(42 days)
The Platelia™ Lyme IgM Assay is a qualitative test intended for use in the presumptive detection of human IgM antibodies to Borrelia burgdorferi in human serum or plasma (K3 EDTA, sodium heparin, or sodium citrate). The EIA test system should be used to test serum or plasma from patients with a history and symptoms of infection with B. burgdorferi. All positive and equivocal specimens should be re-tested with a specific, second-tier test such as Western blot. Positive second-tier results are supportive evidence of infection with B. burgdorferi. The diagnosis of Lyme disease should be made based on history and symptoms (such as erythema migrans), and other laboratory data, in addition to the presence of antibodies to B. burgdorferi. Negative results (either first or second-tier) should not be used to exclude Lyme disease.
The Platelia™ Lyme IgM Assay is a qualitative assay for the detection of human IgM antibodies to Borrelia burgdorferi in human serum or plasma.
The provided text describes the Bio-Rad Platelia™ Lyme IgM Assay and includes performance data from several studies. However, it does not explicitly define acceptance criteria for all the performance metrics presented, nor does it detail a single comprehensive study proving the device meets all acceptance criteria in the typical sense of a clinical trial for a standalone diagnostic device. Instead, it presents various performance characteristics and compares the device's results to clinical diagnoses or to a predicate device.
Here's an analysis based on the provided text, addressing your specific points:
1. Table of Acceptance Criteria and Reported Device Performance
The document provides acceptance criteria specifically for interfering substances. For other performance metrics, it presents observations or comparisons rather than explicitly stated acceptance thresholds.
| Performance Characteristic | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Intra-Assay Precision | Coefficient of variation (CV) < 5% for positive samples (Implied from Conclusion) | Samples close to cut-off (20x tests):- Cut-Off: OD CV = 1.7%, Ratio CV = 1.8%- Grey Zone min: OD CV = 3.3%, Ratio CV = 3.3%- Grey Zone max: OD CV = 2.4%, Ratio CV = 2.4%Various samples (30x tests):- Negative: OD CV = 15%, Ratio CV = 15.2%- Low positive: OD CV = 4.4%, Ratio CV = 4.4%- Medium: OD CV = 3.7%, Ratio CV = 3.7%- High: OD CV = 2.4%, Ratio CV = 2.5%Conclusion: The coefficient of variation was less than 5% for positive samples. |
| Interfering Substances | Slope (a): 0.85 < a < 1.15 | Hemoglobin: 0.907Bilirubin: 0.916Triolein: 0.889Albumin: 0.893 |
| Y-axis intercept (b): < 0.10 | Hemoglobin: 0.071Bilirubin: 0.050Triolein: 0.061Albumin: 0.073 | |
| Correlation coeff: > 0.975 | Hemoglobin: 0.999Bilirubin: 0.999Triolein: 0.997Albumin: 0.999 | |
| a+b: 0.85 < a+b < 1.15 | Hemoglobin: 0.978Bilirubin: 0.966Triolein: 0.950Albumin: 0.966 | |
| Cross Reactivity | Not explicitly stated; results are presented. | Syphilis (N=34): 1 Positive/EquivocalCMV IgM (N=5): 1 Positive/EquivocalEBV IgM (N=5): 5 Positive/EquivocalMumps IgM (N=10): 2 Positive/EquivocalANA (N=10): 1 Positive/EquivocalCRP (N=5): 2 Positive/EquivocalOther conditions (HSV IgM, Toxoplasmosis IgM, Rubella IgM, Measles IgM, VZV IgM, HIV, HAMA, SLE, Rheumatoid Factor) showed 0 Positive/Equivocal. |
| CDC Lyme Disease Panel | Not explicitly stated; results are presented as % agreement with clinical diagnosis. | Platelia™ Lyme IgM: Overall 74.4% agreement with clinical diagnosis (32/43) (Equivocal samples considered positive).Western Blot IgM (for comparison): Overall 54.5% agreement with clinical diagnosis (24/44). |
2. Sample Size Used for the Test Set and Data Provenance
The text describes several test sets:
- Intra-Assay Precision:
- One study used 3 samples, each tested 20 times (total 60 tests).
- Another study used "various samples" (number not specified for distinct samples), each tested 30 times.
- Provenance: Not specified, but generally these are internal lab samples. Retrospective.
- Cross Reactivity:
- Total N = 126 unique samples across various disease conditions.
- Provenance: Not specified. Retrospective.
- Interfering Substances:
- 4 interfering substances (Hemoglobin, Bilirubin, Triolein, Albumin) were tested.
- Sample size for each test: Not explicitly stated, but typically involves a set of samples with and without the interferent at various concentrations. Retrospective.
- CDC Lyme Disease Serum Panel:
- Total N = 43 samples for Platelia™ Lyme IgM performance (1 sample not tested due to insufficient volume from a total of 44 for Western Blot).
