IMMULITE® Cannabinoids is a solid-phase, chemiluminescent enzyme immunoassay designed for use with the IMMULITE" Automated Analyzer for the semiquantitative and qualitative measurement for cannabinoids and metabolites in urine. It is intended strictly for in vitro diagnostic use in the context of a program involving an established confirmatory test for tetrahvdrocannabinol (THC. cannabis, marijuana) and its metabolites

Device Description

IMMULITE® Cannabinoids is a solid-phase. chemiluminescent immunoassay. The solid phase, a polystyrene bead enclosed within an IMMULITE® Test Unit, is coated with a monoclonal antibody specific for cannabinoids. The patient sample and alkaline phosphatase-conjugated 11-nor-A -tetrahvdrocannabinol-9-carboxylic acid (THCA) are simultaneously introduced into the Test Unit, and incubated for 30 minutes at 37°C with intermittent agitation. During this time, cannabinoids in the sample compete with the enzyme-labeled THC for a limited number of antibody binding sites on the bead. Unbound enzyme conjugate is then removed by a centrifugal wash, after which substrate is added and the Test Unit is incubated for a further 10 minutes.

The chemiluminescent substrate, a phosphate ester of adamantyl dioxetane, undergoes hydrolysis in the presence of alkaline phosphatase to vield an unstable intermediate. The continuous production of this intermediate results in a sustained emission of light, thus improving precision by providing a window for multiple readings. The bound complex - and thus also the photon output as measured by the luminometer - is inversely proportional to the concentration of cannabinoids in the sample.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information based on the provided document:

Acceptance Criteria and Device Performance

Acceptance Criteria	Reported Device Performance
Relative Sensitivity (vs. Roche Abuscreen Online THC)	99.2%
Relative Specificity (vs. Roche Abuscreen Online THC)	98.2%
Relative Sensitivity (vs. Abbott AxSYM Cannabinoids)	96.3%
Relative Specificity (vs. Abbott AxSYM Cannabinoids)	99.0%

Note: The document compares the IMMULITE® Cannabinoids assay against two predicate devices. The acceptance criteria are implicitly defined by the performance of these predicate devices as demonstrated by the presented comparison data. No explicit numerical acceptance thresholds are stated, but the intent is to show performance "as well as or better than" the legally marketed devices.

Study Details

2. Sample size used for the test set and data provenance

Sample Size: A total of 456 urine samples were used for the method comparison study.
Data Provenance: Randomly selected drug-free and drug-containing urine samples were obtained from a hospital in Switzerland. The samples were tested on-site. This indicates a retrospective study design using clinical samples.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

The document does not specify the number of experts or their qualifications for establishing ground truth regarding the presence or absence of cannabinoids.

4. Adjudication method for the test set

The document does not explicitly state an adjudication method. However, for discrepant results between the IMMULITE® Cannabinoids assay and the predicate devices, GC/MS (Gas Chromatography/Mass Spectrometry) was used as a confirmatory method to resolve these discrepancies. For example, cases where IMMULITE® was negative and Roche was positive were confirmed by GC/MS (found non-detectable). Similarly, for discrepancies with Abbott AxSYM, GC/MS was used. This implies an ad-hoc adjudication involving a gold standard (GC/MS) for discordant results.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is a chemiluminescent enzyme immunoassay for laboratory use, not an AI-assisted diagnostic tool for human readers. Therefore, the concept of human reader improvement with/without AI assistance does not apply.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done

Yes, a standalone performance study was done. The entire method comparison against the predicate devices (Roche Abuscreen Online THC and Abbott AxSYM Cannabinoids) demonstrates the performance of the IMMULITE® Cannabinoids assay as an automated, instrument-based test, without human intervention in the interpretation of the primary result (though laboratory personnel operate the instrument and perform steps like sample loading). The performance metrics (sensitivity, specificity) are for the device itself.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The primary ground truth for resolving discrepancies between the IMMULITE® Cannabinoids assay and the predicate devices was GC/MS (Gas Chromatography/Mass Spectrometry). GC/MS is considered a gold standard for drug confirmation and quantification.

