Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description and performance studies detail a standard enzyme immunoassay based on chemical reactions and spectrophotometric measurement, with no mention of AI or ML algorithms for data analysis or interpretation.

Therapeutic

No.
This device is an in vitro diagnostic (IVD) tool used for qualitative determination of a cocaine metabolite in human urine, which provides preliminary analytical test results for diagnostic purposes, not for treating or preventing disease.

Diagnostic

Yes

This device is a qualitative diagnostic test intended to detect benzoylecgonine (a cocaine metabolite) in human urine, providing a preliminary analytical test result used for diagnostic purposes (e.g., drug screening).

SaMD (Software as a Medical Device)

No

The device is a laboratory assay consisting of liquid reagents and is intended to be used with clinical chemistry analyzers, which are hardware devices. It is not solely software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The intended use explicitly states it's for the "qualitative determination of benzoylecgonine (a cocaine metabolite) in human urine". This is a diagnostic test performed on a biological sample (urine) to detect a substance related to a medical condition or state (drug use).
Device Description: The description details the reagents and the enzymatic immunoassay method used to analyze the urine sample. This is characteristic of an in vitro diagnostic test.
Anatomical Site: The test is performed on "human urine", which is a biological specimen.
Performance Studies: The document describes performance studies conducted to evaluate the device's accuracy and reliability in analyzing urine samples. This is a requirement for IVD devices.
Predicate Device: The mention of a "Predicate Device" (K113139; Lin-Zhi International, Inc. Cocaine Metabolite Enzyme Immunoassay) indicates that this device is being compared to a previously cleared IVD device.

All of these factors align with the definition and characteristics of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The Pointe Scientific Cocaine Metabolite Enzyme Immunoassay is intended for the qualitative determination of benzoylecgonine (a cocaine metabolite) in human urine at a cutoff value of 150 ng/mL. Rx only.

This assay provides only a preliminary analytical test result. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. Gas or Liquid Chromatograph/Mass Spectrometry (GC/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.

Product codes (comma separated list FDA assigned to the subject device)

DIO

Device Description

The Cocaine Metabolite Enzyme Immunoassay consists of ready-to-use liquid reagents:

. Reagent 1 contains a mouse monoclonal anti-benzoylecgonine antibody, glucose-6-phosphate (G6P) nicotinamide adenine dinucleotide (NAD), stabilizers and sodium azide (0.09%) as a preservative.
Reagent 2 contains glucose-6-phosphate dehydrogenase (G6PDH) labeled with . benzoylecgonine in buffer with sodium azide (0.09%) as a preservative.

The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. Enzyme activity decreases upon binding to the antibody, and the drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, benzoylecgonine-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when drug is present in the sample, antibody binds to the free drug; the unbound benzovlecgonine-labeled G6PDH then exhibits its maximal enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that can be measured spectrophotometrically at a 340 nm primary wavelength.

The assay has a cutoff of 150 ng/mL benzoylecqonine.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

human urine

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Method Comparison Studies:
Sample Size: 114 unaltered clinical urine remnant samples
Data Source: remnant urine samples obtained from a third-party biorepository.
Annotation Protocol: Results obtained through the Pointe Scientific Cocaine Metabolite Enzyme Immunoassay were compared against results obtained from a fully validated and qualified Agilent 6460 LC/MS.

Precision Studies:
Data Source: benzoylecgonine spiked into drug free urine at various concentrations (zero, -75%, -50%, -25%, at the cutoff, 125%, 150%, 175% and 200% of the cutoff). Concentrations were confirmed by LC/MS.
Annotation Protocol: Testing for both the with-in run and betweenrun studies were performed by testing each sample in replicate, with two runs per day, for 20 days.

Interference (Endogenous Substances) Study:
Annotation Protocol: Endogenous compounds were added into drug-free urine, urine sample spiked to 75% of benzoylecgonine and urine spiked to 125% of benzoylecgonine at various concentrations. pH interference was tested with urine samples having pH from 3 to 11, each divided into two aliquots and spiked to 75% and 125% of the cutoff. Specific gravity interference was tested with urine samples ranging from 1.000 g/mL to 1.031 g/mL, each divided into three aliquots (unspiked, 75% cutoff, 125% cutoff).

Cross Reactivity:
Annotation Protocol: Cross-reactivity was established by spiking various concentrations of structurally related and unrelated compounds into drug-free urine. Manufacturer studies performed on another analyzer (Hitachi 717) were referenced after completing proof of principle testing on a subset of structurally and non-structurally related compounds.

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Performance was evaluated at the MedTest Dx site on both the Mindray BS-480 and the Mindray BA-800M clinical chemistry analyzers.

