LogoFDA 510(k) Search
K Number
K150925
Device Name
Immunalysis Benzoylecgonine Urine Enzyme Immunoassay, Immunalysis Benzoylecgonine Urine Calibrators, Immunalysis Benzoylecgonine Urine Control Set
Manufacturer
Immunalysis Corporation
Date Cleared
2015-06-29

(84 days)

Product Code
DIODLJLAS
Regulation Number
862.3250
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP Authorized
Intended Use
The Immunalysis Benzoylecgonine Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a dual cutoff of 150ng/mL and 300ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Benzoylecgonine in human urine with automated clinical chemistry analyzers. This assay is calibrated against Benzoylecgonine. This in-vitro device is for prescription use only. The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as GC-MS or permitting laboratories to establish quality control procedures. The Immunalysis Benzoylecgonine Urine Enzyme Immunoassay Kit provides only a preliminary analytical test result. A more specific alternate chemical must be used in order to obtain a confirmed analytical result. Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography / Mass Spectrometry (LC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used. Immunalysis Benzoylecgonine Urine Calibrators The Immunalysis Benzoylecgonine Urine Calibrators are intended for in vitro diagnostic use for the calibration of assays for the analytes currently listed in the package insert: Benzoylecgonine. The calbrators are designed for prescription use with homogenous enzyme immunoassays on automated clinical chemistry analyzers. Immunalysis Benzoylecgonine Urine Control Set The Immunalysis Benzoylecgonine Urine Control Set is intended for in vitro diagnostic use to monitor the performance of assays for the analyte currently listed in the package insert: Benzoylecgonine. The controls are designed for prescription use with homogenous enzyme immunoassays on automated clinical chemistry analyzers
Device Description
1. The assay consists of antibody/ substrate reagent and enzyme conjugate reagent. The antibody/ substrate reagent includes polyclonal sheep antibodies to Benzoylecgonine, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in HEPES buffer with Sodium Azide as a preservative. The enzyme conjugate reagent includes Benzoylecgonine derivative labeled with glucose-6-phosphate dehydrogenase (G6PDH) in HEPES buffer with Sodium Azide as a preservative. 2. All of the Immunalysis Benzoylecgonine Urine Calibrators and Controls are liquid and ready to use. Each contains a known concentration of a specific drug analyte as a mixture. The negative calibrator is a processed, drug-free synthetic urine matrix with sodium azide as a preservative. The Level 1, 2, 3 and 4 calibrators, as well as the LOW Control 1, HIGH Control 1, LOW Control 2 and HIGH Control 2 are prepared by spiking known concentrations of benzoylecgonine into the negative calibrator matrix. These five calibrators and four controls are sold as individual bottles.
More Information

K113751

Not Found

No
The device description and performance studies focus on a standard enzyme immunoassay and its analytical performance characteristics. There is no mention of AI or ML in the intended use, device description, or performance studies.

No.
This device is an in-vitro diagnostic assay intended for the qualitative and semi-quantitative analysis of Benzoylecgonine in human urine, used for laboratory testing and not for treating a disease or condition.

Yes

This device is an in-vitro diagnostic device intended for the qualitative and semi-quantitative analysis of Benzoylecgonine in human urine. It provides preliminary analytical test results for drug screening, which falls under the purview of diagnostics.

No

The device is an in-vitro diagnostic (IVD) kit consisting of reagents (antibody/substrate and enzyme conjugate) and calibrators/controls, which are physical components used in a laboratory setting with automated clinical chemistry analyzers. It is not solely software.

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

The "Intended Use / Indications for Use" section explicitly states:

  • "This in-vitro device is for prescription use only."
  • "The Immunalysis Benzoylecgonine Urine Calibrators are intended for in vitro diagnostic use..."
  • "The Immunalysis Benzoylecgonine Urine Control Set is intended for in vitro diagnostic use..."

These statements clearly indicate that the device is intended for use in vitro (outside of the body) for diagnostic purposes.

N/A

Intended Use / Indications for Use

Immunalysis Benzoylecgonine Urine Enzyme Immunoassay: The Immunalysis Benzoylecgonine Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a dual cutoff of 150ng/mL and 300ns/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Benzoylecgonine in human urine with automated clinical chemistry analyzers. This assay is calibrated against Benzovlecgonine. This in-vitro device is for prescription use only.

The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as GC-MS or permitting laboratories to establish quality control procedures.

The Immunalysis Benzoylecgonine Urine Enzyme Immunoassay Kit provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography / Mass Spectrometry (LC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

Immunalysis Benzoylecgonine Urine Calibrators: The Immunalysis Benzovlecgonine Urine Calibrators are intended for in vitro diagnostic use for the calibration of assays for the analytes currently listed in the package insert: Benzoylecgonine. The calibrators are designed for prescription use with homogenous enzyme immunoassays on automated clinical chemistry analyzers.

Immunalysis Benzoylecgonine Urine Control Set: The Immunalysis Benzoylecgonine Control Set is intended for in vitro diagnostic use to monitor the performance of assays for the analytes currently listed in the package insert: Benzoylecgonine. The controls are designed for prescription use with homogenous enzyme immunoassays on automated clinical chemistry analyzers

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

DIO, DLJ, LAS

Device Description

  1. The assay consists of antibody/ substrate reagent and enzyme conjugate reagent. The antibody/ substrate reagent includes polyclonal sheep antibodies to Benzoylecgonine, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in HEPES buffer with Sodium Azide as a preservative. The enzyme conjugate reagent includes Benzoylecgonine derivative labeled with glucose-6-phosphate dehydrogenase (G6PDH) in HEPES buffer with Sodium Azide as a preservative.
  2. All of the Immunalysis Benzoylecgonine Urine Calibrators and Controls are liquid and ready to use. Each contains a known concentration of a specific drug analyte as a mixture.

The negative calibrator is a processed, drug-free synthetic urine matrix with sodium azide as a preservative. The Level 1, 2, 3 and 4 calibrators, as well as the LOW Control 1, HIGH Control 1, LOW Control 2 and HIGH Control 2 are prepared by spiking known concentrations of benzoylecgonine into the negative calibrator matrix. These five calibrators and four controls are sold as individual bottles. The concentration of benzoylecgonine in their corresponding calibrators and controls are summarized as follows:

Analyte: Benzoylecgonine Urine Calibrators
Negative: 0ng/mL
Level 1: 150ng/mL
Level 2: 300ng/mL
Level 3: 500ng/mL
Level 4: 1000ng/mL

Analyte: Benzoylecgonine Urine Control Set
LOW Control 1: 112.5ng/mL
HIGH Control 1: 187.5ng/mL
LOW Control 2: 225ng/mL
HIGH Control 2: 375ng/mL

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

laboratories, prescription use only

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

Not Found

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

  1. Precision/ Cutoff Characterization/ Reproducibility:

    • Study Type: Precision/Cutoff Characterization.
    • Sample Size: N=80 determinations for each concentration level.
    • Key Results:
      • For 150ng/mL cutoff: 80 Negative results for concentrations 0, 37.5, 75, 112.5 ng/mL. At 150ng/mL (cutoff), 36 Negative / 44 Positive. 80 Positive results for 187.5, 225, 262.5, 300 ng/mL.
      • For 300ng/mL cutoff: 80 Negative results for concentrations 0, 75, 150, 225 ng/mL. At 300ng/mL (cutoff), 37 Neg / 43 Pos. 80 Positive results for 375, 450, 525, 600 ng/mL.
      • Semi-quantitative analysis results also presented for both cutoffs, showing similar trends with different splits at the cutoff.

