(79 days)
The QMS® Quinidine assay is intended for the quantitative determination of quinidine in human serum or plasma on automated clinical chemistry analyzers.
The results obtained are used in the diagnosis and treatment of quinidine overdose and in monitoring levels of quinidine to help ensure appropriate therapy.
The QMS® Quinidine assay system is a homogeneous assay utilizing particle agglutination technology and is based on the competitive binding principle.
In particle agglutination assays, the degree of agglutination is inversely proportional to the quantity of free drug in the reaction well. Hence, if no drug is present in the sample, the antibodies in the QMS® Quinidine Antibody Reagent (R1) will bind only to the bound drug on the particle which will cause it to agglutinate and will result in higher absorbance. If increased amount of competing drug is present in the sample, this will result in decreased binding of bound drug by the antibody, resulting in a relative decrease in particle agglutination. This in turn results in lower absorbance.
The precise relationship between particle agglutination of the unlabeled drug in the sample is established by measuring the absorbance values of calibrators with known concentration of the The absorbance of unknown samples can be interpolated from the absorbance values of the drug, calibration curve and the concentration of the drug present in the sample can be calculated.
The assay consists of reagents R1: anti-quinidine monoconal and R2: quinidine-oated microparticles. A six-level set of QMS® Quinidine Calibrators (A throu
Here's a breakdown of the acceptance criteria and study information for the QMS® Quinidine assay, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Accuracy (% Recovery) | 100% ± 10% | Mean Percent Recovery: 97.71% (for spiked samples) |
| Linearity (R²) | Not explicitly stated as a numerical AC, but implied good linearity | 0.9995 (correlation coefficient for linear regression) |
| Sensitivity (LDD) | Claim of 0.2 µg/mL supported | Average LDD: 0.09 µg/mL |
| Assay Range | Based on Accuracy, Linearity, Sensitivity | 0.2 to 8.0 µg/mL |
| Precision (Total CV) | < 10% | Control 1: 9.09%Control 2: 6.37%Control 3: 5.83% |
| Interference (% Recovery) | 100% ± 10% (for endogenous substances) | Bilirubin: 103.0%Hemoglobin: 100.0%Triglyceride: 92.18%Total Protein: 99.68%HAMA Type-1: 91.12%HAMA Type-2: 90.65% |
| Calibration Curve Stability | Not explicitly stated as a numerical AC | Supported for 28 days |
| Reagent On-Board Stability | Not explicitly stated as a numerical AC | Supported for 25 days |
2. Sample Size Used for the Test Set and Data Provenance
- Accuracy: Samples analyzed in duplicate. The number of samples for the accuracy study was 3 "theoretical concentrations" of quinidine (2.0, 4.0, 8.0 µg/mL), each tested in duplicate (total 6 measurements).
- Linearity: Not explicitly stated as a number of individual samples, but the study was "based on the NCCLS guideline EP6: Evaluation of the Linearity of Quantitative Measurement." It involved testing 5 theoretical concentrations (0.25, 0.75, 1.5, 3.0, 6.0 µg/mL), each in duplicate.
- Method Comparison: N = 50 (number of patient samples)
- Precision: 80 measurements per control level (for 3 control levels, so 240 total measurements).
- Specificity: N=3 for each cross-reactant.
- Interferences (Endogenous Substances): N=2 for Bilirubin and Hemoglobin, N=3 for Triglyceride and Total Protein.
- Interferences (HAMA): Samples analyzed in duplicate for Control, HAMA Type-1, HAMA Type-2.
- Data Provenance: The document does not specify the country of origin for the human serum/plasma samples. It states that accuracy was determined by spiking USP traceable quinidine into "human serum negative for the drug." Method comparison used "patient samples." The studies appear to be retrospective in nature, as they are laboratory-based validation studies.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of information (number and qualifications of experts) is not applicable for this device and study. The QMS® Quinidine assay is an in vitro diagnostic (IVD) device for quantitative determination of a drug in serum/plasma. Its performance is evaluated against established analytical methods and reference standards, not by human expert interpretation of images or clinical data for ground truth.
