Who is the manufacturer of DRI Cocaine Metabolite Assay?

Microgenics Corporation filed the 510(k) submission for DRI Cocaine Metabolite Assay (K181499).

What is the FDA product code for DRI Cocaine Metabolite Assay?

DIO. It is classified under 21 CFR 862.3250 as a Class 2 device in the Clinical Toxicology panel.

What is the regulatory pathway for DRI Cocaine Metabolite Assay?

510(k) clearance (submission type: Traditional).

Who can help prepare an FDA 510(k) submission like DRI Cocaine Metabolite Assay?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA 510(k) submissions. See https://innolitics.com/services/510ks/ or contact https://innolitics.com/contact.

DRI Cocaine Metabolite Assay

K181499 · Microgenics Corporation · DIO · Jul 6, 2018 · Clinical Toxicology

Device Facts

Record ID	K181499
Device Name	DRI Cocaine Metabolite Assay
Applicant	Microgenics Corporation
Product Code	DIO · Clinical Toxicology
Decision Date	Jul 6, 2018
Decision	SESE
Submission Type	Traditional
Regulation	21 CFR 862.3250
Device Class	Class 2

Intended Use

The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay intended for the qualitative and/or semi-quantitative determination of benzoylecgonine (Cocaine Metabolite) in human urine at a cutoff concentration of either 150 ng/mL or 300 ng/mL. The semi-quantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid Chromatography/tandem mass spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures. The assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography / Mass spectrometry (GC/MS) or Liquid chromatography/ tandem mass spectrometry (LC-MS/MS) is the preferred confirmatory method. Tests for cocaine metabolite cannot distinguish between abused drugs and certain prescribed medications. Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only.

Device Story

DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay for detecting benzoylecgonine in human urine. Input: urine sample; Reagents: mouse monoclonal anti-benzoylecgonine antibody, G6PDH-labeled drug, substrate. Principle: competitive binding between sample drug and labeled drug for antibody sites; free drug allows labeled enzyme to interact with substrate, increasing G6PDH activity. Output: spectrophotometric measurement at 340 nm (NAD to NADH conversion) proportional to drug concentration. Used in clinical laboratories by trained professionals. Results are preliminary; require confirmation via GC/MS or LC-MS/MS. Assists clinicians in identifying potential drug abuse; supports laboratory quality control and specimen dilution for confirmation.

Clinical Evidence

Bench testing only. Precision evaluated per CLSI EP05-A3 (n=80). Accuracy compared to LC-MS/MS (n=100) showed 100% concordance. Specificity and interference studies (CLSI EP07-A2) confirmed no significant cross-reactivity with structurally unrelated compounds or physiological substances (pH, specific gravity, endogenous/exogenous compounds).

Technological Characteristics

Homogeneous enzyme immunoassay; G6PDH-labeled drug competitive binding; spectrophotometric detection at 340 nm. Reagents: mouse monoclonal anti-benzoylecgonine antibody, G6P, NAD, benzoylecgonine analog-labeled G6PDH. Liquid ready-to-use format. Storage: 2-8°C. Analyzed on clinical chemistry analyzers (e.g., Beckman Coulter AU680).

Indications for Use

Indicated for qualitative and/or semi-quantitative determination of benzoylecgonine in human urine for individuals suspected of cocaine use. Intended for use by trained professionals in clinical laboratory settings. Not for distinguishing between abused drugs and certain prescribed medications.

Regulatory Classification

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.

Special Controls

*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).

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Submission Summary (Full Text)