- Provenance: Implied to be from the CDC (Centers for Disease Control and Prevention), which often collects well-characterized samples. Retrospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- Intra-Assay Precision, Cross Reactivity, Interfering Substances: Ground truth is established by the known characteristics of the samples (e.g., spiked interferent, known disease status for cross-reactivity). No human experts are typically involved in establishing ground truth for these analytical performance studies.
- CDC Lyme Disease Serum Panel: The ground truth is referred to as "clinical diagnosis." The document does not specify the number or qualifications of experts who established these clinical diagnoses. It is assumed these diagnoses were made by clinicians based on history, symptoms, and other laboratory data, as per standard medical practice.
4. Adjudication Method for the Test Set
- Intra-Assay Precision, Cross Reactivity, Interfering Substances: No adjudication method is described or typically applicable for these analytical studies. The results are quantitative measurements or direct qualitative classifications based on the assay's cut-offs.
- CDC Lyme Disease Serum Panel: No specific adjudication method is described. The "clinical diagnosis" serves as the reference standard. Equivocal samples were "considered as positive" for the agreement calculation in the table.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
- This is an immunoassay kit, not an AI/imaging device designed for human reader interpretation. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and was not performed.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
- This device is a standalone diagnostic kit. Its performance is evaluated directly based on its ability to detect IgM antibodies, with the results read and interpreted against established cut-offs. The "algorithm" here refers to the biochemical reactions and the interpretation of the optical density (OD) readings according to the kit's instructions. The performance data presented (e.g., precision, cross-reactivity, CDC panel results) are all related to the standalone performance of the assay.
7. The Type of Ground Truth Used
- Intra-Assay Precision: Known sample characteristics (e.g., negative, low positive, medium, high concentrations).
- Cross Reactivity: Known disease conditions of the tested sera.
- Interfering Substances: Known concentrations of spiked interfering substances.
- CDC Lyme Disease Serum Panel: "Clinical diagnosis" of Lyme disease. This represents a form of outcomes data or a robust clinical reference standard, though details on its establishment are limited.
8. The Sample Size for the Training Set
- This document describes performance validation studies for an immunoassay kit. Immunoassay kits are generally developed and optimized through iterative processes. The concept of a distinct "training set" as understood in machine learning (where an algorithm learns from data) does not directly apply in the same way to the development of a biochemical assay like this. The training set would conceptually be the samples used during research and development to optimize reagents, concentrations, reaction times, and cut-off values. This information is typically not detailed in a 510(k) summary for an immunoassay. The text does not provide a sample size for any "training set."
9. How the Ground Truth for the Training Set Was Established
- As explained above, a formal "training set" with ground truth in the AI context isn't directly applicable here. For the samples used during the development and optimization of the assay, the ground truth would have been established through a combination of:
- Reference materials: Known positive and negative control samples.
- Well-characterized patient samples: Samples from patients with confirmed Lyme disease (e.g., by culture, PCR, or clinical diagnosis with confirmatory Western blot) and healthy controls.
- Spiked samples: Samples with known concentrations of Borrelia burgdorferi antibodies or interfering substances.
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510(k) SUMMARY
| Date of Summary | May 13, 2008 | JUN 2 6 2008 |
|---|---|---|
| Product Name | Platelia™ Platelia™ Lyme IgM | |
| Sponsor | Bio-Rad3 Boulevard Raymond Poincaré92430 Marnes-la-CoquetteFrance | |
| Correspondent | MDC Associates, LLCFran White, Regulatory Consultant163 Cabot StreetBeverly, MA 01915 | |
| Substantially Equivalent Device | The Platelia™ Lyme IgM Assay is substantially equivalentto the Mardx B. burgdorferi EIA. | |
| Manufacturer: Mardx Diagnostics, Inc. | ||
| Product: Mardx Lyme Disease EIA (IgM) Test - |
Bio-Rad Platelia" Lyme Substantial Product Attribute Mardx Lyme Disease Test IgM Assay Equivalent The Platelia™ Lyme IgM Intended use The MarDx B. burgdorferi ﮯ ﮨﮯ Assay is a qualitative test Disease Enzyme intended for use in the Immunoassay (EIA) IgM presumptive detection of Test Systems is a human IgM antibodies to qualitative test intended for Borrelia burgdorferi in use in the presumptive human serum or plasma. detection of human IgM The EIA system should be antibodies to Borrelia used to test serum or plasma burgdorferi in human from patients with a history serum. This EIA system and symptoms of infection should be used to test with B. burgdorferi. All serum from patients with a positive and equivocal history and symptoms of specimens should be reinfection with B.
