URINE AMPHETAMINE/METHAMPHETAMINE SCREEN FLEX REAGENT CARTRIDGE

K040133 · Dade Behring, Inc. · DKZ · Apr 8, 2004 · Clinical Toxicology

Device Facts

• Record ID: K040133
• Device Name: URINE AMPHETAMINE/METHAMPHETAMINE SCREEN FLEX REAGENT CARTRIDGE
• Applicant: Dade Behring, Inc.
• Product Code: DKZ · Clinical Toxicology
• Decision Date: Apr 8, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3100
• Device Class: Class 2

Intended Use

The AMPH Flex® reagent cartridge used on the Dimension® clinical chemistry system provides reagents for an in vitro diagnostic test intended for the qualitative and semi-quantitative determination of amphetamines in human urine using a cutoff of either 300, 500, or 1000 ng/mL. Measurements obtained with the AMPH method are used in the diagnosis and treatment of amphetamines use or overdose.

Device Story

The Dimension® AMPH method is an in vitro diagnostic reagent cartridge for use on Dade Behring Dimension® clinical chemistry systems. It utilizes a homogeneous enzyme immunoassay (Emit® technology) to detect amphetamines and methamphetamine in human urine. The assay relies on competition between the drug in the urine specimen and drug labeled with glucose-6-phosphate dehydrogenase (G6PDH) for antibody binding sites. Enzyme activity is inhibited upon binding to the antibody; active enzyme converts NAD to NADH, producing an absorbance change measured spectrophotometrically at 340nm. The device is used in clinical laboratory settings by trained personnel. Results are used by clinicians to aid in the diagnosis and treatment of drug use or overdose. Because the assay provides only preliminary results, positive findings require confirmation via a more specific method like GC/MS. The system provides qualitative or semi-quantitative results based on user-selected cutoffs (300, 500, or 1000 ng/mL).

Clinical Evidence

Bench testing only. Precision/reproducibility evaluated per NCCLS EP5-A (20 days, duplicate analysis). Analytical performance characterized via linearity, sensitivity (125 ng/mL at 1000 ng/mL cutoff; 95 ng/mL at 300/500 ng/mL cutoffs), and specificity (cross-reactivity profiles for various compounds). Method comparison studies performed against the predicate device and GC/MS confirmation on 129-169 urine specimens per cutoff level, demonstrating concordance.

Technological Characteristics

Homogeneous enzyme immunoassay; prepackaged plastic reagent cartridge (Flex®). Designed for use on Dimension® clinical chemistry system. Analyte: Amphetamines/Methamphetamine. Cutoffs: 300, 500, 1000 ng/mL.

Indications for Use

Indicated for the qualitative and semi-quantitative determination of amphetamines in human urine for the diagnosis and treatment of amphetamine use or overdose. Preliminary analytical test result only; requires confirmation by alternate chemical method (e.g., 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

• Syva® Emit® II Plus Amphetamine Assay (K031004)

Submission Summary (Full Text)

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# 510(k) Summary for the Dimension® Urine Amphetamines/Methamethamine Screen Flex® (DF91B)

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.

510(k) Number: K040133

Analyte: Amphetamines/Methamethamine

Type of Test: qualitative or quantitative homogeneous enzyme immunoassay

A. Applicant: Dade Behring Inc.

1. Submitter's Name Andrea M. Tasker Building 500, Mailbox 514 P.O.Box 6101 Newark, DE 19714-6101

2. Submission Preparation Date January 20, 2004

# B. Proprietary and Established Names: Dimension® Urine Amphetamines/Methamethamine Screen Flex® reagent cartridge

### C. Regulatory Information:

1.Regulation section: 21CFR §862.3100 Amphetamine test system

- 2. Classification: Class II
- 3. Product Code: DKZ
- 4. Panel: Toxicology (91)

{1}------------------------------------------------

### D. Intended Use:

1. Indications for Use: The AMPH Flex® reagent cartridge used on the Dimension clinical chemistry system provides reagents for an in vitro diagnostic test intended for the qualitative and semi-quantitative determination of amphetamines in human urine using a cutoff of either 300, 500 or 1000ng/mL. Measurements obtained with the AMPH method are used in the diagnosis and treatment of amphetamines use or overdose.

2. Special conditions for use statements: The AMPH method provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Other chemical confirmation methods are available. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

## E. Device Description:

The Dade Behring Dimension® AMPH method is an in vitro diagnostic device that consists of prepackaged reagents in a plastic cartridge (Flex®) for use on the Dade Behring Dimension® clinical chemistry system.

## F. Substantial Equivalence Inforamtion:

- 1. Predicate Device: Syva® Emit® II Plus Amphetamine Assay
- 2. Predicate K Number(s): K031004
- 3. Comparision with Predicate: This product is substantially equivalent to other Amphetamine enzyme immunoassys, such as the Syva® Emit® II Plus Amphetamine Assay (K031004).