  2. Specificity and Cross-Reactivity:

    • Study Type: Evaluated structurally similar compounds.
    • Key Results:
      • At 150ng/mL cutoff: Benzoylecgonine and m-Hydroxybenzoylecgonine showed 100.00% cross-reactivity (POS). Cocaine at 100,000ng/mL showed 0.15% cross-reactivity (POS). Ecgonine at 59,000ng/mL showed 0.25% cross-reactivity (POS). Ecgonine Methyl Ester, Cocaethylene, Norcocaine showed N.D. (NEG).
      • At 300ng/mL cutoff: Benzoylecgonine and m-Hydroxybenzoylecgonine showed 100.00% cross-reactivity (POS). Cocaine, Ecgonine, Ecgonine Methyl Ester, Cocaethylene, Norcocaine showed N.D. (NEG).
      • Semi-quantitative results were consistent with qualitative results for both cutoffs.

  3. Interference:

    • Study Type: Evaluated structurally non-similar compounds, endogenous compounds, effect of pH, and effect of specific gravity.
    • Key Results:
      • Structurally Non-Similar Compounds: No interference was observed for a wide range of common compounds and drugs tested at both -25% and +25% of the 150ng/mL and 300ng/mL cutoffs.
      • Endogenous Compounds: No interference was observed for a variety of endogenous compounds (e.g., Acetone, Ascorbic Acid, Bilirubin, Creatinine, Ethanol, Glucose, Hemoglobin, Urea) at both -25% and +25% of the 150ng/mL and 300ng/mL cutoffs.
      • Boric Acid: Boric Acid at 1% w/v showed no interference at -25% cutoff, but showed interference (Negative result) at +25% cutoff for both 150ng/mL and 300ng/mL cutoffs. Limitation added to labeling.
      • Effect of pH: No interference was observed across pH values from 3.0 to 11.0 at both -25% and +25% of the 150ng/mL and 300ng/mL cutoffs.
      • Effect of Specific Gravity: No interference was observed across specific gravity values from 1.000 to 1.030 at both -25% and +25% of the 150ng/mL and 300ng/mL cutoffs.

  4. Linearity/ Recovery:

    • Study Type: Linearity/Recovery evaluation.
    • Key Results: Recovery percentages ranged from 91.2% to 108.6% across expected concentrations from 100 ng/mL to 1100 ng/mL.

  5. Method Comparison:

    • Study Type: Comparison with LC/MS Confirmation.
    • Sample Size: Unaltered, anonymous and discarded clinical urine samples (number not explicitly stated but implied by positive/negative counts, e.g., 40 positive and 40 negative samples).
    • Key Results:
      • Qualitative (150ng/mL cutoff):
        • Test Device (+) / LC/MS (+): 40
        • Test Device (+) / LC/MS (-): 1 (Sample contained 124ng/mL Benzoylecgonine by LC-MS/MS)
        • Test Device (-) / LC/MS (+): 0
        • Test Device (-) / LC/MS (-): 39
        • Overall Agreement: 98% for positive, 100% for negative.
      • Qualitative (300ng/mL cutoff):
        • Test Device (+) / LC/MS (+): 40
        • Test Device (+) / LC/MS (-): 0
        • Test Device (-) / LC/MS (+): 0
        • Test Device (-) / LC/MS (-): 40
        • Overall Agreement: 100% for both positive and negative.
      • Semi-Quantitative (150ng/mL cutoff): Results for positive and negative agreement matched the qualitative results for the 150ng/mL cutoff.
      • Semi-Quantitative (300ng/mL cutoff): Results for positive and negative agreement matched the qualitative results for the 300ng/mL cutoff.

  6. Calibrator and Control Analytical Performance:

    • Study Type: Traceability and Stability studies.
    • Key Results:
      • Traceability: All components traced to a commercially available standard solution.
      • Stability (Closed vial): Supported an initial expiration date of 12 months at 25°C.
      • Stability (Open vial): Supported an initial open vial expiration date of 60 days at 5°C.
      • Value Assignment: Calibrators and controls are manufactured and tested by mass spectrometry, adjusted if not within acceptable range.

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

Qualitative Assay Performance (150ng/mL Cutoff):
Agreement (%): Positive 98%, Negative 100%

Qualitative Assay Performance (300ng/mL Cutoff):
Agreement (%): Positive 100%, Negative 100%

Semi-Quantitative Assay Performance (150ng/mL Cutoff):
Agreement (%): Positive 98%, Negative 100%

Semi-Quantitative Assay Performance (300ng/mL Cutoff):
Agreement (%): Positive 100%, Negative 100%

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.

K113751

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

§ 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).

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

June 29, 2015

IMMUNALYSIS CORPORATION JOSEPH GINETE REGULATORY AFFAIRS SPECIALIST II 829 TOWNE CENTER DRIVE POMONA CA 91767

Re: K150925

Trade/Device Name: Immunalysis Benzoylecgonine Urine Enzyme Immunoassay, Immunalysis Benzoylecgonine Urine Calibrators, Immunalysis Benzoylecgonine Urine Control Set Regulation Number: 21 CFR 862.3250 Regulation Name: Cocaine and cocaine metabolite test system Regulatory Class: II Product Code: DIO, DLJ, LAS Dated: April 2, 2015 Received: April 6, 2015

Dear Joseph Ginete:

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. 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the

1

electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Katherine Serrano -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

Indications for Use

510(k) Number (if known) K150925

Device Name

Immunalysis Benzoylecgonine Urine Enzyme Immunoassay Immunalysis Benzoylecgonine Urine Calibrators Immunalysis Benzoylecgonine Urine Control Set

Indications for Use (Describe)

Immunalysis Benzoylecgonine Urine Enzyme Immunoassay

The Immunalysis Benzoylecgonine Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a dual cutoff of 150ng/mL and 300ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Benzoylecgonine in human urine with automated clinical chemistry analyzers. This assay is calibrated against Benzoylecgonine. This in-vitro device is for prescription use only.

The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as GC-MS or permitting laboratories to establish quality control procedures.

The Immunalysis Benzoylecgonine Urine Enzyme Immunoassay Kit provides only a preliminary analytical test result. A more specific alternate chemical must be used in order to obtain a confirmed analytical result. Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography / Mass Spectrometry (LC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

Immunalysis Benzoylecgonine Urine Calibrators

The Immunalysis Benzoylecgonine Urine Calibrators are intended for in vitro diagnostic use for the calibration of assays for the analytes currently listed in the package insert: Benzoylecgonine. The calbrators are designed for prescription use with homogenous enzyme immunoassays on automated clinical chemistry analyzers.

Immunalysis Benzoylecgonine Urine Control Set

The Immunalysis Benzoylecgonine Urine Control Set is intended for in vitro diagnostic use to monitor the performance of assays for the analyte currently listed in the package insert: Benzoylecgonine. The controls are designed for prescription use with homogenous enzyme immunoassays on automated clinical chemistry analyzers

Type of Use (Select one or both, as applicable)
-------------------------------------------------
ü 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 summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92(c).

