(280 days)
The LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay is intended for the qualitative and semi-quantitative determination of 6-Acetylmorphine in neat human oral fluid, collected into the LZI Oral Fluid Collector, at the cutoff value of 4 ng/mL. The assay is designed for prescription use with a number of automated clinical chemistry analyzers.
The semi-quantitative mode is for purposes of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as GCMS and LCMS or (2) permitting laboratories to establish quality control procedures.
The LZI Oral Fluid 6-Acetylmorphine Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay at the cutoff value of 4 ng/mL.
The LZI Oral Fluid 6-Acetylmorphine Controls are for use as assayed quality control materials to monitor the precision of the LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay at the cutoff value of 4 ng/mL.
The assay provides only a preliminary analytical result. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. Gas or liquid chromatography/mass spectrometry (GC/MS or LC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.
The LZI Oral Fluid 6-Acetylmorphine assay is a homogeneous enzyme immunoassay with ready-to-use liquid reagent. The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. Enzyme activity decreases upon binding to the antibody, and the drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, 6-Acetylmorphine-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free drug is present in the sample, antibody would bind to free drug, the unbound 6-Acetylmorphine-labeled G6PDH then exhibits its maximal enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that can be measured spectrophotometrically at 340 nm.
The LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit.
The R1 solution contains mouse monoclonal anti-6-Acetylmorphine antibody, glucose-6phosphate (G6P) nicotinamide adenine dinucleotide (NAD), stabilizers, and sodium azide (0.09%) as a preservative. The R2 solution contains glucose-6-phosphate dehydrogenase (G6PDH) labeled with 6-Acetylmorphine in buffer with sodium azide (0.09%) as preservative.
The LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay calibrators and controls designated for use at the 4 ng/mL cutoffs contain 0, 2, 4, 6, 10, and 20 ng/mL of 6-Acetylmorphine in synthetic oral fluid matrix with sodium azide (0.09%) as preservative. These five calibrators and two controls are sold as individual bottles.
The provided document is a 510(k) premarket notification for the LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay (EIA), its calibrators, and controls. This device is an in-vitro diagnostic test for detecting 6-Acetylmorphine in human oral fluid.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. A table of acceptance criteria and the reported device performance
The document does not explicitly state "acceptance criteria" in a separate section with numerical thresholds for performance metrics. Instead, it presents performance characteristic studies (Precision, Analytical Recovery, Method Comparison), and the results of these studies implicitly demonstrate the device's acceptable performance for determining substantial equivalence to a predicate device. The primary performance characteristic related to diagnostic accuracy is the Method Comparison with clinical samples.
Here's a table summarizing the reported device performance, particularly focusing on the "Method Comparison" results, as this is the most direct measure of accuracy against a reference method:
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay) |
|---|---|---|
| Semi-Quantitative Accuracy (Clinical Samples): | ||
| Agreement with GC/MS (Positive) | High agreement expected | 99.0% agreement with GC/MS for positive samples (10 near cutoff positive and 89 high positive samples correctly identified by immunoassay as positive). |
| Agreement with GC/MS (Negative) | High agreement expected | 100.0% agreement with GC/MS for negative samples (20 negative, 14 <50% of cutoff, and 16 near cutoff negative samples correctly identified by immunoassay as negative). |
| Discrepant Samples (Semi-Quantitative) | Minimal, with explanation | 1 discrepant sample (GC/MS: 4.2 ng/mL positive, Immunoassay: 3.5 ng/mL negative). |
| Qualitative Accuracy (Clinical Samples): | ||
| Agreement with GC/MS (Positive) | High agreement expected | 98.0% agreement with GC/MS for positive samples (9 near cutoff positive and 89 high positive samples correctly identified by immunoassay as positive). |
