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Found 33 results
510(k) Data Aggregation
(209 days)
United Kingdom
Re: K240865
Trade/Device Name: IDS-iSYS Free Testosterone Regulation Number: 21 CFR 862.1680
|
| | Classification: 21 CFR 862.1680
The IDS-iSYS Free Testosterone assay is an in vitro diagnostic device intended for the quantitative determination of free testosterone in human serum or the IDS system. Measurement of free testosterone is used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, impotence in male and in females; hirsutism (excessive hair) and virilization) due to tumors, polycystic ovaries and androgenital syndromes.
The IDS-iSYS Free Testosterone assay consists of a reagent cartridge. The reagent cartridge contains multiple reagents:
- MP3: Magnetic particles coated with Streptavidin in a phosphate Pluronic buffer with sodium azide (NaN3) as preservative (
The provided document describes the analytical performance of the IDS-iSYS Free Testosterone assay but does not detail a device performance study with acceptance criteria in the typical format of a clinical trial for an AI/ML medical device. Instead, it focuses on the analytical characteristics of the in vitro diagnostic device, comparing it to a predicate device and demonstrating its performance through various laboratory tests.
Here's an attempt to structure the information based on your request, with the understanding that not all requested points are directly applicable to this type of IVD submission:
1. Table of Acceptance Criteria and Reported Device Performance
For an in vitro diagnostic device like the IDS-iSYS Free Testosterone, "acceptance criteria" and "reported device performance" are typically defined by analytical performance characteristics, such as sensitivity, precision, linearity, and interference. The document presents these values but does not explicitly state pre-defined acceptance criteria for each measurement that would be found in a clinical study protocol. However, we can infer performance targets based on the data presented and common medical device standards (e.g., CLSI guidelines).
| Acceptance Criteria (Inferred/Generic for IVD) | Reported Device Performance (IDS-iSYS Free Testosterone) |
|---|---|
| Analytical Sensitivity | |
| Limit of Blank (LoB) | 0.08 pg/mL |
| Limit of Detection (LoD) | 0.17 pg/mL |
| Limit of Quantitation (LoQ) | 0.40 pg/mL (with CV =60 yrs) |
* Males: 129 (21-39 yrs), 138 (40-59 yrs), 42 (>=60 yrs)
The provenance of these subjects is not stated, but they are described as "apparently healthy adults and children."
3. Number of Experts Used to Establish Ground Truth and Qualifications
This information is not applicable to this document. The "ground truth" for an IVD device like this is typically established by reference methods or gravimetric preparation of calibrators/controls, not by human expert opinion as would be the case for image-based AI/ML diagnostics. The values are quantitative measurements of a biochemical marker.
4. Adjudication Method for the Test Set
This information is not applicable. Adjudication methods (e.g., 2+1, 3+1) are common in studies where human readers interpret data (like medical images) and their agreement, or lack thereof, needs to be resolved. For an IVD, the "ground truth" is a measured concentration, and the accuracy is assessed against reference standards or established methods.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
This information is not applicable. An MRMC study assesses how human readers' performance changes with and without AI assistance. This device is an in vitro diagnostic assay, directly measuring a biomarker without human interpretation in the workflow described.
6. Standalone (Algorithm Only) Performance
The performance data presented throughout the document (LoB, LoD, LoQ, precision, linearity, cross-reactivity, interference, method comparison, matrix comparison) is the standalone performance of the IDS-iSYS Free Testosterone assay. This device is a fully automated assay system, and its performance is evaluated independent of human interpretive steps.
7. Type of Ground Truth Used
The ground truth for the analytical studies is generally based on:
- Known concentrations: For LoB, LoD, LoQ, linearity, cross-reactivity, and interference, samples are prepared with known or target concentrations of free testosterone and potential interfering substances.
- Comparative methods: For method comparison, a "commercially available quantitative free testosterone ELISA" serves as the comparative method against which the IDS-iSYS Free Testosterone is measured.
- Reference Intervals: For expected values, "95% reference interval for apparently healthy adults and children" was calculated using a non-parametric method, likely referring to the distribution of measurements in that population.
8. Sample Size for the Training Set
This information is not provided and is typically not applicable in the same way it would be for an AI/ML device. For an IVD assay, "training" involves the development and optimization of the assay reagents, protocols, and calibration, rather than training a machine learning model on a distinct dataset. The "training set" for an IVD refers to the samples used to develop and refine the assay's performance characteristics and establish its calibration curve, which is distinct from the analytical validation samples.
9. How the Ground Truth for the Training Set Was Established
This information is not explicitly provided in the document. For an IVD, the "ground truth" for developing a training set (i.e., for calibration) typically involves:
- Gravimetric preparation: Precisely weighing and dissolving a known amount of the analyte (free testosterone) in a suitable matrix to create primary calibrators with accurate, traceable concentrations.
- Reference methods: Using highly accurate and validated reference methods (e.g., LC-MS/MS, though not specified here) to assign values to calibrators or control materials.
- Standardization: Following established industry and regulatory standards (e.g., CLSI guidelines) for calibrator preparation and value assignment to ensure accuracy and traceability.
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(105 days)
Drive Chaska, Minnesota 55318
Re: K233480
Trade/Device Name: Access SHBG Regulation Number: 21 CFR 862.1680
Class 1) - Radioimmunoassay, Testosterones and Dihydrotestosterone Classification Requlation: 21 CFR 862.1680
The Access SHBG assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of Sex Hormone Binding Globulin levels in human serum and plasma using the Access Immunoassay Systems. The Access SHBG assay is indicated for use in the assessment of androgen disorders.
The Access SHBG assay is a sequential two-site immunoenzymatic ("sandwich") assay. The Access SHBG assay consists of the reagent pack, calibrators and QCs. Other items needed to run the assay include substrate and wash buffer. The Access SHBG assay reagent pack, Access SHBG assay calibrators, Access SHBG QCs, 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 FDA 510(k) clearance letter and accompanying summary describe the Acceptance Criteria and the study proving the Access SHBG assay meets these criteria.
Acceptance Criteria and Device Performance
The provided document focuses on the analytical performance of the Access SHBG assay on the Dxl 9000 Access Immunoassay Analyzer, comparing it to a previously cleared predicate device (Access SHBG on Access 2 instrument). The acceptance criteria are largely derived from CLSI (Clinical and Laboratory Standards Institute) guidelines for various analytical performance characteristics.
