The Immunalysis Buprenorphine Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a cutoff of 5ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Buprenorphine in human urine with automated clinical chemistry analyzers. This assay is calibrated against Buprenorphine. This in-vitro diagnostic 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 Buprenorphine 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 Spectroscopy (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 Buprenorphine Urine Controls:

The Immunalysis Buprenorphine Urine Controls are used as control materials in the Immunalysis Buprenorphine Urine Enzyme Immunoassay.

Immunalysis Buprenorphine Urine Calibrators:

The Immunalysis Buprenorphine Urine Calibrators are used as calibrators in the Immunalysis Buprenorphine Urine Enzyme Immunoassay for the qualitative and semiquantitative determination of Buprenorphine in urine on automated clinical chemistry analyzers.

Device Description

The assay consists of antibody/ substrate reagent and enzyme conjugate reagent. The antibody/ substrate reagent includes rabbit antibodies to Buprenorphine, glucose-6phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in Tris buffer with Sodium Azide as a preservative. The enzyme conjugate reagent includes buprenorphine 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

The buprenorphine calibrator and controls consists of a single calibrator at 5ng/mL, a control set containing a LOW control at 3.75ng/mL and a HIGH control at 6.25ng/mL and a calibrator set containing a negative calibrator, a Level 1 calibrator at 5ng/mL, a Level 2 calibrator at 10ng/mL, a Level 3 calibrator at 20ng/mL and a Level 4 calibrator at 40ng/mL.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the Immunalysis Buprenorphine Urine Enzyme Immunoassay, based on the provided 510(k) summary:

This device is an in-vitro diagnostic (IVD) test, not an AI/ML-based device that interprets images or signals using algorithms learned from data. Therefore, many standard AI/ML evaluation criteria, such as MRMC studies, expert adjudication, or separate training/test sets with human-in-the-loop performance, are not applicable here. The "acceptance criteria" for this device are defined by its analytical performance metrics, which show it functions as intended for its intended use.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly listed with numerical targets in the same clear format as for an AI/ML device (e.g., "sensitivity > 90%"). Instead, the acceptability is demonstrated by the device meeting certain performance characteristics (precision, specificity, linearity, non-interference) that are deemed adequate for its intended use as a qualitative and semi-quantitative drug test. The FDA's substantial equivalence determination implies these criteria were met.

The performance studies and their results serve as the "reported device performance" and, by implication, demonstrate meeting the acceptance criteria.

