COZART EIA AMPHETAMINES ORAL FLUID MICROPLATE KIT

K033743 · Cozart Bioscience , Ltd. · DKZ · Jun 3, 2004 · Clinical Toxicology

Device Facts

• Record ID: K033743
• Device Name: COZART EIA AMPHETAMINES ORAL FLUID MICROPLATE KIT
• Applicant: Cozart Bioscience , Ltd.
• Product Code: DKZ · Clinical Toxicology
• Decision Date: Jun 3, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3100
• Device Class: Class 2

Intended Use

The Cozart® EIA Amphetamines Oral Fluid Microplate Kit is intended for use in clinical and forensic laboratories when used in conjunction with the Cozart® RapiScan Oral Fluid collection system. Using this collection system it provides qualitative screening results for amphetamines in human oral fluid at a cutoff concentration of 15ng/ml. This is equal to 45ng/ml in neat oral fluid as the collection system involves a 1:3 dilution of the sample. This assay is for professional use only and provides only a preliminary analytical test result. Clinical consideration and professional judgement must be applied to any drug of abuse test result, particularly in evaluating a preliminary positive result. In order to obtain a more confirmed analytical result a more specific alternative chemical method is needed. Gas Chromatography/Mass Spectrometry (GCMS) is the preferred confirmatory method.

Device Story

The Cozart® EIA Amphetamines Oral Fluid Microplate Kit is a laboratory-based competitive ELISA for detecting amphetamines in human oral fluid. Input consists of oral fluid samples collected via the Cozart® RapiScan system (1:3 dilution). The assay utilizes a microtitre plate coated with antibody and a Horse Radish Peroxidase enzyme conjugate. The reaction is measured spectrophotometrically at 450nm. The device is operated by laboratory professionals in clinical or forensic settings. Results are qualitative; positive findings require confirmation by GC/MS. The device aids in identifying potential amphetamine presence, supporting clinical or forensic decision-making.

Clinical Evidence

Bench testing only. Method comparison study of 163 oral fluid samples compared to GC/MS confirmation. Results: 67 samples screened positive (62 confirmed positive, 5 false positives); 96 samples screened negative (94 confirmed negative, 2 false negatives). Overall agreement with GC/MS was 96%. Precision studies (within-assay, within-day, between-assay, between-day) showed CVs ranging from 2.7% to 12.4%. Specificity testing evaluated 20 unrelated substances (no cross-reactivity) and 11 related compounds (cross-reactivity observed for MDA, MAMP, MBDB, MDMA, MDEA, Fenfluramine, Tyramine).

Technological Characteristics

Competitive ELISA; microtitre plate coated with antibody; Horse Radish Peroxidase enzyme conjugate; substrate/stop solutions; 450nm spectrophotometric detection. Calibrators: 0, 2, 15, 50ng/mL. Manual assay. Standards: BS EN ISO 9001:2000; EN 46001:1996.

Indications for Use

Indicated for qualitative screening of amphetamines in human oral fluid in clinical and forensic laboratory settings. Professional use only; provides preliminary analytical results requiring confirmation by 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

• Amphetamine-Specific Intercept™ MICRO-PLATE EIA (K992918)

Submission Summary (Full Text)

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## PREMARKET NOTIFICATION [510(k)] SUMMARY

# JUN - 3 2004

| Submitter | Cozart® Bioscience Ltd<br>45 Milton Park<br>Abingdon<br>Oxfordshire OX14 4RU<br>UK<br>Tel No: 01235 861483<br>Fax No: 01235 835607 |
|-------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact Person | Dr Roberto Liddi<br>Regulatory Affairs Manager |
| Date | 19th November 2003 |
| Device Name | Cozart® EIA Amphetamines Oral Fluid Microplate Kit |
| Trade Name | Cozart® EIA Amphetamines Oral Fluid Microplate Kit |
| Classification Name | Amphetamine Test System |
| Classification | Class II<br>Code of Federal Regulations Title 21 Food and Drugs<br>Part 862 Clinical Chemistry and Clinical Toxicology Devices<br>Subpart D Clinical Toxicology Test Systems<br>862.3100 Amphetamine test system |
| Establishment Registration No | |

