(84 days)
No
The device description details a standard immunoenzymatic assay based on antibody-antigen binding and colorimetric detection, with no mention of AI or ML algorithms for data analysis or interpretation.
No
Explanation: This device is an in-vitro diagnostic test used to detect an antigen for diagnosis, not to treat a condition.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device "can be used as an aid in the diagnosis of Invasive Aspergillosis," which clearly indicates a diagnostic purpose.
No
The device description clearly outlines a laboratory assay involving physical reagents, microplates, and a spectrophotometer, indicating it is a hardware-based diagnostic test, not software only.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it's for the "detection of Aspergillus galactomannan antigen in adult and pediatric serum samples" and is used "as an aid in the diagnosis of Invasive Aspergillosis." This clearly indicates it's a test performed on a biological sample (serum) to provide information for diagnostic purposes.
- Device Description: The description details a laboratory assay (immunoenzymatic sandwich microplate assay) performed on human serum samples. This is characteristic of an in vitro diagnostic test.
- Performance Studies: The document includes detailed performance studies (sensitivity, specificity, reproducibility, cross-reactivity) conducted on human serum samples, which are standard for evaluating the performance of IVD devices.
- Key Metrics: The inclusion of metrics like sensitivity, specificity, PPV, and NPV are all relevant to the performance evaluation of diagnostic tests.
- Predicate Device: The mention of a predicate device (K023857; Platelia™ Aspergillus EIA) further confirms its classification as an IVD, as predicate devices are used for comparison in the regulatory submission process for new IVDs.
All these elements align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The Platelia™ Aspergillus EIA is an immunoenzymatic sandwich microplate assay for the detection of Aspergillus galactomannan antigen in adult and pediatric serum samples.
The Platelia™ Aspergillus EIA is a test which, when used in conjunction with other diagnostic procedures such as microbiological culture, histological examination of biopsy samples and radiographic evidence, can be used as an aid in the diagnosis of Invasive Aspergillosis.
Product codes (comma separated list FDA assigned to the subject device)
NOM
Device Description
The Platelia™ Aspergillus EIA is a one-stage immunoenzymatic sandwich microplate assay which detects galactomannan in human serum. The assay uses rat EBA-2 monoclonal antibodies, which are directed against Aspergillus galactomannan, and have been characterized in previous studies 19,16. The monoclonal antibodies are used to coat the wells of the microplate and bind the antigen, and to detect the antigen bound to the sensitized microplate (conjugate reagent: peroxidase-linked monoclonal antibodies).
Serum samples are heat-treated in the presence of EDTA in order to dissociate immune complexes and to precipitate serum proteins that could possibly interfere with the test . The treated serum samples and conjugate are added to the wells coated with monoclonal antibodies, and incubated. A monoclonal antibody - galactomannan - monoclonal antibody / peroxidase complex is formed in the presence of galactomannan antigen. The strips are washed to remove any unbound material. Next, the substrate solution is added, which will react with the complexes bound to the well to form a blue color reaction. The enzyme reaction is stopped by the addition of acid, which changes the blue color to yellow. The absorbance (optical density) of specimens and controls is determined with a spectrophotometer set at 450 and 620/630 nm wavelength.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
adult and pediatric
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
A clinical study was conducted on a total of 1954 serum samples from 129 immunocompromised pediatric (Age ≤ 21 years) patients, at high risk for Invasive Aspergillosis (IA) and patients diagnosed with Proven and Probable Invasive Aspergillosis, at three testing centers in the United States to determine the performance characteristics of the Platelia™ Aspergillus EIA.
A total of 1625 pediatric serum samples obtained from 108 immunocompromised pediatric patients at three testing centers in the United States were tested to determine the performance characteristics of the Platelia™ Aspergillus EIA. 80 samples, from 4 control patients with positive galactomannan antigen results coinciding with piperacillin / tazobactam (Zosyn®) therapy were excluded.
The scatter plot depicts galactomannan assay results for the 249 serum samples from 17 patients in this study diagnosed with proven or probable Invasive Aspergillosis as defined by EORTC/NIAID definitions.
A clinical study was previously conducted on a total of 1724 serum samples from 172 bone marrow transplant (BMT) and leukemic patients diagnosed with and without Invasive Aspergillosis, at three testing centers in North America to determine the performance characteristics of the Platelia™ Aspergillus EIA.
A total of 1262 serum samples obtained from 143 bone marrow transplant (BMT) and leukemic patients at three testing centers in North America were previously tested with the Platelia™ Aspergillus EIA test.
This scatter plot depicts galactomannan assay results for the 462 serum samples from 29 patients in this study diagnosed with proven or probable Invasive Aspergillosis as defined by EORTC/NIAID definitions.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Performance Summary:
I. Expected Values:
- A clinical study was conducted on 1954 serum samples from 129 immunocompromised pediatric patients in the United States.
- A total of 1625 pediatric serum samples from 108 immunocompromised pediatric patients were tested. 80 samples from 4 control patients were excluded due to Zosyn® therapy.
- 249 serum samples from 17 pediatric patients were diagnosed with proven or probable Invasive Aspergillosis.
- A clinical study was previously conducted on 1724 serum samples from 172 adult bone marrow transplant (BMT) and leukemic patients in North America.
- 1262 serum samples from 143 adult patients were previously tested.
- 462 serum samples from 29 adult patients were diagnosed with proven or probable Invasive Aspergillosis.