Here is a table summarizing the acceptance criteria and the reported device performance for the analytical studies:
| Performance Characteristic | Acceptance Criteria (from CLSI guidelines or internal design) | Reported Device Performance (Access SHBG on Dxl 9000) |
|---|---|---|
| Method Comparison (compared to predicate) | R$^2$ $\ge$ 0.95 with a slope equal to 1.00 ± 0.09 | R = 1.00, R$^2$ = 0.99, Slope = 1.01 (95% CI: 1.00-1.03), Intercept = -0.019 (95% CI: -0.46 - 0.29) |
| Precision (Within-Laboratory Imprecision) | $\le$ 0.14 nmol/L SD at concentrations $\le$ 2 nmol/L | |
| $\le$ 7.0% CV at concentrations > 2 nmol/L | Sample 1 (0.82 nmol/L): SD = 0.04, CV = 4.6% | |
| Sample 2 (18 nmol/L): SD = 0.5, CV = 2.7% | ||
| Sample 3 (47 nmol/L): SD = 1.3, CV = 2.7% | ||
| Sample 4 (90 nmol/L): SD = 2.6, CV = 2.9% | ||
| Sample 5 (198 nmol/L): SD = 5.1, CV = 2.6% | ||
| Linearity | The assay must demonstrate linearity throughout its analytical measuring interval. | Linear throughout the analytical measuring interval of 0.33 nmol/L - 200 nmol/L. |
| Limit of Blank (LoB) | Not explicitly stated as a number, but derived from the study. | 0.005 nmol/L (maximum observed) |
| Limit of Detection (LoD) | Not explicitly stated as a number, but derived from the study. | 0.01 nmol/L |
| Limit of Quantitation (LoQ) | Not explicitly stated as a number, but derived from the study. | 0.06 nmol/L |
Study Details
The provided document describes analytical verification studies for the Access SHBG assay, not a clinical study involving human readers or AI. Therefore, some of the requested information (e.g., MRMC studies, human reader improvement with AI, ground truth for training AI models, number of experts for AI ground truth) is not applicable or cannot be extracted from this document as it pertains to an immunoassay device, not an AI/ML-based diagnostic system.
Here's the relevant information that can be extracted:
2. Sample Size and Data Provenance:
- Method Comparison: A total of 151 samples were evaluated. The data provenance is implied to be clinical samples (patient samples are mentioned in the CLSI guideline for method comparison), though specific country of origin or whether they were retrospective/prospective is not stated. Given the context of a 510(k) submission for an in-vitro diagnostic, it is highly likely these were de-identified retrospective clinical samples.
- Precision: Five serum samples with varying SHBG concentrations were used. Each sample was assayed in duplicate with two runs per day, over 20 days, on three Dxl 9000 Access Immunoassay Analyzer systems, three reagent lots, and three calibrator lots. This totals 80 measurements per sample (5 samples * 2 duplicates * 2 runs/day * 20 days / 1 instrument * 1 reagent lot * 1 calibrator lot used for reported results).
- Linearity: A native low sample and a spiked high sample were used, along with seven mixtures in between.
- LoB, LoD, and LoQ: Four distinct blank samples were used for LoB. Six to seven samples were used for LoD. 12-13 serum samples were used for LoQ.
3. Number of Experts and Qualifications for Test Set Ground Truth:
- This is an immunoassay device, not an image-based AI system. The ground truth for analytical studies like linearity, precision, and limits of detection is established by the assay itself (measurements of known concentrations, serial dilutions, etc.) and validated against established analytical method guidelines (CLSI). No human experts are involved in establishing ground truth for these analytical performance characteristics in the way they would be for image interpretation tasks.
4. Adjudication Method for Test Set:
- Not applicable. Adjudication methods (e.g., 2+1, 3+1) are typically used in clinical studies where human readers provide interpretations (e.g., radiology reads) that need to be reconciled to form a ground truth. For analytical performance studies of an immunoassay, the "truth" is based on the chemical and instrument measurements and statistical analysis against predefined acceptance criteria.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No, an MRMC comparative effectiveness study was not done. This type of study is relevant for AI systems assisting human readers in diagnostic tasks, such as radiology image interpretation. This document describes the analytical performance of an immunoassay for quantitative determination of SHBG levels, which does not involve human readers interpreting AI output.
6. Standalone Performance:
- Yes, the entire document focuses on the "standalone" analytical performance of the Access SHBG assay on the Dxl 9000 Access Immunoassay Analyzer. The performance described (method comparison, precision, linearity, limits) is the direct output of the instrument and reagents, without human interpretation "in the loop" beyond standard laboratory procedures for operating the instrument.
7. Type of Ground Truth Used:
- For analytical performance studies, the "ground truth" is established through:
- Reference measurements/Predicate device: For method comparison, the results from the previously cleared predicate device (Access SHBG on Access 2 instrument) served as the comparative "truth."
- Known concentrations/mixtures: For linearity, samples with known or precisely diluted concentrations were used.
- Replicate measurements: For precision, repeated measurements establish the variability.
- Blank and low-level samples: For LoB, LoD, and LoQ, these are the "truth" against which the assay's detection capabilities are measured.
- CLSI Guidelines: The studies were designed and evaluated according to CLSI guidelines, which represent a form of accepted scientific and statistical "truth" for validating laboratory assays.
8. Sample Size for Training Set:
- This document describes the validation of an immunoassay device, not an AI/ML model. Therefore, there isn't a "training set" in the context of machine learning. The device's underlying chemistry and physics are "trained" during its development and manufacturing process, but not through a data-driven training set in the way an AI algorithm is.
9. How Ground Truth for Training Set was Established:
- Not applicable, as there is no AI/ML training set in the context of this immunoassay device.
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(65 days)
Chaska, MN 55318
Re: K223405
Trade/Device Name: Access Testosterone Regulation Number: 21 CFR 862.1680
Testosterone Classification Name: Testosterone test system Product Code: CDZ Classification Regulation: 21 CFR 862.1680
The Access Testosterone assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of total testosterone levels in human serum and plasma using the Access Immunoassay Systems.
Measurement of testosterone are used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in males and, in females hirsutism (excessive hair) and virilization) due to tumors, polycystic ovaries, and adrenogenital syndromes.
The Access Testosterone assay is a competitive binding immunoenzymatic assay. The Access Testosterone assay consists of the reagent pack and calibrators. Other items needed to run the assay include substrate and wash buffer. The Access Testosterone assay reagent pack, Access Testosterone 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 provided text describes the analytical performance verification of an in vitro diagnostic device (Access Testosterone Assay) and its substantial equivalence to a previously cleared device, rather than an AI-powered medical device performing image analysis or similar tasks that typically involve human experts for ground truth and MRMC studies.
Therefore, many of the requested elements for an AI device (like human expert adjudication, MRMC studies, effect size of human improvement with AI, or detailed ground truth establishment for a training set) are not applicable to this document.
However, I can extract the relevant information regarding the acceptance criteria and study that proves the device meets them for this in vitro diagnostic device.
Here's the information based on the provided text:
Acceptance Criteria and Device Performance for Access Testosterone Assay
1. Table of Acceptance Criteria and Reported Device Performance
| Test | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Method Comparison | R² ≥ 0.90 and Slope of 1.00 ± 0.14 | R² = 0.98, Slope = 0.95 (95% CI: 0.93, 0.98), Intercept = 0.028 (95% CI: -0.015, 0.071) |
| Linearity (Analytical Measuring Interval) | Linear throughout the analytical measuring interval of 0.4 - 16.0 ng/mL | Linear throughout the analytical measuring interval of 0.4 - 16.0 ng/mL |
| Imprecision (Within-Laboratory) | ≤ 0.14 ng/mL SD at concentrations ≤ 1.4 ng/mL | Sample 1 (0.71 ng/mL): SD = 0.04 (meets criteria) |
| ≤ 10.0% CV at concentrations > 1.4 ng/mL | Sample 2 (2.0 ng/mL): CV = 4.4% (meets criteria) | |
| Sample 3 (4.8 ng/mL): CV = 3.9% (meets criteria) | ||
| Sample 4 (7.1 ng/mL): CV = 4.6% (meets criteria) | ||
| Sample 5 (8.6 ng/mL): CV = 5.9% (meets criteria) | ||
| Sample 6 (14 ng/mL): CV = 7.8% (meets criteria) | ||
| Limit of Blank (LoB) | Not explicitly stated as a numerical acceptance criterion, but determined and accepted. | LoB = 0.2 ng/mL |
| Limit of Detection (LoD) | Not explicitly stated as a numerical acceptance criterion, but determined and accepted. | LoD = 0.4 ng/mL |
| Limit of Quantitation (LoQ) | Not explicitly stated as a numerical acceptance criterion, but determined and accepted. | 20% Within-Laboratory CV LoQ = 0.4 ng/mL |
2. Sample Size Used for the Test Set and Data Provenance
- Method Comparison: 108 serum samples.