Acceptance Criteria (Implied)	Reported Device Performance
Precision/Cutoff Characterization: Consistent and accurate determination of positive/negative results around the 5 ng/mL cutoff, and reproducibility of measurements.	Qualitative: 100% agreement for concentrations ≤ 3.75 ng/mL (Negative) and ≥ 6.25 ng/mL (Positive). At the 5 ng/mL cutoff, 48/80 (60%) were Negative and 32/80 (40%) were Positive. This demonstrates the cutoff serves as a boundary. Semi-Quantitative: 100% agreement for concentrations ≤ 3.75 ng/mL (Negative) and ≥ 6.25 ng/mL (Positive). At the 5 ng/mL cutoff, 33/80 (41.25%) were Negative and 47/80 (58.75%) were Positive. Precision was evaluated over 20 days, 2 runs/day in duplicate (N=80).
Specificity and Cross-Reactivity: Minimal interference from structurally similar compounds and no interference from other common drugs or compounds.	Structurally Related Compounds: Buprenorphine (100% cross-reactivity), NorBuprenorphine (90.91%), Buprenorphine Glucuronide (0.17%), NorBuprenorphine Glucuronide (0.13%). All other listed opioids and common drugs (e.g., 6-Acetyl morphine, Codeine, Heroin, Morphine, Methadone, Oxycodone, etc.) showed "N.D." (Not Detected/<0.05%) for both qualitative and semi-quantitative modes.
Interference: No significant interference from common exogenous or endogenous compounds, or variations in pH and specific gravity.	Structurally Non-Similar Compounds: No interference observed from 90+ listed compounds (e.g., Acetaminophen, Alprazolam, Caffeine, Ibuprofen, etc.) at high concentrations (100,000 ng/mL or 500,000 ng/mL), with correct negative results at -25% cutoff and positive results at +25% cutoff. Endogenous Compounds: Most endogenous compounds (Acetone, Ascorbic Acid, Bilirubin, Creatinine, Ethanol, Glucose, Hemoglobin, Human Serum Albumin, Oxalic Acid, Sodium Azide, Sodium Chloride, Sodium Fluoride, Urea) showed no interference. Exceptions: Boric Acid (1% w/v) and Riboflavin (0.0075 g/dL) caused false negative results at +25% cutoff. This became a known limitation in the labeling. pH Effect: No interference between pH 3.0 and 11.0. Specific Gravity Effect: No interference between specific gravity 1.000 and 1.030.
Linearity/Recovery: Accurate measurement across the expected analytical range for semi-quantitative analysis.	Recovery ranged from 77% (at 55 ng/mL) to 105% (at 35 ng/mL), demonstrating reasonable linearity for semi-quantitative purposes. Expected concentrations ranged from 5 ng/mL to 55 ng/mL.
Method Comparison: Agreement with a accepted confirmatory method (LC/MS).	Qualitative: 100% agreement between the Test Device and LC/MS Confirmation for both positive (40 samples) and negative (40 samples) results. Semi-Quantitative: 100% agreement between the Test Device and LC/MS Confirmation for both positive (40 samples) and negative (40 samples) results.
Stability: Reagents, calibrators, and controls maintain performance over specified storage and use periods.	Closed Accelerated Stability: Supports 1-year expiration for reagents and 12 months for calibrators/controls. All tested levels remained within specifications for up to 40 days of accelerated testing. Open/On-Board Stability (Reagents): Supports 28-day open vial expiration. All replicates for tested levels remained within specifications for up to 28 days. Calibrator and Control Stability (Open Vial): Supports 6-month open vial expiration. All calibrator and control levels were within specifications for up to 13 days of accelerated testing. Real-time studies are ongoing.
Calibrator and Control Traceability & Value Assignment: Accuracy and consistency of calibrator and control values.	Calibrators and controls are traced to a commercially available standard solution from Cerilliant Chemicals. Values are assigned based on Mass Spectrometry results, with adjustments and retesting if outside acceptable ranges.

2. Sample Sizes Used for the Test Set and Data Provenance

Precision/Cutoff Characterization: 80 determinations per concentration level (20 days, 2 runs per day in duplicate) for 9 concentration levels resulting in a total of 720 measurements.
Specificity and Cross-Reactivity: Not explicitly stated as a "sample size" of patient samples, but structurally similar compounds and other drugs were spiked into drug-free urine. Around 30+ compounds were tested at specific concentrations.
Interference: Not explicitly stated as a "sample size" of patient samples, but various non-similar compounds, endogenous compounds, and different pH/specific gravity levels were tested by spiking into drug-free urine containing target analyte at ±25% of cutoff. Around 90+ non-similar compounds and 17 endogenous compounds were tested. pH was tested at 9 levels, and specific gravity at 8 levels.
Linearity/Recovery: A drug-free urine pool spiked with a high concentration, then serially diluted to create 11 different concentration levels.
Method Comparison: 80 "unaltered, anonymous and discarded clinical urine samples" (40 positive, 40 negative based on LC/MS).
Stability Studies: Conducted with a sufficient number of replicates over timepoints to support the claimed stability. Specific "sample sizes" (e.g., number of batches or vials) are not detailed but the methodology (e.g., "replicates") implies sufficient testing.

Data Provenance:

Country of Origin: Not explicitly stated for patient samples. The manufacturer, Immunalysis Corporation, is based in Pomona, CA, USA.
Retrospective or Prospective:
- Precision, Specificity, Interference, Linearity: Lab-based studies, likely prospective, using controlled spiked samples.
- Method Comparison: "Unaltered, anonymous and discarded clinical urine samples obtained from clinical testing laboratories." This suggests retrospective use of existing clinical samples.
- Stability: Prospective, controlled lab studies.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts

Not applicable in the typical sense for this IVD device.

