(50 days)
The LZI Hydrocodone Enzyme Immunoassay is intended for the qualitative and semi-quantitative determination of hydrocodone in human urine at the cutoff values of 100 and 300 ng/mL when calibrated against hydrocodone. 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 Hydrocodone Drugs of Abuse (DAU) Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the LZI Hydrocodone Enzyme Immunoassay at the cutoff values of 100 and 300 ng/mL.
The LZI Hydrocodone Drugs of Abuse (DAU) Controls are for use as assayed quality control materials to monitor the precision of the LZI Hydrocodone Enzyme Immunoassay at the cutoff values of 100 and 300 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 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 Hydrocodone assay is a homogeneous enzyme immunoassay with ready-to-use liquid reagents. 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, hydrocodone-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 hydrocodone-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 Hydrocodone Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit.
The Ri solution contains mouse monoclonal anti-hydrocodone antibody, glucose-6-phosphate (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 hydrocodone in buffer with sodium azide (0.09%) as preservative.
The LZI Hydrocodone Enzyme Immunoassay calibrators and controls designated for use at the 100 ng/mL cutoff contain 0, 50, 75, 100, 125, 150, and 300 ng/mL of hydrocodone in human urine with sodium azide (0.09%) as preservative. These five calibrators and two controls are sold as individual bottles.
The LZI Hydrocodone Enzyme Immunoassay calibrators and controls designated for use at the 300 ng/mL cutoff contain 0. 150. 225. 300. 375. 500. and 800 ng/mL of hydrocodone in human urine with sodium azide (0.09%) as preservative. These five calibrators and two controls are sold as individual bottles.
"The LZI Hydrocodone Enzyme Immunoassay is an in-vitro diagnostic device intended for the qualitative and semi-quantitative detection of hydrocodone in human urine. The device offers two cutoff values: 100 ng/mL and 300 ng/mL. The performance studies evaluate the device's precision, linearity, cross-reactivity, and interference with clinical samples for both cutoff values.
1. A table of acceptance criteria and the reported device performance:
The document primarily presents performance data rather than explicit acceptance criteria. However, for a device of this type, the expectation is high agreement with a gold standard (GC/MS or LC/MS) and consistent performance across various conditions. Based on the provided performance summaries, the implied acceptance criteria would relate to the percentage of agreement with the confirmatory method for clinical samples, and consistent performance for precision, linearity, and minimal interference.
Implied Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (100 ng/mL Cutoff) | Reported Device Performance (300 ng/mL Cutoff) |
|---|---|---|---|
| Method Comparison (Clinical Samples) | High percentage agreement with GC/MS or LC/MS. Near cutoff samples should exhibit predictable behavior (some disagreement expected at the exact cutoff, but generally high accuracy above and below). | Total Agreement: 92.5% Discrepant Samples: - 3 GC/MS/LC/MS Negative samples were LZI EIA Positive (all near cutoff, e.g., 85.1 ng/mL, 97.0 ng/mL). - 3 GC/MS/LC/MS Positive samples were LZI EIA Negative (all near cutoff, e.g., 128.8 ng/mL, 138.5 ng/mL, 146.5 ng/mL). | Total Agreement: 95.0% Discrepant Samples: - 2 GC/MS/LC/MS Negative samples were LZI EIA Positive (both near cutoff, e.g., 206.9 ng/mL, 246.0 ng/mL). - 2 GC/MS/LC/MS Positive samples were LZI EIA Negative (both near cutoff, e.g., 301.0 ng/mL, 306.2 ng/mL). |
| Precision | Consistent classification (positive/negative) for samples clearly above/below cutoff. Some variability allowed at cutoff. | Semi-Quantitative and Qualitative: Consistency for samples at -100.0% to -25.0% of cutoff (all negative) and +25.0% to +100.0% of cutoff (all positive). At 100 ng/mL cutoff: - Semi-Quant: 43 Pos/45 Neg (Total 88) - Qual: 28 Pos/60 Neg (Total 88) | Semi-Quantitative and Qualitative: Consistency for samples at -100.0% to -25.0% of cutoff (all negative) and +25.0% to +100.0% of cutoff (all positive). At 300 ng/mL cutoff: - Semi-Quant: 47 Pos/41 Neg (Total 88) - Qual: 51 Pos/37 Neg (Total 88) |
| Linearity (Recovery) | Percent recovery close to 100% for serially diluted samples over the assay range. | For samples from 25 ng/mL to 300 ng/mL, % Recovery ranged from 96.1% to 102.8%. (5 ng/mL sample showed 73.6% recovery, 0 ng/mL showed N/A, 0.4 ng/mL determined). Regression: y = 1.0139x - 1.174, r2 = 0.9995 | For samples from 100 ng/mL to 800 ng/mL, % Recovery ranged from 100.8% to 105.3%. (10 ng/mL sample showed 124.6% recovery, 0 ng/mL showed N/A, 0.5 ng/mL determined). Regression: y = 1.0316x + 1.1461, r2 = 0.9988 |
| Cross-reactivity | Minimal or no cross-reactivity with structurally unrelated compounds; quantified cross-reactivity for related compounds. | Quantified cross-reactivity for hydrocodone and metabolites (e.g., Hydromorphone 85.08%). Structurally related compounds showed low % cross-reactivity (e.g., Oxycodone 2.1%). No significant cross-reactivity with structurally unrelated compounds. | Quantified cross-reactivity for hydrocodone and metabolites (e.g., Hydromorphone 78.13%). Structurally related compounds showed low % cross-reactivity (e.g., Oxycodone 0.08%). No significant cross-reactivity with structurally unrelated compounds. |
| Interference (Endogenous, pH, Specific Gravity) | No significant interference observed, leading to correct classification (Neg/Pos) for control concentrations. | No significant undesired interference observed with tested endogenous substances, pH values (3-11), or specific gravity levels (1.000-1.030) for both negative (75 ng/mL) and positive (125 ng/mL) controls. | No significant undesired interference observed with tested endogenous substances, pH values (3-11), or specific gravity levels (1.000-1.030) for both negative (225 ng/mL) and positive (375 ng/mL) controls. |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
-
Sample Size for Test Set:
- Precision Studies: For the precision studies (both semi-quantitative and qualitative), at each concentration level, 22 determinations were made "Within Run," and a "Total Precision" of 88 determinations was reported. However, the total number of unique samples used for the precision study is not explicitly stated. The concentrations were prepared by spiking known amounts of hydrocodone.
