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510(k) Data Aggregation
(469 days)
The ARK Lacosamide Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of lacosamide in human serum on automated clinical chemistry analyzers. The measurements obtained are used in monitoring levels of lacosamide to help ensure appropriate therapy.
The ARK Lacosamide Assay is a homogeneous enzyme immunoassay based on competition between drug in the specimen and lacosamide labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for binding to the antibody reagent. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly related to the drug concentration. Active enzyme converts the coenzyme nicotinamide adenine dinucleotide (NAD) to NADH that is measured spectrophotometrically as a rate of change in absorbance. Endogenous serum G6PDH does not interfere with the results because the coenzyme NAD functions only with the bacterial enzyme used in the assay.
The ARK Lacosamide Assay consists of reagents R1 anti-lacosamide polyclonal antibody with substrate and R2 lacosamide labeled with bacterial G6PDH enzyme.
The provided text describes the ARK Lacosamide Assay, a homogeneous enzyme immunoassay for quantitative determination of lacosamide in human serum. This device is intended for monitoring lacosamide levels to ensure appropriate therapy. The substantial equivalence is demonstrated through comparative testing against a predicate device (ARKTM Topiramate Assay, K083799) and various performance characteristic studies.
Here's a breakdown of the acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance:
| Performance Characteristic | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Limit of Quantitation (LoQ) | Acceptable inter-assay precision (<20% CV) and recovery (±15%) | 0.40 ug/mL, with CVs ranging from 3.4% to 5.0% and recoveries from 83.2% to 94.1% for tested concentrations. |
| Measurement Range | N/A (Range established) | 0.40 - 24.00 µg/mL |
| Recovery | Within ±10% of expected sample concentration | Recoveries for various concentrations from 0.40 to 20.00 µg/mL were between 90.4% and 105.8%. |
| Linearity | Percent difference ±10% (for >1.00 µg/mL) or ≤0.20 µg/mL (for ≤1.00 µg/mL) between 1st and 2nd order regressed values. | Linear relationship demonstrated between 0.40 and 25.00 µg/mL (y = 0.9998x - 0.0170). Differences within acceptable limits. |
| Precision (Total CV) | ≤10% total CV | For controls and human serum samples, total CVs ranged from 3.9% to 4.5%. |
| Interfering Substances | Measurement of lacosamide resulted in ≤10% error | All tested interfering substances resulted in ≤10% error (recoveries ranging from 95.8% to 103.5%). |
| Specificity (O-Desmethyl Metabolite) | Not clinically significant (< 3.0% crossreactivity) | Crossreactivity of O-desmethyl lacosamide metabolite was not clinically significant. |
| Crossreactivity (Other Drugs) | Recoveries within 10% of the expected level | Recoveries for 77 compounds ranged from 90.9% to 109.5%. |
| Sample Stability | N/A (Stability demonstrated) | Stable for at least 48 hours at room temperature, 28 days refrigerated, and 34 months frozen. Stable after 3 freeze/thaw cycles. |
| Shelf-life Stability | N/A (Stability demonstrated) | Up to 18 months when stored unopened at 2-8°C. |
| On-Board Stability | N/A (Stability demonstrated) | Up to 60 days on-board the instrument. |
| Calibration Curve Stability | N/A (Stability demonstrated) | Effective up to at least 14 days. |
| Method Comparison (vs. LC-MS/MS) | N/A (Correlation established) | Slope: 1.01 (0.99 to 1.04), y-intercept: 0.03 (-0.10 to 0.15), r2: 0.98 (0.98 to 0.99) |
2. Sample size used for the test set and the data provenance:
- LoQ: 40 replicates (8 replicates x 5 runs) for each of 3 concentrations. Data provenance is implied to be laboratory-generated (pooled human serum supplemented with lacosamide).
- Measurement Range: Not a directly tested "test set" in terms of patient samples; rather, it refers to the range characterized by other studies like recovery and linearity.
- Recovery: Not explicitly stated as a separate "test set" size for recovery studies, but involved adding concentrated lacosamide to pooled human serum. "Two analytical runs of three replicates of each sample were assayed."
- Linearity: Dilutions of a 30.00 µg/mL lacosamide serum sample. "Two analytical runs of three replicates of each sample were assayed."