| Agreement with GC/MS (Negative) | High agreement expected | 100.0% agreement with GC/MS for negative samples (20 negative, 14 <50% of cutoff, and 16 near cutoff negative samples correctly identified by immunoassay as negative). |
| Discrepant Samples (Qualitative) | Minimal, with explanation | 2 discrepant samples (GC/MS: 4.2 ng/mL positive, Immunoassay: negative; GC/MS: 4.4 ng/mL positive, Immunoassay: negative). |
| Precision (Semi-Quantitative & Qualitative): | Consistent results expected | At concentrations significantly below and above the 4 ng/mL cutoff, the device consistently reported 100% negative or positive results respectively in both total and within-run precision studies. At the cutoff (4 ng/mL), results showed a mix of positive/negative, as expected. |
| Analytical Recovery: | Acceptable recovery range | Recoveries ranged from 96.7% to 120.0% across various expected concentrations (1 to 20 ng/mL). |
| Interference and Specificity: | No significant interference | No significant undesired cross-reactants or endogenous substance interference observed, except for Ascorbic Acid above 3 mg/mL causing false negatives. |
| Stability (Shipping/Recovery): | Stable for transport | No significant degradation for up to 72 hours. |
| Stability (Sample Storage): | Stable for specified periods | Samples stable at 2-8℃ for up to 15 days; at -20℃ for up to 113 days (real-time studies ongoing). |
| Stability (Open/Recapped Vial): | Stable for specified periods | Reagents, calibrators, and controls stable for 6 months at 2-8℃. |
| Stability (Closed Vial): | Stable for specified periods | Unopened calibrators and controls stable for 6 months at 2-8℃. |
2. Sample size used for the test set and the data provenance
- Test Set Sample Size: 150 clinical unaltered samples were used for the Method Comparison study (clinical samples).
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). It is referred to as "clinical unaltered samples," suggesting real-world specimens, but further details are not provided in the summary.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
The ground truth for the test set in the Method Comparison study was established by Gas Chromatography/Mass Spectrometry (GC/MS) analysis. This is a laboratory analytical method, not a human expert interpretation. Therefore, the concept of "experts" and their qualifications as typically applied in image analysis or clinical diagnosis scenarios (e.g., radiologists) does not directly apply here. The GC/MS method itself is the "gold standard" or reference method for confirmation.
4. Adjudication method for the test set
Not applicable. Since the ground truth was established by GC/MS, an objective chemical analysis, there was no need for human expert adjudication. The immunoassay results were directly compared to the GC/MS 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
Not applicable. This device is an in-vitro diagnostic assay (an enzyme immunoassay) and does not involve human readers interpreting images or data that would be assisted by AI. The comparison is between the immunoassay's analytical result and a confirmatory chemical method (GC/MS).
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, in a sense. The LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay operates as a standalone analytical device. Its performance is measured independently of a human interpreter's input, generating a preliminary analytical result (positive/negative or semi-quantitative concentration). The "human-in-the-loop" aspect comes after this preliminary result, where a more specific method (like GC/MS) is recommended for confirmation, and clinical judgment is required.
7. The type of ground truth used
The ground truth used for the Method Comparison (clinical samples) was Gas Chromatography/Mass Spectrometry (GC/MS) analysis. This is described as the "preferred confirmatory method" and the "independent analytical method" for establishing substantial equivalence.
8. The sample size for the training set
This document describes a premarket notification for an in-vitro diagnostic device, not a machine learning or AI algorithm. Therefore, the concept of a "training set" in the context of AI models does not apply directly. The development of the immunoassay itself would have involved internal validation and optimization, but specific "training set" sizes are not reported in this regulatory submission.
