(23 days)
The Emit II Plus Oxycodone Assay is a homogeneous enzyme immunoassay with 100 ng/mL cutoff. The assay is intended for in vitro diagnostic use in the qualitative and semiquantitative determination of oxycodone in human urine. The Emit II Plus Oxycodone Assay is designed for use with a number of clinical chemistry analyzers. The semiquantitative mode is for the purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid Chromatography/Mass Spectrometry (LC/MS) or permitting laboratories to establish quality control procedures.
The Emit II Plus Oxycodone Assay provides only a preliminary analytical test result. A more specific alternative chemical method(s) must be used to obtain a confirmed analytical test result. Gas Chromatography/Mass Spectrometry (GC/MS) and LC/MS are the preferred confirmatory methods. Clinical consideration and professional judgement should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.
The Emit® II Plus Oxycodone assay is a homogeneous enzyme immunoassay with 100 ng/mL and 300 ng/mL cutoffs. The assay, used for the detection of oxycodone in human urine, utilizes a two- reagent system. The Antibody/Substrate Reagent 1 is a liquid ready-to-use product comprised of mouse monoclonal antibodies to oxycodone, qucose-6-phosphate (G6P), and nicotinamide adenine dinucleotide (NAD) in a diluent containing bovine serum albumin (BSA), preservatives and stabilizers. The Enzyme Reagent 2 is a liquid, ready-to-use product containing oxymorphone labeled with bacterial recombinant glucose-6 phosphate dehydrogenase (rG6PDH) in a diluent containing bovine serum albumin (BSA), HEPES buffer, preservatives and stabilizers.
The assay kit consists of Reagent 1 and Reagent 2 in plastic containers and is available in three sizes: 1000 mL/500 mL, 115 mL/50 mL, and 28 mL/14 mL. Emit® II Plus assays are designed for use with a number of chemistry analyzers. The Emit® II Plus Oxycodone assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result.
The Siemens Healthcare Diagnostics Inc. Emit II Plus Oxycodone Assay is a homogeneous enzyme immunoassay intended for in vitro diagnostic use in the qualitative and semiquantitative determination of oxycodone in human urine. It has two cutoffs: 100 ng/mL and 300 ng/mL.
The study presented focuses on demonstrating substantial equivalence to the predicate device, DRI Oxycodone Assay (K040411), through non-clinical performance evaluations.
1. Table of Acceptance Criteria and Reported Device Performance:
The document does not explicitly state pre-defined acceptance criteria values (e.g., "sensitivity must be > X"). Instead, the performance is reported as observed agreement rates with the confirmatory method (LC-MS/MS) and precision metrics. The implicit acceptance criterion is that the device's performance is comparable to or meets expected standards for drug screening assays, similar to its predicate.
| Performance Metric | Acceptance Criteria (Implicit from Context) | Reported Device Performance (100 ng/mL Cutoff) | Reported Device Performance (300 ng/mL Cutoff) |
|---|---|---|---|
| Method Comparison (Qualitative Mode) | High agreement with LC-MS/MS for both positives and negatives. Discordant results should be minimal and explainable. | Agreement among positives: 93% (52/56) Agreement among negatives: 100% (44/44) | Agreement among positives: 98% (44/45) Agreement among negatives: 98% (54/55) |
| Method Comparison (Semiquantitative Mode) | High agreement with LC-MS/MS for both positives and negatives. Discordant results should be minimal and explainable. | Agreement among positives: 93% (52/56) Agreement among negatives: 100% (44/44) | Agreement among positives: 98% (44/45) Agreement among negatives: 100% (55/55) |
| Precision (Qualitative Mode) | Consistent classification (positive/negative) at concentrations well below and well above the cutoff, with expected variability near the cutoff. | At cutoff (100 ng/mL): 2 Negative/78 Positive At all other tested levels: 80 Negative or 80 Positive | At cutoff (300 ng/mL): 4 Negative/76 Positive At all other tested levels: 80 Negative or 80 Positive |
| Precision (Semiquantitative Mode) | Consistent classification (positive/negative) at concentrations well below and well above the cutoff, with expected variability near the cutoff. | At cutoff (100 ng/mL): 2 Negative/78 Positive At all other tested levels: 80 Negative or 80 Positive | At cutoff (300 ng/mL): 16 Negative/64 Positive At all other tested levels: 80 Negative or 80 Positive |
| Recovery | Measured concentrations should be close to target concentrations. | Mean Recovery % ranges (among tested concentrations): 96-120% | Mean Recovery % ranges (among tested concentrations): 96-105% |
| Cross-Reactivity (Oxycodone Metabolites) | Expected cross-reactivity with known metabolites; lower cross-reactivity with less active or unrelated metabolites. | Quantified % cross-reactivity for Oxymorphone, Oxymorphone-3-β-glucuronide, Noroxycodone, Noroxymorphone. | Quantified % cross-reactivity for Oxymorphone, Oxymorphone-3-β-glucuronide, Noroxycodone, Noroxymorphone. |