- Linearity Studies: For each cutoff, a drug-free urine pool spiked with hydrocodone was serially diluted. Each dilution was run in 10 replicates ("10 replicates on the AU480 instrument"). The total number of unique samples (dilution points) was 12 for the 100 ng/mL cutoff and 11 for the 300 ng/mL cutoff.
- Method Comparison - Clinical Samples: 80 unaltered clinical urine specimens were tested for each cutoff (100 ng/mL and 300 ng/mL).
- Cross-reactivity Studies: Various potentially interfering substances and structurally related/unrelated compounds were tested. The number of unique samples/compounds or replicates for each is not explicitly stated, but the results for each compound are provided.
- Interference (Endogenous, pH, Specific Gravity):
- Endogenous Compound Interference: Various endogenous compounds were tested. Each compound was spiked into a drug-free urine pool, and then split into 3 portions (unspiked, 75/125 ng/mL hydrocodone, or 225/375 ng/mL hydrocodone). The specific number of unique tests for each compound is not explicitly stated beyond these three spiked concentrations.
- pH Interference: Pooled drug-free processed urine samples were adjusted to 9 different target pH values (3-11). Each pH sample was split into 3 portions (unspiked, negative control, positive control). So, 9 x 3 = 27 test conditions for each cutoff.
- Specific Gravity Interference: Ten drug-free urine samples with specific gravity ranging from 1.000 to 1.030 were used. Each sample was split into 3 portions (unspiked, negative control, positive control). So, 10 x 3 = 30 test conditions for each cutoff.
-
Data Provenance:
- The document does not explicitly state the country of origin for the clinical samples or for the data collection in general.
- The clinical samples used for the Method Comparison were "unaltered clinical urine specimens," suggesting they were collected from patients. The nature of precision, linearity, cross-reactivity, and interference studies (using spiked drug-free urine or prepared solutions) indicates these were laboratory-based, controlled experiments rather than prospective or retrospective analysis of patient data.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
- For the Method Comparison - Clinical Samples, the ground truth was established by GC/MS or LC/MS. This is an analytical laboratory method, not dependent on human expert interpretation in the same way as, for example, radiological imaging.
- Therefore, the concept of "number of experts" or their "qualifications" for establishing ground truth is not applicable in this context. The accuracy of GC/MS or LC/MS as the confirmatory method itself is assumed.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
- Since the ground truth for the clinical samples was established by GC/MS or LC/MS, an instrumental analytical method, there was no human adjudication process involved. The result of the GC/MS or LC/MS determined the ground truth directly.
- For the other studies (precision, linearity, cross-reactivity, interference), the ground truth was based on the known concentrations and compositions of the spiked samples.
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 an in-vitro diagnostic assay for drug detection in urine, which does not involve human readers interpreting images or data directly in a clinical decision-making pathway. The device itself performs the detection, and a laboratory professional would interpret the instrument's output. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Yes, the primary performance studies presented are for the LZI Hydrocodone Enzyme Immunoassay operating in a standalone manner. The "LZI Hydrocodone Enzyme Immunoassay" (EIA) itself is the algorithm/device.
- The device provides a "preliminary analytical result" which then requires "a more specific alternative chemical method... GC/MS or LC/MS" for confirmation. While human oversight is always present in a lab setting, the performance data (precision, linearity, clinical sample comparison, cross-reactivity, interference) are solely reflecting the analytical performance of the assay itself on the AU480 analyzer, without direct human-in-the-loop interaction influencing the result generation. The purpose of the semi-quantitative mode is for laboratories to determine appropriate dilution for confirmation, implying the EIA acts as a screening tool.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
- For the Method Comparison study with clinical samples (the most relevant for assessing diagnostic accuracy), the ground truth was established using Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/Mass Spectrometry (LC/MS). These are highly sensitive and specific analytical techniques widely considered the gold standard for drug quantification and confirmation in toxicology.
- For other studies (Precision, Linearity, Cross-reactivity, Interference), the ground truth for the samples was the known concentration/presence of hydrocodone and other substances as prepared by spiking into drug-free urine pools.
8. The sample size for the training set
- The document does not explicitly mention a separate "training set" as would be typical for machine learning algorithms. The LZI Hydrocodone Enzyme Immunoassay is described as a homogeneous enzyme immunoassay kit with liquid reagents, not an AI or machine learning-based device that undergoes a distinct training phase with a dataset.
- The calibrators used to establish reference curves (0, 50, 75, 100, 125, 150, and 300 ng/mL for the 100 ng/mL cutoff; 0, 150, 225, 300, 375, 500, and 800 ng/mL for the 300 ng/mL cutoff) could be considered analogous to training data for the assay, allowing it to quantify hydrocodone based on enzyme activity. However, these are part of the kit's operation, not a separate training phase.