  • A. Contact Information
1. Manufacturer:Immunalysis Corporation
2. Contact Name:Joseph Ginete
3. Contact Title:Regulatory Affairs Specialist II
4. Address:829 Towne Center Drive Pomona, CA 91767
5. Phone:(909) 482-0840
6. Fax:(909) 482-0850
7. Email:jginete@immunalysis.com
8. Summary prepared on:June 26, 2015
  • B. Device Information

| 1. Trade Name: | Immunalysis Benzoylecgonine Urine Enzyme Immunoassay
Immunalysis Benzoylecgonine Urine Calibrators
Immunalysis Benzoylecgonine Urine Control Set |
|--------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 2. Common Name: | Immunalysis Benzoylecgonine Urine Enzyme Immunoassay
Immunalysis Benzoylecgonine Urine Calibrators
Immunalysis Benzoylecgonine Urine Control Set |
| C. Regulatory Information | |
| 1. Device Classification: | II |
| 2. Regulation Number: | 21 CFR862.3250 Cocaine and Cocaine Metabolite System
21 CFR 862.3200 Clinical Toxicology Calibrator
21 CFR 862.3280 Clinical Toxicology Control Material |
| 3. Panel: | Toxicology(91) |
| 4. Product Code: | DIO
DLJ
LAS |
| D. Legally Marketed Device to Which We are Claiming Equivalence (807.92(A)(3)) | |

| 1. Predicate Devices: | Randox Cocaine Metabolite Assay
Randox Multidrug Calibrator Set
Randox Multidrug Controls, Level 1 and 2 |
|------------------------|----------------------------------------------------------------------------------------------------------------|
| 2. Predicate Company: | Randox Laboratories, Ltd. |
| 3. Predicate K Number: | K113751 |

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  • E. Device Descriptions
      1. The assay consists of antibody/ substrate reagent and enzyme conjugate reagent. The antibody/ substrate reagent includes polyclonal sheep antibodies to Benzoylecgonine, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in HEPES buffer with Sodium Azide as a preservative. The enzyme conjugate reagent includes Benzoylecgonine derivative labeled with glucose-6-phosphate dehydrogenase (G6PDH) in HEPES buffer with Sodium Azide as a preservative.
      1. All of the Immunalysis Benzoylecgonine Urine Calibrators and Controls are liquid and ready to use. Each contains a known concentration of a specific drug analyte as a mixture.

The negative calibrator is a processed, drug-free synthetic urine matrix with sodium azide as a preservative. The Level 1, 2, 3 and 4 calibrators, as well as the LOW Control 1, HIGH Control 1, LOW Control 2 and HIGH Control 2 are prepared by spiking known concentrations of benzoylecgonine into the negative calibrator matrix. These five calibrators and four controls are sold as individual bottles. The concentration of benzoylecgonine in their corresponding calibrators and controls are summarized as follows:

AnalyteBenzoylecgonine Urine Calibrators
NegativeLevel 1Level 2Level 3Level 4
0ng/mL150ng/mL300ng/mL500ng/mL1000ng/mL
BenzoylecgonineBenzoylecgonine Urine Control Set
LOW Control 1HIGH Control 1LOW Control 2HIGH Control 2
112.5ng/mL187.5ng/mL225ng/mL375ng/mL

F. Intended Use

    1. Immunalysis Benzoylecgonine Urine Enzyme Immunoassay: The Immunalysis Benzoylecgonine Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a dual cutoff of 150ng/mL and 300ns/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Benzoylecgonine in human urine with automated clinical chemistry analyzers. This assay is calibrated against Benzovlecgonine. This in-vitro device is for prescription use only.
      The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as GC-MS or permitting laboratories to establish quality control procedures.

The Immunalysis Benzoylecgonine Urine Enzyme Immunoassay Kit provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography / Mass Spectrometry (LC/MS) is the preferred confirmatory method. Clinical

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consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

    1. Immunalysis Benzoylecgonine Urine Calibrators:
      The Immunalysis Benzovlecgonine Urine Calibrators are intended for in vitro diagnostic use for the calibration of assays for the analytes currently listed in the package insert: Benzoylecgonine. The calibrators are designed for prescription use with homogenous enzyme immunoassays on automated clinical chemistry analyzers.
    1. Immunalysis Benzoylecgonine Urine Control Set: The Immunalysis Benzoylecgonine Control Set is intended for in vitro diagnostic use to monitor the performance of assays for the analytes currently listed in the package insert: Benzoylecgonine. The controls are designed for prescription use with homogenous enzyme immunoassays on automated clinical chemistry analyzers

| Item | Cocaine Metabolite Assay K113751 | Immunalysis Benzoylecgonine Urine
EIA |
|-----------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | For the qualitative and semi-
quantitative determination of the presence of
benzoylecgonine in human urine at a cutoff of
300ng/mL | For the qualitative and semi-
quantitative determination of the
presence of benzoylecgonine in human
urine at a cutoff of
150ng/mL and 300ng/mL |
| Type of Product | Analytical Reagents | Same |
| Test Matrix | Urine | Same |
| Cutoff Levels | 300 ng/mL of Benzoylecgonine | 150 ng/mL and 300 ng/mL of
Benzoylecgonine |
| Test System | Homogeneous Enzyme
Immunoassay | Same |
| Materials | Liquid Ready-to-Use Two Reagent
Assay | Antibody/Substrate Reagents and
Enzyme |
| Antibody | Mouse Monoclonal antibodies to
Benzoylecgonine | Polyclonal Sheep antibody to
Benzoylecgonine |
| Storage | 2 - 8°C until expiration date | Same |
| Calibrator and
Control Matrix | Urine | Same |
| Calibrator
Levels | Five levels
0, 150, 300, 500, and 1000 ng/mL | Five levels
0, 150, 300, 500, and 1000 ng/mL |
| Control Levels | Two levels
225 and 375 ng/mL | Four levels
112.5, 187.5, 225, and 375
ng/mL |
| Calibrator and
Control Storage | 2 – 8 °C until expiration date | Same |

G. Comparison of the new device with the predicate device

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IMMUNALYSIS

  • H. The following laboratory performance studies were performed to determine substantial equivalence of the Immunalysis Benzoylecgonine Urine Enzyme Immunoassay to the predicate
      1. Precision/ Cutoff Characterization/ Reproducibility Precision/Cutoff Characterization - Study was performed for 20 days, 2 runs per day in duplicate (N=80) on concentration of ±25%, ±50%, ±75%, and ±100% of the cutoff. The study verified that the cutoff serves as a boundary between a negative and positive interpretation of a qualitative result. In addition, it also verified that product performance relative to the ability of the device to produce the same value during repeated measurements. The instruments used for this was Beckman Coulter AU 400e.
Concentration (ng/mL)% of cutoff# of determinationsResult
0-100%8080 Negative
37.5-75%8080 Negative
75-50%8080 Negative
112.5-25%8080 Negative
150Cutoff8036 Neg / 44 Pos
187.5+25%8080 Positive
225+50%8080 Positive
262.5+75%8080 Positive
300+100%8080 Positive
  • a. The following is a summary table of the Qualitative Analysis for the 150ng/mI_cutoff test data
  • b. The following is a summary table of the Qualitative Analysis for the 300ng/mL cutoff test data results.
Table 3 - Qualitative Analysis (for 300 ng/mL cutoff)
Concentration (ng/mL)% of cutoff# of determinationsResult
0-100%8080 Negative
75-75%8080 Negative
150-50%8080 Negative
225-25%8080 Negative
300Cutoff8037 Neg / 43 Pos
375+25%8080 Positive
450+50%8080 Positive
525+75%8080 Positive
600+100%8080 Positive

c. The following is a summary table of the Semi-Quantitative Analysis for the 150ng/mL cutoff test data results.