II. Reproducibility Studies:
- Reproducibility Studies were previously presented in prior 510(k) submission (K023857).
- Inter-assay and Intra-assay variability were determined using a panel of 6 pooled patient serum samples (one negative, one low positive, two positive, and two high positive) from 3 clinical trial sites in North America.
- Site 1 and 2: Each panel member tested in triplicate (x3) on 3 different days, on one lot. Total 9 replicates.
- Site 3: Each panel member tested in duplicate (x2) on 3 different days, on 1 lot. Total 6 replicates.
- Data analyzed according to NCCLS.
III. Cross-Reactivity Studies:
- Cross-Reactivity Studies were previously presented in prior 510(k) submission (K023857).
- A study to evaluate the effect of potentially interfering medical conditions was performed with one lot of the Platelia™ Aspergillus EIA kit.
- 151 sera samples were tested for cross-reactivity, including various pathologies like Rheumatoid Factor, ANA Positive, Hypergammaglobulinemia (IgG, IgM), Cancer, Non-Viral Cirrhosis, Multiple Transfusions, Multiparous Females, and various viral infections (HAV, HCV, Rubella, CMV, Syphilis, Toxoplasmosis, Mycoplasma). All samples resulted in 0 positives.
IV. Performance Evaluation Studies:
- Additional clinical testing for specificity and sensitivity was conducted at 3 clinical sites in the United States for the pediatric (Age ≤ 21 years) population, in addition to testing done for prior submission (K023857) for adult patients.
- The study included patients without signs of Invasive Aspergillosis, patients with probable Invasive Aspergillosis, and patients with proven Invasive Aspergillosis.
- Proven IA: defined by positive microbiological culture obtained by sterile procedure from the site affected, and histopathological demonstration of the appropriate morphological forms in a host with symptoms attributed to the fungal infection.
- Probable IA: defined as at least one microbiological criterion, and one major or two minor clinical criteria from a site consistent with infection, in a host with symptoms attributed to the fungal infection.
- Possible IA: defined as at least one microbiological criterion, or one major or two minor clinical criteria from a site consistent with infection, in a host with symptoms attributed to the fungal infection.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Sensitivity:
A. Pediatrics (patient sensitivity):
- Proven Aspergillosis (9 patients): 44.4% (4/9), 95% CI: 18.9-73.3%
- Probable Aspergillosis (8 patients): 62.5% (5/8), 95% CI: 30.6-86.3%
- Combined Proven and Probable Aspergillosis (17 patients): 52.9% (9/17), 95% CI: 31.0-73.8%
B. Adults (patient sensitivity previously conducted in K023857): - Proven Aspergillosis (11 patients): 81.8% (9/11), 95% CI: 52.3-94.9%
- Probable Aspergillosis (18 patients): 77.8% (14/18), 95% CI: 54.8-91.0%
- Combined Proven and Probable Aspergillosis (29 patients): 79.3% (23/29), 95% CI: 61.6-90.2%
Specificity:
By Pediatric Patients:
- Combined Sites (108 patients): 87.0% (94/108), 95% CI: 79.4-92.1%
- Site 1 (44 patients): 86.4% (38/44), 95% CI: 73.3-93.6%
- Site 2 (59 patients): 86.4% (51/59), 95% CI: 75.5-93.0%
- Site 3 (5 patients): 100% (5/5), 95% CI: 56.6-100%
By Pediatric Samples:
- Combined Sites (1625 samples): 98.5% (1600/1625), 95% CI: 97.7-99.0%
- Site 1 (794 samples): 98.9% (785/794), 95% CI: 97.9-99.4%
- Site 2 (731 samples): 97.8% (715/731), 95% CI: 96.5-98.6%
- Site 3 (100 samples): 100% (100/100), 95% CI: 96.3-100%
By Adult Patients (previously conducted in K023857):
- Combined Sites (143 patients): 88.8% (127/143), 95% CI: 82.6-93.0%
- Site 1 (28 patients): 78.6% (22/28), 95% CI: 60.5-89.8%
- Site 2 (77 patients): 93.4% (71/77), 95% CI: 84.0-96.4%
- Site 3 (38 patients): 89.5% (34/38), 95% CI: 75.9-95.8%
By Adult Samples (previously conducted in K023857):
- Combined Sites (1262 samples): 98.5% (1243/1262), 95% CI: 97.7-99.0%
- Site 1 (349 samples): 98.0% (342/349), 95% CI: 95.9-99.0%
- Site 2 (560 samples): 98.6% (552/560), 95% CI: 97.2-99.3%
- Site 3 (353 samples): 98.9% (349/353), 95% CI: 97.1-99.6%
Predictive Value:
A. Pediatrics (Study Prevalence 13.6%):
- PPV: 39.1%, 95% CI: 22.2-59.2%
- NPV: 92.2%, 95% CI: 85.3-96.0%
A. Pediatrics (Calculated Prevalence 5%): - PPV: 17.6%, 95% CI: 6.5-39.8%
- NPV: 97.2%, 95% CI: 92.1-99.1%
B. Adults (Study Prevalence 16.9%):
- PPV: 59.0%, 95% CI: 43.4-72.9%
- NPV: 95.5%, 95% CI: 90.5-97.9%
B. Adults (Calculated Prevalence 5%): - PPV: 27.2%, 95% CI: 13.7-46.7%
- NPV: 98.8%, 95% CI: 95.4-99.7%
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.
