(105 days)
The QMS® Lamotrigine assay is intended for the quantitative determination of lamotrigine in human serum or plasma on automated clinical chemistry analyzers.
Lamotrigine concentrations can be used as an aid in management of patients treated with lamotrigine.
The QMS® Lamotrigine Calibrator set is intended for use in calibration of the QMS Lamotrigine assay.
The QMS® Lamotrigine Control set is intended for use in quality control of the QMS Lamotrigine assay.
The QMS Lamotrigine 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-Lamotrigine sheep polyclonal antibody and R2: Lamotriginecoated microparticles. A six-level set of QMS Lamotrigine Calibrators (A through F) is used to calibrate the assay. A three-level set of QMS Lamotrigine Controls (1 thro the assay.
The provided document describes the K062966 QMS® Lamotrigine assay, a homogeneous particle-enhanced turbidimetric immunoassay for the quantitative determination of lamotrigine in human serum or plasma.
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly present a table of "acceptance criteria" with specific pass/fail thresholds for each performance characteristic. Instead, it describes general methods used for testing and states that performance testing verified the device functions as intended and satisfied design specifications. However, we can infer some criteria and the reported performance from the "SUMMARY OF CLINICAL TESTING" section.
| Performance Characteristic | Acceptance Criteria (Inferred) | Reported Device Performance |
|---|---|---|
| Accuracy and Linearity | Demonstrated linearity and accuracy across the reportable range. | Determined by a study based on NCCLS guideline EP6. |
| Sensitivity (LOQ) | Establish the Limit of Quantitation. | Functional Sensitivity (LOQ) determined to be 2.0 µg/mL. |
| Assay Range | Define the reportable range of the assay. | Reportable range: 2.0 to 40.0 µg/mL. |
| Method Comparison | Show correlation with a comparative method. | Correlation studies conducted using NCCLS Guideline EP9. |
| Precision | Demonstrate acceptable precision. | Performed using NCCLS guideline EP5. |
| Specificity | Minimal or no significant cross-reactivity with metabolites and other drugs. | N-2 oxide shows cross-reactivity but is in very minor concentrations. No significant cross-reactivity with other metabolites. |
| Interferences | Minimal or no significant interference from common drugs. | Of 26 drugs tested, none showed cross-reactivity. |
2. Sample Size Used for the Test Set and Data Provenance
The document does not specify the exact sample sizes for the test sets used in each study (Accuracy and Linearity, Sensitivity, Method Comparison, Precision, Specificity, Interferences).
- Data Provenance: The document does not explicitly state the country of origin or if the data was retrospective or prospective. However, given it's a clinical chemistry assay for human serum/plasma, it's highly likely the samples were human biological specimens.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not provided in the document. For an in vitro diagnostic (IVD) assay like this, "ground truth" is typically established by reference methods or validated techniques, not necessarily by "experts" in the same way it would be for imaging diagnostics requiring interpretation.
4. Adjudication Method (e.g., 2+1, 3+1, none) for the Test Set
This information is not applicable and therefore not provided. Adjudication methods are typically relevant for studies involving human interpretation of results (e.g., in imaging or pathology where multiple readers might disagree). For a quantitative chemical assay, the "truth" is determined by the output of a reference instrument or method.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study
A Multi Reader Multi Case (MRMC) comparative effectiveness study was not performed or described. This type of study is relevant for evaluating the performance of human readers, often aided by AI, in complex diagnostic tasks (e.g., radiology). This device is a quantitative immunoassay, not an AI-assisted diagnostic imaging tool.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
This device is a standalone assay kit that performs a quantitative measurement on automated clinical chemistry analyzers. The "algorithm" is the biochemical reaction and measurement process itself, not a separate computational algorithm that assists a human. Therefore, the performance described is the standalone performance of the assay system without human interpretation as a primary component of the diagnostic result. The results (lamotrigine concentrations) are then used by clinicians for patient management.
7. Type of Ground Truth Used
The ground truth for this type of quantitative assay would typically be established by:
- Reference Methods: Highly accurate and precise analytical methods (e.g., Gas Chromatography-Mass Spectrometry (GC-MS) or Liquid Chromatography-Mass Spectrometry (LC-MS)) for determining the true concentration of lamotrigine in samples.
- Spiked Samples: Known concentrations of lamotrigine added to a matrix (e.g., human serum or plasma that is negative for lamotrigine) to assess accuracy and linearity.
- Patient Samples: Used for method comparison against a legally marketed predicate device or a well-established reference method.
The document implicitly refers to these by mentioning "Accuracy and linearity were determined..." and "Correlation studies were conducted using patient samples..." indicating that the "ground truth" for those studies would have been the results from a reference method or the assigned values from spiked samples.
8. Sample Size for the Training Set
The document does not mention a training set because this is a traditional immunoassay, not a machine learning or AI-based device that requires "training." The "training" of such a system involves developing the reagents and optimizing the assay conditions.
9. How the Ground Truth for the Training Set Was Established
As there is no "training set" in the context of machine learning, this question is not applicable. The development of the assay's reagents and protocols is based on extensive biochemical research and optimization studies rather than "ground truth" established for a training dataset.
