Immunalysis Cannabinoids Urine Enzyme Immunoassay, Immunalysis cTHC Urine Calibrators, Immunalysis cTHC Urine Control Set

K151203 · Immunalysis Corporation · LDJ · Jun 5, 2015 · Clinical Toxicology

Device Facts

• Record ID: K151203
• Device Name: Immunalysis Cannabinoids Urine Enzyme Immunoassay, Immunalysis cTHC Urine Calibrators, Immunalysis cTHC Urine Control Set
• Applicant: Immunalysis Corporation
• Product Code: LDJ · Clinical Toxicology
• Decision Date: Jun 5, 2015
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3870
• Device Class: Class 2

Intended Use

The Immunalysis Cannabinoids Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a cutoff of 50ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Cannabinoids in human urine with automated clinical chemistry analyzers. This assay is calibrated against 11-nor-9-carboxy-A9-THC (cTHC). 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 Cannabinoids 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.

Device Story

The Immunalysis Cannabinoids Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay used in clinical laboratories to detect cannabinoids in human urine. The device utilizes an antibody/substrate reagent containing monoclonal and polyclonal antibodies to cannabinoids, G6P, and NAD, and an enzyme conjugate reagent containing a cannabinoid derivative labeled with G6PDH. When cannabinoids are present in the urine sample, they compete with the enzyme-labeled drug for antibody binding sites, modulating enzyme activity. The assay is performed on automated clinical chemistry analyzers. Results are qualitative or semi-quantitative, providing a preliminary screen that requires confirmation via GC-MS or LC/MS. The device includes liquid, ready-to-use calibrators and controls spiked with 11-nor-9-carboxy-Δ9-THC. The output assists healthcare providers in identifying potential drug use, necessitating clinical judgment and confirmatory testing for definitive diagnosis.

Clinical Evidence

Bench testing only. Precision study (N=80) performed over 20 days verified cutoff performance. Specificity and cross-reactivity evaluated against structurally related and non-similar compounds. Interference testing confirmed assay performance is unaffected by endogenous compounds, pH, or specific gravity. Method comparison study against LC/MS (N=80) showed 100% agreement for both qualitative and semi-quantitative modes at the 50ng/mL cutoff.

Technological Characteristics

Homogeneous enzyme immunoassay. Reagents: antibody/substrate (monoclonal/polyclonal antibodies, G6P, NAD) and enzyme conjugate (G6PDH-labeled cannabinoid derivative) in Tris buffer with sodium azide. Liquid, ready-to-use form. Designed for automated clinical chemistry analyzers. Storage at 2-8°C.

Indications for Use

Indicated for the qualitative and semi-quantitative analysis of Cannabinoids in human urine for laboratory use on automated clinical chemistry analyzers. Intended for prescription use only. Provides preliminary analytical test results requiring confirmation by GC-MS or LC/MS.

Regulatory Classification

Identification

A cannabinoid test system is a device intended to measure any of the cannabinoids, hallucinogenic compounds endogenous to marihuana, in serum, plasma, saliva, and urine. Cannabinoid compounds include delta-9-tetrahydrocannabinol, cannabidiol, cannabinol, and cannabichromene. Measurements obtained by this device are used in the diagnosis and treatment of cannabinoid use or abuse and in monitoring levels of cannabinoids during clinical investigational use.

Special Controls

*Classification.* Class II (special controls). A cannabinoid 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).

Submission Summary (Full Text)

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

June 5, 2015

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

Re: K151203

Trade/Device Name: Immunalysis Cannabinoids Urine Enzyme Immunoassay. Immunalysis cTHC Urine Calibrators, Immunalysis cTHC Urine Control Set Regulation Number: 21 CFR 862.3870 Regulation Name: Cannabinoid test system Regulatory Class: II Product Code: LDJ, DLJ, LAS Dated: May 4, 2015 Received: May 5, 2015

Dear Mr. 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

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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 [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/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 [phone] or [phone] or at its Internet address

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

Sincerely yours,

Courtney H. Lias -S

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

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# Indications for Use

510(k) Number (if known)

#### K151203

Device Name

Immunalysis Cannabinoids Urine Enzyme Immunoassay Immunalvsis cTHC Urine Control Set Immunalysis cTHC Urine Calibrators

#### Indications for Use (Describe)

The Immunalysis Cannabinoids Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a cutoff of 50ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Cannabinoids in human urine with automated clinical chemistry analyzers. This assay is calibrated against 11-nor-9-carboxy-A9-THC (cTHC). 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 Cannabinoids 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 cTHC Urine Control Set: The Immunalysis cTHC Urine Control Set is used as control materials in the Immunalysis Cannabinoids Urine Enzyme Immunoassay.

