MONOLISA ANTI-HAV IGM EIA
Device Facts
| Record ID | K063319 |
|---|---|
| Device Name | MONOLISA ANTI-HAV IGM EIA |
| Applicant | Bio-Rad Laboratories |
| Product Code | LOL · Microbiology |
| Decision Date | May 3, 2007 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.3310 |
| Device Class | Class 2 |
| Attributes | Pediatric |
Indications for Use
The MONOLISA™ Anti-HAV IgM EIA is an in vitro enzyme immunoassay kit intended for use in the qualitative detection of IgM antibodies to Hepatitis A virus (anti-HAV IgM) in human (adult and pediatric) serum or plasma (EDTA, Heparin, Citrate, ACD). This assay is indicated for testing specimens from individuals who have signs and symptoms consistent with acute Hepatitis. Assay results, in conjunction with other serological or clinical information, may be used for the laboratory diagnosis of individuals with acute or recent Hepatitis A. Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients, and cord blood or neonatal specimens. WARNING :This assay is not intended for screening blood or solid or soft tissue donors.
Device Story
MONOLISA™ Anti-HAV IgM EIA is an enzyme immunoassay (IgM antibody capture format) for detecting IgM antibodies to Hepatitis A virus (HAV). Input: human serum or plasma specimens. Procedure: specimens, calibrator, and controls incubated in microwells coated with anti-human IgM antibodies; HAV viral antigen and HRP-labeled mouse monoclonal antibody to HAV added; TMB chromogen/substrate solution added. Principle: if IgM anti-HAV is present, HRP binds, causing TMB color change (colorless to blue, then yellow after stopping solution). Output: color intensity measured spectrophotometrically; absorbance compared to cutoff value. Used in clinical laboratories by trained personnel. Results aid diagnosis of acute/recent Hepatitis A in symptomatic patients. Benefits: provides qualitative laboratory confirmation of acute HAV infection.
Clinical Evidence
Multi-center prospective/retrospective study (US and Europe, N=1249). US population (N=404) included symptomatic and high-risk subjects. European population (N=845) included symptomatic, high-risk, hospitalized, and recovered patients. Primary endpoint: positive/negative percent agreement vs comparative assay. Results: Positive percent agreement 100% (86/86); Negative percent agreement 99.1% (1233/1244). Seroconversion panels (N=8) showed equivalent sensitivity to comparator. Cross-reactivity study (N=255) showed no cross-reactivity with other viral/disease states.
Technological Characteristics
Enzyme immunoassay (antibody capture). Components: microplate wells coated with polyclonal anti-human IgM, HRP-labeled mouse monoclonal anti-HAV conjugate, TMB chromogen, hydrogen peroxide substrate, 1N H2SO4 stop solution. Dual wavelength spectrophotometric reading (450 nm/615-630 nm). Requires Bio-Rad microwell plate reader or equivalent with specified bandwidth/linearity. Manual/automated processing.
Indications for Use
Indicated for qualitative detection of anti-HAV IgM in human adult and pediatric serum or plasma. Used for laboratory diagnosis of acute or recent Hepatitis A in individuals with consistent signs/symptoms. Not for screening blood/tissue donors. Performance not established for immunocompromised/immunosuppressed patients, cord blood, or neonates.
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
- DiaSorin ETI-HA-IGMK PLUS (P890014)
Related Devices
- K063318 — MONOLISA ANTI-HAV EIA · Bio-Rad Laboratories · May 3, 2007
- K082050 — LIAISON HAV IGM ASSAY, LIAISON CONTROL HAV IGM · DiaSorin, Inc. · Nov 3, 2008
- K092353 — MONOLISA ANTI-HAV IGM EIA · Bio-Rad Laboratories, Inc. · Oct 29, 2009
Submission Summary (Full Text)
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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
DEVICE ONLY TEMPLATE
A. 510(k) Number:
K063319
B. Purpose for Submission:
New device clearance
C. Measurand:
IgM Antibody to Hepatitis A Virus
D. Type of Test:
Qualitative, ELISA
E. Applicant:
Bio-Rad.
F. Proprietary and Established Names:
MONOLISA™ Anti-HAV IgM EIA
G. Regulatory Information:
1. Regulation section:
21 CFR Part 866.3310, Hepatitis A virus (HAV) Serological Reagents
2. Classification:
Class II
3. Product Code:
LOL
4. Panel:
83 Microbiology
H. Intended Use:
1. Indication(s) for use:
The MONOLISA™ Anti-HAV IgM EIA is an in vitro enzyme immunoassay kit intended for use in the qualitative detection of IgM antibodies to Hepatitis A virus (anti-HAV IgM) in human (adult and pediatric) serum or plasma (EDTA, Heparin, Citrate, ACD). The assay is indicated for testing specimens from individuals who have signs and symptoms consistent with acute Hepatitis. Assay results, in conjunction with other serological or clinical information, may be used for the laboratory diagnosis of individuals with acute or recent Hepatitis A.
Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients, and core blood or neonatal specimens.
Warning: This assay is not intended for screening blood or solid or soft tissue donors.
2. Special condition for use statement(s):
The new device is not intended to be sold over the counter and is for prescription use only. Warnings on applicant labeling state “Under United States federal law
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restricts this device to sale by or on the order of a licensed practitioner or physician".
3. Special instrument Requirements:
Bio-Rad microwell plate or strip reader or equivalent. The spectrophotometer should have the following specifications at wavelength 450 nm:
Bandwidth: 10 nm HBW (Half Band Width) or equivalent
Absorbance Range: 0 to 3.0 Repeatability: ± (0.5% + 0.005) Linearity or
Accuracy: 1% from 0 to 3.0
The instrument should contain a reference filter for reading at 615 to 630 nm. An instrument without a reference filter can be used; however, areas in the bottoms of the wells that are opaque, scratched or irregular may cause absorbance readings that are falsely elevated.
I. Device Description:
Enzyme immunoassay (antibody capture format) for the detection of IgM antibodies to Hepatitis A virus.
J. Substantial Equivalence Information:
1. Predicate device name(s):
DiaSorin ETI-HA-IGMK PLUS
2. Predicate K number(s):
P890014
3. Comparison with predicate:
The following tables summarize similarities and differences between the
MONOLISA™ Anti-HAV IgM EIA kit and the predicate device ETI-HA-IGMK PLUS.
