(101 days)
The QMS® Tobramycin assay is intended for the quantitative determination of tobramycin in human serum or plasma on automated clinical chemistry analyzers.
The results obtained are used in the diagnosis and treatment of tobramycin overdose and in monitoring levels of tobramycin to help ensure appropriate therapy.
The QMS® Tobramycin 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- tobramycin monoclonal antibody and R2: tobramycin -coated microparticles. A six-level set of QMS® Tobramycin Calibrators (A through F) is used to calibrate the assay.
Here's a breakdown of the acceptance criteria and study information for the Seradyn QMS® Tobramycin assay, based on the provided 510(k) summary:
Acceptance Criteria and Device Performance
| Test | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Accuracy | % Recovery: 100 ± 10% | Mean Percent Recovery: 94.14% |
| Linearity | % Recovery: 100 ± 10% | Correlation coefficient (R²): 0.9996 |
| Precision | Total CV: < 10% | Low Control: 7.57% |
| Mid Control: 4.23% | ||
| High Control: 4.26% | ||
| Interferences (Endogenous Substances) | % Recovery: 100 ± 10% | Albumin: 97.66% |
| Bilirubin: 92.27% | ||
| Cholesterol: 105.84% | ||
| Gamma Globulins (IgG): 97.44% | ||
| Hemoglobin (20 mg/dL): 97.16% | ||
| Hemoglobin (500 mg/dL): 108.65% | ||
| Uric Acid: 90.31% | ||
| Rheumatoid Factor: 103.29% | ||
| Triglyceride: 90.98% | ||
| Interferences (HAMA) | % Recovery: 100 ± 10% | HAMA Type-1: 92.58% |
| HAMA Type-2: 93.82% | ||
| Sensitivity (LOQ) | Lowest concentration reliably detected meeting accuracy requirements | 0.4 µg/mL |
| Assay Range | Based on Accuracy, Linearity, Sensitivity | 0.4 to 10 µg/mL |
| Method Comparison | Excellent correlation between predicate and new device | N = 67, Slope = 0.979, y-intercept = -0.086, R = 0.992, R² = 0.984 |
| On-Board Stability (Calibration Curve) | Sufficient stability for intended claim | 14 days |
| On-Board Stability (Reagent) | Sufficient stability for intended claim | 45 days |
Study Details
-
Sample size used for the test set and the data provenance:
- Accuracy: The exact number of spiked samples is not explicitly stated beyond "across the range of the assay," but each sample was analyzed in triplicate. The samples used were human serum negative for the drug. Data provenance is not specified (e.g., country of origin), but it is a retrospective laboratory study using controlled samples.
- Linearity: Similar to accuracy, a tobramycin in human serum pool was diluted, and samples were analyzed in triplicate. Data provenance is not specified.
- Sensitivity (LOQ): Not specified.
- Method Comparison: N = 67 patient samples. Data provenance is not specified, but it's a retrospective comparison using patient samples.
- Precision: 80 measurements per control level (Low, Mid, High) over a period of time (e.g., 20 days with 4 replicates per day, which is a common NCCLS EP5-A2 setup, though not explicitly stated here). Data provenance not specified.
- Interferences: 3 replicates per interfering substance. Data provenance not specified.
- Cross-reactivity: Each cross-reactant drug was tested at a specific concentration (e.g., 30 µg/mL for 5-Fluorocytosine, 200 µg/mL for Amikacin).
- Anticoagulants: Not explicitly stated but implies testing with different types of plasma samples and serum.
-
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable. This is a quantitative immunoassay for a drug, and the "ground truth" for the test set samples is typically established by precisely preparing known concentrations of tobramycin (for accuracy, linearity, sensitivity) or by using a a well-established comparative method (for method comparison). There are no human expert readers involved in establishing the ground truth for these types of in vitro diagnostic tests.
-
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not applicable. As described above, this is laboratory testing of a quantitative assay, not an image interpretation or diagnostic performance study requiring expert adjudication. Recovered concentrations are compared to theoretical concentrations or to a predicate device's results.
