(28 days)
The QMS® Amikacin assay is intended for the quantitative determination of amikacin in human serum or plasma on automated clinical chemistry analyzers.
The results obtained are used in the diagnosis and treatment of amikacin overdose and in monitoring levels of amikacin to ensure appropriate therapy.
The QMS® Amikacin 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 Amikacin 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 drug. The absorbance of unknown samples can be interpolated from the absorbance values of the calibration curve and the concentration of the drug present in the sample can be calculated.
The assay consists of reagents R1: anti-amikacin monoclonal antibody and R2: amikacin-coated microparticles. A six-level set of QMS® Amikacin Calibrators (A through F) is used to calibroothe assay.
Here's a breakdown of the acceptance criteria and study information for the QMS® Amikacin 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: 94.02% (Specific recoveries: 95.87% for 9.2 µg/mL and 92.17% for 18.4 µg/mL) - Meets criteria |
| Linearity | Correlation coefficient (R2) demonstrating linearity | Correlation Coefficient (R2): 0.9998 (Mean Percent Recovery: 100.41% over a range of 1.5 to 42.5 µg/mL; specific recoveries from 95.71% to 111.33%) - Meets criteria |
| Sensitivity | Claimed LDD: 0.8 µg/mL | Average LDD: 0.54 µg/mL - Exceeds claimed performance (better sensitivity) |
| Assay Range | Not explicitly stated as acceptance criteria, but derived from other data | Reportable Range: 1.5 to 50 µg/mL (Based on Accuracy, Linearity, and Sensitivity data) |
| Method Comparison | Excellent correlation with predicate device | Correlation to Abbott TDx/TDxFLx Amikacin: N = 56, Slope = 1.00, y-intercept = 0.25, R = 0.996, R2 = 0.992. Results show excellent correlation. - Meets criteria |
| Precision | Total CV: < 10% | Total CVs: Low Control: 9.94%, Mid Control: 6.22%, High Control: 6.32% - Meets criteria |
| Interferences (Endogenous Substances) | % Recovery: 100 ± 10% | Bilirubin (15mg/dL): 96.40% Hemoglobin (10g/L): 93.42% Triglyceride (1691 mg/dL): 96.30% Total Protein (12 g/dL): 96.00% - All meet criteria |
| Interferences (HAMA) | % Recovery: 100 ± 10% | HAMA Type-1: 100.5% HAMA Type-2: 98.04% - All meet criteria |
| On-Board Stability (Calibration Curve) | 28 days stability supported by data | Supported: 28 days - Meets criteria |
| On-Board Stability (Reagent) | 40 days stability supported by data | Supported: 40 days - Meets criteria |
2. Sample Sizes Used for the Test Set and Data Provenance
- Accuracy: Samples were spiked human serum. No specific number for "samples analyzed" is given, but it mentions "in duplicate." The specific source/country of the human serum is not mentioned. This appears to be a laboratory-controlled, prospective study.
- Linearity: Not explicitly stated, but based on "a study based on the NCCLS guideline EP6." A set of 5 theoretical concentrations was tested, each in duplicate. USP Amikacin was used, indicating an in vitro, laboratory-controlled prospective study.
- Sensitivity: Not explicitly stated, but related to the lowest detectable dose from laboratory measurements.
- Method Comparison: N = 56 patient samples. The data provenance (country of origin, retrospective/prospective) is not explicitly stated, but the mention of "patient samples" suggests retrospective or prospective clinical samples. It does not state if these were collected specifically for this study or were archived.
- Precision: 80 measurements for each of the three control levels over multiple runs/days. This refers to laboratory-controlled measurements of quality control materials.
- Interferences:
- Endogenous Substances: N=2 or N=3 for each interferent tested. These were likely laboratory-prepared samples with added interferents, a prospective study.
- Human Anti-Mouse Antibodies (HAMA): Not explicitly stated, but given as "Rep 1" and "Rep 2" for HAMA Type-1 and Type-2, suggesting laboratory-spiked samples.
- Cross-reactants: No 'N' is listed, but various cross-reactant drugs were tested at specified concentrations. This would be a laboratory-controlled study.
- Anticoagulants: Not explicitly stated, but likely laboratory-controlled comparison of serum and plasma samples, a prospective study.