Platelia™ Aspergillus EIA (K023857)
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.
Not Found
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
§ 866.3040
Aspergillus spp. serological reagents.(a)
Identification. Aspergillus spp. serological reagents are devices that consist of antigens and antisera used in various serological tests to identify antibodies toAspergillus spp. in serum. The identification aids in the diagnosis of aspergillosis caused by fungi belonging to the genusAspergillus. Aspergillosis is a disease marked by inflammatory granulomatous (tumor-like) lessions in the skin, ear, eyeball cavity, nasal sinuses, lungs, and occasionally the bones.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.
0
510(k) SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned 510(k) number is: K060641
| DATE: | February 28, 2006 |
|---|---|
| APPLICANT: | Bio-Rad |
| 3, Boulevard Raymond Poincaré | |
| 92430 Marnes-la-Coquette, France | |
| OFFICIAL CORRESPONDENT: | Dr. Sylvie Confida |
| TELEPHONE: | |
| FAX: | 33-1-47-95-6138 |
| 33-1-47-95-6242 | |
| PRODUCT TRADE NAME: | Bio-Rad Laboratories Platelia™ Aspergillus EIA |
| COMMON NAME: | Aspergillus Antigen EIA |
| CLASSIFICATION NAME: | Antigen, Galactomannan, Aspergillus spp. |
| PREDICATE DEVICE: | Platelia™ Aspergillus EIA |
DEVICE DESCRIPTION
The Platelia™ Aspergillus EIA is a one-stage immunoenzymatic sandwich microplate assay which detects galactomannan in human serum. The assay uses rat EBA-2 monoclonal antibodies, which are directed against Aspergillus galactomannan, and have been characterized in previous studies 19,16. The monoclonal antibodies are used to coat the wells of the microplate and bind the antigen, and to detect the antigen bound to the sensitized microplate (conjugate reagent: peroxidase-linked monoclonal antibodies).
Serum samples are heat-treated in the presence of EDTA in order to dissociate immune complexes and to precipitate serum proteins that could possibly interfere with the test . The treated serum samples and conjugate are added to the wells coated with monoclonal antibodies, and incubated. A monoclonal antibody - galactomannan - monoclonal antibody / peroxidase complex is formed in the presence of galactomannan antigen. The strips are washed to remove any unbound material. Next, the substrate solution is added, which will react with the complexes bound to the well to form a blue color reaction. The enzyme reaction is stopped by the addition of acid, which changes the blue color to yellow. The absorbance (optical density) of specimens and controls is determined with a spectrophotometer set at 450 and 620/630 nm wavelength.
1
INTENDED USE
The Platelia™ Aspergillus EIA is an immunoenzymatic sandwich microplate assay for the detection of Aspergillus galactomannan antigen in adult and pediatric serum samples.
INDICATIONS FOR USE
The Platelia™ Aspergillus EIA is a test which, when used in conjunction with other diagnostic procedures such as microbiological culture, histological examination of biopsy samples and radiographic evidence, can be used as an aid in the diagnosis of Invasive Aspergillosis.
TECHNOLOGICAL CHARACTERISTICS
The following tables summarize similarities and differences between the Platelia™ Aspergillus EIA (Catalog #62793) and Platelia™ Aspergillus EIA (K023857):
| Table 1(a) Similarities between intended use | ||||
|---|---|---|---|---|
| -- | ----------------------------------------------- | -- | -- | -- |
| Similarities in
Function and Use | Platelia™ Aspergillus EIA,
Catalog 62793 | Platelia™ Aspergillus EIA
(K023857) |
|-------------------------------------|----------------------------------------------|----------------------------------------------|
| Intended Use | Galactomannan antigen
detection in serum. | Galactomannan antigen
detection in serum. |
| Matrix | Serum | Serum |
Table 1(b) Differences between intended use
| Differences in
Function and Use | Platelia™ Aspergillus EIA,
Catalog 62793 | Platelia™ Aspergillus EIA
(K023857) |
|------------------------------------|--------------------------------------------------------------------------|------------------------------------------------------------------|
| Intended Use | Detection of galactomannan antigen in adult and pediatric serum samples. | Detection of Aspergillus galactomannan antigen in serum samples. |
2
| Table 2 Similarities between reagents and materials | |||||
|---|---|---|---|---|---|
| -- | ----------------------------------------------------- | -- | -- | -- | -- |
| Similarities in
Components /
Materials | Platelia™ Aspergillus EIA,
Catalog 62793 | Platelia™ Aspergillus EIA
(K023857) |
|----------------------------------------------|-------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------|
| Microplate | 96 well microplate -
antibody coated microwells | 96 well microplate - antibody
coated microwells |
| Reagents | Conjugate, Wash Buffer,
Substrate, TMB Chromogen,
Sample Diluent, Positive
Control, Stop Solution. | Conjugate, Wash Buffer,
Substrate, TMB Chromogen.
