Search Results
Found 93 results
510(k) Data Aggregation
(222 days)
Re: K251630
Trade/Device Name: Atellica IM total PSA II (tPSAII)
Regulation Number: 21 CFR 866.6010
Re: K251630
Trade/Device Name: Atellica IM total PSA II (tPSAII)
Regulation Number: 21 CFR 866.6010
Classification | Class 2 |
| Review Panel | Immunology |
| Product Code | LTJ |
| Regulation Number | 866.6010
Atellica IM total PSA II (tPSAII) assay is for in vitro diagnostic use in the quantitative measurement of total prostate-specific antigen (PSA) in human serum and plasma (EDTA and lithium-heparin) using the Atellica IM Analyzer.
This assay is indicated as an aid in the detection of prostate cancer in conjunction with a digital rectal exam (DRE) in men aged 50 years and older. Prostate biopsy is required for diagnosis of prostate cancer. This assay is further indicated as an aid in the management (monitoring) of patients with prostate cancer.
The Atellica IM total PSA II (tPSAII) assay consists of:
tPSAII ReadyPack® primary reagent pack
- Lite Reagent (10.0 mL/reagent pack): Unlabeled monoclonal mouse anti-fPSA antibody (~250 ng/mL); monoclonal mouse anti-PSA antibody (~180 ng/mL) labeled with acridinium ester; buffer; bovine serum albumin (BSA); preservative.
- Solid Phase (20.0 mL/reagent pack): Monoclonal mouse anti-PSA antibody (~3.5 μg/mL) labeled with biotin and bound to streptavidin paramagnetic particles; buffer; BSA; bovine gamma globulin (BGG); sodium azide (< 0.1%); preservative.
- Storage: Unopened at 2–8°C (Until expiration date on product), Onboard (42 days).
tPSAII CAL (2.0 mL/vial): Purified PSA from human seminal fluid in buffer; BSA; NaN3 (< 0.1%).
- Storage: Unopened at 2–8°C (Until expiration date on product), Opened at 2–8°C (30 days), On the system at room temperature (8 hours).
The tPSAII assay will have two configurations: 100 tests kit and 500 tests kit (5 x 100T in the carton).
N/A
Ask a specific question about this device
(264 days)
**
Trade/Device Name: ADVIA Centaur Cytokeratin Fragment 21-1
Regulation Number: 21 CFR 866.6010
Regulation section: 21 CFR § 866.6010, Tumor-associated antigen immunological test system
2.
|
| Device Type | In vitro diagnostic | Same |
| Classification | Class II | Same |
| CFR section | 866.6010
The ADVIA Centaur Cytokeratin Fragment 21-1 (CYFRA) assay is for in vitro diagnostic use in the quantitative measurement of cytokeratin 19 fragments in human serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur XPT system.
The measurement of cytokeratin 19 is used as an aid in monitoring disease progression during the course of disease and treatment in lung cancer patients. Serial testing for patient CYFRA 21-1 assay values should be used in conjunction with other clinical information used for monitoring lung cancer.
The ADVIA Centaur Cytokeratin Fragment 21-1 assay includes 1 ReadyPack primary reagent pack containing ADVIA Centaur CYFRA Lite Reagent and Solid Phase and ADVIA Centaur CYFRA master curve card.
The ReadyPack consists of the following:
ADVIA Centaur Cytokeratin Fragment 21-1 ReadyPack primary reagent pack; Liquid Lite Reagent 10.0 mL/reagent pack KS19.1 monoclonal antibody acridinium conjugate in buffer containing bovine serum albumin; surfactant; and preservatives.
ADVIA Centaur Cytokeratin Fragment 21-1 ReadyPack primary reagent pack; Liquid Solid Phase Reagent 17.5 mL/reagent pack BM19.21 monoclonal antibody coupled to magnetic microparticle bead in buffer containing bovine serum albumin; surfactant; and preservatives.
ADVIA Centaur Multi-Diluent13 ReadyPack ancillary reagent pack; 2×10.0mL/reagent pack; Buffer; surfactant; sodium azide (< 0.1%)
This assay is a fully automated 1-step sandwich immunoassay using acridinium ester chemiluminescent technology. The Solid Phase contains magnetic microparticles coated with anti-CYFRA 21-1 BM19.21 mouse monoclonal antibody. The Lite Reagent consists of acridinium ester-labeled anti-CYFRA 21-1 KS19.1 mouse monoclonal antibody. A direct relationship exists between the amount of CYFRA 21-1 present in the patient sample and the amount of relative light units (RLUs) detected by the system.
N/A
Ask a specific question about this device
(267 days)
The Atellica IM Thyroglobulin (Tg) assay is for in vitro diagnostic use in the quantitative measurement of thyroglobulin in human serum and plasma (EDTA and lithium heparin) using the Atellica IM Analyzer.
Thyroglobulin measurements are used as an aid in monitoring differentiated thyroid cancer patients who have undergone thyroidectomy with or without radioiodine ablation.
The Atellica IM Thyroglobulin (Tg) assay includes:
- Tg ReadyPack primary reagent pack:
- Lite Reagent: mouse monoclonal anti-human Tg antibody labeled with acridinium ester (~1.13 μg/mL); bovine serum albumin (BSA); mouse IgG; buffer; stabilizers; preservatives (7.5 mL/reagent pack).
- Solid Phase: streptavidin-coated paramagnetic microparticles preformed with biotinylated mouse monoclonal antihuman Tg antibody (~267 μg/mL); BSA; mouse IgG; buffer; stabilizers; preservatives (15.0 mL/reagent pack).
- Ancillary Well Reagent: BSA; bovine gamma globulin; buffer; preservatives (6.0 mL/reagent pack).
- Tg CAL: After reconstitution, human thyroglobulin; BSA; buffer; stabilizers; preservatives (2.0 mL/vial).
The following devices are sold separately:
- Atellica IM Tg MCM:
- MCM 1: After reconstitution, bovine serum albumin (BSA); buffer; stabilizers; preservatives (1.0 mL/vial).
- MCM 2–5: After reconstitution, various levels of human thyroglobulin; BSA; buffer; stabilizers; preservatives (1.0 mL/vial).
Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided FDA 510(k) summary for the Atellica IM Thyroglobulin (Tg) assay:
Device: Atellica IM Thyroglobulin (Tg) Assay
Purpose: Quantitative measurement of thyroglobulin in human serum and plasma as an aid in monitoring differentiated thyroid cancer patients who have undergone thyroidectomy with or without radioiodine ablation.
1. Table of Acceptance Criteria and Reported Device Performance
The provided document describes various performance characteristics, which serve as acceptance criteria for the device. The reported performance is directly from the summary.
