The Cozart RapiScan Oral Fluid Drug Test System - Opiates and Methadone is intended for Point of Care testing in a number of settings such as prescription workplace, drug dependency clinics, and criminal justice. It provides qualitative screening results for opiates and methadone in human oral fluid at a cut-off concentration equivalent to 40ng/mL and 30ng/mL respectively in neat oral fluid. The cozart collection system involves a 1:3 dilution of the oral fluid sample, this dilution factor is corrected for in the Cozart RapiScan Drug Test and therefore the remainder of this document will refer to the cut-offs as 13ng/mL for opiates and 10ng/ml for methadone.

This kit has to be used in conjunction with the Cozart RapiScan instrument. Please refer to the sampling and testing procedures in the instructions for use leaflet.

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 (GC/MS) is the preferred confirmatory method.

It is the responsibility of those organisations required to follow department of transportation (DOT) or the Substance Abuse and Mental Health Services Administration (SAMHSA) Workplace Drug Testing guidelines to determine that this product satisfies the criteria for workplace testing established under DOT and SAMHSA.

Device Description

The Cozart RapiScan opiates and methadone test system is composed of three parts - the oral fluid collection device, the opiates and methadone test cartridge and the Cozart RapiScan instrument.

Oral fluid Collection Device: composed of an oral fluid collector pad, a transport tube containing run buffer and a dispense filter tube.
Opiate and Methadone Test Cartridge: composed of a white reaction strip with immobilized drug sites for opiates and methadone contained in a blue plastic casing. The cartridge also has a pad containing gold labeled anti-morphine and gold labeled anti-methadone antibodies. In addition, the cartridge has a built in control line of sheep anti-mouse IgG antibody.
Cozart RapiScan Instrument: a battery-powered instrument whose function is to automate the analysis of the opiate/methadone test cartridge. It is a hand-held low voltage optical scanner.

AI/ML Overview

Here's an analysis of the Cozart RapiScan Oral Fluid Drug Test System for Opiates and Methadone, based on the provided text:

Acceptance Criteria and Device Performance

The acceptance criteria for the Cozart RapiScan are primarily defined by its ability to accurately detect opiates and methadone in oral fluid at specified cut-off concentrations, as validated against GC/MS. The study demonstrates the device's performance in terms of sensitivity, specificity, precision, and stability under various conditions.

Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance
Opiates Detection
Cut-off Concentration	40 ng/mL in neat oral fluid (equivalent to 13 ng/mL in diluted sample)	The device correctly identified opiates at this cut-off.
Positive Agreement	High agreement with GC/MS for positive samples	Out of 99 RapiScan positive samples for opiates, 93 were confirmed positive by GC/MS.
Negative Agreement	High agreement with GC/MS for negative samples	Out of 124 RapiScan negative samples for opiates, 123 were confirmed negative by GC/MS.
Near Cut-off Performance	Accurate detection for samples within +/- 50% of the cut-off concentration	24 samples were within +/- 50% of the opiate cut-off (20-60ng/mL). The specific accuracy for these 24 samples is not explicitly stated in a consolidated manner, but the overall method comparison suggests acceptable performance. Precision studies indicated 40/40 positive and 0/40 negative for 13 ng/mL in laboratory settings. For point of care settings, 25/25 positive and 1/25 negative for 13 ng/ml.
Methadone Detection
Cut-off Concentration	30 ng/mL in neat oral fluid (equivalent to 10 ng/mL in diluted sample)	The device correctly identified methadone at this cut-off.
Positive Agreement	High agreement with GC/MS for positive samples	Out of 116 RapiScan positive samples for methadone, 116 were confirmed positive by GC/MS.
Negative Agreement	High agreement with GC/MS for negative samples	Out of 115 RapiScan negative samples for methadone, 115 were confirmed negative by GC/MS.
Near Cut-off Performance	Accurate detection for samples within +/- 50% of the cut-off concentration	24 samples were within +/- 50% of the methadone cut-off (15-45ng/mL). The specific accuracy for these 24 samples is not explicitly stated in a consolidated manner, but the overall method comparison suggests acceptable performance. Precision studies indicated 40/40 positive and 0/40 negative for 10 ng/mL in laboratory settings. For point of care settings, 24/25 positive and 2/26 negative for 10 ng/ml.
Sensitivity	Detect drugs at or below 25-50% of the cut-off (implied by experiment design)	Opiates: detection limit between 9.75ng/mL (-25% of cutoff) and 6.5ng/mL (-50% of cutoff). Methadone: detection limit between 7.5ng/mL (-25% of cutoff) and 5ng/mL (-50% of cutoff).
Specificity	Minimal cross-reactivity with common interfering substances and related compounds.	28 potentially interfering substances tested at 100,000ng/mL (Buprenorphine at 10,000ng/mL) showed no cross-reactivity. Lowest concentration to produce a positive was determined for 13 opiate family members and 4 methadone-related substances across three different batches, demonstrating appropriate specificity for these related compounds.
Precision	Consistent results over time and across different operators, especially near the cut-off.	Laboratory: For opiates, spiked samples at 13 ng/mL (cutoff) showed 40/40 positive. For methadone, spiked samples at 10 ng/mL (cutoff) showed 40/40 positive. Consistent results for samples at 0 ng/mL, 6.5 ng/mL (19.5 ng/mL) for opiates and 0 ng/mL, 5 ng/mL (15 ng/mL) for methadone. Point-of-Care: Opiate: 25/25 for 13 ng/mL, 1/25 negative for 13 ng/mL. Methadone: 24/25 for 10 ng/mL, 2/26 negative for 10 ng/mL. This suggests good precision even in varied settings.
Sample Stability	Samples remain stable for accurate testing for a reasonable period.	Stable at both room temperature and 2-8°C for 28 days.
Freeze/Thaw Stability	Samples tolerate multiple freeze/thaw cycles without affecting results.	Samples can undergo up to six freeze/thaw cycles at -20°C prior to testing.
Interference	No interference from common oral fluid contaminants or patient activities.	No interference observed from sample adequacy indicator dye, hemoglobin, smoking, coffee, tea, water, food, orange juice, hard candy, chewing gum, and mouthwash.
Time of Day/Instrument/Operator Comparison	Results should be consistent regardless of time of day, instrument used, or operator.	Sampling at different times of day (morning, midday, evening after fortification at +/- 50% cutoff) had no effect. All three instruments produced unambiguous results. Inexperienced operators yielded unambiguous results for all three operators.
Accuracy/Recovery	Accurate detection of fortified samples at various concentrations around the cut-off.	All samples fortified at or above the cut-off concentration (0, 6.5, 13, 19.5 ng/mL for morphine and 0, 5, 10, 15 ng/mL for methadone) were positive, with the exception of the negative sample fortified at 50% below the cut-off as expected, indicating accurate recovery and detection across the relevant range.
Cut-off Concentration Effectiveness	Clear discrimination at the established cut-off.	All samples fortified at 50% below the cut-off were negative. All samples fortified at the cut-off, 50% above, and 100% above the cut-off were positive for both opiates and methadone.