3. Number of Experts Used to Establish Ground Truth and Qualifications
This document describes the performance characteristics of an in-vitro diagnostic (IVD) device for measuring a drug concentration. The "ground truth" in this context is established by:
- Known Reference Values: For accuracy, linearity, and sensitivity, the ground truth is the spectroscopically pure USP traceable amikacin spiked into human serum at known concentrations.
- Reference Method: For method comparison, the ground truth is considered the results obtained from the predicate device, the Abbott TDx/TDxFLx® Amikacin assay.
Therefore, there were no clinical experts (e.g., radiologists) involved in establishing the "ground truth" in the way one would for image interpretation or diagnosis. The ground truth relies on analytical chemistry principles and a comparative reference method for this type of device.
4. Adjudication Method for the Test Set
Not applicable. This is an analytical device for quantitative measurement, not a human-interpreted diagnostic output requiring adjudication. The performance is assessed by comparing the device's output to known input concentrations or to measurements from a predicate device.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
Not applicable. This is a standalone analytical device, not a human-in-the-loop system where human reader performance is being evaluated or augmented by AI.
6. Standalone (Algorithm Only) Performance
Yes, the studies presented here are entirely standalone performance evaluations of the QMS® Amikacin assay. The device measures amikacin concentration in a sample without human interpretation or intervention in the measurement process itself. The "algorithm" here refers to the underlying chemical reaction and optical detection described in the "Description of Device," which is inherent to the device's operation.
7. Type of Ground Truth Used
- Known (Spiked) Concentrations: For accuracy, linearity, and sensitivity, the ground truth was established by precisely preparing samples with known concentrations of USP traceable amikacin.
- Reference Standard (Predicate Device): For method comparison, the Abbott TDx/TDxFLx® Amikacin assay served as the reference standard to which the new device's results were compared.
8. Sample Size for the Training Set
No information about a "training set" is provided. This is a traditional IVD device, not a machine learning or AI-driven system that would typically have a distinct "training set" and "test set" in the computational sense. The "development" and "validation" of the assay are implied by the studies conducted, but not in the context of training a machine learning model.
9. How Ground Truth for the Training Set Was Established
Not applicable, as no dedicated "training set" is described for this type of device.
{0}------------------------------------------------
NOV - 1 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:
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
October 25, 2005
DEVICE NAME
| Trade Name: | QMS® Amikacin |
|---|---|
| Common Name: | Homogeneous Particle-Enhanced Turbidimetric Immunoassay |
| Device Classification: | 21 CFR 862.3035; Amikacin Test System; Class II |
INTENDED USE
The QMS® Amikacin assay is intended for the quantitative determination of amikacin in human serum or plasma on automated clinical chemistry analyzers.
The results obtained are used in the diagnosis and treatment of amikacin overdose and in monitoring levels of amikacin to ensure appropriate therapy.
LEGALLY MARKETED DEVICE TO WHICH EQUIVALENCY IS CLAIMED
Abbott TDx/TDxFLx Amikacin (K802669)
DESCRIPTION OF DEVICE
The QMS® Amikacin 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 Amikacin 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 drug. The absorbance of unknown samples can be interpolated from the absorbance values of the calibration curve and the concentration of the drug present in the sample can be calculated.
The assay consists of reagents R1: anti-amikacin monoclonal antibody and R2: amikacin-coated microparticles. A six-level set of QMS® Amikacin Calibrators (A through F) is used to calibroothe assay.