| Cross-Reactivity (Structurally Related Compounds) | Minimal to no cross-reactivity with other structurally related compounds, or quantifiable cross-reactivity if present. | Quantified % cross-reactivity for various opiates/opioids/related compounds. Minimal to no cross-reactivity for most. | Quantified % cross-reactivity for various opiates/opioids/related compounds. Minimal to no cross-reactivity for most. |
| Interference (Structurally Unrelated Compounds & Endogenous Substances) | No false positive or false negative results at specified concentrations of common medications and endogenous substances. | All tested compounds yielded Negative at -25% cutoff control and Positive at +25% cutoff control. | All tested compounds yielded Negative at -25% cutoff control and Positive at +25% cutoff control. |
| Specific Gravity and pH | No positive or negative interference over the tested range of specific gravity and pH. | No positive or negative interference observed. | No positive or negative interference observed. |
2. Sample sizes used for the test set and data provenance:
- Method Comparison: 100 unaltered native patient samples were tested for each cutoff (100 ng/mL and 300 ng/mL), totaling 200 samples.
- Precision: Urine pools spiked with oxycodone at nine different levels for each cutoff were used. Each level was tested with two replicates, twice a day, for twenty days (n = 80 per level per cutoff). This means 9 levels * 80 replicates * 2 cutoffs = 1440 tests for precision.
- Recovery: 7 concentrations for the 100 ng/mL cutoff and 13 concentrations for the 300 ng/mL cutoff were evaluated. Each concentration was analyzed in replicates of 5. This means 7 concentrations * 5 replicates + 13 concentrations * 5 replicates = 100 tests for recovery.
- Cross-Reactivity & Interference (Structurally Related, Unrelated, Endogenous): Samples were spiked into drug-free urine and evaluated. The exact number of samples for each compound isn't explicitly stated beyond referencing CLSI guidelines, but it's implied that sufficient replicates were done to determine cross-reactivity percentages or lack thereof.
- Specific Gravity and pH: Drug-free urine pools (with varying SG and pH) were spiked to 3 final oxycodone concentrations. Samples were then evaluated qualitatively and semiquantitatively. The number of samples is not explicitly stated but implied to be sufficient for assessment.
Data Provenance: The document does not explicitly state the country of origin for the native patient samples or whether they were retrospectively or prospectively collected. However, the study was conducted by Siemens Healthcare Diagnostics Inc., based in Newark, DE, USA.
3. Number of experts used to establish the ground truth for the test set and qualifications of those experts:
The ground truth for the method comparison study was established using Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS), which is considered a highly specific and sensitive confirmatory method for drug analyses. This is a laboratory-based analytical technique, not an expert panel.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
No multi-reader adjudication method was used for the test set. The ground truth was established by LC-MS/MS, a quantitative chemical analysis method.
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 MRMC comparative effectiveness study was done. This device is an in vitro diagnostic assay, not an imaging AI device that would typically involve human readers.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
The performance reported is for the standalone device (Emit II Plus Oxycodone Assay) on a clinical chemistry analyzer without human interpretation influencing the result of the assay itself. The results are preliminary and require confirmation by LC/MS or GC/MS, implying a human-in-the-loop step for final clinical interpretation and confirmation. However, the performance of the assay itself is standalone.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc):
The primary ground truth for method comparison was Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS), a highly sensitive and specific chemical analytical method. For spiked samples used in precision, recovery, and cross-reactivity studies, the ground truth was the known concentration of the spiked compound.
8. The sample size for the training set:
This document describes a performance evaluation study for a chemical assay, not a machine learning or AI model. Therefore, there is no "training set" in the context of AI. The assay's parameters would have been developed and optimized during its design phase using internal validation processes, for which detailed sample sizes are not provided in this regulatory submission.