- Method Comparison: 150 unaltered, human serum specimens. The data provenance is described as "human serum specimens" which implies retrospective clinical samples, but the country of origin is not specified. They are "not individually identifiable."
- Precision: 160 replicates for each of 6 samples/controls (quadruplicate twice a day for 20 days). Implied laboratory-generated (tri-level controls and pooled human serum with lacosamide).
- Interfering Substances: For each interfering substance, lacosamide was present at 2 concentrations (2.0 and 15.0 µg/mL). "Two analytical runs of three replicates of each sample (6 replicates total) were assayed." Implied laboratory-generated.
- Specificity (O-Desmethyl Metabolite): Assayed lacosamide at 2 concentrations (2.00 and 15.00 µg/mL) in the absence and presence of the metabolite at 2 concentrations (5.0 and 30.0 µg/mL). Implied laboratory-generated.
- Crossreactivity (Other Drugs): For each of 77 compounds, lacosamide was present at 2 concentrations (2.00 and 15.00 µg/mL). Implied laboratory-generated.
- Sample Stability: Not a statistical "test set" but based on supporting data; implies samples stored under different conditions.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This device is an in vitro diagnostic assay that measures a chemical compound (lacosamide concentration). The "ground truth" for method comparison studies is established by a reference method, not by expert interpretation.
- In the method comparison study, the ARK Lacosamide Assay results were compared against LC-MS/MS (Liquid Chromatography-Mass Spectrometry/Mass Spectrometry). LC-MS/MS is a highly accurate and sensitive analytical chemistry technique, often considered a "gold standard" for quantifying small molecules like drugs in biological matrices.
- Therefore, no human experts were used to establish the ground truth; instead, an established analytical method served as the reference.
4. Adjudication method for the test set:
- Not applicable as the ground truth is established by a quantitative analytical method (LC-MS/MS), not by human interpretation or consensus.
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 device is an in vitro diagnostic assay, not an AI-powered diagnostic imaging or interpretation tool that assists human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the performance characteristics described (LoQ, Measurement Range, Recovery, Linearity, Precision, Interfering Substances, Specificity, Crossreactivity, Stability) are all standalone algorithm (assay) performance studies. The method comparison study also evaluated the standalone performance of the ARK Lacosamide Assay against LC-MS/MS.
- The device explicitly states it is "intended for the quantitative determination of lacosamide in human serum on automated clinical chemistry analyzers," indicating standalone operation with human oversight rather than human-in-the-loop interpretation of complex data.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For the method comparison study, the ground truth was "results from LC-MS/MS," which is a reference analytical method.
- For other performance studies (LoQ, recovery, linearity, precision, interference, specificity, cross-reactivity), the ground truth was based on the known concentrations of lacosamide and interfering substances added to human serum samples.
8. The sample size for the training set:
- This is an in vitro diagnostic assay, not a machine learning or AI model that requires a "training set" in the conventional sense. The development of the assay's reagents and methodologies involves analytical chemistry and biochemical principles rather than statistical training on data.
9. How the ground truth for the training set was established:
- Not applicable for the reasons stated in point 8. The "ground truth" for the development of this assay would be the accurate chemical characterization of lacosamide and its antibodies, and the optimization of the enzymatic reaction to accurately reflect lacosamide concentration.
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(168 days)
The ARK™ Zonisamide Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of zonisamide in human serum or plasma samples on automated clinical chemistry analyzers. Zonisamide concentrations can be used as an aid in management of patients treated with zonisamide.
The ARK™ Zonisamide Calibrator is intended for use in calibration of the ARK Zonisamide Assay.
The ARK™ Zonisamide Control is intended for use in quality control of the ARK Zonisamide Assav.
The ARK Zonisamide Assay is a homogeneous immunoassay based on competition between drug in the specimen and zonisamide labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for binding to the antibody reagent. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly proportional to the drug concentration. Active enzyme converts the coenzyme nicotinamide adenine dinucleotide (NAD) to NADH that is measured spectrophotometrically as a rate of change in absorbance. Endogenous serum G6PDH does not interfere with the results because the coenyzme NAD functions only with the bacterial enzyme used in the assay.
The ARK Zonisamide Assay consists of reagents R1 anti-zonisamide polyclonal antibody with substrate and R2 zonisamide labeled with bacterial G6PDH enzyme. The ARK Zonisamide Calibrator consists of a six-level set to calibrate the assay, and the ARK Zonisamide Control consists of a three-level set used for quality control of the assay.