Table 1: Similarities between kit components and materials
| Similarities in Components / Materials | MONOLISA™ Anti-HAV IgM EIA Catalog# 72495 | ETI-HA-IGMK PLUS Catalog# P001925 |
| --- | --- | --- |
| Conjugate | Peroxidase-labeled mouse monoclonal antibody to HAV. | Peroxidase-labeled mouse monoclonal antibody to HAV. |
| Positive Control | Human plasma, positive for IgM anti-HAV antibodies, diluted in human plasma negative for anti-HAV antibodies. | Human serum/plasma reactive for IgM anti-HAV, diluted with buffer. |
| Chromogen | Tetramethylbenzidine (TMB) | Tetramethylbenzidine (TMB) |
| Substrate | Hydrogen Peroxide | Hydrogen Peroxide |
| Washing Solution | Concentrated buffered solution with Tween 20. | Concentrated buffered solution with detergents. |
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Table 2: Differences between kit components and materials
| Differences in Components / Materials | MONOLISA™ Anti-HAV IgM EIA Catalog# 72495 | ETI-HA-IGMK PLUS Catalog# P001925 |
| --- | --- | --- |
| Solid Phase | Microplate wells coated with polyclonal anti-human IgM antibodies. | Microplate wells coated with mouse monoclonal antibodies to human IgM. |
| Negative Control | Human plasma, negative for IgM anti-HAV antibodies and total anti-HAV antibodies. | Human serum/plasma non-reactive for IgM anti-HAV and reactive for IgG anti-HAV, diluted in buffer. |
| Calibrator | Human plasma, positive for IgM anti-HAV antibodies diluted in buffer. | Human serum/plasma non-reactive for IgM anti-HAV and reactive for IgG anti-HAV diluted with buffer. |
| Conjugate | Ready-to-use | To be diluted. |
| Stopping Solution | 1N H2SO4. | 0.4N H2SO4. |
| Required sample volume | 20 μl | 10 μl |
Table 3: Similarities between kits with regard to function and use
| Similarities in Function and Use | MONOLISA™ Anti-HAV IgM EIA Catalog# 72495 | ETI-HA-IGMK PLUS Catalog# P001925 |
| --- | --- | --- |
| Test Method | EIA (antibody capture) | EIA (antibody capture) |
| Specimen Storage Requirements | Samples may be stored at 2-8°C for up to 24 hours. | Samples may be stored at 2-8°C for up to 24 hours. |
| Format | 96-well microplate | 96-well microplate |
| Intended Use | Assay for the qualitative detection of anti-HAV IgM antibodies in human serum or plasma. | Assay for the qualitative detection of anti-HAV IgM antibodies in human serum or plasma. |
| Wavelength | Dual wavelength reading at 450 nm and 615/630 nm. | Dual wavelength reading at 450 nm and 630 nm. |
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Table 4: Differences between kits with regard to function and use
| Differences in Function and Use | MONOLISA™ Anti-HAV IgM EIA Catalog# 72495 | ETI-HA-IGMK PLUS Catalog# P001925 |
| --- | --- | --- |
| Spectrophotometric Verification of Sample and Reagent Pipeting | Possible (but optional) | NA |
| Cutoff calculation | Mean absorbance of calibrator values divided by 4 | Mean absorbance of the calibrator values + 0.250 |
# K. Standard/Guidance Document Referenced (if applicable):
Class II Special Control Guidance Document, Hepatitis A Virus Serological Assays, issued February 9, 2006.
# L. Test Principle:
The MONOLISA™ Anti-HAV IgM EIA is an enzyme immunoassay (IgM antibody capture format) for the detection of IgM antibodies to Hepatitis A Virus. In the assay procedure, patient specimens, a calibrator, and controls are incubated with anti-human IgM antibodies coated on the microwells. If IgM antibodies to HAV are present in a specimen or control, they bind to the antibody. Excess sample is removed by a wash step. The HAV Viral Antigen and the Conjugate (containing horseradish peroxidase - labeled mouse monoclonal antibody to HAV) are successively added to the microwells and allowed to incubate. The presence of IgM anti-HAV in the sample enables the HAV Viral Antigen and the Conjugate to bind to the solid phase. Excess Conjugate and HAV Viral Antigen are removed by a wash step, and a TMB Chromogen / Substrate solution is added to the microwells and allowed to incubate. If a sample contains anti-HAV IgM, the bound enzyme (HRP) causes the colorless TMB in the Chromogen solution to change to blue. The blue color turns yellow after the addition of a Stopping Solution. If a sample does not contain anti-HAV IgM, the Chromogen / Substrate solution in the well remains colorless during the substrate incubation, and after the addition of the Stopping Solution. The color intensity is measured spectrophotometrically. Absorbance value readings for patient specimens are compared to the cutoff value.
# M. Performance Characteristics (if/when applicable):
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# 1. Analytical performance:
# a. Precision/Reproducibility:
# Within-Laboratory Precision Study:
A 21-member panel was tested: serum samples with the 6 corresponding plasma samples (EDTA K2, EDTA K3, Sodium Citrate, Sodium Heparin, Lithium heparin, ACD) at 3 different levels (1 negative, 1 negative near the cutoff, 1 low positive near the cutoff) were tested on 1 lot, in duplicate, in 2 different runs per day (am and pm), by the same operator for a period of 20 days. The data were analyzed following the CLSI guidance EP5A2. The mean ratio, the Standard Deviation (SD) and percent coefficient of variation (%CV) were calculated for each panel member.