-
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 not an AI-assisted diagnostic device, nor does it involve human readers interpreting results in the way an MRMC study evaluates. It's an automated clinical chemistry analyzer.
-
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the performance studies described (Accuracy, Linearity, Sensitivity, Precision, Method Comparison, Interferences, Stability) are all standalone performance evaluations of the assay system itself. This device is entirely automated; there is no "human-in-the-loop" once the sample is loaded and the assay initiated. The results are quantitative measurements produced directly by the instrument.
-
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For Accuracy and Linearity: The ground truth was established by known, theoretical concentrations of tobramycin prepared by spiking or diluting human serum.
- For Method Comparison: The "ground truth" was essentially the results obtained from the legally marketed predicate device (Abbott TDx/TDxFLx Tobramycin assay). The study aimed to show correlation and agreement with an already established method.
- For Precision: The ground truth was the mean concentration of the control materials run multiple times.
- For Interferences/Cross-reactivity: The ground truth involved known concentrations of tobramycin with the addition of known concentrations of interfering substances or cross-reactants.
-
The sample size for the training set:
- Not applicable. This is a traditional immunoassay, not a machine learning or AI-based device that requires a "training set" in the computational sense. The reagents and assay parameters are developed and optimized through standard biochemical and analytical chemistry processes, not through training on a dataset.
-
How the ground truth for the training set was established:
- Not applicable, as there is no "training set" in the context of this device. Development of the assay's reagents and methodologies would involve empirical testing and optimization to achieve desired analytical performance characteristics.
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Kolo098
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: K060998
COMPANY/CONTACT PERSON
Seradyn, Inc 7998 Georgetown Road, Suite 1000 Indianapolis, IN 46268
Establishment registration No: 1836010
Earl E. Knight III, MPA Regulatory Affairs Associate Telephone: (317) 544-0639 Fax: (317) 610-0018
DATE PREPARED
June 22, 2006
DEVICE NAME
| Trade Name: | QMS® Tobramycin |
|---|---|
| Common Name: | Homogeneous Particle Enhanced Turbidimetric Immunoassay |
| Device Classification: | 21 CFR 862.3900; Tobramycin Test System; Class II |
INTENDED USE
The QMS® Tobramycin assay is intended for the quantitative determination of tobramycin in human serum or plasma on automated clinical chemistry analyzers.
The results obtained are used in the diagnosis and treatment of tobramycin overdose and in monitoring levels of tobramycin to help ensure appropriate therapy.
LEGALLY MARKETED DEVICE TO WHICH EQUIVALENCY IS CLAIMED
Abbott TDx/TDxFLx Tobramycin assay (K802668)
DESCRIPTION OF DEVICE
The QMS® Tobramycin 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- tobramycin monoclonal antibody and R2: tobramycin -coated microparticles. A six-level set of QMS® Tobramycin Calibrators (A through F) is used to calibrate the assay.
JUL 2 1 2006
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COMPARISON OF TECHNOLOGICAL CHARACTERISTICS
| DeviceSeradyn QMS® Tobramycin | PredicateAbbott TDx/TDxFLx Tobramycin | |
|---|---|---|
| Intended Use | The QMS Tobramycin assay is intendedfor the quantitative determination ofTobramycin in human serum or plasma onautomated clinical chemistry analyzers | The TDx/TDxFLx Tobramycin assay is areagent system for the quantitativemeasurement of tobramycin, anaminoglycoside antibiotic drug, in serum orplasma. |
| Indicationsfor Use | The results obtained are used in thediagnosis and treatment of tobramycinoverdose and in monitoring levels oftobramycin to help ensure appropriatetherapy. | The measurements obtained are used in thediagnosis and treatment of tobramycinoverdose and in monitoring levels oftobramycin to ensure appropriate therapy. |
| Methodology | Homogeneous particle-enhancedturbidimetric immunoassay (particleagglutination) | Fluorescence Polarization Immunoassay(FPIA) technology. |
| ReagentComponents | Two (2) reagent system:• Anti-tobramycin AntibodyReagent (R1) in bufferscontaining stabilizers withsodium azide• Tobramycin-coated MicroparticleReagent (R2) in buffer containingstabilizers with sodium azide | Three (3) reagent system:• Pretreatment Solution (P)Surfactant in buffer containingprotein stabilizer and sodium azide.• S Tobramycin Antiserum (Sheep)in buffer with protein stabilizer andSodium azide.• T Tobramycin Fluorescein Tracer inbuffer with protein stabilizer,surfactant and Sodium azide |
| Calibration | QMS TobramycinCalibrators - six levels | Tobramycin Calibrators - six levels |
SUMMARY OF CLINICAL TESTING
Accuracy
Accuracy by Recovery was determined by spiking tobramycin into human serum negative for the drug to achieve concentrations across the range of the assay. The samples were analyzed in triplicate with the QMS Tobramycin assay.
