QMS QUINIDINE. QMS QUINIDINE CALIBRATORS

K052826 · Seradyn, Inc. · LBZ · Dec 23, 2005 · Clinical Toxicology

Device Facts

• Record ID: K052826
• Device Name: QMS QUINIDINE. QMS QUINIDINE CALIBRATORS
• Applicant: Seradyn, Inc.
• Product Code: LBZ · Clinical Toxicology
• Decision Date: Dec 23, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3320
• Device Class: Class 2

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.

Device Story

QMS® Quinidine is a homogeneous particle-enhanced turbidimetric immunoassay (PETIA) for quantitative measurement of quinidine in human serum or plasma. It operates on automated clinical chemistry analyzers using competitive binding; free drug in sample competes with drug-coated microparticles for anti-quinidine antibody binding sites. Agglutination is inversely proportional to drug concentration; absorbance decreases as drug concentration increases. Results are interpolated from a calibration curve. Used in clinical laboratories by technicians/pathologists to monitor therapeutic drug levels and manage overdose. Provides clinicians with quantitative data to adjust dosage or assess toxicity, supporting patient safety and therapeutic efficacy.

Clinical Evidence

Bench testing only. Accuracy by recovery (mean recovery 97.71%); linearity (R²=0.9995, range 0.2–8.0 µg/mL); analytical sensitivity (LDD 0.09 µg/mL). Method comparison study (N=50) against Abbott TDx/TDxFLx showed slope 1.062, y-intercept -0.213, R²=0.978. Precision study (N=80) showed total CV < 10%. Specificity testing evaluated cross-reactivity with quinidine metabolites and common co-administered drugs. Interference testing confirmed no significant impact from bilirubin, hemoglobin, triglycerides, total protein, or HAMA.

Technological Characteristics

Homogeneous particle-enhanced turbidimetric immunoassay (PETIA). Reagents: R1 (anti-quinidine monoclonal antibody) and R2 (quinidine-coated microparticles) in buffers with protein stabilizers and sodium azide. Form factor: liquid reagents for automated clinical chemistry analyzers. Connectivity: analyzer-dependent. Software: rule-based calculation of drug concentration via absorbance interpolation from a 6-level calibration curve.

Indications for Use

Indicated for quantitative determination of quinidine in human serum or plasma for patients requiring monitoring of quinidine levels or diagnosis/treatment of quinidine overdose.

Regulatory Classification

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.

Predicate Devices

• Abbott TDx/TDxFLx Quinidine

Submission Summary (Full Text)

{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: [phone] Fax: [phone]

#### 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}------------------------------------------------

| | Device<br>Seradyn QMS® Quinidine | Predicate<br>Abbott TDx/TDxFLx Quinidine |
|------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The QMS® Quinidine assay is<br>intended for the quantitative<br>determination of quinidine in human<br>serum or plasma on automated<br>clinical chemistry analyzers. | The TDx/TDxFIx Quinidine assay is a<br>reagent system for the quantitative<br>measurement of quinidine in serum or<br>plasma. |
| Indications<br>for Use | The measurements obtained are used<br>in the diagnosis and treatment of<br>quinidine overdose and in monitoring<br>levels of quinidine to ensure<br>appropriate therapy. | The measurements obtained are used<br>in monitoring levels of quinidine 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-Quinidine Antibody Reagent<br>(R1) in buffers containing protein<br>stabilizers with sodium azide<br>• Quinidine-coated Microparticle<br>Reagent (R2) in buffer containing<br>surfactant as stabilizers with<br>sodium azide | Three (3) reagent system:<br>• Pretreatment Solution (P)<br>Surfactant in buffer containing N-<br>N-dimethylformamide and protein<br>stabilizer and sodium azide.<br>• S Quinidine Antiserum (Goat) in<br>buffer with protein stabilizer and<br>Sodium azide.<br>• T Quinidine Fluorescein Tracer in<br>buffer with protein stabilizer<br>surfactant N-N-dimethylformamide<br>and Sodium azide |
| Calibration | QMS Quinidine<br>Calibrators - six levels | X Systems Quinidine<br>Calibrators - 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.

| 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% |
|---------------------------------|-----------------------------|-------|----------------------------|------|------|--------------------------------------------------|
| 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.

| THEORETICAL<br>CONC.<br>(µg/mL) | Rep 1 | Rep 2 | Mean<br>Recovered<br>Conc. | 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<br>(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 | Control<br>Mean | Conc. Of Cross-<br>reactant spiked<br>µg/mL | Mean | SD | CV | Da-Dt | % Cross-<br>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 | 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 | 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 1<br>µg/mL | Rep 2<br>µg/mL | Mean<br>Recovery<br>µg/mL | SD | CV | % Recovery<br>Acceptance Criteria:<br>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. Tested<br>µg/mL | Percent Cross-<br>Reactivity/Conc<br>(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 [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 I ou may of ameral 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 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 -----------------------------------------------------------------------------------------------------------------------------------------------------------