Method Comparison Studies:
Study Type: Method Comparison Studies
Sample Size: 114 unaltered clinical urine remnant samples
Key Results (BS-480): % Agreement among positives is 88.9% (40/45), % Agreement among negatives is 98.6% (68/69).
Key Results (BA-800M): % Agreement among positives is 93.3% (42/45), % Agreement among negatives is 98.6% (68/69).

Precision Studies:
Study Type: Precision studies
Key Results (BS-480 Qualitative Results):

Sample concentration 0 (negative): Within Run (20 observations, 20 Neg/0 Pos), Between Run (80 observations, 80 Neg/0 Pos)
Sample concentration 37.5 (-75% c/o): Within Run (20 observations, 20 Neg/0 Pos), Between Run (80 observations, 80 Neg/0 Pos)
Sample concentration 75 (-50% c/o): Within Run (20 observations, 20 Neg/0 Pos), Between Run (80 observations, 80 Neg/0 Pos)
Sample concentration 112.5 (-25% c/o): Within Run (20 observations, 20 Neg/0 Pos), Between Run (80 observations, 80 Neg/0 Pos)
Sample concentration 150 (cutoff): Within Run (20 observations, 19 Neg/1 Pos), Between Run (80 observations, 68 Neg/12 Pos)
Sample concentration 187.5 (+25% c/o): Within Run (20 observations, 0 Neg/20 Pos), Between Run (80 observations, 0 Neg/80 Pos)
Sample concentration 225 (+50% c/o): Within Run (20 observations, 0 Neg/20 Pos), Between Run (80 observations, 0 Neg/80 Pos)
Sample concentration 262.5 (+75% c/o): Within Run (20 observations, 0 Neg/20 Pos), Between Run (80 observations, 0 Neg/80 Pos)
Sample concentration 300 (+100% c/o): Within Run (20 observations, 0 Neg/20 Pos), Between Run (80 observations, 0 Neg/80 Pos)
These results indicate that the Pointe Scientific Cocaine Metabolite Enzyme Immunoassay has acceptable precision on the BS-480.

Key Results (BA-800M Qualitative Results):

Sample concentration 0 (negative): Within Run (20 observations, 20 Neg/0 Pos), Between Run (80 observations, 80 Neg/0 Pos)
Sample concentration 37.5 (-75% c/o): Within Run (20 observations, 20 Neg/0 Pos), Between Run (80 observations, 80 Neg/0 Pos)
Sample concentration 75 (-50% c/o): Within Run (20 observations, 20 Neg/0 Pos), Between Run (80 observations, 80 Neg/0 Pos)
Sample concentration 112.5 (-25% c/o): Within Run (20 observations, 20 Neg/0 Pos), Between Run (80 observations, 80 Neg/0 Pos)
Sample concentration 150 (cutoff): Within Run (20 observations, 7 Neg/13 Pos), Between Run (80 observations, 41 Neg/39 Pos)
Sample concentration 187.5 (+25% c/o): Within Run (20 observations, 0 Neg/20 Pos), Between Run (80 observations, 0 Neg/80 Pos)
Sample concentration 225 (+50% c/o): Within Run (20 observations, 0 Neg/20 Pos), Between Run (80 observations, 0 Neg/80 Pos)
Sample concentration 262.5 (+75% c/o): Within Run (20 observations, 0 Neg/20 Pos), Between Run (80 observations, 0 Neg/80 Pos)
Sample concentration 300 (+100% c/o): Within Run (20 observations, 0 Neg/20 Pos), Between Run (80 observations, 0 Neg/80 Pos)
These results indicate that the Pointe Scientific Cocaine Metabolite Enzyme Immunoassay has acceptable precision on the BA-800M.

Interference (Endogenous Substances) Study:
Key Results: The listed endogenous compounds (Acetaminophen, Acetone, Ascorbic Acid, Aspirin, Caffeine, Creatinine, Ethanol, Galactose, r-Globulin, Glucose, Hemoglobin, Human Serum Albumin, Ibuprofen, Oxalic Acid, Riboflavin, Sodium Chloride, Urea) were determined not to interfere at the concentrations shown. No positive or negative interference due to pH or specific gravity was observed.

