(86 days)
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No
The document describes a standard enzyme immunoassay (EIA) kit and an automated microplate system (EVOLIS™) that performs the assay steps and measures color intensity spectrophotometrically. The results evaluation is based on comparing absorbance values to a cutoff, which is a deterministic calculation, not an AI/ML algorithm. There is no mention of AI, ML, or related concepts in the text.
No.
The device is an in vitro diagnostic immunoassay kit used to detect antibodies to hepatitis A virus. It is intended to aid in diagnosis or identification of susceptible individuals, not to treat or prevent a disease.
Yes
The device is an in vitro enzyme immunoassay kit intended for use in the qualitative detection of total antibodies to hepatitis A virus, explicitly stated as an "aid in the diagnosis of acute or past hepatitis A virus (HAV) infection."
No
The device is an in vitro diagnostic (IVD) kit that includes reagents and is used with an automated microplate system (hardware). While software controls the system, the core medical device is the assay kit and the hardware used to process it.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the MONOLISA™ Anti-HAV EIA is an "in vitro enzyme immunoassay kit intended for use in the qualitative detection of total antibodies... in human... serum or plasma". This directly aligns with the definition of an in vitro diagnostic device, which is used to examine specimens taken from the human body to provide information for diagnosis, monitoring, or screening.
- Device Description: The description details a laboratory assay procedure involving patient specimens (serum or plasma) and reagents to detect specific antibodies. This is characteristic of an in vitro diagnostic test.
- Performance Studies: The document describes performance studies conducted with human samples (serum and plasma) to evaluate the device's accuracy and reliability in detecting anti-HAV antibodies. This is a requirement for IVD devices to demonstrate their clinical performance.
N/A
Intended Use / Indications for Use
The MONOLISA™ Anti-HAV EIA is an in vitro enzyme immunoassay kit intended for use in the qualitative detection of total antibodies (IgG and IgM) to hepatitis A virus (anti-HAV) in human (adult and pediatric) serum or plasma (EDTA, Heparin, Citrate, ACD). This kit can be used as an aid in the diagnosis of acute or past hepatitis A virus (HAV) infection or as an aid in the identification of HAV-susceptible individuals for vaccination. However, any diagnosis should take into consideration the patient's clinical history and symptoms, as well as serological data. The MONOLISA™ Anti-HAV EIA is intended for manual use and with the Evolis™ Automated Microplate System in the detection of total antibodies to hepatitis A virus.
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.
Product codes (comma separated list FDA assigned to the subject device)
LOL, JJE
Device Description
The MONOLISA™ Anti-HAV EIA is an enzyme immunoassay (competitive assay format) for the detection of total antibodies to hepatitis A virus. In the assay procedure, patient specimens, a Calibrator and controls are incubated with HAV antigen in microwells that have been coated with mouse monoclonal anti-hepatitis A antibodies to HAV present in a specimen or control will complex with the HAV antigen reagent and with antibodies coated on the microwells. Excess sample and HAV Viral Antigen reagent are removed by a wash step. The Conjugate (containing horseradish peroxidase-labeled mouse monoclonal antibody to HAV) is subsequently added to the microwells and incubated. The Coniugate binds to the HAV antigen bound to the microwell, in the absence of antibodies to HAV from the specimen. Excess Conjuqate is removed by a wash step, and a TMB Chromogen/Substrate solution is added to the microwells and allowed to incubate. If a sample does not contain anti-HAV antibodies, the bound enzyme (HRP) causes the colorless tetramethylbenzidine (TMB) in the Chromogen solution to change to blue. The blue color turns vellow after the addition of a Stopping Solution. If a sample contains anti-HAV antibodies, 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 determined by the mean of the Calibrator absorbance values.
The performance of the MONOLISA™ Anti-HAV EIA was evaluated in conjunction with the EVOLIS™ Automated Microplate System. The EVOLIS™ Automated Microplate System is a fully automated microplate analyzer that performs all functions necessary for the complete processing of microplate assays. Functions include: barcode scanning, sample pre-dilutions, sample and reagent dispensing, plate incubations, plate wash cycles, photometric measurement of completed assay plates and results evaluation. The analyzer instrument is controlled via the EVOLIS™ software, a Windows® 2000 application running on a separate dedicated PC. An operator loads the appropriate microplates, assay reagents, and patient and control samples, then selects assay parameters, loads sample information, initiates instrument processing, and generates result reports.