8. The sample size for the training set

The document does not specify a training set sample size. This type of device (immunoassay) is typically developed and validated using a range of samples during its initial design, but the provided study focuses on a clinical test set for performance validation, not on a separate "training set" in the context of machine learning.

9. How the ground truth for the training set was established

As no specific "training set" as understood in machine learning is mentioned, this information is not applicable and not provided in the document. The development of such an assay would involve extensive analytical validation against known standards and characterized samples, but this is distinct from a ground-truthed training set for a machine learning model.

Summary

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Diagnostic Products Corporation 5700 West 96th Street Los Angeles, CA 90045 Tel: (213) 776-0180 Fax: (213) 776-0204

K963916

APR 28 1997

510 (k) Summary of Safety and Effectiveness

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR Part 807.92.

Name:	Diagnostic Products Corporation (DPC)
Address:	5700 West 96th StreetLos Angeles, CA 90045-5597
Telephone Number	(213) 776-0180
Facsimile Number:	(213) 776-0204
Contact Person:	Edward M. Levine, Ph.D.Director of Clinical Affairs
Date of Preparation:	April 3, 1997
Device Name:
Trade:	IMMULITE® Cannabinoids
Catalog #:	LKTHI (100 tests), LKTH5 (500 tests)
Common:	Reagent system designed as a semiquantitativemeasurement for cannabinoids in urine.
CFR:	A device intended to measure any of the cannabinoids,hallucinogenic compounds endogenous to marijuana, inserum, plasma, saliva, and urine. Cannabinoidcompounds include delta-9-tetrahydrocannabinol,cannabidiol, cannabinol, and cannbichromeneMeasurements obtained by this device are used in thediagnosis and treatment of cannabinoid use or abuse andin monitoring levels of cannabinoids during clinicalinvestigational use.
Classification:	Class II device (21 CFR 862.3870), 91-LDJ
Panel:	Toxicology
Accessory Trade:	IMMULITE® Cannabinoids Control Module
Common:	Quality Control Material (assayed & unassayed)
CFR:	A device intended for medical purposes for use in a testsystem to estimate test precision and to detect systematicanalytical deviations that may arise from reagent oranalytical instrument variation.
Classification:	Class I device (21 CFR 862.1660), 82-JJX
Panel:	Immunology

Image /page/0/Picture/6 description: The image shows a logo with the letters "DPC" in a bold, sans-serif font. The letters are connected to each other, forming a single, solid shape. There is a registered trademark symbol in the upper right corner of the logo. The logo is black and the background is white.

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Diagnostic Products Corporation 00 West 96th Street oneles CA 9004 2131 776-0180

Manufacturer:	Diagnostic Products Corporation (DPC)5700 West 96th StreetLos Angeles. CA 90045-5597
Establishment Registration #:	DPC: 2017183
Substantial EquivalentPredicate Device:	Roche Abuscreen Online THC (K961620)Abbott AxSYM Cannabinoids (K951288)and DPC's Third Generation TSHControl Module (K930007)

Description and Intended Use of Device:

Substantial Equivalence Claim:

Diagnostic Products Corporation (DPC) asserts that DPC's IMMULITE* Cannabinoids is substantially equivalent to Roche Abuscreen Online THC and Abbott AxSYM Cannabinoids assays.

Intended Use Equivalence:

The IMMULITE Cannabinoids assay is designed for the semiguantitative and qualitative measurement of cannabinoids in urine. Abuscreen Online THC is an in vitro diagnostic test for the qualitative and semiquantitative detection of cannabinoids in human urine and the AxSYM Cannabinoids assay is a semiquantitative reagent system for the detection of cannabinoids in human urine. Each product is intended strictly for in vitro diagnostic use, and each product provides a preliminary analytical test result

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iagnostic Products Corporation nn West 96th Street Angeles, CA 9004 ax: (213) 776-0204

Technological Comparison to Predicate:

The IMMULITE* Cannabinoids is a chemiluminescent immunoassay. The technology of the IMMULITE® Cannabinoids assay is identical to the technology used in previously cleared and commercially marketed IMMULITE® products.