9. How the ground truth for the training set was established
- As mentioned above, the concept of a "training set" in the context of an AI/ML algorithm is not directly applicable to this enzyme immunoassay device.
- The "ground truth" for the calibrators is their known, precisely manufactured concentrations of hydrocodone in human urine. These calibrators are provided as part of the LZI Hydrocodone Enzyme Immunoassay kit and are used to establish the assay's reference curve, which dictates how the instrument interprets enzyme activity into hydrocodone concentration.
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JUN 1 3 2014
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 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
Device Name and Classification
| Classification Name: | Enzyme Immunoassay, Hydrocodone | |
|---|---|---|
| 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: Proprietary Name: Homogeneous Hydrocodone Enzyme Immunoassay LZI Hydrocodone Enzyme Immunoassay, LZI Hydrocodone Drugs of Abuse (DAU) Calibrators LZI Hydrocodone Drugs of Abuse (DAU) Controls
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Legally Marketed Predicate Device(s)
The LZI Hydrocodone Enzyme Immunoassay (EIA) is substantially equivalent to the Lin-Zhi International. Inc. Oxycodone Enzyme Immunoassay (K120763) manufactured by Lin-Zhi International. Inc. The LZI Hydrocodone 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 Hydrocodone assay is a homogeneous enzyme immunoassay with ready-to-use liquid reagents. 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, hydrocodone-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 hydrocodone-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 Hydrocodone Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit.
The Ri solution contains mouse monoclonal anti-hydrocodone antibody, glucose-6-phosphate (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 hydrocodone in buffer with sodium azide (0.09%) as preservative.
The LZI Hydrocodone Enzyme Immunoassay calibrators and controls designated for use at the 100 ng/mL cutoff contain 0, 50, 75, 100, 125, 150, and 300 ng/mL of hydrocodone in human urine with sodium azide (0.09%) as preservative. These five calibrators and two controls are sold as individual bottles.
The LZI Hydrocodone Enzyme Immunoassay calibrators and controls designated for use at the 300 ng/mL cutoff contain 0. 150. 225. 300. 375. 500. and 800 ng/mL of hydrocodone in human urine 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 Hydrocodone Enzyme Immunoassay is intended for the qualitative and semiquantitative determination of hydrocodone in human urine at the cutoff values of 100 and 300 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 Hydrocodone Drugs of Abuse (DAU) Calibrators are for use as calibrators in the qualitative and semi-quantitative callbration of the LZI Hydrocodone Enzyme Immunoassay at the cutoff values of 100 and 300 ng/mL.
The LZI Hydrocodone Drugs of Abuse (DAU) Controls are for use as assayed quality control materials to monitor the precision of the LZI Hydrocodone Enzyme Immunoassay at the cutoff values of 100 and 300 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 or liguid 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.
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Comparison to Predicate Device
The LZI Hydrocodone Enzyme Immunoassay is substantially equivalent to the Lin-Zhi International, Inc. Oxycodone Enzyme Immunoassay, Calibrators and Controls for Hitachi 717 Systems cleared by the FDA under the premarket notification K120763 for its stated intended use.
The following table compares LZI's Hydrocodone Enzyme Immunoassay with the predicate device.
| DeviceCharacteristics | Subject Device | Predicate Device (K120763) |
|---|---|---|
| LZI Hydrocodone Enzyme Immunoassay,Calibrators and Controls | LZI Oxycodone Enzyme Immunoassay,Calibrators and Controls | |
| Intended Use | The LZI Hydrocodone EnzymeImmunoassay, when used in conjunctionwith the AU480 automated clinicalsystem analyzers, is intended for thequalitative and semi-quantitativedetermination of hydrocodone in humanurine at cutoff values of 100 or 300ng/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 hydrocodone andhydromorphone in urine. The assay provides onlya preliminary analytical result. A more specificalternative chemical method must be used in orderto obtain a confirmed analytical result. Gas orliquid chromatography/mass spectrometry (GC/MSor LC/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. | The LZI Oxycodone EnzymeImmunoassay, when used in conjunctionwith Hitachi 717 automated clinicalsystem analyzers, is intended for thequalitative and semi-quantitativedetermination of oxycodone andoxymorphone in human urine at cutoffvalues of 100 or 300 ng/mL. The assay isdesigned for professional use with anumber of automated clinical chemistryanalyzers.This assay provides a rapid screening procedurefor determining the presence of oxycodone andoxymorphone in urine. The assay provides only apreliminary analytical result. A more specificalternative chemical method must be used in orderto obtain a confirmed analytical result. Gas orliquid chromatography/mass spectrometry (GC/MSor LC/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 | Hydrocodone | Oxycodone |
