THERMO SCIENTIFIC DRI AMPHETAMINES ASSAY

K093114 · Microgenics Corp. · DKZ · May 12, 2010 · Clinical Toxicology

Device Facts

• Record ID: K093114
• Device Name: THERMO SCIENTIFIC DRI AMPHETAMINES ASSAY
• Applicant: Microgenics Corp.
• Product Code: DKZ · Clinical Toxicology
• Decision Date: May 12, 2010
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3100
• Device Class: Class 2

Intended Use

The DRI® Amphetamines Assay is intended for the qualitative or semiquantitative determination of amphetamine and methamphetamine in human urine. The assay has cutoff levels of 500 and 1000 ng/mL. The assay provides a simple and rapid analytical screening procedure for detecting amphetamine and methamphetamine in urine on automated clinical analyzers. The assay is calibrated with methamphetamine. This assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

Device Story

DRI Amphetamines Assay is a liquid, ready-to-use homogeneous enzyme immunoassay for urine drug screening. Input: human urine sample. Principle: competitive binding between G6PDH-labeled drug and sample drug for fixed antibody sites. In absence of sample drug, antibody binds labeled drug, decreasing enzyme activity; in presence of sample drug, labeled drug is displaced, increasing enzyme activity. Output: spectrophotometric measurement at 340 nm (NAD to NADH conversion) proportional to drug concentration. Used in clinical laboratories on automated analyzers by trained personnel. Provides preliminary results requiring GC/MS confirmation. Benefits: rapid screening for amphetamine/methamphetamine abuse.

Clinical Evidence

No clinical studies were performed. Analytical performance was established via bench testing, including precision/reproducibility (n=80 per concentration), linearity (r=0.999), and method comparison against GC/MS using 160 clinical samples. Cross-reactivity and interference studies were conducted to validate specificity.

Technological Characteristics

Liquid, ready-to-use homogeneous enzyme immunoassay. Sensing principle: competition between G6PDH-labeled drug and sample drug for antibody binding sites. Energy source: spectrophotometric measurement at 340 nm. Connectivity: automated clinical analyzer. Storage: 2-8°C. Reagent stability: 60 days on-board.

Indications for Use

Indicated for the qualitative or semiquantitative screening of amphetamine and methamphetamine in human urine on automated clinical analyzers. Intended for use as a preliminary analytical test; requires confirmation by a more specific method like GC/MS.

Regulatory Classification

Identification

An amphetamine test system is a device intended to measure amphetamine, a central nervous system stimulating drug, in plasma and urine. Measurements obtained by this device are used in the diagnosis and treatment of amphetamine use or overdose and in monitoring levels of amphetamine to ensure appropriate therapy.

Special Controls

*Classification.* Class II (special controls). An amphetamine 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 Amphetamines Assay (K943993)

Submission Summary (Full Text)

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## 510(k) SUMMARY

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of Safe Medical Devices Act of 1990 and 21 CFR 807.92

The assigned 510(k) number is: K093114

#### COMPANY/CONTACT PERSON

Hewuan Takkele Regulatory Affairs Specialist Microgenics Corporation Thermo Fisher Scientific, Clinical Diagnostics Division 46360 Fremont Blvd. Fremont, CA 94538 [phone] x31860 Office [phone] Fax [e-mail]

#### DATE PREPARED

May 10, 2010

#### DEVICE NAME

| Trade Name: | Thermo Scientific DRI® Amphetamines Assay |
|------------------------|------------------------------------------------------|
| Common Name: | DRI® Amphetamines Assay |
| Device Classification: | Amphetamine test system, Methamphetamine Test System |
| Regulation number: | 21 CFR 862.3100, 21 CFR 862.3610 |
| Product Code: | DKZ, LAF |

## INTENDED USE

The DRI Amphetamines Assay is intended for the qualitative or semi-quantitative determination of amphetamine and methamphetamine in human urine. The assay has cutoff levels of 500 and 1000 ng/mL. The assay provides a simple and rapid analytical screening procedure for detecting amphetamine and methamphetamine in urine on automated clinical analyzers. The assay is calibrated with methamphetamine.

This assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

#### SUBSTANTIALLY EQUIVILANT PREDICATE DEVICE

Thermo Scientific DR1° Amphetamines Assay is substantially equivalent to the previously cleared CEDIA® DAU Amphetamines Assay (k943993).