Sample Diluent, Positive
Control, Stop Solution. |
Table 3(a) Similarities between assay procedures.
| Similarities in
Assay Procedures | Platelia™ Aspergillus EIA,
Catalog 62793 | Platelia™ Aspergillus EIA
(K023857) |
|---------------------------------------------------------------------------------------------------------------|---------------------------------------------|----------------------------------------|
| Incubation
temperature of the
microplate after
addition of the
conjugate and the
treated sera. | Incubation temperature: 37°C | Incubation temperature: 37°C |
| Incubation time of
the microplate after
addition of the
conjugate and the
treated sera. | Incubation time: 90 ± 5
minutes | Incubation time: 90 ± 5
minutes |
Table 3(b) Differences between assay procedures.
| Differences in
Assay Procedures | Platelia™ Aspergillus EIA,
Catalog 62793 | Platelia™ Aspergillus EIA
(K023857) |
|-----------------------------------------|---------------------------------------------------------------------------------|---------------------------------------------------------|
| Method of treatment
of the sera | Use of either heat block or
boiling water bath for
treatment of the sera. | Use of boiling water bath for
treatment of the sera. |
| Time and
temperature of
treatment | Heat block : 120℃ for 6 min
Boiling water bath: 100℃
for 3 min | Boiling water bath: 100℃ for 3
min |
3
| Table 4 Differences between Available Kit Configurations | ||
|---|---|---|
| ---------------------------------------------------------- | -- | -- |
| Differences in
Components /
Materials | Platelia™ Aspergillus EIA,
Catalog 62793 | Platelia™ Aspergillus EIA
(K023857) |
|---------------------------------------------|---------------------------------------------|--------------------------------------------------------------------|
| Available
Configuration of
Test Kits | Catalog # 62793 96 Test Kit | Catalog # 62793 96 Test Kit
and Catalog # 62794 480 Test
Kit |
Table 5 Differences between Limitations of the Procedure
| Differences in
Limitations of the
Procedure | Platelia™ Aspergillus EIA,
Catalog 62793 | Platelia™ Aspergillus EIA
(K023857) |
|---------------------------------------------------|----------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------|
| Limitation | Warning regarding positive
test results in patients being
treated with Zosyn® and
semi-synthetic ß-lactams. | Warning regarding positive test
results in patients being treated
with Zosyn®. |
Table 6 Differences between Reference Publications
| Differences in
Reference
Publications | Platelia™ Aspergillus EIA,
Catalog 62793 | Platelia™ Aspergillus EIA
(K023857) |
|---------------------------------------------|---------------------------------------------------------------------------------------|----------------------------------------|
| Publications | Publications by Ascioglu et
al, Marr et al, Mattei et al
and Upton et al added. | - |
PERFORMANCE SUMMARY
I. EXPECTED VALUES
The expected prevalence of Invasive Aspergillosis varies with the patient population; rates from 5-20% have been reported 4,7
The following results have been obtained from clinical studies conducted on pediatric (age ≤ 21 years) patients in the United States and on adult patients (age >22 years) in North America.
A .- Pediatrics
A clinical study was conducted on a total of 1954 serum samples from 129 immunocompromised pediatric (Age ≤ 21 years) patients, at high risk for Invasive Aspergillosis (IA) and patients diagnosed with Proven and Probable Invasive Aspergillosis, at three testing centers in the United States to determine the performance characteristics of the Platelia™ Aspergillus EIA. The distribution of index for these populations is shown in the following charts:
4
Pediatric Patients diagnosed without Invasive Aspergillosis (control population)
A total of 1625* pediatric serum samples obtained from 108 immunocompromised pediatric patients at three testing centers in the United States were tested to determine the performance characteristics of the Platelia™ Aspergillus EIA. The distribution of index values for samples is shown in the following chart:
Image /page/4/Figure/2 description: The image is a bar graph titled "Distribution of the Serum Index Value from the Pediatric Control Population (N=1625)". The x-axis is labeled "Index" and shows values ranging from 0-0.1 to >1.5. The y-axis is labeled "Number of Sera" and ranges from 0 to 900. The bar graph shows that the highest number of sera is in the 0.1-0.2 range, with a value of 805.
Image /page/4/Figure/3 description: The image shows the text "Figure 1" in a simple, sans-serif font. The word "Figure" is capitalized, and the number "1" follows it. The text is black against a white background.
*Note: 80 samples, from 4 control patients with positive galactomannan antigen results coinciding with piperacillin / tazobactam (Zosyn®) therapy were excluded.
Pediatric Patients with Invasive Aspergillosis
The scatter plot depicts galactomannan assay results for the 249 serum samples from 17 patients in this study diagnosed with proven or probable Invasive Aspergillosis as defined by EORTC/NIAID definitions.
Not every serum sample from each patient is expected to be positive. The expected prevalence of Invasive Aspergillosis varies with the patient population; rates from 5-20% have been reported3 6. The prevalence rate of this study was 13.6%.
5
Image /page/5/Figure/0 description: The image shows the text "Figure 2" in a simple, sans-serif font. The word "Figure" is capitalized, and the number "2" follows it. The text is black against a white background.
Image /page/5/Figure/1 description: This image shows a scatter plot titled "Pediatric Proven/Probable Aspergillosis: Distribution of Index/Pediatric Patient (N=17)". The x-axis is labeled "Patient Number" and ranges from 0 to 18. The y-axis is labeled "Index" and ranges from 0.0 to >2.0, with a horizontal line at 0.5.
B. Adults
Note: Reproducibility Studies were previously presented in prior 510(k) submission (K023857) for this assay, no new reproducibility studies have been performed.
A clinical study was previously conducted on a total of 1724 serum samples from 172 bone marrow transplant (BMT) and leukemic patients diagnosed with and without Invasive Aspergillosis, at three testing centers in North America to determine the performance characteristics of the Platelia™ Aspergillus EIA. The distribution of index values for these populations is represented in the following charts.