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
Not Found
Anatomical Site
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Indicated Patient Age Range
adult and pediatric
Intended User / Care Setting
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Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Correlation/method comparison:
In this study 688 retrospective samples were tested on the MONOLISA™ Anti-HAV assay using four (4) EVOLIS™ instruments at three sites. The same samples were tested manually (reference method) on the MONOLISA™ Anti-HAV assay.
The positive percent agreement with the reference method, manual testing, is 98.8% (336/340) with a 95% confidence interval of 97.0 - 99.5%. The negative percent agreement with the reference method is 97.4% (339/348) with a 95% confidence interval of 95.2 - 98.6%. The overall percent agreement is 98.1% (675/688) with a 95% confidence interval of 96.8 - 98.9%.
The EVOLIS™ was also evaluated by performing a combination of 2 assays on the same plate. In this study 315 samples were tested with the MONOLISA Anti-HAV assay on a combination plate on EVOLIS™ (both the MQNQLISA™ Anti-HAV EIA and MONOLISA™ Anti-HAV IgM EIA assays were run in a single microplate frame). Results were compared to the same samples tested manually (the reference method, individual plate format) on the MONOLISA™ Anti-HAV assay.
The positive percent agreement with the reference method, manual testing, is 100% (161/61) with a 95% confidence interval of 97.7 - 100%. The negative percent agreement with the reference method is 100% (154/154) with a 95% confidence interval of 97.6 - 100%. The overall percent agreement is 100% (315/315) with a 95% confidence interval of 98.8 - 100%.
Precision Study (Within-Laboratory):
A 21-member panel was tested: three (3) serum samples with six (6) corresponding plasma samples (EDTA K2, EDTA K3, Sodium Citrate, Sodium Heparin, Lithium Heparin, ACD) at three (3) different levels [1 low positive near the cutoff (Panel Set 1), 1 negative near the cutoff (Panel Set 2) and 1 negative (Panel Set 3)]. The kit controls and calibrator were also tested for a total of 24 samples. Two replicates each of the twenty-four (24) samples were assayed twice a day for 20 days. The data were analyzed following the CLSI quidance EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods. The mean ratio, the Standard Deviation (SD) and percent coefficient of variation (%CV) were calculated for each panel member.
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 5 days with the MONOLISA™ Anti-HAV 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. One (1) lot was used at each of 3 sites. The data from all sites were combined to obtain standard deviation (SD) and percent coefficient of variation (CV) for within run, between day, between site and total variance. The data were analyzed according to the principles described in the Clinical Laboratory Standards Institute guidance EP15-A2, User Protocol for Evaluation of Qualitative Test Performance.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Positive percent agreement between EVOLIS™ and manual method (688 samples): 98.8%
Negative percent agreement between EVOLIS™ and manual method (688 samples): 97.4%
Overall percent agreement between EVOLIS™ and manual method (688 samples): 98.1%
Positive percent agreement between EVOLIS™ combination plate and manual method (315 samples): 100%
Negative percent agreement between EVOLIS™ combination plate and manual method (315 samples): 100%
Overall percent agreement between EVOLIS™ combination plate and manual method (315 samples): 100%
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
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Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
0
510(k) Summary
| 1. Company: | Bio-Rad Laboratories
6565 185th Avenue NE
Redmond, WA 98052
Phone: 425 881-8300
Fax: 425 498-1651 | OCT 29 2009 |
|------------------------|---------------------------------------------------------------------------------------------------------------|-------------|
| Contact: | Linda Staswick | |
| Date Summary Prepared: | October 22, 2009 | |
2. Device Name:
| Device Trade Name: | MONOLISA™ Anti-HAV EIA | EVOLIS™ Automated Microplate
System |
|----------------------|----------------------------------------|-------------------------------------------------------------|
| Common Name: | Total Antibody to Hepatitis A
Virus | Automated Laboratory Analyzer |
| Classification Name: | Hepatitis A Test (Total Antibody) | Discrete photometric chemistry
analyzer for clinical use |
| Product Code: | LOL | JJE |
| Regulation Number: | 21 CFR 866.3310 | 21 CFR 862.2160 |
| Regulatory Class: | Class II | Class I |
| Panel: | Microbiology | Chemistry |
3. Substantial Equivalence:
The MONOLISA™ Anti-HAV EIA used with the EVOLIS™ Automated Microplate System is substantially equivalent to the MONOLISA™ Anti-HAV EIA using the manual method (K063318).
