(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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510K SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92
The assigned 510(k) number is:
COMPANY/CONTACT PERSON
Seradyn, Inc 7998 Georgetown Road, Suite 1000 Indianapolis, IN 46268
Establishment registration No: 1836010
Jack Rogers Manager of Regulatory Affairs Telephone: (317) 610-3823 Fax: (317) 610-0018
DATE PREPARED
March 5, 2007
DEVICE NAME
| Trade Name: | Seradyn QMS® Topiramate |
|---|---|
| Common Name: | Homogeneous Particle-Enhanced Turbidimetric Immunoassay |
| Device Classification: | 21 CFR 862.3660; Phenobarbital Test System; Class II |
INTENDED USE
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.
LEGALLY MARKETED DEVICE TO WHICH EQUIVALENCY IS CLAIMED
Seradyn Innofluor® Topiramate assay K970510
DESCRIPTION OF DEVICE
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.
MAY 1 7 2007
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| Device | Predicate | |
|---|---|---|
| Intended Use | Seradyn QMS® TopiramateThe QMS Topiramate assay isintended for the quantitativedetermination of topiramate in humanserum or plasma on automatedclinical chemistry analyzers. | Seradyn Innofluor® TopiramateThe Innofluor Topiramate assay isintended for the quantitativedetermination of total topiramate inserum or heparinized plasma byfluorescence polarization immunoassay(FPIA). The assay system is for use onthe TDx® or the TDxFLx® (TDx/TDxFLx)analyzer. |
| Indications for Use | The measurements obtained are usedin the diagnosis and treatment oftopiramate overdose and inmonitoring levels of topiramate to helpensure appropriate therapy. | The measurements obtained are usedin monitoring levels of topiramate toensure appropriate therapy. |
| Methodology | Homogeneous particle-enhancedturbidimetric immunoassay (particleagglutination) (PETIA) | Fluorescence PolarizationImmunoassay (FPIA) |
| ReagentComponents | Two (2) reagent system:Anti-topiramate Antibody Reagent(R1) in buffers containing proteinstabilizers with sodium azideTopiramate-coated MicroparticleReagent (R2) in buffer containingsurfactant as stabilizers with sodiumazide | Three (3) reagent system:• Topiramate Antiserum (A) (Sheep) inbuffer with protein stabilizer and<0.1% sodium azide• Topiramate-fluorescein Tracer (T) inbuffer with surfactant, proteinstabilizer, and <0.1% sodium azide• Pretreatment Buffer (B) withsurfactant |
COMPARISON OF TECHNOLOGICAL CHARACTERISTICS
SUMMARY OF CLINICAL TESTING
Accuracy
Accuracy by Recovery was determined by diluting the high calibrator to 12 concentrations across the assay range. The samples were analyzed in triplicate.
| THEORETICALCONC.(ug/mL) | Rep 1 | Rep 2 | Rep 3 | MeanResult | % RecoveryAcceptanceCriteria:100±10% |
|---|---|---|---|---|---|
| 32.00 | 33.57 | 32.63 | 31.24 | 32.48 | 101.5% |
| 24.00 | 24.26 | 24.41 | 24.83 | 24.50 | 102.1% |
| 16.00 | 16.88 | 16.57 | 16.78 | 16.74 | 104.6% |
| 8.00 | 8.27 | 8.30 | 8.48 | 8.35 | 104.4% |
| 6.40 | 6.60 | 6.59 | 6.63 | 6.61 | 103.3% |
| 3.20 | 3.45 | 3.41 | 3.54 | 3.47 | 108.4% |
| 2.56 | 2.60 | 2.70 | 2.70 | 2.67 | 104.3% |
| 1.92 | 2.16 | 2.03 | 2.15 | 2.11 | 109.9% |
| 1.60 | 1.59 | 1.71 | 1.66 | 1.65 | 103.1% |
| 1.28 | 1.30 | 1.33 | 1.36 | 1.33 | 103.9% |
| Mean Percent Recovery | 104.6 % |
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Linearity
| EstimatedValue(µg/mL) | DilutionFactor | Result | 1st OrderPredictedResult | 2nd OrderPredictedResult | Percent DifferenceAcceptance Criteria:±10% |
|---|---|---|---|---|---|
| 35 | 0.8750 | 36.57 | 36.76 | 36.78 | -0.04% |
| 30 | 0.7500 | 31.87 | 31.52 | 31.53 | 0.00% |
| 20 | 0.5000 | 20.86 | 21.05 | 21.04 | 0.06% |
| 15 | 0.3750 | 15.89 | 15.82 | 15.80 | 0.09% |
| 10 | 0.2500 | 10.54 | 10.58 | 10.57 | 0.10% |
| 5 | 0.1250 | 5.28 | 5.35 | 5.34 | 0.06% |
| 3 | 0.0750 | 3.11 | 3.25 | 3.25 | -0.02% |
| 2 | 0.0500 | 2.22 | 2.20 | 2.21 | -0.13% |
| 1.5 | 0.0375 | 1.68 | 1.68 | 1.68 | -0.25% |
Linearity by Dilution was determined by a study based on the NCCLS guideline EP6-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach.
