(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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NOV 1 8 2005
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: K051211
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
November 18, 2005
DEVICE NAME
| Trade Name: | QMS® Zonisamide |
|---|---|
| Common Name: | Homogeneous Particle-Enhanced Turbidimetric Immunoassay |
| Device Classification: | 21 CFR 862.3350 Diphenylhydantoin Test System; Class II |
INTENDED USE
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.
LEGALLY MARKETED DEVICE TO WHICH EQUIVALENCY IS CLAIMED
Innofluor® Phenytoin (K955562)
DESCRIPTION OF DEVICE
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.
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| DeviceQMS® Zonisamide | PredicateInnofluor® Phenytoin | |
|---|---|---|
| Intended Use | The QMS Zonisamide assay isintended for the quantitativedetermination of zonisamide in humanserum or plasma on automatedclinical chemistry analyzers. | The Innofluor Phenytoin assay isintended for the quantitativedetermination of total phenytoin. |
| Indicationsfor Use | Zonisamide concentrations can beused as an aid in management ofpatients treated with zonisamide. | Therapeutic drug monitoring. |
| Methodology | Homogeneous particle-enhancedturbidimetric immunoassay (particleagglutination) | Fluorescence PolarizationImmunoassay (FPIA) technology. |
| ReagentComponents | Two (2) reagent system:• Anti-Zonisamide Antibody Reagent(R1) in buffers containingstabilizers with sodium azide• Zonisamide-coated MicroparticleReagent (R2) in buffer containingstabilizers with sodium azide | Three (3) reagent system:• A Phenytoin Antiserum (Sheep)in buffer with protein stabilizerand Sodium azide.• T Phenytoin Fluorescein Tracerin buffer with protein stabilizer,surfactant and Sodium azide• B Pre-Treatment Buffer withsurfactant and Sodium azide |
| Calibration | QMS Zonisamide Calibrators – sixlevels | Innofluor Phenytoin Calibrators –six levels |
| QualityControl | QMS Zonisamide Controls – threelevels | N/A |
COMPARISON OF TECHNOLOGICAL CHARACTERISTICS
SUMMARY OF CLINICAL TESTING
Accuracy and Linearity
Accuracy and linearity were determined by a study based on the NCCLS guideline EP6: Evaluation of the Linearity of Quantitative Measurement.
Sensitivity
The Analytical Sensitivity or Least Detectable Dose (LDD) of the assay was determined to be 1.0 ug/mL.
The Functional Sensitivity or Limit of Quantitation (LOQ) of the assay was determined to be 3.0 µg/mL.
Assay Range
Based on the Accuracy, Linearity, and Sensitivity (LDD and LOQ) data, the package insert claim for the reportable range for the assay is 3.0 to 50.0 µg/mL.
Method Comparison
Correlation studies were conducted using NCCLS Guideline EP9: Method Comparison and Bias Estimation Using Patient Samples as a guideline
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Precision
A precision study was performed using the National Committee for Clinical Laboratory Standards (NCCLS) guideline EP5: Evaluation of Precision Performance of Clinical Chemistry Devices.
Specificity
There are two known major metabolites of zonisamide (NAZ) and sulfamoyl acetyl phenol (SMAP). Testing results indicated that there is no significant cross-reactivity for either of these metabolites.
Interferences
Interference studies were conducted using NCCLS Guideline EP7: Interference Testing in Clinical Chemistry. The results of the study indicated that of 26 drugs tested, none showed crossreactivity in the QMS zonisamide assay system.
CONCLUSION
As summarized above, the QMS® Zonisamide assay is substantially equivalent to the Innofluore Phenytoin 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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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with its wings spread, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circle around the eagle. The eagle is black, and the text is also black.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
NOV 1 8 2005
Mr. Jack Rogers Manager of Regulatory Affairs Seradyn. Inc. 7998 Georgetown Road. Suite 1000 Indianapolis, IN 46268
Re: K051211
Trade/Device Name: QMS® Zonisamide Assay QMS® Zonisamide Calibrator Set QMS® Zonisamide Control Set Regulation Number: 21 CFR 862.3350
Regulation Name: Diphenylhydantoin test system Regulatory Class: Class II Product Code: NWM, LAS, DLJ Dated: November 9, 2005 Received: November 10, 2005
Dear Mr. Rogers:
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 indictions 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, Dr 10 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, isting 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
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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) 276-0484. 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 (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours.
Alberto Gutt
Alberto Gutierrez, Ph.D. 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): K051211
QMS® Zonisamide Device Name:
Indications for Use:
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.
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 Signoff
Office of in Vitro Diagnostic Device Evaluation and Safety
51000 K051211
Page 1 of
§ 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.