The data summary is shown in the following table:
MONOLISA™ Anti-HAV IgM EIA Precision Results by Panel Member Signal to Cutoff (S/CO)
| Panel Member | N | Mean S/CO | Within run1 | | Between Run 2 | | Between Day 3 | | Total4 | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) |
| Negative Control C0 | 40 | 0.08 | NA | NA | 0.01 | 11.0% | 0.00 | 0.8% | 0.01 | 11.0% |
| Positive Control C1 | 40 | 2.03 | NA | NA | 0.08 | 4.2% | 0.05 | 2.5% | 0.10 | 4.8% |
| serum 1 | 80 | 0.05 | 0.00 | 5.5% | 0.01 | 14.1% | 0.00 | 7.7% | 0.01 | 17.0% |
| EDTA K2 1 | 80 | 0.05 | 0.00 | 6.3% | 0.01 | 13.4% | 0.00 | 6.4% | 0.01 | 16.1% |
| EDTA K3 1 | 80 | 0.05 | 0.00 | 6.3% | 0.01 | 15.2% | 0.00 | 4.6% | 0.01 | 17.1% |
| Sodium Citrate 1 | 80 | 0.05 | 0.00 | 6.7% | 0.01 | 14.0% | 0.00 | 0.0% | 0.01 | 15.5% |
| Sodium Heparin 1 | 80 | 0.05 | 0.00 | 6.7% | 0.01 | 12.6% | 0.00 | 5.6% | 0.01 | 15.4% |
| Lithium Heparin 1 | 80 | 0.05 | 0.00 | 6.7% | 0.01 | 14.5% | 0.00 | 7.6% | 0.01 | 17.7% |
| ACD A | 80 | 0.05 | 0.00 | 6.3% | 0.01 | 14.0% | 0.00 | 0.4% | 0.01 | 15.3% |
| Serum 2 | 80 | 0.55 | 0.02 | 3.7% | 0.02 | 4.0% | 0.02 | 3.6% | 0.04 | 6.5% |
| EDTA K2 2 | 80 | 0.66 | 0.02 | 3.5% | 0.03 | 4.9% | 0.03 | 5.3% | 0.05 | 8.0% |
| EDTA K3 2 | 80 | 0.65 | 0.02 | 3.3% | 0.04 | 6.1% | 0.03 | 4.7% | 0.05 | 8.3% |
| Sodium Citrate 2 | 80 | 0.65 | 0.03 | 5.0% | 0.03 | 5.0% | 0.02 | 3.8% | 0.05 | 8.0% |
| Sodium Heparin 2 | 80 | 0.57 | 0.01 | 2.5% | 0.02 | 3.7% | 0.03 | 4.8% | 0.04 | 6.6% |
| Lithium Heparin 2 | 80 | 0.57 | 0.02 | 2.7% | 0.04 | 6.1% | 0.02 | 4.0% | 0.05 | 7.8% |
| ACD 2 | 80 | 0.68 | 0.03 | 5.2% | 0.04 | 6.3% | 0.03 | 4.4% | 0.06 | 9.2% |
| Serum 3 | 80 | 1.33 | 0.03 | 2.1% | 0.06 | 4.8% | 0.06 | 5.2% | 0.09 | 7.4% |
| EDTA K2 3 | 80 | 1.44 | 0.03 | 2.5% | 0.06 | 4.8% | 0.06 | 4.7% | 0.09 | 7.2% |
| EDTA K3 3 | 80 | 1.35 | 0.07 | 6.2% | 0.07 | 5.4% | 0.05 | 4.5% | 0.11 | 9.4% |
| Sodium Citrate 3 | 80 | 1.44 | 0.04 | 3.1% | 0.05 | 4.2% | 0.06 | 5.2% | 0.09 | 7.4% |
| Sodium Heparin 3 | 80 | 1.36 | 0.02 | 2.1% | 0.06 | 5.1% | 0.06 | 4.7% | 0.09 | 7.2% |
| Lithium Heparin 3 | 80 | 1.35 | 0.05 | 4.1% | 0.07 | 5.8% | 0.05 | 4.3% | 0.10 | 8.3% |
| ACD 3 | 80 | 1.47 | 0.04 | 3.5% | 0.10 | 8.4% | 0.06 | 5.1% | 0.13 | 10.5% |
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NA: Not Applicable
1 Within Run: variability of the assay performance from replicate to replicate
2Between Run: variability of the assay performance from Run to Run
3Between Day: variability of the assay performance from Day to Day
4Total: total variability of the assay performance includes within run, between run and between day.
# Reproducibility Study:
A 6 member panel consisting of diluted plasma specimens (negative and different levels of positive) was tested in triplicate, once a day for 3 days on 3 lots* of MONOLISA™ Anti-HAV IgM EIA at 3 separate clinical trial sites. Each panel was coded with a different number on each day tested in order to blind the operator to the expected value of the sample. *3 different lots were used at the Bio-Rad site and 2 lots were used on each of the external sites. The data from all reagent lots and sites were combined to obtain standard deviation (SD) and percent coefficient of variation (CV) for within run, between day, between lot, between site and total variance. The data were analyzed according to the principles described in the Clinical Laboratory Standards Institute guidance EP5-A2, revised November 2004 and ISO/TR 22971:2005. The PROC GLM procedure in SAS® was used to estimate the variance components of the model. The model was $y =$ site + lot (site) + day (lot site) + error.
The summaries are shown in the following tables:
MONOLISA™ Anti-HAV IgM EIA Reproducibility Results by Panel Member Signal to Cutoff (S/CO)
| Test site | Panel Member | N | Mean S/CO | Within Run1 | | Between Day2 | | Between Lot3 | | Total4 | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Site #1 | P1 | 18 | 0.05 | 0.03 | 74.6 | 05 | 0 | 05 | 0 | 0.03 | 74.6 |
| | P2 | 18 | 0.69 | 0.03 | 4.7 | 0.06 | 8.1 | 05 | 0 | 0.06 | 9.4 |
| | P3 | 18 | 1.10 | 0.04 | 3.6 | 0.07 | 6.7 | 05 | 0 | 0.08 | 7.6 |
| | P4 | 18 | 1.69 | 0.05 | 2.7 | 0.13 | 7.6 | 05 | 0 | 0.14 | 8.1 |
| | P5 | 18 | 3.26 | 0.07 | 2.2 | 0.03 | 1.1 | 05 | 0 | 0.08 | 2.4 |
| | P6 | 18 | 4.19 | 0.19 | 4.6 | 0.00 | 0.0 | 0.05 | 1.1 | 0.20 | 4.7 |
| Site#2 | P1 | 18 | 0.06 | 0.00 | 6.4 | 0.01 | 12.2 | 0.00 | 6.7 | 0.01 | 15.4 |
| | P2 | 18 | 0.82 | 0.02 | 2.8 | 0.06 | 7.0 | 05 | 0 | 0.06 | 7.5 |
| | P3 | 18 | 1.27 | 0.05 | 3.8 | 0.08 | 6.6 | 0.11 | 8.6 | 0.15 | 11.5 |
| | P4 | 18 | 2.01 | 0.12 | 5.7 | 0.14 | 7.0 | 05 | 0 | 0.18 | 9.1 |
| | P5 | 18 | 3.8 | 0.15 | 4.0 | 0.20 | 5.2 | 05 | 0 | 0.25 | 6.6 |
| | P6 | 18 | 4.8 | 0.14 | 2.8 | 0.38 | 7.9 | 05 | 0 | 0.40 | 8.3 |
| | P1 | 27 | 0.04 | 0.00 | 6.7 | 0.01 | 13.0 | 0.00 | 11.7 | 0.01 | 18.7 |
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| Site #3 | P2 | 27 | 0.71 | 0.02 | 3.3 | 0.03 | 4.0 | 0.04 | 6.1 | 0.06 | 8.0 |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | P3 | 27 | 1.12 | 0.05 | 4.3 | 0.02 | 2.1 | 0.09 | 7.7 | 0.10 | 9.1 |