| Cutoff | 100 or 300 ng/ml | 100 or 300 ng/ml |
| Matrix | Urine | Urine |
| CalibratorsLevel | 100 ng/mL Cutoff: 5 Levels0, 50, 100, 150, and 300 ng/mL300 ng/mL Cutoff: 5 Levels0, 150, 300, 500, and 800 ng/mL | 0, 50, 100, 300, 500, and 800ng/mL |
| Controls Level | 100 ng/mL Cutoff: 2 Levels(75 ng/mL, 125 ng/mL)300 ng/mL Cutoff: 2 Levels(225 ng/mL, 375 ng/mL) | 100 ng/mL Cutoff: 2 Levels(75 ng/mL, 125 ng/mL)300 ng/mL Cutoff: 2 Levels(225 ng/mL, 375 ng/mL) |
| Storage | 2-8 °C until expiration date | 2-8 °C until expiration date |
(
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Performance Characteristics Summary:
AU480 Analyzer
Precision: 100 ng/mL Cutoff
Semi-Quantitative Positive/Negative Results:
The following concentrations were determined with reference curves from 5 calibrators. Typical results were measured as ng/mL. Positive/Negative results are as follows:
| 100 ng/mL Cutoff Result: | Within Run (N=22) | Total Precision (N=88) | |||
|---|---|---|---|---|---|
| Hydrocodone | % of Cutoff | Number of | Immunoassay | Number of | Immunoassay |
| Concentration | Determination | Result | Determination | Result | |
| 0 ng/mL | -100.0% | 22 | 22 Negative | 88 | 88 Negative |
| 25 ng/mL | -75.0% | 22 | 22 Negative | 88 | 88 Negative |
| 50 ng/mL | -50.0% | 22 | 22 Negative | 88 | 88 Negative |
| 75 ng/mL | -25.0% | 22 | 22 Negative | 88 | 88 Negative |
| 100 ng/mL | 100.0% | 22 | 8 Pos/14 Neg | 88 | 43 Pos/45 Neg |
| 125 ng/mL | +25.0% | 22 | 22 Positive | 88 | 88 Positive |
| 150 ng/mL | +50.0% | 22 | 22 Positive | 88 | 88 Positive |
| 175 ng/mL | +75.0% | 22 | 22 Positive | 88 | 88 Positive |
| 200 ng/mL | +100.0% | 22 | 22 Positive | 88 | 88 Positive |
Qualitative Positive/Negative Results:
The following concentrations were evaluated. Typical qualitative results were measured as ΔOD (mAu). Positive/Negative results are as follows:
| 100 ng/mL Cutoff Result: | Within Run (N=22) | Total Precision (N=88) | |||
|---|---|---|---|---|---|
| HydrocodoneConcentration | % of Cutoff | Number ofDetermination | ImmunoassayResult | Number ofDetermination | ImmunoassayResult |
| 0 ng/mL | -100.0% | 22 | 22 Negative | 88 | 88 Negative |
| 25 ng/mL | -75.0% | 22 | 22 Negative | 88 | 88 Negative |
| 50 ng/mL | -50.0% | 22 | 22 Negative | 88 | 88 Negative |
| 75 ng/mL | -25.0% | 22 | 22 Negative | 88 | 88 Negative |
| 100 ng/mL | 100.0% | 22 | 7 Pos/ 15 Neg | 88 | 28 Pos/60 Neg |
| 125 ng/mL | +25.0% | 22 | 22 Positive | 88 | 88 Positive |
| 150 ng/mL | +50.0% | 22 | 22 Positive | 88 | 88 Positive |
| 175 ng/mL | +75.0% | 22 | 22 Positive | 88 | 88 Positive |
| 200 ng/mL | +100.0% | 22 | 22 Positive | 88 | 88 Positive |
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AU480 Analyzer
Precision: 300 ng/mL Cutoff
Semi-Quantitative Positive/Negative Results:
The following concentrations were determined with reference curves from 5 calibrators. Typical results were measured as ng/mL. Positive/Negative results are as follows:
| 300 ng/mL Cutoff Result: | Within Run (N=22) | Total Precision (N=88) | |||
|---|---|---|---|---|---|
| HydrocodoneConcentration | % of Cutoff | Number ofDetermination | ImmunoassayResult | Number ofDetermination | ImmunoassayResult |
| 0 ng/mL | -100.0% | 22 | 22 Negative | 88 | 88 Negative |
| 75 ng/mL | -75.0% | 22 | 22 Negative | 88 | 88 Negative |
| 150 ng/mL | -50.0% | 22 | 22 Negative | 88 | 88 Negative |
| 225 ng/mL | -25.0% | 22 | 22 Negative | 88 | 88 Negative |
| 300 ng/mL | 100.0% | 22 | 14 Pos/ 8 Neg | 88 | 47 Pos/ 41 Neg |
| 375 ng/mL | +25.0% | 22 | 22 Positive | 88 | 88 Positive |
| 450 ng/mL | +50.0% | 22 | 22 Positive | 88 | 88 Positive |
| 525 ng/mL | +75.0% | 22 | 22 Positive | 88 | 88 Positive |
| 600 ng/mL | +100.0% | 22 | 22 Positive | 88 | 88 Positive |
Qualitative Positive/Negative Results:
The following concentrations were evaluated. Typical qualitative results were measured as ΔOD (mAu). Positive/Negative results are as follows:
| 300 ng/mL Cutoff Result: | Within Run (N=22) | Total Precision (N=88) | |||
|---|---|---|---|---|---|
| Hydrocodone | % of Cutoff | Number of | Immunoassay | Number of | Immunoassay |
| Concentration | Determination | Result | Determination | Result | |
| 0 ng/mL | -100.0% | 22 | 22 Negative | 88 | 88 Negative |
| 75 ng/mL | -75.0% | 22 | 22 Negative | 88 | 88 Negative |
| 150 ng/mL | -50.0% | 22 | 22 Negative | 88 | 88 Negative |
| 225 ng/mL | -25.0% | 22 | 22 Negative | 88 | 88 Negative |
| 300 ng/mL | 100.0% | 22 | 11 Pos/11 Neg | 88 | 51 Pos/37 Neg |
| 375 ng/mL | +25.0% | 22 | 22 Positive | 88 | 88 Positive |
| 450 ng/mL | +50.0% | 22 | 22 Positive | 88 | 88 Positive |
| 525 ng/mL | +75.0% | 22 | 22 Positive | 88 | 88 Positive |
| 600 ng/mL | +100.0% | 22 | 22 Positive | 88 | 88 Positive |
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Linearity: 100 ng/mL Cutoff