Table 4 - Semi-Quantitative Analysis (for 150ng/mL cutoff)
Concentration (ng/mL)% of cutoff# of determinationsResult
0-100%8080 Negative
37.5-75%8080 Negative
75-50%8080 Negative
112.5-25%8080 Negative

7

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Table 4 - Semi-Quantitative Analysis (for 150ng/mL cutoff)
Concentration (ng/mL)% of cutoff# of determinationsResult
150Cutoff8025 Neg / 55 Pos
187.5+25%8080 Positive
225+50%8080 Positive
262.5+75%8080 Positive
300+100%8080 Positive

d. The following is a summary table of the Semi-Quantitative Analysis for the 300ng/mL cutoff test data results.

Table 5 - Semi-Quantitative Analysis (for 300ng/mL cutoff)
Concentration (ng/mL)% of cutoff# of determinationsResult
0-100%8080 Negative
75-75%8080 Negative
150-50%8080 Negative
225-25%8080 Negative
300Cutoff8024 Neg / 56 Pos
375+25%8080 Positive
450+50%8080 Positive
525+75%8080 Positive
600+100%8080 Positive
  1. Specificity and Cross-Reactivity - Structurally similar compounds were spiked into drug free urine at levels that will yield a result that is equivalent to the cutoffs. The study verified assay performance relative to the ability of the device to exclusively determine certain drugs. The instrument used for this test was a Beckman Coulter AU 400e.

a. The qualitative result summary table for the 150ng/mL cutoff is outlined below:

Table 6 - Structurally Related Compounds (for 150 ng/mL cutoff) - Qualitative
CompoundConcentration Tested (ng/mL)ResultCross-Reactivity (%)
Benzoylecgonine150POS100.00
m-Hydroxybenzoylecgonine150POS100.00
Cocaine100,000POS0.15
Ecgonine59,000POS0.25
Ecgonine Methyl Ester100,000NEGN.D.
Cocaethylene100,000NEGN.D.
Norcocaine100,000NEGN.D.

b. The qualitative result summary table for the 300ng/mL cutoff is outlined below:

Table 7 - Structurally Related Compounds (for 300 ng/mL cutoff) - Qualitative
CompoundConcentration Tested (ng/mL)ResultCross-Reactivity (%)
Benzoylecgonine300POS100.00
m-Hydroxybenzoylecgonine300POS100.00
Cocaine100,000NEGN.D.
Ecgonine100,000NEGN.D.
Ecgonine Methyl Ester100,000NEGN.D.
Cocaethylene100,000NEGN.D.

8

IMMUNALY

Table 7 - Structurally Related Compounds (for 300 ng/mL cutoff) - Qualitative
CompoundConcentration Tested (ng/mL) Result Cross-Reactivity (%)
Norcocaine100,000NEGN.D.
c. The semi-quantitative result summary table for the 150ng/mL cutoff is

-Qualifi outlined below:

Table 8 - Structurally Related Compounds (for 150ng/mL cutoff) – Semi-Quantitative
CompoundConcentration Tested (ng/mL)ResultCross-Reactivity (%)
Benzoylecgonine150POS100.00
m-Hydroxybenzoylecgonine150POS100.00
Cocaine100,000POS0.15
Ecgonine59,000POS0.25
Ecgonine Methyl Ester100,000NEGN.D.
Cocaethylene100,000NEGN.D.
Norcocaine100,000NEGN.D.

d. The semi-quantitative result summary table for the 300ng/mL cutoff is outlined below:

Table 9 - Structurally Related Compounds (for 300ng/mL cutoff) – Semi-Quantitative
CompoundConcentration Tested (ng/mL)ResultCross-Reactivity (%)
Benzoylecgonine300POS100.00
m-Hydroxybenzoylecgonine300POS100.00
Cocaine100,000NEGN.D.
Ecgonine100,000NEGN.D.
Ecgonine Methyl Ester100,000NEGN.D.
Cocaethylene100,000NEGN.D.
Norcocaine100,000NEGN.D.
    1. Interference Structurally non-similar compounds, endogenous compounds, the effect of pH and the effect of specific gravity was evaluated by spiking the potential interferent into drug free urine containing the target analyte at ±25% of the cutoff. All potential interferents analyzed verified that assay performance is unaffected by externally ingested compounds or an internally existing physiological condition. The instrument used for this test was a Beckman Coulter AU 400e.
    • a. The following is a table of the structurally non-similar compounds for the 150ng/mL cutoff:
Table 10 - Structurally Non-Similar Compounds (for 150ng/mL cutoff)
CompoundConcentration
Tested
(ng/mL)-25% Cutoff
(112.5ng/mL)+25% Cutoff
(187.5ng/mL)
ResultInterference?ResultInterference?
4-Bromo-
2,5,Dimethoxyphenethylamine100,000NegativeNoPositiveNo
6-Acetylcodeine100,000NegativeNoPositiveNo
6-Acetylmorphine100,000NegativeNoPositiveNo
7-Aminoclonazepam100,000NegativeNoPositiveNo
7-Aminoflunitrazepam100,000NegativeNoPositiveNo
7-Aminonitrazepam100,000NegativeNoPositiveNo
11-hydroxy-delta-9-THC100,000NegativeNoPositiveNo
Table 10 - Structurally Non-Similar Compounds (for 150ng/mL cutoff)
Concentration-25% Cutoff+25% Cutoff
CompoundTested(112.5ng/mL)(187.5ng/mL)
(ng/mL)ResultInterference?ResultInterference?
11-nor-9 carboxy-delta-THC100,000NegativeNoPositiveNo
Acetaminophen500,000NegativeNoPositiveNo
Acetylsalicylic Acid500,000NegativeNoPositiveNo
Alprazolam100,000NegativeNoPositiveNo
Amitriptyline100,000NegativeNoPositiveNo
Amobarbital100,000NegativeNoPositiveNo
S-(+) Amphetamine100,000NegativeNoPositiveNo
Benzylpiperazine100,000NegativeNoPositiveNo
Bromazepam100,000NegativeNoPositiveNo
Buprenorphine100,000NegativeNoPositiveNo
Bupropion100,000NegativeNoPositiveNo
Butabarbital100,000NegativeNoPositiveNo
Butalbital100,000NegativeNoPositiveNo
Caffeine500,000NegativeNoPositiveNo
Cannabidiol100,000NegativeNoPositiveNo
Cannabinol100,000NegativeNoPositiveNo
Carbamazeprine100,000NegativeNoPositiveNo
Carisoprodol100,000NegativeNoPositiveNo
Chlordiazepoxide100,000NegativeNoPositiveNo
Chlorpromazine100,000NegativeNoPositiveNo
cis-Tramadol100,000NegativeNoPositiveNo
Clobazam100,000NegativeNoPositiveNo
Clomipramine100,000NegativeNoPositiveNo
Clonazepam100,000NegativeNoPositiveNo
Clozapine100,000NegativeNoPositiveNo
Codeine100,000NegativeNoPositiveNo
Cotinine100,000NegativeNoPositiveNo
Cyclobenzaprine100,000NegativeNoPositiveNo
Dehydronorketamine100,000NegativeNoPositiveNo
Delta-9-THC100,000NegativeNoPositiveNo
Demoxepam100,000NegativeNoPositiveNo
Desakylflurazepam100,000NegativeNoPositiveNo
Desipramine100,000NegativeNoPositiveNo
Dextromethorphan100,000NegativeNoPositiveNo
Diazepam100,000NegativeNoPositiveNo
Digoxin100,000NegativeNoPositiveNo
Dihydrocodeine100,000NegativeNoPositiveNo
Diphenhydramine500,000NegativeNoPositiveNo
Doxepin100,000NegativeNoPositiveNo
EDDP100,000NegativeNoPositiveNo
1R,2S(-)-Ephedrine100,000NegativeNoPositiveNo
1S,2R(+)-Ephedrine100,000NegativeNoPositiveNo
Ethyl B D glucuronide100,000NegativeNoPositiveNo
Table 10 - Structurally Non-Similar Compounds (for 150ng/mL cutoff)
Concentration-25% Cutoff+25% Cutoff
CompoundTested(112.5ng/mL)(187.5ng/mL)
(ng/mL)ResultInterference?ResultInterference?
Ethylmorphine100,000NegativeNoPositiveNo
Fenfluramine100,000NegativeNoPositiveNo
Fentanyl100,000NegativeNoPositiveNo
Flunitrazepam100,000NegativeNoPositiveNo
Fluoxetine100,000NegativeNoPositiveNo
Flurazepam100,000NegativeNoPositiveNo
Haloperidol100,000NegativeNoPositiveNo
Heroin100,000NegativeNoPositiveNo
Hexobarbital100,000NegativeNoPositiveNo
Hydrocodone100,000NegativeNoPositiveNo
Hydromorphone100,000NegativeNoPositiveNo
Ibuprofen500,000NegativeNoPositiveNo
Imipramine100,000NegativeNoPositiveNo
Ketamine100,000NegativeNoPositiveNo
Lamotrignine100,000NegativeNoPositiveNo
Levorphanol Tartrate100,000NegativeNoPositiveNo
Lidocaine100,000NegativeNoPositiveNo
Lorazepam100,000NegativeNoPositiveNo
Lorazepam Glucuronide50,000NegativeNoPositiveNo
Lormetazepam100,000NegativeNoPositiveNo
LSD100,000NegativeNoPositiveNo
Maprotiline100,000NegativeNoPositiveNo
MDA100,000NegativeNoPositiveNo
MDEA100,000NegativeNoPositiveNo
MDMA100,000NegativeNoPositiveNo
Meperidine100,000NegativeNoPositiveNo
Meprobamate100,000NegativeNoPositiveNo
Methadone100,000NegativeNoPositiveNo
Methamphetamine100,000NegativeNoPositiveNo
Methaquolone100,000NegativeNoPositiveNo
Methoxetamine100,000NegativeNoPositiveNo
Methylone100,000NegativeNoPositiveNo
Methylphenidate100,000NegativeNoPositiveNo
Midazolam100,000NegativeNoPositiveNo
Morphine100,000NegativeNoPositiveNo
Morphine 3-D-glucuronide100,000NegativeNoPositiveNo
Morphine 6-D-glucuronide50,000NegativeNoPositiveNo
Nalorphine100,000NegativeNoPositiveNo
Naloxone100,000NegativeNoPositiveNo
Naltrexone100,000NegativeNoPositiveNo
Naproxen100,000NegativeNoPositiveNo
N-desmethyltapentadol100,000NegativeNoPositiveNo
Nitrazepam100,000NegativeNoPositiveNo
Table 10 - Structurally Non-Similar Compounds (for 150ng/mL cutoff)
CompoundConcentration
Tested
(ng/mL)-25% Cutoff
(112.5ng/mL)+25% Cutoff
(187.5ng/mL)
ResultInterference?ResultInterference?
Norbuprenorphine50,000NegativeNoPositiveNo
Norcodeine100,000NegativeNoPositiveNo
Nordiazepam100,000NegativeNoPositiveNo
Norketamine100,000NegativeNoPositiveNo
Normorphine100,000NegativeNoPositiveNo
Norproxyphene100,000NegativeNoPositiveNo
Norpseudoephedrine100,000NegativeNoPositiveNo
Nortriptyline100,000NegativeNoPositiveNo
Olanzapine100,000NegativeNoPositiveNo
Oxazepam100,000NegativeNoPositiveNo
Oxycodone100,000NegativeNoPositiveNo
Oxymorphone100,000NegativeNoPositiveNo
PCP100,000NegativeNoPositiveNo
Pentazocine100,000NegativeNoPositiveNo
Pentobarbital100,000NegativeNoPositiveNo
Phenobarbital100,000NegativeNoPositiveNo
Phentermine100,000NegativeNoPositiveNo
Phenylephedrine100,000NegativeNoPositiveNo
Phenylpropanolamine100,000NegativeNoPositiveNo
Phenytoin100,000NegativeNoPositiveNo
PMA100,000NegativeNoPositiveNo
Prazepam100,000NegativeNoPositiveNo
Propoxyphene100,000NegativeNoPositiveNo
Propranolol100,000NegativeNoPositiveNo
Protriptyline100,000NegativeNoPositiveNo
R,R(-)-Pseudoephedrine100,000NegativeNoPositiveNo
S,S(+)-Pseudoephedrine100,000NegativeNoPositiveNo
Ranitidine100,000NegativeNoPositiveNo
Ritalinic Acid100,000NegativeNoPositiveNo
Salicylic Acid100,000NegativeNoPositiveNo
Secobarbital100,000NegativeNoPositiveNo
Sertraline100,000NegativeNoPositiveNo
Sufentanil Citrate50,000NegativeNoPositiveNo
Tapentadol100,000NegativeNoPositiveNo
Temazepam100,000NegativeNoPositiveNo
Theophylline100,000NegativeNoPositiveNo
Thioridazine100,000NegativeNoPositiveNo
Trazodone100,000NegativeNoPositiveNo
Triazolam100,000NegativeNoPositiveNo
Trifluoromethylphenyl-piperazine100,000NegativeNoPositiveNo
Trimipramine100,000NegativeNoPositiveNo
Venlafaxine100,000NegativeNoPositiveNo
Table 10 - Structurally Non-Similar Compounds (for 150ng/mL cutoff)
CompoundConcentration
Tested
(ng/mL)-25% Cutoff
(112.5ng/mL)
Result-25% Cutoff
(112.5ng/mL)
Interference?+25% Cutoff
(187.5ng/mL)
Result+25% Cutoff
(187.5ng/mL)
Interference?
Verapamil100,000NegativeNoPositiveNo
Zolpidem Tartrate100,000NegativeNoPositiveNo