| | P4 | 27 | 1.77 | 0.06 | 3.4 | 0.08 | 4.3 | 0.10 | 5.8 | 0.14 | 8.0 |
| | P5 | 27 | 3.26 | 0.09 | 2.8 | 0.10 | 3.1 | 0.13 | 4.0 | 0.19 | 5.8 |
| | P6 | 27 | 3.93 | 0.10 | 2.6 | 0.10 | 2.5 | 0.20 | 5.1 | 0.25 | 6.3 |
1. Within Run: variability of the assay performance from replicate to replicate
2. Between Day: variability of the assay performance from Day to Day
3. Between Lot: variability of the assay performance from Lot to Lot
4. Total: total variability of the assay performance includes within run, between day and between lot.
5. Negative variances were rounded to zero, per statistical convention.
MONOLISA™ Anti-HAV IgM EIA Reproducibility summary by Panel Member Signal to Cutoff (S/CO).
| Panel Member | N | Mean S/CO | Within Run1 | | Between Day2 | | Between Lot3 | | Between Site5 | | Total4 | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| P1 | 63 | 0.05 | 0.02 | 37.8 | 0.00 | 0.0 | 0.00 | 8.1 | 0.01 | 19.6 | 0.02 | 43.3 |
| P2 | 63 | 0.74 | 0.03 | 3.6 | 0.05 | 6.4 | 0.02 | 2.6 | 0.06 | 8.0 | 0.08 | 11.1 |
| P3 | 63 | 1.16 | 0.05 | 3.9 | 0.06 | 5.3 | 0.08 | 6.8 | 0.07 | 5.8 | 0.13 | 11.1 |
| P4 | 63 | 1.82 | 0.08 | 4.2 | 0.11 | 6.3 | 0.05 | 3.0 | 0.15 | 8.1 | 0.21 | 11.5 |
| P5 | 63 | 3.41 | 0.11 | 3.0 | 0.13 | 3.7 | 0.09 | 2.5 | 0.29 | 8.5 | 0.35 | 10.1 |
| P6 | 63 | 4.25 | 0.14 | 3.3 | 0.21 | 5.0 | 0.14 | 3.2 | 0.43 | 10.1 | 0.52 | 12.2 |
1. Within Run: variability of the assay performance from replicate to replicate
2. Between Day: variability of the assay performance from Day to Day
3. Between Lot: variability of the assay performance from Lot to Lot
4. Between site: variability of the assay performance from Site to Site
5. Total: total variability of the assay performance includes within run, between day between lot and between Site.
## Reproducibility study on Negative and Positive Controls:
The negative and positive controls were tested in triplicate, once a day by 3 different operators for 3 days. The data were analyzed according to the principles described in the Clinical Laboratory Standards Institute guidance EP5-A2, revised November 2004 and ISO/TR 22971:2005.
## b. Linearity/assay reportable range:
NA
## c. Traceability, Stability, Expected values (controls, calibrators, or method):
Controls and calibrators are provided specifically designed for use in conjunction with the performance of the assay.
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# d. Detection limit:
NA
# e. Analytical specificity:
The potential for cross reactivity to other disease states, or viruses was evaluated for the MONOLISA™ Anti-IgM HAV EIA Assay and the comparative assay. In addition, samples containing rheumatoid factors, autoantibodies, anti-mouse antibodies were tested. In total, 255 specimens (including both serum and plasma) from 16 groups of potential cross-reactivity were tested. FDA approved methods were used to confirm the disease state of each specimen. The results are summarized in the following table.
# Potential cross reactivity study
| Clinical condition | Number tested | MONOLISA™ Anti-HAV IgM EIA nonreactive |
| --- | --- | --- |
| Hepatitis C (HCV) | 15 | 15 |
| Hepatitis B (HBV) HBs Ag | 15 | 15 |
| Hepatitis B (HBV) anti HBc | 15 | 15 |
| Human Immunodeficiency Virus (HIV) | 15 | 15 |
| Epstein Barr Virus (EBV) IgG | 15 | 15 |
| Epstein Barr Virus (EBV) IgM | 15 | 15 |
| Cytomegalovirus (CMV) IgG | 15 | 15 |
| Cytomegalovirus (CMV) IgM | 15 | 15 |
| Rubella IgG | 15 | 15 |
| Toxoplasmosis IgG | 15 | 15 |
| Toxoplasmosis IgM | 15 | 15 |
| Mumps IgG | 15 | 15 |
| Varicella Zoster Virus(VZV) IgG | 15 | 15 |
| Varicella Zoster Virus(VZV) IgM | 15 | 15 |
| Anti Nuclear Antibody (ANA) | 15 | 15 |
| Human Anti Mouse Antibody (HAMA) | 15 | 15 |
| Rheumatoid Arthritis | 15 | 15 |
| Total Samples tested | 255 | 255 |
All the 255 specimens were found nonreactive with HAV IgM with MONOLISA™ Anti-HAV IgM and with the predicate assay.
# f. Assay cut-off: N/A
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2. Comparison studies:
a. Method comparison with predicate device:
MONOLISA™ Anti-IgM HAV EIA was compared to the DiaSorin ETI-HA-IGMK PLUS assays.
b. Matrix comparison: N/A
3. Clinical studies:
a. Clinical sensitivity:
See Performance Characteristics below
b. Clinical specificity:
See Performance Characteristics below
c. Other clinical supportive data (when a and b are not applicable):
## Clinical Performance
A multi-center prospective and retrospective study was conducted to evaluate the clinical performance of the MONOLISA™ Anti-HAV IgM EIA assay among individuals with signs or symptoms and those at high risk for Hepatitis infection. Specimens were collected in 3 different geographical areas: 404 specimens were collected in the US and 929 were collected in Europe (France and Italy).
The US population consisted of 174 subjects with signs and symptoms of Hepatitis. In this group, 60% were male and 40% were female, and they ranged in age from 17 to 72 years (mean age of 38). The group was Caucasian (13.2%), Black or African American (4.6%), Hispanic or Latino (2.9%), and Asian (41.9%), with the remaining 1.1% represented by multiple ethnic groups. The ethnicity of 36.8% was unknown. Among these subjects, 23 (13.2%) were pediatric samples.