9. How the ground truth for the training set was established:
As this is not an AI/machine learning device, there isn't a "training set" in that sense. The assay works based on established biochemical principles (enzyme immunoassay). Its development would involve calibrating and optimizing its response to known concentrations of oxycodone and its metabolites, using chemically prepared standards and samples quantified by reference methods.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
October 18, 2017
SIEMENS HEALTHCARE DIAGNOSTICS INC. ALAN HALEY REGULATORY AND CLINICAL AFFAIRS SPECIALIST 500 GBC DRIVE, M/S 514 NEWARK, DE 19702
Re: K172910
Trade/Device Name: Emit II Plus Oxycodone Assay Regulation Number: 21 CFR 862.3650 Regulation Name: Opiate test system Regulatory Class: II Product Code: DJG Dated: September 21, 2017 Received: September 25, 2017
Dear Alan Haley:
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/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/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Courtney H. Lias -S
Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K172910
Device Name Emit II Plus Oxycodone Assay
Indications for Use (Describe)
The Emit II Plus Oxycodone Assay is a homogeneous enzyme immunoassay with 100 ng/mL cutoff. The assay is intended for in vitro diagnostic use in the qualitative and semiquantitative determination of oxycodone in human urine. The Emit II Plus Oxycodone Assay is designed for use with a number of clinical chemistry analyzers. The semiquantitative mode is for the purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid Chromatography/Mass Spectrometry (LC/MS) or permitting laboratories to establish quality control procedures.
The Emit II Plus Oxycodone Assay provides only a preliminary analytical test result. A more specific alternative chemical method(s) must be used to obtain a confirmed analytical test result. Gas Chromatography/Mass Spectrometry (GC/MS) and LC/MS are the preferred confirmatory methods. Clinical consideration and professional judgement should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.
| 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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SIEMI
510(k) Summary
This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of Safe Medical Device Act of 1990 and 21 CFR 807.92.
1. Submitter
| Company | Siemens Healthcare Diagnostics Inc. |
|---|---|
| Address | 500 GBC Drive, M/S 514 Newark, DE 19702 |
| Contact | Alan Haley |
| Telephone | 302.631.9883 |
| Fax | 302.631.6299 |
| Date of Preparation | October 16, 2017 |
2. Device Information
| Trade Name | Emit® II Plus Oxycodone Assay |
|---|---|
| Common Name | Enzyme Immunoassay, Opiates |
| Classification Name | Opiate Test System |
| Regulation | 21 CFR 862.3650 |
| Device Class | Class II |
| Product Code | DJG |
3. Identification of Predicate
| Trade Name | DRI Oxycodone Assay |
|---|---|
| 510(k) Submitter | Microgenics Corp. |
| 510(k) Number | K040411 |
| Clearance Date | May 27, 2004 |
Device Description 4.
The Emit® II Plus Oxycodone assay is a homogeneous enzyme immunoassay with 100 ng/mL and 300 ng/mL cutoffs. The assay, used for the detection of oxycodone in human urine, utilizes a two- reagent system. The Antibody/Substrate Reagent 1 is a liquid ready-to-use product comprised of mouse monoclonal antibodies to oxycodone, qucose-6-phosphate (G6P), and nicotinamide adenine dinucleotide (NAD) in a diluent containing bovine serum albumin (BSA), preservatives and stabilizers. The Enzyme Reagent 2 is a liquid, ready-to-use product containing oxymorphone labeled with bacterial recombinant glucose-6 phosphate dehydrogenase (rG6PDH) in a diluent containing bovine serum albumin (BSA), HEPES buffer, preservatives and stabilizers.
The assay kit consists of Reagent 1 and Reagent 2 in plastic containers and is available in three sizes: 1000 mL/500 mL, 115 mL/50 mL, and 28 mL/14 mL. Emit® II Plus assays are designed for use with a number of chemistry analyzers. The Emit® II Plus Oxycodone assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result.
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SIEMENS
5. Intended Use Statement
The Emit® II Plus Oxycodone Assay is a homogeneous enzyme immunoassay with 100 ng/mL and 300 ng/mL cutoffs. The assay is intended for in vitro diagnostic use in the qualitative and semiguantitative determination of oxycodone in human urine. The Emit® II Plus Oxycodone Assay is designed for use with a number of clinical chemistry analyzers. The semiquantitative mode is for the purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liguid Chromatography/Mass Spectrometry (LC/MS) or permitting laboratories to establish quality control procedures.
The Emit® II Plus Oxycodone Assay provides only a preliminary analytical test result. A more specific alternative chemical method(s) must be used to obtain a confirmed analytical test result. Gas Chromatography/Mass Spectrometry (GC/MS) and LC/MS are the preferred confirmatory methods. Clinical consideration and professional judgement should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.