Immunalysis cTHC Urine Calibrators: The Immunalysis cTHC Urine Calibrators are used as calibrators in the Immunalysis Cannabinoids Urine Enzyme Immunoassay for the qualitative and semi-quantitative determination of Cannabinoids in urine on automated clinical chemistry analyzers.

Type of Use (Select one or both, as applicable)

| <div style="display:flex; align-items:center;"> <input checked="true" type="checkbox"/> <span>For Transportation (49 CFR 390 Subpart B)</span> </div> | <div style="display:flex; align-items:center;"> <input type="checkbox"/> <span>For-Hire Operation (49 CFR 390 Subpart C)</span> </div> |
|-------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------|
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> 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

| 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: | [phone] |
| | 6. Fax: | [phone] |
| | 7. Email: | [e-mail] |
| | 8. Summary prepared on: | June 03, 2015 |
| B. Device Information | | |
| | 1. Trade Name: | Immunalysis Cannabinoids Urine Enzyme Immunoassay<br>Immunalysis cTHC Urine Control Set<br>Immunalysis cTHC Urine Calibrators |
| | 2. Common Name: | Immunalysis Cannabinoids Urine Enzyme Immunoassay<br>Immunalysis cTHC Urine Control Set<br>Immunalysis cTHC Urine Calibrators |
| | 3. Device Classification: | II |
| | 4. Regulation Number: | CFR 862.3870 Enzyme Immunoassay, Cannabinoids<br>CFR 862.3200 Calibrator, Drug Specific<br>CFR 862.3280 Clinical Toxicology Control Materials |
| | 5. Panel: | Toxicology(91) |
| | 6. Product Code: | LDJ<br>DLJ<br>LAS |

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# IMMUNALYSIS

- C. Legally Marketed Device to Which We are Claiming Equivalence (807.92(A)(3))

| 1. Predicate Device: | LZI Cannabinoids (cTHC) Enzyme Immunoassay |
|------------------------|----------------------------------------------|
| | LZI Cannabinoids (cTHC) Drugs of Abuse (DAU) |
| | Calibrators |
| | LZI Cannabinoids (cTHC) Drugs of Abuse (DAU) |
| | Controls |
| 2. Predicate Company: | Lin-Zhi Internationals, Inc. |
| 3. Predicate K Number: | K110239 |

### D. Device Description

- 1. The assay consists of antibody/ substrate reagent and enzyme conjugate reagent. The antibody/ substrate reagent includes monoclonal and polyclonal antibodies to Cannabinoids, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in Tris buffer with Sodium Azide as a preservative. The enzyme conjugate reagent includes Cannabinoids derivative labeled with glucose-6-phosphate dehydrogenase (G6PDH) in Tris buffer with Sodium Azide as a preservative. Calibrators and controls are sold separately. Reagents are liquid, ready to use
- 2. All of the Immunalysis cTHC 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 and HIGH Control are prepared by spiking known concentrations of 11-nor-9-carboxy-Δ'-THC (cTHC) into the negative calibrator matrix. The negative calibrator, Level 1 calibrator, Level 2 calibrator, Level 3 calibrator, Level 4 calibrator and two controls are sold as individual bottles. The concentration of cTHC in their corresponding calibrators and controls are summarized as follows:

| Table 1 Immunalysis cTHC Urine Calibrators and Controls | | | | | | |
|---------------------------------------------------------|------------------|---------|----------|-----------|---------------|----------------|
| Analyte | cTHC Calibrators | | | | cTHC Controls | |
| | Level 1 | Level 2 | Level 3 | Level 4 | LOW Control 1 | HIGH Control 1 |
| cTHC | 20ng/mL | 50ng/mL | 100ng/mL | 2000ng/mL | 37.5ng/mL | 62.5ng/mL |

### E. Intended Use

- 1. The Immunalysis Cannabinoids Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a cutoff of 50ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Cannabinoids in human urine with automated clinical chemistry analyzers. This assay is calibrated against cTHC. This in-vitro device is for prescription use only.