3002336046

Performance Standards

BS EN ISO 9001:2000; EN 46001:1996

### Substantial Equivalence

Amphetamine-Specific Intercept™ MICRO-PLATE EIA, 510(k) no. K992918

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| Parameter | Cozart® EIA Amphetamines Oral Fluid Microplate Kit | Amphetamine-Specific MICRO-PLATE EIA, 510(k) no. K992918 | InterceptTM |
|-------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------|-------------|
| Intended Use | Qualitative test for amphetamines in human oral fluid with a 45ng/ml cutoff.<br>Recommend confirmation of positive results by GC/MS. | Qualitative test for amphetamines in human oral fluid with a 100ng/ml cutoff.<br>Recommend confirmation of positive results by GC/MS. | |
| Target Population | Clinical and forensic samples. | Clinical samples. | |
| Design | Competitive ELISA | Competitive ELISA | |
| Enzyme | Horse Radish Peroxidase | Horse Radish Peroxidase | |
| Results | Read spectrophotometrically at 450nm. | Read spectrophotometrically at 450nm. | |
| Calibrators | 0, 2, 15, 50ng/mL | 0, 50, 100, 200ng/mL | |
| Matrix | Human Oral Fluid | Human Oral Fluid | |
| Controls | None supplied but Cozart recommends using external controls. | Unknown | |
| Method Comparison | 163 samples were tested, 67 screened positive for amphetamines, of which 62 were confirmed positive by GC/MS. 96 samples screened negative for amphetamines and 94 were confirmed negative by GC/MS. 96% Agreement as compared to GC/MS. | 89% Agreement as compared to GC/MS | |
| Precision | CV (%) of 2.7-12.4% | CV (%) of 3.5 - 7.9% | |
| Sensitivity | 1.2ng/mL | Unknown | |
| Specificity | 20 potential interferents tested - none cross-reacted. | 47 potential interferents tested - none cross-reacted. | |

#### Introduction

The Cozart® EIA Amphetamines Oral Fluid Microplate Kit is a laboratory based test for the detection of amphetamines in human oral fluid using a cutoff equivalent to 45ng/mL. The device detailed above was compared to Gas Chromatography/Mass Spectrometry (GC/MS).

Cozart® Bioscience Ltd is the manufacturer of the Amphetamine Oral Fluid Kit. We Cozares Bloodience this device from another manufacturer and the device is not marketed under another product name.

#### Intended Use

The Cozart® EIA Amphetamines Oral Fluid Microplate Kit is intended for use in clinical and forensic laboratories when used in conjunction with the Cozart® RapiScan Oral Fluid collection system. Using this collection system it provides qualitative screening results for amphetamines in human oral fluid at a cutoff concentration of 15ng/ml. This is equal to 45ng/mL in undiluted oral fluid as the collection system involves a 1:3 dilution of the sample.

The remainder of this document will refer to the 15ng/mL cutoff.

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This assay is for professional use only and provides only a preliminary Clinical consideration and professional judgement must be analytical test result. applied to any drug of abuse test result, particularly in evaluating a preliminary positive result. In order to obtain a more confirmed analytical result a more specific alternative chemical method is needed. Gas Chromatography/Mass Spectrometry (GC/MS) is the preferred confirmatory method.

#### Target Population

The target population for the Cozart® EIA Amphetamines Oral Fluid Microplate Kit is clinical and forensic samples.

#### Where Used

The Cozart® EIA Amphetamines Oral Fluid Microplate Kit is designed for use in clinical and forensic laboratories. For professional use only.

#### Design

As can be seen from the Principle of the Test section in the pack insert, the Cozart® EIA Amphetamines Oral Fluid Microplate Kit is a competitive ELISA for the detection of amphetamines in human oral fluid.

#### Materials

The Cozart® EIA Amphetamines Oral Fluid Microplate kit supplies the following reagents - a microtitre plate coated with antibody, enzyme conjugate reagent, wash buffer, substrate solution, stop solution and four calibrators (0, 2, 15 and 50ng/ml amphetamine in oral fluid matrix).

#### Performance

#### Method Comparison

The Cozart EIA Amphetamines Oral Fluid Microplate Kit was compared to Gas Chromatography/Mass Spectrometry (GC/MS). All the samples were tested with the Cozart® EIA Amphetamines Oral Fluid Microplate Kit according to the pack insert enclosed.