To demonstrate linearity for purposes of sample dilution and quality control (see semiquantitative results section) over the entire assay range, a drug free-urine pool spiked with hydrocodone at 300 ng/ml. was serially diluted. Each sample was run in 10 replicates on the AU480 instrument and the average was used to determine percent recovery compared to the expected target value. When comparing the result (y) and target (x) value, using the least squares regression technique, the regression equation and correlation are as follow:
v = 1.0139x - 1.174. r2 = 0.9995
| Target Concentration(ng/mL) | Determined(ng/mL) | % Recovery |
|---|---|---|
| 300 | 299.0 | 99.7% |
| 250 | 254.2 | 101.7% |
| 200 | 205.6 | 102.8% |
| 175 | 177.3 | 101.3% |
| 150 | 152.6 | 101.7% |
| 125 | 124.9 | 99.9% |
| 100 | 98.2 | 98.2% |
| 75 | 73.3 | 97.8% |
| 50 | 48.1 | 96.1% |
| 25 | 24.1 | 96.4% |
| 5 | 3.7 | 73.6% |
| 0 | 0.4 | N/A |
Linearity: 300 ng/mL Cutoff
To demonstrate linearity for purposes of sample dilution and quality control (see semiquantitative results section) over the entire assay range, a drug free-urine pool spiked with hydrocodone at 800 ng/mL was serially diluted. Each sample was run in 10 replicates on the A U480 instrument and the average was used to determine percent recovery compared to the expected target value. When comparing the result (y) and target (x) value, using the least squares regression technique, the regression equation and correlation are as follow:
y = 1.0316x + 1.1461, r2 = 0.9988
| Target Concentration(ng/mL) | Determined(ng/mL) | % Recovery |
|---|---|---|
| 800 | 806.3 | 100.8% |
| 700 | 736.9 | 105.3% |
| 500 | 510.1 | 102.0% |
| 425 | 445.5 | 104.8% |
| 375 | 393.2 | 104.9% |
| 300 | 304.4 | 101.5% |
| 225 | 230.7 | 102.5% |
| 150 | 152.9 | 101.9% |
| 100 | 104.0 | 104.0% |
| 10 | 12.5 | 124.6% |
| 0 | 0.5 | N/A |
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Method Comparison - Clinical Samples: 100 ng/mL Cutoff
Eighty (80) unaltered clinical urine specimens were tested with the LZI Hydrocodone Enzyme Immunoassay and confirmed with GC/MS or LC/MS. Specimens having a hydrocodone and hydromorphone total concentration greater than 100 ng/mL by GC/MS or LC/MS are defined as positive, and specimens with total concentrations below 100 ng/mL by GC/MS or LC/MS are defined as negative in the table below. The correlation results are summarized as follows: (near cutoff samples are defined as ± 50% of the cutoff value). Adjusted Total hydrocodone and hydromorphone GC/MS or LC/MS values corrected for cross-reactivity (Hydrocodone Cross = 100%, Hydromorphone Cross = 85%) were compared with the EIA result.
| 100 ng/mLCutoff | Neg | < 50 % ofthe cutoff | Near CutoffNeg. | Near CutoffPos. | High Pos. | %Agree-ment |
|---|---|---|---|---|---|---|
| Positive | 0 | 0 | 3* | 5 | 32 | 92.5 % |
| Negative | 20 | 4 | 13 | 3** | 0 | 92.5 % |
| 100 ng/mLCutoff | GC/MS orLC/MS | LZI EIA | Adjusted TotalHydrocodone+ HydromorphoneGC/MS or LC/MS(ng/mL) | LZI EIA(ng/mL) |
|---|---|---|---|---|
| Sample #37* | - | + | 85.1 | 100.5 |
| Sample #39* | - | + | 97.0 | 105.4 |
| Sample #40* | - | + | 97.0 | 101.6 |
| Sample #44** | + | - | 128.8 | 93.1 |
| Sample #45** | + | - | 138.5 | 93.7 |
| Sample #46** | + | - | 146.5 | 88.1 |
Semi-Quantitative & Qualitative Data:
{8}------------------------------------------------
Method Comparison - Clinical Samples: 300 ng/mL Cutoff
Eighty (80) unaltered clinical urine specimens were tested with the LZI Hydrocodone Enzyme Immunoassay and confirmed with GC/MS or LC/MS. Specimens having a hydrocodone and hydromorphone total concentration greater than 300 ng/mL by GC/MS or LC/MS are defined as positive, and specimens with total concentrations below 300 ng/mL by GC/MS or LC/MS are defined as negative in the table below. The correlation results are summarized as follows: (near cutoff samples are defined as ± 50% of the cutoff value). Adjusted Total hydrocodone and hydromorphone GC/MS or LC/MS values corrected for cross-reactivity (Hydrocodone Cross = 100%, Hydromorphone Cross = 78%)were compared with the EIA result.
| 300 ng/mLCutoff | Neg | < 50 % of thecutoff | Near CutoffNeg. | Near CutoffPos. | High Pos. | %Agreement |
|---|---|---|---|---|---|---|
| Positive | 0 | 0 | 2* | 6 | 32 | 95.0 % |
| Negative | 20 | 12 | 6 | 2** | 0 | 95.0 % |
| 300 ng/mLCutoff | GC/MS orLC/MS | LZI EIA | Adjusted TotalHydrocodone+ HydromorphoneGC/MS or LC/MS(ng/mL) | LZI EIA(ng/mL) |
|---|---|---|---|---|
| Sample #36* | - | + | 206.9 | 375.5 |
| Sample #39* | - | + | 246.0 | 323.1 |
| Sample #41** | + | - | 301.0 | 252.8 |
| Sample #43** | + | - | 306.2 | 254.1 |
Semi-Quantitative & Qualitative Data:
{9}------------------------------------------------
AU480 Analyzer
Cross-reactivity: 100 ng/mL Cutoff
Various potentially interfering substances were tested for interference with the assay. Test compounds were spiked into the drug-free urine pool to various concentrations and evaluated against the cutoff calibrator. The tables below list the concentration of each test compound that gave a response approximately equivalent to that of the cutoff calibrator (as positive) or the maximal concentration of the compound tested that gave a response below the response of the cutoff calibrator (as negative).