4. Adjudication Method for the Test Set
This is not applicable as the studies involve quantitative measurements and comparisons to reference values or other assays, not human interpretation requiring 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 done. This type of study is typically used for medical imaging devices where human readers interpret cases with and without AI assistance. This document describes the analytical performance of a quantitative immunoassay.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies presented are all standalone performance evaluations of the QMS® Quinidine assay. The device itself is an automated clinical chemistry analyzer for quantitative determination, meaning it operates without direct human interpretive input beyond sample loading and results reporting. The performance metrics (accuracy, linearity, precision, etc.) are inherent to the assay's ability to measure quinidine concentrations.
7. The Type of Ground Truth Used
The ground truth for the various studies includes:
- Spiked Concentrations: For accuracy and linearity, USP traceable quinidine was spiked into human serum to create samples with known theoretical concentrations.
- Reference Method Results: For method comparison, the Abbott TDx/TDxFLx Quinidine assay served as the reference method, and its results were compared to the QMS® Quinidine assay.
- Known Concentrations/Materials: For sensitivity, specificity, and interference studies, samples with known concentrations of drug, cross-reactants, or interfering substances were used.
8. The Sample Size for the Training Set
The document describes the validation studies for the QMS® Quinidine assay. For an IVD device like this, the "training set" would typically refer to the data used during the development and optimization of the assay's reagents and methodology. This information is not provided in this 510(k) summary, as it generally focuses on the final validation results, not the developmental process.
9. How the Ground Truth for the Training Set Was Established
As the "training set" information is not provided, the method for establishing its ground truth is also not available in this document. During development, ground truth would likely be established using highly accurate reference methods, certified reference materials, and meticulously prepared known-concentration samples, similar to the validation methods but on a smaller scale and iteratively.
{0}------------------------------------------------
DEC 2 3 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: K052826
COMPANY/CONTACT PERSON
Seradyn, Inc 7998 Georgetown Road, Suite 1000 Indianapolis, IN 46268
Establishment registration No: 1836010
Jack Rogers Manager of Requlatory Affairs Telephone: (317) 610-3823 Fax: (317) 610-0018
DATE PREPARED
October 4, 2005
DEVICE NAME
| Trade Name: | QMS® Quinidine |
|---|---|
| Common Name: | Homogeneous Particle-Enhanced Turbidimetric Immunoassay |
| Device Classification: | 21 CFR 862.3320; Enzyme Immunoassay, Quinidine; Class II |
INTENDED USE
The QMS® Quinidine assay is intended for the quantitative determination of quinidine in human serum or plasma on automated clinical chemistry analyzers.
The results obtained are used in the diagnosis and treatment of quinidine overdose and in monitoring levels of quinidine to help ensure appropriate therapy.
LEGALLY MARKETED DEVICE TO WHICH EQUIVALENCY IS CLAIMED
Abbott TDx/TDxFLx Quinidine
DESCRIPTION OF DEVICE
The QMS® Quinidine assay system is a homogeneous assay utilizing particle agglutination technology and is based on the competitive binding principle.
In particle agglutination assays, the degree of agglutination is inversely proportional to the quantity of free drug in the reaction well. Hence, if no drug is present in the sample, the antibodies in the QMS® Quinidine Antibody Reagent (R1) will bind only to the bound drug on the particle which will cause it to agglutinate and will result in higher absorbance. If increased amount of competing drug is present in the sample, this will result in decreased binding of bound drug by the antibody, resulting in a relative decrease in particle agglutination. This in turn results in lower absorbance.
The precise relationship between particle agglutination of the unlabeled drug in the sample is established by measuring the absorbance values of calibrators with known concentration of the The absorbance of unknown samples can be interpolated from the absorbance values of the drug, calibration curve and the concentration of the drug present in the sample can be calculated.