Adult Patients diagnosed without Invasive Aspergillosis (control population)
A total of 1262 serum samples obtained from 143 bone marrow transplant (BMT) and leukemic patients at three testing centers in North America were previously tested with the Platelia™ Aspergillus EIA test. The distribution of index values is shown in the following chart.
6
Image /page/6/Figure/0 description: The image shows the text "Figure 3" in a simple, sans-serif font. The word "Figure" is capitalized, and the number "3" is placed directly after it. The text is black against a white background.
Image /page/6/Figure/1 description: The image is a bar graph titled "Distribution of the Serum Index Value from the Adult Control Population (N=1262)". The x-axis is labeled "Index" and shows index ranges from 0-0.1 to >1.5. The y-axis is labeled "Number of Sera" and ranges from 0 to 800. The bar graph shows that the majority of the adult control population has a serum index value between 0.1 and 0.2, with 662 people falling into this range.
Adult Patients diagnosed with Invasive Aspergillosis
Note: Reproducibility Studies were previously presented in prior 510(k) submission (K023857) for this assay, no new reproducibility studies have been performed.
This scatter plot depicts galactomannan assay results for the 462 serum samples from 29 patients in this study diagnosed with proven or probable Invasive Aspergillosis as defined by EORTC/NIAID definitions. Not every serum sample from each patient is expected to be positive. The expected prevalence of Invasive Aspergillosis varies with the patient population; rates from 5-20% have been reported 4.7. The prevalence rates for this previous study was 16.9%.
7
Image /page/7/Figure/0 description: The image shows the text "Figure 4". The text is written in a simple, sans-serif font and is black. The background is white.
Image /page/7/Figure/1 description: This image is a scatter plot titled "Adult Proven/ Probable Aspergillosis: Distribution of Index/ Adult Patient (N=29)". The x-axis is labeled "Patient Number" and ranges from 0 to 30. The y-axis is labeled "Index" and ranges from 0.0 to greater than or equal to 2.0, with a horizontal line at 0.5.
The following graphs represent examples of a patient without clinical signs or symptoms of Invasive Aspergillosis (negative for Aspergillus) and a patient with proven or probable Invasive Aspergillosis (positive for Aspergillus) respectively.
Negative patient
Image /page/7/Figure/4 description: The image is a graph titled "CONTROL PATIENT" with "Days" on the x-axis and "Index" on the y-axis. The y-axis ranges from 0 to 1.6, and there is a horizontal line at the index of 0.5. The graph shows a fluctuating line that generally stays below the index of 0.2, with a few peaks around days 22, 32, and 52.
Platelia™ Aspergillus EIA (K060641) 510(k) Summary
8
Positive patient
Image /page/8/Figure/1 description: The image is a graph titled "PROVEN INVASIVE ASPERGILLOSIS PATIENT". The x-axis is labeled "Days" and ranges from 0 to 60. The y-axis is labeled "Index" and ranges from 0 to 1.6. The graph shows a line plot with data points indicating the index value over time, with a horizontal line at the 0.5 index value.
II. REPRODUCIBILITY STUDIES
Note: Reproducibility Studies were previously presented in prior 510(k) submission (K023857) for this assay, no new reproducibility studies have been performed.
Inter-assay and Intra-assay variability for the Platelia™ Aspergillus EIA were determined in a study using a panel of 6 pooled patient serum samples (one negative, one low positive, two positive, and two high positive) obtained at 3 clinical trial sites in North America. Each of the 6 panel members was tested in triplicate (x3) on 3 different days, on one lot, at two sites (total number of replicates at each site = 9). Each of the 6 panel members was tested in duplicate (x2) on 3 different days, on 1 lot, at a third site (total number of replicates at the third site = 6). One (1) operator performed all precision testing at each site. The data were analyzed according to the National Committee for Clinical Laboratory Standards (NCCLS).
The mean optical density (OD) and mean index value, standard deviation (SD), percent coefficient of variation (%CV), within run precision (intraassay) and within site (interassay) precision for each panel member at each site are illustrated below in the following tables.