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### IMMUNALYSIS

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 Cannabinoids 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.

- 2. Immunalysis cTHC Urine Control: The Immunalysis cTHC Urine Controls are used as control materials in Immunalysis Cannabinoids Urine Enzyme Immunoassay.
- 3. Immunalysis cTHC Urine Calibrators: The Immunalysis cTHC Urine Calibrators are used as calibrators in the Immunalysis Cannabinoids Urine Enzyme Immunoassay for the qualitative and semi-quantitative determination of Cannabinoids in urine on automated clinical chemistry analyzers.

| Item | Cannabinoids Assay K110239 | Immunalysis Cannabinoids Urine EIA |
|-----------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | For the qualitative and semi-<br>quantitative determination of the<br>presence of Cannabinoids in human<br>urine at a cutoff of 25ng/mL,<br>50ng/mL and 100ng/mL | For the qualitative and semi-quantitative<br>determination of the presence of<br>Cannabinoids in human urine at a cutoff of<br>50ng/mL |
| Type of Product | Analytical Reagents | Analytical Reagents |
| Measured Analytes | Cannabinoids | Cannabinoids |
| Test Matrix | Urine | Urine |
| Cutoff Levels | 25ng/mL, 50ng/mL and 100ng/mL of<br>Cannabinoids | 50ng/mL of Cannabinoids |
| Test System | Homogeneous Enzyme Immunoassay | Homogenous Enzyme Immunoassay |
| Materials | Liquid Ready-to-Use Two Reagent<br>Assay (R1 and R2) | Antibody/Substrate Reagents and Enzyme<br>Labeled Conjugate |
| Mass Spectroscopy<br>Confirmation | Required for preliminary positive<br>analytical results | Required for preliminary positive<br>analytical results |
| Antibody | Mouse Monoclonal antibodies to<br>Cannabinoids | Monoclonal and polyclonal antibodies to<br>Cannabinoids |
| Storage | 2 – 8°C until expiration date | 2 – 8°C until expiration date |
| Calibrator Form | Liquid | Liquid |
| Calibrator Levels | Three sets of Five (5) Levels | Five (5) Levels (including negative) |
| Control Levels | Three sets of Two (2) Levels | Two (2) Levels |

- F. Comparison of the new device with the predicate device

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- G. The following laboratory performance studies were performed to determine substantial equivalence of the Immunalysis Cannabinoids Urine Enzyme Immunoassay to the predicate
- 1. 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. The instruments used for this was Beckman Coulter AU 400e.

| 50ng/mL cutoff test data results. | | | |
|-----------------------------------------------------|-------------|---------------------|-------------------------|
| Table 2 - Qualitative Analysis (for 50ng/mL cutoff) | | | |
| Concentration (ng/mL) | % of cutoff | # of determinations | Result |
| 0 | -100% | 80 | 80 Negative |
| 12.5 | -75% | 80 | 80 Negative |
| 25 | -50% | 80 | 80 Negative |
| 37.5 | -25% | 80 | 80 Negative |
| 50 | Cutoff | 80 | 40 Negative/40 Positive |
| 62.5 | +25% | 80 | 80 Positive |
| 75 | +50% | 80 | 80 Positive |
| 87.5 | +75% | 80 | 80 Positive |
| 100 | +100% | 80 | 80 Positive |

- a. The following is a summary table of the Qualitative Analysis for the
b. The following is a summary table of the Semi-Quantitative Analysis for the 50ng/mL cutoff test data results.