163 samples were tested through the Cozart® EIA Amphetamines Oral Fluid Microplate Kit, 67 screened positive and 62 were confirmed positive by GC/MS. 96 samples screened negative and 94 were confirmed negative by GC/MS. Of the 163 samples tested 17 were between -50% cutoff and +50% cutoff.

| New Device | GC/MS Negs | GC/MS Negs between<br>50% Cutoff<br>and Cutoff | GC/MS<br>between<br>+50%<br>Cutoff and<br>Cutoff | Total<br>GC/MS Pos | Percent<br>Agreement<br>with GC/MS | |
|------------|------------|------------------------------------------------|--------------------------------------------------|--------------------|------------------------------------|----|
| Pos | 67 | 5 | 0 | 8 | 62 | 93 |
| Neg | 96 | 94 | 9 | 0 | 2 | 98 |

96% overall agreement as compared with GC/MS

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#### Precision

The precision obtained for the Cozart® EIA Amphetamines Oral Fluid Microplate Kit produced CVs less than 11%. The total precision for the kit produced CVs less than 13%. The Cozart® EIA Amphetamines Oral Fluid Microplate Kit is a qualitative manual ELISA assay and CVs of less than 10% are acceptable for this assay type.

#### Sensitivity

The sensitivity of the Cozart® EIA Amphetamines Oral Fluid Microplate Kit is 1.2ng/ml.

#### Specificity

Twenty potentially interfering unrelated substances were tested for cross reactivity in the Cozart® EIA Amphetamines Oral Fluid Microplate Kit and none were found to cross react. Eleven related compounds were tested and 7 showed a level of cross reactivity.

#### Cutoff Concentration

Testing samples at the cutoff concentration, 50% above and 50% below were carried out to validate the cutoff concentration. The absorbances obtained for the 7.5ng/ml sample were all higher than the 15ng/ml cutoff calibrator. Similarly the absorbances obtained for the 22.5ng/ml sample were all lower than the 15ng/ml cutoff calibrator.

#### Interference Studies

A range of parameters including alcohol, sample adequacy indicator dye, haemoglobin, smoking, coffee, tea, water, food, orange juice, hard candy, chewing gum and mouthwash were tested for interference in the Cozart® EIA Amphetamines Oral Fluid Microplate Kit. No interference was observed with any of the parameters.

#### Stopped Assay Stability

The stability of the stopped assay was investigated by reading the absorbance at 450nm at times 0, 5, 10, 15, 30, 45 and 60 minutes. The Cozart® EIA Amphetamines Oral Fluid Microplate Kit must be read within 15 minutes at 450nm.

#### Assay Drift

Sample addition at time 0, 2.5, 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5 and 25 minutes was investigated. Little change was observed across the plate and therefore sample addition to a Cozart® EIA Amphetamines Oral Fluid Microplate Kit must take place within 25 minutes.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

# JUN - 3 2004

Dr. Roberto Liddi Regulatory Affairs Manager Cozart Bioscience Ltd. 45 Milton Park Abington, Oxfordshire United Kingdom OX14 4RU

Re: k033743

Trade/Device Name: Cozart® EIA Amphetamines Oral Fluid Microplate Kit Regulation Number: 21 CFR 862.3100 Regulation Name: Amphetamine test system Regulatory Class: Class II Product Code: DKZ. Dated: May 3, 2004 Reccived: May 3, 2004

Dear Dr. Liddi:

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 r ou may) ateres 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 or uny I edelar sthates and 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).

Image /page/4/Picture/11 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)" around the perimeter. Inside the circle is a stylized image of an eagle.

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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, rr you stions 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 I ou may 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.

Jean 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

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### Indications for Use

| 510(k) Number: | K033743 |
|----------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Device Name: | Cozart® EIA Amphetamines Oral Fluid Microplate Kit |
| Indications For Use: | The Cozart® EIA Amphetamines Oral Fluid Microplate Kit is<br>intended for use in clinical and forensic laboratories when<br>used in conjunction with the Cozart® RapiScan Oral Fluid<br>collection system. Using this collection system it provides<br>qualitative screening results for amphetamines in human<br>oral fluid at a cutoff concentration of 15ng/ml. This is equal<br>to 45ng/ml in neat oral fluid as the collection system involves<br>a 1:3 dilution of the sample. |
| | This assay is for professional use only and provides only a<br>preliminary analytical test result. Clinical consideration and<br>professional judgement must be applied to any drug of abuse test<br>result, particularly in evaluating a preliminary positive result. In<br>order to obtain a more confirmed analytical result a more specific<br>alternative chemical method is needed. Gas Chromatography/Mass<br>Spectrometry (GCMS) is the preferred confirmatory method. |

Prescription Use _____________________________________________________________________________________________________________________________________________________________

### AND/OR

Over-The-Counter Use

(Part 21 CFR 801 Subpart D)

(21 CFR 807 Subpart C)

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

Concurence at CDRH Office of In Vitro Diagnostic Devices (OIVD)

**Division Sign-Off**

Office of In Vitro Diagnostic Device Evaluation and Sc

510(k) KOS

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