9
| Site | Panel Member | Neg | Low Pos | Pos #1 | Pos #2 | High Pos#1 | High Pos #2 | Neg Control | CO Control | Pos Control | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| OD | Index | OD | Index | OD | Index | OD | Index | OD | Index | OD | Index | OD | Index | OD | Index | OD | Index | ||
| Site 1 | N | 9 | 9 | 9 | 9 | 9 | 9 | 9 | 9 | 9 | 9 | 9 | 9 | 3 | 3 | 6 | 6 | 3 | 3 |
| Mean | 0.052 | 0.09 | 0.445 | 0.74 | 0.702 | 1.17 | 0.931 | 1.563 | 1.227 | 2.06 | 2.887 | 4.83 | 0.046 | 0.08 | 0.606 | 1.00 | 2.216 | 3.67 | |
| Within Run | |||||||||||||||||||
| (Intra-assay) SD | 0.002 | 0.00 | 0.022 | 0.03 | 0.059 | 0.09 | 0.044 | 0.08 | 0.051 | 0.09 | 0.089 | 0.17 | N/A | N/A | 0.02 | 0.03 | N/A | N/A | |
| %CV | N/A | N/A | 4.8% | 4.4% | 8.4% | 7.6% | 4.7% | 5.1% | 4.2% | 4.4% | 3.1% | 3.6% | N/A | N/A | 3.7% | 3.4% | N/A | N/A | |
| Total | |||||||||||||||||||
| (Inter-assay) SD | 0.036 | 0.04 | 0.051 | 0.08 | 0.070 | 0.14 | 0.044 | 0.25 | 0.058 | 0.29 | 0.169 | 0.58 | N/A | N/A | 0.102 | 0.03 | 0.317 | 0.12 | |
| %CV | N/A | N/A | 11.5% | 10.4% | 10.0% | 11.6% | 4.7% | 15.7% | 4.7% | 14.3% | 5.9% | 11.9% | N/A | N/A | 16.9% | 2.8% | 14.3% | 3.3% | |
| Site 2 | Panel Member | ||||||||||||||||||
| N | 9 | 9 | 9 | 9 | 9 | 9 | 9 | 9 | 9 | 9 | 9 | 9 | 3 | 3 | 6 | 6 | 3 | 3 | |
| Mean | 0.040 | 0.10 | 0.280 | 0.70 | 0.364 | 0.89 | 0.602 | 1.49 | 0.801 | 2.01 | 1.361 | 3.43 | 0.074 | 0.18 | 0.415 | 1.00 | 1.197 | 2.97 | |
| Within Run | |||||||||||||||||||
| (Intra-assay) SD | 0.006 | 0.01 | 0.041 | 0.09 | 0.023 | 0.07 | 0.045 | 0.11 | 0.046 | 0.10 | 0.047 | 0.11 | N/A | N/A | 0.00 | 0.01 | N/A | N/A | |
| %CV | N/A | N/A | 14.5% | 13.0% | 6.4% | 7.6% | 7.5% | 7.1% | 5.7% | 4.8% | 3.5% | 3.2% | N/A | N/A | 1.1% | 1.1% | N/A | N/A | |
| Total | |||||||||||||||||||
| (Inter-assay) SD | 0.006 | 0.03 | 0.058 | 0.19 | 0.083 | 0.18 | 0.057 | 0.28 | 0.042 | 0.53 | 0.079 | 1.00 | N/A | N/A | 0.094 | 0.01 | 0.068 | 0.54 | |
| %CV | N/A | N/A | 20.8% | 27.3% | 22.7% | 19.8% | 9.5% | 18.7% | 5.3% | 26.5% | 5.8% | 29.2% | N/A | N/A | 22.7% | 0.9% | 5.7% | 18.2% | |
| Site 3 | Panel Member | ||||||||||||||||||
| N | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 3 | 3 | 6 | 6 | 3 | 3 | |
| Mean | 0.049 | 0.10 | 0.388 | 0.81 | 0.652 | 1.36 | 0.830 | 1.73 | 1.158 | 2.41 | 2.378 | 4.96 | 0.059 | 0.12 | 0.480 | 1.00 | 1.652 | 3.45 | |
| Within Run | |||||||||||||||||||
| (Intra-assay) SD | 0.003 | 0.01 | 0.009 | 0.02 | 0.082 | 0.17 | 0.068 | 0.14 | 0.094 | 0.20 | 0.126 | 0.25 | N/A | N/A | 0.028 | 0.06 | N/A | N/A | |
| %CV | N/A | N/A | 2.4% | 2.4% | 12.5% | 12.2% | 8.2% | 8.2% | 8.1% | 8.2% | 5.3% | 5.1% | N/A | N/A | 5.8% | 5.8% | N/A | N/A | |
| Total | |||||||||||||||||||
| (Inter-assay) SD | 0.012 | 0.03 | 0.078 | 0.13 | 0.068 | 0.15 | 0.104 | 0.25 | 0.082 | 0.15 | 0.111 | 0.34 | N/A | N/A | 0.028 | 0.04 | 0.056 | 0.23 | |
| %CV | N/A | N/A | 20.0% | 15.8% | 10.5% | 11.1% | 12.5% | 14.3% | 7.1% | 6.2% | 4.7% | 6.8% | N/A | N/A | 5.8% | 4.1% | 3.4% | 6.6% |
N/A = not opplicable
NCCLS EP5-A, Vol. 19, No. 2. Page 24, Equation (C2)
NCCLS EPS-A, Vol. 19, No 2. Page 25, Equation (C3) and Equation (C4)
III. CROSS-REACTIVITY STUDIES
Note: Cross-Reactivity Studies were previously presented in prior 510(k) submission (K023857) for this assay, no new cross-reactivity studies have been performed.
A study to evaluate the effect of potentially interfering medical conditions unrelated to Invasive Aspergillosis was performed with one lot of the Platelia™ Aspergillus EIA kit. The following serum samples were tested for cross-reactivity with the Platelia™ Aspergillus EIA. A total of 151 sera were tested.
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| Pathology | # Samples Tested | # Positives |
|---|---|---|
| Rheumatoid Factor | 10 | 0 |
| ANA Positive | 10 | 0 |
| IgG Hypergammaglobulinemia | 10 | 0 |
| IgM Hypergammaglobulinemia | 10 | 0 |
| Cancer* | 11 | 0 |
| Non-Viral Cirrhosis (primary biliary; | ||
| alcohol induced; drug induced) | 10 | 0 |
| Multiple Transfusions | 10 | 0 |
| Multiparous Females | 10 | 0 |
| HAV | 10 | 0 |
| HCV | 10 | 0 |
| Rubella | 10 | 0 |
| CMV | 10 | 0 |
| Syphilis (RPR+) | 10 | 0 |
| Toxoplasmosis | 10 | 0 |
| Mycoplasma | 10 | 0 |
- One each of bladder, breast(2), colon, endometrial, lung, prostate, renal, and squamous(3).