| Table 3 - Semi-Quantitative Analysis (for 50ng/mL cutoff) | | | |
|-----------------------------------------------------------|-------------|---------------------|-------------------------|
| Concentration (ng/mL) | % of cutoff | # of determinations | Result |
| 0 | -100% | 80 | 80 Negative |
| 12.5 | -75% | 80 | 80 Negative |
| 25 | -50% | 80 | 80 Negative |
| 37.5 | -25% | 80 | 80 Negative |
| 50 | Cutoff | 80 | 38 Negative/42 Positive |
| 62.5 | +25% | 80 | 80 Positive |
| 75 | +50% | 80 | 80 Positive |
| 87.5 | +75% | 80 | 80 Positive |
| 100 | +100% | 80 | 80 Positive |

- 2. Specificity and Cross-Reactivity - Structurally similar compounds were spiked into drug free urine at levels that will vield 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.

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| below: | | | |
|------------------------------------------------------------------------------|------------------------------|----------|----------------------|
| Table 4 - Structurally Related Compounds (for 50 ng/mL cutoff) - Qualitative | | | |
| Compound | Concentration Tested (ng/mL) | Result | Cross-Reactivity (%) |
| 11-nor-9-carboxy- Δ9-THC | 50 | Positive | 100.0 |
| (±) 11-Hydroxy- Δ9-THC | 100 | Positive | 50.0 |
| 11-nor- Δ8-carboxy-THC | 40 | Positive | 125.0 |
| Cannabinol | 75 | Positive | 66.7 |
| Cannabidiol | 1,000,000 | Negative | <0.005 |
| Δ9-THC | 50 | Positive | 100.0 |

- a. The qualitative result summary table for the 50ng/mL cutoff is outlined
b. The semi-quantitative result summary table for the 50ng/mL cutoff is outlined below:

| Table 5 - Structurally Related Compounds (for 50ng/mL cutoff) – Semi-Quantitative | | |
|-----------------------------------------------------------------------------------|------------------------------|----------------------|
| Compound | Concentration Tested (ng/mL) | Cross-Reactivity (%) |
| 11-nor-9-carboxy- Δ9-THC | 50 | 100.0 |
| (±) 11-Hydroxy- Δ9-THC | 100 | 50.0 |
| 11-nor- Δ8-carboxy-THC | 40 | 125.0 |
| Cannabinol | 75 | 66.7 |
| Cannabidiol | 1,000,000 | <0.005 |
| Δ9-THC | 50 | 100.0 |

- 3. 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 summary table of the structurally non-similar compounds for the 50ng/mL cutoff :