{0}------------------------------------------------ Image /page/0/Picture/0 description: The image contains the logos of the Department of Health and Human Services and the Food and Drug Administration (FDA). The Department of Health and Human Services logo is on the left, and the FDA logo is on the right. The FDA logo is a blue square with the letters "FDA" in white, followed by the words "U.S. Food & Drug Administration" in blue. July 6, 2018 Microgenics Corporation Emily Chien Regulatory Affairs Specialist II 46500 Kato Road Fremont, California 94538 Re: K181499 Trade/Device Name: DRI Cocaine Metabolite Assay Regulation Number: 21 CFR 862.3250 Regulation Name: Cocaine and cocaine metabolite test system Regulatory Class: Class II Product Code: DIO Dated: June 5. 2018 Received: June 7, 2018 Dear Emily Chien: 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. Iisting 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. 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. 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); 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. {1}------------------------------------------------ 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm. For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100). Sincerely, Paula Caposino -S for Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health Enclosure {2}------------------------------------------------ | DEPARTMENT OF HEALTH AND HUMAN SERVICES | | |-------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Food and Drug Administration | | | Indications for Use | | | | Form Approved: OMB No. 0910-0120 | | | Expiration Date: 06/30/2020 | | | See PRA Statement below. | | 510(k) Number ( if known ) | K181499 | | Device Name | DRI Cocaine Metabolite Assay | | Indications for Use (Describe) | The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay intended for the qualitative and/or semi- quantitative determination of benzoylecgonine (Cocaine Metabolite) in human urine at a cutoff concentration of either 150 ng/mL or 300 ng/mL. | | | The semi-quantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid Chromatography/tandem mass spectrometry (LC- MS/MS) or permitting laboratories to establish quality control procedures. | | | The assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography / Mass spectrometry (GC/MS) or Liquid chromatography/ tandem mass spectrometry (LC-MS/MS) is the preferred confirmatory method. Tests for cocaine metabolite cannot distinguish between abused drugs and certain prescribed medications. | | | Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only. | | 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) | CONTINUE ON A SEPARATE PAGE IF NEEDED. This section applies only to requirements of the Paperwork Reduction Act of 1995. ***DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.*** The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to: Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov "An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number." FORM FDA 3881 (7/17) . - {3}------------------------------------------------ # 5. 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: | Microgenics Corporation Thermo Fisher Scientific 46500 Kato Road Fremont, CA 94538 Phone: 510-979-5000 FAX: 510-979-5002 | | Correspondent Contact Information: | Emily Chien Regulatory Affairs Specialist II Email: Emily.Chien@thermofisher.com Phone: 510-979-5000 FAX: 510-979-5002 | | Device Common Name: | Cocaine Metabolite Enzyme Immunoassay | | Trade or Proprietary Name | DRI Cocaine Metabolite Assay | | 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: | Diagnostic Reagents, Inc. | | Predicate Device Premarket Notification #: | K960187 | #### B. Date Summary Prepared July 06, 2018 July 06, 2018 ## C. Description of Device The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay using ready-touse liquid reagents. The assay uses a specific antibody, which can detect benzoylecgonine in urine. The assay is based on the competition of an enzyme glucose-6-phosphate dehydrogenase (G6PDH) labeled drug and the drug from the urine sample for a fixed amount of specific antibody binding sites. In the presence of free drug from the sample, the free drug occupies the antibody binding sites, allowing