- Linearity: Low sample (native serum), high sample (native serum spiked with Testosterone antigen), and mixtures of low and high samples. (Specific N not further detailed for mixtures, but implies multiple points across measuring interval).
- Imprecision: Six (6) serum samples (2 native, 3 pooled native, 1 spiked native). Each tested in replicates of two (2) per run, with two (2) runs per day for a minimum of 20 days on each instrument and reagent lot combination. (N=88 for each sample shown in table corresponds to total replicates across the study design).
- LoB: Four blank samples.
- LoD: Seven serum samples containing low levels of Testosterone.
- LoQ: Twelve serum samples containing low levels of Testosterone.
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, given it's an IVD, samples would be collected for analytical performance testing.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Experts
- Not applicable (N/A). This device is an in vitro diagnostic assay for quantitative determination of a hormone level. Ground truth (or reference values) for analytical performance are established through established analytical methods, reference materials (e.g., USP Reference Material for Standardization and Traceability), and quantitative measurement procedures, not by human expert opinion or interpretation of images.
4. Adjudication Method for the Test Set
- N/A. Adjudication by human experts is not relevant for establishing the analytical performance of an in vitro diagnostic assay.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and its effect size of human readers improve with AI vs. without AI assistance
- N/A. This is not an AI-powered device involving human readers or interpretation. It's an in vitro diagnostic assay.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
- Yes, in essence. The studies described (Method Comparison, Linearity, Imprecision, LoB/LoD/LoQ) demonstrate the analytical performance of the device itself (the Access Testosterone Assay on the Dxl 9000 Access Immunoassay Analyzer) in a standalone, automated manner. There is no human interpretation component where performance needs to be evaluated.
7. The Type of Ground Truth Used
- Analytical Ground Truth:
- Reference Method/Predicate Device: For method comparison, the "previously cleared system" (Access Testosterone assay on the Access 2 instrument) serves as the reference for comparison, indicating that its results are considered the comparative "ground truth."
- Known Concentrations/Standards/Reference Materials: For linearity, imprecision, and limit studies, samples with known or characterized concentrations (e.g., native serum, spiked samples, blank samples) and established reference materials (USP Reference Material) are used.
- Statistical Models/Calculations: LoB, LoD, and LoQ are determined statistically based on measurements of blank and low-level samples, following CLSI guidelines.
8. The Sample Size for the Training Set
- N/A. This is an in vitro diagnostic device, not an AI/machine learning model that undergoes a "training" phase with a data set in the conventional sense. The "training" in manufacturing involves calibrating the instrument and reagents according to established protocols, not learning from a dataset.
9. How the Ground Truth for the Training Set was Established
- N/A. As above, there is no "training set" in the context of an AI model for this device. Calibration and quality control procedures ensure the analytical performance by using calibrators and controls with known values, which are traceable to reference materials (e.g., USP Reference Material).
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(338 days)
Indianapolis, Indiana 46250
Re: K211685
Trade/Device Name: Elecsys Testosterone II Regulation Number: 21 CFR 862.1680
|
| Product Codes,
Regulation Numbers | CDZ
21 CFR 862.1680
Immunoassay for the in vitro quantitative determination of testosterone in human serum and plasma.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on the cobas e 601 immunoassay analyzer.Measurements of testosterone are used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in males and, in females hirsutism (excessive hair) and virilization) due to tumors, polycystic ovaries, and adrenogenital syndromes.
The Elecsys Testosterone II immunoassay makes use of a competitive test principle using streptavidin-coated microparticles and electrochemiluminescence detection. Results are determined using a calibration curve that is generated specifically on each instrument by a 2point calibration and master curve provided with the reagent bar code. The Elecsys Testosterone II reagent kit consists of a Reagent Pack (R1, R2, and M (Streptavidin-coated microparticles)).
The Elecsys Testosterone II device is an immunoassay for the in vitro quantitative determination of testosterone in human serum and plasma. The device is intended for use on the cobas e 601 immunoassay analyzer.
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria for the Elecsys Testosterone II are based on various analytical performance characteristics. The table below summarizes some of the key performance criteria and the reported performance of the candidate device (Elecsys Testosterone II, K211685) in comparison to its predicate device (Elecsys Testosterone II, K093421).
| Feature | Acceptance Criteria (Predicate) | Reported Performance (Candidate) |
|---|---|---|
| Precision | Refer to CLSI EP05-A | 21-day precision: Evaluated according to CLSI guideline EP05-A3. Protocol: 2 replicates of 2 controls and 5 samples, 2 runs/day over 21 days with 1 reagent lot. Repeatability and intermediate precision calculated. 5-day precision: Evaluated on one cobas e 601 analyzer according to CLSI guideline EP05-A3. Protocol: 5 aliquots of each control (PreciControl Universal Level 1 & 2) and human serum samples per run, 1 run/day for 5 days with 3 lots. Repeatability and intermediate precision calculated. |
| LoB | 1.2 ng/dL | 1.50 ng/dL or 0.052 nmol/L |
| LoD | Same as predicate | 2.50 ng/dL or 0.087 nmol/L |
| LoQ | Same as predicate | 12.0 ng/dL or 0.416 nmol/L |
| Measuring Range | 2.50-1500 ng/dL or 0.087-52.0 nmol/L | 2.50-1500 ng/dL or 0.087-52.0 nmol/L (defined by Limit of Detection and maximum of master curve). |
| Cross-Reactivity | Various specific values | DHEA-S: 0.003%, Androstenedione: 3.15%, Danazol: 0.504%, Estradiol: 0.211%, Ethisterone: 3.57%, 19-Norethisterone: 5.51%, Norgestrel: 0.539%, △5-Androstene-3β17β-diol: 0.289%, Testosterone propionate: 0.718%, 5α-Androstane-3β, 17β-diol: 2.15%, 5α-Dihydrotestosterone: 1.30%, 11β-OH-Testosterone: 20.6%, 11keto-Testosterone: 4.87%, Prednisone: n.d., Prednisolone: n.d., Progesterone: 0.009%, Cortisol: n.d., Cortisone: n.d., Dexamethasone: n.d., Estrone: n.d., DHEA: 0.014%. |
| Biotin Interference |
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(98 days)
The LIAISON® Testosterone xt is a direct, competitive, chemiluminescence immunoassay (CLIA) intended for the quantitative determination of testosterone in human serum and EDTA plasma on the LIAISON® XL Analyzer. The assay is intended for in vitro diagnostic use.
Measurement of testosterone is used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in males and, in females hirsutism (excessive hair) and virilization (masculinization) due to tumors, polycystic ovaries, and adrenogenital syndromes.
The test has to be performed on the LIAISON® XL Analyzer.