| Table 6 - Structurally Non-Similar Compounds (for 50ng/mL cutoff) | | | | | |
|-------------------------------------------------------------------|---------------------------------|-------------------------|---------------|-------------------------|---------------|
| Compound | Concentration<br>Tested (ng/mL) | -25% Cutoff (37.5ng/mL) | | +25% Cutoff (62.5ng/mL) | |
| 6-Acetylmorphine | 100,000 | Negative | No | Positive | No |
| 7-Aminoclonazepam | 100,000 | Negative | No | Positive | No |
| Acetaminophen | 500,000 | Negative | No | Positive | No |
| Alprazolam | 100,000 | Negative | No | Positive | No |
| Amitriptyline | 100,000 | Negative | No | Positive | No |
| Amobarbital | 100,000 | Negative | No | Positive | No |
| S-(+)-Amphetamine | 100,000 | Negative | No | Positive | No |
| Benzoylecgonine | 500,000 | Negative | No | Positive | No |
| Benzylpiperazine | 100,000 | Negative | No | Positive | No |
| 4-Bromo-<br>2,5,Dimethoxyphenethylamine | 100,000 | Negative | No | Positive | No |
| Table 6 - Structurally Non-Similar Compounds (for 50ng/mL cutoff) | | | | | |
| | Concentration | -25% Cutoff (37.5ng/mL) | | +25% Cutoff (62.5ng/mL) | |
| Compound | Tested (ng/mL) | Result | Interference? | Result | Interference? |
| Bromazepam | 100,000 | Negative | No | Positive | No |
| Buprenorphine | 100,000 | Negative | No | Positive | No |
| Bupropion | 100,000 | Negative | No | Positive | No |
| Butabarbital | 100,000 | Negative | No | Positive | No |
| Caffeine | 500,000 | Negative | No | Positive | No |
| Carbamazepine | 100,000 | Negative | No | Positive | No |
| Carisoprodol | 100,000 | Negative | No | Positive | No |
| Chlordiazepoxide | 100,000 | Negative | No | Positive | No |
| Chlorpromazine | 100,000 | Negative | No | Positive | No |
| Clobazam | 100,000 | Negative | No | Positive | No |
| Clomipramine | 100,000 | Negative | No | Positive | No |
| Clonazepam | 100,000 | Negative | No | Positive | No |
| Cocaine | 100,000 | Negative | No | Positive | No |
| Codeine | 100,000 | Negative | No | Positive | No |
| Cotinine | 100,000 | Negative | No | Positive | No |
| Cyclobenzaprine | 100,000 | Negative | No | Positive | No |
| N-Desmethyltapentadol | 100,000 | Negative | No | Positive | No |
| Despiramine | 100,000 | Negative | No | Positive | No |
| Dextromethorphan | 100,000 | Negative | No | Positive | No |
| Diazepam | 100,000 | Negative | No | Positive | No |
| Dihydrocodeine | 100,000 | Negative | No | Positive | No |
| Diphenhydramine (DPH) | 500,000 | Negative | No | Positive | No |
| Doxepin | 100,000 | Negative | No | Positive | No |
| Ecgonine | 100,000 | Negative | No | Positive | No |
| Ecgonine methyl ester | 100,000 | Negative | No | Positive | No |
| 2-ethylidene-1,5-dimethyl-<br>3,3-diphenylpyrrolidine<br>(EDDP) | 100,000 | Negative | No | Positive | No |
| 1R,2S(-)-Ephedrine | 100,000 | Negative | No | Positive | No |
| 1S,2R(+)-Ephedrine | 100,000 | Negative | No | Positive | No |
| Ethyl ẞ-D-glucuronide | 100,000 | Negative | No | Positive | No |
| Ethylmorphine | 100,000 | Negative | No | Positive | No |
| Fenfluramine | 100,000 | Negative | No | Positive | No |
| Fentanyl | 100,000 | Negative | No | Positive | No |
| Flunitrazepam | 100,000 | Negative | No | Positive | No |
| Flurazepam | 100,000 | Negative | No | Positive | No |
| Heroin | 100,000 | Negative | No | Positive | No |
| Hexobarbital | 100,000 | Negative | No | Positive | No |
| Hydrocodone | 100,000 | Negative | No | Positive | No |
| Hydromorphone | 100,000 | Negative | No | Positive | No |
| Ibuprofen | 100,000 | Negative | No | Positive | No |
| Imipramine | 100,000 | Negative | No | Positive | No |
| Ketamine | 100,000 | Negative | No | Positive | No |
| Lamotrigine | 100,000 | Negative | No | Positive | No |
| Table 6 - Structurally Non-Similar Compounds (for 50ng/mL cutoff) | | | | | |
| Compound | Concentration<br>Tested (ng/mL) | -25% Cutoff (37.5ng/mL) | | +25% Cutoff (62.5ng/mL) | |
| | | Result | Interference? | Result | Interference? |