the drug-labeled G6PDH to interact with the substrate, resulting in enzyme activity. In the absence of drug from the sample, the specific antibody {4}------------------------------------------------ binds to the drug labeled with G6PDH and the enzyme activity is inhibited. This phenomenon creates a direct relationship between the drug concentration in the urine and the enzyme activity. The enzyme G6PDH activity is determined spectrophotometrically at 340 mm by measuring its ability to convert nicotinamide adenine dinucleotide (NAD) to NADH. The assay consists of reagents (A and E). Reagent A: Contains mouse monoclonal anti-benzoylecgonine antibody, glucose-6-phosphate (G6P), and nicotinamide adenine dinucleotide (NAD) in Tris buffer with sodium azide as preservative. Reagent E: Contains benzoylecgonine analog labeled with glucose-6-phosphate dehydrogenase (G6PDH) in HEPES buffer with sodium azide as preservative. #### D. Intended Use The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay intended for the qualitative and/or semi-quantitative determination of benzoylecgonine (Cocaine Metabolite) in human urine at a cutoff concentration of either 150 ng/mL or 300 ng/mL. The semi-quantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid Chromatography/tandem mass spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures. The assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography / Mass spectrometry (GC/MS) or Liquid chromatography/tandem mass spectrometry (LC-MS/MS) is the preferred confirmatory method. Tests for cocaine metabolite cannot distinguish between abused drugs and certain prescribed medications. Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only. {5}------------------------------------------------ # E. Comparison to Predicate Device | Characteristics | Candidate Device: DRI Cocaine Metabolite Assay | Predicate Device: Cocaine Metabolite Enzyme Immunoassay (K960187) | |----------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Intended Use | The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay intended for the qualitative and/or semi- quantitative determination of benzoylecgonine (Cocaine Metabolite) in human urine at a cutoff concentration of either 150 ng/mL or 300 ng/mL. | This homogeneous cocaine metabolite enzyme immunoassay is intended to be used for qualitative and semi-quantitative determination of benzoylecgonine (cocaine metabolite) in human urine with either 300 ng/ml or 150 ng/ml as a cutoff calibrator. | | Operating Principle (Technology) | DRI | Same | | Measured Analyte | Benzoylecgonine | Same | | Test Matrix | Urine | Same | | Cut-off Levels | 150 ng/mL and 300 ng/mL | Same | | Methodology | Homogeneous Enzyme Immunoassay | Same | | Reagents Form | Liquid ready-to-use. | Same | | Antibody | Mouse monoclonal antibodies | Same | | Storage | 2-8 °C until expiration date | Same | | Principal Operator | Trained professionals | Same | | Calibrator Levels for Semi-Quant | 5 point calibrator | 3 point calibrator | # F. Test Principle The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay using ready-touse liquid reagents. The assay uses a specific antibody, which can detect benzoylecgonine in urine. The DRI technology is based on the competition of an enzyme glucose-6-phosphate dehydrogenase (G6PDH) labeled drug and the drug from the urine sample for a fixed amount of specific antibody binding sites. In the presence of free drug from the sample, the free drug occupies the antibody binding sites, allowing the drug-labeled G6PDH to interact with the substrate, resulting in enzyme activity. In the absence of drug from the sample, the specific antibody binds to the drug labeled with G6PDH and the enzyme activity is inhibited. This phenomenon creates a direct relationship between the drug concentration in the urine and the enzyme activity. The enzyme G6PDH activity is determined spectrophotometrically at 340 nm by measuring its ability to convert nicotinamide adenine dinucleotide (NAD) to NADH. {6}------------------------------------------------ #### G. Summary of Supporting Data #### 1. Analytical Performance: Performance is evaluated at the manufacturer's site on the Beckman Coulter AU680 clinical analyzer. #### a) Precision Precision studies were performed in accordance