Cross Reactivity:
Key Results (BA-800M):

Benzoylecgonine (Target Concentration 150 ng/mL): %Cross Reactivity Calculated based on Analyzer Recovered Concentration 113.43%, %Cross Reactivity Calculated based on Cutoff Concentration 100.00 %
Cocaine (Target Concentration 10,000 ng/mL): %Cross Reactivity Calculated based on Analyzer Recovered Concentration 1.52%, %Cross Reactivity Calculated based on Cutoff Concentration 1.50 %
Meperidine (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %

Key Results (BS-480):

Benzoylecgonine (Target Concentration 150 ng/mL): %Cross Reactivity Calculated based on Analyzer Recovered Concentration 105.37%, %Cross Reactivity Calculated based on Cutoff Concentration 100.00 %
Cocaine (Target Concentration 10,000 ng/mL): %Cross Reactivity Calculated based on Analyzer Recovered Concentration 1.62%, %Cross Reactivity Calculated based on Cutoff Concentration 1.50 %
Meperidine (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %

Key Results (Referenced Cross Reactivity Testing on Hitachi 717):
Structurally Related Cocaine Compound:

Benzoylecgonine (Target Concentration 150 ng/mL): % Cross Reactivity 96.03 %
Benzoylecgonine (Target Concentration 300 ng/mL): % Cross Reactivity 102.10 %
Cocaethylene (Target Concentration 4,000 ng/mL): % Cross Reactivity 4.58 %
Cocaine (Target Concentration 25,000 ng/mL): % Cross Reactivity 0.62%
Ecgonine (Target Concentration 400,000 ng/mL): % Cross Reactivity 0.03 %
Ecgonine, Methyl Ester (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Norcocaine (Target Concentration 30,000 ng/mL): % Cross Reactivity 0.68 %
Atropine (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %

Structurally Unrelated Pharmacological Compounds:

Acetaminophen (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Acetylsalicylic Acid (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Amobarbital (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Amoxicillin (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Amphetamine (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Bupropion (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Captopril (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Caffeine (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Chlordiazepoxide (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Chlorpheniramine (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Chlorpomazine (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Codeine (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Dextromethorphan (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Diazepam (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Digoxin (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Enalapril (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Fluoxetine (Target Concentration 100,000 ng/mL): % Cross Reactivity 0.01 %
Glyburide (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Ibuprofen (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Lidocaine (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Meperidine (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Methadone (Target Concentration 100,000 ng/mL): % Cross Reactivity 0.01 %
Methamphetamine (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Methaqualone (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Morphine (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Nicodine (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Nifedipine (Target Concentration 100,000 ng/mL): % Cross Reactivity 0.00 %
Oxazepam (Target Concentration 100,000 ng/mL): % Cross Reactivity 0.00 %
Phencyclidine (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Phenobarbital (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Propoxyphene (Target Concentration 100,000 ng/mL): % Cross Reactivity 0.00 %
Ranitidine (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Salicyluric acid (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Secobarbital (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
11-nor- THC-COOH (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Valproic Acid (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %
Verapamil (Target Concentration 500,000 ng/mL): % Cross Reactivity 0.00 %

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

BS-480:
% Agreement among positives is 88.9% (40/45)
% Agreement among negatives is 98.6% (68/69)

BA-800M:
% Agreement among positives is 93.3% (42/45)
% Agreement among negatives is 98.6% (68/69)

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K113139

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 862.3250 Cocaine and cocaine metabolite test system.

(a)
Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine metabolite (benzoylecgonine) in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of cocaine use or overdose.(b)
Classification. Class II (special controls). A cocaine and cocaine metabolite 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).

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food & Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

March 12, 2020

MedTest Dx William Cripps Director, R&D, OA/RA 5449 Research Drive Canton, MI 48188

Re: K191638

Trade/Device Name: Pointe Scientific Cocaine Metabolite Enzyme Immunoassay Regulation Number: 21 CFR 862.3250 Regulation Name: Cocaine And Cocaine Metabolite Test System Regulatory Class: Class II Product Code: DIO Dated: January 27, 2020 Received: January 28, 2020

Dear William Cripps:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

Please note that if you modify your IVD in the future to exceed any of the limitations to the exemption found in 21 CFR 862.9(c), your device will require a new 510(k) prior to marketing this device in the United States and will not be exempt from the premarket notification requirements so long as it exceeds the limitations to the exemption found in 21 CFR 862.9.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to 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.

1

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 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4. Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Marianela Perez-Torres, Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

2

Indications for Use

510(k) Number (if known) K191638

Device Name

Pointe Scientific Cocaine Metabolite Enzyme Immunoassay

Indications for Use (Describe)

Indications For Use: The Pointe Scientific Cocaine Metabolite Enzyme Immunoassay is intended for the qualitative determination of benzoylecgonine (a cocaine metabolite) in human urine at a cutoff value of 150 ng/mL. Rx only.