{1}------------------------------------------------
| DeviceSeradyn QMS® Amikacin | PredicateAbbott TDx/TDxFLx Amikacin | |
|---|---|---|
| Intended Use | The QMS Amikacin assay is for thequantitative determination of amikacinin human serum or plasma onautomated clinical chemistryanalyzers | The TDx/TDxFLx Amikacin assay isa reagent system for thequantitative measurement ofamikacin, an aminoglycosideantibiotic drug, in serum or plasma. |
| Indicationsfor Use | The results obtained are used in thediagnosis and treatment of amikacinoverdose and in monitoring levels ofamikacin to ensure appropriatetherapy. | The measurements obtained areused in the diagnosis and treatmentof amikacin overdose and inmonitoring levels of amikacin toensure appropriate therapy. |
| Methodology | Homogeneous particle-enhancedturbidimetric immunoassay (particleagglutination) | Fluorescence PolarizationImmunoassay (FPIA) technology. |
| ReagentComponents | Two (2) reagent system:• Anti-amikacin Antibody Reagent(R1) in buffers containingstabilizers with sodium azide• Amikacin-coated MicroparticleReagent (R2) in buffer containingstabilizers with sodium azide | Three (3) reagent system:• Pretreatment Solution (P)Surfactant in buffer containingprotein stabilizer and sodiumazide.• S Amikacin Antiserum (Sheep) inbuffer with protein stabilizer andSodium azide.• T Amikacin Fluorescein Tracer inbuffer with protein stabilizer,surfactant and Sodium azide |
| Calibration | QMS AmikacinCalibrators - six levels | Amikacin Calibrators - six levels |
COMPARISON OF TECHNOLOGICAL CHARACTERISTICS
SUMMARY OF CLINICAL TESTING
Accuracy
Accuracy by Recovery was determined by spiking USP traceable amikacin into human serum negative for the drug to achieve concentrations of 18.4 and 9.2ug/mL. The samples were analyzed in duglicate with the QMS Amikacin assay.
| THEORETICALCONC.(µG/ML) | Rep 1 | Rep 2 | MeanRecoveredConc. | SD | CV | % RecoveryAcceptanceCriteria:$100±10%$ |
|---|---|---|---|---|---|---|
| 9.2 | 8.92 | 8.72 | 8.82 | 0.14 | 1.59% | 95.87 |
| 18.4 | 16.79 | 17.13 | 16.96 | 0.17 | 1.00% | 92.17 |
| Mean Percent Recovery | 94.02 |
{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 Amikacin against resulted in a line with a correlation coefficient (R2) of 0.9998, demonstrating that the assay is linear.
| THEORETICALCONC.(µg/mL) | Rep 1 | Rep 2 | MeanRecoveredConc. | SD | CV | % Recovery |
|---|---|---|---|---|---|---|
| 1.5 | 1.77 | 1.57 | 1.67 | 0.10 | 5.99 | 111. 33% |
| 6.5 | 6.44 | 6.51 | 6.48 | 0.04 | 0.54 | 99.69% |
| 15.0 | 14.84 | 14.49 | 14.67 | 0.18 | 1.19 | 97.80% |
| 27.5 | 26.69 | 25.95 | 26.32 | 0.37 | 1.41 | 95.71% |
| 42.5 | 41.24 | 41.63 | 41.44 | 0.20 | 0.47 | 97.51% |
| Mean Percent Recovery | 100.41% |
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 0.54 ug/mL, supporting a claim of 0.8 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 1.5 to 50 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 amikacin in serum assayed by the QMS® Amikacin assay to the Abbott TDx/TDxFLx® Amikacin 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 = 56 Slope = 1.00 y-intercept = 0.25 R = 0.996 R2 = 0.992
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.
| Within Run | Between Day | Total | ||||||
|---|---|---|---|---|---|---|---|---|
| N | Meanµg/mL | SD | CV (%) | SD | CV (%) | SD | CV (%) | |
| Low Control | 80 | 4.09 | 0.22 | 5.37 | 0.19 | 4.77 | 0.41 | 9.94 |
| Mid Control | 80 | 12.00 | 0.21 | 1.79 | 0.08 | 0.70 | 0.74 | 6.22 |
| High Control | 80 | 24.37 | 0.47 | 1.93 | 0.40 | 1.65 | 1.54 | 6.32 |
Acceptance Criteria: < 10% total CV
Specificity
There are no metabolites of amikacin.