{2}------------------------------------------------

### I. Device Performance Characteristics: Method Comparison (cutoff=300 ng/mL)

129 native urine specimens were tested with the AMPH Flex® cartridge on the Dimension system (cutoff=300 ng/mL ) and with the Syva® Emit® II Plus Amphetamines Assay (9C309UL) on the Syva 30R Biochemical System (cutoff=300 ng/mL ). All 129 specimens were also analyzed by GC/MS. Positives by GC/MS were determined by using the criteria of amphetamine plus methamphetamine > 300 ng/mL since there are no SAMSHA confirmation guidelines for the 300 cutoff. 24 of these had total amphetamines by GC/MS within 25% of the 300 ng/mL cutoff.

#### Comparison to Predicate Method

# Syva 30R® Biochemical System (cutoff 300 ng/mL)

AMPH Flex® Reagent Cartridge on the Dimension® clinical chemistry system (cutoff 300 ng/mL )

| | + | - |
|---|----|----|
| + | 70 | 2 |
| - | 2 | 55 |

Discrepants (ng/mL):

| GC/MS | GC/MS | GC/MS | Dim | Syva |
|-------|-------|-------|------|------|
| Meth | Amph | Total | AMPH | 30R |
| 242 | 61.1 | 303 | 315 | 273 |
| 433 | <lod | 433 | 325 | 298 |
| 275 | 70.2 | 345 | 278 | 300 |
| 363 | <lod | 363 | 204 | 301 |

< lod : less than the limit of detection, < 25 ng/mL

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# Comparison to Reference Method

# GCMS

(cutoff 300 ng/mL methamphetamine and amphetamine)

| AMPH Flex®<br>Reagent Cartridge<br>on Dimension®<br>clinical chemistry<br>system (cutoff 300<br>ng/mL) | + | - |
|--------------------------------------------------------------------------------------------------------|----|----|
| + | 72 | 0 |
| - | 8 | 49 |

Discrepants (ng/mL):

| GC/MS | GC/MS | GC/MS | Dim |
|-------|-------|-------|------|
| Meth | Amph | Total | AMPH |
| 253 | 47.2 | 300 | 95 |
| 311 | < lod | 311 | 240 |
| 326 | < lod | 326 | 189 |
| 313 | < lod | 313 | 240 |
| 363 | < lod | 363 | 204 |
| 255 | 67.3 | 322 | 271 |
| 275 | 70.2 | 345 | 278 |
| 279 | 71 | 350 | 296 |

< lod: less than the limit of detection of 25 ng/mL

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#### Method Comparison (cutoff=500 ng/mL )

129 native urine specimens were tested with the AMPH Flex® cartridge on the Dimension® system (cutoff=500 ng/mL ) and with the Syva® Emit® II Plus Amphetamines Assay (9C309UL) on the Syva 30R® Biochemical System (cutoff=500 ng/mL ). All 129 specimens were also analyzed by GC/MS. Positives by GC/MS were determined using the newly proposed SAMHSA guidelines by following the criteria of ≥ 250 ng/mL methamphetamine and ≥ 100 ng/mL amphetamine or > 250 ng/mL amphetamine regardless of the methamphetamine concentration. 28 of these had total amphetamines by GC/MS within 25% of the 500 ng/mL cutoff.

### Comparison to Predicate Method

Syva 30R® Biochemical System (cutoff 500 ng/mL)

-

+ AMPH Flex® + Reagent Cartridge 43 0 on the Dimension® clinical chemistry system (cutoff 500 1 85 ng/mL )

Discrepants (ng/mL):

| GC/MS | GC/MS | Dim | Syva |
|-------|-------|------|------|
| Meth | Amph | AMPH | 30R |
| 556 | 62.7 | 405 | 598 |

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## Comparison to Reference Method

### GCMS

(cutoff ≥ 250 ng/mL amphetamine

or

≥ 250 ng/mL metamphetamine and

# ≥ 100 ng/mL amphetamine)

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AMPH Flex® Reagent Cartridge on Dimension® clinical chemistry system (cutoff 500 ng/mL )

Discrepants (ng/mL):

| GC/MS | GC/MS | Dim |
|-------|-------|------|
| Meth | Amph | AMPH |
| 410 | 36.7 | 550 |
| 506 | 43.6 | 572 |
| 513 | 44.8 | 564 |
| 528 | 47.9 | 572 |
| 561 | 48.6 | 507 |
| 577 | 50.5 | 574 |
| 514 | 56.1 | 534 |
| 495 | 58.4 | 548 |
| 598 | 64.5 | 561 |
| 286 | 169 | 366 |
| 281 | 173 | 388 |
| 254 | 174 | 344 |
| 300 | 179 | 398 |
| 315 | 186 | 393 |