The 230 subjects from the high-risk group for Hepatitis A include intravenous drug users (N=55), homosexual males (N=15), sex workers (N=39), prison history (N=92), high-risk sex partners (N=25), high-risk occupation/health care workers (N=4). Many had more than 1 high-risk behavior or risk factor. The group was Caucasian (7.4%), Black or African American (74.3%), Hispanic or Latino (15.2%), Asian (0.4%), Native Hawaiian or other Pacific Islander (0.4%), and American Indian or Alaska native (0.9%), with the remaining 1.3% represented by multiple ethnic groups. In this group, 81% were male and 19% were female, and they ranged in age from 18 to 70 years (mean age of 45). Among these 230 subjects, 2 (0.9%) were pediatric samples.
The European population consisted of 253 specimens collected from patients with signs and symptoms of Hepatitis. In this group, 51% were male and 49% were female and they ranged in age from 1 to 105 years (mean age of 53).
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Sixty-two (62) specimens were collected from a population at high risk for hepatitis composed of intravenous drug users (30), subjects who had clotting factor disorders (7) and MSM patients (25). The group was 87% male and 13% female and ranged in age from 21 to 75 years (mean age of 40).
There were 345 specimens from an asymptomatic hospitalized population and 34 were from healthcare workers (for HAV pre-vaccination screening).
One hundred and fifty one (151) patients had recovered HAV infection.
Among these 845 European samples, 36 (4.3%) were from pediatric subjects.
## Percent Agreement:
The results obtained with MONOLISA™ Anti-HAV IgM EIA were compared with the results obtained using the comparative assay. The positive and negative percent agreements and the 95% exact confidence between MONOLISA™ Anti-HAV IgM EIA and the comparative assay were calculated. To determine the percent agreement on borderline results the following criteria were used:
- Specimens that were borderline with the comparative assay and reactive with MONOLISA™ Anti-HAV IgM EIA were considered as false positives for MONOLISA™ Anti-HAV IgM EIA assay
- Specimens that were borderline with the comparative assay and non reactive with MONOLISA™ Anti-HAV IgM EIA were considered as false negatives for MONOLISA™ Anti-HAV IgM EIA
The results obtained with the US specimens and with the European specimens are presented in the following tables:
MONOLISA™ Anti-HAV IgM EIA versus the comparative assay results in the US population (N=404)
| Subject category | Comparative assay: Positive | | | Comparative assay : Borderline | | | Comparative assay: Negative | | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | MONOLISA™ Anti-HAV IgM EIA | | | MONOLISA™ Anti-HAV IgM EIA | | | MONOLISA™ Anti-HAV IgM EIA | | | |
| | R | BRD | N R | R | BR D | NR | R | BRD | NR | |
| Subjects with signs and symptoms | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 171 | 174 |
| Subjects with high risk for Hepatitis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 229 | 230 |
| Total | 1 | 0 | 0 | 0 | 0 | 0 | 2^{b} | 1^{a b} | 400 | 404 |
R: Reactive, NR: Nonreactive, BRD: Borderline
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${}^{a}$ the borderline sample with MONOLISA was considered as "false positive" ${}^{b}$ these samples were found HAV IgG reactive.
| | Positive percent agreement | 95% Exact Confidence interval | Negative percent agreement | 95% Exact Confidence interval |
| --- | --- | --- | --- | --- |
| Total | 100% (1/1) | NA | 99.3% (400/403) | 97.8– 99.9% |
MONOLISA $^{TM}$ Anti-HAV IgM EIA versus the comparative assay results in the European population ( $N = 845$ )
| Subject category | Comparative assay: Positive | | | Comparative assay: Borderline | | | Comparative assay: Negative | | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | MONOLISA™ Anti-HAV IgM EIA | | | MONOLISA™ Anti-HAV IgM EIA | | | MONOLISA™ Anti-HAV IgM EIA | | | |
| | R | BR D | NR | R | BR D | NR | R | BR D | NR | |
| General hospitalized population | 1 | 0 | 0 | 0 | 0 | 0 | 1 | \( 1^b \) | 342 | 345 |
| Sign / Symptoms of Hepatitis | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 250 | 253 |
| Subjects with high risk for Hepatitis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 62 | 62 |
| Healthcare workers | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 34 | 34 |
| Infected/ recovered HAV | 0 | 0 | 0 | \( 2^a \) | 0 | 0 | 1 | 0 | 148 | 151 |
| Total | 1 | 0 | 0 | \( 2^c \) | 0 | 0 | \( 5^c \) | \( 1^c \) | 836 | 845 |
| | Positive percent agreement | 95% Exact Confidence interval | Negative percent agreement | 95% Exact Confidence interval |
| --- | --- | --- | --- | --- |
| Total | 100% (1/1) | N/A | 99.0% (836/844) | 98.1-99.6 |
R: Reactive, NR: Nonreactive, BRD: Borderline
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${}^{a}$ the 2 borderline samples with the comparative assay were considered "false positive" with MONOLISA
${}^{\mathrm{b}}$ the borderline sample with MONOLISA was considered as "false positive"
these samples were found HAV IgG Reactive
# Acute HAV Infection:
Among the retrospective samples, 84 were from subjects with a medical history and laboratory results indicative of acute Hepatitis A. The subjects included $56\%$ male, $37\%$ female; the gender was not available for $7\%$ . The mean age was 21, and subjects ranged from 1 to 55 years. Among them 39 were pediatric subjects.
The results are presented in the following table:
Comparison of Results for MONOLISA™ Anti-HAV IgM EIA versus the comparative assay on Acute HAV infection in the adult and pediatric European Population (N=84):
| | Comparative assay: Positive | | | Comparative assay: Borderline | | | Comparative assay : Negative | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | MONOLISA™ Anti-HAV IgM EIA | | | MONOLISA™ Anti-HAV IgM EIA | | | MONOLISA™ Anti-HAV IgM EIA | | | total |
| | R | BRD | NR | R | BRD | NR | R | BR D | NR | |
| Adults | 45 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 45 |
| Pediatrics | 39 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 39 |
| Total | 84 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 84 |
R: Reactive, NR: Nonreactive, BRD: Borderline
The positive agreement was $100\%$ (84/84) with a $95\%$ exact confidence interval of $96.5\%$ to $100\%$ .