4. Description of the Device:
The MONOLISA™ Anti-HAV EIA is an enzyme immunoassay (competitive assay format) for the detection of total antibodies to hepatitis A virus. In the assay procedure, patient specimens, a Calibrator and controls are incubated with HAV antigen in microwells that have been coated with mouse monoclonal anti-hepatitis A antibodies to HAV present in a specimen or control will complex with the HAV antigen reagent and with antibodies coated on the microwells. Excess sample and HAV Viral Antigen reagent are removed by a wash step. The Conjugate (containing horseradish peroxidase-labeled mouse monoclonal antibody to HAV) is subsequently added to the microwells and incubated. The Coniugate binds to the HAV antigen bound to the microwell, in the absence of antibodies to HAV from the specimen. Excess Conjuqate is removed by a wash step, and a TMB Chromogen/Substrate solution is added to the microwells and allowed to incubate. If a sample does not contain anti-HAV antibodies, the bound enzyme (HRP) causes the colorless tetramethylbenzidine (TMB) in the Chromogen solution to change to blue. The blue color turns vellow after the addition of a Stopping Solution. If a sample contains anti-HAV antibodies, 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 determined by the mean of the Calibrator absorbance values.
The performance of the MONOLISA™ Anti-HAV EIA was evaluated in conjunction with the EVOLIS™ Automated Microplate System. The EVOLIS™ Automated Microplate System is a
1
fully automated microplate analyzer that performs all functions necessary for the complete processing of microplate assays. Functions include: barcode scanning, sample pre-dilutions, sample and reagent dispensing, plate incubations, plate wash cycles, photometric measurement of completed assay plates and results evaluation. The analyzer instrument is controlled via the EVOLIS™ software, a Windows® 2000 application running on a separate dedicated PC. An operator loads the appropriate microplates, assay reagents, and patient and control samples, then selects assay parameters, loads sample information, initiates instrument processing, and generates result reports.
5. Intended Use:
The MONOLISA™ Anti-HAV ElA is an in vitro enzyme immunoassay kit intended for use in the qualitative detection of total antibodies (loG and IgM) to hepatitis A virus (anti-HAV) in human (adult and pediatric) serum or plasma (EDTA, Heparin, Citrate, ACD). This kit can be used as an aid in the diagnosis of acute or past hepatitis A virus (HAV) infection or as an aid in the identification of HAV-susceptible individuals for vaccination. However, any diagnosis should take into consideration the patient's clinical history and symptoms, as well as serological data. The MONOLISA™ Anti-HAV EIA is intended for manual use and with the Evolis™ Automated Microplate System in the detection of total antibodies to hepatitis A virus.
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.
6. Technological Characteristics
The following tables summarize similarities and differences between the MONOLISA™ Anti-HAV ElA tested manually and the MONOLISA™ Anti-HAV EIA tested with the EVOLIS™ Automated Microplate System.