IV. PERFORMANCE EVALUATION STUDIES
Additional clinical testing to evaluate the specificity and sensitivity of the Platelia™ Aspergillus EIA was conducted at 3 clinical sites located in the United States for the pediatric (Age ≤ 21 years ) population. This testing was performed in addition to the testing done for prior submission (K023857) for adult patients. The study was conducted using samples from the following patient populations*:
- patients without signs of Invasive Aspergillosis ●
- patients with probable Invasive Aspergillosis ●
- patients with proven Invasive Aspergillosis .
- The Invasive Fungal Infection Cooperative Group (IFICG) of the European Organization for Research (EORTC) and the Mycosis Study Group (MSG of the National Institute of Allergy and Infectious Diseases (NIAID) have defined criteria for diagnosis of Invasive Aspergillosis (IA) in patients with hematologic malignancy or hematopoetic stem cell transplant.
Proven Invasive Aspergillosis is defined by positive microbiological culture obtained by sterile procedure from the site affected, and histopathological demonstration of the appropriate morphological forms in a host with symptoms attributed to the fungal infection.
Probable Invasive Aspergillosis is defined as at least one microbiological criterion, and one major or two minor clinical criteria from a site consistent with infection, in a host
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with symptoms attributed to the fungal infection.
Possible Invasive Aspergillosis is defined as at least one microbiological criterion, or one major or two minor clinical criteria from a site consistent with infection, in a host with symptoms attributed to the fungal infection
SENSITIVITY
A. PEDIATRICS
Results from this study have been analyzed in terms of patient sensitivity. Sensitivity testing was conducted using the Platelia™ Aspergillus EIA at three sites on a combined total of 17 immunocompromised pediatric patients diagnosed with Proven or Probable Invasive Aspergillosis.
Table 3
| DIAGNOSIS | NUMBER OF
PATIENTS | SENSITIVITY | 95%
CONFIDENCE
INTERVAL |
|-----------------------------------------------|-----------------------|--------------|-------------------------------|
| Proven Aspergillosis | 9 | 44.4% (4/9) | 18.9-73.3% |
| Probable Aspergillosis | 8 | 62.5% (5/8) | 30.6-86.3% |
| Combined Proven and
Probable Aspergillosis | 17* | 52.9% (9/17) | 31.0-73.8% |
*Note: 9 of the 17 patients gave negative Aspergillus galactomannan antigen results. All of the 9 patients with negative Aspergillus galactomannan antigen results received therapy with multiple antifungal agents. The concomitant use of mold-active anti-fungal therapy in some patients with Invasive Aspergillosis may result in reduced sensitivity 13
B. ADULTS
Note: Reproducibility Studies were previously presented in prior 510(k) submission (K023857) for this assay, no new reproducibility studies have been performed.
Sensitivity testing was previously conducted using the Platelia™ Aspergillus EIA at three sites on a combined total of 29 Bone Marrow Transplant (BMT) and Leukemia adult patients diagnosed with Proven or Probable Invasive Aspergillosis.
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Table 4
| DIAGNOSIS | NUMBER OF
PATIENTS | SENSITIVITY | 95% CONFIDENCE
INTERVAL |
|-----------------------------------------------|-----------------------|---------------|----------------------------|
| Proven Aspergillosis | 11 | 81.8% (9/11) | 52.3-94.9% |
| Probable Aspergillosis | 18 | 77.8% (14/18) | 54.8-91.0% |
| Combined Proven and
Probable Aspergillosis | 29 | 79.3% (23/29) | 61.6-90.2% |
SPECIFICITY
SPECIFICITY BY PEDIATRIC PATIENTS
Specificity testing was conducted using the Platelia™ Aspergilllus EIA at three sites on a combined total of 108* immunocrompomised pediatric patients without signs of Invasive Aspergillosis (control patients).
Table 5
| SITE | NUMBER OF
PATIENTS | SPECIFICITY | 95% CONFIDENCE
INTERVAL |
|----------------|-----------------------|----------------|----------------------------|
| 1 | 44 | 86.4 % (38/44) | 73.3-93.6% |
| 2 | 59 | 86.4%(51/59) | 75.5-93.0% |
| 3 | 5 | 100% (5/5) | 56.6-100% |
| Combined Sites | 108 | 87.0%(94/108) | 79.4-92.1% |
*Note: 4 patients with positive galactomannan antigen results coinciding with piperacillin / tazobactam therapy were excluded.
SPECIFICITY BY PEDIATRIC SAMPLES
Specificity testing was conducted using the Platelia™ Aspergilllus EIA at three sites on a combined total of 1625* samples obtained from 108 immunocrompomised pediatric patients without signs of Invasive Aspergillosis (control patients).