Hydrocodone and Metabolites:
| Compound | ConcentrationEquivalent to CutoffConcentration (ng/mL) | % Cross-reactivity |
|---|---|---|
| Hydrocodone | 100 | 101.60% |
| Hydromorphone | 125 | 85.08% |
| Hydromorphone Glucuronide | 200 | 52.15% |
| Dihydrocodeine | 2,000 | 4.98% |
| Norhydrocodone | 18,000 | 0.57% |
Structurally Related Compounds:
| Compound | ConcentrationEquivalent to CutoffConcentration (ng/mL) | % Cross-reactivity |
|---|---|---|
| 6-mono acetylmorphine | 6,500 | 1.6% |
| Codeine | 3,000 | 3.5% |
| Codeine-6-Glucuronide | 15,000 | 0.6% |
| Dextromethorphan | 100,000 | 0.0% |
| Levorphanol | 20,000 | 0.5% |
| Morphine | 5,000 | 2.0% |
| Morphine 3-Glucuronide | 13,000 | 0.8% |
| Morphine 6-Glucuronide | 50,000 | 0.2% |
| Nalbuphine | 100,000 | 0.0% |
| Naloxone | 100,000 | 0.0% |
| Naltrexone | 100,000 | 0.0% |
| Norbuprenorphine | 100,000 | 0.0% |
| Norcodeine | 100,000 | 0.0% |
| Noroxycodone | 100,000 | 0.0% |
| Noroxymorphone | 100,000 | 0.0% |
| Oxycodone | 5,000 | 2.1% |
| Oxymorphone | 7,500 | 1.3% |
| Thebaine | 12,000 | 0.8% |
No significant cross-reactivity with structurally un-related compounds was observed.
The labeling contains the list of structurally unrelated compounds that were tested.
{10}------------------------------------------------
AU480 Analyzer
Cross-reactivity: 300 ng/mL Cutoff
Various potentially interfering substances were tested for interference with the assay. Test compounds were spiked into the drug-free urine pool to various concentrations and evaluated against the cutoff calibrator. The tables below list the concentration of each test compound that gave a response approximately equivalent to that of the cutoff calibrator (as positive) or the maximal concentration of the compound tested that gave a response below the response of the cutoff calibrator (as negative).
Hydrocodone and Metabolites:
| Compound | ConcentrationEquivalent to CutoffConcentration (ng/mL) | % Cross-reactivity |
|---|---|---|
| Hydrocodone | 300 | 99.70% |
| Hydromorphone | 375 | 78.13% |
| Hydromorphone Glucuronide | 625 | 49.15% |
| Dihydrocodeine | 8,750 | 3.32% |
| Norhydrocodone | 30,000 | 0.51% |
Structurally Related Compounds:
| Compound | ConcentrationEquivalent to CutoffConcentration (ng/mL) | % Cross-reactivity |
|---|---|---|
| 6-monoacetylmorphine | 30,000 | 1.00% |
| Codeine | 13,400 | 2.16% |
| Codeine-6-Glucuronide | 80,000 | 0.37% |
| Dextromethorphan | 100,000 | 0.00% |
| Levorphanol | 100,000 | 0.32% |
| Morphine | 22,000 | 1.30% |
| Morphine 3-Glucuronide | 37,000 | 0.73% |
| Morphine 6-Glucuronide | 100,000 | 0.17% |
| Nalbuphine | 100,000 | 0.01% |
| Naloxone | 100,000 | 0.03% |
| Naltrexone | 100,000 | 0.01% |
| Norbuprenorphine | 100,000 | 0.01% |
| Norcodeine | 100,000 | 0.02% |
| Noroxycodone | 100,000 | 0.02% |
| Noroxymorphone | 100,000 | 0.27% |
| Oxycodone | 20,000 | 0.08% |
| Oxymorphone | 35,000 | 0.90% |
| Thebaine | 25,000 | 0.75% |
No significant cross-reactivity with structurally un-related compounds was observed.
The labeling contains the list of structurally unrelated compounds that were tested.
{11}------------------------------------------------
Interference: 100 ng/mL Cutoff
Endogenous Compound Interference Study: 100 ng/mL Cutoff
Various endogenous compounds were tested for interference with the assay. Test compounds were spiked into a pool of drug-free processed urine to the spiked concentrations listed in the table below. Each of these samples were split into three portions each and either left unspiked or further spiked to either 75 or 125 ng/mL of hydrocodone (the negative and positive control concentrations, respectively). These samples were then evaluated in both semi-quantitative or qualitative mode. The tables below list the positive or negative result of each test sample relative to the cutoff calibrator (positive above the cutoff calibrator and negative below the cutoff calibrator).