6. Technological Characteristics
(a) Comparison to Predicate
| ltem | DRI Oxycodone Assay(K040411) | Emit® II Plus Oxycodone Assay(Proposed) |
|---|---|---|
| Intended Use | The DRI® Oxycodone assay isintended to be used for the qualitativeand semi-quantitative determination ofthe presence of oxycodone in humanurine at cutoffs of 100 ng/mL and300 ng/mL. | Same |
| Analyte | Oxycodone | Same |
| Matrix | Urine | Same |
| Storage | 2°C to 8°C until expiration date | Same |
| Type of Test | Homogeneous enzymeimmunoassay | Same |
| Reagent Form | Liquid, Ready to Use | Same |
| ReagentComposition | Antibody/substrate reagent andenzyme conjugate/reagent. Theantibody substrate reagent includesmouse monoclonal anti-oxycodonederivative antibody, glucose-6-phosphate and NAD in buffer withpreservative. The enzyme conjugatereagent includes oxycodone derivativelabeled with glucose-6-phosphatedehydrogenase in buffer withpreservative. | Same |
| Cutoffs | 100 ng/mL oxycodone300 ng/mL oxycodone | Same |
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SIEMEN
(b) Non-Clinical Performance Evaluation
The data that appear in this section were collected on the Viva-E® Analyzer using the Emil® II Plus Oxycodone Assay. Summary results for each study are provided. The results represent typical assay performance.
(i) Method Comparison
A total of 100 unaltered native patient samples were tested for each cutoff. Samples were evaluated using the Emit® II Plus Oxycodone Assay on the Viva-E® instrument and Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS).
Results for the 100 ng/mL assay cutoff are presented below:
| Table A. Method Comparison Results (100 ng/mL Cutoff) | |||
|---|---|---|---|
| LC-MS/MS | |||||
|---|---|---|---|---|---|
| Low Negative(Less than 50% below the cutoff concentration) | Near Cutoff Negative(Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive(Between the cutoff and 50% above the cutoff concentration) | High Positive(greater than 50% above the cutoff concentration) | ||
| Qualitative Mode | |||||
| Emit® | Positive | 0 | 0 | 9 | 43 |
| Negative | 31 | 13 | 4 | 0 | |
| Agreement among positives is 52/56 = 93% | |||||
| Agreement among negatives is 44/44 = 100% | |||||
| Semiquantitative Mode | |||||
| Emit® | Positive | 0 | 0 | 9 | 43 |
| Negative | 31 | 13 | 4 | 0 | |
| Agreement among positives is 52/56 = 93% | |||||
| Agreement among negatives is 44/44 = 100% |
Table B. Discordant Results (100 ng/mL Cutoff)
| Emit® | LC-MS/MS | |||
|---|---|---|---|---|
| Sample # | Semiquantitative(ng/mL) | Qualitative(Pos/Neg) | Oxycodone(ng/mL) | Oxymorphone(ng/mL) |
| OXY-471 | 85 | Neg | 100 | 0 |
| OXY-9128 | 90 | Neg | 102 | 0 |
| OXY-9129 | 96 | Neg | 103 | 0 |
| OXY-9130 | 93 | Neg | 103 | 0 |
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Results for the 300 ng/mL assay cutoff are presented below.
Table C. Method Comparison Results (300 ng/mL Cutoff)
| LC-MS/MS | |||||
|---|---|---|---|---|---|
| Low Negative(Less than 50% below the cutoff concentration) | Near Cutoff Negative(Between 50% below the cutoff and the cutoff concentration)) | Near Cutoff Positive(Between the cutoff and 50% above the cutoff concentration) | High Positive(greater than 50% above the cutoff concentration) | ||
| Qualitative Mode | |||||
| Emit® | Positive | 0 | 1 | 11 | 33 |
| Emit® | Negative | 42 | 12 | 1 | 0 |
| Agreement among positives is 44/45 = 98% | |||||
| Agreement among negatives is 54/55 = 98% | |||||
| Semiquantitative Mode | |||||
| Emit® | Positive | 0 | 0 | 11 | 33 |
| Emit® | Negative | 42 | 13 | 1 | 0 |
| Agreement among positives is 44/45 = 98% | |||||
| Agreement among negatives is 55/55 = 100% |
Table D. Discordant Results (300 ng/mL Cutoff)
| Sample # | Emit® | LC-MS/MS | ||
|---|---|---|---|---|
| Semiquantitative (ng/mL) | Qualitative (Pos/Neg) | Oxycodone (ng/mL) | Oxymorphone (ng/mL) | |
| OXY-161 | 263 | Neg | 318 | 0 |
| OXY-665 | 288 | Pos | 182 | 29.1 |
(ii) Precision
Repeatability and Within-Lab Precision were determined by assaying urine pools spiked with oxycodone at nine different levels for each cutoff. The testing sequence for each level consisted of two replicates, twice a day, for twenty days (n = 80) for each cutoff. Precision data were evaluated according to the Clinical and Laboratory Standards Institute (CLSI) Guideline EP05-A3.