9

10

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  • b. The following is a table of the structurally non-similar compounds for the 300ng/mL cutoff:
Table 11 - Structurally Non-Similar Compounds (for 300ng/mL cutoff)
CompoundConcentration
Tested
(ng/mL)-25% Cutoff
(225ng/mL)+25% Cutoff
(375ng/mL)
ResultInterference?ResultInterference?
4-Bromo-
2,5,Dimethoxyphenethylamine100,000NegativeNoPositiveNo
6-Acetylcodeine100,000NegativeNoPositiveNo
6-Acetylmorphine100,000NegativeNoPositiveNo
7-Aminoclonazepam100,000NegativeNoPositiveNo
7-Aminoflunitrazepam100,000NegativeNoPositiveNo
7-Aminonitrazepam100,000NegativeNoPositiveNo
11-hydroxy-delta-9-THC100,000NegativeNoPositiveNo
11-nor-9 carboxy-delta-THC100,000NegativeNoPositiveNo
Acetaminophen500,000NegativeNoPositiveNo
Acetylsalicylic Acid500,000NegativeNoPositiveNo
Alprazolam100,000NegativeNoPositiveNo
Amitriptyline100,000NegativeNoPositiveNo
Amobarbital100,000NegativeNoPositiveNo
S-(+) Amphetamine100,000NegativeNoPositiveNo
Benzylpiperazine100,000NegativeNoPositiveNo
Bromazepam100,000NegativeNoPositiveNo
Buprenorphine100,000NegativeNoPositiveNo
Bupropion100,000NegativeNoPositiveNo
Butabarbital100,000NegativeNoPositiveNo
Butalbital100,000NegativeNoPositiveNo
Caffeine500,000NegativeNoPositiveNo
Cannabidiol100,000NegativeNoPositiveNo
Cannabinol100,000NegativeNoPositiveNo
Carbamazeprine100,000NegativeNoPositiveNo
Carisoprodol100,000NegativeNoPositiveNo
Chlordiazepoxide100,000NegativeNoPositiveNo
Chlorpromazine100,000NegativeNoPositiveNo
cis-Tramadol100,000NegativeNoPositiveNo
Clobazam100,000NegativeNoPositiveNo
Clomipramine100,000NegativeNoPositiveNo
Clonazepam100,000NegativeNoPositiveNo
Clozapine100,000NegativeNoPositiveNo
Codeine100,000NegativeNoPositiveNo

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Table 11 - Structurally Non-Similar Compounds (for 300ng/mL cutoff)
CompoundConcentration
Tested
(ng/mL)-25% Cutoff
(225ng/mL)
ResultInterference?+25% Cutoff
(375ng/mL)
ResultInterference?
Cotinine100,000NegativeNoPositiveNo
Cyclobenzaprine100,000NegativeNoPositiveNo
Dehydronorketamine100,000NegativeNoPositiveNo
Delta-9-THC100,000NegativeNoPositiveNo
Demoxepam100,000NegativeNoPositiveNo
Desakylflurazepam100,000NegativeNoPositiveNo
Desipramine100,000NegativeNoPositiveNo
Dextromethorphan100,000NegativeNoPositiveNo
Diazepam100,000NegativeNoPositiveNo
Digoxin100,000NegativeNoPositiveNo
Dihydrocodeine100,000NegativeNoPositiveNo
Diphenhydramine500,000NegativeNoPositiveNo
Doxepin100,000NegativeNoPositiveNo
EDDP100,000NegativeNoPositiveNo
1R,2S(-)-Ephedrine100,000NegativeNoPositiveNo
1S,2R(+)-Ephedrine100,000NegativeNoPositiveNo
Ethyl ẞ-D-glucuronide100,000NegativeNoPositiveNo
Ethylmorphine100,000NegativeNoPositiveNo
Fenfluramine100,000NegativeNoPositiveNo
Fentanyl100,000NegativeNoPositiveNo
Flunitrazepam100,000NegativeNoPositiveNo
Fluoxetine100,000NegativeNoPositiveNo
Flurazepam100,000NegativeNoPositiveNo
Haloperidol100,000NegativeNoPositiveNo
Heroin100,000NegativeNoPositiveNo
Hexobarbital100,000NegativeNoPositiveNo
Hydrocodone100,000NegativeNoPositiveNo
Hydromorphone100,000NegativeNoPositiveNo
Ibuprofen500,000NegativeNoPositiveNo
Imipramine100,000NegativeNoPositiveNo
Ketamine100,000NegativeNoPositiveNo
Lamotrignine100,000NegativeNoPositiveNo
Levorphanol Tartrate100,000NegativeNoPositiveNo
Lidocaine100,000NegativeNoPositiveNo
Lorazepam100,000NegativeNoPositiveNo
Lorazepam Glucuronide50,000NegativeNoPositiveNo
Lormetazepam100,000NegativeNoPositiveNo
LSD100,000NegativeNoPositiveNo
Maprotiline100,000NegativeNoPositiveNo
MDA100,000NegativeNoPositiveNo
MDEA100,000NegativeNoPositiveNo
MDMA100,000NegativeNoPositiveNo
Meperidine100,000NegativeNoPositiveNo

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Table 11 - Structurally Non-Similar Compounds (for 300ng/mL cutoff)
CompoundConcentration
Tested
(ng/mL)-25% Cutoff
(225ng/mL)
Result-25% Cutoff
(225ng/mL)
Interference?+25% Cutoff
(375ng/mL)
Result+25% Cutoff
(375ng/mL)
Interference?
Meprobamate100,000NegativeNoPositiveNo
Methadone100,000NegativeNoPositiveNo
Methamphetamine100,000NegativeNoPositiveNo
Methaquolone100,000NegativeNoPositiveNo
Methoxetamine100,000NegativeNoPositiveNo
Methylone100,000NegativeNoPositiveNo
Methylphenidate100,000NegativeNoPositiveNo
Midazolam100,000NegativeNoPositiveNo
Morphine100,000NegativeNoPositiveNo
Morphine 3-D-glucuronide100,000NegativeNoPositiveNo
Morphine 6-D-glucuronide50,000NegativeNoPositiveNo
Nalorphine100,000NegativeNoPositiveNo
Naloxone100,000NegativeNoPositiveNo
Naltrexone100,000NegativeNoPositiveNo
Naproxen100,000NegativeNoPositiveNo
N-desmethyltapentadol100,000NegativeNoPositiveNo
Nitrazepam100,000NegativeNoPositiveNo
Norbuprenorphine50,000NegativeNoPositiveNo
Norcodeine100,000NegativeNoPositiveNo
Nordiazepam100,000NegativeNoPositiveNo
Norketamine100,000NegativeNoPositiveNo
Normorphine100,000NegativeNoPositiveNo
Norproxyphene100,000NegativeNoPositiveNo
Norpseudoephedrine100,000NegativeNoPositiveNo
Nortriptyline100,000NegativeNoPositiveNo
Olanzapine100,000NegativeNoPositiveNo
Oxazepam100,000NegativeNoPositiveNo
Oxycodone100,000NegativeNoPositiveNo
Oxymorphone100,000NegativeNoPositiveNo
PCP100,000NegativeNoPositiveNo
Pentazocine100,000NegativeNoPositiveNo
Pentobarbital100,000NegativeNoPositiveNo
Phenobarbital100,000NegativeNoPositiveNo
Phentermine100,000NegativeNoPositiveNo
Phenylephedrine100,000NegativeNoPositiveNo
Phenylpropanolamine100,000NegativeNoPositiveNo
Phenytoin100,000NegativeNoPositiveNo
PMA100,000NegativeNoPositiveNo
Prazepam100,000NegativeNoPositiveNo
Propoxyphene100,000NegativeNoPositiveNo
Propranolol100,000NegativeNoPositiveNo
Protriptyline100,000NegativeNoPositiveNo
R,R(-)-Pseudoephedrine100,000NegativeNoPositiveNo