| Acceptance Criteria Category | Specific Acceptance Criteria (implicit from study design) | Reported Device Performance |
|---|---|---|
| Detection Capability | LoB, LoD, LoQ determined per CLSI EP17-A2 | LoB: 0.039 ng/mL (0.059 pmol/L) LoD: 0.044 ng/mL (0.067 pmol/L) LoQ: 0.050 ng/mL (0.076 pmol/L) |
| Precision | Precision determined per CLSI EP05-A3 (within-laboratory and repeatability) | Repeatability (CV%): 1.2% - 6.4% across various concentrations Within-Laboratory Precision (CV%): 2.3% - 9.0% across various concentrations |
| Reproducibility | Reproducibility determined per CLSI EP05-A3 (across sites, runs, days) | Reproducibility (CV%): 1.9% - 5.8% across various concentrations |
| Linearity | Linearity determined per CLSI EP06-ed2 within stated assay range | Linear for 0.050–150 ng/mL (0.076–227 pmol/L) |
| Specimen Equivalence | Performance equivalence across serum, EDTA plasma, lithium heparin plasma | Performance confirmed equivalent across serum, EDTA plasma, lithium heparin plasma, and associated gel barrier tubes. |
| Interferences (HIL) | Bias < 10% for Hemoglobin, Bilirubin, Lipemia at specified concentrations | No bias > 10% observed for tested HIL substances. |
| Interferences (Other Substances) | Bias < 10% for various common substances/medications/biomarkers at specified concentrations | No bias > 10% observed for tested other substances. |
| Cross-Reactivity | Cross-reactivity < 1.0% for specified substances (T3, T4, TSH, Galectin-3, T2) | Cross-reactivity < 1.0% for tested substances. |
| Reagent Stability | Defined on-board and reconstituted calibrator stability | 28 days on-board; Calibrators stable 45 days (2-8°C) / 60 days (≤ -20°C, thaw once). |
| Sample Stability | Defined stability for various sample types and storage conditions | Stable 3-4 days (2-8°C), 4 days (RT), 12-24 months (frozen); ≤ 4 freeze-thaw cycles. |
| High Dose Hook Effect | No hook effect within a specified concentration range | No hook effect up to 80,000 ng/mL (121,200 pmol/L). |
| Expected Values | Reference intervals established per CLSI EP28-A3c | Healthy Adults: 2.44–74.9 ng/mL Post-thyroidectomy adults: < 1.27 ng/mL |
| Clinical Performance | Sensitivity and specificity calculated by comparing assay results to structural disease (SD) at a defined cut-off (0.2 ng/mL). Confidences intervals for these parameters. | Sensitivity: 98.2% (95% CI: 94.6%, 100.0%) Specificity: 53.4% (95% CI: 47.8%, 58.0%) PPV: 10.0% (95% CI: 8.7%, 11.2%) NPV: 99.8% (95% CI: 99.5%, 100.0%) |
2. Sample Size Used for the Test Set and Data Provenance
- Clinical Performance Test Set Sample Size: 291 serum samples collected from 189 subjects.
- Data Provenance:
- The document states "A prospective, multi-center study was conducted." This indicates prospective data collection across multiple sites.
- The country of origin is not explicitly stated in the provided text.
- All samples were from subjects diagnosed with differentiated thyroid cancer, 6 or more weeks following thyroidectomy or radioiodine ablation.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
- The document does not specify the number of experts or their qualifications for establishing the ground truth (structural disease). It simply states: "SD [Structural Disease] was established and classified as either positive or negative by cross-sectional or functional imaging results."
- This suggests that the ground truth was derived from standard clinical imaging reports rather than a consensus of independent expert readers specifically for this study.
4. Adjudication Method for the Test Set
- The document does not describe an adjudication method for the test set's ground truth (structural disease). It implies that the imaging results themselves provided the classification. This means there was no adjudication process as typically seen with multiple human readers reviewing images.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
- No, an MRMC comparative effectiveness study was not done.
- This study is for an in vitro diagnostic (IVD) assay (a lab test), not an AI-assisted imaging or diagnostic tool where human readers work with or without AI. The performance metrics presented are for the analytical and clinical performance of the assay itself, comparing its results to a ground truth (structural disease status), not to human reader performance or improvement with AI.
6. If a Standalone Performance Study Was Done
- Yes, this is effectively a standalone (algorithm only) performance study.
- The Atellica IM Tg assay is an automated in vitro diagnostic device. Its performance characteristics (sensitivity, specificity, precision, linearity, etc.) are evaluated intrinsically, independent of human interpretation of the assay result values. The output is a quantitative measurement of thyroglobulin.
7. The Type of Ground Truth Used
- Ground truth for clinical performance: Structural disease (SD) status obtained from "cross-sectional or functional imaging results."
- Ground truth for analytical performance (LoB, LoD, LoQ, Precision, etc.): Established through laboratory protocols and reference materials (e.g., CLSI guidelines, certified reference materials like BCR CRM 457, spiked samples, control materials).
8. The Sample Size for the Training Set
- The document does not specify a separate training set or its sample size for the Atellica IM Tg assay.
- For IVD assays like this, the "training" is typically inherent in the assay's development and optimization process (e.g., reagent formulation, calibration curve development), which uses various known samples and standards, rather than a distinct, labeled "training dataset" as would be seen for a machine learning algorithm. The performance characteristics studies presented are akin to a "verification/validation set."
9. How the Ground Truth for the Training Set Was Established
- As a traditional IVD assay, there isn't a "training set" in the sense of a machine learning model.
- Ground truth for assay development and calibration: This would have been established using reference materials (like BCR CRM 457), characterized control samples, and potentially a large panel of clinically characterized patient samples used during the assay's development and optimization phases. These activities are part of the broader product development lifecycle rather than a distinct "training set" with ground truth generated by experts in the context of a clinical study for submission. Standardization is explicitly noted as traceable to BCR CRM 457, which serves as a primary standard for establishing the quantitative accuracy of the assay.
Ask a specific question about this device
(85 days)
Chaska, Minnesota 55318
Re: K240927
Trade/Device Name: Access Thyroglobulin Regulation Number: 21 CFR 866.6010
Classification Description: Tumor-associated antigen immunological test system Classification Requlation: 21 CFR 866.6010
Access Thyroglobulin assay is a paramagetic particle, chemiluminescent immunossay for the quantitative determination of thyroglobulin levels in human serum and plasma using the Access Immunoassay Systems. This device is intended to aid in monitoring for the presence of persistent or recurrent/metastatic disease in patients who have differentiated thyroid cancer (DTC) and have had thyroid surgery (with or without ablative therapy), and who lack serum thyroglobulin antibodies.
The Access Thyroglobulin assay consists of the reagent pack and calibrators. Other items needed to run the assay include the Access Thyroglobulin Sample Diluent, substrate and wash buffer. The Access Tg assay along with the Access wash buffer and substrate are designed for use with the Access Immunoassay Systems in a clinical laboratory setting.
Lumi-Phos PRO substrate was used with this pack. The modification does not affect the indications of the device or alter the fundamental scientific technology of the device.
The provided text is a 510(k) summary for the Access Thyroglobulin assay, which is a diagnostic device and not an AI/ML device. Therefore, many of the requested categories related to AI/ML device studies, such as "Number of experts used to establish the ground truth," "Adjudication method," "MRMC comparative effectiveness study," and "sample size for the training set," are not applicable.
However, I can extract the relevant information regarding acceptance criteria and study results for this diagnostic device.
Acceptance Criteria and Reported Device Performance for Access Thyroglobulin Assay (K240927)
1. Table of Acceptance Criteria and the Reported Device Performance
| Performance Metric | Acceptance Criteria (Implicit from reported results and CLSI guidelines) | Reported Device Performance (Access Thyroglobulin on Dxl 9000) |
|---|---|---|
| Method Comparison | Slope of 1.00 (95% CI covering 1.00); Intercept of 0.00 (95% CI covering 0.00); High Correlation Coefficient (R close to 1.00) | Slope: 1.00 (0.99 - 1.00); Intercept: 0.0044 (-0.029 - 0.021); Correlation Coefficient R: 1.00 |
| Imprecision (Within-lab/Total) | CV ≤ 10.0% at concentrations > 1.0 ng/mL; SD ≤ 0.1 ng/mL at concentrations ≤ 1.0 ng/mL | Achieved across all tested concentrations (e.g., 8.4% at 0.30 ng/mL, 6.8% at 5.5 ng/mL, 6.3% at 22 ng/mL, 2.5% at 111 ng/mL, 3.6% at 376 ng/mL, 3.6% at 417 ng/mL) |
| Reproducibility | Not explicitly stated as a separate acceptance criterion, but results imply meeting acceptable reproducibility for clinical use. | Example: Within-run CV 5.9% (0.34 ng/mL), Reproducibility CV 7.4% (0.34 ng/mL); Within-run CV 2.5% (402 ng/mL), Reproducibility CV 5.9% (402 ng/mL) |
| Linearity | Assay demonstrates linearity across the measuring interval. | Demonstrated linearity across the measuring interval. |
| Limit of Blank (LoB) | Not explicitly stated as a numerical criterion, but a low value is expected for accurate detection. | 0.03 ng/mL |
| Limit of Detection (LoD) | Not explicitly stated as a numerical criterion, but a low value is expected for accurate detection. | 0.05 ng/mL |
| Limit of Quantitation (LoQ) ≤20% within-lab CV | ≤ 0.1 ng/mL at 20% within-lab CV (explicitly stated criteria) | 0.1 ng/mL |
2. Sample sizes used for the test set and the data provenance
- Method Comparison: N = 187 samples. Data provenance is not specified (e.g., country of origin, retrospective/prospective).
