QMS AMIKACIN REAGENTS

K052815 · Seradyn, Inc. · KLQ · Nov 1, 2005 · Clinical Toxicology

Device Facts

• Record ID: K052815
• Device Name: QMS AMIKACIN REAGENTS
• Applicant: Seradyn, Inc.
• Product Code: KLQ · Clinical Toxicology
• Decision Date: Nov 1, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3035
• Device Class: Class 2

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.

Device Story

QMS Amikacin is a homogeneous particle-enhanced turbidimetric immunoassay for quantitative measurement of amikacin in human serum or plasma. It operates on automated clinical chemistry analyzers using competitive binding; anti-amikacin monoclonal antibodies (R1) and amikacin-coated microparticles (R2) react with patient samples. Presence of amikacin in the sample inhibits particle agglutination, resulting in decreased absorbance proportional to drug concentration. The device is used in clinical laboratories by technicians. Healthcare providers use the resulting concentration values to adjust antibiotic dosing, ensure therapeutic efficacy, and manage potential toxicity or overdose. The assay provides a rapid, automated alternative to traditional methods, facilitating timely clinical decision-making for patients undergoing aminoglycoside therapy.

Clinical Evidence

Bench testing only. Performance established via precision (total CV < 10%), linearity (1.5–50 µg/mL, R²=0.9998), and analytical sensitivity (0.54 µg/mL). Method comparison with predicate (n=56) yielded Passing-Bablok regression y=1.00x + 0.245 (r=0.992). Interference testing showed <10% error for common substances (bilirubin, hemoglobin, triglycerides, protein, HAMA). Matrix equivalence confirmed across 9 tube types.

Technological Characteristics

Homogeneous particle-enhanced turbidimetric immunoassay. Reagents: R1 (anti-amikacin monoclonal antibody, mouse ascites, sodium azide preservative), R2 (amikacin-coated microparticles, stabilizers, sodium azide). Photometric measurement of agglutination inhibition. Liquid form. Designed for automated clinical chemistry analyzers. No internal software algorithm; relies on analyzer-specific photometric rate calculation.

Indications for Use

Indicated for quantitative determination of amikacin in human serum or plasma for patients requiring monitoring of amikacin levels for therapy or diagnosis of overdose.

Regulatory Classification

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.

Predicate Devices

• TDx/TDxFLx Amikacin Assay (k802669)

Submission Summary (Full Text)

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# 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: [phone] Fax: [phone]

#### 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.

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| | Device<br>Seradyn QMS® Amikacin | Predicate<br>Abbott TDx/TDxFLx Amikacin |
|------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The QMS Amikacin assay is for the<br>quantitative determination of amikacin<br>in human serum or plasma on<br>automated clinical chemistry<br>analyzers | The TDx/TDxFLx Amikacin assay is<br>a reagent system for the<br>quantitative measurement of<br>amikacin, an aminoglycoside<br>antibiotic drug, in serum or plasma. |
| Indications<br>for Use | The results obtained are used in the<br>diagnosis and treatment of amikacin<br>overdose and in monitoring levels of<br>amikacin to ensure appropriate<br>therapy. | The measurements obtained are<br>used in the diagnosis and treatment<br>of amikacin overdose and in<br>monitoring levels of amikacin to<br>ensure appropriate therapy. |
| Methodology | Homogeneous particle-enhanced<br>turbidimetric immunoassay (particle<br>agglutination) | Fluorescence Polarization<br>Immunoassay (FPIA) technology. |
| Reagent<br>Components | Two (2) reagent system:<br>• Anti-amikacin Antibody Reagent<br>(R1) in buffers containing<br>stabilizers with sodium azide<br>• Amikacin-coated Microparticle<br>Reagent (R2) in buffer containing<br>stabilizers with sodium azide | Three (3) reagent system:<br>• Pretreatment Solution (P)<br>Surfactant in buffer containing<br>protein stabilizer and sodium<br>azide.<br>• S Amikacin Antiserum (Sheep) in<br>buffer with protein stabilizer and<br>Sodium azide.<br>• T Amikacin Fluorescein Tracer in<br>buffer with protein stabilizer,<br>surfactant and Sodium azide |
| Calibration | QMS Amikacin<br>Calibrators - 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.

| THEORETICAL<br>CONC.<br>(µG/ML) | Rep 1 | Rep 2 | Mean<br>Recovered<br>Conc. | SD | CV | % Recovery<br>Acceptance<br>Criteria:<br>$100±10%$ |
|---------------------------------|-------|-------|----------------------------|------|-------|----------------------------------------------------|
| 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 |

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#### 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.

| THEORETICAL<br>CONC.<br>(µg/mL) | Rep 1 | Rep 2 | Mean<br>Recovered<br>Conc. | 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.

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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.

| | | | Within Run | | Between Day | | Total | |
|--------------|----|---------------|------------|--------|-------------|--------|-------|--------|
| | N | Mean<br>µg/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 | Interferent<br>Concentration | N | Target<br>(No Interferent)<br>µg/mL | Mean<br>Recovery<br>µg/mL | % Recovery<br>Acceptance<br>Criteria:<br>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 1<br>µg/mL | Rep 2<br>µg/mL | Mean<br>Recovery<br>µg/mL | SD | CV | % Recovery<br>Acceptance Criteria:<br>$100\pm10%$ |
|----------------|----------------|----------------|---------------------------|------|------|---------------------------------------------------|
| HAMA<br>Type-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 |
| HAMA<br>Type-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 |

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| Cross-reactant Drug | Conc. Tested<br>ug/mL | Percent Cross-<br>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.

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# 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).

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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 [phone]. 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 [phone] or [phone] 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

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# 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