specimens per plasma matrix (Li-heparin, Na-heparin, K2-EDTA, Sodium citrate).
- Precision/Reproducibility: Human serum pools (3) and controls (2) tested in replicates over multiple days/runs/sites.
- Data Provenance:
- Clinical Performance: Multi-center study conducted in the U.S. Retrospective (samples were obtained for routine testing, from hospitalized patients, etc.).
- Expected Values: Prospective study of apparently healthy individuals from New Mexico (high prevalence region) and Indiana (low prevalence region) in the U.S.
- Other studies (Analytical Sensitivity, Cross-reactivity, Precision/Reproducibility, Interfering Substances, Serum/Plasma Comparison) are likely laboratory-based studies conducted by the manufacturer, with samples possibly sourced from commercial vendors or clinical sites.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
The ground truth for the clinical performance study was established by an "FDA-cleared reference method." A second FDA-cleared anti-HAV IgM assay was used for discrepant analysis, and for a subset of concordant specimens.
- Number of Experts: Not applicable, as the ground truth was established by laboratory assays (reference methods), not by individual experts or a consensus thereof.
- Qualifications of Experts: Not applicable.
4. Adjudication Method for the Test Set
For the comparative testing (clinical performance):
- The primary comparison was against a "1st reference anti-HAV IgM assay."
- Discrepant Analysis: For discrepant and several concordant samples, a "second FDA cleared anti-HAV IgM assay" was used for additional testing.
- Adjudication Rule: The second predicate agreed with the Elecsys outcome in 7 of 10 discrepant samples and with the first predicate in 2 of 10. No consensus was obtained in the remaining specimen.
- This indicates a form of 2-assay adjudication where a third assay (the Elecsys in this case) is compared against two reference assays. The "ground truth" for the overall agreement calculation appears to be based on the initial primary reference assay, with the secondary assay used to investigate discrepancies.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, an MRMC comparative effectiveness study was not done.
- This device is an in vitro diagnostic (IVD) immunoassay, not an imaging or interpretation device that would typically involve multiple human readers. The performance is assessed in terms of agreement with a reference laboratory method.
- Effect Size of Human Readers with/without AI Assistance: Not applicable, as no human reader component or AI assistance is described for the interpretation of this immunoassay.
6. Standalone Performance Study
- Yes, a standalone study was done. The entire clinical performance section, particularly the "COMPARATIVE TESTING" and "ANALYTICAL SENSITIVITY" sections, evaluates the algorithm's (the immunoassay's) performance independently against established reference methods and panels. The reported Positive Percent Agreement and Negative Percent Agreement are measures of the device's standalone performance relative to the chosen reference.
7. Type of Ground Truth Used
- Expert Consensus: Not used for establishing the primary ground truth.
- Pathology: Not applicable.
- Outcomes Data: Not explicitly mentioned as the primary ground truth source.
- Reference Assay/Method: The primary ground truth for the clinical performance was established by an "FDA-cleared reference method" (the Abbott Axsym HAVAB-M 2.0 Assay). For discrepant samples, a second FDA-cleared anti-HAV IgM assay was used for further investigation. For analytical sensitivity, the ground truth was based on commercially available HAV seroconversion panels and comparator assays (Abbott Axym HAVAB-M 2.0 and Abbott HAVAB-M).
8. Sample Size for the Training Set
- Not explicitly stated within the provided document. IVD assays like this immunoassay typically undergo extensive laboratory development and optimization during which various samples might be used for "training" or optimization. However, the document focuses on the validation and performance testing of the finalized assay. Manufacturers often do not disclose specific "training set" sizes for IVD assays in 510(k) submissions, as the development process involves reagent formulation and analytical optimization rather than a distinct "machine learning training set" in the common sense.
9. How the Ground Truth for the Training Set Was Established
- Not explicitly stated in the document. Similar to point 8, the specific methodology for establishing ground truth during the assay's development or "training" phase is not detailed. It is reasonable to assume that standard laboratory practices, including the use of well-characterized positive and negative control samples, reference materials, and expert knowledge of HAV infection serology, would have been employed during the optimization and development of the Elecsys Anti-HAV IgM immunoassay.