Sensitivity
The LOQ of the assay is defined as the lowest drug concentration for which acceptable inter-assay precision is observed (≤20% CV, with recovery ± 15%).
Based on the results, the package insert claim for LOQ will be 1.5 µg/mL.
Assay Range
Based on the Accuracy, Linearity, and Sensitivity (LOQ) data, the package insert claim for the reportable range for the assay will be 1.5 to 32.0 µg/mL.
Method Comparison
A study was conducted according to NCCLS Guideline EP9-A2: Method Comparison and Bias Estimation Using Patient Samples to compare accuracy of recovery of topiramate assayed by the QMS® Topiramate assay to that of the predicate Innofluor® Topiramate assay.
Mean values for the innofluor reference method were plotted against those for the QMS method. The results using Passing - Bablok parameters are:
N = 148 Slope = 0.962 y-intercept = 0.228 R² = 0.986
Results show excellent correlation between the two assays.
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Precision
A precision study was performed using the National Committee for Clinical Laboratory Standards (NCCLS) guideline EP5-A2: Evaluation of Precision Performance of Quantitative Measurement Methods.
| Within Run | BETWEEN DAY | Total | ||||||
|---|---|---|---|---|---|---|---|---|
| Control | N | Mean(µg/mL) | SD | CV (%) | SD | CV (%) | SD | CV (%) |
| 1 | 80 | 2.94 | 0.0813 | 2.77 | 0.0617 | 2.10 | 0.1238 | 4.22 |
| 2 | 80 | 10.14 | 0.1858 | 1.83 | 0.2371 | 2.34 | 0.3418 | 3.37 |
| 3 | 80 | 25.69 | 0.8295 | 3.23 | 0.7374 | 2.87 | 1.1405 | 4.44 |
Acceptance Criteria: < 10% total CV
Specificity
Metabolites of topiramate are found primarily in urine of patients being administered topiramate therapy. 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.
Interferences
Interference studies were conducted using NCCLS Guideline EP7-A2: Interference Testing in Clinical Chemistry.
1) Endogenous Substances and HAMA
Clinically high concentrations of the following potential interferents were added to serum with known levels of topiramate (approximately 5 and 20 µg/mL). Each sample was assayed using the QMS Topiramate assay, along with a serum control of topiramate. All substances resulted in ≤10% error in detecting topiramate.
| Interfering | Interferent |
|---|---|
| Substance | Concentration |
| Albumin | 12 g/dL |
| Bilirubin | 70 mg/mL |
| Cholesterol | 250 mg/mL |
| Gamma-Globulin | 12 g/dL |
| HAMA-1* | Normal Serum Levels |
| HAMA-2* | Normal Serum Levels |
| Hemoglobin | 1000 mg/dL |
| Heparin | 185.5 USP/mL |
| Rheumatoid Factor | 500 IU/mL |
| Triglycerides | 825 mg/dL |
| Uric Acid | 30 mg/dL |
- Human anti-mouse antibodies
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2) Common Co-Administered Drugs
Studies were conducted to examine if any of the commonly administered compounds have any effect on the recovery of topiramate concentration of each compound was spiked into normal human serum with known levels of topiramate (approximately 5 and 20 ug/mL ) and assayed along with a serum control of topiramate. All compound resulted in ≤10% error in detecting topiramate.