Table E. Precision (100 ng/mL Cutoff)
| Urine Pool | % of | # of | Qualitative | Semiquantitative | ||
|---|---|---|---|---|---|---|
| (ng/mL) | Cutoff | Results | Repeatability | Within-Lab | Repeatability | Within-Lab |
| 0 | -100 | 80 | 80 Negative | 80 Negative | 80 Negative | 80 Negative |
| 25 | -75 | 80 | 80 Negative | 80 Negative | 80 Negative | 80 Negative |
| 50 | -50 | 80 | 80 Negative | 80 Negative | 80 Negative | 80 Negative |
| 75 | -25 | 80 | 80 Negative | 80 Negative | 80 Negative | 80 Negative |
| 80 | 2 Negative/ | 2 Negative/ | 2 Negative/ | 2 Negative/ | ||
| 100 | Cutoff | 78 Positive | 78 Positive | 78 Positive | 78 Positive80 Positive80 Positive80 Positive80 Positive | |
| 125 | +25 | 80 | 80 Positive | 80 Positive | 80 Positive | |
| 150 | +50 | 80 | 80 Positive | 80 Positive | 80 Positive | |
| 175 | +75 | 80 | 80 Positive | 80 Positive | 80 Positive | |
| 200 | +100 | 80 | 80 Positive | 80 Positive | 80 Positive |
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| Urine Pool(ng/mL) | % ofCutoff | # ofResults | Qualitative | Semiquantitative | ||
|---|---|---|---|---|---|---|
| 0 | -100 | 80 | 80 Negative | 80 Negative | 80 Negative | 80 Negative |
| 75 | -75 | 80 | 80 Negative | 80 Negative | 80 Negative | 80 Negative |
| 150 | -50 | 80 | 80 Negative | 80 Negative | 80 Negative | 80 Negative |
| 225 | -25 | 80 | 80 Negative | 80 Negative | 80 Negative | 80 Negative |
| 300 | Cutoff | 80 | 4 Negative/76 Positive | 4 Negative/76 Positive | 16 Negative/64 Positive | 16 Negative/64 Positive |
| 375 | +25 | 80 | 80 Positive | 80 Positive | 80 Positive | 80 Positive |
| 450 | +50 | 80 | 80 Positive | 80 Positive | 80 Positive | 80 Positive |
| 525 | +75 | 80 | 80 Positive | 80 Positive | 80 Positive | 80 Positive |
| 600 | +100 | 80 | 80 Positive | 80 Positive | 80 Positive | 80 Positive |
Table F. Precision (300 ng/mL cutoff)
(iii) Recovery
Oxycodone samples were prepared by spiking known levels of oxycodone into drug-free urine. A total of 7 concentrations were evaluated for oxycodone at the 100 ng/mL cutoff and 13 concentrations were evaluated for oxycodone at the 300 ng/mL cutoff. Spiked samples were analyzed in replicates of 5. Results are shown in Table G for the 100 ng/mL cutoff; Table H for the 300 ng/mL cutoff.
Table G. Recovery Results (100 ng/mL Cutoff)
| TargetConcentration(ng/mL) | Mean MeasuredConcentration(ng/mL) | MeanRecovery (%) |
|---|---|---|
| 50 | 60 | 120 |
| 75 | 79 | 105 |
| 100 | વેદ | વેદ |
| 125 | 123 | ರಿ8 |
| 200 | 196 | ರಿ8 |
| 300 | 306 | 102 |
| 400 | 385 | વેદ |
Table H. Recovery Results (300 ng/mL Cutoff)
| TargetConcentration(ng/mL) | Mean MeasuredConcentration(ng/mL) | MeanRecovery (%) |
|---|---|---|
| 100 | 101 | 101 |
| 150 | 145 | 97 |
| 200 | 191 | 96 |
| 225 | 216 | 96 |
| 300 | 304 | 101 |
| 375 | 374 | 100 |
| 400 | 414 | 104 |
| 500 | 525 | 105 |
| 600 | 621 | 104 |
| 700 | 723 | 103 |
| 800 | 803 | 100 |
| 900 | 893 | 99 |
| 1000 | 969 | 97 |
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SIEMEN
(iv) Oxycodone Metabolites
Oxycodone metabolites were spiked into negative urine and evaluated by dose-response to determine the level that would give a response approximately equivalent to the cutoff response. Percent cross-reactivity was calculated according to CLSI EP07-A2.