| TheoreticalConc.(ug/mL) | Rep 1(ug/mL | Rep 2(ug/mL) | Rep 3(ug/mL) | MeanRecoveredConc.(ug/mL) | SD | CV(%) | % RecoveryAcceptanceCriteria:100±10% |
|---|---|---|---|---|---|---|---|
| 1.5 | 1.39 | 1.32 | 1.37 | 1.36 | 0.036 | 2.65 | 90.67% |
| 3.0 | 2.82 | 2.82 | 2.71 | 2.78 | 0.064 | 2.30 | 92.67% |
| 4.5 | 4.24 | 4.39 | 4.26 | 4.30 | 0.081 | 1.88 | 95.56% |
| 6.0 | 5.77 | 5.87 | 5.95 | 5.86 | 0.090 | 1.54 | 97.67% |
| Mean Percent Recovery | 94.14% |
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Linearity
A tobramycin in human serum pool was diluted with human serum negative for tobramycin to achieve concentrations across the range of the assay. The samples were analyzed in triplicate with the QMS Tobramycin assay.
A linear regression analysis plot of the data resulted in a line with a correlation coefficient (R') of 0.9996, demonstrating that the assay is linear.
| TheoreticalConc.(µg/mL) | Rep 1(µg/mL) | Rep 2(µg/mL) | Rep 3(µg/mL) | MeanRecoveredConc.(µg/mL) | SD | CV(%) | % RecoveryAcceptanceCriteria:100±10% |
|---|---|---|---|---|---|---|---|
| 0.465 | 0.42 | 0.51 | 0.52 | 0.48 | 0.055 | 11.395 | 104.05% |
| 0.929 | 0.94 | 0.95 | 0.83 | 0.91 | 0.067 | 7.3437 | 97.60% |
| 1.858 | 1.85 | 1.79 | 1.82 | 1.82 | 0.030 | 1.6484 | 97.95% |
| 3.716 | 3.54 | 3.51 | 3.55 | 3.53 | 0.021 | 0.5892 | 95.08% |
| 5.574 | 5.51 | 5.42 | 5.49 | 5.47 | 0.047 | 0.8634 | 98.19% |
| 7.432 | 7.39 | 7.36 | 7.24 | 7.33 | 0.079 | 1.0828 | 98.63% |
| 9.290 | 9.22 | 9.30 | 9.35 | 9.29 | 0.066 | 0.7059 | 100.00% |
| 11.148 | 10.96 | 11.05 | 11.10 | 11.04 | 0.071 | 0.6428 | 99.00% |
| 13.006 | 13.03 | 12.89 | 13.07 | 13.00 | 0.095 | 0.7272 | 99.93% |
| 14.864 | 15.11 | 14.55 | 14.96 | 14.87 | 0.290 | 1.949 | 100.06% |
| 16.722 | 15.30 | 16.81 | 16.65 | 16.25 | 0.829 | 5.1034 | 97.20% |
| 18.580 | 18.65 | 18.54 | 17.33 | 18.17 | 0.732 | 4.0302 | 97.81% |
Sensitivity
The Functional Sensitivity or Limit of Quantitation (LOQ) of the assay is defined as the lowest concentration of an analyte that can be reliably detected and at which the total error meets accuracy requirements. The LOQ was determined to be 0.4 µg/mL.