with CLSI Guideline EP05-A3. Samples were prepared by spiking Benzoylecgonine (Cocaine Metabolite) into drug free urine at the cutoff, 25%, 50%, 75% and 100% above and below the cutoff and tested in both qualitative and semi-quantitative modes. Results presented below were generated by testing all samples in replicates of 2, twice per day for 20 days, total n=80. The results for both cutoffs are summarized in the tables below. | Spiked Concentration (ng/mL) | % of Cutoff (150 ng/mL) | Total Precision (n=80) | | |------------------------------------|----------------------------|------------------------|-----------------------------------------------| | | | # of Determinants | Immunoassay Results (Negative/Positive) | | 0 | -100% | 80 | 80/0 | | 37.5 | -75% | 80 | 80/0 | | 75 | -50% | 80 | 80/0 | | 112.5 | -25% | 80 | 80/0 | | 150 | 100% | 80 | 22/58 | | 187.5 | +25% | 80 | 0/80 | | 225 | +50% | 80 | 0/80 | | 262.5 | +75% | 80 | 0/80 | | 300 | +100% | 80 | 0/80 | # Qualitative Study Analysis for 150 ng/mL cutoff #### Qualitative Study Analysis for 300 ng/mL cutoff {7}------------------------------------------------ | Spiked | % of Cutoff (300 ng/mL) | Total Precision (n=80) | | |--------------------------|----------------------------|------------------------|-----------------------------------------------| | Concentration (ng/mL) | | # of Determinants | Immunoassay Results (Negative/Positive) | | 0 | -100% | 80 | 80/0 | | 75 | -75% | 80 | 80/0 | | 150 | -50% | 80 | 80/0 | | 225 | -25% | 80 | 80/0 | | 300 | 100% | 80 | 31/49 | | 375 | +25% | 80 | 0/80 | | 450 | +50% | 80 | 0/80 | | 525 | +75% | 80 | 0/80 | | 600 | +100% | 80 | 0/80 | # Semi-Quantitative Study Analysis for 150 ng/mL cutoff | Spiked | % of Cutoff (150 ng/mL) | Total Precision (n=80) | | |--------------------------|----------------------------|------------------------|-----------------------------------------------| | Concentration (ng/mL) | | # of Determinants | Immunoassay Results (Negative/Positive) | | 0 | -100% | 80 | 80/0 | | 37.5 | -75% | 80 | 80/0 | | 75 | -50% | 80 | 80/0 | | 112.5 | -25% | 80 | 80/0 | | 150 | 100% | 80 | 19/61 | | 187.5 | +25% | 80 | 0/80 | | 225 | +50% | 80 | 0/80 | | 262.5 | +75% | 80 | 0/80 | | 300 | +100% | 80 | 0/80 | # Semi-Quantitative Study Analysis for 300 ng/mL cutoff | Spiked Concentration (ng/mL) | % of Cutoff (150 ng/mL) | Total Precision (n=80) | | |------------------------------------|----------------------------|------------------------|-----------------------------------------------| | | | # of Determinants | Immunoassay Results (Negative/Positive) | | 0 | -100% | 80 | 80/0 | | 75 | -75% | 80 | 80/0 | | 150 | -50% | 80 | 80/0 | | 225 | -25% | 80 | 80/0 | | 300 | 100% | 80 | 22/58 | | 375 | +25% | 80 | 0/80 | {8}------------------------------------------------ | Spiked Concentration (ng/mL) | % of Cutoff (150 ng/mL) | Total Precision (n=80) | | |------------------------------------|----------------------------|------------------------|-----------------------------------------------| | | | # of Determinants | Immunoassay Results (Negative/Positive) | | 450 | +50% | 80 | 0/80 | | 525 | +75% | 80 | 0/80 | | 600 | +100% | 80 | 0/80 | ## b) Spike Recovery The study was performed for 21 replicates. This study was carried out by testing spiked samples containing Benzoylecgonine (Cocaine Metabolite) at the cutoff calibrator and control levels. The spiked samples were prepared by spiking Benzoylecgonine (Cocaine Metabolite) into drug free urine. Samples were tested in both qualitative and semi-quantitative mode. The qualitative results for both cutoffs are summarized in the tables below. | Replicates | 112.5 ng/mL (n=21) | 187.5 ng/mL (n=21) | |-----------------|-----------------------|-----------------------| | 1 | Negative | Positive | | 2 | Negative | Positive | | 3 | Negative | Positive | | 4 | Negative | Positive | | 5 | Negative | Positive | | 6 | Negative | Positive | | 7 | Negative | Positive | | 8 | Negative | Positive | | 9 | Negative | Positive | | 10 | Negative | Positive | | 11 | Negative | Positive | | 12 | Negative | Positive | | 13 | Negative | Positive | | 14 | Negative | Positive | | 15 | Negative | Positive | | 16 | Negative | Positive | | 17 | Negative | Positive | | 18 | Negative | Positive | | 19 | Negative | Positive | | 20 | Negative | Positive | | 21 | Negative | Positive | | Overlap | No | No | | Relative to C/O | All 21 below C/O | All 21 above C/O | # Qualitative Data for 150 ng/mL cutoff {9}------------------------------------------------ | Replicates | 225 ng/mL (n=21) | 375 ng/mL (n=21) | |-----------------|---------------------|---------------------| | 1 | Negative | Positive | | 2 | Negative | Positive | | 3 | Negative | Positive | | 4 | Negative | Positive | | 5 | Negative | Positive | | 6 | Negative | Positive | | 7 | Negative | Positive | | 8 | Negative | Positive | | 9 | Negative | Positive | | 10 | Negative | Positive | | 11 | Negative | Positive | | 12 | Negative | Positive | | 13 | Negative | Positive | | 14 | Negative | Positive | | 15 | Negative | Positive | | 16 | Negative | Positive | | 17 | Negative | Positive | | 18 | Negative | Positive | | 19 | Negative | Positive | | 20 | Negative | Positive | | 21 | Negative | Positive | | Overlap | No | No | | Relative to C/O | All 21 below C/O | All 21 above C/O | # Qualitative Data for 300 ng/mL cutoff # c) Analytical Recovery and Linearity Linearity studies were performed in accordance with CLSI Guideline EP06-A. To demonstrate the dilution linearity for purposes of sample dilution and quality control of the entire assay range, drug free urine was spiked to the high level calibrator using Benzoylecgonine (Cocaine Metabolite) (1000 ng/mL) and diluted with drug free urine to generate 9 intermediate levels. Each sample was run in replicates of five in semi-quantitative mode and the average was used to determine percent recovery compared to the expected target value. The percent recovery is summarized in the table below. | Level | Expected Concentration (ng/mL) | Observed Concentration (ng/mL) | Recovery (%) | |-------|--------------------------------------|--------------------------------------|--------------| | 1 | 0 | 0.6 | N/A | {10}------------------------------------------------ | Level | Expected Concentration (ng/mL) | Observed Concentration (ng/mL) | Recovery (%) | |-------|--------------------------------------|--------------------------------------|--------------| | 2 | 102.5 | 103.6 | 101.1 | | 3 | 205.0 | 213.6 | 104.2 | | 4 | 307.5 | 294.8 | 95.9 | | 5 | 410.0 | 413.8 | 100.9 | | 6 | 512.5 | 510.4 | 99.6 | | 7 | 615.0 | 640.6 | 104.2 | | 8 | 717.5 | 781.4 | 108.9 | | 9 | 820.0 | 880.0 | 107.3 | | 10 | 922.5 | 952.0 | 103.2 | | 11 | 1025.0 | 1025.0 | 100.0 | # d) Method Comparison and Accuracy The method comparison study was performed in accordance with CLSI Guideline EP09-A3. One hundred patient samples were analyzed by the DRI Cocaine Metabolite Assay in both qualitative and semi-quantitative modes and the results were compared to LC-MS/MS. The overall concordance between LC-MS/MS and DRI Cocaine Metabolite Assay is 100%. The qualitative and semi-quantitative results for both cutoffs are summarized in the tables below. # Semi-Quantitative Mode Accuracy study with LC-MS/MS as reference method for 150 ng/mL cutoff | Candidate Device Results | Negative by LC- MS/MS | < 50% of Cutoff concentration by LC-MS/MS (< 75 ng/mL) | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration as determined by LC-MS/MS) (75-149 ng/mL) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration as determined by LC-MS/MS) (150-225 ng/mL) | High Positives (Greater than 50% above cutoff concentration (> 225 ng/mL) | |--------------------------------|-----------------------------|--------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------| | Positive | 0 | 0 | 0 | 6 | 44 | | Negative | 45 | 0 | 5 | 0 | 0 | Agreement among Positives: 50/50 = 100% Agreement among Negative: 50/50 = 100% {11}------------------------------------------------ Semi-Quantitative Mode Accuracy study with LC-MS/MS as reference method for 300 ng/mL cutoff | Candidate Device Results | Negative by LC- MS/MS | < 50% of Cutoff concentration by LC-MS/MS (< 150 ng/mL) | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration as determined by LC-MS/MS) (150-299 ng/mL) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration as determined by LC-MS/MS) (300-450 ng/mL) | High Positives (Greater than 50% above cutoff concentration (> 450 