- Imprecision: For each sample, N = 88 or 80. Data provenance is not specified.
- Reproducibility: For each sample, N = 75. Data provenance is not specified.
- Linearity, LoB, LoD, LoQ: Sample sizes for specific points within the linearity study or number of samples for LoB/LoD/LoQ determinations are not explicitly given, but the studies were conducted using "multiple samples," "multiple reagent lots," and "multiple days." Data provenance is not specified.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This is a quantitative immunoassay for measuring thyroglobulin levels. The 'ground truth' for such a device is established by the analytical reference measurement procedures using a reference method or known concentrations, rather than expert consensus on diagnostic images or clinical assessments. Therefore, this question is not applicable in the context of this device.
4. Adjudication method for the test set
Not applicable for a quantitative immunoassay. The comparison is statistical analysis of measured values against a predicate device or expected values from reference materials.
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
Not applicable. This is not an AI/ML device involving human readers or interpretation.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
The device is an automated immunoassay system. The performance studies ("Method Comparison," "Imprecision," "Reproducibility," "Linearity," "Detection Capability") represent the standalone performance of the assay and instrument without human interpretation of raw signals influencing the final quantitative result.
7. The type of ground truth used
For this immunoassay device, the "ground truth" implicitly refers to:
- Reference measurements from the predicate device (Access 2 Immunoassay System): Used for the method comparison study.
- Known concentrations/reference materials: Used to assess imprecision, linearity, and detection capabilities (LoB, LoD, LoQ) against expected values.
8. The sample size for the training set
Not applicable. This is a traditional diagnostic device, not an AI/ML device that requires a training set.
9. How the ground truth for the training set was established
Not applicable, as there is no training set for this type of device.
Ask a specific question about this device
(18 days)
Chaska, Minnesota 55318
Re: K241423
Trade/Device Name: Access Thyroglobulin Regulation Number: 21 CFR 866.6010
Classification Description: Tumor-associated antigen immunological test system Classification Regulation: 21 CFR 866.6010
Access Thyroglobulin assay is a paramagetic particle, chemiluminescent immunossay for the quantitative determination of thyroglobulin levels in human serum and plasma using the Access Immunoassay Systems. This device is intended to aid in monitoring for the presence of persistent or recurrent/metastatic disease in patients who have differentiated thyroid cancer (DTC) and have had thyroid surgery (with or without ablative therapy), and who lack serum thyroglobulin antibodies.
The Access Thyroqlobulin assay consists of the reagent pack and calibrators. Other items needed to run the assay include the Access Thyroglobulin Sample Diluent, substrate and wash buffer. The Access Tq assay along with the Access wash buffer and substrate are designed for use with the Access Immunoassay Systems in a clinical laboratory setting.
The change does not impact or change the other components that are used with this reagent pack. The modification does not affect the indications of the device or alter the fundamental scientific technology of the device.
A description of the reagent pack is provided below.
| Well | Ingredients |
|---|---|
| R1a: | Dynabeads* paramagnetic particles coated with streptavidinand coupled to biotinylated mouse monoclonalantithyroglobulin antibodies, suspended in a TRIS buffer withprotein (bovine), < 0.1% sodium azide, and 0.1% ProClin**300. |
| R1b: | Mouse monoclonal anti-thyroglobulin-alkaline phosphatase(bovine) conjugate in a TRIS buffer with protein (bovine,murine), < 0.1% sodium azide, and 0.1% ProClin 300. |
| R1c: | HEPES buffer with protein (bovine and mouse), < 0.1% sodiumazide, and 0.5% ProClin 300. |
The provided document is a 510(k) Premarket Notification from the FDA for the Access Thyroglobulin assay. It does not describe an AI/ML-based medical device. Therefore, many of the requested criteria about AI/ML studies (such as MRMC studies, ground truth establishment for training sets, number of experts for test set ground truth, etc.) are not applicable to this submission.
The acceptance criteria and study proving the device meets them are related to the analytical performance of an immunoassay, not a software algorithm.
Here's a breakdown based on the provided text, addressing the applicable points and noting where information is not present or not relevant to AI/ML:
1. A table of acceptance criteria and the reported device performance
The document focuses on demonstrating substantial equivalence to a predicate device, primarily through a matrix comparison study for a new sample type (plasma in addition to serum). The "acceptance criteria" are implied by the statistical analyses and acceptable ranges for slope, intercept, and correlation coefficient in the matrix comparison, aiming for agreement between the new sample type and the established serum sample type.
Acceptance Criteria (Implied by Study Design for Matrix Comparison):
For the Matrix Comparison study, the implicit acceptance criteria are that the Passing-Bablok linear regression results (slope, intercept, and correlation coefficient) demonstrate substantial equivalence between the new sample types (Li-heparin plasma, Na-heparin plasma) and serum. While explicit numeric acceptance criteria are not stated, typically for such comparisons, a slope close to 1, an intercept close to 0, and a high correlation coefficient (e.g., >0.97) are expected within their confidence intervals.
Reported Device Performance (Matrix Comparison):
| Plasma/Serum | N | Range (ng/mL) | Slope (95% CI) | Intercept (95% CI) | Correlation Coefficient (r) |
|---|---|---|---|---|---|
| Li-heparin plasma vs Serum | 45 | 0.227 to 494.070 | 1.000 (0.983; 1.015) | 0.163 (-0.212; 0.712) | 0.999 |
| Na-heparin plasma vs Serum | 45 | 0.227 to 494.070 | 1.021 (1.010; 1.039) | 0.147 (-0.246; 0.952) | 0.999 |
Other Performance Claims Transferred from Predicate:
The document states that claims for "method comparison, imprecision, reproducibility, high-dose hook effect, linearity, dilution recovery, detection capability and analytical specificity are being transferred from file K220972." This implies these studies were performed and met acceptance criteria for the predicate device, and the current modification (addition of plasma sample type) does not invalidate them. Explicit tables for these are not in the provided text.
2. Sample sizes used for the test set and the data provenance
- Test Set Sample Size: For the Matrix Comparison study, 45 matched sets of serum and plasma samples were used for each comparison (Li-heparin plasma vs Serum, and Na-heparin plasma vs Serum). The minimum specified was 40 matched sets.
- Data Provenance: The document does not specify the country of origin of the data or whether the study was retrospective or prospective. Given it's a clinical lab device, the samples would typically be from clinical settings.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This is not applicable as the device is an immunoassay, not an AI/ML device relying on human interpretation of images or other complex data for ground truth. The "ground truth" here is the quantitative measurement of thyroglobulin by the predicate method (serum measurement) against which the new sample type (plasma measurement) is compared. The reference values are analytical measurements, not expert consensus.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
Not applicable for an immunoassay analytical validation. The ground truth (serum concentration) is established by the assay itself, not by human adjudication.