Here's a breakdown of the acceptance criteria and the study details for the ARK Zonisamide Assay, based on the provided 510(k) summary:
Acceptance Criteria and Device Performance
| Test/Characteristic | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Limit of Quantitation (LOQ) | <20% CV with ±15% recovery | 2.0 µg/mL (with corresponding recovery and precision) |
| Recovery | % Recovery close to 100% (within reasonable analytical limits, e.g., ±15%) | Ranges from 85.3% to 110.0% for concentrations 2.0 - 50.0 µg/mL |
| Linearity | % Difference ±10% between predicted 1st and 2nd order regressed values (±15% below 3.0 µg/mL) | Ranges from -7.0% to 2.7% for concentrations 2.4 - 48.0 µg/mL |
| Assay Range | Defined range of quantitative measurement | 2.0 to 50.0 µg/mL |
| Method Comparison (Correlation Coefficient) | High correlation (e.g., r² > 0.90) with predicate device | r² = 0.93 (0.91 to 0.95 95% CI) |
| Precision (Total CV) | <10% Total CV | Ranges from 4.5% to 5.9% for various concentration levels |
| Interfering Substances | Error ≤10% in the presence of listed interferents | Error ≤10% for all tested interfering substances |
| Drug Interference | Error ≤10% in the presence of listed drug compounds | Error ≤10% for all tested drug compounds |
| Anticoagulants | No significant difference in recovery between serum and plasma | No significant difference between serum and plasma samples |
| Sample Stability (Room Temp) | Stable for at least 24 hours | Stable for at least 24 hours (22°C) |
| Sample Stability (Refrigerated) | Stable for a specified duration | Stable for 28 days (2-8°C) |
| Sample Stability (Frozen) | Stable for a specified duration | Stable for 56 days |
| Sample Stability (Freeze/Thaw) | Stable after 3 successive freeze/thaw cycles | Stable after 3 successive freeze/thaw cycles |
| Calibration Curve Stability | Effective for a specified duration | Effective up to 46 days |
| Reagent On-Board Stability | Effective for a specified duration | Effective up to 32 days (uncapped) and 46 days (capped) |
Study Details
-
Sample sizes used for the test set and the data provenance:
- LOQ: 20 replicates for each sample. Data provenance not specified (likely laboratory-prepared samples).
- Recovery: 20 replicates for each sample. Data provenance not specified (likely laboratory-prepared samples with added drug).
- Linearity: Zonisamide concentrations ranged from 0.8 to 80.0 ug/mL, with dilutions made proportionally. Data provenance not specified (likely laboratory-prepared samples).
- Method Comparison: 176 samples. Data provenance not specified.
- Precision: 160 replicates per control level and human serum level (quadruplicate twice a day for 20 days). Data provenance not specified (likely laboratory-prepared controls and pooled human serum specimens).
- Interfering Substances: Zonisamide levels of approximately 15 and 45 µg/mL, spiked with various interferents. Specific number of samples per interferent not specified, but each was "evaluated." Data provenance not specified (likely laboratory-prepared samples).
- Metabolites: Zonisamide levels of 15 µg/mL and 45 µg/mL, spiked with NAZ (50.0, 10.0 µg/mL) and SMAP (50.0, 10.0 µg/mL). Data provenance not specified (likely laboratory-prepared samples).
- Drug Interference: Zonisamide levels of approximately 15 and 45 µg/mL, spiked with various drug compounds. Specific number of samples per drug not specified, but each was "assayed." Data provenance not specified (likely laboratory-prepared samples).
- Anticoagulants: Not explicitly stated, but "studies were conducted" on serum and plasma. Data provenance not specified.
- Sample Stability: Not explicitly stated, but "serum specimens were shown to be stable" under various conditions. Data provenance not specified.
- On-Board Stability: "Supporting data" cited, but specific sample sizes and provenance not detailed.
-
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- No expert ground truth was described for the test set. The ground truth for analytical performance studies (LOQ, recovery, linearity, precision) is typically established by precisely preparing samples with known concentrations. For method comparison, the predicate device serves as the comparative "truth."
-
Adjudication method for the test set:
- Not applicable, as this is an in vitro diagnostic assay and not an image-based or qualitative diagnostic device requiring expert adjudication.