| Compound | CompoundConcentration(µg/mL) | Compound | CompoundConcentration(µg/mL) |
|---|---|---|---|
| Acetaminophen | 31 | Lamotrigine | 45 |
| Acetazolamide | 40 | Levetiracetam | 124 |
| Alprazolam | 2.0 | Methysergide | 5.2 |
| Amitriptyline | 1.0 | Metoprolol | 5.25 |
| Acetylsalicylic acid | 67 | Nadolol | 121 |
| Atenolol | 10.33 | Naproxen | 509 |
| Caffeine | 60 | Nimodipine | 75 |
| Carbamazepine | 30 | Nortriptyline | 1.0 |
| Chlorthalidone | 64 | Phenelzine | 14.38 |
| Clonazepam | 0.18 | Phenobarbital | 40 |
| Clorazepate | 2.0 | Primidone | 40 |
| Diazepam | 5.1 | Protriptyline | 1.03 |
| Dichlorphenamide | 32 | Salicylic Acid | 598 |
| Ethosuxamide | 252 | Sulfanilamide | 1500 |
| Famotidine | 0.97 | Tolbutamide | 642 |
| Felbamate | 243.33 | Valproic Acid | 100.67 |
| Flurazepam | 17.5 | Verapamil | 1.6 |
| Furosemide | 3.7 | Viagabatrin | 112 |
| Gabapentin | 93 | Zonisamide | 122 |
| Hydrochlororthiazide | 6.0 |
Drugs tested that that may cross react with >10% error:
- . Ibuprofen
- Phenytoin .
- Tiagabine .
3) Anticoagulants
Studies were conducted to determine the performance characteristics of the assay for both serum and plasma samples containing topiramate.
The results indicate that there is 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, within the experimental error for the spiking study.
A claim for assay application to both serum and plasma samples is thus supported.
On-Board Stability
1) Calibration Curve stability
Calibration curve stability of a period of 27 days is supported by the data.
2) Reagent On-Board Stability
A 60 day on-board reagent stability claim is supported by the data.
CONCLUSION
As summarized above, the Seradyn QMS® Topiramate assay is substantially equivalent to the Seradyn Innofluor® Topiramate assay. Substantial equivalence has been demonstrated through performance testing to verify that the device functions as intended and that design specifications have been satisfied.
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Image /page/5/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo features a stylized eagle with three wing segments, symbolizing health, services, and people. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Seradyn. Inc. c/o Mr. Jack Rogers Manager of Regulatory Affairs 7998 Georgetown Road, Suite 1000 Indianapolis, IN 46268-5620
MAY 1 7 2007
K070645 Trade/Device Name: Seradyn OMS® Topiramate Regulation Number: 21 CFR 862.3660 Regulation Name: Phenobarbital test system. Regulatory Class: Class II Product Code: NWM Dated: March 05, 2007 Received: March 08, 2007
Dear Mr. Rogers:
Re:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2 -
This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0490. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely vours.
Jean M. Cooper, M.S., D.V.M.
Yean M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known): K010645
Seradyn QMS® Topiramate Device Name:
Indications for Use:
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.
Prescription Use X (Part 21 CFR 801 Subpart D)
AND/OR ·
Over-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic-Devices (OIVD)
Division Sign-Off
Office of in Vitro Diagnostic Device Evaluation and Safety
§ 862.3350 Diphenylhydantoin test system.
(a)
Identification. A diphenylhydantoin test system is a device intended to measure diphenylhydantoin, an antiepileptic drug, in human specimens. Measurements obtained by this device are used in the diagnosis and treatment of diphenylhydantoin overdose and in monitoring levels of diphenylhydantoin to ensure appropriate therapy.(b)
Classification. Class II.