This assay provides only a preliminary analytical test result. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. Gas or Liquid Chromatograph/Mass Spectrometry (GC/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.

Type of Use (Select one or both, as applicable)
☑ Prescription Use (Part 21 CFR 801 Subpart D)	☐ Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) SUMMARY

This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of Safe Medical Device Act of 1990 and 21 CFR 807.92.

a. Device Information

Category	Comments
Sponsor	MedTest Dx
5449 Research Drive
Canton, MI 48188
Phone: 734-487-8300
Fax: 734-483-1592
Correspondent Contact
Information	William Cripps
Director, R&D/RA/QA
Email: wcripps@medtestdx.com
Phone: 734-487-8300 ext. 120
Fax: 734-483-1592
Device 510(k) Number	K191638
Device Common Name	Cocaine Metabolite Enzyme Immunoassay
Trade or Proprietary
Name	Pointe Scientific Cocaine Metabolite Enzyme
Immunoassay
Candidate Device
Product Code,
Classification,
Classification Name &
Panel	DIO, Class II, 21 CFR 862. 3250 – Cocaine Metabolite
Test System, 91 – Toxicology

Predicate Device Information

Predicate Device	Cocaine Metabolite Enzyme Immunoassay
Predicate Device
Manufacturer	Lin-Zhi International, Inc.
Predicate Device
Premarket
Notification #:	K113139

b. Date Summary Prepared

June 17, 2019 Updated January 27, 2020 Updated February 3, 2020 Updated February 26, 2020

4

c. Description of Device

The Cocaine Metabolite Enzyme Immunoassay consists of ready-to-use liquid reagents:

. Reagent 1 contains a mouse monoclonal anti-benzoylecgonine antibody, glucose-6-phosphate (G6P) nicotinamide adenine dinucleotide (NAD), stabilizers and sodium azide (0.09%) as a preservative.
Reagent 2 contains glucose-6-phosphate dehydrogenase (G6PDH) labeled with . benzoylecgonine in buffer with sodium azide (0.09%) as a preservative.

The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. Enzyme activity decreases upon binding to the antibody, and the drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, benzoylecgonine-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when drug is present in the sample, antibody binds to the free drug; the unbound benzovlecgonine-labeled G6PDH then exhibits its maximal enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that can be measured spectrophotometrically at a 340 nm primary wavelength.

The assay has a cutoff of 150 ng/mL benzoylecqonine.

d. Intended Use

The Pointe Scientific Cocaine Metabolite Enzyme Immunoassay is intended for the qualitative determination of benzoylecgonine (a cocaine metabolite) in human urine at a cutoff value of 150 ng/mL. Rx only.

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 or Liquid Chromatograph/Mass Spectrometry (GC/MS or LC/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.

5

e. Comparison to Predicate Device

The chart below illustrates the similarities between the Pointe Scientific Cocaine Metabolite Enzyme Immunoassay and the predicate, Lin-Zhi International (LZI) Cocaine Metabolite Enzyme Immunoassay.

Characteristics	Cocaine Metabolite Enzyme	Lin-Zhi International (LZI)
	Immunoassay (Proposed Device)	K113139 (Predicate Device)
Intended Use	The Pointe Scientific Cocaine Metabolite
Enzyme Immunoassay is intended for the
qualitative determination of
benzoylecgonine (a cocaine metabolite) in
human urine at a cutoff value of 150 ng/mL.
Rx only.	To be used for the qualitative and
semi-quantitative determination of
benzoylecgonine in human urine, at a
cutoff value of 150 ng/mL. This assay
is designed for prescription use with a
number of clinical chemistry analyzers.
	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 or Liquid Chromatograph/Mass
Spectrometry (GC/MS or LC/MS) are the
preferred confirmatory methods. Clinical
consideration and professional judgment
should be exercised with any drug of abuse
test result, particularly when the preliminary
result is positive.	The semi-quantitative mode is for
purposes of (1) enabling laboratories
to determine an appropriate dilution of
the specimen for confirmation by a
confirmatory method such as GCMS or
(2) permitting laboratories to establish
quality control procedures.
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 or Liquid
Chromatograph/Mass Spectrometry
(GC/MS or LC/MS) is the preferred
confirmatory method. Clinical
consideration and professional
judgment should be exercised with any
drug of abuse test result, particularly
when the preliminary result is positive.
Contents	The assay consists of ready-to-use liquid
reagents. Reagent 1 contains a mouse
monoclonal anti-benzoylecgonine antibody,
glucose-6-phosphate (G6P) nicotinamide
adenine dinucleotide (NAD), stabilizers and
sodium azide (0.09%) as a preservative.
Reagent 2 contains glucose-6-phosphate
dehydrogenase (G6PDH) labeled with
benzoylecgonine in buffer with sodium azide
(0.09%) as a preservative	Same
Analyte	Benzoylecgonine	Same
Cutoff	150 ng/mL	Same
Matrix	Urine	Same
Calibrators	2 Levels (0 ng/mL, 150 ng/mL)	5 Levels (0, 75, 150, 300, 1000 ng/mL)
Controls	2 levels (112.5 ng/mL, 187.5 ng/mL)	Same
Storage	2-8°C until expiration date	Same