For IVD devices like this immunoassay, the "ground truth" for the test set is established by:

Preparation of controlled samples: For precision, specificity, interference, and linearity studies, samples are prepared in a laboratory with known concentrations of the analyte or interfering substances. This is the "ground truth" for these studies.
Reference Method Analysis: For method comparison, the "ground truth" is established by a more definitive analytical method, in this case, Gas Chromatography/Mass Spectrometry (GC-MS) or Liquid Chromatography / Mass Spectrometry (LC/MS). These are established analytical chemistry techniques, not subject to expert interpretation in the same way as, for example, a radiological image. Therefore, human experts are not used to establish this kind of ground truth.

4. Adjudication Method for the Test Set

Not applicable. As the ground truth is established by known sample concentrations or definitive analytical methods (GC-MS/LC/MS), there is no need for human expert adjudication.

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

Not applicable. This device is an automated in-vitro diagnostic immunoassay for chemical analysis of urine, not an AI/ML-based diagnostic aid for human readers (e.g., radiologists, pathologists). It does not involve "human readers" interpreting results that would then be assisted by AI. The device provides a direct analytical result.

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

Essentially, yes, but not for an "algorithm" in the AI sense. The primary performance data (Precision, Specificity, Interference, Linearity, Method Comparison) demonstrates the device's analytical performance on its own, producing qualitative and semi-quantitative results for Buprenorphine in urine. It operates as a "standalone" analytical instrument providing results.

7. The Type of Ground Truth Used

Controlled Spike-ins: For Precision, Specificity/Cross-Reactivity, Interference, and Linearity, the ground truth was established by manufacturing urine samples with known, precisely measured concentrations of Buprenorphine or other compounds.
Reference Standard (LC/MS Confirmation): For the Method Comparison study, the ground truth was established by Liquid Chromatography / Mass Spectrometry (LC/MS), which is considered the preferred confirmatory method for drug testing in urine.

8. The Sample Size for the Training Set

Not applicable in the AI/ML sense. This is a traditional enzyme immunoassay, not an AI/ML device that requires a training set to learn relationships from data. Its "training" involves chemical reagent formulation and instrument calibration.

9. How the Ground Truth for the Training Set Was Established

Not applicable in the AI/ML sense. For a chemical assay, the equivalent of "establishing ground truth for training" would involve:

Chemical Formulation: Developing the immunoassay reagents (antibodies, enzymes, substrates) based on known chemical principles to specifically react with Buprenorphine.
Calibration: Using precisely measured standard solutions (calibrators) with known concentrations of Buprenorphine to establish the assay's response curve. The document states: "Calibrators and controls are manufactured and are tested by mass spectrometry. If any of the analytes are out of the acceptable range, then the calibrator or control is adjusted and retested. Values are assigned to the calibrator and controls once the Mass spectrometry results are within the acceptable ranges." This process essentially establishes the "ground truth" for the device's internal calibration.

Summary

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K141406

510(k) SUMMARY

JUL 0 1 2014

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
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 30, 2014
	B. Device Information
	1. Trade Name:	Immunalysis Buprenorphine Urine Enzyme Immunoassay
		Immunalysis Buprenorphine Urine Controls
		Immunalysis Buprenorphine Urine Calibrators
	2. Common Name:	Immunalysis Buprenorphine Urine Enzyme Immunoassay
		Immunalysis Buprenorphine Urine Controls
		Immunalysis Buprenorphine Urine Calibrators
	3. Device Classification:	II
4.	Regulation Number:	CFR 862.3650 Opiate Test System
		CFR 862.3200 Clinical Toxicology Calibrator
		CFR 862.3280 Clinical Toxicology Control Materials
	5. Panel:	Toxicology(91)
6.	Product Code:	DJG
		DLJ
		LAS
C. Legally Marketed Device to Which We are Claiming Equivalence (807.92(A)(3))
1.	Predicate Device:	CEDIA Buprenorphine Assay

1.	Predicate Device:	CEDIA Buprenorphine AssayCEDIA Buprenorphine ControlsCEDIA Buprenorphine Calibrators
2.	Predicate Company:	Microgenics
3.	Predicate K Number:	K040316

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D. Device Description

E. Intended Use

Immunalysis Buprenorphine Urine Enzyme Immunoassay:

Immunalysis Buprenorphine Urine Controls:

The Immunalysis Buprenorphine Urine Controls are used as control materials in the Immunalysis Buprenorphine Urine Enzyme Immunoassay.