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JUN 2 2 2010
SUBMITTED BY:
Kelly French Regulatory Affairs Consultant Roche Diagnostics 9115 Hague Road Indianapolis, IN 46250 Phone: (317) 521-3208 Fax: (317) 521-2324 Email: kelly.french@roche.com
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 DeviceAbbott Axsym HAVAB-M 2.0Assay (P790019/S011 |
| Assay Protocol | μ-Capture test principle | Direct Binding principle |
| Detection Protocol | Electrochemiluminescenceimmunoassay (ECLIA) | MEIA |
| Traceability/Standardization | Roche Internal Standard | Not Given |
| Sample Type | Human serum and plasma | Same |
| InstrumentPlatform | Elecsys 2010(Request for CLIA categorizationhas been made to add theMODULAR ANALYTICS E170,cobas e 411, and cobas e 601analyzers according to theReplacement Reagent andInstrument Policy). | AxSYM System |
| Interpretation ofResults | $\ge$ 1.10 Reactive$\ge$ 0.90 - $<$ 1.10 Grayzone$<$ 0.9 Negative | $>$ 1.20 Reactive0.80 -1.20 Grayzone$<$ 0.80 Nonreactive |
| 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 single sample of both theNegative and Positive Controlsmust be tested as a means ofevaluating the assay calibration.Once the calibration is accepted andstored, all subsequent samples maybe tested without further calibrationunless one or more of the followingoccur:• A reagent pack with a new lotnumber is used• Either of the AxSYM HAVAB-M2.0 Control values is out of itsspecified range• The MEIA Optics VerificationUpdate has been performed |
| Controls | Elecsys PreciControl Anti-HAVIgM | Abbott AxSYM HAVAB-M 2.0Controls |
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 percentagreement % (x/n) | 95 % confidenceinterval | Negative percentagreement %(x/n) | 95 % confidenceinterval |
| Routine HAVtesting | 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 forhepatitis | 0.00 (0/0) | 0.00 - 100 | 100 (215/215) | 98.3 - 100 |
| Signs andsymptoms | 0.00 (0/0) | 0.00 - 100 | 99.5 (211/212) | 97.4 - 99.99 |
| Characterizedacute HAV | 98.3 (117/119) | 94.1 - 99.8 | 73.3 (11/15) | 44.9 - 92.2 |
| Pediatric/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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I
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|---|---|---|---|---|---|---|---|
| Total | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | C0VICE | 3Ar- AND R-1-1-1-1-1-1-1-1-1-1-1-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2- | 000 | 001 | 000ﺎ ﻟﻠ |
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 |
-
Repeatability = within-run precision
-
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
- 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-abilityj | Inter-mediateprecisionk | Between-day | Between-site | Repro-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 |
- Repeatability = within-run precision
k) Intermediate precision = between-run
- SD = standard deviation
m) COI = cutoff index
") PC = PreciControl A-HAVIGM
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| Reproducibility on MODULAR ANALYTICS E170 analyzer | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Sample | MeanCOIm | Repeat-abilityjSDCOI | CV% | IntermediateprecisionkSDCOI | CV% | Between-daySDCOI | CV% | Between-siteSDCOI | CV% | Repro-ducibility (total)SDCOI | CV% |
| 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
- 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.tested | Elecsys Anti-HAV IgM/ReferenceNeg/Neg | Elecsys Anti-HAV IgM/ReferenceEquivocal/ Neg | Elecsys Anti-HAV IgM/Reference Neg/Equivocal | Elecsys Anti-HAV IgM/ReferencePos/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 withinvarious 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 withinvarious 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 IgMElecsys® PreciControl Anti-HAV IgM |
|---|---|
| Regulation Number: | 21 CFR §866.331021 CFR §862.1660 |
| Regulation Name: | Hepatitis A Virus Serological AssaysQuality Control Material |
| Regulatory Class: | Class II |
| Product Code: | LOLJJX |
| 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
{13}------------------------------------------------
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 (800) 638-2041 or (301) 796-7100 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
§ 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.