Study Details

Sample sizes used for the test set and the data provenance:
- Method Comparison Test Set:
  - Total Samples: 454 oral fluid samples.
  - Opiates: 99 RapiScan positive (93 GC/MS confirmed), 124 RapiScan negative (123 GC/MS confirmed). (Total: 223 samples for opiates analysis against GC/MS)
  - Methadone: 116 RapiScan positive (116 GC/MS confirmed), 115 RapiScan negative (115 GC/MS confirmed). (Total: 231 samples for methadone analysis against GC/MS)
  - Special Samples:
    - 24 opiate samples within +/- 50% of cut-off (14 previously diluted with blank saliva).
    - 24 methadone samples within +/- 50% of cut-off (20 previously diluted with blank saliva).
  - Provenance: All samples were oral fluid.
    - 99 opiate-positive samples and 116 methadone-positive samples were from "drug users enrolled at a drug rehabilitation clinic."
    - 103 opiate-negative samples and 102 methadone-negative samples were from "drug free volunteers."
    - 21 opiate-negative samples and 13 methadone-negative samples were from "known drug users."
    - The samples were tested by Cozart Bioscience Ltd staff, and GC/MS performed by FSS Chepstow UK, University of Glasgow, Scotland, and The Analytical Laboratory at Cozart Bioscience Ltd, UK. This suggests a retrospective collection of samples from clinics and volunteers, followed by prospective testing with the RapiScan and GC/MS. The origin is primarily the UK.
- Precision Test Set (Laboratory): Four oral fluid samples (negative, cutoff, 50% above cutoff, 50% below cutoff) tested in duplicate every day for 20 days (4 samples * 2 duplicates * 20 days = 160 tests per drug).
- Precision Test Set (Point of Care - POC): Four oral fluid samples (spiked at 0, 6.5, 13, 19.5 ng/mL for opiates and 0, 5, 10, 15 ng/mL for methadone) from drug-free volunteers, tested up to 9 times at 3 POC sites.
- Sensitivity Test Set: Eight negative oral fluid samples, fortified at 50% above cut-off and serially diluted.
- Specificity Test Set: Not explicitly stated, but 28 potentially interfering substances and 13 opiate/4 methadone related substances were tested.
- Cutoff Concentration Test Set: 8 fortified oral fluid samples at various concentrations (cutoff, +/- 50% cutoff, +/- 100% cutoff).
- Interference Studies Test Set: Not explicitly stated, but various parameters (dye, hemoglobin, common consumables) were tested.
- Stability Studies Test Set: Four fortified samples (2 at 50% above cutoff, 2 at 50% below cutoff) and two negative samples from volunteers.
- Time of Day Comparison Test Set: Samples from 4 volunteers at 3 different times of day, fortified.
- Instrument Comparison Test Set: Samples from 4 volunteers, fortified, tested on 3 different instruments.
- Operator Comparison Test Set: Samples from 4 volunteers, fortified, tested by "inexperienced operators" (number not specified, but likely at least 3 given the results statement mentions "all three operators").
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The ground truth for the test set (method comparison) was established by Gas Chromatography/Mass Spectrometry (GC/MS). While GC/MS is an analytical method, not human experts, it is considered the "preferred confirmatory method" and gold standard for drug testing. The performing laboratories were FSS Chepstow UK, University of Glasgow, Scotland, and The Analytical Laboratory at Cozart Bioscience Ltd, UK. The qualifications of the GC/MS operators are implied to be standard for analytical laboratory personnel competent in this method.
Adjudication method for the test set:
- Not applicable in the typical sense for medical imaging or clinical decision-making. The "adjudication" here is the direct comparison of the Cozart RapiScan qualitative result (positive/negative) against the quantitative GC/MS result, using the defined cut-off concentrations. Discrepancies would be identified based on whether the RapiScan result matched the GC/MS result relative to the cut-off.
If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is a point-of-care test read by an instrument, not by human readers interpreting complex images or data. The instrument automatically displays results as "positive or negative," eliminating human subjectivity in reading.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the performance study described is essentially a standalone algorithm performance study. The Cozart RapiScan instrument, which incorporates the device's "algorithm" for reading the test cartridge, operates without human interpretation of the test line. The human interaction involves initiating the test and reading the displayed digital result (positive or negative). The study evaluates the objective output of this system compared to the gold standard. The note that the "Cozart RapiScan instrument must be used to read the cartridges, this eliminates the subjectivity of reading by eye" further supports this being a standalone evaluation of the device's automated reading.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The ground truth used was Gas Chromatography/Mass Spectrometry (GC/MS), which is the "preferred confirmatory method" and considered the analytical gold standard for drug detection and quantification in biological samples.
The sample size for the training set:
- The document does not explicitly state a separate training set size. The studies described are performance validation studies. It's common for such devices (especially those using immunoassay principles rather than complex machine learning algorithms) not to have a distinct "training set" in the sense of AI/ML models. The design and optimization of the immunoassay itself (e.g., antibody selection, cut-off determination) would be based on internal development and verification processes that precede the formal validation studies presented here.
How the ground truth for the training set was established:
- As no explicit training set is mentioned in the context of advanced machine learning, the concept of establishing ground truth for a training set in the typical AI/ML sense is not directly applicable. For the development of the immunoassay, the "ground truth" for calibrating the system and establishing the cut-off concentrations would likely have involved controlled samples with known concentrations of opiates and methadone, confirmed by analytical methods like GC/MS during the R&D phase of the test's design. The "Cutoff Concentration" study described within the document is part of the verification of these established cutoffs.