6

f. Performance Data

Performance was evaluated at the MedTest Dx site on both the Mindray BS-480 and the Mindray BA-800M clinical chemistry analyzers.

Method Comparison Studies

Method comparison studies were performed following CLSI EP-12A2, using remnant urine samples obtained from a third-party biorepository. Results obtained through the Pointe Scientific Cocaine Metabolite Enzyme Immunoassay were compared aqainst results obtained from a fully validated and qualified Agilent 6460 LC/MS. Included below is the precision and accuracy data for the analytical reference method on the Agilent 6460 LC/MS.

When analyzing Benzoylecqonine reference materials from Cerilliant with the reference LC/MS method, the following results were obtained.

Benzoylecgonine Std	Mean (ng/mL)	%CV
Level 1	19.13	5.3
Level 2	25.81	6.5
Level 3	136.13	5.3

Precision

Accuracy

Reference Level	Assigned Value	Recovered Value	% Recovery
Level 1	10 ng/mL	10.70 ng/mL	107.0
Level 2	18.75 ng/mL	20.11 ng/mL	107.2
Level 3	25 ng/mL	25.80 ng/mL	103.2
Level 4	75 ng/mL	69.89 ng/mL	93.2
Level 5	150 ng/mL	149.89 ng/mL	99.9
Level 6	250 ng/mL	274.49 ng/mL	109.7

Traceability

All standards used in the LC/MS methods are certified reference materials obtained from Cerilliant.

BS-480:

114 unaltered clinical urine remnant samples were evaluated on 3 nonconsecutive days by the Pointe Scientific Cocaine Metabolite Enzyme Immunoassay and compared to LC/MS. Results from the qualitative study are presented below.

| Candidate
Device
Results | Negative | 225 ng/mL
by LC/MS |
|--------------------------------|----------|------------------------|-----------------------------|------------------------------|------------------------|
| Positive | 0 | 0 | 1 | 4 | 36 |
| Negative | 56 | 8 | 4 | 5 | 0 |

% Agreement among positives is 88.9% (40/45)

% Agreement among negatives is 98.6% (68/69)

7

Discordant Results

| Cutoff Value | Pointe Scientific Cocaine Metabolite
Enzyme Immunoassay Result | Drug Metabolite LC/MS
Value Result |
|--------------|-------------------------------------------------------------------|---------------------------------------|
| 150 ng/mL | Positive | Negative (102 ng/mL) |
| 150 ng/mL | Negative | Positive (222 ng/mL) |
| 150 ng/mL | Negative | Positive (214 ng/mL) |
| 150 ng/mL | Negative | Positive (156 ng/mL) |
| 150 ng/mL | Negative | Positive (165 ng/mL) |
| 150 ng/mL | Negative | Positive (164 ng/mL) |

BA-800M

114 unaltered clinical urine remnant samples were evaluated on 3 nonconsecutive days by the Pointe Scientific Cocaine Metabolite Enzyme Immunoassay and compared to LC/MS. Results from the qualitative study are presented below.

| Candidate
Device
Results | Negative | 225 ng/mL
by LC/MS |
|--------------------------------|----------|------------------------|-----------------------------|------------------------------|------------------------|
| Positive | 0 | 0 | 1 | 6 | 36 |
| Negative | 56 | 8 | 4 | 3 | 0 |

% Agreement among positives is 93.3% (42/45)

% Agreement among negatives is 98.6% (68/69)

Discordant Results

| Cutoff Value | Pointe Scientific Cocaine Metabolite
Enzyme Immunoassay Result | Drug Metabolite LC/MS
Value Result |
|--------------|-------------------------------------------------------------------|---------------------------------------|
| 150 ng/mL | Positive | Negative (102 ng/mL) |
| 150 ng/mL | Negative | Positive (214 ng/mL) |
| 150 ng/mL | Negative | Positive (156 ng/mL) |
| 150 ng/mL | Negative | Positive (164 ng/mL) |

Precision Studies

Precision studies were conducted in accordance with CLSI EP05-A3. Precision was determined by spiking benzoylecgonine into drug free urine at various concentrations (zero, -75%, -50%, -25%, at the cutoff, 125%, 150%, 175% and 200% of the cutoff). Concentrations were confirmed by LC/MS. Testing for both the with-in run and betweenrun studies were performed by testing each sample in replicate, with two runs per day, for 20 days. The qualitative results are presented below as Positive/Negative.