-
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 in vitro diagnostic assay, not an AI-assisted diagnostic tool for human readers.
-
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, the entire submission describes the standalone performance of the ARK Zonisamide Assay. Its function is to quantitatively determine zonisamide concentrations in samples, which is an algorithm-only (analytical assay) performance.
-
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Analytical Ground Truth: For most studies (LOQ, recovery, linearity, interfering substances, drug interference, metabolites), the ground truth was established through gravimetrical or volumetric preparation of samples with known, spiked concentrations of zonisamide or interfering substances.
- Comparative Ground Truth: For the method comparison study, the predicate device (QMS® Zonisamide Assay) served as the reference for comparison.
-
The sample size for the training set:
- The document does not describe a "training set" in the context of machine learning or AI. This assay is a chemical immunoassay, not a learning algorithm. The studies described are analytical validation studies to characterize the performance of the chemical reaction and measurement system.
-
How the ground truth for the training set was established:
- As there is no described training set, this question is not applicable.
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(115 days)
The ARK™ Topiramate Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of topiramate in human serum or plasma on automated clinical chemistry analyzers. The results obtained are used in the diagnosis and treatment of topiramate overdose and in monitoring levels of topiramate to help ensure appropriate therapy.
The ARK™ Topiramate Calibrator is intended for use in calibration of the ARK Topiramate Assav.
The ARKTM Topiramate Control is intended for use in quality control of the ARK Topiramate Assay.
The ARK Topiramate Assay is a homogeneous immunoassay based on competition between drug in the specimen and topiramate epitope labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for binding to the antibody reagent. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly proportional to the drug concentration. Active enzyme converts the coenzyme nicotinamide adenine dinucleotide (NAD) to NADH that is measured spectrophotometrically as a rate of change in absorbance. Endogenous serum G6PDH does not interfere with the results because the coenyzme NAD functions only with the bacterial enzyme used in the assay.
The ARK Topiramate Assay consists of reagents R1 anti-topiramate polyclonal antibody with substrate and R2 topiramate epitope labeled with bacterial G6PDH enzyme. The ARK Topiramate Calibrator consists of a six-level set to calibrate the assay, and the ARK Topiramate Control consists of a three-level set used for quality control of the assay.
Here's a breakdown of the acceptance criteria and the studies that prove the device meets them, based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Limit of Quantitation (LOQ) | ≤20% CV with ±15% recovery | 1.5 µg/mL |
| Accuracy (Analytical Recovery) | Percent recoveries within 10% of theoretical levels | All reported values from 1.5 µg/mL to 55.0 µg/mL were within 10% of theoretical (e.g., 95.6% to 107.1% recovery). Example: 1.5 µg/mL recovered 95.6%, 55.0 µg/mL recovered 107.1%. |
| Linearity | Percent difference ≤ ±10% between predicted 1st and 2nd order regressed values | Demonstrated linearity between 1.2 and 54.0 µg/mL. Max % Difference outside this range was -18.14% at 0.6 µg/mL. All values within 1.2-54.0 µg/mL were within ±10%. |
| Assay Range | Not explicitly stated as acceptance criteria, but defined as output. | 1.5 µg/mL to 54.0 µg/mL |
| Precision (Total CV) | <10% total CV | Sample 1 (2.4 µg/mL): 4.2% CVSample 2 (10.2 µg/mL): 2.7% CVSample 3 (40.2 µg/mL): 3.2% CV |
| Interfering Substances | Measurement of topiramate resulted in ≤10% error | All tested substances (e.g., Albumin, Bilirubin, Cholesterol, Hemoglobin) at clinically high concentrations resulted in ≤10% error. |
| Metabolites (Cross-Reactivity) | Measurement of topiramate resulted in ≤10% error | 9-Hydroxy-topiramate at 40.0 µg/mL resulted in 8.6% error for low topiramate and 3.2% error for high topiramate. |
| Drug Interference | Measurement of topiramate resulted in ≤10% error | All tested co-administered drugs (e.g., Acetaminophen, Carbamazepine, Phenobarbital, Valproic Acid) at high concentrations resulted in ≤10% error. |
| Anticoagulants | No significant difference between serum and plasma recovery | Results indicated no significant difference between serum and plasma recovery. |
| Calibration Curve Stability | Not explicitly stated as acceptance criteria, but reported. | Effective up to 49 days. |
| Reagent On-board Stability | Not explicitly stated as acceptance criteria, but reported. | Effective for up to 60 days. |
2. Sample Size Used for the Test Set and Data Provenance
- Accuracy: Not explicitly stated as a "test set" in the traditional sense. Samples were human serum negative for topiramate, spiked with known topiramate concentrations. Six replicates were performed for each concentration. Data provenance is implied to be laboratory-generated through spiking.