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
Not applicable. This is not an AI/ML device, and there are no "human readers" interpreting images assisted by AI.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, in a sense. The "standalone" performance for this device refers to its analytical performance as a laboratory test. The Matrix Comparison study assesses the device's capability to accurately measure thyroglobulin in plasma samples compared to serum samples, without human interpretive input affecting the measurement itself. The results shown in point 1 demonstrate this "standalone" analytical performance.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The ground truth for the matrix comparison study was the quantitative thyroglobulin concentration measured in human serum using the previously cleared Access Thyroglobulin assay. The new sample types (plasma) were compared to these established serum values.
8. The sample size for the training set
Not applicable. This is not an AI/ML device that requires a training set. The assay's parameters are determined through reagent development and analytical validation, not machine learning training.
9. How the ground truth for the training set was established
Not applicable, as there is no training set for this type of device.
Ask a specific question about this device
(80 days)
Chaska, Minnesota 55318
Re: K240479
Trade/Device Name: Access OV Monitor Regulation Number: 21 CFR 866.6010
OV Monitor Common Name: OV Monitor Chemiluminescence Immunoassay Classification Regulation: 21 CFR 866.6010
The Access OV Monitor assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of CA 125 antigen levels in human serum and plasma using the Access Immunoassay Systems. This device is indicated for use in the measurement of CA 125 antigen to aid in the management of ovarian cancer patients. Serial testing for patient CA 125 antigen concentrations should be used in conjunction with other clinical methods used for monitoring ovarian cancer.
The Access OV Monitor assay is a sandwich immunoenzymatic assay. The Access OV Monitor assay consists of the reagent pack and calibrators. Other items needed to run the assay include substrate and wash buffer. The Access OV Monitor assay reagent pack, Access OV Monitor assay calibrators, along with the UniCel Dxl Wash Buffer II are designed for use with the Dxl 9000 Access Immunoassay Analyzer in a clinical laboratory setting.
The document provided is an FDA 510(k) clearance letter and a 510(k) summary for the Beckman Coulter Access OV Monitor assay. This device is an in vitro diagnostic (IVD) immunoassay for measuring CA 125 antigen levels to aid in the management of ovarian cancer patients.
The information requested pertains to the performance study design for AI/ML-based diagnostic devices, which is typically quite different from the validation of an immunoassay. Specifically, sections like "Number of experts used to establish ground truth", "Adjudication method", "Multi-Reader Multi-Case (MRMC) comparative effectiveness study", and "Effect size of how much human readers improve with AI vs without AI assistance" are relevant to AI/ML device validation studies, not typically to immunoassay validation.
An immunoassay like the Access OV Monitor is validated by demonstrating its analytical performance characteristics (e.g., precision, linearity, limits of detection) and method comparison against a predicate device, rather than by human reader studies or expert consensus on images.
Therefore, many of the requested fields are not applicable to this type of device and the information provided in the document. However, I will do my best to extract the relevant information where it exists and explicitly state when a requested criteria is not applicable.
Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided FDA 510(k) summary for the Access OV Monitor assay:
Device: Access OV Monitor Immunoassay
The study primarily focuses on demonstrating the substantial equivalence of the new Access OV Monitor assay run on the Dxl 9000 Access Immunoassay Analyzer to its predicate device (Access OV Monitor assay on the Access Immunoassay System, K023597). This is achieved by comparing their analytical performance characteristics.
1. Table of Acceptance Criteria and Reported Device Performance
Note: The document does not explicitly state "acceptance criteria" in a tabulated format for each performance metric, but rather lists the study results and implies they met predefined criteria (e.g., "met the acceptance criteria of R2 ≥ 0.90 and slope 1.00 ± 0.09"). The "acceptance criteria" column below is inferred from these statements and typical IVD validation expectations.
| Performance Metric | Implied Acceptance Criteria (Inferred from text) | Reported Device Performance (Access OV Monitor on Dxl 9000) |
|---|---|---|
| Method Comparison | ||
| R² (Concordance) | R² ≥ 0.90 | 1.00 |
| Slope | 1.00 ± 0.09 | 0.98 (95% CI: 0.97 - 0.99) |
| Intercept | (Not explicitly stated numeric criterion, evaluated with CI) | -0.14 (95% CI: -0.38 - 0.13) |
| Imprecision (Within-Laboratory/Total %CV) | (Performance depends on concentration level; generally, lower %CV desired) | Ranged from 2.6% to 6.1% for concentrations > 15 U/mL. SD of 0.2 for concentrations ≤ 15 U/mL. (See full table in source document) |
| Linearity | Device should be linear across its analytical measuring interval | Linear throughout the analytical measuring interval of approximately 2.0 - 5,000 U/mL |
| Limit of Blank (LoB) | (Specific value to be determined and met; typically lowest possible) | 0.5 U/mL |
| Limit of Detection (LoD) | (Specific value to be determined and met) | 0.7 U/mL |
| Limit of Quantitation (LoQ) | (Specific value to be determined and met) | 2.0 U/mL |
| Measuring Range | Consistent with predicate and intended use | 2.0 - 5,000 U/mL (Compared to predicate's 0.5 - 5000 U/mL) |
| Sample Volume | (Not an "acceptance criterion" but a characteristic change) | 30 uL (Predicate: 25 uL) |
| Substrate | (Not an "acceptance criterion" but a characteristic change) | Lumi-Phos PRO substrate (Predicate: Access Substrate) |
2. Sample Size Used for the Test Set and Data Provenance
- Method Comparison Study: 152 samples.
- Imprecision Study: 120 replicates per sample level (e.g., Sample 1, Sample 2, etc, see N column in table). "Multiple samples" tested in triplicate in 2 runs per day for a minimum of 20 days.
- Data Provenance: The document does not specify the country of origin of the data or whether samples were retrospective or prospective. It is typical for immunoassay validation studies to use a mix of clinical samples (retrospective) and spiked samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
- Not Applicable. This is an immunoassay, not an AI/ML diagnostic imaging device. The "ground truth" for the performance characteristics of an immunoassay is its analytical measurements, often compared against a reference method or validated predicate, not expert consensus on images.
4. Adjudication Method for the Test Set
- Not Applicable. See point 3.
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
- Not Applicable. This is an immunoassay, not an AI/ML diagnostic imaging device intended to assist human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
- Not Applicable. This is an immunoassay, the "performance" is the analytical output of the instrument-reagent system itself, which is inherently "standalone" in generating the quantitative result. There's no separate "algorithm" performance in the sense of an AI model.
7. The Type of Ground Truth Used
For an immunoassay, "ground truth" refers to the true concentration of the analyte, which is established through:
- Reference Methods: Highly accurate and precise methods not explicitly detailed but implied by standard validation practices.
- Comparative Measurements against a Predicate Device: The current study uses the predicate device (Access OV Monitor on the Access Immunoassay System) as its primary comparator to establish substantial equivalence.
- Known Concentrations: For linearity and limits studies, samples are often prepared at known concentrations (e.g., by diluting a high-concentration sample).
8. The Sample Size for the Training Set
- Not Applicable. This is an immunoassay, not an AI/ML device that requires a "training set" in the machine learning sense. The assay is "trained" or developed through biological and chemical methods, and its performance is characterized through analytical validation.
9. How the Ground Truth for the Training Set was Established
- Not Applicable. See point 8.
Ask a specific question about this device
(90 days)
Chaska, Minnesota 55318
Re: K240403
Trade/Device Name: Access BR Monitor Regulation Number: 21 CFR 866.6010
Classification Name: Tumor-associated antigen immunological test system Classification Regulation: (21 CFR 866.6010
The Access BR Monitor assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of CA 15-3 antigen levels in human serum and plasma (heparin) using the Access Immunoassay Systems. This device is indicated for use in the measurement of CA 15-3 antigen to aid in the management of breast cancer patients. Serial testing for CA 15-3 antigen concentrations should be used in conjunction with other clinical methods for monitoring breast cancer.