{6}------------------------------------------------

#### Method Comparison (cutoff=1000 ng/mL )

169 native urine specimens were tested with the AMPH Flex® cartridge on the Dimension system (cutoff=1000 ng/mL ) and with the Syva® Emit® II Plus Amphetamines Assay (9C309UL) on the Syva 30R® Biochemical System (cutoff=500 ng/mL ). Total amphetamine and methamphetamine values by GC/MS were reported for these 169 specimens. Positives by Confirmation GC/MS were determined according to the SAMHSA requirements by following the criteria of > 500 ng/mL methamphetamine and ≥ 200 ng/mL amphetamine or ≥ 500 ng/mL amphetamine regardless of the methamphetamine concentration.

Separate amphetamine and methamphetamine values were available for only 129 of thes 169 specimens. Since separate amphetamine and methamphetamine values are required for confirmation testing according to the SAMSHA guidelines, only those 129 samples were represented in the box plot shown in Table 10. Of these 129, there were 9 which had total amphetamines by GC/MS within 25% of the 1000 ng/mL cutoff.

#### Comparison to Predicate Method

# Syva 30R® Biochemical System (cutoff 1000 ng/mL)

| | + | |
|------------------------------------------------------|----|-----|
| AMPH Flex®<br>Reagent Cartridge<br>on the Dimension® | 62 | 0 |
| clinical chemistry<br>system (cutoff 1000<br>ng/mL ) | | 102 |

Discrepants (ng/mL):

| GC/MS | GC/MS | Dim | Syva |
|-------|-------|------|------|
| Meth | Amph | AMPH | 30R |
| 713 | 534 | 929 | 1134 |
| 494 | 844 | 922 | aar |

aar: above assay range, > 2000 ng/mL

{7}------------------------------------------------

# Comparison to Reference Method

GC/MS

(cutoff ≥ 500 ng/mL amphetamine

or

≥ 500 ng/mL metamphetamine and ≥ 200 ng/mL amphetamine)

AMPH Flex® Reagent Cartridge on Dimension® clinical chemistry system (cutoff 1000 ng/mL )

| | - | |
|---|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----|
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Discrepants (ng/mL):

| GC/MS | GC/MS | Dim |
|-------|-------|------|
| Meth | Amph | AMPH |
| 1223 | 118 | 1264 |
| 1209 | 127 | 1347 |
| 1112 | 172 | 1395 |
| 1183 | 174 | 1314 |
| 1213 | 177 | 1414 |
| 1194 | 180 | 1367 |
| 631 | 202 | 627 |
| 652 | 214 | 375 |
| 713 | 534 | 929 |
| 496 | 615 | 682 |
| 390 | 624 | 681 |
| 333 | 635 | 648 |
| 494 | 844 | 922 |
| 161 | 1032 | 770 |

{8}------------------------------------------------

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/8/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)" arranged around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird-like figure, with three stylized lines representing its wings or body.

Public Health Service

# APR - 8 2004

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Andrea M. Tasker Senior Regulatory Affairs and Compliance Manger Dade Behring, Inc Chemistry/ Immunochemistry Glasgow Business Community; BLDG. 500 PO Box 6101 Newark, DE 19714

Re: k040133

> Trade/Device Name: Dimension® Urine Amphetamine/ Methamphetamine Screen Flex® reagent cartridge (DF91B) Regulation Number: 21 CFR 862.3100 Regulation Name: Amphetamine Test System Regulatory Class: Class II Product Code: DKZ Dated: January 20, 2004 Received: January 21, 2004

Dear Ms. Tasker :

We have reviewed vour 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 enclosurc) 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 complics 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 (OS) regulation (21 CFR Part 820).

{9}------------------------------------------------

#### 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,

Jean M. Cooper, MS, DVM.

Yean M. Cooper, MS, D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

{10}------------------------------------------------

#### Indications For Use Statement

Device Name:

K040133

Dimension@ Urine Amphetamine/Methamphetamine Screen Flex® reagent cartridge (DF91B)

#### Indications for Use:

The AMPH Flex® reagent cartridge used on the Dimension® clinical chemistry system provides reagents for an in virro diagnostic test intended for the qualitative and semi-quantitative determination of amphetamines in human urine using a cutoff of either 300, 500 or 1000ng/mL. Measurements obtained with the AMPH method are used in the diagnosis and treatment of amphetamines use or overdose.

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

Jm. T

Andrea M. Tasker Regulatory Affairs and Compliance Manager

January 20, 2004

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109)

OR

Over-the-counter Use (Optional format 1-2-96)

Carol Benson
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

stnka K040133

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