The LIAISON® Testosterone xt assay's method for quantitative determination of testosterone is a direct, competitive, chemiluminescence immunoassay (CLIA). Specific antibody to testosterone is bound to magnetic particles (solid phase) and testosterone is linked to an isoluminol derivative. During the incubation, testosterone is dissociated from its binding protein and competes with labeled testosterone for binding sites on the antibody. After the incubation, the unbound material is removed with a wash cycle. Subsequently, the starter reagents are added and a flash chemiluminescent reaction is initiated. The light signal is measured by a photomultiplier as relative light units (RLU) and is inversely proportional to the concentration of testosterone present in calibrators, controls, or samples.
The LIAISON® Testosterone xt is an in vitro diagnostic device consisting of reagents provided in individual compartments within a plastic container called the Reagent Integral. The components provided in the unitized Reagent Integral include: PMP (paramagnetic particles), conjugate and assay buffer. All reagents in the integral are supplied ready to use. The assay configuration for the LIAISON® Testosterone xt allows for the performance of 100 tests.
The two-point calibrators are provided in the same kit box, but separate from the Reagent Integral. The two-point calibrators are supplied ready to use.
The LIAISON® Testosterone xt assay is performed on the LIAISON® XL Analyzer (Model 10050; originally FDA cleared under K103529), a fully automated system with continuous loading combining the chemiluminescence technology with magnetic microparticles as the solid phase.
Here's a breakdown of the acceptance criteria and study information for the LIAISON® Testosterone xt device, extracted from the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria (Predicate Device) | Reported Device Performance (LIAISON® Testosterone xt) |
|---|---|---|
| Assay Measuring Range | 0.16 - 15.0 ng/mL | Extended: 0.024 – 15.0 ng/mL |
| Limit of Blank (LoB) | ≤ 0.031 ng/mL | Improved: ≤ 0.005 ng/mL |
| Limit of Detection (LoD) | 0.098 ng/mL | Improved: 0.010 ng/mL |
| Limit of Quantitation (LoQ) | 0.160 ng/mL | Improved: 0.024 ng/mL |
| Method Comparison | y = 0.9390x – 0.1002 (vs. commercially available immunoassay) | |
| 95% CI for slope: 0.92 to 0.96 | ||
| 95% CI for intercept: -1.88 to 1.80 ng/dL | y = 0.99x – 1.77 ng/dL (vs. CDC HoSt Testosterone RMP ID-LC-MS/MS values) | |
| 95% CI for slope: 0.97 to 1.02 | ||
| 95% CI for intercept: -3.22 to -0.35 ng/dL | ||
| Precision (Total/Across Lots %CV) | 7.9% – 14.0% | Improved: 3.5% – 7.9 % |
| Linearity (Serum) | Observed Analyte = 0.9942x – 16.062; R² = 0.9959 | Observed Analyte = 0.995x + 0.0346; R² = 0.9928 |
| Linearity (SST Serum) | Observed Analyte = 1.0188x - 14.531; R² = 0.9965 | Observed Analyte = 1.0225x - 57.853; R² = 0.9914 |
| Linearity (EDTA plasma) | Observed Analyte = 1.0057x - 13.029; R² = 0.9913 | Observed Analyte = 1.0337x - 31.889; R² = 0.9955 |
| Recovery (Mean %) | 97% | 99% |
| Recovery (Range %) | 91% - 105% | 93% - 105% |
| Open Use Stability: Reagent Integral | 4 weeks | Extended: 8 weeks |
| Open Use Stability: Calibrators | 4 weeks | Extended: 8 weeks |
| Calibration Curve Stability | 7 days | Extended: 28 days |
2. Sample Size for the Test Set and Data Provenance
The provided document does not explicitly state the sample sizes used for each specific test (e.g., method comparison, precision, linearity, recovery). It only summarizes the results in "Table 6-2: Comparison to Predicate Device" and refers to "verification and validation activities" without detailing the exact number of samples for each.
The data provenance is not specified in terms of country of origin. The studies appear to be retrospective analyses of device performance characteristics, as they involve testing the LIAISON® Testosterone xt against existing methods or conditions to demonstrate equivalence and improved performance over the predicate device.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
This information is not explicitly provided in the document. For the "Method Comparison," it refers to "commercially available immunoassay" and "CDC HoSt Testosterone RMP ID-LC-MS/MS values." The latter, CDC HoSt Testosterone RMP ID-LC-MS/MS, likely represents a highly accurate and standardized reference method, which serves as a widely accepted ground truth in laboratory medicine, rather than relying on individual expert consensus for each measurement. No human experts are mentioned for ground truth establishment.
4. Adjudication Method for the Test Set
No explicit adjudication method is mentioned. The studies focus on direct quantitative analytical performance comparisons rather than subjective human interpretation.
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. The LIAISON® Testosterone xt is an in vitro diagnostic device, specifically a chemiluminescence immunoassay (CLIA), for the quantitative determination of testosterone. It is an automated laboratory test, not an AI-assisted diagnostic imaging or interpretation tool that involves human readers. Therefore, an MRMC comparative effectiveness study involving human readers and AI is not relevant to this device.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, this is effectively a standalone device performance study. The LIAISON® Testosterone xt is an automated system where the measurement of testosterone is performed by the analyzer (LIAISON® XL Analyzer) without human intervention in the analytical process itself. The performance metrics (LoB, LoD, LoQ, precision, linearity, recovery) are all measures of the algorithm's and instrument's direct analytical capability.
7. The Type of Ground Truth Used
The ground truth used for method comparison was:
- For the predicate device: A "commercially available immunoassay."
- For the LIAISON® Testosterone xt: "CDC HoSt Testosterone RMP ID-LC-MS/MS values." This is a highly accurate, reference method-based measurement, representing the gold standard for testosterone quantification. Other ground truths were established by controlled experiments for limits (e.g., dilution series for LoB, LoD, LoQ), spiked samples for recovery, and replicated measurements for precision.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning or AI. This device is an immunoassay, not an AI model that requires a distinct training phase with a labeled dataset in the typical sense. Its development would involve analytical validation using various samples to optimize reagent formulation, assay parameters, and calibration, but not as a machine learning training set.
9. How the Ground Truth for the Training Set was Established
As explained above, there is no "training set" in the machine learning sense for this immunoassay. The development and validation of an immunoassay involve:
- Reference materials: Use of certified reference materials or reference methods (like ID-LC-MS/MS) to establish accurate values for calibrators and controls.
- Spiked samples: Samples with known concentrations of testosterone added.
- Clinical samples: Testing a range of patient samples representing the intended use population, comparing results to established methods.
- Statistical analysis: Extensive statistical methods are used during development and validation to ensure accuracy, precision, linearity, and other performance characteristics.
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(214 days)
102 27 Cz
Re: K191350
Trade/Device Name: ACTIVE® Free Testosterone RIA Regulation Number: 21 CFR 862.1680
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| Product Codes: | CDZ |
| Regulation Number: | 21 CFR 862.1680
Radioimmunoassay for the quantitative measurement of free testosterone in human serum. This assay is intended for in vitro diagnostic use.
Free testosterone test is used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in males and, in female's hirsutism (excessive hair) and virilization (masculinization) due to tumors, polycystic ovaries, and adrenogenital syndromes.