8

	Within Run		Between Run
Sample
concentration
(ng/mL)	No.
Observations	# Neg/#Pos	No.
Observations	# Neg/#Pos
0 (negative)	20	20/0	80	80/0
37.5 (-75% c/o)	20	20/0	80	80/0
75 (-50% c/o)	20	20/0	80	80/0
112.5 (-25% c/o)	20	20/0	80	80/0
150 (cutoff)	20	19/1	80	68/12
187.5 (+25% c/o)	20	0/20	80	0/80
225 (+50% c/o)	20	0/20	80	0/80
262.5 (+75% c/o)	20	0/20	80	0/80
300 (+100% c/o)	20	0/20	80	0/80

BS-480 Qualitative Results (Pos/Neg):

These results indicate that the Pointe Scientific Cocaine Metabolite Enzyme Immunoassay has acceptable precision on the BS-480.

	Within Run		Between Run
Sample
concentration
(ng/mL)	No.
Observations	# Neg/#Pos	No.
Observations	# Neg/#Pos
0 (negative)	20	20/0	80	80/0
37.5 (-75% c/o)	20	20/0	80	80/0
75 (-50% c/o)	20	20/0	80	80/0
112.5 (-25% c/o)	20	20/0	80	80/0
150 (cutoff)	20	7/13	80	41/39
187.5 (+25% c/o)	20	0/20	80	0/80
225 (+50% c/o)	20	0/20	80	0/80
262.5 (+75% c/o)	20	0/20	80	0/80
300 (+100% c/o)	20	0/20	80	0/80

These results indicate that the Pointe Scientific Cocaine Metabolite Enzyme Immunoassay has acceptable precision on the BA-800M.

Interference (Endogenous Substances) Study

Interference studies were conducted following a modification to CLSI EP07.

The following endogenous compounds were added into drug-free urine, urine sample spiked to 75% of benzoylecgonine and urine spiked to 125% of benzoylecgonine at various concentrations. The substances listed in the table below were determined not to interfere at the concentration shown.

9

To test for possible positive and/or negative interference from pH, urine samples having pH from 3, 4, 5, 6, 7, 8, 9, 10 and 11 were used. Each of these samples were divided into two aliquots for each drug and spiked to 75% of the cutoff and 125% of the cutoff. No positive or negative interference due to pH was observed.

Qualitative results were identical for the BS-480 and BA-800M analyzers.

			Qualitative Result
Interfering
Substances	Spiked
[]
(mg/dL)	0 ng/mL
(Pos/Neg)	112.5 ng/mL
Control
(Pos/Neg)	187.5 ng/mL
Control
(Pos/Neg)
Acetaminophen	10	Neg	Neg	Pos
Acetone	1000	Neg	Neg	Pos
Ascorbic Acid	400	Neg	Neg	Pos
Aspirin	10	Neg	Neg	Pos
Caffeine	10	Neg	Neg	Pos
Creatinine	500	Neg	Neg	Pos
Ethanol	1000	Neg	Neg	Pos
Galactose	10	Neg	Neg	Pos
r-Globulin	500	Neg	Neg	Pos
Glucose	1500	Neg	Neg	Pos
Hemoglobin	300	Neg	Neg	Pos
Human Serum
Albumin	500	Neg	Neg	Pos
Ibuprofen	10	Neg	Neg	Pos
Oxalic Acid	100	Neg	Neg	Pos
Riboflavin	7.5	Neg	Neg	Pos
Sodium Chloride	3000	Neg	Neg	Pos
Urea	2000	Neg	Neg	Pos

BS-480 and BA-800M Interference

To test for possible positive and/or negative interference from pH, urine samples having pH from 3, 4, 5, 6, 7, 8, 9, 10 and 11 were used. Each of these samples were divided into two aliquots for each drug and spiked to 75% of the cutoff and 125% of the cutoff. No positive or negative interference due to pH was observed.

| Interfering pH | Spiked
[]
(mg/dL) | Qualitative Result | | |
|----------------|-------------------------|----------------------|-------------------------------------|-------------------------------------|
| | | 0 ng/mL
(Pos/Neg) | 112.5 ng/mL
Control
(Pos/Neg) | 187.5 ng/mL
Control
(Pos/Neg) |
| pH 3 | --- | Neg | Neg | Pos |
| pH 4 | --- | Neg | Neg | Pos |
| pH 5 | --- | Neg | Neg | Pos |
| pH 6 | --- | Neg | Neg | Pos |