Immunalysis Buprenorphine Urine Calibrators:

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Comparison of the new device with the predicate device F

Item	Predicate Device (K040316)	Test Device
Intended Use	For the qualitative and semi-quantitative determination of thepresence of buprenorphine in humanurine at a cutoff of 5 ng/ml	For the qualitative and semi-quantitative determination of thepresence of buprenorphine in humanurine at a cutoff of 5 ng/ml
Type of Product	Analytical Reagents	Analytical Reagents
Measured Analytes	Buprenorphine	Buprenorphine
Test Matrix	Urine	Urine
Cutoff Levels	5ng/mL of Buprenorphine	5ng/mL of Buprenorphine
Test System	Homogenous Enzyme Immunoassay	Homogenous Enzyme Immunoassay
Materials	Buffer 1, Buffer 2, Lyophilized Reagentla and Lyophilized Reagent	Antibody/ Substrate Reagents andEnzyme Labeled Conjugate
Mass SpectroscopyConfirmation	Required for preliminary positiveanalytical results	Required for preliminary positiveanalytical results
Antibody	Mouse monoclonal anti-buprenorphinederivative	Rabbit Monoclonal Antibody toBuprenorphine
Storage	2 - 8°C until expiration date	2 - 8°C until expiration date
Calibrator Form	Liquid	Liquid
Calibrator Levels	One (1) Level (5ng/mL)	One (1) Level (5ng/mL)
Control Set Levels	Two (2) Levels (3ng/mL and 7ng/mL)	Two (2) Levels (3.75ng/mL and6.25ng/mL)
Calibrator SetLevels	Five (5) Levels (0, 5, 20, 50 and 75ng/mL)	Five (5) Levels (0, 5, 10, 20 and 40ng/mL)

G. The following laboratory performance studies were performed to determine substantial equivalence of the Immunalysis Buprenorphine 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. In addition, it also verified the product performance relative to the ability of the device to produce the same value during repeated measurements. The instrument used for this test was a Beckman Coulter AU 400e.
- a. The following is a summary table of the Qualitative Analysis for the 5ng/mL cutoff test data results.

Concentration (ng/mL)	% of cutoff	# of determinations	Result
0	-100%	80	80 Negative
1.25	-75%	80	80 Negative
2.5	-50%	80	80 Negative
3.75	-25%	80	80 Negative
5	Cutoff	80	48 Negative/32 Positive
6.25	+25%	80	80 Positive
7.5	+50%	80	80 Positive
8.75	+75%	80	80 Positive
10	+100%	80	80 Positive

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b. The follówing is a summary table of the Semi-Quantitative Analysis for the 5ng/mL cutoff test data results.

Semi-Quantitative Analysis (for 5ng/mL cutoff)
Concentration (ng/mL)	% of cutoff	# of determinations	Result
0	-100%	80	80 Negative
1.25	-75%	80	80 Negative
2.5	-50%	80	80 Negative
3.75	-25%	80	80 Negative
5	Cutoff	80	33 Negative/ 47 Positive
6.25	+25%	80	80 Positive
7.5	+50%	80	80 Positive
8.75	+75%	80	80 Positive
10	+100%	80	80 Positive

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 cutoff. 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.