The radioimmunoassay of free testosterone is a competitive assay. The procedure follows the basic principle of radioimmunoassay where there is competition between a radioactive and a non-radioactive antigen for a mixed number of antibody binding sites. The amount of [125]]-labeled testosterone analog bound to the antibody is inversely proportional to the concentration of unlabeled free testosterone present. The separation of the free and bound antigen is achieved by decanting or aspirating the antibody-coated tubes. A standard curve is constructed and unknown free testosterone values are obtained from the curve by interpolation.
Kit Content:
Free Testosterone Antibody-Coated Tubes: 2 x 50 tubes (ready-to-use)
125|-labeled Testosterone Analog Tracer (YELLOW): one 22 mL vial (ready-to-use)
Calibrators: one 1.0 mL vial labeled 0, and seven 0.5 mL vials labeled 1-7 (ready-to-use)
Controls: two 0.5 mL vials labeled 1, 2 (ready-to-use)
The provided text describes the Immunotech ACTIV\u00AE Free Testosterone RIA device, a radioimmunoassay for the quantitative measurement of free testosterone in human serum. This is an in vitro diagnostic device and the information provided is a 510(k) summary, which is typically for demonstrating substantial equivalence to a legally marketed predicate device.
Here's an analysis of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly present "acceptance criteria" for overall device performance in the form of pass/fail thresholds for clinical utility. Instead, it provides a summary of the analytical performance characteristics and reference ranges, which are the results of validation studies conducted to support the device's claims and demonstrate its performance.
| Performance Characteristic | Acceptance Criteria (Implicit from CLSI guidelines and typical IVD requirements) | Reported Device Performance |
|---|---|---|
| Sensitivity | - Limit of Blank (LoB) |
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(79 days)
/Device Name: ADVIA Centaur® Testosterone II (TSTII), ADVIA Centaur® SHBG Regulation Number: 21 CFR 862.1680
Product Code | CDZ |
| Regulation Number | 862.1680
Product Code | CDZ |
| Regulation Number | 862.1680
ADVIA Centaur® Testosterone II (TSTII)
The ADVIA Centaur® Testosterone II (TSTI) assav is for in the quantitative determination of total testosterone (bound and unbound) in human serum and plasma using the ADVIA Centaur XP system.
Measurements of testosterone are used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in males and, in females, hirsutism (excessive hair) and virilization) due to tumors, polycystic ovaries, and adrenogenital syndromes.
ADVIA Centaur® SHBG
The ADVIA Centaur® SHBG assay is an in vitro diagnostic immunoassay for the quantitative determination of sex hormone-binding globulin (SHBG) in human serum and plasma using the ADVIA Centaur XP system.
The ADVIA Centaur SHBG assay is intended for use as an aid in the diagnosis of androgen disorders.
The re-standardized ADVIA Centaur® Testosterone II (TSTII) and the ADVIA Centaur® SHBG are in vitro diagnostic immunoassays for use on the ADVIA Centaur® XP system. The ADVIA Centaur® Testosterone II (TSTII) assay quantitatively determines total testosterone in human serum and plasma. The ADVIA Centaur® SHBG assay quantitatively determines sex hormone-binding globulin (SHBG) in human serum and plasma. The submission includes details on the ingredients of the reagents for both assays.
Here's a breakdown of the acceptance criteria and study information for the ADVIA Centaur® Testosterone II (TSTII) and ADVIA Centaur® SHBG based on the provided text, formatted as requested:
1. Table of Acceptance Criteria and Reported Device Performance:
| Performance Characteristic | Acceptance Criteria (ADVIA Centaur® Testosterone II (TSTII)) | Reported Device Performance (ADVIA Centaur® Testosterone II (TSTII)) | Acceptance Criteria (ADVIA Centaur® SHBG) | Reported Device Performance (ADVIA Centaur® SHBG) |
|---|---|---|---|---|
| Detection Limits | ||||
| Limit of Blank (LoB) | (Implicitly good performance relative to predicate) | 2.50 ng/dL | (Not explicitly provided in this document) | (Previously established, see K151986 & K091867) |
| Limit of Detection (LoD) | (Implicitly good performance relative to predicate) | 5.00 ng/dL (95% probability) | (Not explicitly provided in this document) | (Previously established, see K151986 & K091867) |
| Limit of Quantitation (LoQ) | (Total CV of 20%) | 7.00 ng/dL (at 20% CV) | (Not explicitly provided in this document) | (Previously established, see K151986 & K091867) |
| Precision | (Implicitly good performance relative to predicate) | See table below for detailed CVs across various samples and concentrations. Generally, Within-Run CVs are lower than Within-Lab CVs. | (Not explicitly provided in this document) | (Previously established, see K151986 & K091867) |
| Linearity | Bias from linear fit estimate |
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(143 days)
Business Park Boldon NE35 9PD GB
Re: K190121
Trade/Device Name: IDS SHBG Regulation Number: 21 CFR 862.1680
The IDS SHBG assay is an in vitro diagnostic device intended for the quantitative determination of SHBG in human serum or plasma on the IDS System. Results are to be used as an aid in the diagnosis of androgen disorders
The IDS SHBG assay is an in vitro diagnostic device intended for the quantitative determination of sex hormone binding globulin (SHBG) in human serum and plasma on the IDS-iSYS Multi-Discipline Automated System. Results are to be used in conjunction with other clinical and laboratory data to assist the clinician in the diagnosis of androgen disorders.
The assay is based on chemiluminescence technology. 5 uL of patient sample or calibrators are incubated with biotinylated monoclonal anti-SHBG antibody, an acridinium labelled monoclonal anti-SHBG conjugate and streptavidin labelled magnetic particles. The magnetic particles are captured using a magnet and a wash step performed to remove any unbound analyte. Trigger reagents are added; the resulting light emitted by the acridinium label is directly proportional to the concentration of analyte in the original sample.
The IDS SHBG assay is an in vitro diagnostic device consisting of ready to use reagents provided in individual compartments within the reagent cartridge.
The reagent cartridge contains:
- Magnetic particles magnetic particles coated with streptavidin in a phosphate buffer containing preservatives
- -Biotin antibody - monoclonal anti-SHBG labelled with biotin in a buffer containing proteins and preservatives
- Conjugate monoclonal anti-SHBG labelled with an acridinium ester derivative in a buffer containing proteins and preservatives The calibrators consist of:
- Calibrators A and B are included in the assay kit. The calibrators consist of a human serum matrix with defined concentrations of SHBG and preservatives. Together with a lot specific master calibration curve, the calibrators will be used to perform adjustment of the master calibration curve.
The provided document is a 510(k) summary for the IDS SHBG assay, an in vitro diagnostic device for the quantitative determination of Sex Hormone Binding Globulin (SHBG). The document details the device's performance characteristics and compares it to a predicate device to demonstrate substantial equivalence.
Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text:
Key Takeaway: This document describes the validation of an in vitro diagnostic (IVD) assay, not an AI/ML-based diagnostic device that typically involves human readers or image analysis. Therefore, many of the requested categories (e.g., number of experts, adjudication method, MRMC studies, human reader improvement with AI, standalone AI performance) are not applicable to this type of device and study. The ground truth in this context is established by reference methods or validated reference materials, typical for IVD assays.