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### SUMMARY AND EXPLANATION OF THE TEST

Amphetamines are synthetic derivatives of ephedrine. The most common amphetamines include d-amphetamine, d-methamphetamine, and d, I-amphetamine. They act as stimulants for the central nervous system. Amphetamine is the most sympathomimetic amine. When amphetamine is ingested, it is either

rapidly deactivated in the liver or excreted unchanged into the urine. Other ephedrine derivatives such as methamphetamine can be metabolized and excreted in urine as amphetamine.

The DRI Amphetamines Assay is a liquid ready-to-use homogeneous enzyme immunoassay. The assay uses specific antibodies, which can detect amphetamine and/or methamphetamine in urine with minimal cross-reactivity to various over-the-counter structurally unrelated compounds. The assay is based on the competition of an enzyme glucose-6-phosphate dehydrogenase (G6PDH) labeled drug and the drug from the urine sample for a fixed amount of specific antibody binding sites. 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. In the presence of free drug, the free drug occupies the antibody binding sites, allowing the drug-labeled G6PDH to interact with the substrate, resulting in enzyme activity. This phenomenon creates a direct relationship between drug concentration in urine and the enzyme activity. The enzyme activity is determined spectrophotometrically at 340 nm by measuring its ability to convert nicotinamide adenine dinucleotide (NAD) to NADH.

| Comparison | CEDIA® Amphetamines Assay (K943993) | Thermo Scientific<br>DRI® Amphetamines Assay (K093114) |
|-------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended<br>Use | The CEDIA® Amphetamines assay is an in-vitro<br>diagnostic medical device intended for the qualitative<br>and semi quantitative assay of amphetamines in<br>human urine.<br>The assay provides only a preliminary analytical test<br>result. A more specific alternative chemical method<br>must be used to obtain a confirmed analytical result.<br>Gas chromatography/mass spectrometry (GC/MS) is<br>the preferred confirmatory method.1 Clinical<br>consideration and professional judgment should be<br>applied to any drug of abuse test result particularly<br>when preliminary positive results are used. | The DRI Amphetamines Assay is intended for the<br>qualitative or semi-quantitative determination of<br>amphetamine and methamphetamine in human<br>urine. The assay has cutoff levels of 500 and 1000<br>ng/mL. The assay provides a simple and rapid<br>analytical screening procedure for detecting<br>amphetamine and methamphetamine in urine on<br>automated clinical analyzers. The assay is<br>calibrated with methamphetamine.<br>This assay provides only a preliminary analytical<br>test result. A more specific alternative chemical<br>method must be used in order to obtain a<br>confirmed analytical result. Gas<br>chromatography/mass spectrometry (GC/MS) is the<br>preferred confirmatory method. Clinical<br>consideration and professional judgment should be<br>applied to any drug of abuse test result, particularly<br>when preliminary positive results are used. |
| Test<br>Principle | The CEDIA Amphetamines assay uses recombinant<br>DNA technology (US Patent No. 4708929)<br>to produce a unique homogeneous enzyme<br>immunoassay system.7 This assay is based on<br>the bacterial enzyme β-galactosidase, which has<br>been genetically engineered into two inactive<br>fragments. These fragments spontaneously<br>reassociate to form fully active enzyme that, in the<br>assay format, cleaves a substrate, generating a color<br>change that can be measured spectrophotometrically.<br>In the assay, drug in the sample competes with drug<br>conjugated to one inactive fragment of | The DRI Amphetamines Assay is a liquid ready-to-<br>use homogeneous enzyme immunoassay. The<br>assay uses specific antibodies, which can detect<br>amphetamine and/or methamphetamine in urine<br>with minimal cross-reactivity to various over-the-<br>counter structurally unrelated compounds. The<br>assay is based on the competition of an enzyme<br>glucose-6-phosphate dehydrogenase (G6PDH)<br>labeled drug and the drug from the urine sample for<br>a fixed amount of specific antibody binding sites. In<br>the absence of free drug from the sample, the<br>specific antibody binds the drug labeled with |