Structurally Related Compounds - Qualitative
Compound	Concentration Tested (ng/mL)	Result	Cross-Reactivity (%)
Buprenorphine	5	N/A	100.00
NorBuprenorphine	5.5	POS	90.91
Buprenorphine Glucuronide	3,000	POS	0.17
NorBuprenorphine Glucuronide	4,000	POS	0.13
6-Acetyl morphine	100,000	NEG	N.D.
Codeine	100,000	NEG	N.D.
Dihydrocodeine	100,000	NEG	N.D.
EDDP	100000	NEG	N.D.
EMDP	100,000	NEG	N.D.
Ethyl Morphine	100,000	NEG	N.D.
Heroin	100,000	NEG	N.D.
Hydrocodone	100,000	NEG	N.D.
Hydromorphone	100,000	NEG	N.D.
LAAM	100,000	NEG	N.D.
Levorphanol	100,000	NEG	N.D.
Methadone	100,000	NEG	N.D.
Meperidine	100,000	NEG	N.D.
Morphine 3 Glucuronide	100,000	NEG	N.D.
Morphine 6 Glucuronide	100,000	NEG	N.D.
Morphine	100,000	NEG	N.D.
Nalorphine	100,000	NEG	N.D.
Naloxone	100,000	NEG	N.D.
Naltrexone	100,000	NEG	N.D.
Norpropoxyphene	100,000	NEG	N.D.
Oxycodone	100,000	NEG	N.D.
Oxymorphone	100,000	NEG	N.D.
Diacetyl Morphine	100,000	NEG	N.D.

a. The qualitative result summary table is outlined below:
N.D. = Not Detected (<0.05%)

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b. The semi-quantitative result summary table is outlined below:

Structurally Related Compounds - Semi-Quantitative
Compound	Concentration Tested (ng/mL)	Cross-Reactivity (%)
Buprenorphine	5	100.00
NorBuprenorphine	5.5	90.91
Buprenorphine Glucuronide	3,000	0.17
NorBuprenorphine Glucuronide	4,000	0.13
6-Acetyl morphine	100,000	N.D.
Codeine	100,000	N.D.
Dihydrocodeine	100,000	N.D.
EDDP	100000	N.D.
EMDP	100,000	N.D.
Ethyl Morphine	100,000	N.D.
Heroin	100,000	N.D.
Hydrocodone	100,000	N.D.
Hydromorphone	100,000	N.D.
LAAM	100,000	N.D.
Levorphanol	100,000	N.D.
Methadone	100,000	N.D.
Meperidine	100,000	N.D.
Morphine 3 Glucuronide	100,000	N.D.
Morphine 6 Glucuronide	100,000	N.D.
Morphine	100,000	N.D.
Nalorphine	100,000	N.D.
Naloxone	100,000	N.D.
Naltrexone	100,000	N.D.
Norpropoxyphene	100,000	N.D.
Oxycodone	100,000	N.D.
Oxymorphone	100,000	N.D.
Diacetyl Morphine	100,000	N.D.

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. Boric Acid and Riboflavin caused a false negative response at the concentrations tested. All other 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 5ng/mL cutoff