- Linearity: A 60.0 µg/mL serum sample was prepared and proportionally diluted with human serum negative for topiramate. Topiramate concentrations ranged from 0.6 to 60.0 µg/mL. Data provenance is laboratory-generated.
- Method Comparison: 113 samples.
- Data Provenance: Not explicitly stated for this particular study (e.g., country of origin, retrospective/prospective). However, given the context of a 510(k) for an in vitro diagnostic, these samples would typically come from patients, likely collected retrospectively or prospectively for method validation purposes.
- Precision: Tri-level controls were used. Each level was assayed in quadruplicate, twice a day for 20 days (N=160 for each level). Data provenance is laboratory-generated.
- Interfering Substances: Samples were human serum with known levels of topiramate (approximately 5 and 20 µg/mL) spiked with high concentrations of various interfering substances. Data provenance is laboratory-generated.
- Metabolites: Samples were human serum with known levels of topiramate spiked with 9-hydroxy-topiramate. Data provenance is laboratory-generated.
- Drug Interference: Samples were normal human serum with known levels of topiramate (approximately 5 and 20 µg/mL) spiked with high concentrations of various drug compounds. Data provenance is laboratory-generated.
- Anticoagulants: Not explicitly detailed, but implied to involve testing serum and plasma samples containing topiramate. Data provenance is laboratory-generated.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
Not applicable. This is an in vitro diagnostic device for quantitative determination of a drug in serum/plasma. The "ground truth" for the test set (e.g., known concentrations for accuracy, reference method results for method comparison) is established through analytical techniques, not expert adjudication of images or clinical cases.
4. Adjudication Method for the Test Set
Not applicable. As noted above, this device performance is assessed through analytical measurements against known concentrations or a reference method, not through expert adjudication in the context of diagnostic interpretation.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No, an MRMC comparative effectiveness study was not done. This type of study is typically conducted for diagnostic imaging devices where human readers interpret cases, and the AI's impact on their performance is evaluated. This device is an automated in vitro diagnostic assay.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the studies presented are all standalone validations of the analytical performance of the ARK Topiramate Assay. The device is intended for quantitative determination on automated clinical chemistry analyzers, meaning it operates without direct human-in-the-loop interpretation of its primary output.
7. The Type of Ground Truth Used
The ground truth used for these studies includes:
- Known Reference Concentrations: For accuracy and linearity studies, serum samples were spiked with precisely measured, highly pure topiramate to create samples with known theoretical concentrations.
- Reference Method Results: For the method comparison study, results from the ARK Topiramate Assay were compared against a "commercially available FPIA Immunoassay." The results from this predicate method served as the reference or ground truth for comparison.
- Known Spiked Levels: For interference, metabolite, and drug interference studies, known quantities of the interfering substance, metabolite, or drug were added to samples with known topiramate concentrations.
8. The Sample Size for the Training Set
Not applicable. This document describes the validation of a predefined assay, not the development or training of a machine learning algorithm. Therefore, there is no "training set" in the context of an AI/ML device. The reagents are pre-formulated for the immunoassay.
9. How the Ground Truth for the Training Set was Established
Not applicable for the same reason as point 8.
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(70 days)
The Seradyn QMS® Topiramate assay is intended for the quantitative determination of topiramate in human serum or plasma on automated clinical chemistry analyzers.
The results obtained are used in the diagnosis and treatment of topiramate overdose and in monitoring levels of topiramate to help ensure appropriate therapy.
The Seradyn QMS® Topiramate assay is a homogeneous particle-enhanced turbidimetric immunoassay. The assay is based on competition between drug in the sample and drug coated onto a micronariticle for antibody binding sites of the topiramate antibody reagent. The topiramate-coated micropariticle peagent is rapidly agglutinated in the presence of the anti-topiramate antibody reagent and in the abserved of any competing drug in the sample. The rate of absorbance change is measured photometrically. When a smale containing topiramate is added, the agglutination reaction is partially inhibited, slowing down the rate of absorbance change. A concentration-dependent classic agglutination inhibition curve can be obtained with maximum rate of agglutination at the lowest topiramate concentration and the lowest agglutination rate at the highest topiramate concentration.