9. How the ground truth for the training set was established
As explained above, the concept of a "training set" as understood for AI/ML devices is not applicable here. The immunoassay is a biochemical reaction-based test. Its development is based on established principles of immunology and enzyme kinetics, and its performance characteristics are demonstrated through analytical and clinical validation studies as detailed in the document (precision, recovery, method comparison to GC/MS). Ground truth for these internal development and validation steps would also have relied on reference analytical methods like GC/MS or gravimetric preparation of known concentration samples.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
February 13, 2015
LIN-ZHI INTERNATIONAL, INC. BERNICE LIN, PH.D. VP OF OPERATIONS 670 ALMANOR AVE SUNNYVALE CA 94085
Re: K141205
Trade/Device Name: LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay LZI Oral Fluid 6-Acetylmorphine Calibrators LZI Oral Fluid 6-Acetylmorphine Controls Regulation Number: 21 CFR 862.3650 Regulation Name: Opiate test system Regulatory Class: II Product Code: DJG, DKB, DIF Dated: February 2, 2015 Received: February 4, 2015
Dear Dr. Bernice Lin:
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 (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Stayce Beck -S
For:
Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K141205
Device Name LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay LZI Oral Fluid 6-Acetylmorphine Calibrators LZI Oral Fluid 6-Acetylmorphine Controls
Indications for Use (Describe)
The LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay is intended for the qualitative and semi-quantitative determination of 6-Acetylmorphine in neat human oral fluid, collected into the LZI Oral Fluid Collector, at the cutoff value of 4 ng/mL. The assay is designed for prescription use with a number of automated clinical chemistry analyzers.
The semi-quantitative mode is for purposes of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as GCMS and LCMS or (2) permitting laboratories to establish quality control procedures.
The LZI Oral Fluid 6-Acetylmorphine Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay at the cutoff value of 4 ng/mL.
The LZI Oral Fluid 6-Acetylmorphine Controls are for use as assayed quality control materials to monitor the precision of the LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay at the cutoff value of 4 ng/mL.
The assay provides only a preliminary analytical result. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. Gas or liquid chromatography/mass spectrometry (GC/MS or LC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.
Type of Use (Select one or both, as applicable)
| Prescription Use (Part 21 CFR 801 Subpart D) |
|---|
| Over-The-Counter Use (21 CFR 801 Subpart C) |
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This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
Introduction
According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.
Submitter name, Address, and Contact
Lin-Zhi International, Inc. 670 Almanor Avenue Sunnyvale, CA 94085 Phone: (408) 732-3856 Fax: (408) 732-3849 e-mail: bclin@lin-zhi.com
| Contact: | Bernice Lin, Ph.D. |
|---|---|
| VP Operations |
Preparation Date
February 12, 2015
Device Name and Classification
| Classification Name: | Enzyme Immunoassay, Opiates |
|---|---|
| Class II, DJG (91 Toxicology), | |
| 21 CFR 862.3650 | |
| Drug Specific Calibrators, | |
| Class II, DLJ (91 Toxicology), | |
| 21 CFR 862.3200 | |
| Drug Specific Controls, | |
| Class I, LAS (91 Toxicology), | |
| 21 CFR 862.3280 | |
| Common Name: | Homogeneous Oral Fluid 6-Acetylmorphine Enzyme Immunoassay |
| Proprietary Name: | LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay, |
| LZI Oral Fluid 6-Acetylmorphine Calibrators | |
| LZI Oral Fluid 6-Acetylmorphine Controls |
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Legally Marketed Predicate Device(s)
The LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay (EIA) (K141205) is substantially equivalent to the Lin-Zhi International, Inc. 6-Acetylmorphine Enzyme Immunoassay, Calibrators and Controls for Hitachi 717 Systems (K101195) manufactured by Lin-Zhi International. Inc. The LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay is identical or similar to its predicate in terms of intended use, method principle, device components, and clinical performance.
Device Description
The LZI Oral Fluid 6-Acetylmorphine assay is a homogeneous enzyme immunoassay with ready-to-use liquid reagent. The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. Enzyme activity decreases upon binding to the antibody, and the drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, 6-Acetylmorphine-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free drug is present in the sample, antibody would bind to free drug, the unbound 6-Acetylmorphine-labeled G6PDH then exhibits its maximal enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that can be measured spectrophotometrically at 340 nm.
The LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit.
The R1 solution contains mouse monoclonal anti-6-Acetylmorphine antibody, glucose-6phosphate (G6P) nicotinamide adenine dinucleotide (NAD), stabilizers, and sodium azide (0.09%) as a preservative. The R2 solution contains glucose-6-phosphate dehydrogenase (G6PDH) labeled with 6-Acetylmorphine in buffer with sodium azide (0.09%) as preservative.
The LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay calibrators and controls designated for use at the 4 ng/mL cutoffs contain 0, 2, 4, 6, 10, and 20 ng/mL of 6-Acetylmorphine in synthetic oral fluid matrix with sodium azide (0.09%) as preservative. These five calibrators and two controls are sold as individual bottles.
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Intended Use
The LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay is intended for the qualitative and semi-quantitative determination of 6-Acetylmorphine in neat human oral fluid, collected into the LZI Oral Fluid Collector, at the cutoff value of 4 ng/mL. The assay is designed for prescription use with a number of automated clinical chemistry analyzers.
The semi-quantitative mode is for purposes of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as GC/MS or (2) permitting laboratories to establish quality control procedures.
The LZI Oral Fluid 6-Acetylmorphine Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay at the cutoff value of 4 ng/mL.
The LZI Oral Fluid 6-Acetylmorphine Controls are for use as assayed quality control materials to monitor the precision of the LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay at the cutoff value of 4 ng/mL.
The assay provides only a preliminary analytical result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.
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Comparison to Predicate Device
The LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay (K141205) is substantially equivalent to the Lin-Zhi International, Inc. 6-Acetylmorphine Enzyme Immunoassay, Calibrators and Controls for Hitachi 717 Systems cleared by the FDA under the premarket notification K101195 for its stated intended use.
The following table compares LZI's Oral Fluid 6-Acetylmorphine Enzyme Immunoassay with the predicate device.
| DeviceCharacteristics | Subject Device (K141205)LZI Oral Fluid 6-AcetylmorphineEnzyme Immunoassay, Calibrators andControls | Predicate Device (K101195)LZI 6-Acetylmorphine EnzymeImmunoassay, Calibrators and Controls |
|---|---|---|
| Intended Use | The LZI Oral Fluid 6-AcetylmorphineEnzyme Immunoassay, when used inconjunction with the Beckman AU400eautomated clinical system analyzers, isintended for the qualitative and semi-quantitative determination of 6-Acetylmorphine in neat human oral fluid,collected into the LZI Oral FluidCollector, at the cutoff value 4 ng/mL.The assay is designed for prescription usewith a number of automated clinicalchemistry analyzers.This assay provides a rapid screening procedurefor determining the presence of 6-Acetylmorphinein oral fluid. The assay provides only apreliminary analytical result. A more specificalternative chemical method must be used in orderto obtain a confirmed analytical result. Gaschromatography/mass spectrometry (GC/MS) is thepreferred confirmatory method. Clinicalconsideration and professional judgment should beexercised with any drug of abuse test result,particularly when the preliminary test result ispositive. | The LZI 6-Acetylmorphine EnzymeImmunoassay, when used in conjunctionwith Hitachi 