Structurally Non-Similar Compounds (for 5ng/mL cutoff)
Compound	Concentration Tested (ng/mL)	-25% Cutoff (3.75ng/mL)		+25% Cutoff (6.25ng/mL)
		Result	Interference?	Result	Interference?
4-Bromo-2,5,Dimethoxyphenethylamine	100,000	Negative	No	Positive	No
6-Acetylcodeine	100,000	Negative	No	Positive	No
7-Aminoclonazepam	100,000	Negative	No	Positive	No
7-Aminoflurazepam	100,000	Negative	No	Positive	No
7-Aminonitrazepam	100,000	Negative	No	Positive	No
Acetaminophen	500,000	Negative	No	Positive	No
Acetylsalicylic Acid	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
Structurally Non-Similar Compounds (for 5ng/mL cutoff)
Compound	Concentration Tested (ng/mL)	-25% Cutoff (3.75ng/mL)		+25% Cutoff (6.25ng/mL)
		Result	Interference?	Result	Interference?
S-(+) Amphetamine	100,000	Negative	No	Positive	No
Benzoylecgonine	500,000	Negative	No	Positive	No
Benzylpiperazine	100,000	Negative	No	Positive	No
Bromazepam	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
Cannabidiol	100,000	Negative	No	Positive	No
Cannabinol	100,000	Negative	No	Positive	No
Carbamazeprine	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
Delta-9-THC	100,000	Negative	No	Positive	No
Demoxepam	100,000	Negative	No	Positive	No
Desakylflurazepam	100,000	Negative	No	Positive	No
Desipramine	100,000	Negative	No	Positive	No
Diazepam	100,000	Negative	No	Positive	No
Dihydrocodeine	100,000	Negative	No	Positive	No
Diphenhydramine	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
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
EtG	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
Fluoxetine	100,000	Negative	No	Positive	No
Flurazepam	100,000	Negative	No	Positive	No
Hexobarbital	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
Lamotrignine	100,000	Negative	No	Positive	No
Lidocaine	100,000	Negative	No	Positive	No
Lorazepam	100,000	Negative	No	Positive	No
Compound	ConcentrationTested (ng/mL)	-25% Cutoff (3.75ng/mL)Result	Interference?	+25% Cutoff (6.25ng/mL)Result	Interference?
Lorazepam Glucuronide	50,000	Negative	No	Positive	No
Lormetazepam	100,000	Negative	No	Positive	No
LSD	100,000	Negative	No	Positive	No
Maprotiline	100,000	Negative	No	Positive	No
(+)-MDA	100,000	Negative	No	Positive	No
MDEA	100,000	Negative	No	Positive	No
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	500,000	Negative	No	Positive	No
Methaquolone	100,000	Negative	No	Positive	No
Methylphenidate	100,000	Negative	No	Positive	No
Midazolam	100,000	Negative	No	Positive	No
Naproxen	100,000	Negative	No	Positive	No
N-desmethyltapentadol	100,000	Negative	No	Positive	No
Nitrazepam	100,000	Negative	No	Positive	No
Nordiazepam	100,000	Negative	No	Positive	No
Norcodeine	100,000	Negative	No	Positive	No
Normorphine	100,000	Negative	No	Positive	No
Norpseudoephedrine	100,000	Negative	No	Positive	No
Nortriptyline	100,000	Negative	No	Positive	No
Oxazepam	100,000	Negative	No	Positive	No
Oxazepam Glucuronide	50,000	Negative	No	Positive	No
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
Phenylephrine	100,000	Negative	No	Positive	No
Phenytoine	100,000	Negative	No	Positive	No
PMA	100,000	Negative	No	Positive	No
PPA	100,000	Negative	No	Positive	No
Propoxyphene	100,000	Negative	No	Positive	No
Propranolol	100,000	Negative	No	Positive	No
Protriptyline	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
Salicylic Acid	100,000	Negative	No	Positive	No
Secobarbital	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
Structurally Non-Similar Compounds (for 5ng/mL cutoff)
Compound	ConcentrationTested (ng/mL)	-25% Cutoff (3.75ng/mL)		+25% Cutoff (6.25ng/mL)
		Result	Interference?	Result	Interference?
11-nor-9 carboxy THC	100,000	Negative	No	Positive	No
Theophylline	100,000	Negative	No	Positive	No
Thioridazine	100,000	Negative	No	Positive	No
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	5,000	Negative	No	Positive	No
Venlafaxine	100,000	Negative	No	Positive	No
Zolpidem Tartrate	100,000	Negative	No	Positive	No

Immunalysis Corporation

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Immunalysis Corporation

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Immunalysis Corporation

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b. The following is a summary table of the endogenous compounds results for the 5ng/mL cutoff

Endogenous Compounds (for 5ng/mL cutoff)
Compound	ConcentrationTested (ng/mL)	-25% Cutoff (3.75ng/mL)		+25% Cutoff (6.25ng/mL)
		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
Boric Acid	1% w/v	Negative	No	Negative	Yes
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	0.300 g/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	Negative	Yes
Sodium Azide	1% w/v	Negative	No	Positive	No
Sodium Chloride	6.0 g/dL	Negative	No	Positive	No
Sodium Flouride	1% w/v	Negative	No	Positive	No
Urea	6.0 g/dL	Negative	No	Positive	No

c. Boric Acid and Riboflavin interfere with the assay and the limitations have been added to the labeling regarding these two compounds.

d. The following is a summary table of the effect of pH results for the 5ng/mL cutoff

Effect of pH (for 5ng/mL cutoff)
Test Parameter	Value	-25% Cutoff (3.75ng/mL)		+25% Cutoff (6.25ng/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

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Effect of Specific Gravity (for 5ng/mL cutoff) - Qualitative
Test Parameter	Value	-25% Cutoff (3.75ng/mL)		+25% Cutoff (6.25ng/mL)
		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

e. The following is a summary table of the effect of specific gravity result for the Engiml
1. Linearity/ Recovery A drug free urine pool was spiked with a 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.