1. Table of Acceptance Criteria and Reported Device Performance
The document describes several analytical performance characteristics that serve as "acceptance criteria" for the IDS SHBG assay. These are primarily related to the accuracy, precision, limits of detection, and specificity of the assay.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Precision (Reproducibility) | Within-run and total precision (CV%) to be within acceptable limits for a quantitative assay. | Within Run CV: 1.7% to 3.7% across various SHBG concentration levels (e.g., IQC 1: 1.7% at 5.57 nmol/L; CV 3: 3.7% at 201.67 nmol/L). |
| Total CV: 3.2% to 5.0% across various SHBG concentration levels (e.g., IQC 3: 3.2% at 96.82 nmol/L; CTL3: 5.0% at 93.43 nmol/L). | ||
| (Compared favorably to predicate which reported 2.5-3.8% within run and 3.1-6.5% total precision.) | ||
| Linearity/Reportable Range | Assay to be linear over its claimed measuring range; accuracy demonstrated for automated dilution. | Measuring Range: Linear from 1.60 to 180.00 nmol/L for serum and K2 EDTA plasma (R2 values of 0.999 and 0.998 respectively). |
| Reportable Range: 0.30 to 720.00 nmol/L with automated 1:4 dilution for samples >180 nmol/L. | ||
| Recovery (Automated Dilution): 87% to 100% when compared to predicate for samples in the 180-720 nmol/L range (Mean recovery: 93%). | ||
| Detection Limits (LoB, LoD, LoQ) | Limits should be sufficiently low to meet diagnostic needs. | LoB: 0.01 nmol/L |
| LoD: 0.15 nmol/L | ||
| LoQ: 0.30 nmol/L | ||
| Traceability of Calibrator | Calibrator values must fall within specified acceptable ranges and internal quality controls within their respective ranges with defined precision. | Calibrator A: 0.10 to 0.30 nmol/L, precision CV ≤ 11%. Verified through internal QC procedures. |
| Calibrator B: 110.00 to 130.00 nmol/L, precision CV ≤ 8%. Verified through internal QC procedures. | ||
| Internal QC controls: CV ≤ 11% for IQC1, ≤ 8% for IQC2 and IQC3. Results from Table 11 show these were met (e.g., IQC1 Total CV 4.1%, IQC2 Total CV 3.4%, IQC3 Total CV 3.2%). | ||
| Analytical Specificity (Interference) | No significant interference from common biological substances and exogenous compounds up to tested concentrations. | No significant interference found for: |
- Triglycerides: up to 3000 mg/dL
- Haemoglobin: up to 500 mg/dL
- Bilirubin (conjugated/unconjugated): up to 40 mg/dL
- Total Protein: up to 12 g/dL
- Biotin: up to 6000 ng/mL (and 1500 ng/mL)
- Rheumatoid Factor: up to 7000 IU/mL
- HAMA: up to 3000 ng/mL
- Cholesterol: up to 456 mg/dL
- Various common drugs (e.g., Acetaminophen, Ibuprofen, Ascorbic acid, Creatinine, Dopamine, Tetracycline, Tolbutamide, Tolazamide, Uric Acid). |
| Analytical Specificity (Cross-Reactivity) | No significant cross-reactivity with structurally similar compounds or other biological substances up to tested concentrations. | Low/No significant cross-reactivity observed (50y:** 14.85 – 65.21 nmol/L (n=180)
Premenopausal Females: 20.30 – 140.18 nmol/L (n=206)
Postmenopausal Females: 11.30 – 127.31 nmol/L (n=120)
(Based on 671 apparently healthy adults from the United States). |
2. Sample Size Used for the Test Set and Data Provenance
- Precision/Reproducibility: 14 serum-based samples at different SHBG concentration levels covering the assay range. Tested across 21 days for one kit lot. (Table 11 shows individual sample IDs, CTLs, CALBs, IQCs)
- Linearity/Assay Reportable Range:
- Linearity: A high human serum sample and a low human serum sample, plus 14 evenly spaced dilutions created by mixing high and low samples.
- Automated Post-dilution Accuracy: 9 native samples with known SHBG concentrations obtained from the predicate device.
- Traceability of Calibrator:
- Value assignment of Internal Reference Standards (IRs): At least 24 runs using three iSYS instruments, 2 kit lots, 3 replicates for each run. Serial dilutions of WHO 2nd international standard 08/266 used.
- Value assignment of kit calibrators: At least 20 runs (14 runs using previous IR lot, 6 runs using international standard) using one iSYS instrument, 2 replicates for each run.
- Value assignment verification: Internal quality controls at 3 SHBG levels tested in five replicates in one run and on each of three different iSYS instruments.
- Correlation study (2-point calibration vs. IS 08/266 curve): 189 samples (139 serum, 50 K2 EDTA plasmas). Tested in two replicates using three lots (MB1, MB2, MB3) on one iSYS instrument.
- Detection Limit (LoB, LoD, LoQ):
- LoB: LoB sample run in 12 replicates for each of 5 runs over 3 days, by one operator, on one different instrument for each of 3 manufacture batches (MB1, MB2B, MB3) = total 60 replicates per lot.
- LoD: 7 LoD samples measured in duplicate. For each of 3 kit lots, 5 assays over 3 days by one operator on a different instrument = total 70 replicates per lot.
- LoQ: Panel of 9 samples measured in singlicate two times per day. For each of 3 kit lots, 10 assays over 5 days by one operator on a different instrument = total 90 replicates per lot.
- Analytical Specificity (Interference): Two serum samples (low and high SHBG conc.) spiked with potential interferents. Control samples were also run. Number of replicates for each specific test not detailed but implied to be sufficient for statistical comparison.
- Analytical Specificity (Cross-Reactivity): Low and high SHBG samples spiked with various cross-reactants. Number of replicates for each specific test not detailed.
- Method Comparison: 136 samples, selected to represent a wide range of SHBG concentrations (2.54 - 172.12 nmol/L).
- Matrix Comparison: 69 samples (68 native, 1 diluted) covering a range of 0.51 to 238.45 nmol/L.
- Expected Values/Reference Range: 671 serum samples from apparently healthy adults (21-77 years old). Data Provenance: From the United States. Retrospective/Prospective: Not explicitly stated, but typically such studies for establishing reference ranges are retrospective collections of banked samples or a prospective study designed to collect samples from a healthy population.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
Not Applicable (N/A).
This is an in vitro diagnostic (IVD) assay quantifying a biomarker (SHBG). "Ground truth" for an IVD assay is established through:
- Reference Methods: Such as the WHO 2nd international standard 08/266 for SHBG, against which the calibrators are standardized.
- Known Concentrations: Use of accurately prepared standards, spiked samples, or samples extensively characterized by reference methods.
- Clinical Data: For expected values, SHBG concentrations are measured in samples from defined healthy populations.
Therefore, the concept of "experts establishing ground truth" in the way it applies to image interpretation or AI-assisted diagnostics (e.g., radiologists labeling images) is not relevant here. The ground truth is analytical and based on metrological traceability to international standards.
4. Adjudication Method for the Test Set
N/A.
Adjudication methods (like 2+1, 3+1) are relevant for subjective interpretations (e.g., radiology reads) where discrepancies between readers need to be resolved to establish a definitive ground truth. For a quantitative IVD assay like IDS SHBG, the "reading" is a numerical output from the instrument based on chemical reactions. Accuracy is determined by comparison to reference materials or established methods, not by human adjudication of interpretations.
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
N/A.
This is an IVD assay, not an AI/ML diagnostic for human interpretation. No MRMC study or human reader improvement with AI assistance is applicable.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
N/A.