The Access BR Monitor assay, Access BR Monitor Calibrators, and the Access Immunoassay analyzers comprise the Dxl 9000 Access Immunoassay Amalyzer for the quantitative determination of CA 15-3 antigen levels in human serum and plasma (heparin) using the Dxl 9000 Access Immunoassay Analyzer.
Here's a breakdown of the acceptance criteria and study information for the Access BR Monitor device, based on the provided FDA document:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Method Comparison | Not explicitly stated as numerical acceptance criteria for slope, intercept, or correlation coefficient, but inferred by comparison to predicate. | Comparing Dxl 9000 to Access 2: - Slope: 0.95 (95% CI: 0.94 - 0.96) - Intercept: 0.70 (95% CI: 0.31 - 1.4) - Correlation Coefficient (R): 1.00(Implied acceptance if comparable to predicate) |
| Imprecision (Within-Laboratory) | - SD ≤ 1.5 U/mL at concentrations ≤ 15 U/mL - CV ≤ 10.0% at concentrations ≥ 15 U/mL | Met acceptance criteria. - Sample 1 (4.2 U/mL): SD 0.1, CV 3.4% - Sample 2 (19 U/mL): CV 2.9% - Sample 3 (34 U/mL): CV 3.2% - Sample 4 (79 U/mL): CV 3.0% - Sample 5 (105 U/mL): CV 3.0% - Sample 6 (425 U/mL): CV 3.2% - Sample 7 (825 U/mL): CV 4.0% |
| Linearity | Not explicitly stated numerically, but stated as being linear throughout the analytical measuring interval. | Met acceptance criterion, indicating linearity throughout the analytical measuring interval (0.8 – 1,000 U/mL). |
| Limit of Blank (LoB) | 0.4 U/mL | Met acceptance criterion. LoB estimate: 0.1 U/mL. |
| Limit of Detection (LoD) | 0.5 U/mL | Met acceptance criterion. LoD estimate: 0.3 U/mL. |
| Limit of Quantitation (LoQ) | Not explicitly stated numerically, but two different LoQ definitions are provided. | - 20% CV LoQ estimate: 0.3 U/mL - LoQ at 20% within-laboratory imprecision estimate: 0.8 U/mL |
2. Sample Size Used for the Test Set and Data Provenance
- Method Comparison: N = 163 samples.
- Data Provenance: Not specified in the provided text (e.g., country of origin, retrospective or prospective).
- Imprecision:
- Sample 1, 2: N = 126
- Sample 3, 4, 5, 6, 7: N = 120
- Data Provenance: Not specified.
- Linearity, LoB, LoD, LoQ: Sample sizes not explicitly stated for these specific studies, beyond the "N" for method comparison and imprecision.
- Data Provenance: Not specified.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
There is no mention of experts or ground truth establishment for the test set in the provided document. The studies described are analytical performance studies (method comparison, imprecision, linearity, limits) of an immunoassay device, which typically compare the device's measurements against a reference method or predetermined values, not against expert consensus on clinical diagnoses.
4. Adjudication Method for the Test Set
Not applicable, as the studies are analytical performance assessments of an immunoassay, not studies involving human interpretation or adjudication of clinical cases.
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
No, an MRMC comparative effectiveness study was not done. This device is an immunoassay for measuring CA 15-3 antigen levels, not an AI-assisted diagnostic imaging or interpretation tool that would involve human readers.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done
Yes, the studies described (Method Comparison, Imprecision, Linearity, LoB, LoD, LoQ) are all examples of standalone performance evaluations of the immunoassay system. The device itself (Access BR Monitor on the Dxl 9000 Access Immunoassay Analyzer) operates as an "algorithm only" in the sense that it automates the measurement of the analyte; there is no human-in-the-loop for the measurement process itself.
7. The Type of Ground Truth Used
The "ground truth" for these analytical studies is either:
- Reference method/Predicate device results: For the method comparison study, the Access 2 Immunoassay System served as the reference (predicate) for comparison.
- Known concentrations/values: For studies like Imprecision, Linearity, LoB, LoD, and LoQ, calibrated samples or controls with known or expected analyte concentrations are used as the reference against which the device's measurements are assessed. The document refers to "predetermined values" or "calculated estimates" based on established statistical methods (e.g., CLSI guidelines).
8. The Sample Size for the Training Set
Not applicable. This device is an immunoassay, not a machine learning or AI model that requires a "training set." Its calibration is established through a stored calibration curve, as mentioned in the "Comparison of Technological Characteristics" table.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" in the context of an AI/ML model for this immunoassay device. The "calibration curve" for the immunoassay is established using calibrators, which are materials with known concentrations of the analyte, manufactured and tested according to quality control standards.
Ask a specific question about this device
(90 days)
LL55 4EL United Kingdom
Re: K233946
Trade/Device Name: IMMULITE 2000 BR-MA Regulation Number: 21 CFR 866.6010
Classification Name: | Tumor-associated antigen immunological test system |
| Regulation Number: | 21 CFR 866.6010
For in vitro diagnostic use with the IMMULITE® 2000 Systems Analyzers - for the quantitative measurement of CA15-3 antigen in human serum and plasma, as an aid in the detection of recurrence in previously treated stage III breast cancer patients, and in the management of metastatic breast cancer patients by monitoring disease progression or response to treatment. Serial testing for patient CA15-3 values should be used in conjunction with other clinical methods used for detecting early recurrence in stage III disease and for monitoring response to treatment in patients with metastatic breast cancer.
The IMMULITE® 2000 BR-MA assay was cleared under K013984. The components of the cleared assay were modified to reduce biotin interference. The modified IMMULITE® 2000 BR-MA Assay is comprised of the following components: BR-MA Bead Pack (L2BR12), BR-MA Reagent Wedge (L2BRA2) - Well 1, BR-MA Reagent Wedge (L2BRA2) - Well 2, and BR-MA Adjustors (LBRL, LBRH). The IMMULITE 2000 BR-MA is a solid-phase, two-step chemiluminescent immunometric assay. There are two incubation cycles of 30 minutes each. During the initial 30-minute cycle, the patient sample is incubated with biotinylated antibody coated bead (bead pack) and a buffer (reagent wedge well 1). The biotinylated antibody on the bead captures the antigen in the patient sample. On completion of the first 30-minute cycle, unbound sample/buffer are then removed via a centrifugal wash. During the second 30-minute cycle, alkaline phosphatase antibody conjugate in buffer (reagent wedge well 2) is added to complete the bead pair immunocomplex sandwich consisting of capture Ab-antigen-detection Ab. On completion of the second 30-minute cycle, unbound conjuqate is removed by centrifugal wash. The amount of alkaline phosphatase bound is directly proportional to the patient sample. Following the two 30-minute incubation periods. IMMULITE chemiluminescent substrate (L2SUBM) is added for a further 5-minute incubation period to generate the luminogenic reaction. The chemiluminescent substrate undergoes hydrolysis in the alkaline phosphatase to yield an unstable intermediate, which then emits photons. The sustained emissions are measured by the luminometer. The resulting relative light units are proportional to the concentration of CA15-3 in the sample, which is expressed as U/mL.
The retrieved document describes the acceptance criteria and performance of the IMMULITE 2000 BR-MA assay, which is a tumor-associated antigen immunological test system for CA15-3. The modifications to the device primarily focus on reducing biotin interference.