| Levorphanol Tartrate | 100,000 | Negative | No | Positive | No |
| Lidocaine | 100,000 | Negative | No | Positive | No |
| Lorazepam | 100,000 | Negative | No | Positive | No |
| Lysergic acid diethylamide<br>(LSD) | 100,000 | Negative | No | Positive | No |
| Maprotiline | 100,000 | Negative | No | Positive | No |
| (+)-3,4-<br>Methylenedioxyamphetamin<br>e (MDA) | 100,000 | Negative | No | Positive | No |
| 3,4-methylenedioxy-N-<br>ethyl-amphetamine (MDEA) | 100,000 | Negative | No | Positive | No |
| 3,4-methylenedioxy-<br>methamphetamine (MDMA) | 100,000 | Negative | No | Positive | No |
| Meperidine | 100,000 | Negative | No | Positive | No |
| Meprobamate | 100,000 | Negative | No | Positive | No |
| Methadone | 500,000 | Negative | No | Positive | No |
| S(+)-Methamphetamine | 100,000 | Negative | No | Positive | No |
| Methaquolone | 100,000 | Negative | No | Positive | No |
| Methylphenidate | 100,000 | Negative | No | Positive | No |
| Morphine | 100,000 | Negative | No | Positive | No |
| Morphine-3β-D-glucuronide | 100,000 | Negative | No | Positive | No |
| Morphine-6ß-D-glucuronide | 100,000 | Negative | No | Positive | No |
| Nalorphine | 100,000 | Negative | No | Positive | No |
| Naloxone | 100,000 | Negative | No | Positive | No |
| Naltrexone | 100,000 | Negative | No | Positive | No |
| Nitrazepam | 100,000 | Negative | No | Positive | No |
| Norbuprenorphine | 100,000 | Negative | No | Positive | No |
| Norcodeine | 100,000 | Negative | No | Positive | No |
| Nordiazepam | 100,000 | Negative | No | Positive | No |
| Normorphine | 100,000 | Negative | No | Positive | No |
| Norpropoxyphene | 100,000 | Negative | No | Positive | No |
| Nortriptyline | 100,000 | Negative | No | Positive | No |
| Oxezepam | 100,000 | Negative | No | Positive | No |
| Oxycodone | 100,000 | Negative | No | Positive | No |
| Oxymorphone | 100,000 | Negative | No | Positive | No |
| Phencyclidine (PCP) | 100,000 | Negative | No | Positive | No |
| Pentazocine | 100,000 | Negative | No | Positive | No |
| Pentobarbital | 100,000 | Negative | No | Positive | No |
| Phenobarbital | 100,000 | Negative | No | Positive | No |
| Phentermine | 100,000 | Negative | No | Positive | No |
| Phenylepherine | 100,000 | Negative | No | Positive | No |
| Phenylpropanolamine | 100,000 | Negative | No | Positive | No |
| Phenytoin | 100,000 | Negative | No | Positive | No |
| para-Methoxyamphetamine | 100,000 | Negative | No | Positive | No |
| Table 6 - Structurally Non-Similar Compounds (for 50ng/mL cutoff) | | | | | |
| Compound | Concentration<br>Tested (ng/mL) | -25% Cutoff (37.5ng/mL) | | +25% Cutoff (62.5ng/mL) | |
| | | Result | Interference? | Result | Interference? |
| (PMA) | | | | | |
| Prazepam | 100,000 | Negative | No | Positive | No |
| Propoxyphene | 100,000 | Negative | No | Positive | No |
| Propranolol | 100,000 | Negative | No | Positive | No |
| Protripyline | 100,000 | Negative | No | Positive | No |
| R,R(-)-Pseudoephedrine | 100,000 | Negative | No | Positive | No |
| S,S(+)-Pseudoephedrine | 100,000 | Negative | No | Positive | No |
| Ranitidine | 100,000 | Negative | No | Positive | No |
| Ritalinic Acid | 100,000 | Negative | No | Positive | No |
| Salicyclic Acid | 100,000 | Negative | No | Positive | No |
| Secobarbial | 100,000 | Negative | No | Positive | No |
| Sertraline | 100,000 | Negative | No | Positive | No |
| Sufentanil Citrate | 100,000 | Negative | No | Positive | No |
| Temazepam | 100,000 | Negative | No | Positive | No |
| Theophylline | 100,000 | Negative | No | Positive | No |
| Thiordazine | 100,000 | Negative | No | Positive | No |
| cis-Tramadol | 100,000 | Negative | No | Positive | No |
| Trazodone | 100,000 | Negative | No | Positive | No |
| Triazolam | 100,000 | Negative | No | Positive | No |
| Trifluoromethylphenyl-piperazine | 100,000 | Negative | No | Positive | No |
| Trimipramine | 100,000 | Negative | No | Positive | No |
| Venlafaxine | 100,000 | Negative | No | Positive | No |
| Zolpidem | 100,000 | Negative | No | Positive | No |