| Endogenous Substance | Spiked Concentration(mg/dL) | Spiked Hydrocodone Concentration | ||
|---|---|---|---|---|
| 0ng/mL | 75 Controlng/mL | 125 Controlng/mL | ||
| Acetone | 1000 | Neg | Neg | Pos |
| Ascorbic Acid | 500 | Neg | Neg | Pos |
| Creatinine | 500 | Neg | Neg | Pos |
| Ethanol | 1000 | Neg | Neg | Pos |
| Galactose | 10 | Neg | Neg | Pos |
| y-Globulin | 500 | Neg | Neg | Pos |
| Glucose | 3000 | Neg | Neg | Pos |
| Hemoglobin | 300 | Neg | Neg | Pos |
| HSA | 500 | Neg | Neg | Pos |
| Oxalic Acid | 100 | Neg | Neg | Pos |
| Riboflavin | 0.3 | Neg | Neg | Pos |
| Urea | 6000 | Neg | Neg | Pos |
| Sodium Chloride | 1000 | Neg | Neg | Pos |
{12}------------------------------------------------
AU480 Analyzer
pH Interference Study: 100 ng/mL Cutoff
Pooled drug-free processed urine samples were adjusted to the target pH values (3 - 11) using 1N HCI or 1N NaOH. These samples were split into three portions each and either left unspiked or further spiked to either 75 or 125 ng/mL of hydrocodone (the negative and positive control concentrations, respectively). These samples were then evaluated in both semi-quantitative or qualitative mode. The tables below list the positive or negative result of each test sample relative to the cutoff calibrator (positive above the cutoff calibrator and negative below the cutoff calibrator).
| Spiked Hydrocodone Concentration | |||
|---|---|---|---|
| pH | 0 ng/mL | 75 Controlng/mL | 125 Controlng/mL |
| pH 3 | Neg | Neg | Pos |
| pH 4 | Neg | Neg | Pos |
| pH 5 | Neg | Neg | Pos |
| pH 6 | Neg | Neg | Pos |
| pH 7 | Neg | Neg | Pos |
| pH 8 | Neg | Neg | Pos |
| pH 9 | Neg | Neg | Pos |
| pH 10 | Neg | Neg | Pos |
| pH 11 | Neg | Neg | Pos |
Specific Gravity: 100 ng/mL Cutoff
Ten drug-free urine samples with specific gravity ranging in value from 1.000 to 1.030 were split into three portions each and either left un-spiked to a final hydrocodone concentration of either 75 or 125 ng/mL (the negative and positive control concentrations, respectively). These samples were then evaluated in semi-quantitative and qualitative modes. The tables below list the positive or negative result of each test sample relative to the cutoff calibrator (positive above the cutoff calibrator and negative below the cutoff calibrator).
| SpecificGravity | Spiked Hydrocodone Concentration | ||
|---|---|---|---|
| 0 ng/mL | 75 Controlng/mL | 125 Controlng/mL | |
| 1.000 | Neg | Neg | Pos |
| 1.005 | Neg | Neg | Pos |
| 1.007 | Neg | Neg | Pos |
| 1.010 | Neg | Neg | Pos |
| 1.015 | Neg | Neg | Pos |
| 1.017 | Neg | Neg | Pos |
| 1.020 | Neg | Neg | Pos |
| 1.025 | Neg | Neg | Pos |
| 1.027 | Neg | Neg | Pos |
| 1.030 | Neg | Neg | Pos |
No significant undesired endogenous substance interference, pH interference, or specific gravity interference was observed at the 100 ng/mL Cutoff.
{13}------------------------------------------------
Interference: 300 ng/mL Cutoff
Endogenous Compound Interference Study: 300 ng/mL Cutoff
Various endogenous compounds were tested for interference with the assay. Test compounds were spiked into a pool of drug-free processed urine to the spiked concentrations listed in the table below. Each of these samples were split into three portions each and either left unspiked or further spiked to either 225 or 375 ng/mL of hydrocodone (the negative and positive control concentrations, respectively). These samples were then evaluated in both semi-quantitative or qualitative mode. The tables below list the positive or negative result of each test sample relative to the cutoff calibrator (positive above the cutoff calibrator and negative below the cutoff calibrator).
| Endogenous Substance | Spiked Concentration(mg/dL) | Spiked Hydrocodone Concentration | ||
|---|---|---|---|---|
| 0ng/mL | 225 Controlng/mL | 375 Controlng/mL | ||
| Acetone | 1000 | Neg | Neg | Pos |
| Ascorbic Acid | 500 | Neg | Neg | Pos |
| Creatinine | 500 | Neg | Neg | Pos |
| Ethanol | 1000 | Neg | Neg | Pos |
| Galactose | 10 | Neg | Neg | Pos |
| y-Globulin | 500 | Neg | Neg | Pos |
| Glucose | 3000 | Neg | Neg | Pos |
| Hemoglobin | 300 | Neg | Neg | Pos |
| HSA | 500 | Neg | Neg | Pos |
| Oxalic Acid | 100 | Neg | Neg | Pos |
| Riboflavin | 0.3 | Neg | Neg | Pos |
| Urea | 6000 | Neg | Neg | Pos |
| Sodium Chloride | 1000 | Neg | Neg | Pos |
{14}------------------------------------------------
pH Interference Study: 300 ng/mL Cutoff
Pooled drug-free processed urine samples were adjusted to the target pH values (3 - 11) using IN HCl or 1N NaOH. These samples were split into three portions each and either left unspiked or further spiked to either 225 or 375 ng/mL of hydrocodone (the negative and positive control. concentrations, respectively). These samples were then evaluated in both semi-quantitative or qualitative mode. The tables below list the positive or negative result of each test sample relative to the cutoff calibrator (positive above the cutoff calibrator and negative below the cutoff calibrator).