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| tested with a specific, second-tier test such as Western blot. Positive second-tier results are supportive evidence of infection with B. burgdorferi. The diagnosis of Lyme disease should be made based on history and symptoms (such as erythema migrans), and other laboratory data, in addition to the presence of antibodies to B. burgdorferi. Negative results (either first or second-tier) should not be used to exclude Lyme disease. | burgdorferi. All positive and equivocal specimens should be re-tested with a highly specific, second-tier test such as Western blot. Positive second-tier results are supportive evidence of infection with B. burgdorferi. The diagnosis of Lyme disease should be made based on history and symptoms (such as erythema migrans), and other laboratory data, in addition to the presence of antibodies to B. burgdorferi. Negative results (either first or second-tier) should not be used to exclude Lyme disease. | ||
|---|---|---|---|
| Sample | Plasma or serum | Serum | √ |
| Testmethodology | ELISA | ELISA | √ |
PRODUCT DESCRIPTION
The Platelia™ Lyme IgM Assay is a qualitative assay for the detection of human IgM antibodies to Borrelia burgdorferi in human serum or plasma.
INTENDED USE
The Platelia™ Lyme IgM Assay is a qualitative test intended for use in the presumptive detection of human IgM antibodies to Borrelia burgdorferi in human serum or plasma. The EIA system should be used to test serum or plasma from patients with a history and symptoms of infection with B. burgdorferi. All positive and equivocal specimens should be re-tested with a specific, second-tier test such as Western blot. Positive second-tier results are supportive evidence of infection with B. burgdorferi. The diagnosis of Lyme disease should be made based on history and symptoms (such as erythema migrans), and other laboratory data, in addition to the presence of antibodies to B. burgdorferi. Negative results (either first or second-tier) should not be used to exclude Lyme disease.
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SUMMARY OF TECHNOLOGY
The Platelia™ Lyme IgM Assay is an enzyme immunoassay with capture of the IgM on the solid phase. Anti-human u-chains antibodies are coated on the solid phase (wells of the microplate). A mixture of the Borrelia B31 antigen and the monoclonal anti-Borrelia antigen antibody labeled with peroxidase is used as the conjugate.
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PERFORMANCE DATA
Bio-Rad confirms that any/all data provided in this submission may be released upon request.
Intra-Assay Precision
To confirm the intra assay precision of the Platelia™ Lyme assay two studies were run.
- Three samples close to the cut off value were tested 20 times during the same run, O according to the assessed kit's protocol.
- Various samples spanning the assay range were tested 30 times during the same run, o according to the assessed kit's protocol.
Samples close to the grey zone (20x)
| Sample | OD | RATIO | ||||
|---|---|---|---|---|---|---|
| Mean | SD | CV | Mean | SD | CV | |
| Cut-Off | 0.30 | 0.005 | 1.7% | 0.99 | 0.02 | 1.8% |
| Grey Zone min | 0.27 | 0.009 | 3.3% | 0.87 | 0.029 | 3.3% |
| Grey Zone max | 0.36 | 0.009 | 2.4% | 1.19 | 0.029 | 2.4% |
Various samples (30x)
| Sample | OD | RATIO | ||||
|---|---|---|---|---|---|---|
| Mean | SD | CV | Mean | SD | CV | |
| Negative | 0.08 | 0.013 | 15% | 0.24 | 0.04 | 15.2% |
| Low positive | 0.42 | 0.019 | 4.4% | 1.17 | 0.052 | 4.4% |
| Medium | 0.67 | 0.025 | 3.7% | 1.88 | 0.070 | 3.7% |
| High | 1.57 | 0.038 | 2.4% | 4.23 | 0.104 | 2.5% |
Conclusion:
The coefficient of variation was less than 5% for positive samples.
Cross Reactivity
The following potentially cross-reactive sera were run on the Platelia Lyme IgM assay.
Platelia™ Lyme IgM
| Disease Condition | N | Positive / Equivocal |
|---|---|---|
| Syphilis | 34 | 1 |
| CMV IgM | 5 | 1 |
| EBV IgM | 5 | 5 |
| HSV IgM | 10 | 0 |
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| Disease Condition | N | Positive / Equivocal |
|---|---|---|
| Toxoplasmosis IgM | 10 | 0 |
| Rubella IgM | 10 | 0 |
| Measles IgM | 10 | 0 |
| Mumps IgM | 10 | 2 |
| VZV IgM | 6 | 0 |
| HIV | 10 | 0 |
| Antinuclear Antibodies (ANA) | 10 | 1 |
| Heterophile Antibodies (HAMA) | 10 | 0 |
| CRP | 5 | 2 |
| SLE | 2 | 0 |
| Rheumatoid Factor | 9 | 0 |
Interfering Substances
The following potentially interfering substances were tested on the Platelia Lyme IgM.