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b. The following is a summary table of the endogenous compounds results for the 50ng/mL cutoff:

| Table 7 - Endogenous Compounds (for 50ng/mL cutoff) | | | | | |
|-----------------------------------------------------|---------------------------------|-------------------------|---------------|-------------------------|---------------|
| | Concentration<br>Tested (ng/mL) | -25% Cutoff (37.5ng/mL) | | +25% Cutoff (62.5ng/mL) | |
| Compound | | Result | Interference? | Result | Interference? |
| Acetone | 1.0 g/dL | Negative | No | Positive | No |
| Ascorbic Acid | 1.5 g/dL | Negative | No | Positive | No |
| Bilirubin | 0.002 g/dL | Negative | No | Positive | No |
| Creatinine | 0.5 g/dL | Negative | No | Positive | No |
| Ethanol | 1.0 g/dL | Negative | No | Positive | No |
| Galactose | 0.01 g/dL | Negative | No | Positive | No |
| γ-Globulin | 0.5 g/dL | Negative | No | Positive | No |
| Glucose | 2.0 g/dL | Negative | No | Positive | No |
| Hemoglobin | 300 mg/dL | Negative | No | Positive | No |
| Human Serum Albumin | 0.5 g/dL | Negative | No | Positive | No |
| Oxalic Acid | 0.1 g/dL | Negative | No | Positive | No |
| Riboflavin | 0.0075 g/dL | Negative | No | Positive | No |
| Sodium Azide | 1% w/v | Negative | No | Positive | No |
| Sodium Chloride | 6.0 g/dL | Negative | No | Positive | No |

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| Table 7 - Endogenous Compounds (for 50ng/mL cutoff) | | | | |
|-----------------------------------------------------|------------------------------|-------------------------|-------------------------|--|
| Compound | Concentration Tested (ng/mL) | -25% Cutoff (37.5ng/mL) | +25% Cutoff (62.5ng/mL) | |
| | | Result Interference? | Result Interference? | |
| Sodium Fluoride | 1% w/v | Negative No | Positive No | |
| Urea | 6.0 g/dL | Negative No | Positive No | |

- c. The following is a summary table of Boric Acid for the 50ng/mL cutoff results:

| Table 8 - Boric Acid (for 50ng/mL cutoff) | | | | | |
|-------------------------------------------|------------------------------|-------------------------|---------------|-------------------------|---------------|
| Compound | Concentration Tested (ng/mL) | -25% Cutoff (37.5ng/mL) | | +25% Cutoff (62.5ng/mL) | |
| | | Result | Interference? | Result | Interference? |
| Boric Acid | 1% w/v | Negative | No | Positive | No |

## d. The following is a summary table of the effect of pH results for the 50ng/mL cutoff:

| Table 9 - Effect of pH (for 50ng/mL cutoff) | | | | | |
|---------------------------------------------|-------|-------------------------|---------------|-------------------------|---------------|
| Test Parameter | Value | -25% Cutoff (37.5ng/mL) | | +25% Cutoff (62.5ng/mL) | |
| | | Result | Interference? | Result | Interference? |
| pH | 3.0 | Negative | No | Positive | No |
| pH | 4.0 | Negative | No | Positive | No |
| pH | 5.0 | Negative | No | Positive | No |
| pH | 6.0 | Negative | No | Positive | No |
| pH | 7.0 | Negative | No | Positive | No |
| pH | 8.0 | Negative | No | Positive | No |
| pH | 9.0 | Negative | No | Positive | No |
| pH | 10.0 | Negative | No | Positive | No |
| pH | 11.0 | Negative | No | Positive | No |