Summary

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1620920

NOV 5 2002

PREMARKET NOTIFICATION [510(k)] SUMMARY

Submitter:	Cozart Bioscience Ltd45 Milton ParkAbingdonOxfordshire OX14 4RUUnited KingdomTel No: 01235 861483Fax No: 01235 835607
Contact Person:	Dr Roberto LiddiQuality Assurance & Regulatory Affairs Manager
Date:	23rd October 2002
Device Name:	Cozart RapiScan
Trade Name:	Cozart RapiScan Oral Fluid Drug Test System-Opiate/Methadone
Classification Name:	Methadone Test SystemOpiate Test System
Classification:	Class IICode of Federal Regulations Title 21 Food and DrugsPart 862 Clinical Chemistry and Clinical ToxicologyDevicesSubpart D Clinical Toxicology Test SystemsSection 862.3620 Methadone Test SystemSection 862.3650 Opiate Test System

Establishment Registration No.: 3002336046

Performance Standards:	BS EN ISO 9001:1994, EN 46001:1996
Substantial Equivalence:	RapidOne Opiates Test, 510(k) no. K971961

Introduction

The Cozart RapiScan Oral Fluid Drug Test System for Opiates and Methadone is a point of care test (POCT) for the detection of both opiates and methadone in human oral fluid using cutoffs of 40 and 30 ng/mL respectively, in neat oral fluid. The performance of the Cozart RapiScan opiates and methadone test was compared to GC/MS. Cozart Bioscience Ltd is the manufacturer of the Cozart RapiScan Oral Fluid Drug Test System- Opiate/Methadone. We have not purchased this device from another manufacturer and the device is not marketed under another product name.

RapidOne Methadone Test, 510(k) no. K992325

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Intended Use

This kit has to be used in conjunction with the Cozart RapiScan instrument. Please refer to the sampling and testing procedures in the instructions for use leaflet.

Where Used

The Cozart RapiScan opiates and methadone test is designed for point of care testing. All users of the test are trained by a Cozart representative, at the end of the training programme a certificate is issued.

Design and Materials

As can be seen from the Principle of the Test section in the package insert, the Cozart RapiScan opiates and methadone test system is a point of care test for the detection of opiates and methadone in human oral fluid.

The Cozart RapiScan opiates and methadone test system is composed of three parts - the oral fluid collection device, the opiates and methadone test cartridge and the Cozart RapiScan instrument.

1. Oral fluid Collection Device

This device is composed of an oral fluid collector pad, a transport tube containing run buffer and a dispense filter tube. The oral fluid collection pad is manufactured by Oral fluid Diagnostic Systems Inc, New York, USA. It is composed of a white plastic handle and a cellulose pad with a perforated edge. The white plastic handle incorporates a sample adequacy indicator, when 1mL of oral fluid has been collected the indicator in the handle turns blue.

The dispense filter tube pushes the sample pad down to the bottom of the transport tube and assists in mixing the oral fluid and buffer. The top of the tube is partially sealed incorporating a dropper dispense facility into the top. Six drops of the sample are added to the cartridge with the dispense filter tube.

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2. Opiate and Methadone Test Cartridge

This is composed of a white reaction strip with immobilized drug sites for opiates and methadone contained in a blue plastic casing. The cartridge also has a pad containing gold labeled anti-morphine and gold labeled anti-methadone antibodies. In addition, the cartridge has a built in control line of sheep anti-mouse IgG antibody to ascertain that complete lateral transfer of specimen has been achieved. The opiate and methadone test cartridge is a single use device which should be disposed of after use.

3. Cozart RapiScan Instrument

The Cozart RapiScan instrument is a battery-powered instrument whose function is to automate the analysis of the opiate/methadone test cartridge. It is a hand-held low voltage optical scanner (complies with Electromagnetic Compatibility (EMC) Directive 89/336/EEC).

The cartridge is inserted into the machine for reading and is removed after the test has been read. Results are displayed on the screen as positive or negative. The Cozart RapiScan instrument must be used to read the cartridges, this eliminates the subjectivity of reading by eye.

The instrument is supplied with pre-printed non-disposable system test, positive QC and negative QC cartridges. The system test cartridge (labeled with SYS) is designed to test whether the instrument is functioning correctly. This should be performed at regular intervals throughout the use of the machine or when the instrument has been manhandled eg. dropped. The instrument displays SYSTEM TEST PASS or SYSTEM TEST FAIL on the screen of the instrument. The positive and negative OC cartridges (labeled with POC and NOC) should be analysed at regular intervals in the same way as a test sample.