2
| Parameter | MONOLISA™ Anti-HAV EIA tested
with the EVOLIS™ Automated
Microplate System | MONOLISA™ Anti-HAV EIA tested
manually |
|---------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use/Indications
for Use | The MONOLISA™ Anti-HAV EIA is
an in vitro enzyme immunoassay kit
intended for use in the qualitative
detection of total antibodies (IgG and
IgM) to hepatitis A virus (anti-HAV) in
human (adult and pediatric) serum or
plasma (EDTA, Heparin, Citrate,
ACD) | The MONOLISA™ Anti-HAV EIA is
an in vitro enzyme immunoassay kit
intended for use in the qualitative
detection of total antibodies (IgG and
IgM) to hepatitis A virus (anti-HAV) in
human (adult and pediatric) serum or
plasma (EDTA, Heparin, Citrate,
ACD) |
| Assay procedure | Per the instructions in the package
insert | Per the instructions in the package
insert |
| Plate incubation | 60 ± 5 minutes at 37°C + 2°C | 60 ± 5 minutes at 37°C + 2°C |
| Plate washing | Wash with ≥ 370 µL of Working Wash
Solution per well, and 30 - 60 second
soak between each wash cycle for a
total of 5 cycles. | Wash with ≥ 370 µL of Working Wash
Solution per well, and 30 - 60 second
soak between each wash cycle for a
total of 5 cycles. |
| Result interpretation | Result interpretations, based on
sample O.D.s, are determined
according to package insert criteria. | Result interpretations, based on
sample O.D.s, are determined
according to package insert criteria. |
| Photometric
measurement of
completed assay plates | Read absorbance using 450 nm filter
with 620 nm as the reference | Read absorbance using 450 nm filter
with 615 to 630 nm as the reference |
Table 1: Similarities between devices
Table 2. Differences h
| Parameter | MONOLISA™ Anti-HAV EIA tested
with the EVOLIS™ Automated
Microplate System | MONOLISA™ Anti-HAV EIA tested
manually |
|----------------------------------------------------------------------|----------------------------------------------------------------------------------|-------------------------------------------------------------|
| Sample and reagent
dispensing | Samples and reagents are dispensed
by the automated system | Samples and reagents are dispensed
manually |
| Barcode reading | Sample and reagent ID are verified
automatically | NA or can be performed manually
with barcode wand |
| Plate incubation | Plates are automatically moved to
the incubation chamber | Plates are moved manually to an
incubation chamber |
| Plate wash cycles | Plates are automatically washed | Plates are moved manually to an
automated plate washer |
| Data management | Archives and retrieves data and
sample information | NA |
| Spectrophotometric
verification of sample and
reagent pipeting | Performed automatically | Optional verification visually or with
microplate reader |
7. Performance Characteristics:
The performance of the MONOLISA™ Anti-HAV EIA with the EVOLIS™ Automated Microplate System was compared to the MONOLISA™ Anti-HAV EIA tested manually, which had previously received marketing clearance from the Agency. Substantial equivalence of the MONOLISA™ Anti-HAV EIA, using manual equipment, was determined May 3, 2007 (K063318).
3
Correlation/method comparison
Studies have been performed with the MONOLISA™ Anti-HAV EIA on the EVOLIS™ Automated System and compared to the results of testing the same kits and samples with the manual method. In this study 688 retrospective samples were tested on the MONOLISA™ Anti-HAV assay using four (4) EVOLIS™ instruments at three sites. The same samples were tested manually (reference method) on the MONOLISA™ Anti-HAV assay. The positive, negative and overall percent agreement along with the 95% confidence interval are presented below. In determining the percent agreement on borderline results, specimens that were borderline with the reference assay and negative with EVOLIS™ were considered as false negative for the EVOLIS™ specimens that were borderline with the reference assay and reactive with EVOLIS™ were considered as false positive for the EVOLIS™.
| Manual Anti-HAV Results | EVOLIS TM Anti-HAV Results | |||
|---|---|---|---|---|
| Reactive | Borderline | Nonreactive | Total | |
| Reactive | 336 | 2 | 1 | 339 |
| Borderline | 2 | 0 | 1 | 3 |
| Nonreactive | 2 | 5 | 339 | 346 |
| Total | 340 | 7 | 341 | 688 |
Table 2: MONOLISA™ Anti-HAV EIA on EVOLIS™ vs. Manual Results
The positive percent agreement with the reference method, manual testing, is 98.8% (336/340) with a 95% confidence interval of 97.0 - 99.5%. The negative percent agreement with the reference method is 97.4% (339/348) with a 95% confidence interval of 95.2 - 98.6%. The overall percent agreement is 98.1% (675/688) with a 95% confidence interval of 96.8 - 98.9%.