The assay consists of reagents R1: anti-quinidine monoconal and R2: quinidine-oated
microparticles. A six-level set of QMS® Quinidine Calibrators (A throu
{1}------------------------------------------------
| DeviceSeradyn QMS® Quinidine | PredicateAbbott TDx/TDxFLx Quinidine | |
|---|---|---|
| Intended Use | The QMS® Quinidine assay isintended for the quantitativedetermination of quinidine in humanserum or plasma on automatedclinical chemistry analyzers. | The TDx/TDxFIx Quinidine assay is areagent system for the quantitativemeasurement of quinidine in serum orplasma. |
| Indicationsfor Use | The measurements obtained are usedin the diagnosis and treatment ofquinidine overdose and in monitoringlevels of quinidine to ensureappropriate therapy. | The measurements obtained are usedin monitoring levels of quinidine toensure appropriate therapy. |
| Methodology | Homogeneous particle-enhancedturbidimetric immunoassay (particleagglutination) | Fluorescence PolarizationImmunoassay (FPIA) technology. |
| ReagentComponents | Two (2) reagent system:• Anti-Quinidine Antibody Reagent(R1) in buffers containing proteinstabilizers with sodium azide• Quinidine-coated MicroparticleReagent (R2) in buffer containingsurfactant as stabilizers withsodium azide | Three (3) reagent system:• Pretreatment Solution (P)Surfactant in buffer containing N-N-dimethylformamide and proteinstabilizer and sodium azide.• S Quinidine Antiserum (Goat) inbuffer with protein stabilizer andSodium azide.• T Quinidine Fluorescein Tracer inbuffer with protein stabilizersurfactant N-N-dimethylformamideand Sodium azide |
| Calibration | QMS QuinidineCalibrators - six levels | X Systems QuinidineCalibrators - six levels |
SUMMARY OF CLINICAL TESTING
Accuracy
Accuracy by Recovery was determined by spiking USP traceable quinidine into human serum negative for the drug to achieve concentrations across the assay range. The samples were analyzed in duplicate with the QMS Quinidine assay.
| THEORETICALCONC.(µg/mL) | Rep 1 | Rep 2 | MeanRecoveredConc. | SD | CV | % RecoveryAcceptanceCriteria:100±10% |
|---|---|---|---|---|---|---|
| 2.0 | 2.06 | 1.81 | 1.94 | 0.12 | 6.50 | 97.00 |
| 4.0 | 3.94 | 3.95 | 3.95 | 0.01 | 0.13 | 98.75 |
| 8.0 | 7.81 | 7.76 | 7.79 | 0.02 | 0.32 | 97.38 |
| Mean Percent Recovery 97.71 |
{2}------------------------------------------------
Linearity
Linearity by Dilution was determined by a study based on the NCCLS guideline EP6: Evaluation of the Linearity of Quantitative Measurement.
A linear regression analysis plot of USP Quinidine against recovered quinidine resulted in a line with a correlation coefficient (R2) of 0.9995, demonstrating that the assay is linear.
| THEORETICALCONC.(µg/mL) | Rep 1 | Rep 2 | MeanRecoveredConc. | SD | CV | % Recovery | |
|---|---|---|---|---|---|---|---|
| 0.25 | 0.25 | 0.18 | 0.22 | 0.04 | 15.90 | 88.00 | |
| 0.75 | 0.71 | 0.73 | 0.72 | 0.01 | 1.39 | 96.00 | |
| 1.5 | 1.42 | 1.41 | 1.42 | 0.01 | 0.35 | 94.67 | |
| 3.0 | 2.98 | 2.98 | 2.98 | 0.00 | 0.00 | 99.33 | |
| 6.0 | 6.22 | 6.18 | 6.2 | 0.02 | 0.32 | 103.33 | |
| Mean Percent Recovery | 96.27 |
Sensitivity
The Analytical Sensitivity or Least Detectable Dose (LDD) of the assay is defined as the concentration at which the lowest concentration is distinguishable from zero with 95% confidence.
The average LDD is 0.09 ug/mL, supporting a claim of 0.2 ug/mL
Assay Range
Based on the Accuracy, Linearity, and Sensitivity (LDD) data, the package insert claim for the reportable range for the assay will be 0.2 to 8.0 µg/mL.
Method Comparison
A study was conducted according to NCCLS Guideline EP9: Method Comparison and Bias Estimation Using Patient Samples to compare accuracy of recovery of quinidine in serum assayed by the QMS® Quinidine assay to the Abbott TDx/TDxFLx® Quinidine assay.