This is not an AI/ML algorithm. The "device" is a fully automated immunoassay system (IDS-iSYS Multi-Discipline Automated System) that performs the biochemical analysis and reports a quantitative result without human "interpretation" of a signal beyond reading the numerical output. Its performance is evaluated as a standalone analytical system.
7. The Type of Ground Truth Used
The ground truth for the analytical performance studies (precision, linearity, detection limits, specificity, method comparison) is based on:
- International Reference Standards: Specifically, the WHO 2nd international standard for SHBG (IS 08/266) for traceability and calibration. This is the primary reference.
- Known Concentrations/Spiked Samples: Samples with defined, known concentrations of SHBG or interferents, prepared in a laboratory setting.
- Comparison to a Legally Marketed Predicate Device: The Siemens ADVIA Centaur SHBG assay (K151986) was used as a comparative method to assess agreement and accuracy (e.g., for method comparison and automated dilution accuracy).
- Healthy Population Data: For expected values/reference ranges, a large cohort of apparently healthy individuals were tested to establish population-specific normal ranges.
8. The Sample Size for the Training Set
N/A (for AI/ML 'training set' in the traditional sense).
For an IVD assay, the equivalent of a "training set" would be the samples and calibrators used during the assay's development and optimization phases to set parameters, establish reagent formulations, and fine-tune the system. This information is typically proprietary development data and is not explicitly detailed as a 'training set' in 510(k) summaries, which focus on the final validation/test data.
The closest analogous "training" or "calibration" process mentioned is the traceability and value assignment of calibrators:
- Value assignment of secondary standards (IRs) involves at least 24 runs (using 3 instruments, 2 kit lots, 3 replicates) comparing to the WHO international standard.
- Value assignment of IDS SHBG kit calibrators A and B involves at least 20 runs (1 instrument, 2 replicates) using the secondary standards and IS-08/266.
These processes are used to establish the calibration curve for the assay.
9. How the Ground Truth for the Training Set Was Established
N/A (for AI/ML 'training set').
As explained in point 8, the concept of a "training set" for an IVD assay is different from that for AI/ML. The "ground truth" for establishing the calibration and parameters of the assay is based on:
- Metrological traceability to the WHO 2nd international standard for SHBG (IS 08/266). This involved serial dilutions of the international standard in SHBG-depleted human serum to create reference points.
- Use of internal reference calibrators (IRs) that were themselves value-assigned against the WHO standard.
The goal is that the assay's measurements accurately reflect the true concentration of SHBG as defined by an international reference.
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(138 days)
Trade/Device Name: FastPack IP Sex Hormone Binding Globulin Immunoassay Regulation Number: 21 CFR 862.1680
CDZ – SHBG Assay |
| Regulation Numbers: | 21 CFR § 862.1680
FastPack® IP SHBG is a chemiluminescent immunoassay intended for the quantitative determination of Sex Hormone Binding Globulin in human serum and plasma on the FastPack® System. The FastPack® IP SHBG assay is intended for use as an aid in the diagnosis of androgen disorders.
The FastPack® IP Sex Hormone Binding Globulin Immunoassay employs a sandwich immunoassay principle. Endogenous SHBG in a patient sample, calibrator, or control is dispensed into a FastPack® reagent pack. In the reagent pack, the sample binds with a monoclonal anti-SHBG antibody covalently linked to alkaline phosphatase (ALP) and a different monoclonal anti-SHBG antibody linked to biotin will bind to streptavidin coated paramagnetic particles (PMP). After incubation, washing steps (using a Tris buffer containing detergents) occur to separate bound from unbound anti-SHBG monoclonal antibody-ALP, a chemiluminogenic substrate mixture is added to the system. This mixture contains indoxyl-3-phosphate, a substrate for ALP, and lucigenin (N,N dimethyl-9,9'-biacridinium dinitrate). ALP dephosphorylates indoxyl-3-phosphate to indol-3-ol, which subsequently undergoes oxidation. As a result, lucigenin is reduced to form a dioxetane structure that is cleaved to yield N-methylacridone. This compound produces a sustained luminescent glow following excitation. The raw relative luminescence units (RLUs) generated are measured by a photomultiplier tube in the FastPack® Analyzer and are directly proportional to the concentration of SHBG in the sample. The entire reaction sequence takes place at 37 ± 0.5 ℃ and is protected from external light.
Here's an analysis of the provided text regarding the FastPack® IP Sex Hormone Binding Globulin Immunoassay's acceptance criteria and studies:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state formal "acceptance criteria" for all performance characteristics in a separate section. However, based on the comparative effectiveness study against a predicate device and the presented performance data, we can infer some implied acceptance ranges or targets for the new device.
| Performance Characteristic | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Precision (%CV) | Similar to or better than predicate (≤ 5.5% for all listed). Stated target: Within-run: ≤ 10%, Between-run: ≤ 8%, Between-day: ≤ 8% | Reagent lot 1, analyzer 1, calibrator lot 1: |
- Within-Run: 2.74% - 6.95%
- Between-Run: 0.00% - 7.79%
- Between-Day: 0.00% - 4.96%
- Total: 3.21% - 7.06%
Reagent lot 2, analyzer 2, calibrator lot 2:
- Within-Run: 4.16% - 7.74%
- Between-Run: 0.00% - 6.56%
- Between-Day: 1.25% - 7.44%
- Total: 5.04% - 11.53%
Reagent lot 3, analyzer 3, calibrator lot 3:
- Within-Run: 3.4% - 9.60%
- Between-Run: 0.0% - 7.21%
- Between-Day: 0.0% - 6.05%
- Total: 4.0% - 12.05% |
| Linearity | Assay linear within a specified range (Predicate: 0.33 - 200 nmol/L) | Linear from LOQ (0.80 nmol/L) to 174 nmol/L |
| Interfering Substances | No interference at specified levels (similar to predicate) | No interference with listed compounds (e.g., conjugated bilirubin 40 mg/dL, hemoglobin 1.0 g/dL, lipid 1000 mg/dL, d-Biotin 0.2 mg/dL) and cross-reactants (e.g., Transferrin 0.5 g/dL, Testosterone 2.5 mg/dL, etc.) at specified concentrations. Rheumatoid factor up to 1000 IU/mL and human anti-mouse IgG up to 4 µg/mL also showed no cross-reactivity. Six known heterophile samples did not generate detectable interference. |
| Method Comparison | Strong correlation to predicate (Predicate R2 = 0.94) | R = 0.985, Slope (95% CI): 0.993 (0.967-1.019), y-intercept (95% CI): -0.614 (-2.21 to 0.982), R2 = 0.971 |
| Sample Type Equivalence| Equivalence between serum and plasma | Strong correlation between serum and lithium-heparin plasma via Passing-Bablok regression: Slope (95% CI): 0.960 (0.920-1.00), y-intercept (95% CI): 1.859 (-0.89 to 4.61), R = 0.990, R2 = 0.979. Absolute bias 1.117 nmol/L, % Bias 1.928%. |
| LOB | Not explicitly stated for acceptance, but a calculated value | 0.08 nmol/L SHBG |
| LOD | Not explicitly stated for acceptance, but a calculated value | 0.20 nmol/L SHBG |
| LOQ | Lowest sample with
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(101 days)
Trade/Device Name: Free Testosterone AccuBind ELISA Test System Regulation Number: 21 CFR 862.1680
| Class I, Reserved |
| | Regulation Number / Panel: | 862.1680
The Free Testosterone AccuBind® ELISA Test System is an Enzyme Immunoassay (EIA) for the quantitative measurement of free testosterone in human serum. Measurement of free testosterone is used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, impotence in males and in females; hirsutism (excessive hair) and virilization (masculinization) due to tumors, polycystic ovaries and androgenital syndromes.