Linearity/ Recovery
Expected Concentration (ng/mL)	Mean Concentration (ng/mL)	Recovery (%)
5	5.0	100
10	9.9	99
15	13.7	91
20	20.2	101
25	24.2	97
30	29.5	98
35	36.7	105
40	39.3	98
45	40.8	91
50	40.9	82
55	42.4	77

a. Summary results are listed in the following table
------------------------------------------------------	--

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 5ng/mL cutoff

	LC/MS Confirmation
	(+)	(-)
Test Device	(+)	40	0
	(-)	0	40

b. The following is a summary table of qualitative assay performance for the 5ng/mL cutoff

Type	<2.5ng/mL	2.5~4.9 ng/mL	5~7.5 ng/mL	>7.5 ng/mL	Agreement (%)
Qualitative/ Positive	0	0	4	36	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 5ng/mL cutoff

	LC/MS Confirmation
	(+)	(-)
Test Device	(+)	40	0
	(-)	0	40

d. The following is a summary table of semi-quantitative assay performance for the 5nq/mL cutoff

Assay Performance verified by LC/MS - 5ng/mL Cutoff
Type	Buprenorphine Concentration				Agreement (%)
	<2.5ng/mL	2.5 ~ 4.9 ng/mL	5 ~ 7.5 ng/mL	>7.5 ng/mL
Semi-Quantitative/ Positive	0	0	4	36	100%
Semi-Quantitative / Negative	36	4	0	0	100%

Stability -

a. A closed accelerated stability study was performed on reagents, calibrators and controls at 25°C to establish the initial expiration dating. The stability study supported an initial expiration date of 1 year for reagents. This stability study supported an initial expiration date of 12 months for calibrators and controls. The instrument used for this test was a Beckman Coulter AU 400e.

1. The following is a summary of the qualitative stability data. The 0 and 3.75ng/mL levels were negative in comparison to the 5ng/mL cutoff for Day 0. 2. 8. 16. 24. 32 and 40. The 6.25ng/mL level was positive in comparison to the 5ng/mL cutoff for Day 0, 2, 8, 16, 24, 32 and 40. This accelerated stability study was performed to establish initial expiration dating. Real time stability studies are ongoing.
1. The following is a summary of the semi-quantitative stabilility data for the 5ng/mL cutoff. The 3.75ng/mL level was negative in comparison to the 5ng/mL cutoff for Day 0, 2, 8, 16, 24, 32 and 40. The 6.25ng/mL level was positive in comparison to the 5ng/mL cutoff for Day 0, 2, 8, 16, 24, 32 and 40. This accelerated stability study was performed to establish initial expiration dating. Real time stability studies are ongoing.
b. An open/ on-board stability study was performed on reagents to establish expiration dating when reagents are opened and stored on board the instrument at 2°C to 8°C. The stability study supported an initial open vial expiration date of 28 days. The instrument used for this test was a Beckman Coulter AU 400e.
- 1. The following is a summary of the qualitative open/ on-board stability data for the 5ng/mL cutoff. All replicates for the 3.75ng/mL level were negative in comparison to the 5ng/mL cutoff for Day 0, 7, 14, 21 and 28. All replicates of the 6.25ng/mL level were positive in comparison to the 5ng/mL cutoff for Day 0, 7, 14, 21 and 28.
- 1. The following is a summary of the semi-quantitative open/ onboard stability data for the 5ng/mL cutoff. The mean of the replicates for the 3.75ng/mL level were negative in comparison to the 5ng/mL cutoff for Day 0, 7, 14, 21 and 28. The mean of the replicates of the 6.25ng/mL level were positive in comparison to the 5ng/mL cutoff for Day 0, 7, 14, 21 and 28.
1. Calibrator and Control Traceability - all components of the calibrator and controls have been traced to a commercially available standard solution from Cerilliant Chemicals.