## COMPARISON OF TECHNOLOGICAL CHARACTERISTICS

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| | ß-galactosidase for antibody binding site. If drug is<br>present in the sample, it binds to antibody,<br>leaving the inactive enzyme fragments free to form<br>active enzyme. If drug is not present in<br>the sample, antibody binds to drug conjugated on the<br>inactive fragment, inhibiting the reassociation of<br>inactive ß-galactosidase fragments, and no active<br>enzyme will be formed.<br>The amount of active enzyme formed and resultant<br>absorbance change are proportional to<br>the amount of drug present in the sample. | G6PDH and causes a decrease in enzyme activity.<br>In the presence of free drug, the free drug occupies<br>the antibody binding sites, allowing the drug-<br>labeled G6PDH to interact with the substrate,<br>resulting in enzyme activity. This phenomenon<br>creates a direct relationship between drug<br>concentration in urine and the enzyme activity. The<br>enzyme activity is determined<br>spectrophotometrically at 340 nm by measuring its<br>ability to convert nicotinamide adenine dinucleotide<br>(NAD) to NADH. |
|----------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Cutoff | 500 and 1000 ng/mL | 500 and 1000 ng/mL |
| Matrix | Human Urine | Human Urine |
| Reagents | Lyophilized | Liquid Ready-to-Use |
| | Two reagent assay (R1 and R2) | Two reagent assay (R1 and R2) |
| Calibrators | Liquid ready-to-use | Liquid ready-to-use |
| | (0, 500, 1000, 3000, 5000 ng/mL) | (0, 500, 1000, 1500, 2000 ng/mL) |
| Controls | Liquid ready-to-use | Liquid ready-to-use |
| | (375 and 625, 750 and 1250 ng/mL) | (375 and 625, 750 and 1250 ng/mL) |
| Storage<br>Condition | 2-8°C | 2-8°C |

## PERFORMANCE TESTING SUMMARY

#### Precision and Accuracy

Samples spiked with d-amphetamine and d-methamphetamine were tested for precision in qualitative and semi-quantitative assays following a randomized CLSI protocol. The precision study met the design specifications in both the qualitative and semi-quantitative assays. In the qualitative study, all negative samples recovered as negative and all positive samples recovered as positive. In the semi-quantitative study, the within run %CV for was less than or equal to 6.2% and the total run %CV was less than or equal to 6.9%.

#### Method Comparison

Samples were tested by DRI qualitative and semi-quantitative assay and compared to GC/MS. The method comparison exhibited results greater than 96% total agreement between the DRI methods and GC/MS for both qualitative and semi-quantitative assays. Discordant results were obtained when the assay was used to detect amphetamine and methamphetamine analytes individually. The assay detects the presence of both amphetamine and methamphetamine analytes with 100% cross reactivity to both drugs. Therefore samples tested for one analyte may appear discordant due to the presence of the other analyte.

The method comparison results meet the design input specifications.

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#### Dilution Recovery

Samples were tested to demonstrate linearity throughout the assay range. Results showed that recovery was less than ±4% error of the expected value for levels tested from 0 to 2000 ng/ml.. The results met the design input specification for levels tested throughout the assay range, and the assay dilutes in a linear fashion.

#### On-Board Open Vial reagent Stability

Uncapped reagents were stored in an analyzer and all calibrators and controls were tested in qualitative and semi-quantitative assay. Reagents stored on the analyzer are stable for a minimum of 60 days.

#### CONCLUSION

As summarized, the Thermo Scientific DRI® Amphetamines Assay is substantially equivalent to the CEDIA® Amphetamines 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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Image /page/4/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized depiction of an eagle or bird-like figure with three curved lines representing its wings or body. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES-USA" is arranged in a circular fashion around the bird-like figure.

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002

Microgenics, Inc. C/O Hewuan Takkele 46360 Fremont Blvd. Fremont, CA 94538

Re: k093114

Trade/Device Name: DRI Amphetamines Assay Regulation Number: 21 CFR 862.3100 Regulation Name: Amphetamine test system Regulatory Class: Class II Product Code: DKZ, LAF Dated: May 7, 2010 Received: May 10, 2010

MAY 1 2 2010

Dear Ms. Takkele:

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 class II (Special Controls), 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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). 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

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Page 2

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), 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" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at [phone]. For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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 ( 301 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Signature

Courtney C. Harper, 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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# Indication for Use

## 510(k) Number (if known): K093114

Device Name: DRI® Amphetamines Assay

## Indication for Use:

The DRI Amphetamines Assay is intended for the qualitative or semi-quantitative determination of amphetamine and methamphetamine in human urine. The assay has cutoff levels of 500 and 1000 ng/mL. The assay provides a simple and rapid analytical screening procedure for detecting amphetamine and methamphetamine in urine on automated clinical analyzers. The assay is calibrated with methamphetamine.

This assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used in order to obtain a con firmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

Prescription Use × (21 CFR Part 801 Subpart D)

And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

## (PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Division State Officer

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K093114