717 automated clinicalsystem analyzers, is intended for thequalitative and semi-quantitativedetermination of 6-Acetylmorphine inhuman urine, at a cutoff value of 10ng/mL. The assay is designed forprofessional use with a number ofautomated clinical chemistry analyzers.This assay provides a rapid screening procedurefor determining the presence of 6-Acetylmorphinein urine. The assay provides only a preliminaryanalytical result. A more specific alternativechemical method must be used in order to obtain aconfirmed analytical result. Gas or liquidchromatography/mass spectrometry (GC/MS orLC/MS) is the preferred confirmatory method.Clinical consideration and professional judgmentshould be exercised with any drug of abuse testresult, particularly when the preliminary test resultis positive. |
| Analyte | 6-Acetylmorphine | 6-Acetylmorphine |
| Cutoff | 4 ng/ml | 10 ng/mL |
| Matrix | Oral fluid | Urine |
| Calibrator | 5 Levels | 5 Levels |
| Levels | (0, 2, 4, 10, 20 ng/mL) | (0, 5, 10, 20, 40 ng/mL) |
| Control Levels | 2 Levels | 2 Levels |
| (2 ng/mL, 6 ng/mL) | (7.5 ng/mL, 12.5 ng/mL) | |
| Storage | 2-8 ℃ until expiration date | 2-8 ℃ until expiration date |
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Performance Characteristics Summary: Beckman AU400e Analyzer
Precision:
| 4 ng/mL Cutoff Result: | |||||
|---|---|---|---|---|---|
| Sample Concentration | % of Cutoff | Total Precision | Within Run Precision | ||
| Number of Determination | Immunoassay Result | Number of Determination | Immunoassay Result | ||
| 0 ng/mL | -100.0% | 80 | 80 Negative | 20 | 20 Negative |
| 1 ng/mL | -75.0% | 80 | 80 Negative | 20 | 20 Negative |
| 2 ng/mL | -50.0% | 80 | 80 Negative | 20 | 20 Negative |
| 3 ng/mL | -25.0% | 80 | 80 Negative | 20 | 20 Negative |
| 4 ng/mL | 100.0% | 80 | 32 Pos/48 Neg | 20 | 8 Pos/12 Neg |
| 5 ng/mL | +25.0% | 80 | 80 Positive | 20 | 20 Positive |
| 6 ng/mL | +50.0% | 80 | 80 Positive | 20 | 20 Positive |
| 7 ng/mL | +75.0% | 80 | 80 Positive | 20 | 20 Positive |
| 8 ng/mL | +100.0% | 80 | 80 Positive | 20 | 20 Positive |
Semi-Quantitative Positive/Negative Results:
Qualitative (ΔΟD Value) Positive/Negative Results:
| 4 ng/mL Cutoff Result: | Total Precision | Within Run Precision | ||||
|---|---|---|---|---|---|---|
| SampleConcentration | % of Cutoff | Number ofDetermination | ImmunoassayResult | Number ofDetermination | ImmunoassayResult | |
| 0 ng/mL | -100.0% | 80 | 80 Negative | 20 | 20 Negative | |
| 1 ng/mL | -75.0% | 80 | 80 Negative | 20 | 20 Negative | |
| 2 ng/mL | -50.0% | 80 | 80 Negative | 20 | 20 Negative | |
| 3 ng/mL | -25.0% | 80 | 80 Negative | 20 | 20 Negative | |
| 4 ng/mL | 100.0% | 80 | 18 Pos/62 Neg | 20 | 4 Pos/16 Neg | |
| 5 ng/mL | +25.0% | 80 | 80 Positive | 20 | 20 Positive | |
| 6 ng/mL | +50.0% | 80 | 80 Positive | 20 | 20 Positive | |
| 7 ng/mL | +75.0% | 80 | 80 Positive | 20 | 20 Positive | |
| 8 ng/mL | +100.0% | 80 | 80 Positive | 20 | 20 Positive |
Analytical Recovery:
| Expected Value(ng/mL) | Observed Value(ng/mL) | % Recovery |
|---|---|---|
| 1 | 1.2 | 120.0 |
| 2 | 2.2 | 110.0 |
| 4 | 4.3 | 107.5 |
| 6 | 5.8 | 96.7 |
| 8 | 8.1 | 101.3 |
| 10 | 10.1 | 101.0 |
| 12 | 12.1 | 100.8 |
| 14 | 15.0 | 107.1 |
| 16 | 16.8 | 105.0 |
| 18 | 18.8 | 104.4 |
| 20 | 20.6 | 103.0 |
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Method Comparison: Clinical Samples
From a total of one-hundred-fifty (150) clinical unaltered samples
Clinical Samples Correlation Results: Semi-Quantitative Accuracy Study