Here's a breakdown of the requested information based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly list "acceptance criteria" against "reported device performance" in a single table. Instead, it presents performance characteristic studies that implicitly demonstrate the device meets certain standards. I've aggregated these into a table format below, using typical performance metrics for such devices. The "Acceptance Criteria" are implied by common laboratory standards (e.g., CLSI guidelines) and the successful outcome of the tests.
| Performance Metric | Implied Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Detection Limits | Determined in accordance with CLSI EP17-A2. | LoB = 0.21 U/mL, LoD = 0.30 U/mL, LoQ = 1 U/mL. |
| Linearity/Measuring Interval | Linearity across the assay range, ADL ≤ 15% at each level. | Confirmed across the assay range (1 - 300 U/mL) with acceptable ADL at each individual level. |
| Method Comparison | Strong correlation with the currently marketed device. | N=274 serum samples. Correlation Coefficients: Lot 1 ($Y = 0.98x + 0.71$) = 0.989; Lot 2 ($Y = 0.99x + 0.16$) = 0.992; Lot 3 ($Y = 1.04x - 0.79$) = 0.990. Statistical method: Passing-Bablok regression. |
| Assay Precision (Within-Lab) | %CV within acceptable limits for the assay. | 5 serum samples tested. %CV ranged from 7.1% to 7.4% (Total/Within-Lab). Within-Run %CV ranged from 4.8% to 6.8%. |
| Assay Reproducibility | %CV within acceptable limits across multiple lots and days. | 5 serum samples tested across 3 reagent lots. Total Reproducibility %CV ranged from 4.5% to 6.0%. |
| Recovery | Expected recovery within an acceptable range (e.g., 90-110%). | % Recovery for spiked samples ranged from 92% to 105%. |
| Interference | No significant interference from tested endogenous/exogenous substances up to specified concentrations. | No significant interference observed for Hemoglobin (381 mg/dL), Conjugated and Unconjugated Bilirubin (200 mg/L), Intralipid (3000 mg/dL), Biotin (3500 ng/mL), and several chemotherapy drugs (e.g., 5-Fluorouracil 1000 µg/mL). Note: The key improvement is reduced biotin interference from 100 ng/mL (predicate) to 3500 ng/mL. |
| Cross-Reactivity | No detectable cross-reactivity with specified tumor markers. | No detectable specificity (cross-reactivity) for Alpha-fetoprotein, CA125, CA19-9, and Carcinoembryonic Antigen at high concentrations. |
| Hook Effect | No hook effect within the assay range and beyond. | No hook effect observed up to 80,000 U/mL (well above the measuring interval of 300 U/mL). |
| Reference Range Verification | Verification of existing reference range with healthy samples. | 94% (65 out of 69) of normal female samples fell within the existing reference range (6.4 - 58 U/mL) across three lots. |
| Matrix Comparison | Comparable values across different specimen types. | Comparable values demonstrated for serum, Lithium Heparin, and EDTA plasma samples. |
2. Sample Size Used for the Test Set and Data Provenance
- Detection Limits (LoB, LoD, LoQ): The specific sample size for determining LoB, LoD, and LoQ is not explicitly stated as a number of individual patient samples, but the study was conducted "in accordance with CLSI EP17-A2," which provides methodologies for these determinations.
- Linearity/Measuring Interval: A high and low sample pool were used to prepare a panel of ten levels. The number of individual patient samples contributing to these pools is not specified.
- Method Comparison: 274 patient samples.
- Assay Precision: Five serum samples. Each tested in duplicate over 20 days, two runs per day (total 80 replicates per sample). Total N for data points is 400 (5 samples * 80 replicates).
- Assay Reproducibility: Five serum samples. Each tested over 5 days, with 5 replicates per sample (total 25 replicates per sample) across 3 reagent lots. Total N of data points is 375 (5 samples * 25 replicates * 3 reagent lots).
- Recovery: 5 neat samples spiked with 3 different concentrations of CA15-3 solution.
- Interference: Not specified as a number of patient samples, but various compounds were tested.
- Hook Effect: Not specified as a number of patient samples.
- Reference Range Verification: 69 apparently healthy female samples across 3 lots (total 207 results).
- Matrix Comparison: Not explicitly specified, but "comparable values to serum samples" were demonstrated across SST, Lithium Heparin, and EDTA tube types.
Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective. It refers to human serum and plasma samples and "patient samples" and "apparently healthy female samples" without further geographical or temporal details.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This information is not applicable to this type of device. The IMMULITE 2000 BR-MA is an in vitro diagnostic assay that quantitatively measures CA15-3 antigen. Its performance characteristics are established through analytical studies (e.g., precision, linearity, interference) and comparisons to a predicate device or established laboratory methods, rather than through expert interpretation of outputs to establish a "ground truth" (as might be seen in imaging AI, for example). The ground truth for this device is the actual concentration of the analyte, verified through reference methods or spiked samples with known concentrations.
4. Adjudication Method for the Test Set
Not applicable. As described above, this device's performance is not evaluated through expert adjudication of results but rather by comparing its quantitative measurements to known values or to a predicate device, and assessing its analytical characteristics.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance
Not applicable. This is an in vitro diagnostic assay, not an AI-assisted diagnostic imaging or interpretation system requiring human "readers." The "human reader" concept is not relevant here.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
The device is an automated in vitro diagnostic assay. Its primary function is to perform quantitative measurements of CA15-3. The performance studies described (detection limits, linearity, precision, etc.) are all standalone performance evaluations of the assay itself, without a "human-in-the-loop" component in the sense of interpreting an output that then needs human review for diagnosis. The device provides a quantitative result (U/mL), which is then used by a clinician in conjunction with other clinical methods. So, yes, the performance data presented are for the standalone analytical performance of the device.
7. The Type of Ground Truth Used
The ground truth used in the performance studies includes:
- Known concentrations: For linearity, recovery, interference, and hook effect studies, samples are often prepared with known concentrations of the analyte or interferents.
- Reference methods/Predicate device: For method comparison, results from the candidate device are compared against results from the legally marketed predicate device.
- Statistical methods: Established CLSI (Clinical and Laboratory Standards Institute) guidelines provide the statistical framework and generally accepted methodologies for determining metrics like LoB, LoD, LoQ, precision, and linearity.
- Clinically defined healthy populations: For reference range verification, samples from "apparently healthy female samples" are used.
8. The Sample Size for the Training Set
The document describes performance studies for a modified in vitro diagnostic assay. These studies are typically for verification and validation, not for "training" an algorithm in the sense of machine learning. There is no mention of a "training set" in the context of algorithm development or machine learning. The studies primarily evaluate the analytical performance of the modified assay components.
9. How the Ground Truth for the Training Set Was Established
As there is no mention of a "training set" for an algorithm, this question is not applicable. The device's mechanism is based on immunometric assay principles using chemical reactions, not on training data for a machine learning model.
Ask a specific question about this device
(458 days)
Indianapolis, Indiana 46250
Re: K221890
Trade/Device Name: Elecsys Tg II Regulation Number: 21 CFR 866.6010
Thyroglobulin | |
| Regulation Number | 866.6010
Immunoassay for the in vitro quantitative determination of thyroglobulin in human serum and plasma. Determination of Tg is used as an aid in monitoring for the presence of persistent or recurrent/metastatic disease in patients who have differentiated thyroid cancer (DTC) and have had thyroid surgery (with or without ablative therapy). The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.
The Tg II immunoassay makes use of a two-step, double antigen sandwich principle using a biotinylated monoclonal Tg-specific antibody and monoclonal Tg-specific antibodies labeled with a ruthenium complex. The Tg II immunoassay is intended for the in vitro quantitative determination of thyroglobulin in human serum and plasma. Determination of Tg is used to aid in monitoring for the presence of persistent or recurrent/metastatic disease in patients who have differentiated thyroid cancer (DTC) and have had thyroid surgery (with or without ablative therapy). It is intended for use on the cobas e immunoassay analyzers. Results are determined via a calibration curve which is instrument-specifically generated by 2-point calibration and a master curve provided via the reagent barcode or e-barcode.