| pH | Spiked Hydrocodone Concentration | ||
|---|---|---|---|
| 0 ng/mL | 225 Controlng/mL | 375 Controlng/mL | |
| pH 3 | Neg | Neg | Pos |
| pH 4 | Neg | Neg | Pos |
| pH 5 | Neg | Neg | Pos |
| pH 6 | Neg | Neg | Pos |
| pH 7 | Neg | Neg | Pos |
| pH 8 | Neg | Neg | Pos |
| pH 9 | Neg | Neg | Pos |
| pH 10 | Neg | Neg | Pos |
| pH 11 | Neg | Neg | Pos |
Specific Gravity: 300 ng/mL Cutoff
Ten drug-free urine samples with specific gravity ranging in value from 1.000 to 1.030 were split into three portions each and either left un-spiked to a final hydrocodone concentration of either 225 or 375 ng/mL (the negative and positive control concentrations, respectively). These samples were then evaluated in semi-quantitative and qualitative modes. The tables below list the positive or negative result of each test sample relative to the cutoff calibrator (positive above the cutoff calibrator and negative below the cutoff calibrator).
| SpecificGravity | Spiked Hydrocodone Concentration | ||
|---|---|---|---|
| 0 ng/mL | 225 Controlng/mL | 375 Controlng/mL | |
| 1.000 | Neg | Neg | Pos |
| 1.005 | Neg | Neg | Pos |
| 1.007 | Neg | Neg | Pos |
| 1.010 | Neg | Neg | Pos |
| 1.015 | Neg | Neg | Pos |
| 1.017 | Neg | Neg | Pos |
| 1.020 | Neg | Neg | Pos |
| 1.025 | Neg | Neg | Pos |
| 1.027 | Neg | Neg | Pos |
| 1.030 | Neg | Neg | Pos |
No significant undesired endogenous substance interference, pH interference, or specific gravity interference was observed at the 300 ng/mL Cutoff.
{15}------------------------------------------------
Stability for Calibrators and Controls: 100 ng/mL Cutoff
Current open-vial calibrator/control stability studies at Cold Temperature (2-8°C), Room temperature (~25 ℃), and Accelerated Temperature (30℃) are on-going and have been carried out up to Day 92 at this time. Results from open-vial studies indicate that degradation is minimal at all three conditions up to Day 92 and based on the Arrhenius Equation, suggest an open-vial stability of up to 18 months.
Real-time data for closed-vial calibrator/control stability studies at Cold Temperature (2-8ºC) are on-going have been carried out up to Day 114. Results from closed-vial studies indicate that degradation is minimal up to Day 114 as compared to Day 1.
Stability for Calibrators and Controls: 300 ng/mL Cutoff
Current open-vial calibrator/control stability studies at Cold Temperature (2-8°C), Room temperature (~25 ℃), and Accelerated Temperature (30℃) are on-going and have been carried out up to Day 225 at this time. Results from open-vial studies indicate that degradation is minimal at all three conditions up to Day 225 and based on the Arrhenius Equation, suggest an open-vial stability of up to 18 months.
Real-time data for closed-vial calibrator/control stability studies at Cold Temperature (2-8ºC) are on-going have been carried out up to Day 114. Results from closed-vial studies indicate that degradation is minimal up to Day 114 as compared to Day 1.
Summary:
The information provided in this pre-market notification demonstrates that the LZI Hydrocodone 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 chromatography/mass spectrometry (GC/MS or LC/MS), an independent analytical method. The information supplied in this pre-market notification provides reasonable assurance that the LZI Hydrocodone Enzyme Immunoassay is safe and effective for its stated intended use.
{16}------------------------------------------------
Image /page/16/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three stripes representing the department's three main goals: protecting the health of all Americans, providing essential human services, and strengthening the nation's health and well-being. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - (USA)" is arranged in a circular fashion around the eagle.
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
June 13, 2014
LIN-ZHI INTERNATIONAL, INC. BERNICE LIN VP OPERATIONS 670 ALMANOR AVE SUNNYVALE CA 94085
Re: K141055
Trade/Device Name: LZI Hydrocodone Enzyme Immunoassay, LZI Hydrocodone Drugs of Abuse (DAU) Calibrators, LZI Hydrocodone Drugs of Abuse (DAU) Controls Regulation Number: 21 CFR 862.3650 Regulation Name: Opiate test system Regulatory Class: II Product Code: DJG, DLJ, LAS Dated: April 21, 2014 Received: April 24, 2014
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
{17}------------------------------------------------
Page 2-Dr. Bernice Lin
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/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 (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/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
{18}------------------------------------------------
Indications for Use
510(k) Number (if known) K141055
Device Name
LZI Hydrocodone Enzyme Immunoassay and LZI Hydrocodone Calibrators and Controls ・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・
Indications for Use (Describe)
The LZI Hydrocodone Enzyme Immunoassay is intended for the qualitative and semi-quantitative determination of hydrocodone in human urine at the cutoff values of 100 and 300 ng/mL when calibrated against hydrocodone. 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) rapriviting laboratories to establish quality control procedures.
The LZI Hydrocodone Drugs of Abuse (DAU) Calibrators are for use as calibrators in the qualitative and semiquantitative calibration of the LZI Hydrocodone Enzyme Immunoassay at the cutoff value of 100 and 300 reg/mL. The LZI Hydrocodone Drugs of Abuse (DAU) Controls are for use as assayed quality control materials to tigniter the precision of the LZI Hydrocodone Enzyme Immunoassay at the cutoff value of 100 and 300 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 (GCMS or LC/MS) is the preferred confirmatory method). Clinical consideration and professional judgment should be execcised with 2011 is of abuse test result, particularly when the preliminary test result is positive
Type of Use (Select one or both, as applicable)
2 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 ・ふ ・ Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)
Denise Johnson-lyles -S
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§ 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).