The EVOLIS™ was also evaluated by performing a combination of 2 assays on the same plate. In this study 315 samples were tested with the MONOLISA Anti-HAV assay on a combination plate on EVOLIS™ (both the MQNQLISA™ Anti-HAV EIA and MONOLISA™ Anti-HAV IgM EIA assays were run in a single microplate frame). Results were compared to the same samples tested manually (the reference method, individual plate format) on the MONOLISA™ Anti-HAV assay.
Table 3: MONOLISA™ Anti-HAV EIA on EVOLIS™ Combination Plate Testing vs. Manual Results
| | | EVOLIS™ Anti-HAV Results
Individual Plate | | | |
|----------------------------------------------|----------|----------------------------------------------|-------------|-------|--|
| Manual Anti-HAV Results
Combination Plate | Reactive | Borderline | Nonreactive | Total | |
| Reactive. | 161 | 0 | 0 | 161 | |
| Borderline | 0 | 0 | 0 | 0 | |
| Nonreactive | 0 | 0 | 154 | 154 | |
| Total | 161 | 0 | 154 | 315 | |
The positive percent agreement with the reference method, manual testing, is 100% (161/61) with a 95% confidence interval of 97.7 - 100%. The negative percent agreement with the reference method is 100% (154/154) with a 95% confidence interval of 97.6 - 100%. The overall percent agreement is 100% (315/315) with a 95% confidence interval of 98.8 - 100%.
4
Precision Study (Within-Laboratory)
In precision studies a 21-member panel was tested: three (3) serum samples with six (6) corresponding plasma samples (EDTA K2, EDTA K3, Sodium Citrate, Sodium Heparin, Lithium Heparin, ACD) at three (3) different levels [1 low positive near the cutoff (Panel Set 1), 1 negative near the cutoff (Panel Set 2) and 1 negative (Panel Set 3)]. The kit controls and calibrator were also tested for a total of 24 samples. Two replicates each of the twenty-four (24) samples were assayed twice a day for 20 days. The data were analyzed following the CLSI quidance EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods. 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 tables, which summarize testing with the EVOLIS™ Automated System:
| N | Mean | Within run¹ | Between Run² | Between Day³ | Total⁴ | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Panel Member | CO/S | SD | % CV | SD | % CV | SD | % CV | SD | % CV | |
| Positive Control | 80 | 4.63 | 0.208 | 4.5 | 0.312 | 6.7 | 0.750 | 16.2 | 0.839 | 18.1 |
| Negative Control | 765 | 0.36 | 0.012 | 3.4 | 0.023 | 6.4 | 0.014 | 4.1 | 0.030 | 8.3 |
| Cutoff Control | 80 | 0.91 | 0.032 | 3.5 | 0.067 | 7.4 | 0.098 | 10.8 | 0.123 | 13.6 |
| Serum (1) | 80 | 1.13 | 0.051 | 4.6 | 0.060 | 5.3 | 0.107 | 9.5 | 0.133 | 11.8 |
| EDTA K2 (1) | 80 | 1.16 | 0.042 | 3.7 | 0.064 | 5.5 | 0.080 | 6.9 | 0.111 | 9.6 |