The Elecsys Tg II device is an immunoassay intended for the in vitro quantitative determination of thyroglobulin in human serum and plasma, used as an aid in monitoring for the presence of persistent or recurrent/metastatic disease in patients who have differentiated thyroid cancer (DTC) and have had thyroid surgery.
Here's an analysis of its acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The provided document doesn't explicitly list "acceptance criteria" for all performance measures in a comparative table against the reported performance. However, based on the studies conducted and their results, one can infer the implicit acceptance criteria by observing the measured performance and statements like "All deviations from linearity met the specification" or "Non-significant interferences were defined as %interferences within ± 10 %".
Below is a table summarizing the reported device performance, with inferred acceptance criteria where direct ones are not explicitly stated, but are implied by the reported "met specifications" or similar statements.
| Performance Characteristic | Inferred Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Clinical Performance | ||
| Sensitivity | High sensitivity required for monitoring recurrent/metastatic disease (e.g., >90%). | 98.91% (91/92) with 95% CI: (94.10%; 99.81%) |
| Specificity | Acceptable specificity for the intended use (the exact value is not explicitly stated as an initial acceptance criterion, but the reported value is presented as performance). | 53.42% (234/438) with 95% CI: (48.74%; 58.05%) |
| Negative Predictive Value (NPV) | High NPV desired for ruling out disease (-ve result, truly -ve). | 99.89% with 95% CI: (99.42%; 99.98%) (calculated at 4.99% prevalence) |
| Positive Predictive Value (PPV) | Acceptable PPV for the intended use. | 10.03% with 95% CI: (9.16%; 11.03%) (calculated at 4.99% prevalence) |
| Analytical Performance | ||
| Limit of Blank (LoB) | Must be very low (e.g., in the picogram/mL range) to detect low levels of Tg. No explicit criterion given, but the reported value is the outcome of the study designed to determine it. | 0.02 ng/mL (Determined according to CLSI EP17-A2) |
| Limit of Detection (LoD) | Must be very low, enabling early detection of disease recurrence. No explicit criterion given, but the reported value is the outcome of the study designed to determine it. | 0.04 ng/mL (Determined according to CLSI EP17-A2) |
| Limit of Quantitation (LoQ) | %CV of within-laboratory precision ≤ 20% and %bias within ±15%. | 0.1 ng/mL (%CV for samples around this level ranged from 7.56% to 4.00% for repeatability, and within-laboratory CVs were 9.34%, 8.75%, 5.67% for HS1, HS2, HS3 respectively, all below 20%. Bias not explicitly shown in summary table but met criteria.) |
| Linearity | Deviations from linearity ≤ ±10% for values ≥0.3 ng/mL and within ±0.03 ng/mL for values <0.3 ng/mL. | All deviations from linearity met the specification. |
| Measuring Range | To cover a broad range of clinically relevant Tg concentrations. | 0.1 ng/mL – 500 ng/mL. Extended measuring interval is 500 – 5,000 ng/mL for 1:10 diluted samples. |
| High-Dose Hook Effect | No hook effect within clinically relevant high concentrations (e.g., up to 120,000 ng/mL or higher, implying reliable readings even at very high concentrations). | No hook effect observed up to ≥ 120,000 ng/mL Tg. |
| Matrix Comparison | Performance with Li-heparin, K2-EDTA, and K3-EDTA plasma should be similar to serum. | Matrix comparison studies showed that performance of Elecsys Tg II assay with these matrices are similar. |
| Biotin Interference | Non-significant interference, generally defined as %interference within ± 10%. | Biotin interference claim is set to 1200 ng/mL in labeling (meaning up to this concentration, interference is acceptably low, i.e., within ±10%). |
| Endogenous Substance and Pharmaceutical Interference | Non-significant interferences, defined as %interferences within ± 10 % at tested concentrations. | Non-significant interferences observed for Bilirubin, Hemoglobin, Intralipid, Biotin, IgG, Albumin, and 17 commonly used pharmaceuticals, and special drugs at tested concentrations (e.g., Iodide, Amiodarone, L-T4, etc.). |
| HAMA Interference | No significant HAMA interference (e.g., recovery within acceptable range, like ±10-20%). | No significant HAMA interference at 805 µg/L HAMA. |
| Cross-Reactivity | Cross-reactivity should be minimal (e.g., within a small percentage). | TSH: Within ±0.36% at 1000 mIU/L. TBG: Within ±0.0001% at 200000 ng/mL. |
| Stability | ||
| Shelf-life Stability | Reagent stable for the stated shelf-life (e.g., 15 months). | Data support a shelf-life of up to 15 months at 2-8°C. |
| Reagent After Opening | Reagent stable for a specified duration after first opening (e.g., 84 days) when stored at 2-8°C. | Up to 84 days (12 weeks) after opening, stored at 2-8°C. |
| On-board Reagent Stability | Reagent stable for a specified duration on the analyzer (e.g., 28 days). | Up to 28 days (4 weeks). |
| Sample Stability | Samples stable for specified durations under different storage conditions (e.g., 14 days at 2-8°C, 24 months at -20°C). | 14 days at 2-8°C, 14 days at 15-25°C, and 24 months at -20 (± 5)°C for serum, Li-Heparin plasma, K2-EDTA and K3-EDTA plasma. |
Study Information:
2. Sample Size Used for the Test Set and Data Provenance
-
Clinical Performance Study (Combined Cohorts):
- Sample Size: 530 samples available for analysis.
- Data Provenance:
- Origin: Collected from 9 sites across the U.S.
- Nature:
- Longitudinal Cohort: Serum samples collected from subjects 4-12 weeks post-thyroidectomy (with/without radioiodine ablation) and at 4 additional time points (6, 12, 18, 24 months post-surgery/ablation).
- Cross-sectional Cohort: Samples collected from subjects with structural disease at a single visit. This cohort was used to increase the number of observations from patients with structural disease.
-
Reference Range Study:
- Sample Size: 244 healthy males and 219 healthy females (total 463).
- Data Provenance: Not explicitly stated (e.g., age range is given, but not country of origin, retrospective/prospective).
-
Expected Values in DTC post-thyroidectomy:
- Sample Size: 127 subjects with differentiated thyroid cancer (100 female; 27 male) with no evidence of disease for 4 or more years post-total/near total thyroidectomy.
- Data Provenance: Not explicitly stated.
-
Precision (Within-laboratory): 84 runs for each sample.
-
Reproducibility (Site-to-site): 146-149 runs for each sample.
-
LoB, LoD, LoQ, Linearity, Hook Effect, Interference, Cross-reactivity, Stability Studies: Varying number of samples/replicates as described in the respective sections (e.g., LoB/LoD: 5 native samples, 2 replicates/run, 6 runs over 4 days; LoQ: 7 low-level human serum samples, 5 replicates/run, 1 run/day over 5 days).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not explicitly state the number of experts or their specific qualifications for establishing the ground truth of "structural disease" in the clinical study. However, the definition of structural disease is provided:
- Ground Truth Definition: "Structural disease was defined as evidence of disease on ultrasound, cross sectional or functional imaging, or biopsy proven disease as determined by the investigator."
- Implied Experts: This definition suggests that the "investigator" (likely a medical professional such as an endocrinologist, radiologist, or pathologist, depending on the type of evidence) determined the presence of structural disease. The number of such investigators involved in determining ground truth per patient or across the study is not specified.