Performing the Test

A oral fluid sample is collected from the mouth by placing the sample pad under the tongue ensuring the pad is pointing downwards. This process can take from 1-10 minutes. Once the indicator in the sample pad has turned blue and 1mL of oral fluid has been collected the sample pad is removed from the mouth and placed into the transport tube. The pad is removed from the plastic handle along the perforated edge. The dispense filter tube is pushed into the transport tube purple end down until the sample pad is pushed to the bottom of the tube. The sample is then ready for testing.

The opiates and methadone test cartridge is removed from its foil pouch and placed on a flat surface. The transfer tube is carefully and very slowly inverted until it is horizontal. To add the sample, gently squeeze the end of the filter tube transferring 6 drops of sample into the cartridge. Once the liquid has appeared in the cartridge window, this takes between 2 and 60 seconds, the cartridge is then inserted into the Cozart RapiScan instrument. Pressing the start button initiates the timer to countdown 6 minutes after which the instrument automatically reads the cartridge and displays the results on the instrument screen. The results are displayed as positive or negative.

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The Cozart RapiScan test cartridge and sample collection device are designed for use with the Cozart RapiScan instrument. The cartridges must be read with the instrument and not by eye. In addition to the quality control cartridges supplied with the instrument, other quality control specimens with known drug concentrations should be run through the test procedure following appropriate federal, state and local guidelines concerning the running of external quality controls. These are not supplied with the Cozart RapiScan opiates and methadone test system.

Interpreting the Result

The result is displayed on the screen of the Cozart RapiScan instrument as positive or negative. This means that the diluted sample has methadone or an opiate present. The dilution factor should be taken into consideration when interpreting the results, that is, 1mL of oral fluid is diluted in 2mL of Cozart RapiScan buffer (x3 dilution factor). 10ng/mL of methadone in a diluted sample will produce a positive result, this is equivalent to 30ng/mL in neat oral fluid. Similarly, 13ng/mL of morphine will produce a positive result, this is equivalent to 40ng/mL morphine in neat oral fluid. The test provides only a preliminary result and in order to obtain a more confirmed result Gas Chromatography/Mass Spectrometry (GC/MS) analysis should be performed.

Performance:

Method Comparison

The method comparison study using the Cozart RapiScan Opiates and Methadone test system was performed at Cozart Bioscience Ltd by Cozart Bioscience staff. The GC/MS was performed by FSS Chepstow UK, University of Glasgow, Scotland, and The Analytical Laboratory at Cozart Bioscience Ltd, UK.

A total of 454 Oral fluid samples were tested in the Cozart RapiScan Drug Test System according to the package insert.

99 samples from drug users enrolled at a drug rehabilitation clinic, were positive for opiates by the Cozart RapiScan System, of these samples 93 were confirmed positive by GC/MS. The GC/MS employs the set cut-off of 40ng/mL for Opiates in neat oral fluid.

124 samples were negative for opiates, 123 of these samples were confirmed negative by GC/MS. Of the negative samples 103 were from drug free volunteers, and the remaining 21 were from known drug users.

24 of all samples tested were within +50% to - 50% of the opiate cut-off. Of these, 14 had been previously diluted with blank saliva to give a concentration within the range of 60ng/mL to 20ng/mL.

116 samples from drug users enrolled at a drug rehabilitation clinic, were positive for Methadone by the Cozart RapiScan System and 116 were confirmed positive by GC/MS. The GC/MS employs the set cut-off of 30ng/mL for Methadone in neat oral fluid

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115 samples were negative in the Cozart RapiScan System and were confirmed negative by GC/MS. 102 of these samples were from drug free volunteers, and the remaining 13 were from known drug users.

24 of all samples tested were within -50% to +50% of the methadone cut-off. Of these, 20 had previously been diluted with blank saliva to give a concentration within the range 45ng/mL to 15ng/mL.

Precision

Four oral fluid samples were tested in duplicate every day for twenty days. The samples were a negative sample spiked with drug at the cutoff concentration and negative samples spiked to 50% above and below the cutoff.

