DRI METHADONE METABOLITE (100/300) ASSAY, CALIBRATORS AND CONTROLS

K081378 · Thermo Fisher Scientific · DJR · Jan 14, 2009 · Clinical Toxicology

Device Facts

• Record ID: K081378
• Device Name: DRI METHADONE METABOLITE (100/300) ASSAY, CALIBRATORS AND CONTROLS
• Applicant: Thermo Fisher Scientific
• Product Code: DJR · Clinical Toxicology
• Decision Date: Jan 14, 2009
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3620
• Device Class: Class 2

Intended Use

The DRI Methadone Metabolite (100/300) Assay is intended for the qualitative and semi-quantitative determination of the presence of Methadone Metabolite (2-ethylidene-1,5-dighenyl-3,3-diphenylpyrrolidine or EDDP) in human urine at cutoffs of 100 and 300 ng/mL. The assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography / Mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. Tests for methadone metabolite cannot distinguish between abused drugs and certain prescribed medications. Certain foods or medications may interfere with test for methadone metabolite and cause false positive results. The DRI Methadone Metabolite Calibrators are intended for use in calibration of the DRI Methadone Metabolite (100/300) Assay. The DRI Methadone Metabolite Controls are intended for use in the DRI Methadone Metabolite (100/300) Assay to detect and monitor systematic deviations from accuracy resulting from reagent or instrument defects.

Device Story

Assay uses liquid ready-to-use reagents for EDDP detection in human urine; utilizes homogeneous enzyme immunoassay principle; competition between drug-labeled G6PDH and free drug in sample for antibody binding sites; enzyme activity measured spectrophotometrically at 340 nm; direct relationship between drug concentration and enzyme activity; used on clinical chemistry analyzers (e.g., Hitachi 917) by professional laboratory personnel; provides preliminary results requiring GC/MS confirmation; aids in monitoring drug presence; clinical judgment required for interpretation.

Clinical Evidence

No clinical studies performed. Analytical performance established via bench testing. Precision evaluated per CLSI EP5-A (N=80 per concentration). Method comparison conducted on 100 clinical specimens against GC/MS; qualitative agreement 93-100% and semi-quantitative agreement 98-100% depending on cutoff. Linearity r=0.9990. Analytical specificity tested against numerous endogenous/exogenous substances and structurally related compounds; no significant interference observed.

Technological Characteristics

Homogeneous enzyme immunoassay; liquid ready-to-use reagents (R1: mouse monoclonal anti-EDDP, G6P, NAD; R2: EDDP-G6PDH conjugate); spectrophotometric detection at 340 nm; calibrators and controls liquid ready-to-use; traceable to Cerilliant methadone standard; validated on Hitachi 917 analyzer; sodium azide preservative.

Indications for Use

Indicated for qualitative and semi-quantitative detection of Methadone Metabolite (EDDP) in human urine at 100 and 300 ng/mL cutoffs. Intended for clinical toxicology use to provide preliminary results; requires confirmatory testing (e.g., GC/MS). Not for distinguishing between illicit abuse and prescribed medications.

Regulatory Classification

Identification

A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by this device are used in the diagnosis and treatment of methadone use or overdose and to determine compliance with regulations in methadone maintenance treatment.

Special Controls

*Classification.* Class II (special controls). A methadone test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (*e.g.,* programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).

Predicate Devices

• CEDIA DAU EDDP Assay (K980746)
• CEDIA DAU Multi-Drug Calibrators (K980853)
• MGC DAU Control Sets: Primary, Clinical, Select (K040758)

Submission Summary (Full Text)

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#### 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: K081378

## COMPANY/CONTACT PERSON

Thermo Fisher Scientific Microgenics Corporation 46360 Fremont Blvd. Fremont, CA 94538

Establishment registration No: 2937369

Jack Rogers Manager of Regulatory Affairs Telephone: [phone] Fax: [phone]

#### DATE PREPARED

December 3, 2008

#### DEVICE NAME

| Trade Name: | DRI® Methadone Metabolite (100/300) Assay |
|------------------------|----------------------------------------------------------------|
| | DRI® Methadone Metabolite Urine Calibrators |
| | DRI® Methadone Metabolite Urine Controls |
| Common Name: | Methadone Test System |
| Device Classification: | 21 CFR 862.3620 Methadone Test System; Class II |
| | 21 CFR 862.3200 Clinical Toxicology Calibrator; Class II |
| | 21 CFR 862.3280 Clinical Toxicology Control Material; Class II |

#### INTENDED USE

The DRI Methadone Metabolite (100/300) Assay is intended for the qualitative and semi-quantitative determination of the presence of Methadone Metabolite (2-ethylidene-1,5-dighenyl-3,3-diphenylpyrrolidine or EDDP) in human urine at cutoffs of 100 and 300 ng/mL.

The assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography / Mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. Tests for methadone metabolite cannot distinguish between abused drugs and certain prescribed medications. Certain foods or medications may interfere with test for methadone metabolite and cause false positive results.

The DRI Methadone Metabolite Calibrators are intended for use in calibration of the DRI Methadone Metabolite (100/300) Assay.

The DRI Methadone Metabolite Controls are intended for use in the DRI Methadone Metabolite (100/300) Assay to detect and monitor systematic deviations from accuracy resulting from reagent or instrument defects.

JAN 1 4 2009

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## LEGALLY MARKETED DEVICE TO WHICH EQUIVALENCY IS CLAIMED

The DRI Methadone Metabolite (100/300) Assay is substantially equivalent to the previously cleared CEDIA DAU EDDP Assay (K980746, Microgenics Corporation).

The DRI Methadone Metabolite Calibrators are substantially equivalent to the previously cleared CEDIA DAU Multi-Drug Calibrators (K980853, Microgenics Corporation).

The DRI Methadone Metabolite Controls are substantially equivalent to the previously cleared MGC DAU Control Sets: Primary, Clinical, Select (K040758, Microgenics Corporation).

## DESCRIPTION OF DEVICE

The DRI Methadone Metabolite (100/300) Assay utilizes liquid ready-to-use reagents. The Antibody/Substrate Reagent (R1) contains mouse monoclonal anti-EDDP antibody, glucose-6-phosphate (G6P), and nicotinamide adenine dinucleotide (NAD) in Tris buffer with sodium azide as a preservative. The Conjugate Reagent (R2) contains EDDP-derivative labeled with glucose-6-phosphate Enzyme dehydrogenase (G6PDH) in Tris buffer with sodium azide as a preservative.

The assay uses specific antibodies that can detect EDDP in human urine without cross-reactivity to the The assay is based on competition between drug labeled with glucose-6parent drug methadone. phosphate dehydrogenase (G6PDH) and free drug from the sample for a fixed number of specific antibody binding sites. In the presence of free drug from the sample, the free drug occupies the antibody binding sites, allowing the drug-labeled G6PDH to interact with the substrate, resulting in enzyme activity. In the absence of free drug from the sample, the specific antibody binds the drug labeled with G6PDH and causes a decrease in enzyme activity. This phenomenon creates a direct relationship between drug concentration in urine and enzyme activity. This enzyme activity is determined spectrophotometrically at 340 nm by measuring its ability to convert nicotinamide adenine dinucleotide (NAD) to NADH.

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2015

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| Comparison | DRI Methadone Metabolite (100/300)<br>Assay | Predicate Device - CEDIA DAU EDDP<br>Assay |
|----------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Qualitative and semi-quantitative<br>determination of the presence of<br>Methadone Metabolite (2-ethylidene-1,5-<br>dimethyl-3,3-diphenylpyrrolidine or EDDP)<br>in human urine at cutoffs of 100 and 300<br>ng/mL. | Qualitative and semi-quantitative assay of<br>EDDP (2-ethylidene-1,5-dimethyl-3,3-<br>diphenylpyrrolidine or EDDP) in human<br>urine. |
| Test Principle | Homogeneous Enzyme Immunoassay<br>based on competition between a drug<br>labeled with glucose-6-phosphate<br>dehydrogenase (G6PDH) and free drug<br>from the urine sample for a fixed amount<br>of specific antibody binding sites, | Homogeneous Enzyme Immunoassay<br>based on competition between a drug<br>labeled with ß-galactosidase, and free<br>drug from the urine sample for a fixed<br>amount of specific antibody binding sites. |
| | Direct relationship between drug<br>concentration in urine and enzyme<br>activity. | Direct relationship between drug<br>concentration in urine and enzyme<br>activity. |
| | Enzyme activity is determined<br>spectrophotometrically at 340 nm by<br>measuring its ability to convert<br>nicotinamide adenine dinucleotide (NAD)<br>to NADH. | Enzyme activity is determined<br>spectrophotometrically at 570 nm by<br>measuring its ability to convert CPRG to<br>CPR. |
| Cutoff | 100 and 300 ng/mL | 100 ng/mL |
| Matrix | Human urine | Human urine |
| Reagents | Liquid Ready-to-Use<br>Two reagent assay (R1 and R2) | Lyophilized (reconstitution required)<br>Two reagent assay (R1 and R2) |
| Calibrators | Liquid ready-to-use<br>(0, 100, 300, 500, 1000 ng/mL) | Liquid ready-to-use<br>(0, 100, 500, 2000 ng/mL) |
| Controls | Liquid ready-to-use<br>(± 25% from cutoffs) | Liquid ready-to-use<br>(± 25% from cutoffs) |

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# COMPARISON OF TECHNOLOGICAL CHARACTERISTICS

10.000

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## SUMMARY OF CLINICAL TESTING

### Sensitivity

Sensitivity measured semi-quantitatively as limit of quantitation (LOQ) was 14 ng/mL.