ng/mL) | |--------------------------------|-----------------------------|---------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------| | Positive | 0 | 0 | 0 | 6 | 44 | | Negative | 45 | 0 | 5 | 0 | 0 | Agreement among Positives: 50/50 = 100% Agreement among Negative: 50/50 = 100% # Qualitative Accuracy study with LC-MS/MS as reference method for 150 ng/mL cutoff | Candidate Device Results | Negative by LC- MS/MS | < 50% of Cutoff concentration by LC-MS/MS (< 75 ng/mL) | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration as determined by LC-MS/MS) (75 - 149 ng/mL) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration as determined by LC-MS/MS) (150-225 ng/mL) | High Positives (Greater than 50% above cutoff concentration (> 225 ng/mL) | |--------------------------------|-----------------------------|--------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------| | Positive | 0 | 0 | 0 | 6 | 44 | | Negative | 45 | 0 | 5 | 0 | 0 | Agreement among Positives: 50/50 = 100% Agreement among Negative: 50/50 = 100% Qualitative Accuracy study with LC-MS/MS as reference method for 300 ng/mL cutoff {12}------------------------------------------------ | Candidate Device Results | Negative by LC- MS/MS | < 50% of Cutoff concentration by LC-MS/MS (< 150 ng/mL) | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration as determined by LC-MS/MS) (150-299 ng/mL) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration as determined by LC-MS/MS) (300-450 ng/mL) | High Positives (Greater than 50% above cutoff concentration (> 450 ng/mL) | |--------------------------------|-----------------------------|---------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------| | Positive | 0 | 0 | 0 | 6 | 44 | | Negative | 45 | 0 | 5 | 0 | 0 | Agreement among Positives: 50/50 = 100% Agreement among Negative: 50/50 = 100% # e) Specificity The cross-reactivity of Cocaine and its metabolites were evaluated by adding known amounts of each compound to drug-free negative urine. The results are summarized in the tables below. | Cocaine and metabolites | Tested Concentration (ng/mL) | Cross-reactivity (%) | |--------------------------|---------------------------------|-------------------------| | Benzoylecgonine | 150 | 100 | | Cocaine | 25,000 | 0.6 | | Cocaethylene | 30,000 | 0.5 | | Ecgonine | 90,000 | 0.17 | | Ecgonine Methyl Ester | 100,000 | <0.15 | | m-hydroxybenzoylecgonine | 300 | 50 | | Norcocaine | 100,000 | <0.15 | #### Cross reactivity of Cocaine and its metabolites for 150 ng/mL cut off ## Cross reactivity of Cocaine and its metabolites for 300 ng/mL cut-off | Cocaine and metabolites | Tested Concentration (ng/mL) | Cross-reactivity (%) | |--------------------------|---------------------------------|-------------------------| | Benzoylecgonine | 300 | 100 | | Cocaine | 50,000 | 0.6 | | Cocaethylene | 60,000 | 0.5 | | Ecgonine | 160,000 | 0.19 | | Ecgonine Methyl Ester | 100,000 | <0.3 | | m-hydroxybenzoylecgonine | 600 | 50 | | Norcocaine | 100,000 | <0.3 | Structurally unrelated compounds were evaluated by adding each substance to Benzoylecgonine spiked at 112.5 ng/mL (-25% of the 150 ng/mL cutoff concentration), 187.5 ng/mL (+25% of the 150 {13}------------------------------------------------ ng/mL cutoff concentration), 225 ng/mL (-25% of the 300 ng/mL cutoff concentration) and 375 ng/mL (+25% of the 300 ng/mL cutoff concentration), at the concentrations indicated. As shown in the table below, the controls were detected accurately, low control as negative and the high control as positive, indicating that all the compounds evaluated exhibited no significant cross-reactivity at the concentrations tested. | | Tested Concentration | Spiked Benzoylecgonine Level | | |-------------------------------------|------------------------------------|--------------------------------------|---------------------------------------| | Structurally Unrelated | | Low Control | High Control | | Compounds | (ng/mL) | Positive/ Negative | Positive/ Negative | | 11-nor-Δ9 -THC-COOH | 100,000 | Negative | Positive | | 1R,2S(-)-Ephedrine | 100,000 | Negative | Positive | | 1S,2R(+)-Ephedrine | 100,000 | Negative | Positive | | Acetaminophen | 1,000,000 | Negative | Positive | | Acetylsalicylic acid | 1,000,000 | Negative | Positive | | Acyclovir | 75,000 | Negative | Positive | | Albuterol | 1,000,000 | Negative | Positive | | Amikacin | 1,000,000 | Negative | Positive | | Amitriptyline | 100,000 | Negative | Positive | | Amobarbital | 100,000 | Negative | Positive | | Amoxicillin | 1,000,000 | Negative | Positive | | Amphetamine | 1,000,000 | Negative | Positive | | Azithromycin | 75,000 | Negative | Positive | | Benzocaine | 1,000,000 | Negative | Positive | | Buprenorphine | 100,000 | Negative | Positive | | Bupropion | 100,000 | Negative | Positive | | Caffeine | 100,000 | Negative | Positive | | Calcium Carbonate | 5,000,000 | Negative | Positive | | Carbamazepine | 100,000 | Negative | Positive | | Carisoprodol | 100,000 | Negative | Positive | | Chlorpromazine | 500,000 | Negative | Positive | | Chlorzoxazone | 1,000,000 | Negative | Positive | | cis-Tramadol | 1,000,000 | Negative | Positive | | Clomipramine | 100,000 | Negative | Positive | | Clonidine | 100,000 | Negative | Positive | | Codeine | 1,000,000 | Negative | Positive | | Cotinine | 100,000 | Negative | Positive | | Dapsone | 100,000 | Negative | Positive | | Desipramine | 100,000 | Negative | Positive | | Dextromethorphan | 100,000 | Negative | Positive | | Dihydrocodeine | 100,000 | Negative | Positive | | Diphenhydramine | 1,000,000 | Negative | Positive | | | Tested Concentration (ng/mL) | Spiked Benzoylecgonine Level | | | Structurally Unrelated Compounds | | Low Control Positive/ Negative | High Control Positive/ Negative | | Doxepine | 500,000 | Negative | Positive | | Doxycycline Hyclate | 100,000 | Negative | Positive | | EDDP | 100,000 | Negative | Positive | | Ethyl β-D-glucuronide | 100,000 | Negative | Positive | | Fentanyl | 100,000 | Negative | Positive | | Fluconazole | 100,000 | Negative | Positive | | Fluoxetine | 50,000 | Negative | Positive | | Gabapentin | 100,000 | Negative | Positive | | Gentamicin | 100,000 | Negative | Positive | | Haloperidol | 100,000 | Negative | Positive | | Heroin | 100,000 | Negative | Positive | | Hydrocodone | 100,000 | Negative | Positive | | Hydromorphone | 100,000 | Negative | Positive | | Hydroxyzine | 100,000 | Negative | Positive | | Hyoscyamine HCl | 75,000 | Negative | Positive | | Ibuprofen | 5,000,000 | Negative | Positive | | Imipramine | 100,000 | Negative | Positive | | Indomethacin | 75,000 | Negative | Positive | | Lamotrigine | 1,000,000 | Negative | Positive | | Levofloxacin | 75,000 | Negative | Positive | | Lidocaine | 1,000,000 | Negative | Positive | | Lithium heparin | 5,000,000 | Negative | Positive | | Loratadine | 500,000 | Negative | Positive | | LSD | 100,000 | Negative | Positive | | Maprotiline | 100,000 | Negative | Positive | | Meperidine | 1,000,000 | Negative | Positive | | Mesoridazine | 1,000,000 | Negative | Positive | | Methadone | 1,000,000 | Negative | Positive | | Methamphetamine | 100,000 | Negative | Positive | | Methylphenidate | 100,000 | Negative | Positive | | Metoclopramide | 1,000,000 | Negative | Positive | | Metronidazole | 100,000 | Negative | Positive | | Morphine | 200,000 | Negative | Positive | | Morphine-3β-D-glucuronide | 100,000 | Negative | Positive | | Morphine-6β-D-glucuronide | 100,000 | Negative | Positive | | Nalbuphine | 1,000,000 | Negative | Positive | | Nalorphine | 100,000 | Negative | Positive | | Naloxone | 100,000 | Negative | Positive | | Naltrexone | 1,000,000 | Negative | Positive | | | Spiked Benzoylecgonine Level | | | | Structurally Unrelated Compounds | Tested Concentration (ng/mL) | Low Control Positive/ Negative | High Control Positive/ Negative | | Naproxen | 5,000,000 | Negative | Positive | | Nitrazepam | 100,000 | Negative | Positive | | Norbuprenorphine | 100,000 | Negative | Positive | | Norcodeine | 100,000 | Negative | Positive | | Nordiazepam | 100,000 | Negative | Positive | | Norfluoxetine HCl | 1,000,000 | Negative | Positive | | Norketamine | 100,000 | Negative | Positive | | Norproxyphene | 100,000 | Negative | Positive | | Nortriptyline | 100,000 | Negative | Positive | | Ofloxacin | 100,000 | Negative | Positive | | Omeprazole | 75,000 | Negative | Positive | | Oxazepam | 1,000,000 | Negative | Positive | | Oxycodone | 100,000 | Negative | Positive | | Oxymorphone | 100,000 | Negative | Positive | | Paroxetine | 100,000 | Negative | Positive | | PCP | 1,000,000 | Negative | Positive | | Phenelzine | 75,000 | Negative | Positive | | Phenobarbital | 1,000,000 | Negative | Positive | | Promethazine | 100,000 | Negative | Positive | | Propoxyphene | 750,000 | Negative | Positive | | Ranitidine | 100,000 | Negative | Positive | | Risperidone | 100,000 | Negative | Positive | | Scopolamine | 1,000,000 | Negative | Positive | | Secobarbital | 1,000,000 | Negative | Positive | | Sertraline | 100,000 | Negative | Positive | | Spironolactone | 750,000 | Negative | Positive | | Stavudine | 100,000 | Negative | Positive | | Tapentadol | 100,000 | Negative | Positive | | Terbinafine | 750,000 | Negative | Positive | | Thiopental | 1,000,000 | Negative | Positive | | Thioridazine | 750,000 | Negative | Positive | | Tobramycin | 1,000,000 | Negative | Positive | | Tolmetin | 750,000 | Negative | Positive | | Trazodone | 1,000,000 | Negative | Positive | | Trimethoprim | 1,000,000 | Negative | Positive | | Vancomycin | 1,000,000 | Negative | Positive | | Venlafaxine | 1,000,000 | Negative | Positive | | Verapamil | 100,000 | Negative | Positive | | Zolpidem Tartrate | 100,000 | Negative | Positive | # Structurally unrelated compounds spiked at the concentration listed below into Low and High control urine for 150 ng/mL cut-off {14}------------------------------------------------ {15}------------------------------------------------ {16}------------------------------------------------ | | | Spiked Benzoylecgonine Level | | |-------------------------------------|------------------------------------|--------------------------------------|---------------------------------------| | Structurally Unrelated Compounds | Tested Concentration (ng/mL) | Low Control Positive/ Negative | High Control Positive/ Negative | | 11-nor-Δ 9-THC-COOH | 100,000 | Negative | Positive | | 1R,2S(-)-Ephedrine | 100,000 | Negative | Positive | | 1S,2R(+)-Ephedrine | 100.000 | Negative | Positive | | Acetaminophen | 1,000,000 | Negative | Positive | | Acetylsalicylic acid | 1,000,000 | Negative | Positive | | Acyclovir | 75,000 | Negative | Positive | | Albuterol | 1,000,000 | Negative | Positive | | Amikacin | 1,000,000 | Negative | Positive | | Amitriptyline | 100,000 | Negative | Positive | | Amobarbital | 100,000 | Negative | Positive | | Amoxicillin | 1,000,000 | Negative | Positive | | Amphetamine | 1,000,000 | Negative | Positive | | Azithromycin | 75,000 | Negative | Positive | | Benzocaine | 1,000,000 | Negative | Positive | | Buprenorphine | 100,000 | Negative | Positive | | Bupropion | 100,000 | Negative | Positive | | Caffeine | 100,000 | Negative | Positive | | Calcium Carbonate | 5,000,000 | Negative | Positive | | Carbamazepine | 100,000 | Negative | Positive | | Carisoprodol | 100,000 | Negative | Positive | | Chlorpromazine | 500,000 | Negative | Positive | | Chlorzoxazone | 1,000,000 | Negative | Positive | | cis-Tramadol | 1,000,000 | Negative | Positive | | Clomipramine | 100,000 | Negative | Positive | | Clonidine | 100,000 | Negative | Positive | | Codeine | 1,000,000 | Negative | Positive | | Cotinine | 100,000 | Negative | Positive | | Dapsone | 100,000 | Negative | Positive | | Desipramine | 100,000 | Negative | Positive | | Dextromethorphan | 100,000 | Negative | Positive | | Dihydrocodeine | 100,000 | Negative | Positive | | Diphenhydramine | 1,000,000 | Negative | Positive | | Doxepine | 500,000 | Negative | Positive | | Doxycycline Hyclate | 100,000 | Negative | Positive | | EDDP | 100,000 | Negative | Positive | | Ethyl β-D-glucuronide | 100,000 | Negative | Positive | | Fentanyl | 100,000 | Negative | Positive | | Fluconazole | 100,000 | Negative | Positive | | | | Spiked Benzoylecgonine Level | | | Structurally Unrelated Compounds | Tested Concentration (ng/mL) | Low Control Positive/ Negative | High Control Positive/ Negative | | Fluoxetine | 50,000 | Negative | Positive | | Gabapentin | 100,000 | Negative | Positive | | Gentamicin | 100,000 | Negative | Positive | | Haloperidol | 100,000 | Negative | Positive | | Heroin | 100,000 | Negative | Positive | | Hydrocodone | 100,000 | Negative | Positive | | Hydromorphone | 100,000 | Negative | Positive | | Hydroxyzine | 100,000 | Negative | Positive | | Hyoscyamine HCl | 75,000 | Negative | Positive | | Ibuprofen | 5,000,000 | Negative | Positive | | Imipramine | 100,000 | Negative | Positive…