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Table 11 - Structurally Non-Similar Compounds (for 300ng/mL cutoff)
Concentration-25% Cutoff (225ng/mL)+25% Cutoff (375ng/mL)
CompoundTested (ng/mL)ResultInterference?ResultInterference?
S,S(+)-Pseudoephedrine100,000NegativeNoPositiveNo
Ranitidine100,000NegativeNoPositiveNo
Ritalinic Acid100,000NegativeNoPositiveNo
Salicylic Acid100,000NegativeNoPositiveNo
Secobarbital100,000NegativeNoPositiveNo
Sertraline100,000NegativeNoPositiveNo
Sufentanil Citrate50,000NegativeNoPositiveNo
Tapentadol100,000NegativeNoPositiveNo
Temazepam100,000NegativeNoPositiveNo
Theophylline100,000NegativeNoPositiveNo
Thioridazine100,000NegativeNoPositiveNo
Trazodone100,000NegativeNoPositiveNo
Triazolam100,000NegativeNoPositiveNo
Trifluoromethylphenyl-
piperazine100,000NegativeNoPositiveNo
Trimipramine100,000NegativeNoPositiveNo
Venlafaxine100,000NegativeNoPositiveNo
Verapamil100,000NegativeNoPositiveNo
Zolpidem Tartrate100,000NegativeNoPositiveNo

c. The following is a summary table of the endogenous compounds results for the 150ng/mL cutoff:

Table 12 - Endogenous Compounds (for 150ng/mL cutoff)
Concentration-25% Cutoff+25% Cutoff
CompoundTested(112.5ng/mL)(187.5ng/mL)
(ng/mL)ResultInterference?ResultInterference?
Acetone1.0 g/dLNegativeNoPositiveNo
Ascorbic Acid1.5 g/dLNegativeNoPositiveNo
Bilirubin0.002 g/dLNegativeNoPositiveNo
Creatinine0.5 g/dLNegativeNoPositiveNo
Ethanol1.0 g/dLNegativeNoPositiveNo
Galactose0.01 g/dLNegativeNoPositiveNo
y-Globulin0.5 g/dLNegativeNoPositiveNo
Glucose2.0 g/dLNegativeNoPositiveNo
Hemoglobin0.300 g/dLNegativeNoPositiveNo
Human Serum Albumin0.5 g/dLNegativeNoPositiveNo
Oxalic Acid0.1 g/dLNegativeNoPositiveNo
Riboflavin0.0075 g/dLNegativeNoPositiveNo
Sodium Azide1% w/vNegativeNoPositiveNo
Sodium Chloride6.0 g/dLNegativeNoPositiveNo
Sodium Fluoride1% w/vNegativeNoPositiveNo
Urea6.0 g/dLNegativeNoPositiveNo

d. The following is a summary table of the endogenous compounds results for the 300ng/mL cutoff:

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Table 13 - Endogenous Compounds (for 300ng/mL cutoff)
CompoundConcentration
Tested
(ng/mL)-25% Cutoff
(225ng/mL)
Result-25% Cutoff
(225ng/mL)
Interference?+25% Cutoff
(375ng/mL)
Result+25% Cutoff
(375ng/mL)
Interference?
Acetone1.0 g/dLNegativeNoPositiveNo
Ascorbic Acid1.5 g/dLNegativeNoPositiveNo
Bilirubin0.002 g/dLNegativeNoPositiveNo
Creatinine0.5 g/dLNegativeNoPositiveNo
Ethanol1.0 g/dLNegativeNoPositiveNo
Galactose0.01 g/dLNegativeNoPositiveNo
γ-Globulin0.5 g/dLNegativeNoPositiveNo
Glucose2.0 g/dLNegativeNoPositiveNo
Hemoglobin0.300 g/dLNegativeNoPositiveNo
Human Serum Albumin0.5 g/dLNegativeNoPositiveNo
Oxalic Acid0.1 g/dLNegativeNoPositiveNo
Riboflavin0.0075 g/dLNegativeNoPositiveNo
Sodium Azide1% w/vNegativeNoPositiveNo
Sodium Chloride6.0 g/dLNegativeNoPositiveNo
Sodium Fluoride1% w/vNegativeNoPositiveNo
Urea6.0 g/dLNegativeNoPositiveNo
e. The following is a summary table of the Boric Acid for the 150ng/mL

cutoff results:

Table 14 – Boric Acid (for 150ng/mL cutoff)
CompoundConcentration Tested (ng/mL)-25% Cutoff (112.5ng/mL)+25% Cutoff (187.5ng/mL)
ResultInterference?ResultInterference?
Boric Acid1% w/vNegativeNoNegativeYes

f. The following is a summary table of the Boric Acid for the 300ng/mL cutoff results:

Table 15 - Boric Acid (for 300ng/mL cutoff)
CompoundConcentration Tested (ng/mL)-25% Cutoff (225ng/mL)+25% Cutoff (375ng/mL)
ResultInterference?ResultInterference?
Boric Acid1% w/vNegativeNoNegativeYes

g. The following is a summary table of the Boric Acid for the 150ng/mL cutoff results:

Table 16 - Boric Acid (for 150ng/mL cutoff)
Concentration-50% Cutoff+50% Cutoff
CompoundTested(75ng/mL)(225ng/mL)
(ng/mL)ResultInterference?ResultInterference?
Boric Acid1% w/vNegativeNoNegativeYes

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  • h. The following is a summary table of the Boric Acid for the 300ng/mL cutoff results:
Table 17 – Boric Acid (for 300ng/mL cutoff)
CompoundConcentration
Tested
(ng/mL)-50% Cutoff
(150ng/mL)+50% Cutoff
(450ng/mL)
Boric Acid1% w/vNegativeNoNegativeYes
  • i. Boric Acid interferes with the assay and the limitations have been added to the labeling regarding this compound.
  • j. The following is a summary table of the effect of pH results for the 150ng/mL cutoff:
Table 18 - Effect of pH (for 150ng/mL cutoff)
-25% Cutoff
(112.5ng/mL)+25% Cutoff
(187.5ng/mL)
Test ParameterValueResultInterference?ResultInterference?
pH3.0NEGNoPOSNo
pH4.0NEGNoPOSNo
pH5.0NEGNoPOSNo
pH6.0NEGNoPOSNo
pH7.0NEGNoPOSNo
pH8.0NEGNoPOSNo
pH9.0NEGNoPOSNo
pH10.0NEGNoPOSNo
pH11.0NEGNoPOSNo

k. The following is a summary table of the effect of pH results for the 300ng/mL cutoff:

Table 19 - Effect of pH (for 300ng/mL cutoff)
Test ParameterValue-25% Cutoff (225ng/mL)+25% Cutoff (375ng/mL)
ResultInterference?ResultInterference?
pH3.0NEGNoPOSNo
pH4.0NEGNoPOSNo
pH5.0NEGNoPOSNo
pH6.0NEGNoPOSNo
pH7.0NEGNoPOSNo
pH8.0NEGNoPOSNo
pH9.0NEGNoPOSNo
pH10.0NEGNoPOSNo
pH11.0NEGNoPOSNo