4. Adjudication Method for the Test Set
The document does not explicitly describe an adjudication method (e.g., 2+1, 3+1) for establishing the ground truth of structural disease. It states that structural disease was "determined by the investigator." This implies a single determination rather than a consensus or adjudicated process among multiple experts for each case.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not explicitly done. The study focuses on the standalone performance of the Elecsys Tg II assay rather than comparing human reader performance with and without AI assistance. The device itself is an immunoassay, not an AI imaging interpretation tool that would typically involve human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies presented are primarily standalone (algorithm only) performance evaluations. The Elecsys Tg II is an automated immunoassay system, and its performance (sensitivity, specificity, precision, accuracy, linearity, stability, etc.) is measured directly on biological samples without active human interpretation assistance in the analytical or clinical performance reported here. The "results are determined via a calibration curve which is instrument-specifically generated."
7. The Type of Ground Truth Used
- Clinical Performance Study: The ground truth for the clinical performance study (sensitivity, specificity, NPV, PPV) was based on structural disease (SD+ or SD-). This was determined by:
- Evidence of disease on ultrasound.
- Cross-sectional or functional imaging.
- Biopsy-proven disease.
- These were "determined by the investigator."
- Analytical Studies: For analytical performance (LoB, LoD, LoQ, linearity, interference, stability), the ground truth generally involved:
- Reference standards/materials: e.g., CRM 457.
- Known analyte concentrations: Obtained by spiking or using characterized serum pools.
- Clinical laboratory standards: (e.g., CLSI guidelines).
8. The Sample Size for the Training Set
The document does not mention a separate "training set" for the Elecsys Tg II device in the context of machine learning or AI algorithms. As an immunoassay, the "training" analogous to an AI system would be the development and optimization of the assay reagents, protocols, and calibration curves. The provided information relates to the validation of the final product. The "calibration curve" is established for the assay, which is a form of internal "training" for the instrument's interpretation of signal to concentration.
9. How the Ground Truth for the Training Set Was Established
As noted above, for an immunoassay, there isn't a "training set" in the typical AI sense. The development of the assay relies on establishing accurate measurements against recognized reference standards and materials (e.g., CRM 457, characterized serum pools with known thyroglobulin concentrations). These standards serve as the "ground truth" to ensure the assay accurately quantifies thyroglobulin. The assay is then calibrated using these standards to accurately relate the measured signal (chemiluminescent emission) to the thyroglobulin concentration in patient samples.
Ask a specific question about this device
(267 days)
Drive Chaska, Minnesota 55318
Re: K223921
Trade/Device Name: Access CEA Regulation Number: 21 CFR 866.6010
Classification Name: Tumor-associated antigen immunological test system Classification Regulation: 21 CFR 866.6010
The Access CEA assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of Carcinoembryonic Antigen (CEA) levels in human serum, using the Access Immunoassay Systems. CEA measured by the Access Immunoassay Systems is used as an aid in the management of cancer patients in whom changing CEA concentrations have been observed.
The Access CEA assay is a two-site immunoenzymatic "sandwich" assay using two mouse monoclonal anti-CEA antibodies (MAb) which react with different epitopes of CEA. The Access CEA reagent kit is in a liguid ready-to-use format designed for optimal performance on Beckman Coulter's immunoassay analyzers. Each reagent kit contains two reagent packs. Other items needed to run the assay include substrate, calibrators, and wash buffer.
The provided text describes the 510(k) submission for the Beckman Coulter Access CEA assay on the Dxl 9000 Access Immunoassay Analyzer. This document focuses on demonstrating substantial equivalence to a predicate device (Access CEA on the Access Immunoassay Analyzer), primarily through analytical performance studies rather than clinical or AI-assisted diagnostic studies.
Therefore, many of the requested criteria related to AI performance, human reader studies, and expert ground truth are not applicable or cannot be extracted from this document. The information provided is characteristic of a submission for an in vitro diagnostic (IVD) device, which relies heavily on analytical performance characteristics.
Here's the breakdown based on the provided text:
1. Acceptance Criteria and Reported Device Performance
The document provides acceptance criteria and performance for various analytical studies.
| Study Type | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Method Comparison | R² ≥ 0.90 and slope 1.00 ± 0.10 | N=153Concentration Range*: 0.46 - 1071 ng/mLSlope: 0.98Slope 95% Cl: 0.97 - 0.99Intercept: 0.058Intercept 95% Cl: 0.0015 - 0.17Correlation Coefficient R: 1.00The results met the acceptance criteria. |
| Imprecision | (Not explicitly stated in a single overall criterion, but implied to meet industry standards and internal acceptance limits, often expressed as %CV limits for different concentrations.) The acceptance is based on the presented %CV values being acceptable. | Repeatability (Within-run): %CV range 1.8-3.5%Between-run: %CV range 0.8-2.5%Between-day: %CV range 1.2-3.1%Within-Laboratory (Total): %CV range 2.5-5.2% |
| Linearity | Implicitly, results should demonstrate linearity across the stated analytical measuring interval. | The Access CEA assay is linear on the Dxl 9000 Access Immunoassay Analyzer throughout the analytical measuring interval of 0.2 - 1,000 ng/mL. |
| Limit of Blank (LoB) | Implicitly, the estimated LoB should be within acceptable limits (no specific numerical criterion given). | The claimed LoB estimate for the Access CEA assay is 0.09 ng/mL. |
| Limit of Detection (LoD) | Implicitly, the estimated LoD should be within acceptable limits (no specific numerical criterion given). | The claimed LoD estimate for the Access CEA assay is 0.1 ng/mL. |
| Limit of Quantitation (LoQ) | Implicitly, the claimed LoQ should be scientifically justified and within acceptable limits (no specific numerical criterion given). | The claimed LoQ determined for Access CEA assay is 0.2 ng/mL. |
2. Sample size used for the test set and the data provenance:
- Method Comparison: A total of 153 serum samples were evaluated.
- Imprecision: Multiple samples (7 distinct concentration levels) were tested with a minimum of three replicates in 2 runs per day for a minimum of 20 days. The "N" column in the table refers to the total number of measurements for each sample level (e.g., 126 for Sample 1, 120 for Sample 2, etc.).
- Data Provenance: The document does not specify the country of origin of the data or whether the samples were retrospective or prospective. This is typical for IVD analytical performance studies.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This information is not applicable to this type of device and study. The ground truth for analytical performance studies like Method Comparison, Imprecision, Linearity, LoB, LoD, and LoQ is established by the reference measurement method (in this case, the predicate device for method comparison, or precise measurements by the instrument itself for other analytical characteristics) and laboratory standards, not by expert human interpretation like a radiologist reading an image.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- This is not applicable. Adjudication methods are used in studies involving human interpretation or challenging diagnoses, not for analytical performance of an IVD assay measuring a biomarker concentration.
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 not applicable. This is an in vitro diagnostic device (immunoassay for CEA), not an AI-powered image analysis or diagnostic assist device for human readers. No human interpretation or AI assistance study was performed or required for this type of submission.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- This is not applicable in the context of AI algorithms. The device itself (Access CEA assay on the Dxl 9000 Access Immunoassay Analyzer) is a standalone automated analytical instrument. Its performance is evaluated as an "algorithm only" in the sense that it performs the measurement independently, but it's a chemical and optical measurement process, not an AI algorithm.
7. The type of ground truth used:
- For the Method Comparison study, the "ground truth" or reference method was the predicate device (Access CEA on the Access Immunoassay Analyzer).
- For other analytical studies (Imprecision, Linearity, LoB, LoD, LoQ), the ground truth is established through controlled spiking, dilutions, and repeated measurements according to established analytical validation guidelines (e.g., CLSI EP-05-A3 for imprecision). These are intrinsic analytical properties of the assay and instrument combination, verified against laboratory standards.
8. The sample size for the training set:
- This is not applicable as this is not an AI/machine learning device that requires a "training set" in the conventional sense. The development of an immunoassay involves optimizing reagents, antibodies, and instrument parameters, which is a different process from training a machine learning model.
9. How the ground truth for the training set was established:
- This is not applicable for the reasons stated in point 8.
Ask a specific question about this device
Page 1 of 10