Mean values for the TDx reference method were plotted against those for the QMS on Hitachi 717. The results using Passing - Bablok parameters are:
N = 50 Slope = 1.062 y-intercept = -0.213 R² = 0.978
Results show excellent correlation between the two assays.
{3}------------------------------------------------
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.
| Control | N | Mean(µg/mL) | Within Run | BETWEEN DAY | Total | |||
|---|---|---|---|---|---|---|---|---|
| SD | CV (%) | SD | CV (%) | SD | CV (%) | |||
| 1 | 80 | 1.02 | 0.06 | 5.83 | 0.01 | 1.53 | 0.09 | 9.09 |
| 2 | 80 | 3.17 | 0.08 | 2.45 | 0.00 | 0.00 | 0.20 | 6.37 |
| 3 | 80 | 5.18 | 0.08 | 1.62 | 0.00 | 0.00 | 0.30 | 5.83 |
Acceptance Criteria: < 10% total CV
Specificity
O-Desmethylquinidine; include: 3-Hydroxyquinidine; Quinidine-N-oxide; Metabolites of quinidine 2-Oxoquinidinone; and 10,11-Dihydroquinidinediol. The most important metabolite is 3-Hydroxyquinidine, serum levels of which can approach those of quinidine in patients receiving conventional doses of the drug. It is also reported to have an antiarrhythmic potency similar to that of quinidine.
| N | ControlMean | Conc. Of Cross-reactant spikedµg/mL | Mean | SD | CV | Da-Dt | % Cross-Reactivity | |
|---|---|---|---|---|---|---|---|---|
| 3-Hydroxyquinidine | 3 | 5.71 | 5 | 5.78 | 0.12 | 2.01 | 0.06 | 1.27 |
| Quinidine-N-oxide | 3 | 5.72 | 5 | 8.99 | 0.27 | 2.96 | 3.28 | 65.60 |
| O-Desmethylquinidine | 3 | 5.72 | 5 | 6.55 | 0.02 | 0.35 | 0.84 | 16.80 |
| 2-Oxoquinidinone | 3 | 5.71 | 5 | 6.09 | 0.03 | 0.47 | 0.38 | 7.60 |
| 10,11-Dihydroquinidinediol | 3 | 5.37 | 5 | 5.99 | 0.17 | 2.81 | 0.63 | 12.53 |
Interferences
Interference studies were conducted using NCCLS Guideline EP7: Interference Testing in Clinical Chemistry.
1) Endogenous Substances
| Interfering Substance | InterferentConcentration | N | Target(No Interferent)µg/mL | MeanRecoveryµg/mL | % RecoveryAcceptanceCriteria:100±10% |
|---|---|---|---|---|---|
| Bilirubin | 15 mg/dL | 2 | 5.82 | 5.98 | 103.0 |
| Hemoglobin | 10 g/L | 2 | 5.82 | 5.84 | 100.0 |
| Triglyceride | 1127 mg/dL | 3 | 6.05 | 5.58 | 92.18 |
| Total Protein | 12 g/dL | 3 | 6.32 | 6.30 | 99.68 |
2) HAMA
| Rep 1µg/mL | Rep 2µg/mL | MeanRecoveryµg/mL | SD | CV | % RecoveryAcceptance Criteria:100±10% | |
|---|---|---|---|---|---|---|
| Control | 6.59 | 6.24 | 6.42 | 0.18 | 2.73 | ------ |
| HAMA Type-1 | 5.79 | 5.91 | 5.85 | 0.08 | 1.37 | 91.12 |
| HAMA Type-2 | 5.80 | 5.84 | 5.82 | 0.02 | 0.34 | 90.65 |
{4}------------------------------------------------
| Cross-reactant Drug | Conc. Testedµg/mL | Percent Cross-Reactivity/Conc(µg/mL) |
|---|---|---|
| Acetominophen | 200 | ND |
| Acetyl cysteine | 1000 | ND |
| Acetylsalycilic acid | 3000 | ND |
| Ampicillin | 50 | ND |
| Ascorbic acid | 30 | -0.51 |
| Cefoxitin | 1000 | ND |
| Cyclosporine | 600 | ND |
| Digitoxin | 0.25 | ND |
| Digoxin | 0.02 | 0.02 |
| Disopyramide | 50 | 0.76 |
| Ephedrin | 1000 | ND |
| Furosemide | 100 | ND |
| Hydrochlorothiazide | 40 | ND |
| Ibuprofen | 7000 | ND |
| Isoproterenol | 0.06 | ND |
| Levodpa | 1000 | ND |
| Lidocaine | 50 | ND |
| Metronidazole | 1000 | ND |
| N-Acetylprocainamide | 400 | ND |
| Phenylbutazone | 1000 | ND |
| Phenytoin (DPH) | 200 | ND |
| Procainamide | 100 | ND |
| Propranolol | 1 | 4.33 |
| Quinine | 5 | 14.80 |
| Reserpine | 1000 | ND |
| Rifampicin | 50 | ND |
| Tetracycline | 2000 | ND |
| Theophylline | 200 | ND |
3) Common Co-Administered Drugs
*ND = not detected
4) Anticoagulants
Studies were conducted to determine the performance characteristics of the assay for both serum and plasma samples containing quinidine.