Table I. Oxycodone Metabolite Cross-Reactivity (100 ng/mL cutoff)
| Compound | Concentration(ng/mL) | % Cross-Reactivity |
|---|---|---|
| Oxycodone | 100 | 100.0 |
| Oxymorphone | 119 | 84.0 |
| Oxymorphone-3-β-glucuronide | 1,700 | 5.9 |
| Noroxycodone | 11,000 | 0.9 |
| Noroxymorphone | 31,000 | 0.3 |
Table J. Oxycodone Metabolite Cross-Reactivity (300 ng/mL cutoff)
| Compound | Concentration(ng/mL) | % Cross-Reactivity |
|---|---|---|
| Oxycodone | 310 | 96.8 |
| Oxymorphone | 400 | 75.0 |
| Oxymorphone-3-β-glucuronide | 5,800 | 5.2 |
| Noroxycodone | 35,000 | 0.9 |
| Noroxymorphone | 81,000 | 0.4 |
(v) Structurally Related Compounds
Structurally similar drugs were spiked into drug-free urine and percent cross-reactivity was evaluated at both cutoffs according to CLSI EP07-A2. Drugs eliciting a positive response were evaluated by doseresponse to determine the lowest level of cross-reactant that would generate a positive result relative to the cutoff.
| Table K. Structurally Related Compounds (100 ng/mL Cutoff) | ||
|---|---|---|
| -- | ------------------------------------------------------------ | -- |
| Compound | Concentration(ng/mL) | % Cross-Reactivity |
|---|---|---|
| 6-Acetylcodeine | 100,000 | 0.01 |
| 6-Acetylmorphine | 100,000 | 0.01 |
| Buprenorphine | 100,000 | 0.01 |
| Codeine | 340,000 | 0.03 |
| Dextromethorphan | 200,000 | <0.01 |
| Dihydrocodeine | 100,000 | 0.02 |
| Heroin | 300,000 | 0.01 |
| Hydrocodone | 1,000,000 | <0.01 |
| Hydromorphone | 1,000,000 | <0.01 |
| Levorphanol | 200,000 | <0.01 |
| Morphine | 1,000,000 | <0.01 |
| Morphine 3-ß-D-glucuronide | 1,000,000 | <0.01 |
| Nalorphine | 100,000 | 0.02 |
| Naloxone | 16,000 | 0.63 |
| Naltrexone | 500,000 | 0.02 |
| Norcodeine | 1,000,000 | <0.01 |
| Normorphine | 1,000,000 | <0.01 |
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| Compound | Concentration (ng/mL) | % Cross-reactivity |
|---|---|---|
| 6-Acetylcodeine | 100,000 | <0.01 |
| 6-Acetylmorphine | 100,000 | 0.02 |
| Buprenorphine | 100,000 | <0.01 |
| Codeine | 1,000,000 | 0.03 |
| Dextromethorphan | 200,000 | <0.01 |
| Dihydrocodeine | 100,000 | 0.02 |
| Heroin | 300,000 | <0.01 |
| Hydrocodone | 1,000,000 | <0.01 |
| Hydromorphone | 1,000,000 | <0.01 |
| Levorphanol | 200,000 | <0.01 |
| Morphine | 1,000,000 | <0.01 |
| Morphine 3-β-D-glucuronide | 1,000,000 | <0.01 |
| Nalorphine | 100,000 | 0.02 |
| Naloxone | 46,000 | 0.65 |
| Naltrexone | 500,000 | 0.02 |
| Norcodeine | 1,000,000 | <0.01 |
| Normorphine | 1,000,000 | <0.01 |
Table L. Structurally Related Compounds (300 ng/mL Cutoff)
(vi) Structurally Unrelated Compounds
The interference of structurally unrelated compounds and common over the counter drugs was evaluated qualitatively and semiquantitatively according to CLSI EP07-A2 at the concentrations listed below. For each cutoff, the compounds were spiked into two levels of controls at +/- 25% of the cutoff concentration. At the stated concentration, the sample did not give a false response relative to the 100 ng/mL or 300 ng/mL cutoffs.