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    1. The following is a summary table of the effect of specific gravity results for the 150ng/mL cutoff:
Table 20 - Effect of Specific Gravity (for 150ng/mL cutoff)
Test ParameterValue-25% Cutoff
(112.5ng/mL)+25% Cutoff
(187.5ng/mL)
ResultInterference?ResultInterference?
Specific Gravity1.000NEGNoPOSNo
Specific Gravity1.002NEGNoPOSNo
Specific Gravity1.005NEGNoPOSNo
Specific Gravity1.010NEGNoPOSNo
Specific Gravity1.015NEGNoPOSNo
Specific Gravity1.020NEGNoPOSNo
Specific Gravity1.025NEGNoPOSNo
Specific Gravity1.030NEGNoPOSNo

m. The following is a summary table of the effect of specific gravity results for the 300ng/mL cutoff:

Table 21 - Effect of Specific Gravity (for 300ng/mL cutoff)
-25% Cutoff
(225ng/mL)+25% Cutoff
(375ng/mL)
Test ParameterValueResultInterference?ResultInterference?
Specific Gravity1.000NEGNoPOSNo
Specific Gravity1.002NEGNoPOSNo
Specific Gravity1.005NEGNoPOSNo
Specific Gravity1.010NEGNoPOSNo
Specific Gravity1.015NEGNoPOSNo
Specific Gravity1.020NEGNoPOSNo
Specific Gravity1.025NEGNoPOSNo
Specific Gravity1.030NEGNoPOSNo
  1. Linearity/ Recovery - A drug free urine pool was spiked with high concentration of the target analyte as a high value specimen. Additional pools were made by serially diluting the high value specimen. The study verified assay linearity in the semi-quantitative mode. The instrument used for this test was a Beckman Coulter AU 400e.

a. The following is a summary table of the linearity/recovery:

Table 22 - Linearity/ Recovery
Expected Concentration (ng/mL)Mean Concentration (ng/mL)Recovery (%)
10098.998.9
150162.9108.6
200194.797.4
300304.5101.5
400419.7104.9
500489.998.0
600602.8100.5
700736.4105.2
800803.1100.4
900946.0105.1
1000996.099.6

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Table 22 - Linearity/ Recovery
Expected Concentration (ng/mL)Mean Concentration (ng/mL)Recovery (%)
11001003.191.2
5. Method Comparison - Unaltered, anonymous and discarded clinical urine samples obtained from clinical testing laboratories were analyzed with the test device. The study verified that the product performance can be verified by Mass Spectrometry. The instrument used for this test was a Beckman Coulter AU 400e and an Agilent 6430 Liquid Chromatography Tandem Mass Spectrometry.
a. The following is a comparison table of qualitative assay performance for the 150ng/mL cutoff:
Table 23 - Method Comparison (for 150ng/mL cutoff) – Qualitative
LC/MS Confirmation
(+)(-)
Test Device(+)401
(-)039
b. The following is a summary table of qualitative assay performance for the 150ng/mL cutoff:
Table 24 - Assay Performance verified by LC/MS – 150ng/mL Cutoff
Type225 ng/mLAgreement (%)
Qualitative/ Positive01*43698
Qualitative/

*Sample contained 124ng/mL Benzoylecgonine by LC-MS/MS

3

36

Negative

c. The following is a comparison table of qualitative assay performance for the 300ng/mL cutoff:

0

0

100

Table 25 - Method Comparison (for 300ng/mL cutoff) – Qualitative

LC/MS Confirmation
(+)(-)
Test
Device(+)400
(-)040

d. The following is a summary table of the qualitative assay performance for the 300ng/mL cutoff:

Table 26 - Assay Performance verified by LC/MS – 300ng/mL Cutoff
TypeBenzoylecgonine ConcentrationAgreement
(%)
450 ng/mL
Qualitative/
Positive00436100
Qualitative/
Negative36400100

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  • e. The following is a comparison table of semi-quantitative assay performance for the 150ng/mL cutoff:
    Table 27 - Method Comparison (for 150ng/mL cutoff) - Semi-Quantitative
LC/MS Confirmation
+
Test+40
Device39
  • f. The following is a summary table of semi-quantitative assay performance for the 150ng/mL cutoff:
Table 28 - Assay Performance verified by LC/MS – 150ng/mL Cutoff
Type225 ng/mLAgreement (%)
Semi-Quantitative/
Positive01*43698
Semi-Quantitative /
Negative36300100

*Sample contained 124ng/mL Benzoylecgonine by LC-MS/MS

  • g. The following is a comparison table of semi-quantitative assay performance for the 300ng/mL cutoff:
    Table 29 - Method Comparison (for 300ng/mL cutoff) - Semi-Quantitative
LC/MS Confirmation
(+)(-)
Test
Device(+)400
(-)040

h. The following is a summary table of semi-quantitative assay performance for the 300ng/mL cutoff:

Table 30 - Assay Performance verified by LC/MS – 300ng/mL Cutoff
TypeBenzoylecgonine ConcentrationAgreement
(%)
450 ng/mL
Semi-Quantitative/
Positive00436100
Semi-Quantitative /
Negative36400100
  • Calibrator and Control Analytical Performance Immunalysis Benzoylecgonine 6. Urine Calibrators and Controls
    • a. Benzoylecgonine Urine Calibrators and Controls Traceability all components of the calibrators and controls have been traced to a commercially available standard solution.
    • b.Benzoylecgonine Urine Calibrators and Controls Stability A closed vial stability study was performed at 25℃ to establish the initial vial expiration dating. The stability study supported an initial expiration date of 12 months. The instrument used for this test was an Agilent 1200 Series Liquid Chromatograph coupled to Agilent 6410 Tandem Mass Spectrometer. All calibrator levels (1, 2, 3, and 4) and all control levels (Low Control 1 and 2 and High Control 1 and 2) for Benzoylecgonine

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were within specifications for Day 0, 8, 16, 24, 32, and 40. This accelerated stability study was performed to establish initial expiration dating. Real time stability studies are ongoing.

  • c. Benzoylecgonine Urine Calibrators and Controls Stability An open vial stability study was performed at 5℃ to establish the initial open vial expiration dating. The stability study supported an initial open vial expiration date of 60 days. The instrument used for this test was an Agilent 1200 Series Liquid Chromatograph coupled to Agilent 6410 Tandem Mass Spectrometer. All calibrator levels (1, 2, 3, and 4) and all control levels (Low Control 1 and 2 and High Control 1 and 2) for Benzoylecgonine were within specifications for Day 0, 19, 26, 33, 41, and 60. This stability study was performed to establish initial expiration dating.
  • d.Benzoylecgonine Urine Calibrators and Controls Value Assignment -Calibrators and controls are manufactured and are tested by mass spectrometry. If any of the analytes are not of the acceptable range, then the calibrator and controls is adjusted and re-tested. Values are assigned to the calibrators and controls once the mass spectrometry results are within the acceptable ranges.
  • I. Conclusion

The information provided in this pre-market notification demonstrates that the Immunalysis Benzoylecgonine Urine Enzyme Immunoassay is substantially equivalent to the legally marketed predicate device for its general intended use.