10

| Interfering pH | Spiked
[]
(mg/dL) | Qualitative Result | | |
|----------------|-------------------------|----------------------|-------------------------------------|-------------------------------------|
| | | 0 ng/mL
(Pos/Neg) | 112.5 ng/mL
Control
(Pos/Neg) | 187.5 ng/mL
Control
(Pos/Neg) |
| pH 7 | --- | Neg | Neg | Pos |
| pH 8 | --- | Neg | Neg | Pos |
| pH 9 | --- | Neg | Neg | Pos |
| pH 10 | --- | Neg | Neg | Pos |
| pH 11 | --- | Neg | Neg | Pos |

To test for possible positive and/or negative interference from specific gravity, urine samples having specific gravity ranging from 1.000 g/mL to 1.031 g/mL were used. Each of these samples were divided into three aliquots and two were spiked to 75% of the cutoff and 125% of the cutoff, the third was not spiked. No positive or negative interference due to specific gravity was observed.

| Specific Gravity of
Specimen
(g/mL) | 0 ng/mL
(Pos/Neg) | 112.5 ng/mL Control
(Pos/Neg) | 187.5 ng/mL Control
(Pos/Neg) |
|-------------------------------------------|----------------------|----------------------------------|----------------------------------|
| 1.000 | Neg | Neg | Pos |
| 1.000 | Neg | Neg | Pos |
| 1.004 | Neg | Neg | Pos |
| 1.010 | Neg | Neg | Pos |
| 1.013 | Neg | Neg | Pos |
| 1.017 | Neg | Neg | Pos |
| 1.018 | Neg | Neg | Pos |
| 1.020 | Neg | Neg | Pos |
| 1.021 | Neg | Neg | Pos |
| 1.021 | Neg | Neg | Pos |
| 1.025 | Neg | Neg | Pos |
| 1.031 | Neg | Neg | Pos |

BS-480 Specific Gravity Interference

BA-800M Specific Gravity Interference

| Specific Gravity of
Specimen | Qualitative Result
0 ng/mL
(Pos/Neg) | Qualitative Result
112.5 ng/mL Control
(Pos/Neg) | Qualitative Result
187.5 ng/mL Control
(Pos/Neg) |
|---------------------------------|--------------------------------------------|--------------------------------------------------------|--------------------------------------------------------|
| 1.009 | Neg | Neg | Pos |
| 1.012 | Neg | Neg | Pos |
| 1.017 | Neg | Neg | Pos |
| 1.018 | Neg | Neg | Pos |
| 1.020 | Neg | Neg | Pos |
| 1.020 | Neg | Neg | Pos |
| 1.024 | Neg | Neg | Pos |
| 1.026 | Neg | Neg | Pos |
| 1.029 | Neg | Neg | Pos |

11

Cross Reactivity

Cross-reactivity was established by spiking various concentrations of structurally related and unrelated compounds into drug-free urine. Following a "least burdensome approach", manufacturer studies performed on another analyzer have been referenced after completing proof of principle testing on a subset of structurally and non-structurally related compounds. Right to Reference Letter is located in Appendix F.

Proof of Principle Testing performed on Mindray BA-800M and Mindray BS-480:

| Cross Reactant | Target
Concentration
(ng/mL) | %Cross Reactivity
Calculated based
on Analyzer
Recovered
Concentration | %Cross
Reactivity
Calculated based
on Cutoff
Concentration |
|-----------------|------------------------------------|------------------------------------------------------------------------------------|------------------------------------------------------------------------|
| Benzoylecgonine | 150 | 113.43% | 100.00 % |
| Cocaine | 10,000 | 1.52% | 1.50 % |

BA-800M Structurally Related Compounds

BA-800M Structurally Unrelated Pharmacological Compounds:

| Cross-reactant | Target Concentration
(ng/mL) | % Cross Reactivity |
|----------------|---------------------------------|--------------------|
| Meperidine | 500,000 | 0.00 % |

BS-480 Structurally Related Compounds

| Cross Reactant | Target
Concentration
(ng/mL) | %Cross Reactivity | |
|-----------------|------------------------------------|---------------------------------------------------------------|------------------------------------------------|
| | | Calculated based
on Analyzer
Recovered
Concentration | Calculated based
on Cutoff
Concentration |
| Benzoylecgonine | 150 | 105.37% | 100.00 % |
| Cocaine | 10,000 | 1.62% | 1.50 % |