| Table M. Structurally Unrelated Compounds (100 ng/mL and 300 ng/mL Cutoffs) | |||
|---|---|---|---|
| Compound | 100 ng/mL Cutoff | 300 ng/mL Cutoff | |||
|---|---|---|---|---|---|
| Concen-tration(µg/mL) | -25% | +25% | -25% | +25% | |
| Control | Control | Control | Control | ||
| (75 ng/mL) | (125 ng/mL) | (225 ng/mL) | (375 ng/mL) | ||
| 10, 11-Dihydrocarbamazepine | 85 | Negative | Positive | Negative | Positive |
| Acetaminophen | 1,000 | Negative | Positive | Negative | Positive |
| Acetylsalicylic Acid | 1,500 | Negative | Positive | Negative | Positive |
| Amitriptyline | 100 | Negative | Positive | Negative | Positive |
| Amoxicillin | 500 | Negative | Positive | Negative | Positive |
| AZT (Zidovudine) | 2,000 | Negative | Positive | Negative | Positive |
| Benzoylecgonine | 1,000 | Negative | Positive | Negative | Positive |
| Brompheniramine | 75 | Negative | Positive | Negative | Positive |
| Caffeine | 1,000 | Negative | Positive | Negative | Positive |
| Captopril | 500 | Negative | Positive | Negative | Positive |
| Chlordiazepoxide | 100 | Negative | Positive | Negative | Positive |
| Chlorpromazine | 10 | Negative | Positive | Negative | Positive |
| Cimetidine | 1,000 | Negative | Positive | Negative | Positive |
| Clomipramine | 2.5 | Negative | Positive | Negative | Positive |
| Clonidine | 1,000 | Negative | Positive | Negative | Positive |
| Cyclobenzaprine | 125 | Negative | Positive | Negative | Positive |
| d-Amphetamine | 700 | Negative | Positive | Negative | Positive |
| Desipramine | 800 | Negative | Positive | Negative | Positive |
| Diazepam | 100 | Negative | Positive | Negative | Positive |
| Compound | Concentration (µg/mL) | 100 ng/mL Cutoff | 300 ng/mL Cutoff | ||
| -25% Control (75 ng/mL) | +25% Control (125 ng/mL) | -25% Control (225 ng/mL) | +25% Control (375 ng/mL) | ||
| Digoxin | 0.01 | Negative | Positive | Negative | Positive |
| Diphenhydramine | 1,000 | Negative | Positive | Negative | Positive |
| d-Methamphetamine | 500 | Negative | Positive | Negative | Positive |
| Doxepine | 100 | Negative | Positive | Negative | Positive |
| EDDP | 1,000 | Negative | Positive | Negative | Positive |
| EMDP | 100 | Negative | Positive | Negative | Positive |
| Enalapril | 500 | Negative | Positive | Negative | Positive |
| Fentanyl | 200 | Negative | Positive | Negative | Positive |
| Fluoxetine | 500 | Negative | Positive | Negative | Positive |
| Glutethimide | 500 | Negative | Positive | Negative | Positive |
| Haloperidol | 100 | Negative | Positive | Negative | Positive |
| Hydroxyzine | 500 | Negative | Positive | Negative | Positive |
| Ibuprofen | 1,000 | Negative | Positive | Negative | Positive |
| Imipramine | 200 | Negative | Positive | Negative | Positive |
| Ketamine | 100 | Negative | Positive | Negative | Positive |
| Ketorolac Tromethamine | 400 | Negative | Positive | Negative | Positive |
| LAAM (L-a Acetlymethadol) | 25 | Negative | Positive | Negative | Positive |
| L-Cotinine | 100 | Negative | Positive | Negative | Positive |
| Levofloxacin | 100 | Negative | Positive | Negative | Positive |
| Levothyroxine (L- Thyroxine) | 50 | Negative | Positive | Negative | Positive |
| Lidocaine | 1,000 | Negative | Positive | Negative | Positive |
| Lormetazepam | 1 | Negative | Positive | Negative | Positive |
| LSD | 10 | Negative | Positive | Negative | Positive |
| MDMA (Ecstasy) | 1,000 | Negative | Positive | Negative | Positive |
| Meperidine | 800 | Negative | Positive | Negative | Positive |
| Methadone | 500 | Negative | Positive | Negative | Positive |
| Methaqualone | 600 | Negative | Positive | Negative | Positive |
| NAPA (N-Acetylprocainamide) | 400 | Negative | Positive | Negative | Positive |
| Naproxen | 1,000 | Negative | Positive | Negative | Positive |
| Nicotinic Acid | 500 | Negative | Positive | Negative | Positive |
| Nifedipine | 500 | Negative | Positive | Negative | Positive |
| Nordiazepam | 100 | Negative | Positive | Negative | Positive |
| Nortryptiline | 250 | Negative | Positive | Negative | Positive |
| Oxazepam | 300 | Negative | Positive | Negative | Positive |
| Perphenazine | 150 | Negative | Positive | Negative | Positive |
| Phencyclidine | 1,000 | Negative | Positive | Negative | Positive |
| Phenobarbital | 500 | Negative | Positive | Negative | Positive |
| Phenelzine | 100 | Negative | Positive | Negative | Positive |