The assay consists of reagents R1: anti-topiramate polyclonal antibody and R2: topiramate-ooated microparticles. A six-level set of Seradyn QMS® Topiramate Cali three-level set of Seradyn QMS® Topiramate Controls is used for quality control of the assay.
Here's an analysis of the Seradyn QMS® Topiramate assay based on the provided 510(k) summary, structured to address your specific points:
Seradyn QMS® Topiramate Assay Study Analysis
1. Table of Acceptance Criteria and Reported Device Performance:
| Performance Metric | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Accuracy (Recovery) | 100 ± 10% | Mean Percent Recovery: 104.6%. Individual recoveries ranged from 101.5% to 109.9%. All concentrations (3.20 to 32.00 µg/mL) met the acceptance criteria. |
| Linearity | Percent Difference: ±10% | All measured concentrations (1.5 to 35 µg/mL) showed a percent difference from the predicted result well within ±10% (ranging from -0.25% to 0.10%). |
| Sensitivity (LOQ) | ≤20% CV; recovery ± 15% | 1.5 µg/mL (Claimed in package insert). Specific data for LOQ meeting these criteria is not directly presented in the table, but the claim is based on observed acceptable inter-assay precision and recovery. |
| Assay Range | Based on Accuracy, Linearity, and Sensitivity (LOQ) | 1.5 to 32.0 µg/mL (Claimed reportable range). |
| Precision (Total CV) | < 10% | Control 1 (2.94 µg/mL): 4.22% CV < 10%Control 2 (10.14 µg/mL): 3.37% CV < 10%Control 3 (25.69 µg/mL): 4.44% CV < 10% (All controls met the acceptance criteria). |
| Specificity | Unlikely to be affected by topiramate metabolites | "Metabolites of topiramate are found primarily in urine... They are not however seen at clinically significant levels in plasma or serum. The QMS topiramate assay serum and plasma results are unlikely to be affected by metabolism of topiramate drug." (Qualitative claim, no specific numerical criterion). |
| Interferences (Endogenous & HAMA) | ≤10% error in detecting topiramate | All tested substances (Albumin, Bilirubin, Cholesterol, Gamma-Globulin, HAMA-1, HAMA-2, Hemoglobin, Heparin, Rheumatoid Factor, Triglycerides, Uric Acid) resulted in ≤10% error. |
| Interferences (Co-Administered Drugs) | ≤10% error in detecting topiramate | Most tested drugs (list provided) resulted in ≤10% error. Specific drugs identified as potentially cross-reacting with >10% error: Ibuprofen, Phenytoin, Tiagabine. This implies the device does not meet the criteria for these specific drugs. |
| Interferences (Anticoagulants) | No significant difference in recovery between serum and plasma samples | "No significant difference between the recovery of topiramate in serum or plasma. The collection tubes evaluated show no adverse effects on the recovery of topiramate." (Qualitative claim). |
| Calibration Curve Stability | N/A (implicit: stable for claimed period) | Supported for a period of 27 days. |
| Reagent On-Board Stability | N/A (implicit: stable for claimed period) | Supported for 60 days. |
| Method Comparison | Excellent correlation with predicate | N = 148, Slope = 0.962, y-intercept = 0.228, R² = 0.986. The report states: "Results show excellent correlation between the two assays." (Qualitative interpretation of quantitative results). |
2. Sample Size for the Test Set and Data Provenance:
- Accuracy: 12 concentrations for recovery study, each analyzed in triplicate (total of 36 measurements).
- Linearity: 9 concentrations, number of replicates not specified.
- Sensitivity (LOQ): Not specified directly, but implies multiple measurements around the LOQ value to determine CV and recovery.
- Precision: 3 controls, N=80 for each (total 240 measurements for precision components).
- Method Comparison: N = 148 patient samples.
- Interference (Endogenous & HAMA): Not explicitly stated, but for each interferent, samples with two known topiramate levels (approx. 5 and 20 µg/mL) were assayed.
- Interference (Co-Administered Drugs): Not explicitly stated, but for each compound, normal human serum with two known topiramate levels (approx. 5 and 20 µg/mL) was assayed.