Abuscreen Online Automated Assays are based on the kinetic interaction of microparticles in a solution (KIMS) as measured by changes in light transmission. In the absence of sample drug, free antibody binds to drug-microparticle conjugates, causing the formation of particle aggregates When a urine sample containing the drug in question is present, this drug competes with the particle-bound drug derivative for free antibody. Antibody bound to sample drug is no longer available to promote particle aggregation, and subsequent particle lattice formation is inhibited.

As the aggregation reaction proceeds in the absence of sample drug, the absorbance change increases. Conversely the presence of sample drug diminishes the increasing absorbance in proportion to the concentration of drug in the sample drug content is determined relative to the value obtained for a known cutoff concentration of drug.

The AxSYM Cannabinoids assay utilizes fluorescence Polarization Immunoassay (FPIA) technology. In the FPIA reaction process, specimen analyte-tracer compete for binding sites on antibodies. If the specimen contains a high concentration of the analyte, then specimen analyte binds to the antibodies, leaving the analyte-tracer unbound. If the specimen contains a low concentration (or no concentration) of the analyte. then few or no analyte molecules bind to the antibodies. leaving the antibodies open for the analyte-tracer to bind. FPIA optics measure the change in polarized light to determine the concentration of unbound analyte-tracers. and therefore the concentration of analytes in the specimen (fluorescence polarization).

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Diagnostic Products Corporation
5700 West 96th Street
Los Angeles, CA 90045
Tel: (213) 776-0180
Fax: (213) 776-0204

Performance Equivalence - Method Comparison

The IMMULITE Cannabinoids procedure was compared to two commercially available immunoassays for cannabinoids, Roche Abuscreen OnLine THC and Abbott AxSYM Cannabinoids Assay on a total of 456 urine samples with a range from nondetectable to over 2500 ng/mL. Randomly selected drug-free and drug-containing urine samples were obtained from a Hospital in Switzerland, and tested on site. The results of the comparisons are presented in the tables below

		IMMULITE Cannabinoids		Relative	Relative
		Pos.	Neg.	Sensitivity	Specificity
Roche Abuscreen	Pos.	235	2	99.2%	98.2%
Online	Neg.	4	215

The two cases where IMMULITE results were negative and Roche results were positive were both found nondetectable by the GC/MS procedure. The GC/MS values for the four cases where IMMULITE results were positive and Roche results were negative ranged from nondetectable to 80 ng/mL.

	IMMULITE Cannabinoids		Relative	Relative
	Pos.	Neg.	Sensitivity	Specificity
Abbott AxSYM Pos.	237	9	96.3%	99.0%
Neg.	2	208

The nine cases where IMMULITE results were negative and Abbott AxSYM results were positive were all found nondetectable by the GC/MS procedure. The two cases where IMMULITE results were positive and Abbott AxSYM results were negative were both 18 ng/mL in the GC/MS procedure.

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in Products Cornoration

Substantial Equivalence Claim for the IMMULITE Cannabinoids Control Module

Diagnostic Products Corporation (DPC) asserts that the IMMULITE Cannabinoids Control Module, which is sold separately from the IMMULITE Cannabinoids kit, is substantially equivalent to other commercially available assayed controls, such as DPC's Third Generation TSH Control Module (K930007).

Intended Use Equivalence:

Each product is designed for monitoring day-to-day performance of a particular assay. Each product is intended strictly for in vitro diagnostic use, and is supplied lyophilized. requiring reconstitution.

The controls are intended to be assayed as an unknown, in the same manner as a patient sample, in the context of an internal quality control program

Clinical Studies:

Not applicable

Conclusion

The conclusions drawn from the nonclinical tests demonstrate that the device is safe, effective, and performs as well as or better than the legally marketed device.

Edward Loomis

Edward M. Levine, Ph.D.
Director of Clinical Affairs

4/4/97

Dute

Regulation Number and Section

§ 862.3870 Cannabinoid test system.

(a)
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 includedelta -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.(b)
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).