| Phenytoin | 1,000 | Negative | Positive | Negative | Positive |
| Procainamide | 1,000 | Negative | Positive | Negative | Positive |
| Procyclidine | 800 | Negative | Positive | Negative | Positive |
| Promethazine | 100 | Negative | Positive | Negative | Positive |
| Propoxyphene | 1,000 | Negative | Positive | Negative | Positive |
| Protriptyline | 200 | Negative | Positive | Negative | Positive |
| Pseudoephedrine | 1,000 | Negative | Positive | Negative | Positive |
| Quinacrine | 1,000 | Negative | Positive | Negative | Positive |
| Ranitidine | 1,000 | Negative | Positive | Negative | Positive |
| Compound | Concentration (µg/mL) | 100 ng/mL Cutoff | 300 ng/mL Cutoff | ||
| -25% Control (75 ng/mL) | +25% Control (125 ng/mL) | -25% Control (225 ng/mL) | +25% Control (375 ng/mL) | ||
| Ritalin (Methylphenidate) | 1,000 | Negative | Positive | Negative | Positive |
| Salicylic Acid | 500 | Negative | Positive | Negative | Positive |
| Scopolamine | 500 | Negative | Positive | Negative | Positive |
| Secobarbital | 1,000 | Negative | Positive | Negative | Positive |
| Tapentadol | 100 | Negative | Positive | Negative | Positive |
| THC (11-nor-9-Carboxy-Δ9-THC) | 100 | Negative | Positive | Negative | Positive |
| Thioridazine | 100 | Negative | Positive | Negative | Positive |
| Tramadol | 1,000 | Negative | Positive | Negative | Positive |
| Trazodone | 5 | Negative | Positive | Negative | Positive |
| Trimethoprim | 1,000 | Negative | Positive | Negative | Positive |
| Triprolidine (zymine) | 50 | Negative | Positive | Negative | Positive |
| Tyramine | 100 | Negative | Positive | Negative | Positive |
| Verapamil | 500 | Negative | Positive | Negative | Positive |
| Zolpidem | 100 | Negative | Positive | Negative | Positive |
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(vii) Endogenous Substances
Endogenous substances were evaluated qualitatively and semiquantitatively according to CLSI EP07-A2 at the concentrations listed below. The compounds were spiked into two levels of controls at +/- 25% of the cutoff concentration for each cutoff. At the stated concentrations, the sample did not give a false response relative to the 100 ng/mL or 300 ng/mL cutoffs.
| 100 ng/mL Cutoff | 300 ng/mL Cutoff | ||||
|---|---|---|---|---|---|
| Compound | Concen- tration | -25%Control(75 ng/mL) | +25%Control(125 ng/mL) | -25%Control(225 ng/mL) | +25%Control(375 ng/mL) |
| Acetone | 1.0 g/dL | Negative | Positive | Negative | Positive |
| Ascorbic Acid | 1.5 g/dL | Negative | Positive | Negative | Positive |
| Conjugated Bilirubin | 2.0 mg/dL | Negative | Positive | Negative | Positive |
| UnconjugatedBilirubin | 2.0 mg/dL | Negative | Positive | Negative | Positive |
| Creatinine | 0.5 g/dL | Negative | Positive | Negative | Positive |
| Ethanol | 1.0 g/dL | Negative | Positive | Negative | Positive |
| Galactose | 1.0 g/dL | Negative | Positive | Negative | Positive |
| Gamma Globulin | 0.5 g/dL | Negative | Positive | Negative | Positive |
| Glucose | 2.0 g/dL | Negative | Positive | Negative | Positive |
| Hemoglobin | 115 mg/dL | Negative | Positive | Negative | Positive |
| Human SerumAlbumin | 0.5 g/dL | Negative | Positive | Negative | Positive |
| Oxalic Acid | 0.1 g/dL | Negative | Positive | Negative | Positive |
| Riboflavin | 7.5 mg/dL | Negative | Positive | Negative | Positive |
| Sodium Azide | 1% w/v | Negative | Positive | Negative | Positive |
| Sodium Chloride | 6.0 g/dL | Negative | Positive | Negative | Positive |
| Sodium Fluoride | 1% w/v | Negative | Positive | Negative | Positive |
| Urea | 6.0 g/dL | Negative | Positive | Negative | Positive |
Table N. Endogenous Substances (100 ng/mL and 300 ng/mL Cutoffs)
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(viii) Specific Gravity and pH
Drug free urine pools with specific gravity values ranging from 1.002 to 1.035 and pH values ranging from 3.0 to 11.0 were prepared and spiked to final concentrations of 75 ng/mL, 125 ng/mL and 375 ng/mL oxycodone. These samples were then evaluated in qualitative and semiquantitative modes. No positive or negative interference was observed.
(ix) Conclusion
The proposed Syva Emit® II Plus Oxycodone assay is substantially equivalent to the legally marketed predicate device based on intended use, principle and the performance characteristics above.
§ 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).