BS-480 Structurally Unrelated Pharmacological Compounds:

| Cross-reactant | Target Concentration
(ng/mL) | % Cross Reactivity |
|----------------|---------------------------------|--------------------|
| Meperidine | 500,000 | 0.00 % |

Referenced Cross Reactivity Testing on Hitachi 717:

The following tables summarizes the approximate quantity of each compound that is equivalent in assay reactivity to the 150 ng/mL benzoylecgonine cutoff. Results are expressed as a minimum concentration of metabolite or compound required to produce a response approximately equivalent to the cutoff concentration of the assay or the maximal concentration of the compound tested that gave a response with crossreactivity below the cutoff calibrator. The percent cross-reactivity of those compounds are presented below.

12

| Cross-reactant | Target Concentration
(ng/mL) | % Cross Reactivity |
|------------------------|---------------------------------|--------------------|
| Benzoylecgonine | 150 | 96.03 % |
| Benzoylecgonine | 300 | 102.10 % |
| Cocaethylene | 4,000 | 4.58 % |
| Cocaine | 25,000 | 0.62% |
| Ecgonine | 400,000 | 0.03 % |
| Ecgonine, Methyl Ester | 500,000 | 0.00 % |
| Norcocaine | 30,000 | 0.68 % |
| Atropine | 500,000 | 0.00 % |

Structurally Related Cocaine Compound (as found in Appendix F):

Structurally Unrelated Pharmacological Compounds (as found in Appendix F):

| Cross-reactant (ng/mL) | % Cross Reactivity |
|----------------------|-------- | Acetaminophen | 500,000 | Acetylsalicylic Acid | 500,000 | Amobarbital | 500,000 | Amoxicillin | 500,000 | Amphetamine | 500,000 | Bupropion | 500,000 | Captopril | 500,000 | Caffeine | 500,000 | Chlordiazepoxide | 500,000 | Chlorpheniramine | 500,000 | Chlorpomazine | 500,000 | Codeine | 500,000 | Dextromethorphan | 500,000 | Diazepam | 500,000 | Digoxin | 500,000 | Enalapril | 500,000 | Fluoxetine | 100,000 | Glyburide | 500,000 | Ibuprofen | 500,000 | Lidocaine | 500,000 | Meperidine | 500,000 | Methadone | 100,000 | Methamphetamine | 500,000 | Methaqualone | 500,000 | Morphine | 500,000 | Nicodine | 500,000 | Nifedipine | 100,000 | Oxazepam | 100,000 | Phencyclidine | 500,000 | Phenobarbital | 500,000 | Target Concentration
-------------------------|--------------------|
| 0.00 % |
| 0.00 % |
| 0.00 % |
| 0.00 % |
| 0.00 % |
| 0.00 % |
| 0.00 % |
| 0.00 % |
| 0.00 % |
| 0.00 % |
| 0.00 % |
| 0.00 % |
| 0.00 % |
| 0.00 % |
| 0.00 % |
| 0.00 % |
| 0.01 % |
| 0.00 % |
| 0.00 % |
| 0.00 % |
| 0.00 % |
| 0.01 % |
| 0.00 % |
| 0.00 % |
| 0.00 % |
| 0.00 % |
| 0.00 % |
| 0.00 % |
| 0.00 % |
| 0.00 % |

13

| Cross-reactant | Target Concentration
(ng/mL) | % Cross Reactivity |
|------------------|---------------------------------|--------------------|
| Propoxyphene | 100,000 | 0.00 % |
| Ranitidine | 500,000 | 0.00 % |
| Salicyluric acid | 500,000 | 0.00 % |
| Secobarbital | 500,000 | 0.00 % |
| 11-nor- THC-COOH | 500,000 | 0.00 % |
| Valproic Acid | 500,000 | 0.00 % |
| Verapamil | 500,000 | 0.00 % |

Traceability

Two levels of calibrators (0 and 150 ng/mL) and two levels of control material (112.5 ng/mL, 187.5 ng/mL) are available for use with the Pointe Scientific Cocaine Metabolite Enzyme Immunoassay. A commercially available benzoylecgonine standard solution from Cerilliant Analytical Reference Standards is used and traceable to NIST standard. This standard solution is made into a secondary (lower concentration) stock solution. The secondary stock solution is then spiked into the calibrators and controls to the desired concentration. The concentrations are confirmed by GC/MS.

Conclusion

We feel that the enclosed data supports a determination that the Pointe Scientific Cocaine Metabolite Enzyme Immunoassay is substantially equivalent in terms of composition and performance to the product marketed by Lin-Zhi International.