# Performance of MONOLISA™ Anti-HAV EIA in Pediatric subjects:
Sixty-one (61) pediatric samples were tested during the US and European clinical studies in addition to the 39 samples from acute HAV infection. Among the US population, 23 had signs and symptoms of hepatitis and 2 were from the high risk group. In the European population, 3 belonged to the general hospitalized population, 23 had signs and symptoms of hepatitis, 2 were from the high risk group, 3 were healthcare workers, 5 had recovered from Hepatitis A infection. The results from these pediatric samples are summarized in the following table.
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Comparison of Results for MONOLISA™ Anti-HAV IgM EIA versus the comparative assay in the Pediatric European and US Population (N=61)
| Subject category | Comparative assay: Positive | | | Comparative assay: Borderline | | | Comparative assay: Negative | | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | MONOLISA™ Anti-HAV IgM EIA | | | MONOLISA™ Anti-HAV IgM EIA | | | MONOLISA™ Anti-HAV IgM EIA | | | |
| | R | BRD | NR | R | BRD | NR | R | BRD | NR | |
| European pediatric s | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 35 | 36 |
| US pediatric s | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 24 | 25 |
| Total | 0 | 0 | 0 | 0 | 0 | 0 | 0^{a} | 0 | 59 | 61 |
R: Reactive, NR: Nonreactive, BRD: Borderline
<sup>a</sup>these samples were found HAV IgG Reactive
| | Positive percent agreement | 95% Exact Confidence interval | Negative percent agreement | 95% Exact Confidence interval |
| --- | --- | --- | --- | --- |
| Total | 0 | N/A | 96.7% (59/61) | 88.6 – 99.6 |
Including the combined US and European Sites, the positive percent agreement of the MONOLISA™ Anti-HAV IgM EIA with the comparative assay was 100% (86/86), with a 95% exact confidence interval of 96.6% to 100%. The negative percent agreement of the MONOLISA™ Anti-HAV IgM EIA with the comparative assay was 99.1% (1233/1244) with a 95% exact confidence interval of 98.4% to 99.6%.
## Seroconversion Panels:
Eight commercially available HAV seroconversion panels were tested using MONOLISA™ Anti-HAV IgM EIA and the comparative assay to determine the sensitivity of the assay. The results are summarized in the following table:
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MONOLISA™ Anti-HAV IgM EIA Seroconversion panels Results
| Panel ID | MONOLISA™ Anti-HAV IgM EIA | Anti-HAV IgM Comparative Assay | |
| --- | --- | --- | --- |
| | Post bleed day of first reactive result | Post bleed day of first reactive result | Difference in Days to Reactive result |
| 07467A | 0 | 0 | 0 |
| 60160K | 0 | 0 | 0 |
| 60162K | 0 | 0 | 0 |
| HAV01 | 0 | 0 | 0 |
| RP-004 | 6 | 6 | 0 |
| RP-013 | 8 | 8 | 0 |
| PHT901 | 12 | 12 | 0 |
| PHT902 | 16 | 16 | 0 |
| Panel ID | MONOLISA™ Anti-HAV IgM EIA | Anti-HAV IgM Comparative Assay | |
| --- | --- | --- | --- |
| | Post bleed day of last reactive result* | Post bleed day of last reactive result* | Difference in Days from last Reactive result |
| HAV01 | 91^{a} | 77 | +14 |
a: last bleed of the panel
For all seroconversion panels, both MONOLISATM Anti-HAV IgM EIA and the comparative assay detected HAV IgM antibodies at the same first bleed. MONOLISATM Anti-HAV IgM EIA appears to detect IgM for a longer period than the comparator assay for qualitative determination of IgM antibody to Hepatitis A.
Among seroconversion panels beginning with samples negative for anti-HAV antibodies and having subsequent samples to 5-6 months, one (PHT-902) becomes borderline after 5 months and one (PHT-901) gives a negative result after more than 20 months. Another seroconversion panel (RP-013) with samples collected through 6 months has a declining ratio but still remains positive. The other panels contain members collected through 2 to 3 months.
4. Clinical cut-off:
See assay cut-off previously described in this document
5. Expected values/Reference range:
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# Healthy individuals:
The expected results of the MONOLISA™ Anti-HAV IgM EIA assay were determined in presumably healthy individuals from the Mid-west US (St Louis), the Western US (California and Washington) and from Europe (Parma, Italy).
In the Mid-west, the population was 55% female and 45% male, with ages that ranged from 1 to 96 years. 48% (134) were pediatric specimens. The majority of the subjects were White/Caucasian (64%) and 32% were black or African American; for 4% data were not available. In the Western US, 73% were from California and 27% were from Washington. The population was 56% female and 44% male, with ages that ranged from 15 to 90 years. In Europe, the population was 50% female and 50% male, with ages that ranged from 18 to 87 years.
The expected results for the US and for Europe are presented below. The percent of Anti-HAV IgM reactive results with MONOLISA™ Anti-HAV IgM EIA were 0.4% for the US and 0.7% for Europe.
Expected Results for MONOLISA™ Anti-HAV IgM EIA in subjects from the Midwest US (N=280)
| MONOLISA™ Anti-HAV IgM EIA | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Age Range | Gender | Reactive | | Borderline | | Nonreactive | |
| | | N | % | N | % | N | % |
| < 10 | Female | 0 | N/A | 0 | N/A | 35 | 100.0% |
| | Male | 0 | N/A | 0 | N/A | 38 | 100.0% |
| 10 -19 | Female | 0 | N/A | 0 | N/A | 38 | 100.0% |
| | Male | 0 | N/A | 0 | N/A | 23 | 100.0% |
| 20- 29 | Female | 0 | N/A | 0 | N/A | 5 | 100.0% |
| | Male | 0 | N/A | 0 | N/A | 3 | 100.0% |
| 30 -39 | Female | 0 | N/A | 0 | N/A | 10 | 100.0% |
| | Male | 0 | N/A | 0 | N/A | 9 | 100.0% |
| 40 -49 | Female | 0 | N/A | 0 | N/A | 13 | 100.0% |
| | Male | 0 | N/A | 0 | N/A | 8 | 100.0% |
| 50 -59 | Female | 1 | 5.6% | 1 | 5.6% | 16 | 88.9% |
| | Male | 0 | N/A | 0 | N/A | 17 | 100.0% |
| 60 -69 | Female | 0 | N/A | 0 | N/A | 14 | 100.0% |
| | Male | 0 | N/A | 0 | N/A | 13 | 100.0% |
| 70-79 | Female | 0 | N/A | 0 | N/A | 9 | 100.0% |
| | Male | 0 | N/A | 0 | N/A | 6 | 100.0% |
| 80-89 | Female | 0 | N/A | 0 | N/A | 13 | 100.0% |
| | Male | 0 | N/A | 0 | N/A | 6 | 100.0% |
| >=90 | Female | 0 | N/A | 0 | N/A | 0 | N/A |
| | Male | 0 | N/A | 0 | N/A | 2 | 100.0% |
| Total | | 1* | 0.4% | 1** | 0.4% | 278 | 99.3% |
*1 subject was reactive with a result of 2.25 (S/CO)
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** 1subject gave a borderline result of 1.04 (S/CO).