| EDTA K3 (1) | 80 | 1.16 | 0.044 | 3.8 | 0.091 | 7.9 | 0.077 | 6.7 | 0.127 | 11.0 |
| Sodium Citrate (1) | 80 | 1.12 | 0.047 | 4.2 | 0.090 | 8.0 | 0.084 | 7.5 | 0.131 | 11.8 |
| Sodium Heparin (1) | 80 | 1.24 | 0.061 | 4.9 | 0.084 | 6.8 | 0.111 | 9.0 | 0.152 | 12.3 |
| Lithium Heparin (1) | 80 | 1.18 | 0.036 | 3.1 | 0.077 | 6.6 | 0.120 | 10.2 | 0.147 | 12.5 |
| ACD (1) | 80 | 0.40 | 0.011 | 2.7 | 0.026 | 6.4 | 0.038 | 9.4 | 0.047 | 11.7 |
| Serum (2) | 80 | 0.64 | 0.023 | 3.6 | 0.033 | 5.1 | 0.022 | 3.4 | 0.045 | 7.1 |
| EDTA K2 (2) | 80 | 0.63 | 0.021 | 3.4 | 0.038 | 6.0 | 0.030 | 4.8 | 0.053 | 8.4 |
| EDTA K3 (2) | 80 | 0.62 | 0.019 | 3.1 | 0.043 | 7.0 | 0.030 | 4.9 | 0.056 | 9.1 |
| Sodium Citrate (2) | 80 | 0.63 | 0.020 | 3.1 | 0.044 | 7.0 | 0.037 | 5.9 | 0.061 | 9.7 |
| Sodium Heparin (2) | 80 | 0.68 | 0.022 | 3.3 | 0.042 | 6.2 | 0.070 | 10.4 | 0.085 | 12.6 |
| Lithium Heparin (2) | 80 | 0.61 | 0.020 | 3.2 | 0.037 | 6.1 | 0.044 | 7.1 | 0.061 | 9.9 |
| ACD (2) | 80 | 0.59 | 0.014 | 2.4 | 0.041 | 7.0 | 0.058 | 9.8 | 0.073 | 12.3 |
| Serum (3) | 80 | 0.41 | 0.008 | 1.9 | 0.026 | 6.3 | 0.019 | 4.7 | 0.033 | 8.1 |
| EDTA K2 (3) | 80 | 0.41 | 0.019 | 4.6 | 0.031 | 7.7 | 0.017 | 4.1 | 0.040 | 9.9 |
| EDTA K3 (3) | 80 | 0.41 | 0.013 | 3.0 | 0.029 | 7.1 | 0.019 | 4.6 | 0.037 | 8.9 |
| Sodium Citrate (3) | 80 | 0.43 | 0.011 | 2.7 | 0.028 | 6.5 | 0.021 | 4.9 | 0.037 | 8.6 |
| Sodium Heparin (3) | 80 | 0.43 | 0.008 | 2.0 | 0.025 | 5.9 | 0.039 | 9.1 | 0.047 | 11.0 |
| Lithium Heparin (3) | 80 | 0.40 | 0.014 | 3.5 | 0.027 | 6.8 | 0.037 | 9.2 | 0.048 | 12.0 |
| ACD (3) | 80 | 1.07 | 0.036 | 3.4 | 0.081 | 7.6 | 0.141 | 13.2 | 0.167 | 15.6 |
Table 4: MONOLISA™ Anti-HAV EIA Precision Results by Panel Member Cutoff to Signal (CO/S)
1 Within Run: variability of the assay performance from replicate to replicate
2 Between Run: variability of the assay performance from run to run
3 Between Day: variability of the assay performance from day to day
4 Total: total variability of the assay performance includes within run, between run and between day.
54 replicates did not meet volume verification requirements
5
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 5 days with the MONOLISA™ Anti-HAV 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. One (1) lot was used at each of 3 sites.
The data from all sites were combined to obtain standard deviation (SD) and percent coefficient of variation (CV) for within run, between day, between site and total variance. The data were analyzed according to the principles described in the Clinical Laboratory Standards Institute guidance EP15-A2, User Protocol for Evaluation of Qualitative Test Performance. The summaries are shown in the following tables:
| Test
Site | ID # | Panel Member | N | Mean
(CO/S) | Within Run¹ | | Between Day² | | Total³ | |
|--------------|------|-------------------|----|----------------|-------------|-----|--------------|------|--------|------|
| | | | | | SD | %CV | SD | %CV | SD | %CV |
| Site #1 | P1 | Negative | 30 | 0.41 | 0.024 | 5.8 | 0.000⁴ | 0.0 | 0.024 | 5.8 |
| | P2 | High Negative | 30 | 0.81 | 0.044 | 5.5 | 0.000⁴ | 0.0 | 0.044 | 5.5 |
| | P3 | Low Positive | 30 | 1.32 | 0.080 | 6.1 | 0.027 | 2.0 | 0.084 | 6.4 |
| | P4 | Low Positive | 30 | 2.14 | 0.163 | 7.7 | 0.082 | 3.8 | 0.183 | 8.6 |
| | P5 | Positive | 30 | 2.85 | 0.147 | 5.1 | 0.120 | 4.2 | 0.190 | 6.7 |
| | P6 | Positive | 30 | 4.06 | 0.125 | 3.1 | 0.271 | 6.7 | 0.298 | 7.3 |
| | P7 | Positive Control | 30 | 3.70 | 0.180 | 4.9 | 0.229 | 6.2 | 0.292 | 7.9 |
| | P8 | Negative Control | 30 | 0.39 | 0.020 | 5.1 | 0.009 | 2.2 | 0.021 | 5.5 |
| | P9 | Cutoff Calibrator | 30 | 0.96 | 0.066 | 6.8 | 0.033 | 3.4 | 0.073 | 7.6 |
| Site #2 | P1 | Negative | 30 | 0.41 | 0.026 | 6.4 | 0.000⁴ | 0.0 | 0.026 | 6.4 |
| | P2 | High Negative | 30 | 0.82 | 0.049 | 6.0 | 0.029 | 3.5 | 0.057 | 6.9 |
| | P3 | Low Positive | 30 | 1.32 | 0.061 | 4.6 | 0.059 | 4.4 | 0.084 | 6.4 |
| | P4 | Low Positive | 30 | 2.17 | 0.153 | 7.1 | 0.080 | 3.7 | 0.173 | 8.0 |
| | P5 | Positive | 30 | 2.83 | 0.125 | 4.4 | 0.167 | 5.9 | 0.208 | 7.4 |
| | P6 | Positive | 30 | 4.05 | 0.158 | 3.9 | 0.327 | 8.1 | 0.363 | 9.0 |
| | P7 | Positive Control | 30 | 3.74 | 0.153 | 4.1 | 0.253 | 6.8 | 0.295 | 7.9 |
| | P8 | Negative Control | 27 | 0.38 | 0.011 | 2.8 | 0.011 | 2.8 | 0.015 | 3.9 |
| | P9 | Cutoff Calibrator | 27 | 0.95 | 0.039 | 4.1 | 0.014 | 1.5 | 0.042 | 4.4 |
| Site #3 | P1 | Negative | 30 | 0.40 | 0.017 | 4.3 | 0.012 | 3.0 | 0.021 | 5.3 |
| | P2 | High Negative | 30 | 0.78 | 0.041 | 5.3 | 0.051 | 6.5 | 0.065 | 8.4 |
| | P3 | Low Positive | 30 | 1.28 | 0.047 | 3.6 | 0.072 | 5.6 | 0.086 | 6.7 |
| | P4 | Low Positive | 30 | 2.08 | 0.094 | 4.5 | 0.116 | 5.6 | 0.149 | 7.2 |
| | P5 | Positive | 30 | 2.77 | 0.104 | 3.7 | 0.201 | 7.3 | 0.226 | 8.2 |
| | P6 | Positive | 30 | 4.02 | 0.187 | 4.7 | 0.285 | 7.1 | 0.341 | 8.5 |
| | P7 | Positive Control | 30 | 3.64 | 0.173 | 4.7 | 0.383 | 10.5 | 0.420 | 11.5 |
| | P8 | Negative Control | 30 | 0.38 | 0.025 | 6.5 | 0.016 | 4.4 | 0.030 | 7.9 |
| | P9 | Cutoff Calibrator | 30 | 0.93 | 0.059 | 6.3 | 0.056 | 6.0 | 0.081 | 8.7 |
Table 5: MONOLISA™ Anti-HAV ElA Reproducibility Results by Panel Member Cutoff to Signal (CO/S)
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 Total: total variability of the assay performance includes within run and between day