Platelia™ Lyme IgM
| AcceptanceCriteria | Hemoglobin | Bilirubin | Triolein | Albumin | |
|---|---|---|---|---|---|
| Slope (a) | $0.85< a <1.15$ | 0.907 | 0.916 | 0.889 | 0.893 |
| Y axis intercept (b) | $<0.10$ | 0.071 | 0.050 | 0.061 | 0.073 |
| Correlation coeff | $>0.975$ | 0.999 | 0.999 | 0.997 | 0.999 |
| a+b | $0.85< a+b <1.15$ | 0.978 | 0.966 | 0.950 | 0.966 |
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:
CDC Lyme Disease Serum Panel
| Timefromonset | Platelia™ Lyme IgM | Western Blot IgM | ||||||
|---|---|---|---|---|---|---|---|---|
| Positive orequivocal | Negative | Total | %agreementwith clinicaldiagnosis (1) | Positive | Negative | Total | %agreementwith clinicaldiagnosis (1) | |
| Normals | 1 | 4 | 5 | 80.0%(4/5) | 0 | 5 | 5 | 100.0%(5/5) |
| 0-1Month | 4 | 1 | 5 | 80.0%(4/5) | 3 | 2 | 5 | 60.0%(3/5) |
| 1-2Months | 6 | 2 | 8 | 75.0%(6/8) | 7 | 1 | 8 | 87.5%(7/8) |
| 3-12Months | 14 | 3 | 17 (2) | 82.4%(14/17) | 6 | 12 | 18 | 33.3%(6/18) |
| > 1 Year | 4 | 4 | 8 | 50.0%(4/8) | 3 | 5 | 8 | 37.5%(3/8) |
| Total | 29 | 14 | 43 (2) | 74.4%(32/43) | 19 | 25 | 44 | 54.5%(24/44) |
Performance of Platelia™ Lyme IgM Assay on Lyme CDC panel
(1) Equivocal samples considered as positive; 10 One sample not tested due to insufficient sample volume
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Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with its wings spread, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the eagle. The eagle is black, and the text is also black. The logo is simple and recognizable.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Fran White Regulatory Consultant Bio-Rad 163 Cabot Street Beverly, MA 01915
JUN 2 6 2008
K081362 Re: Trade/Device Name: Platelia™ Lyme IgM Regulation Number: 21 CFR 866.3830 Regulation Name: Treponema pallidum treponemal test reagent Regulatory Class: Class II Product Code: LSR Dated: May 14, 2008 Received: May 15, 2008
Dear Ms. White:
We have reviewed your Section 510(k) premarket notification of intent to market the we have feviewed your bookers a determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices the increations for abo bannerce prior to May 28, 1976, the enactment date of the marketed in meerstate oominered prob wies 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 approval of a promation applicans of the Act. The general controls uevice, subject to the general convirements for annual registration, listing of devices, provisions of the Free ractice, 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 (I MA), it may be subject to sam adallitie 21, Code of Federal Regulations (CFR), Parts arrecting your act 1100 cc, 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 I lease be advisod that I 27 b issueser ination that your device complies with other from that FDA has made a leveral statutes and regulations administered by other requirements of the Precess of the Act's requirements, including, but not I cacrai agencies: "Four mass compey 1 CFR Part 807); labeling (21 CFR Parts 801 and minted to: registration and nothing (2) == == ================================================================================================================================ (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 advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at 240-276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. 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 (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours.
Sally attaym
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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Indications for Use
510(k) Number (if known):
KO81362
Device Name:
Platelia™ Lyme IgM
Indications for Use:
The Platelia™ Lyme IgM Assay is a qualitative test intended for use in the presumptive detection of human IgM antibodies to Borrelia burgdorferi in human serum or plasma (K3 EDTA, sodium heparin, or sodium citrate). The EIA test system should be used to test serum or plasma from patients with a history and symptoms of infection with B. burgdorferi. All positive and equivocal specimens should be re-tested with a specific, second-tier test such as Western blot. Positive second-tier results are supportive evidence of infection with B. burgdorferi. The diagnosis of Lyme disease should be made based on history and symptoms (such as erythema migrans), and other laboratory data, in addition to the presence of antibodies to B. burgdorferi. Negative results (either first or second-tier) should not be used to exclude Lyme disease.
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 OF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
Ludlow M. Cook
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) KD81362
Page 1 of 1
§ 866.3830
Treponema pallidum treponemal test reagents.(a)
Identification. Treponema pallidum treponemal test reagents are devices that consist of the antigens, antisera and all control reagents (standardized reagents with which test results are compared) which are derived from treponemal sources and that are used in the fluorescent treponemal antibody absorption test (FTA-ABS), theTreponema pallidum immobilization test (T.P.I.), and other treponemal tests used to identify antibodies toTreponema pallidum directly from infecting treponemal organisms in serum. The identification aids in the diagnosis of syphilis caused by bacteria belonging to the genusTreponema and provides epidemiological information on syphilis.(b)
Classification. Class II (performance standards).