The kit consists of seven (7) vials of serum reference calibrators for Free Testosterone with two (2) controls (one low and one high); one (1) vial of Testosterone (Analog)-horseradish peroxidase (HRP) conjugate in a protein stabilizing matrix; one 96-well testosterone antibody-coated microplate; one (1) vial of concentrated wash solution; two (2) vials for tetramethy(benzidine (TMB) substrate solution preparation; and one (1) vial of stop reaction solution.
The provided document describes the analytical performance of the Monobind Inc. Free Testosterone AccuBind® ELISA Test System, an in vitro diagnostic device, rather than an AI/ML-driven device. Therefore, many of the requested criteria often associated with AI/ML device studies (e.g., number of experts for ground truth, MRMC studies, human-in-the-loop performance, training set details) are not applicable to this type of medical device.
However, I can extract the relevant information regarding the device's acceptance criteria and the study that proves it meets them as presented in the document.
Here's the breakdown:
1. Table of Acceptance Criteria and Reported Device Performance
For this type of in-vitro diagnostic device, "acceptance criteria" are typically defined by regulatory standards and good laboratory practices (e.g., CLSI guidelines). The document presents analytical performance data against these established industry benchmarks rather than explicit numerical acceptance criteria beyond what is internally defined for successful assay development and validation (e.g., precision specifications).
| Performance Metric | Acceptance Criteria (Implicit from Industry Standards/Good Practice) | Reported Device Performance (Representative Lot / Combined Lot) |
|---|---|---|
| Precision | Low %CV for within-run and total precision across concentrations. | Within-Run CV: 3.6-7.9% (Representative Lot), 4.23-5.95% (Combined Lot) |
| Total CV: 7.8-12.4% (Representative Lot), 7.20-9.43% (Combined Lot) | ||
| Linearity (Accuracy) | High correlation coefficient (R) and slope close to 1. | y = 1.0149x - 0.6028, R = 0.9888 (Excellent linearity) |
| Recovery | Percent recovery close to 100% for spiked samples. | 98.7% - 105.2% (Across 5 patient samples) |
| Reagent/Kit Stability | Demonstrates stability for stated shelf life and open-vial stability. | 2 years (unopened kit), 61 days (open kit, calibrators, controls, enzyme reagent, TMB, plate) |
| Sample Stability | Demonstrates stability for specified storage conditions. | 61 days (serum at 2-8°C), 31 days (frozen serum at -20°C) |
| Detection Limits | Defined LOB, LOD, LOQ based on CLSI EP17-A. | LoB: 0.0295 pg/ml; LoD: 0.0519 pg/ml; LoQ: 0.0519 pg/ml |
| Cross-Reactivity | Generally low cross-reactivity (10% difference) observed. | |
| Method Comparison | Strong correlation with predicate device (high R, slope near 1, low intercept). | y = 1.017x - 0.244, Correlation Coefficient = 0.997 (Excellent agreement) |
| Interferences | No significant interference at specified concentrations for various substances. | Most substances showed no significant interference at the tested concentrations. |
2. Sample Size Used for the Test Set and Data Provenance
- Precision Study:
- Sample Size: For the representative lot, 3 control samples were tested, with 80 measurements per sample (duplicate, two times per day for 20 days). 3 serum pools were also tested in the same manner (N=32 readings for the representative lot table, N=80 for combined lot table). For the combined lot precision, 3 controls and 3 patient samples (serum pools) were used, with a total of 80 measurements per sample.
- Data Provenance: Not explicitly stated, but typical for in vitro diagnostic device validation, these would be controlled laboratory studies using clinical samples (serum pools and control materials). No mention of country of origin or retrospective/prospective clinical data for the performance evaluation (this differs from the reference range determination).
- Linearity Study: 11 concentrations of sample preparations.
- Recovery Study: 5 serum samples (containing different levels of endogenous testosterone).
- Reference Range Determination: 261 male and female serum samples.
- Data Provenance: Not specified for the 261 samples, but typically these samples are collected under ethical guidelines from a relevant population.
- Cross-Reactivity Study: Specific compounds were tested with male serum spiked samples and blank serum spiked samples. No specific number of replicates per compound is given, but "aliquots from pool of human serum" are mentioned for testosterone cypionate and undecanoate.
- Method Comparison Study: 137 samples.
- Data Provenance: Not explicitly stated, but these would be clinical samples with varying testosterone levels.
- Interferences Study: Charcoal-stripped human serum spiked with known concentrations of interferent.
3. Number of Experts Used to Establish the Ground Truth and Qualifications of Experts
- Not Applicable. For an in-vitro diagnostic assay for quantitative measurement of an analyte like Free Testosterone, the "ground truth" is established by the analytical method itself (the assay's ability to accurately measure the target analyte) and validated against reference methods or calibrated materials. There are no human "experts" establishing image-based ground truth as would be the case for AI/ML diagnostic tools. The predicate device serves as a comparative "ground truth" for method comparison.
4. Adjudication Method for the Test Set
- Not Applicable. This is an in-vitro diagnostic assay, not an AI/ML system requiring human adjudication of results. The results are quantitative measurements.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No. This is an in-vitro diagnostic assay, not an imaging AI/ML device that assists human readers. Therefore, an MRMC study is not relevant or performed.
6. Standalone (Algorithm Only) Performance
- Yes (inherently). The device itself is the "standalone" measurement system. Its performance (precision, linearity, recovery, sensitivity, specificity, interference) is evaluated on its own. There isn't a separate "human-in-the-loop" component as would be found in an AI-assisted diagnostic workflow.
7. The Type of Ground Truth Used
The ground truth for this device's performance validation is established through:
* Known Concentrations: For precision (control materials with known values), linearity (prepared concentrations), recovery (spiked samples with known additions), detection limits (analyzing blanks and low-concentration samples).
* Reference Methods/Predicate Device: For method comparison, the predicate device (EiAsy Free Testosterone EIA) serves as the comparator.
* Established Analytical Principles: The fundamental biochemical reactions and measurement principles of the ELISA platform.
* CLSI Guidelines: Adherence to established Clinical and Laboratory Standards Institute (CLSI) guidelines (e.g., EP06-A, C28-A3, EP17-A, EP07-A2) for validation studies provides the framework for defining acceptable performance.
8. The Sample Size for the Training Set
- Not Applicable. This is an in-vitro diagnostic assay, not an AI/ML device that requires a distinct "training set" in the context of machine learning model development. The development and optimization of the assay's reagents and protocol are analogous to "training" in a general sense, but no specific numerical sample size is defined as a training set for an algorithm.
9. How the Ground Truth for the Training Set Was Established
- Not Applicable. As above, there is no AI/ML "training set." The "ground truth" for developing such an assay comes from fundamental biochemical understanding, chemical synthesis of reagents, and iterative optimization of assay conditions to achieve desired analytical performance characteristics. This involves standard laboratory development practices common to IVD manufacturing.
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