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 | 15mg/dL | 2 | 21.65 | 20.87 | 96.40 |
| Hemoglobin | 10g/L | 2 | 17.32 | 16.18 | 93.42 |
| Triglyceride | 1691 mg/dL | 3 | 24.03 | 23.14 | 96.30 |
| Total Protein | 12 g/dL | 3 | 24.03 | 23.07 | 96.00 |
2)
| Rep 1µg/mL | Rep 2µg/mL | MeanRecoveryµg/mL | SD | CV | % RecoveryAcceptance Criteria:$100\pm10%$ | |
|---|---|---|---|---|---|---|
| HAMAType-1 | 20.68 | 20.13 | 20.41 | 0.27 | 1.35 | 100.5 |
| Control | 20.29 | 20.33 | 20.31 | 0.02 | 0.10 | 100.0 |
| HAMAType-2 | 16.97 | 16.99 | 16.98 | 0.01 | 0.05 | 98.04 |
| Control | 16.99 | 17.65 | 17.32 | 0.33 | 1.91 | 100.0 |
{4}------------------------------------------------
| Cross-reactant Drug | Conc. Testedug/mL | Percent Cross-Reactivity |
|---|---|---|
| 5-Fluorocytosine | 30 | -0.39 |
| Amphotericin | 100 | 1.33 |
| Ampicillin | 50 | ND |
| Carbenicillin | 2500 | ND |
| Cephalexin | 320 | ND |
| Cephalosporin C | 1000 | ND |
| Cephalothin | 1000 | ND |
| Chloramphenicol | 250 | 0.55 |
| Clindamycin | 2000 | ND |
| Erythromycin | 500 | ND |
| Ethacrynic acid | 400 | ND |
| Furosemide | 100 | 1.00 |
| Fusidic acid | 1000 | ND |
| Gentamicin | 100 | ND |
| Kanamycin A | 400 | ND |
| Kanamycin B | 400 | ND |
| Lincomycin | 2000 | ND |
| Methicillin | 200 | 0.41 |
| Methotrexate | 500 | ND |
| Methylprednisolone | 200 | 0.638 |
| Neomycin | 1000 | ND |
| Netilmycin | 125 | ND |
| Oxytetracycline | 2000 | ND |
| Penicillin V | 100 | 1.38 |
| Prednisolone | 12 | 2.36 |
| Rifampicin | 500 | ND |
| Spectinomycin | 100 | ND |
| Streptomycin | 400 | ND |
| Sulfadiazine | 1000 | ND |
| Sulfamethoxazole | 400 | ND |
| Tetracycline | 2000 | ND |
| Tobramycin | 100 | 0.32 |
| Trimethoprim | 200 | ND |
| Vancomycin | 400 | ND |
3) Common Co-Administered Drugs
*ND
4) Anticoagulants
Studies were conducted to determine the performance characteristics of the assay for both serum and plasma samples containing amikacin.
The results indicate that there is no significant difference between the recovery of amikacin in serum or plasma. The collection tubes evaluated show no adverse effects on the recovery of amikacin, 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.
2) Reagent On-Board Stability
A 40 day on-board reagent stability claim is supported by the data.
CONCLUSION
As summarized above, the QMS® Amikacin assay is substantially equivalent to the Abbott TDxFLx® Amikacin 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
Image /page/5/Picture/1 description: The image shows the seal of the U.S. Department of Health and Human Services. The seal features a stylized caduceus, a symbol often associated with medicine and healthcare, with a single snake entwined around a staff. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES . USA" are arranged in a circular pattern around the symbol. The seal is in black and white.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
NOV - 1 2005
Mr. Jack Rogers, MS, RAC Manger of Regulatory Affairs Seradyn, Inc. 7998 Georgetown Road Suite 1000 Indianapolis, IN 46268-5620
Re: K052815
Trade/Device Name: QMS® Amikacin Regulation Number: 21 CFR 862.3035 Regulation Name: Amikacin test system Regulatory Class: Class II Product Code: KLO Dated: October 3, 2005 Received: October 4, 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 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 complish 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) 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 Gutierrez, Ph.D.
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): K052815
QMS® Amikacin Device Name:
Indications for Use:
The QMS® Amikacin assay is intended for the quantitative determination of amikacin in human serum or plasma on automated clinical chemistry analyzers.
The results obtained are used in the diagnosis and treatment of amikacin overdose and in monitoring levels of amikacin to 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)
Stacey Phillips
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
Page 1 of
510(k) K052815
§ 862.3035 Amikacin test system.
(a)
Identification. An amikacin test system is a device intended to measure amikacin, an aminoglycoside antibiotic drug, in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of amikacin overdose and in monitoring levels of amikacin to ensure appropriate therapy.(b)
Classification. Class II.