Assay Range
Based on the Accuracy, Linearity, and Sensitivity data, the package insert claim for the reportable range for the assay will be 0.4 to 10 ug/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 tobramycin in serum assayed by the QMS® Tobramycin assay to the Abbott TDx/TDxFLx Tobramycin assay.
Mean values for the TDx reference method were plotted against those for the QMS on Hitachi 917 . The results, using Passing - Bablok parameters, are:
N = 67 Slope = 0.979 y-intercept = - 0.086 R = 0.992 R2 = 0.984
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 Clinical Chemistry Devices.
| N | Meanµg/mL | Within Run | Between Day | Total | ||||
|---|---|---|---|---|---|---|---|---|
| SD | CV (%) | SD | CV (%) | SD | CV (%) | |||
| Low Control | 80 | 1.11 | 0.022 | 1.98 | 0.054 | 4.86 | 0.084 | 7.57 |
| Mid Control | 80 | 3.83 | 0.050 | 1.31 | 0.120 | 3.13 | 0.162 | 4.23 |
| High Control | 80 | 8.06 | 0.131 | 1.63 | 0.057 | 0.71 | 0.343 | 4.26 |
Acceptance Criteria: < 10% total CV
Specificity
The QMS Tobramycin assay utilizes a mouse derived (ascites) tobramycin monoclonal antibody directed against tobramycin. There are no metabolites of tobramycin.
Interferences
Interference studies were conducted using NCCLS Guideline EP7-A2: Interference Testing in Clinical Chemistry.
| InterferingSubstance | InterferentConcentration | N | Target(No Interferent)µg/mL | MeanRecoveryµg/mL | % RecoveryAcceptanceCriteria:100±10% |
|---|---|---|---|---|---|
| Albumin | 12 g/dL | 3 | 8.53 | 8.33 | 97.66% |
| Bilirubin | 400 mg/dL | 3 | 8.41 | 7.76 | 92.27% |
| Cholesterol | 500 mg/dL | 3 | 7.02 | 7.43 | 105.84% |
| Gamma Globulins(IgG) | 12 g/dL | 3 | 7.02 | 6.84 | 97.44% |
| Hemoglobin | 20 mg/dL | 3 | 8.09 | 7.86 | 97.16% |
| Hemoglobin | 500 mg/dL | 3 | 8.09 | 8.79 | 108.65% |
| Uric Acid | 20 mg/dL | 3 | 7.02 | 6.34 | 90.31% |
| Rheumatoid Factor | 705 IU/mL | 3 | 6.99 | 7.22 | 103.29% |
| Triglyceride | 1200 mg/dL | 3 | 6.89 | 7.58 | 90.98% |
A. Endogenous Substances
B. HAMA
| Rep 1µg/mL | Rep 2µg/mL | Rep 3µg/mL | MeanRecoveryµg/mL | SD | %CV | % RecoveryAcceptanceCriteria:100±10% | |
|---|---|---|---|---|---|---|---|
| HAMAType-1 | 7.53 | 7.42 | 7.53 | 7.49 | 0.08 | 1.08% | 92.58% |
| Control | 8.11 | 8.14 | 8.03 | 8.09 | 0.08 | 0.99% | 100.00% |
| HAMAType-2 | 7.49 | 7.69 | 7.60 | 7.59 | 0.06 | 0.79% | 93.82% |
| Control | 8.11 | 8.14 | 8.03 | 8.09 | 0.08 | 0.99% | 100.00% |
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| Cross-reactantDrug | Conc. Testedµg/mL | Percent Cross-Reactivity |
|---|---|---|
| 5-Fluorocytosine | 30 | 0.29 |
| Acetaminophen | 200 | ND |
| Amikacin | 200 | 12.41 |
| Amphotericin B | 100 | ND |
| Ampicillin | 50 | ND |
| Carbenicillin | 2500 | -0.13 |
| Cefamandole Nafate | 250 | ND |
| Cephalexin | 320 | ND |
| Cephalosporin C | 1000 | ND |
| Cephalothin | 1000 | ND |
| Chloramphenicol | 250 | ND |
| Clindamycin | 2000 | ND |
| Ephedrine | 1000 | ND |
| Erythromycin | 500 | ND |
| Ethacrynic Acid | 400 | ND |
| Furosemide | 100 | ND |
| Fusidic Acid | 1000 | ND |
| Gentamicin | 100 | ND |
| Ibuprofen | 7000 | ND |
| Kanamycin A | 400 | 6.86 |
| Kanamycin B | 400 | 6.61 |
| Lincomycin | 2000 | ND |
| Methicillin | 200 | -0.25 |
| Methotrexate | 500 | ND |
| Methylprednisolone | 200 | ND |
| Neomycin | 1000 | ND |
| Netilmycin | 125 | ND |
| Oxytetracycline | 2000 | ND |