- e. The following is a summary table of the effect of specific gravity results for 50ng/mL cutoff:

| Table 10 - Effect of Specific Gravity (for 50ng/mL cutoff) | | | | | | |
|------------------------------------------------------------|-------|-------------------------|---------------|-------------------------|---------------|--|
| | | -25% Cutoff (37.5ng/mL) | | +25% Cutoff (62.5ng/mL) | | |
| Test Parameter | Value | Result | Interference? | Result | Interference? | |
| Specific Gravity | 1.000 | Negative | No | Positive | No | |
| Specific Gravity | 1.002 | Negative | No | Positive | No | |
| Specific Gravity | 1.005 | Negative | No | Positive | No | |
| Specific Gravity | 1.010 | Negative | No | Positive | No | |
| Specific Gravity | 1.015 | Negative | No | Positive | No | |
| Specific Gravity | 1.020 | Negative | No | Positive | No | |
| Specific Gravity | 1.025 | Negative | No | Positive | No | |
| Specific Gravity | 1.030 | Negative | No | Positive | No | |

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- 4. 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 instrument used for this test was a Beckman Coulter AU 400e.

| Table 11 - Linearity/ Recovery | | |
|--------------------------------|----------------------------|--------------|
| Expected Concentration (ng/mL) | Mean Concentration (ng/mL) | Recovery (%) |
| 20 | 19.3 | 96.3 |
| 40 | 40.4 | 101.0 |
| 50 | 52.1 | 104.3 |
| 60 | 64.4 | 107.4 |
| 80 | 77.8 | 97.3 |
| 100 | 101.2 | 101.2 |
| 120 | 128.4 | 107.0 |
| 140 | 144.5 | 103.2 |
| 160 | 156.1 | 97.5 |
| 180 | 173.1 | 96.2 |
| 200 | 219.4 | 109.7 |
| 220 | 223.7 | 101.7 |

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

- 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 50ng/mL cutoff:

Table 12 - Method Comparison (for 50ng/mL cutoff) - Qualitative

| | LC/MS Confirmation | | |
|----------------|--------------------|-----|----|
| | (+) | (-) | |
| Test<br>Device | (+) | 40 | 0 |
| | (-) | 0 | 40 |

b. The following is a summary table of qualitative assay performance for the 50ng/mL cutoff:

| Table 13 - Assay Performance verified by LC/MS – 50ng/mL Cutoff | | | | | |
|-----------------------------------------------------------------|----------------------------|-------------|-------------|------------------|-----|
| Type | Cannabinoids Concentration | | | Agreement<br>(%) | |
| | <25ng/mL | 25~49 ng/mL | 50~75 ng/mL | > 75 ng/mL | |
| Qualitative/ Positive | 0 | 0 | 10 | 30 | 100 |
| Qualitative/ Negative | 36 | 4 | 0 | 0 | 100 |

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- c. The following is a comparison table of semi-quantitative assay performance for the 50ng/mL cutoff:
Table 14 - Method Comparison (for 50ng/mL cutoff) - Semi-Quantitative

| | LC/MS Confirmation | |
|----------------|--------------------|-----|
| | (+) | (-) |
| Test<br>Device | 40 | 0 |
| (+) | 0 | 40 |

d. The following is a summary table of semi-quantitative assay performance for the 50ng/mL cutoff:

| Table 15 - Assay Performance verified by LC/MS – 50ng/mL Cutoff | | | | | |
|-----------------------------------------------------------------|----------------------------|---------------|---------------|------------|---------------|
| Type | Cannabinoids Concentration | | | | Agreement (%) |
| | < 25ng/mL | 25 ~ 49 ng/mL | 50 ~ 75 ng/mL | > 75 ng/mL | |
| Semi-Quantitative/ Positive | 0 | 0 | 10 | 30 | 100 |
| Semi-Quantitative / Negative | 36 | 4 | 0 | 0 | 100 |

- 6. Calibrator and Control Analytical Performance Immunalysis cTHC Urine Calibrators and Controls
- a. cTHC Calibrator and Control Traceability all components of the calibrator and controls have been traced to a commercially available standard solution
- b.cTHC Calibrators and Controls Stability A closed vial stability study was performed at 25°C 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 and High Control) for cTHC 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.cTHC 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 and High Control) for cTHC were within specifications for Day 0, 7, 14, 21, 30, 45 and 60. This stability study was performed to establish initial expiration dating.
- d.cTHC Calibrator and Control 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.

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## H. Conclusion

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