Opiate	Opiate Concentration (ng/mL)
	0	6.5	13	19.5
Positive	0	0	40	40
Negative	40	40	0	0

Acceptable results were obtained as can be seen in the table below:

Methadone	Methadone Concentration (ng/mL)
	0	5	10	15
Positive	0	0	40	40
Negative	40	40	0	0

To check whether the use of the Cozart RapiScan Drug Test System Opiates/Methadone might be somehow influenced by a testing environment different from a laboratory setting, and by being used by untrained personnel, an extended Precision Study was conducted at 3 Point Of Care sites. Four oral fluid samples were collected from drug free volunteers and aliquots were fortified with Morphine and Methadone at the concentrations shown below just prior to onsite testing. The samples were tested up to 9 times for each site. The table below shows the results obtained.

Opiate	Opiate Concentration (ng/mL)
	0	6.5	13	19.5
Positive	0	0	25	25
Negative	25	26	1	0

Methadone	Methadone Concentration (ng/ml)
	0	5	10	15
Positive	0	0	24	23
Negative	25	26	2	2

Sensitivity

Eight negative oral fluid samples fortified with morphine and methadone at 50% above the cutoff concentration were serially diluted in increments of 25% of the cutoff concentration of the assay. The lowest concentration of drug detected above the detection cutoff is the detection limit. The detection limit for opiates is between 9.75ng/ml (-25% of the cut off value) and 6.5ng/ml (-50% of the cut off value) and for

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methadone is between 7.5ng/ml (-25% of the cut off value) and 5ng/ml (-50% of the cut off value).

Specificity

The specificity can be defined as the extent to which related or unrelated compounds cross-react with the antibody employed in the assay. Twenty-eight potentially interfering substances were tested at 100,000ng/mL for cross-reactivity in the Cozart RapiScan opiates and methadone test and none were found to cross-react. Burrenorphine was tested at 10.000ng/mL due to the stock solution being at 100,000ng/mL.

The lowest concentration to produce a positive was determined for a number of related substances. Thirteen different members of the opiate family were tested morphine, 6-monoacetylmorphine, codeine, dihydrocodeine, nalorphine, oxycodone, hydromorphone, hydrocodone, oxymorphone, norcodeine, heroin and morphine-3-glucuronide. Similarly, methadone and three of its metabolites were 1-x-acetylmethadol (LAAM). 2-ethylidene-1.5-dimethyl-3.3tested diphenylpyrrolidine (EDDP), 2-ethylidene-5-methyl-3.3-diphenylpyrroline (EMDP). This experiment was carried out on three different batches of opiate/methadone test cartridges.

Cutoff Concentration

The cutoff concentration was determined by preparing 8 fortified oral fluid samples at the cutoff concentration. 50% above and below the cutoff concentrations and 100% above and below the cutoff concentrations. All the samples fortified at 50% below the cutoff were negative for both methadone and opiates. All the samples fortified at the cutoff concentration. 50% above and below the cutoff concentration and 100% above and below the cutoff concentration were positive for both opiates and methadone.

Interference Studies

A range of parameters including 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 RapiScan opiates and methadone test system. No interference was observed with any of the parameters.

Sample Stability

Samples were collected from volunteers, two were fortified with morphine and methadone at 50% above the cutoff and two were fortified with morphine and methadone at 50% below the cutoff concentration. The fortified samples and also two negative samples were then stored at both room temperature and 2-8°C and tested at day 0. 3. 7. 14. 21 and 28 in the Cozart RapiScan opiates and methadone test system. Samples are stable at both room temperature and 2-8°C for 28 days.

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Freeze/Thaw Stability

Samples were collected from volunteers, two were fortified with morphine and methadone at 50% above the cutoff and two were fortified with morphine and methadone at 50% below the cutoff concentration. The fortified samples and also two negative samples were then subjected to six freeze/thaw cycles at -20°C before testing in the Cozart RapiScan opiates and methadone test system. Samples can undergo up to six freeze/thaw cycles prior to testing.

Time of Day Comparison

This experiment was designed to investigate whether sampling at different times of the day would have an effect on the results obtained with the Cozart RapiScan opiates and methadone test. Samples were collected from four volunteers at three different times of the day - morning, midday and evening. The morning sample was taken before breakfast. the midday sample was taken before lunch and the evening sample before bed. Each sample was then fortified with morphine and methadone at 50% above and below the cutoff concentration and tested. Sampling at different times of the day had no effect on the results obtained with the Cozart RapiScan opiates and methadone test system.