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1. Calibrator and Control Stability An open accelerated stability study was performed at 37°C to establish the initial open vial expiration dating. The stability study supported an initial open vial expiration date of 6 months. The instrument used for this test was a Beckman Coulter AU 400e. All calibrator levels (5, 10, 20 and 40ng/mL) and control levels (3.75 and 6.25ng/mL) were within specifications for Day 0, 3, 7, 10 and 13. This accelerated stability study was performed to establish initial expiration dating. Real time stability studies are ongoing.
မှ.
စာ Calibrator and Control Value Assignment - calibrators and controls are manufactured and are tested by mass spectrometry. If any of the analytes are out of the acceptable range, then the calibrator or control is adjusted and retested. Values are assigned to the calibrator and controls once the Mass spectrometry results are within the acceptable ranges.

H. Conclusion

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

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 10903 New Hampshire Avente Document Control Center - WO66-G609 Silver Spring, MI) 20993-0002

July 1, 2014

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

Re: K141406

Trade/Device Name: Immunalysis Buprenorphine Urine Enzyme Immunoassay Immunalysis Buprenorphine Urine Controls Immunalysis Buprenorphine Urine Calibrators

Regulation Number: 21 CFR 862.3650 Regulation Name: Opiate test system Regulatory Class: II Product Code: DJG. DLJ. LAS Dated: May 23, 2014 Received: May 28, 2014

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 cither class II (Snecial 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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Page 2-Mr. Ginete

electronic product radiation control provisions (Scctions 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/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.lda.gov/MedicalDevices/Safety/ReportalProblem/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,

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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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: December 31, 2013 See PRA Statement on last page.

510(k) Number (if known) K141406

Device Name

Immunalysis Burrenorphine Urine Enzyme Immunalysis Buprenorphine Urine Controls and Calibrators

Indications for Use (Describe)

Immunalysis Buprenorphine Urine Enzyme Immunoassay:

The Inmunalysis Buprenorphine Urine Enzyne Inmunoassay is a homogeneous corzyme immunoassay with a cutoff of Sng/mL. The assay is intended for use in laboratories for the quantitative and semi-quantitative analysis of Buprenorphine with automated clinical chemistry analyzers. This assay is calibrated against Burrenorphine. This in-vitro diagnostic device is for preseription use only.

The semi-quanitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the speciment for confirmation by a confirmatory method such as GC-MS or permitting laboratories to establish quality control procedures. The Immunalysis Buprenorphine Urine Enryne 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 Liguid Chromatography / Mass Spectrospopy (LC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be any drug of abuse test result, particularly when preliminary positive results are used.

Immunalysis Buprenorphine Urine Controls:

The Immunalysis Buprenomhine Urine Control naterials in the Inimunalysis Buprenorphine Urine Enzyne Immunoassay.

Immunalysis Buprenorphine Urine Calibrators:

The Innunalysis Buprenomhine Urine Calibrators are used as calibrators in the Immunalysis Bunrenomhine Urine Enzyme Immunoassy for the qualitative and semination of Burgnomhine in urine on automated clinical chemistry analyzers.

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

X Prescription Use (Part 21 CFR 801 Subpart D)

| Over-The-Counter Use (21 CFR 801 Subpart C)

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

enise Johnson-lyles -

Regulation Number and Section

§ 862.3650 Opiate test system.

(a)
Identification. An opiate test system is a device intended to measure any of the addictive narcotic pain-relieving opiate drugs in blood, serum, urine, gastric contents, and saliva. An opiate is any natural or synthetic drug that has morphine-like pharmocological actions. The opiates include drugs such as morphine, morphine glucoronide, heroin, codeine, nalorphine, and meperedine. Measurements obtained by this device are used in the diagnosis and treatment of opiate use or overdose and in monitoring the levels of opiate administration to ensure appropriate therapy.(b)
Classification. Class II (special controls). An opiate 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).