- Interference (Anticoagulants): Not explicitly stated, but implied comparison of serum and plasma.
Data Provenance: The document does not specify the country of origin of the data. The studies are described as clinical testing, but it's common for these types of in vitro diagnostic studies to use banked or commercially sourced human serum/plasma samples, often without explicit geographical tags in 510(k) summaries. All studies appear to be prospective in the sense that they were designed experiments to evaluate the new device's performance against predefined criteria or a predicate device.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications:
This device is an in vitro diagnostic (IVD) assay for quantitative determination of a drug concentration. The "ground truth" here is the actual concentration of topiramate in the samples. This is typically established through:
- Reference materials: For linearity and accuracy by recovery, known concentrations are prepared by precise dilution of a high calibrator.
- Reference method/predicate device: For method comparison, the predicate Innofluor® Topiramate assay serves as the reference for comparison of patient sample results.
Therefore, no human experts were used to establish the "ground truth" in the way they would be for image analysis or disease diagnosis. The "ground truth" is defined by laboratory standards, precise dilutions, and the established performance of a reference or predicate method.
4. Adjudication Method for the Test Set:
Not applicable, as the ground truth is quantitative (actual concentration) and not based on human interpretation requiring adjudication.
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 diagnostic imaging where multiple human readers interpret cases, and AI assistance might impact their performance. For a quantitative IVD assay, the performance is measured directly by analytical metrics (accuracy, precision, linearity, etc.) and comparison to a predicate device or reference method, not by human reader performance.
6. Standalone Performance:
Yes, the studies described (Accuracy, Linearity, Sensitivity, Precision, Specificity, Interferences, Stability) evaluate the algorithm's entire workflow (reagent interaction, measurement, and result calculation) standalone, without human-in-the-loop performance influencing the primary measurements. The assay quantifies topiramate concentration directly.
7. Type of Ground Truth Used:
- Known concentrations: For Accuracy by Recovery, Linearity, Sensitivity studies. These are prepared laboratory standards.
- Predicate device results: For Method Comparison, the results from the Seradyn Innofluor® Topiramate assay (K970510) on patient samples serve as the comparison point.
- Laboratory-spiked samples: For interference studies, known amounts of interferent and topiramate are added to serum samples.
8. Sample Size for the Training Set:
The document does not provide a sample size for a "training set." This assay is a homogeneous particle-enhanced turbidimetric immunoassay (PETIA), which is a chemical reaction-based method, not a machine learning or AI algorithm that typically requires a large "training set" of data in the common sense. The "development" or "optimization" of the assay would involve various experiments, but these are not usually referred to as a "training set" in the context of conventional IVD development. The calibration of the device uses a six-level set of Seradyn QMS® Topiramate Calibrators, but this is for operational calibration, not model training.
9. How the Ground Truth for the Training Set Was Established:
As noted above, the concept of a "training set" with established ground truth as in AI/ML is not directly applicable to this type of chemical immunoassay. The "ground truth" for calibrators and controls used in assay development and validation would be established through highly accurate reference methods, gravimetric/volumetric preparation, and traceability to established standards for the analyte (topiramate).
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(191 days)
The QMS Zonisamide assay is intended for the quantitative determination of zonisamide in human serum or plasma on automated clinical chemistry analyzers.
Zonisamide concentrations can be used as an aid in management of patients treated with zonisamide.
The QMS® Zonisamide Calibrator set is intended for use in calibration of the QMS Zonisamide assay.
The QMS® Zonisamide Control set is intended for use in quality control of the QMS Zonisamide assay.
The QMS Zonisamide assay system is a homogeneous assay utilizing particle agglutination technology and is based on the competitive binding principle.
The assay consists of reagents R1: anti-Zonisamide rabbit polyclonal antibody and R2: Zonisamidecoated microparticles. A six-level set of QMS® Zonisamide Calibrators (A through F) is used to calibrate the assay. A three-level set of QMS® Zonisamide Controls (1 through 3) is used for quality control of the assay.
The provided text describes the QMS® Zonisamide assay, a homogeneous particle-enhanced turbidimetric immunoassay for the quantitative determination of zonisamide in human serum or plasma. The information focuses on demonstrating its substantial equivalence to a legally marketed predicate device (Innofluor® Phenytoin) through performance testing.