#### Precision

A precision study was performed using the CLSI guideline EP5-A2: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline - Second Edition

For qualitative mode, acceptance criteria required that all samples spiked at levels below the cutoff read as negative and all samples spiked at levels above the cutoff read as positive.

For semi-quantitative mode, target within-run precision was less than or equal to 8% CV and target total-run precision was less than or equal to 10% CV.

The within-run and total-run precision at all levels of the 300 cutoff and the 300 cutoff met target specifications in both qualitative and semi-quantitative modes.

#### Cutoff Characterization - Spike Recovery

In qualitative mode, the control levels were recovered accurately, with the negative controls recovering less than the cutoff calibrators and the positive controls recovering greater than the cutoff calibrators. No overlap was observed between cutoff levels and their ± 25% levels, with 95% statistical confidence. The precision of the 21 replicates was < 1% CV.

In semi-quantitative mode, recovery was less than 15% error of the nominal values and the precision of the 21 replicates was below 3% CV.

#### Linearity - Dilution Recovery

A high sample containing around 1000 ng/mL methadone metabolite was serially diluted in 10% increments with analyte-free urine. Recovery was within 10% of expected values, with a correlation coefficient of r = 0.9990.

#### Interferences

Results demonstrate that no significant interference was observed from endogenous and exogenous unne substances at the tested concentrations and the pH range of 4 to 11.

#### Specificity

Cross-reactivity to metabolites and structurally related compounds was tested on spiked samples in both the qualitative and semi-quantitative modes. All compounds tested negative, with rate below the 100 ng/mL cutoff rate and with dose recovered less than 100 ng/mL, indicating that the assay does not cross react with compounds at the tested concentrations.

#### Method Comparison

A total of 100 unaltered patient urine samples containing various concentrations of methadone metabolite were tested in both qualitative and semi-quantitative modes. Approximately 10% of the samples included in the study had concentrations between cutoff and 50% above the cutoff, and approximately 10% of the samples had concentrations between cutoff and 50% below the cutoff.

Samples were tested by:

- . DRI Methadone Metabolite Assay (on-test method)
- o CEDIA DAU EDDP Assay (predicate device)
- . GC/MS (reference analytical method)

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#### Qualitative Results

At the 100 ng/mL cutoff, the overall concordance between the DRI Assay and the predicate CEDIA Assay was 95%. The overall concordance between DRI and GC/MS was also 95%.

At the 300 cutoff, the overall concordance between the DRI and GC/MS was 99%.

#### Semi-quantitative Results

At the 100 cutoff, the overall concordance between the DRI Assay and the predicate CEDIA Assay was 99%. The overall concordance to GC/MS was also 99%.

At the 300 cutoff, the overall concordance between the DRI Assay and GC/MS was 100%.

## CONCLUSION

As summarized, the DRI Methadone Metabolite (100/300) Assay is substantially equivalent to the CEDIA DAU EDDP 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 logo for the U.S. Department of Health & Human Services. The logo consists of a circular border with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle with its wings spread, symbolizing the department's mission to protect the health of all Americans.

#### Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Thermo Fisher Scientific Microgenics Corporation c/o Mr. Jack Rogers Manager of Regulatory Affairs 46360 Fremont Blvd. Fremont, CA 94538

JAN 1 4 2009

k081378 Re:

Trade Name: DRI® Methadone Metabolite (100/300) Assay, DRI® Methadone Metabolite Urine Calibrators, DRI® Methadone Metabolite Urine Control Regulation Number: 21 CFR §862.3620 Regulation Name: Methadone Test System Regulatory Class: Class II Product Code: DJR, DKB, DIF Dated: January 6, 2009 Received: January 7, 2009

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 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 [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/dsma/dsmamain.html.

Sincerely yours,

Coy C. He

Courtney C. Harper, Ph.D. Acting Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

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# Indications for Use

## 510(k) Number (if known): K081378

Device Name: DRI Methadone Metabolite (100/300) Assay

#### Indications for Use:

The DRI Methadone Metabolite (100/300) Assay is intended for the qualitative and semi-quantitative determination of the presence of Methadone Metabolite (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine or EDDP) in human urine at cutoffs of 100 and 300 ng/mL.

The DRI Methadone Metabolite Calibrators are intended for use in calibration of the DRI Methadone Metabolite (100/300) Assay.

The DRI Methadone Metabolite Controls are intended for use in the DRI Methadone Metabolite (100/300) Assay to detect and monitor systematic deviations from accuracy resulting from reagent or instrument defects.

The assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography / Mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical and professional iudoment should be applied to any drug of abuse test result. particularly when preliminary results are used. Tests for methadone metabolite cannot distinguish between abused drugs and certain prescribed medications. Certain foods or medications may interfere with tests for methadone metabolite and cause false positive results.

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)

Division/Sign-Off

Office of in Vitro Diagnostic Device Evaluation and Safety 51 Offic

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