Expected Results for MONOLISA™ Anti-HAV IgM EIA in subjects from the Western US (N= 245)
| MONOLISA™ Anti-HAV IgM EIA | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Age Range | Gender | Reactive | | Borderline | | Nonreactive | |
| | | N | % | N | % | N | % |
| <19 | Female | 0 | N/A | 0 | N/A | 5 | 100.0% |
| | Male | 0 | N/A | 0 | N/A | 5 | 100.0% |
| 20-29 | Female | 0 | N/A | 0 | N/A | 26 | 100.0% |
| | Male | 0 | N/A | 0 | N/A | 24 | 100.0% |
| 30-39 | Female | 0 | N/A | 0 | N/A | 20 | 100.0% |
| | Male | 0 | N/A | 0 | N/A | 18 | 100.0% |
| 40-49 | Female | 0 | N/A | 0 | N/A | 18 | 100.0% |
| | Male | 0 | N/A | 0 | N/A | 22 | 100.0% |
| 50-59 | Female | 1 | 2.6% | 0 | N/A | 38 | 97.4% |
| | Male | 0 | N/A | 1 | 4.8% | 20 | 95.2% |
| 60-69 | Female | 0 | N/A | 0 | N/A | 12 | 100.0% |
| 70-79 | Male | 0 | N/A | 0 | N/A | 12 | 100.0% |
| | Female | 0 | N/A | 0 | N/A | 9 | 100.0% |
| | Male | 0 | N/A | 0 | N/A | 2 | 100.0% |
| 80-89 | Female | 0 | N/A | 0 | N/A | 6 | 100.0% |
| | Male | 0 | N/A | 0 | N/A | 4 | 100.0% |
| >=90 | Female | 0 | N/A | 0 | N/A | 1 | 100.0% |
| | Male | 0 | N/A | 0 | N/A | 0 | N/A |
| Unknown | Female | 0 | N/A | 0 | N/A | 1 | 100.0% |
| Total | | 1* | 0.4% | 1** | 0.4% | 243 | 99.2% |
*1 subject was reactive with a result of 1.34 (S/CO)
** 1subject gave a borderline result of 0.96 (S/CO).
Expected Results for MONOLISA™ Anti-HAV IgM EIA in subjects from Italy, Europe (N= 285)
| MONOLISA™ Anti-HAV IgM EIA | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Age Range | Gender | Reactive | | Borderline | | Nonreactive | |
| | | N | % | N | % | N | % |
| < 19 | Female | 0 | N/A | 0 | N/A | 1 | 100.0% |
| | Male | 0 | N/A | 0 | N/A | 1 | 100.0% |
| 20-29 | Female | 0 | N/A | 0 | N/A | 3 | 100.0% |
| | Male | 0 | N/A | 0 | N/A | 2 | 100.0% |
| 30-39 | Female | 0 | N/A | 0 | N/A | 7 | 100.0% |
| | Male | 0 | N/A | 0 | N/A | 7 | 100.0% |
| 40-49 | Female | 0 | N/A | 0 | N/A | 21 | 100.0% |
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| | Male | 0 | N/A | 0 | N/A | 19 | 100.0% | 19 |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 50-59 | Female | 0 | N/A | 0 | N/A | 22 | 100.0% | 22 |
| | Male | 0 | N/A | 0 | N/A | 27 | 100.0% | 27 |
| 60-69 | Female | 1 | 2.5% | 1 | 2.5% | 41 | 95.0% | 43 |
| | Male | 0 | N/A | 0 | N/A | 27 | 100.0% | 27 |
| 70-79 | Female | 1 | 3.6% | 0 | N/A | 31 | 96.4% | 32 |
| | Male | 0 | N/A | 0 | N/A | 37 | 100% | 37 |
| 80-89 | Female | 0 | N/A | 0 | N/A | 13 | 100% | 13 |
| | Male | 0 | N/A | 0 | N/A | 23 | 100% | 23 |
| Total | | 2* | 0.7% | 1** | 0.4% | 282 | 98.9% | 285 |
*2 subjects gave reactive results of 3.4 and 1.2 (S/CO)
** 1 subject gave a borderline result of 1.07 (S/CO)
## Adult subjects at high risk for viral hepatitis:
Expected results of asymptomatic prospective high-risk subjects determined from a multi-center study in the US and in Europe are reported in the following tables.
A total of 230 US Subjects were at high risk for viral hepatitis including intravenous drug users (N=55), homosexual males (N=15), sex workers (N=39), prison history (N=92), high-risk sex partners (N=25), high-risk occupation/health care workers (N=4). Many had more than 1 high-risk behavior or risk factor.
Subjects were from Los Angeles, CA, (86.5%), Santa Ana, CA (4.3%), or Miami, FL (9.1%). The group was Caucasian (7.4%), Black or African American (74.3%), Hispanic or Latino (15.2%), Asian (0.4%), Native Hawaiian or other Pacific Islander (0.4%), and American Indian or Alaska native (0.9%), with the remaining 1.3% represented by multiple ethnic groups.
The subjects were 81% male and 19% female, and ranged in age from 18 to 70 years (mean age of 45). The data are reported in Table 4.
The percent of Anti-HAV IgM reactive results with MONOLISA™ Anti-HAV IgM EIA in this high-risk asymptomatic population was 0%.
The European group (N=62) was 87% male and 13% female and ranged in age from 21 to 75 years (mean age of 40). It consisted of intravenous drug users (30), subjects who had clotting factor disorders (7) and MSM patients (25). The data are reported in Table 5.
The percent of Anti-HAV IgM reactive results with MONOLISA™ Anti-HAV IgM EIA in this high-risk asymptomatic population was 0%.