The results indicate that there is no significant difference between the recovery of quinidine in serum or plasma. The collection tubes evaluated show no adverse effects on the recovery of quinidine, 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 28 days is supported by the data.
Reagent On-Board Stability 2)
A 25 day on-board reagent stability claim is supported by the data.
CONCLUSION
As summarized above, the QMS® Quinidine assay is substantially equivalent to the Abbott TDxYTDxFLxF Quinidine assay. Substantial equivalence has been demonstrated through performance testing to verify that the device functions as intended and that design specifications have been satisfied.
{5}------------------------------------------------
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Image /page/5/Picture/2 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged in a circular pattern around the symbol. The caduceus is a common symbol associated with healthcare and medicine. The logo is black and white.
DEC 2 3 2005
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Mr. Jack Roger Manager of Regulatory Affairs Seradyn, Inc. 7998 Georgetown Road Suite 100 Indianapolis, IN 46268
K052826 Re:
Trade/Device Name: QMS® Quinidine Regulation Number: 21 CFR 862.3320 Regulation Name: Digoxin test system Regulatory Class: Class II Product Code: LBZ Dated: October 4, 2005 Received: October 5, 2005
Dear Mr. Rogers:
We have reviewed your Section 510(k) premarket notification of intent to market the device wt nave reviewed your becament of (s) for the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for use stated in the enorosary to regars) the enactment date of the Medical Device Amendments, or to conninered pror to May 20, 1976, in accordance with the provisions of the Federal Food, Drug, devices that have been require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The r ou may, mere revolvisions 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), if your do received to such additional controls. Existing major regulations affecting your device it may be subject to bach as 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 that + 21 the al statutes and regulations administered by other Federal agencies. You must or any vith 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).
{6}------------------------------------------------
Page 2 -
This letter will allow you to begin marketing your device as described in your Section 510(k) This letter writ anow you to oogh manieting of substantial equivalence of your device to a legally premarket notification: "The I DTF intering sification 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, If you destions on the promotion and advertising of your device, please contact the Office of In of quostions on the promotion 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 I ou may of ameral 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 Guts
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
{7}------------------------------------------------
Indications for Use
510(k) Number (if known): K052826
QMS® Quinidine Device Name:
Indications for Use:
The QMS® Quinidine assay is intended for the quantitative determination of quinidine in human serum or plasma on automated clinical chemistry analyzers.
The results obtained are used in the diagnosis and treatment of quinidine The lesults obtainou are assume of quinidine to help ensure appropriate therapy.
× 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)
Ann chappie
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
Page 1 of _
510/1/1 1 16 52824 -----------------------------------------------------------------------------------------------------------------------------------------------------------
§ 862.3320 Digoxin test system.
(a)
Identification. A digoxin test system is a device intended to measure digoxin, a cardiovascular drug, in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of digoxin overdose and in monitoring levels of digoxin to ensure appropriate therapy.(b)
Classification. Class II.