| 4 ng/mLCutoff | Negative | < 50 % of thecutoffconcentrationby GC/MSanalysis | Near CutoffNegative(Between 50 %below the cutoffand the cutoffconcentration) | Near CutoffPositive(Between thecutoff and 50 %above the cutoffconcentration) | High Positive(Greater than50 % above thecutoffconcentration) | %Agreement |
|---|---|---|---|---|---|---|
| Positive | 0 | 0 | 0 | 10 | 89 | 99.0% |
| Negative | 20 | 14 | 16 | 1 * | 0 | 100.0% |
Discrepant samples determined as compared to the Estimated GC/MS Total Value
| DiscrepantSample# | GC/MS6AM(ng/mL) | Pos/NegResult | AU400eImmunoassaySemi-QuantitativeResult (ng/mL) | Pos/NegResult |
|---|---|---|---|---|
| 51* | 4.2 | + | 3.5 | - |
Clinical Samples Correlation Results: Qualitative Accuracy Study (ΔΟD, mAu)
| 4 ng/mLCutoff | Negative | < 50 % of thecutoffconcentrationby GC/MSanalysis | Near CutoffNegative(Between 50 %below the cutoffand the cutoffconcentration) | Near CutoffPositive(Between thecutoff and 50 %above the cutoffconcentration) | High Positive(Greater than50 % above thecutoffconcentration) | %Agreement |
|---|---|---|---|---|---|---|
| Positive | 0 | 0 | 0 | 9 | 89 | 98.0% |
| Negative | 20 | 14 | 16 | 2* | 0 | 100.0% |
| DiscrepantSample# | GC/MS6AM(ng/mL) | Pos/NegResult | AU400eImmunoassayQualitativeResult (mAu) | CutoffΔOD(mAu) | Pos/NegResult |
|---|---|---|---|---|---|
| 51* | 4.2 | + | 662.9 | 678.6 | - |
| 52* | 4.4 | + | 675.3 | 701.6 | - |
Endogenous Compound Interference and Specificity - Cross-Reactivity:
No significant undesired cross reactants or endogenous substance interference was observed at physiologically relevant concentrations. Ascorbic Acid concentrations above 3 mg/mL cause false-negative results. See product insert for list of compounds tested.
Shipping/Recovery Stability Study:
No significant sample degradation occurred following real-time and accelerated stability studies up to 72 hours. All sample shipments are based on the assumption of a 24 hour priority overnight delivery.
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Sample Storage Stability Study:
No significant sample degradation occurred following real-time stability studies. Based on realtime studies, samples can be stored at 2-8 ℃ for up to 15 Days. Based on real-time studies, samples can be stored at -20 ℃ for up to 113 Days. Real-time stability studies are on-going.
Open (and re-capped) vial Stability for Reagent and Calibrator/Control:
Real time (2-8°C) and accelerated stability studies (at room temperature. ~25°C and 30°C) were performed. Results indicated that opened and recapped calibrators and controls are stable for 6 months when stored at (2-8℃).
Closed vial Stability for Calibrator/Control:
Real time (2-8°C) stability studies were performed. Results indicated that unopened calibrators and controls are stable for 6 months when stored at 2-8℃.
Summary:
The information provided in this pre-market notification demonstrates that the LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay is substantially equivalent to the legally marketed predicate device for its general intended use. Substantial equivalence was demonstrated through comparison of intended use and physical properties to the commercially available predicate device as confirmed by gas chromatography/mass spectrometry (GC/MS), an independent analytical method. The information supplied in this pre-market notification provides reasonable assurance that the LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay is safe and effective for its stated intended use.
§ 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).