Here's an analysis of the acceptance criteria and the studies performed, formatted as requested:
1. Table of Acceptance Criteria and the Reported Device Performance
| Acceptance Criteria Category | Specific Criteria/Study Goal | Reported Device Performance |
|---|---|---|
| Accuracy and Linearity | To evaluate the accuracy and linearity of the assay | Demonstrated accuracy and linearity based on NCCLS guideline EP6. |
| Sensitivity | Analytical Sensitivity (Least Detectable Dose - LDD) | 1.0 µg/mL |
| Functional Sensitivity (Limit of Quantitation - LOQ) | 3.0 µg/mL | |
| Assay Range | Reportable range for the assay | 3.0 to 50.0 µg/mL (Package insert claim based on Accuracy, Linearity, and Sensitivity data) |
| Method Comparison | Correlation with another method (implicit: to show agreement with a recognized method) | Correlation studies conducted using NCCLS Guideline EP9 (no specific correlation values provided in the summary). |
| Precision | To evaluate the precision performance of the assay | Precision study performed using NCCLS guideline EP5 (no specific precision values provided in the summary). |
| Specificity | No significant cross-reactivity with major metabolites (NAZ and SMAP) | No significant cross-reactivity for NAZ and SMAP. |
| Interferences | No significant cross-reactivity with common interfering substances/drugs | Of 26 drugs tested, none showed cross-reactivity. |
2. Sample Size Used for the Test Set and the Data Provenance
The document does not explicitly state the sample sizes used for the test sets in the accuracy, linearity, method comparison, precision, specificity, or interference studies.
Regarding data provenance:
- The studies were conducted using well-established NCCLS guidelines, implying standardized laboratory testing.
- The method comparison used "patient samples," suggesting a clinical context, but no specifics about country of origin or whether it was retrospective or prospective are provided.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
This information is not provided in the document. The studies described are primarily analytical performance studies of a quantitative assay, where the "ground truth" for assay accuracy and calibration would typically be established by reference methods or gravimetric preparation of standards, not by human expert interpretation.
4. Adjudication Method for the Test Set
This information is not applicable and therefore, not provided. Adjudication methods (like 2+1, 3+1) are typically used in studies involving human interpretation (e.g., image analysis, clinical diagnosis) where there might be inter-reader variability. For an automated quantitative assay, the "ground truth" is typically determined by objective reference methods or precise measurements, not by expert consensus adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not performed. This type of study is relevant for diagnostic devices that involve significant human interpretation (e.g., radiologists reading images) and the AI's impact on human performance. The QMS® Zonisamide assay is a quantitative determination assay performed on automated clinical chemistry analyzers, not an interpretive diagnostic tool requiring human readers in that sense.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies described are inherently standalone performance tests of the assay. The QMS® Zonisamide assay is a laboratory test system designed to provide quantitative results directly from automated analyzers. The reported performance metrics (accuracy, linearity, sensitivity, precision, specificity, interferences) evaluate the device's capability to accurately and reliably measure zonisamide concentrations without direct human interpretation influencing the measurement outcome.
7. The Type of Ground Truth Used
The ground truth for this type of quantitative assay would typically be established through:
- Reference Methods / Gravimetric Standards: For accuracy and linearity, highly precise and accurate reference methods or gravimetrically prepared standards with known zonisamide concentrations would be used.
- Known Concentrations: For sensitivity, specificity, and interference studies, samples with precisely known concentrations of zonisamide, metabolites, or interfering substances would be utilized.
- Patient Samples: For method comparison studies, the "ground truth" would be the results obtained from an established comparative method on actual patient samples.
The document does not explicitly detail the exact methods used for establishing ground truth for each study but implies standard laboratory practices using "patient samples" for method comparison and reference to NCCLS guidelines for other analytical performance.
8. The Sample Size for the Training Set
This information is not applicable and therefore, not provided. The QMS® Zonisamide assay is a biochemical immunoassay, not a machine learning or AI algorithm that requires a separate "training set" in the context of supervised learning. The assay's performance is driven by its reagent formulation, reaction kinetics, and instrument calibration, not by an algorithm trained on a dataset.
9. How the Ground Truth for the Training Set Was Established
This information is not applicable as there is no "training set" in the context of an immunoassay. The chemical and biological principles of the assay itself, along with the manufacturing and quality control of the reagents and calibrators, establish its analytical performance capabilities.
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