Instrument Comparison

This experiment was designed to investigate whether different instruments would produce different results with the Cozart RapiScan opiates and methadone test system. Samples were collected from four volunteers and spiked with morphine and methadone at 50% above and below the cutoff concentration then tested. All the testing was performed by a single operator with the same set of samples to ensure the only variable was the instrument. All three instruments produced unambiguous results.

Operator Comparison

This experiment was designed to ensure that the Cozart RapiScan opiates and methadone test system is not sensitive to operator effects. Samples were collected from four volunteers and fortified with morphine and methadone at 50% above and below the cutoff concentration. The samples were tested by inexperienced operators with the same instrument. The results for each sample were unambiguous for all three operators.

Accuracy/Recovery

Samples were collected from four volunteers and fortified with morphine and methadone at 50% above and below the cutoff concentration. This gave samples from four individuals at three concentrations - 0, 6.5 and 19.5ng/mL for morphine and 0, 5 and 15ng/mL for methadone. To these samples drug was added at 50% above and below the cutoff concentration, at the cutoff concentration and 100% above the cutoff concentration. The samples were tested in the Cozart RapiScan opiates and methadone test system. All samples were positive with the exception of the negative sample fortified with drug at 50% below the cutoff concentration as expected.

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New Filter Tube

This experiment was designed to ensure that the sample testing volume from the new plunger. Previous testing showed that four drops from the old plunger were equal, on average, to six drops from the new plunger. Four different operators, weighted two sample each, one with the old system and one with the new system. This operation was repeated ten times. The balance used was a FX-40 AND Electronic balance [(d=0.0001g) serial no. 05704015], which is periodically calibrated according to Standard Operating Procedures. The results show no significant difference in weight between the two systems.

Chemical Safety

The sample collection contains Bovine Serum Albumin (BSA) obtained from a BSE free source. The cartridges are composed of a nitrocellulose membrane which may explode at high temperatures.

Human Factors

There are no human factors incorporated in any of the kit components.

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Image /page/8/Picture/1 description: The image shows a logo with a stylized depiction of three curved lines resembling waves or abstract wings. Above the lines, the text "AAN SERVICES USA" is arranged in a semi-circular fashion. Below the lines, the word "DEPARTM" is partially visible, also arranged in a semi-circular manner. The logo appears to be a stylized representation of a government agency or organization, possibly related to services in the USA.

5 2002 NOV

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Dr. Roberto Liddi QA/RA Manager Cozart Bioscience Limited 45 Milton Park Abingdon Oxfordshire, OX 14 4RU

K020920 Re:

Trade/Device Name: Cozart RapiScan Oral Fluid Drug Test System - Opiate/Methadone Regulation Number: 21 CFR § 862.3620 and 21 CFR § 862.3650 Regulation Name: Immunoassay, Methadone/ Immunoassay, Opiates Regulatory Class: II Product Code: DJR, DJG Dated: October 3, 2002 Received: October 8, 2002

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 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 the Code of Federal Regulations. Title 21, Parts 800 to 898. 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Putman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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K020920 510(k) Number (if known):

Device Name:_ Cozart RapiScan Oral Fluid Drug Test System- Opiate/Methadone

Indications For Use:

This kit has to be used in conjunction with the Cozart RapiScan instrument. Please refer to the sampling and testing procedures in the instructions for use leaflet.

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 Gas Chromatography/Mass Spectrometry (GC/MS) is the preferred needed. confirmatory method.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Tricia Caughin

(Division Sign-Off) Division of Clinical Laborate:

510(k) Number __

(Optional Format 3 10 98)

✓

Regulation Number and Section

§ 862.3650 Opiate test system.

(a)
Identification. An opiate test system is a device intended to measure any of the addictive narcotic pain-relieving opiate drugs in blood, serum, urine, gastric contents, and saliva. An opiate is any natural or synthetic drug that has morphine-like pharmocological actions. The opiates include drugs such as morphine, morphine glucoronide, heroin, codeine, nalorphine, and meperedine. Measurements obtained by this device are used in the diagnosis and treatment of opiate use or overdose and in monitoring the levels of opiate administration to ensure appropriate therapy.(b)
Classification. Class II (special controls). An opiate 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).