Expected results for MONOLISA™ Anti-HAV IgM EIA in the US High risk Group for Viral Hepatitis A (N=230)
| MONOLISA™ Anti-HAV IgM EIA | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Age Range | Gender | Reactive | | Borderline | | Nonreactive | |
| | | N | % | N | % | N | % |
| < 19 | Female | 0 | N/A | 0 | N/A | 1 | 100.0% |
| | Male | 0 | N/A | 0 | N/A | 1 | 100.0% |
| 20-29 | Female | 0 | N/A | 0 | N/A | 3 | 100.0% |
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| | Male | 0 | N/A | 0 | N/A | 2 | 100.0% | 2 |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 30 -39 | Female | 0 | N/A | 0 | N/A | 7 | 100.0% | 7 |
| | Male | 0 | N/A | 0 | N/A | 36 | 100.0% | 36 |
| 40 -49 | Female | 0 | N/A | 0 | N/A | 24 | 100.0% | 24 |
| | Male | 0 | N/A | 1 | 1.2 % | 84 | 98.8% | 85 |
| 50 -59 | Female | 0 | N/A | 0 | N/A | 7 | 100.0% | 7 |
| | Male | 0 | N/A | 0 | N/A | 51 | 100.0% | 51 |
| 60 -69 | Female | 0 | N/A | 0 | N/A | 1 | 100.0% | 1 |
| | Male | 0 | N/A | 0 | N/A | 10 | 100.0% | 10 |
| 70-79 | Female | 0 | N/A | 0 | N/A | 0 | N/A | 0 |
| | Male | 0 | N/A | 0 | N/A | 2 | 100.0% | 2 |
| Total | | 0 | N/A | 1 | 0.4% | 229 | 99.6% | 230 |
Expected results for MONOLISA™ Anti-HAV IgM EIA in the European High risk group for Viral Hepatitis A (N=62)
| MONOLISA™ Anti-HAV IgM EIA | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Age Range | Gender | Reactive | | Borderline | | Nonreactive | |
| | | N | % | N | % | N | % |
| < 19 | Female | 0 | N/A | 0 | N/A | 0 | N/A |
| | Male | 0 | N/A | 0 | N/A | 0 | N/A |
| 20-29 | Female | 0 | N/A | 0 | N/A | 5 | 100.0% |
| | Male | 0 | N/A | 0 | N/A | 11 | 100.0% |
| 30 -39 | Female | 0 | N/A | 0 | N/A | 2 | 100.0% |
| | Male | 0 | N/A | 0 | N/A | 14 | 100.0% |
| 40 -49 | Female | 0 | N/A | 0 | N/A | 1 | 100.0% |
| | Male | 0 | N/A | 0 | N/A | 14 | 100.0% |
| 50 -59 | Female | 0 | N/A | 0 | N/A | 0 | N/A |
| | Male | 0 | N/A | 0 | N/A | 11 | 100.0% |
| 60 -69 | Female | 0 | N/A | 0 | N/A | 0 | N/A |
| | Male | 0 | N/A | 0 | N/A | 2 | 100.0% |
| 70-79 | Female | 0 | N/A | 0 | N/A | 0 | N/A |
| | Male | 0 | N/A | 0 | N/A | 2 | 100.0% |
| >80 | Female | 0 | N/A | 0 | N/A | 0 | N/A |
| | Male | 0 | N/A | 0 | N/A | 0 | N/A |
| Total | | 0 | N/A | 0 | N/A | 62 | 100.0% |
# N. Proposed labeling:
The labeling is sufficient and it satisfies the requirement of 21 CFR Part 809.10.
# WARNINGS and PRECAUTIONS:
For in vitro diagnostic use only
1. The MONOLISA™ Anti-IgM HAV EIA contains human source material used in
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the preparation of Negative Control (C0), Positive Control (C1) and Calibrator (C2) that has been tested with either FDA or CE approved methods and found non-reactive for Hepatitis B surface antigen (HBsAg), antibodies to Hepatitis C Virus (HCV) and antibodies to Human Immunodeficiency Viruses (HIV-1 and HIV-2).
2. The HAV Viral Antigen reagent (R6) has been treated with formalin to inactivate the virus.
3. No known test method can offer complete assurance that infectious agents are absent. Therefore, all human blood derivatives, reagents and human specimens should be handled as if capable of transmitting infectious disease. It is recommended that reagents and human specimens be handled in accordance with the OSHA Standard on Bloodborne Pathogens. Biosafety Level 2 or other appropriate biosafety practices should be used for materials that contain or are suspected of containing infectious agents.
4. The following is a list of potential chemical hazards contained in some kit components (See section 4: REAGENTS):
4.1 ProClin™ 300 (0.1% and 0.25%) are biocidal preservatives that may cause sensitization by skin contact; prolonged or repeated exposure may cause allergic reaction in certain sensitive individuals.
4.2 The 1N Sulfuric Acid (H₂SO₄) Stopping Solution is irritating to skin and severely irritating or corrosive to eyes, depending on the amount and length of exposure; greater exposures can cause eye damage, including permanent impairment of vision. In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. Keep away from strong bases, reducing agents and metals; do not pour water into this component. Waste from this material is considered hazardous acidic waste. However, if permitted by local, regional, and national regulations, it can be neutralized to pH 6-9 for non-hazardous disposal if operators are trained and equipped to do so.
4.3 Sodium azide (< 0.1%), a biocidal preservative, may be detrimental if enough is ingested. Sodium azide may react with certain metals, including lead or copper often found in plumbing, to form highly explosive metal azides. Flush with copious amounts of water when pouring dilute solutions down the drain to prevent explosive build-up.
5. Biological spills: Human source material spills should be treated as potentially infectious. Spills not containing acid should be immediately decontaminated, including the spill area, materials, and any contaminated surfaces or equipment, with an appropriate chemical disinfectant that is effective for the potential biohazards relative to the samples involved (commonly a 1:10 dilution of bleach, 70-80% Ethanol or Isopropanol, an iodophor [such as 0.5% Wescodyne™ Plus], or a phenolic, etc.) and wiped dry.
6. Spills containing acid should be appropriately absorbed or neutralized, and wiped dry. The area should be decontaminated with an appropriate agent. Materials used to absorb the spill should be disposed of as biohazardous waste.
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NOTE: DO NOT PLACE SOLUTIONS CONTAINING BLEACH INTO THE AUTOCLAVE.
7. Dispose of all specimens and material used to perform the test as though they contain an infectious agent. Laboratory chemical or biohazardous wastes must be handled and discarded in accordance with all local, regional and national regulations.
O. Conclusion:
The submitted material in this premarket notification is complete and supports a substantial equivalence decision.