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Table 6
| SITE | NUMBER OF
SAMPLES | SPECIFICITY | 95% CONFIDENCE
INTERVAL |
|----------------|----------------------|-------------------|----------------------------|
| 1 | 794 | 98.9%(785/794) | 97.9-99.4% |
| 2 | 731 | 97.8%(715/731) | 96.5-98.6% |
| 3 | 100 | 100% (100/100) | 96.3-100% |
| Combined Sites | 1625 | 98.5% (1600/1625) | 97.7-99.0% |
*Note: 80 samples from 4 patients with positive galactomannan antigen results coinciding with piperacillin / tazobactam therapy were excluded.
SPECIFICITY BY ADULT PATIENTS
Note: Reproducibility Studies were previously presented in prior 510(k) submission (K023857) for this assay, no new reproducibility studies have been performed.
Specificity testing was previously conducted using the Platelia™ Aspergillus EIA at three sites on a combined total of 143 Bone Marrow Transplant (BMT) and Leukemia adult patients without signs of Invasive Aspergillosis (control patients).
Table 7
| SITE | NUMBER OF
PATIENTS | SPECIFICITY | 95% CONFIDENCE
INTERVAL |
|----------------|-----------------------|-----------------|----------------------------|
| 1 | 28 | 78.6% (22/28) | 60.5-89.8% |
| 2 | 77 | 93.4% (71/77) | 84.0-96.4% |
| 3 | 38 | 89.5% (34/38) | 75.9-95.8% |
| Combined Sites | 143 | 88.8% (127/143) | 82.6-93.0% |
SPECIFICITY BY ADULT SAMPLES
Note: Reproducibility Studies were previously presented in prior 510(k) submission (K023857) for this assay, no new reproducibility studies have been performed.
Specificity testing was previously conducted using the Platelia™ Aspergillus EIA at three sites on a combined total of 1262 samples obtained from 143 Bone Marrow Transplant (BMT) and Leukemia adult patients without signs of Invasive Aspergillosis (control patients).
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Table 8
| SITE | NUMBER OF
SAMPLES | SPECIFICITY | 95% CONFIDENCE
INTERVAL |
|----------------|----------------------|-------------------|----------------------------|
| 1 | 349 | 98.0% (342/349) | 95.9-99.0% |
| 2 | 560 | 98.6% (552/560) | 97.2-99.3% |
| 3 | 353 | 98.9% (349/353) | 97.1-99.6% |
| Combined Sites | 1262 | 98.5% (1243/1262) | 97.7-99.0% |
PREDICTIVE VALUE
Positive and negative predictive values have been analyzed for the two patient populations. Based on the actual average of 13.6% prevalence rate in pediatrics and 16.9% prevalence rate in adults observed in this study, positive and negative predictive values have been calculated as below:
A. PEDIATRICS
Study Prevalence 13.6%
| PPV: 39.1% | 95% Confidence Interval : 22.2-59.2% |
|---|---|
| NPV: 92.2% | 95% Confidence Interval : 85.3-96.0% |
B. ADULTS
Study Prevalence 16.9%
| PPV: 59.0% | 95% Confidence Interval: | 43.4-72.9% |
|---|---|---|
| NPV: 95.5% | 95% Confidence Interval: | 90.5-97.9% |
The expected prevalence of Invasive Aspergillosis varies with the patient population: rates from 5-20% have been reported 47. For patient populations on the lower end of the published prevalence, the positive and negative prevalence have been re-calculated using a 5% prevalence rate.
A. PEDIATRICS
Calculated Prevalence 5%
| PPV : 17.6% | 95% Confidence Interval : 6.5-39.8% |
|---|---|
| NPV : 97.2% | 95% Confidence Interval : 92.1-99.1% |
B. ADULTS
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Calculated Prevalence 5%
:
.
:
:
.
PPV: 27.2% 95% Confidence interval: 13.7-46.7% NPV: 98.8% 95% Confidence Interval: 95.4-99.7%
Platelia™ Aspergillus EIA (K060641) 510(k) Summary
:
:
.
: -
:
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/16/Picture/1 description: The image is a black and white logo for the U.S. Department of Health and Human Services. The logo features a stylized eagle with its wings spread, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle. The eagle is facing to the right. The logo is simple and clean, and it is easily recognizable.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
JUN 2 2006
Ms. Priya Bondre Regulatory Affairs Representative Bio-Rad Laboratories Diagnostics Group 6565 185th Avenue, NE Redmond. WA 98052
Re: K060641
Trade/Device Name: Platelia™ Aspergillus EIA Regulation Number: 21 CFR 866.3040 Regulation Name: Aspergillus Spp. Serological Reagents Regulatory Class: Class I Product Code: NOM Dated: February 28, 2006 Received: March 10, 2006
Dear Ms. Bondre:
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 either class II (Special Controls) or class III (PMA), 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 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2 -
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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240)276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html
Sincerely yours.
Sally, a story
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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Bio-Rad Laboratories Platelia™ Aspergillus EIA Premarket 510(k) Notification February 28, 2006
Indications for Use
510(k) Number (if known): Not known at this time
Device Name: Platelia™ Aspergillus EIA
Indications For Use:
The Platelia™ Aspergillus ElA is an immunoenzymatic sandwich microplate assay for the detection of Aspergillus galactomannan antigen in adult and pediatric serum samples.
The Platelia™ Aspergillus ElA is a test which, when used in conjunction with other diagnostic procedures such as microbiological culture, histological examination of biopsy samples and radiographic evidence, can be used as an aid in the diagnosis of invasive aspergillosis.
Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Freddie he Poole
Division Sign off
ivision Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) Kob 064