{0}------------------------------------------------
K062966 JAN 12 2007
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: K062966
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
January 8, 2007
DEVICE NAME
| Trade Name: | QMS® Lamotrigine |
|---|---|
| Common Name: | Homogeneous Particle-Enhanced Turbidimetric Immunoassay |
| Device Classification: | 21 CFR 862.3350 Diphenylhydantoin Test System; Class II |
INTENDED USE
The QMS Lamotrigine assay is intended for the quantitative determination of lamotrigine in human serum or plasma on automated clinical chemistry analyzers.
Lamotrigine concentrations can be used as an aid in management of patients treated with lamotrigine.
The QMS Lamotrigine Calibrator set is intended for use in calibration of the QMS Lamotrigine assay.
The QMS® Lamotrigine Control set is intended for use in quality control of the QMS Lamotrigine assay.
LEGALLY MARKETED DEVICE TO WHICH EQUIVALENCY IS CLAIMED
QMS® Zonisamide assay (K051211)
DESCRIPTION OF DEVICE
The QMS Lamotrigine 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-Lamotrigine sheep polyclonal antibody and R2: Lamotriginecoated microparticles. A six-level set of QMS Lamotrigine Calibrators (A through F) is used to calibrate
the assay. A three-level set of QMS Lamotrigine Controls (1 thro the assay.
{1}------------------------------------------------
| DeviceQMS® Lamotrigine | PredicateQMS® Zonisamide | |
|---|---|---|
| Intended Use | The QMS Lamotrigine assay isintended for the quantitativedetermination of lamotrigine inhuman serum or plasma onautomated clinical chemistryanalyzers. | The QMS Zonisamide assay isintended for the quantitativedetermination of zonisamide inhuman serum or plasma onautomated clinical chemistryanalyzers. |
| Indicationsfor Use | Lamotrigine concentrations can beused as an aid in management ofpatients treated with lamotrigine. | Zonisamide concentrations can beused as an aid in management ofpatients treated with zonisamide. |
| Methodology | Homogeneous particle-enhancedturbidimetric immunoassay (particleagglutination) | Homogeneous particle-enhancedturbidimetric immunoassay (particleagglutination) |
| ReagentComponents | Two (2) reagent system:• Anti-Lamotrigine AntibodyReagent (R1) in bufferscontaining stabilizers withsodium azide• Lamotrigine-coated MicroparticleReagent (R2) in buffer containingstabilizers with sodium azide | Two (2) reagent system:• Anti-Zonisamide AntibodyReagent (R1) in bufferscontaining stabilizers withsodium azide• Zonisamide-coated MicroparticleReagent (R2) in buffer containingstabilizers with sodium azide |
| Calibration | QMS Lamotrigine Calibrators - sixlevels | QMS Zonisamide Calibrators - sixlevels |
| QualityControl | QMS Lamotrigine Controls - threelevels | QMS Zonisamide Controls - threelevels |
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 Functional Sensitivity or Limit of Quantitation (LOQ) of the assay was determined to be 2.0 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 2.0 to 40.0 µg/mL.
Method Comparison
Correlation studies were conducted using NCCLS Guideline EP9: Method Companison and Bias Estimation Using Patient Samples as a guideline to compare accuracy of Lamorigine
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.
{2}------------------------------------------------
Specificity
There is one pharmacclogically inactive metabolite, N-2 glucuronide. Three other minor metabolites, N-5 glucuronide, N-2 oxide, and N-2 methyl have been proposed in literature. Testing results indicated that for N-2 oxide there is cross-reactivity, however, this metabolite is present in human serum in only very minor concentrations. No studies to date have been able to quantify the N-2 oxide metabolite in serum due to its extremely low concentration. Results for the other metabolites indicated that there is no significant cross-reactivity.
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 cross-reactivity in the QMS lamotrigine assay system.
CONCLUSION
As summarized above, the QMS® Lamotrigine assay is substantially equivalent to the QMS Zonisamide assay. Substantial equivalence has been demonstrated through performance testing to verify that the device functions as intended and that design specifications have been satisfied.
{3}------------------------------------------------
Image /page/3/Picture/0 description: The image is a black and white logo for the Department of Health & Human Services USA. The logo features a stylized eagle with its wings spread, enclosed within a circle. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES · USA" is arranged around the upper half of the circle.
Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002
JUN 0 9 2000
Seradyn Inc. C/O Mr. Jack Rogers 7998 Georgetown Road, Suite 100 Indiannapolis, IN 46268
Re: K062966
Trade/Device Name: OMS® Lamotrigine Regulation Number: 21 CFR 862.3350 Regulation Name: Diphenylhydantoin Test System Regulatory Class: Class II Product Code: ORH, LAS, DLJ Dated: December 20, 2006 Received: December 21, 2006
Dear Mr. Rogers:
This letter corrects our substantially equivalent letter of January 12, 2007.
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 (PMA). 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 additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 CFF). Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
{4}------------------------------------------------
Page 2
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
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 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours.
CA
Courtney C. Harper, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
{5}------------------------------------------------
Indications for Use
510(k) Number (if known): K012966
QMS® Lamotrigine Device Name:
Indications for Use:
The QMS® Lamotrigine assay is intended for the quantitative determination of lamotrigine in human serum or plasma on automated clinical chemistry analyzers.
Lamotrigine concentrations can be used as an aid in management of patients treated with lamotrigine.
The QMS® Lamotrigine Calibrator set is intended for use in calibration of the QMS Lamotrigine assay.
The QMS® Lamotrigine Control set is interded for use in quality control of the QMS Lamotrigine assay.
Prescription Use × (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
Page 1 of_
510(k) K062966
§ 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.