4 Negative variances were rounded to zero, per statistical convention.
6
| Panel
Member | N | Mean
CO/S | Within Run1 | | Between Day2 | | Between Site3 | | Total4 | |
|-----------------|----|--------------|-------------|-----|--------------|-----|---------------|-----|--------|-----|
| | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| P1 | 90 | 0.41 | 0.023 | 5.7 | 0.005 | 1.2 | 0.004 | 1.1 | 0.024 | 5.9 |
| P2 | 90 | 0.80 | 0.045 | 5.6 | 0.033 | 4.1 | 0.014 | 1.7 | 0.058 | 7.2 |
| P3 | 90 | 1.30 | 0.064 | 4.9 | 0.054 | 4.2 | 0.0005 | 0.0 | 0.084 | 6.4 |
| P4 | 90 | 2.13 | 0.140 | 6.6 | 0.091 | 4.3 | 0.0005 | 0.0 | 0.167 | 7.9 |
| P5 | 90 | 2.82 | 0.126 | 4.5 | 0.157 | 5.6 | 0.0005 | 0.0 | 0.201 | 7.1 |
| P6 | 90 | 4.04 | 0.159 | 3.9 | 0.273 | 6.8 | 0.0005 | 0.0 | 0.316 | 7.8 |
| P7 | 90 | 3.69 | 0.169 | 4.6 | 0.276 | 7.5 | 0.0005 | 0.0 | 0.324 | 8.8 |
| P8 | 87 | 0.38 | 0.019 | 5.1 | 0.012 | 3.1 | 0.0005 | 0.0 | 0.023 | 6.0 |
| P9 | 87 | 0.95 | 0.056 | 5.9 | 0.038 | 4.0 | 0.0005 | 0.0 | 0.068 | 7.1 |
Table 6: MONOLISA™ Anti-HAV EIA Reproducibility Summary by Panel Member Cutoff to Signal (CO/S) All Three Sites
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 Site: variability of the assay performance from site to site
4 Total: total variability of the assay performance includes within run and between site §Negative variances were rounded to zero, per statistical convention.
Pipettor and washer carry-over
The pipette carryover study verified that the disposable tip pipettes on the EVOLIS™ do not carry residuals from one sample or well to another. In a washer carryover study, it was verified that the washer on the EVOLIS™ does not carry residuals from one well to another during the washing steps.
Pipetting accuracy
Dve studies were performed to determine pipetting accuracy for samples and reagents with the EVOLIS™ Automated Microplate System. These studies were conducted using 2 different volumes for samples and controls, and demonstrated pipetting accuracy with a CV of ≤7.7% across the microwell plate.
8. Conclusion
The MONOLISA™ Anti-HAV EIA tested with the EVOLIS™ Automated Microplate System demonstrated equivalent performance to the MONOLISA™ Anti-HAV EIA tested with the manual assay method, which had previously received FDA 510(k) clearance.
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Image /page/7/Picture/0 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized eagle with three lines representing its wings and a wavy line representing its body. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993
Bio-Rad Laboratories Attn: Linda Staswick 6565 185" Ave. NE Redmond, WA 98052
OCT 2 9 2009
Re: K092355
Trade/Device Name: MONOLISA™ Anti-HAV EIA with the EVOLISTM Automated Microplate System Regulation Number: 21 CFR 866.3310 Regulation Name: Hepatitis A virus (HAV) serological assays Regulatory Class: Class II Product Codes: LOL, JJE Dated: July 30, 2009 Received: August 4, 2009
Dear Ms. Staswick:
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, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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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Page 2 - Linda Staswick
CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/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/cdrh/industry/support/index.html.
Sincerely yours,
Jolatt
Sallie Haire, Ph.D.
Sally Hojvat, Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics Center for Devices and Radiological Health
Enclosure
9
Indications for Use
510(k) Number (if known): K092355
Device Name: MONOLISA™ Anti-HAV EIA
Indication For Use:
The MONOLISA™ Anti-HAV EIA is an in vitro enzyme immunoassay kit intended for use in the qualitative detection of total antibodies (IgG and IgM) to hepatitis A virus (anti-HAV) in human (adult and pediatric) serum or plasma (EDTA, Heparin, Citrate, ACD). This kit can be used as an aid in the diagnosis of acute or past hepatitis A virus (HAV) infection or as an aid in the identification of HAV-susceptible individuals for vaccination. However, any diagnosis should take intoconsideration the patient's clinical history and symptoms, as well as serological data. The MONOLISA™ Anti-HAV EIA is intended for manual use and with the EVOLIS™ Automated Microplate System in the detection of total antibodies to hepatitis A virus.
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 soft tissue donors.
Prescription Use X (21 CFR Part 801 Subpart D) Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
And/Or
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
Uwe Schuf
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K072355