| Penicillin V | 100 | -0.20 |
| Prednisolone | 12 | 0.33 |
| Rifampicin | 500 | ND |
| Sisomycin | 100 | ND |
| Spectinomycin | 100 | ND |
| Streptomycin | 400 | ND |
| Sulfadiazine | 1000 | ND |
| Sulfamethoxazole | 400 | ND |
| Tetracycline | 2000 | ND |
| Trimethoprim | 200 | -0.70 |
| Vancomycin | 400 | ND |
C. Common Co-Administered Drugs
*ND = Not Detected
D. Anticoagulants
Studies were conducted to determine the performance characteristics of the assay for both serum and plasma samples containing tobramycin.
The results indicate that there is no significant difference between the recovery of tobramycin in serum or plasma. The collection tubes evaluated show no adverse effects on the recovery of tobramycin, within the experimental error for the spiking study.
A claim for assay application to both serum and plasma samples is thus supported.
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On-Board Stability
1) Calibration Curve stability
Calibration curve stability of a period of 14 days is supported by the data.
2) Reagent On-Board Stability
A 45 day on-board reagent stability claim is supported by the data.
CONCLUSION
The QMS® Tobramycin assay has been shown to be substantially equivalent to the Abbott TDx 77DxFLx Tobramycin assay. The performance testing verifies that the device functions as intended and that design specifications have been satisfied.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo features a stylized caduceus, a symbol often associated with medicine and healthcare. The words "U.S. Department of Health & Human Services USA" are arranged in a circular pattern around the caduceus.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
JUL 2 1 2006
Earl E. Knight III, MPA Regulatory Affairs Associate Seradyn. Inc. 7998 Georgetown Road, Suite 1000 Indianapolis, IN 46268-5620
Re: K060998
Trade/Device Name: QMS® Tobramycin Regulation Number: 21 CFR& 862.3900 Regulation Name: Tobramycin test system Regulatory Class: Class II Product Code: LCR Dated: June 29, 2006 Received: June 30, 2006
Dear Mr. Knight:
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. Ilsting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If vour 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) 276-0484. 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 Guti
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
1060998 510(k) Number (if known):
QMS® Tobramycin Device Name:
Indications for Use:
The QMS® Tobramycin assay is intended for the quantitative determination of tobramycin in human serum or plasma on automated clinical chemistry analyzers.
The results obtained are used in the diagnosis and treatment of tobramycin overdose and in monitoring levels of tobramycin 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 nce of of CDRH, coRH. (Office Cortice of of the In Vitro Vitro Diagr Diagnostic Devices (OIVD)
Livision Sign-Off
Office of In Vitro Diagnostic Device
Evaluation and Safety
§ 862.3900 Tobramycin test system.
(a)
Identification. A tobramycin test system is a device intended to measure tobramycin, an aminoglycoside antibiotic drug, in plasma and serum. Measurements obtained by this device are used in the diagnosis and treatment of tobramycin overdose and in monitoring levels of tobramycin to ensure appropriate therapy.(b)
Classification. Class II.