(110 days)
The ARK Fentanyl Assay is an immunoasay intended for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL. The assay is intended for use in laboratories with automated clinical chemistry analyzers. This in vitro diagnostic device is for prescription use only.
The ARK Fentanyl Assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/tandem Mass Spectrometry (LC-MS/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug test result, particularly when the prelininary test result is positive.
The ARK Fentanyl Assay is a homogeneous enzyme immunoassay technique used for the analysis of a specific compound in human urine. The assay is based on competition between drug in the specimen and drug labeled with recombinant glucose-6-phosphate dehydrogenase (rG6PDH) for antibody binding sites. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly proportional to the drug concentration. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH in the presence of glucose-6-phosphate (G6P), resulting in an absorbance change that is measured spectrophotometrically. Endogenous G6PDH does not interfere because the coenzyme NAD functions only with the bacterial enzyme used in the assay.
The ARK Fentanyl Assay consists of reagents R1 anti-fentanyl polyclonal antibody with substrate and R2 fentanyl derivative labeled with bacterial recombinant G6PDH enzyme.
The provided text describes the performance characteristics of the ARK Fentanyl Assay, an immunoassay for the qualitative detection of fentanyl in human urine. Here's a breakdown of the requested information based on the document:
1. A table of acceptance criteria and the reported device performance
The document does not explicitly state "acceptance criteria" in a typical quantitative pass/fail table format for all parameters. Instead, it presents various performance studies with their results, implying that these results met the internal criteria for the manufacturer to claim substantial equivalence. The precision table comes closest to showing performance relative to a cutoff.
| Performance Characteristic | Acceptance Criteria (Implied/Direct) | Reported Device Performance |
|---|---|---|
| Precision | Clarity on positive/negative results around cutoff (1.0 ng/mL) | At Cutoff (1.0 ng/mL): 97 Negative, 63 Positive results out of 160. At +25% Cutoff (1.25 ng/mL) and above: 160/160 (100%) Positive. At -25% Cutoff (0.75 ng/mL) and below: 160/160 (100%) Negative. |
| Analytical Specificity (Cross-reactivity) | Detection of fentanyl and its major metabolite (Norfentanyl); minimal cross-reactivity with other substances. | Norfentanyl: 10% cross-reactivity (at 2.5 ng/mL). Other fentanyl analogs showed varying cross-reactivity (e.g., Acetyl fentanyl: 83.33% at 1.2 ng/mL). Other opioids, structurally similar, and functional analogs tested negative at high concentrations (e.g., Morphine: 100 µg/mL). |
| Interference (Structurally Unrelated Compounds) | No false results in presence of common drugs/substances. | No false negative or false positive results observed for 36 tested compounds at high concentrations (e.g., Acetaminophen 500 µg/mL, Ibuprofen 500 µg/mL) when spiked into urine at ±50% of the cutoff concentration. |
| Interference (Endogenous Substances) | No interference from common endogenous substances in urine. | No interference observed for 14 tested endogenous substances (e.g., Acetone 1000 mg/dL, Glucose 3000 mg/dL) at high concentrations when spiked into urine at ±50% of the cutoff concentration. |
| Interference (Specific Gravity & pH) | No interference across physiological range. | No interference observed for specific gravity (1.001 to 1.030) and pH (3.0 to 11.0) when tested at ±50% of the cutoff concentration. |
| Interference (Boric Acid) | No interference. | No interference observed with 1% w/v boric acid when tested at ±50% of the cutoff concentration. |
| Method Comparison (Concordance with LC-MS/MS) | High agreement with confirmatory method, especially at and away from cutoff. | Total samples: 150. High Positive (>1.5 ng/mL LC-MS/MS): 64/64 (100%) Positive by ARK. Low Negative (<0.5 ng/mL LC-MS/MS): 50/51 (98%) Negative by ARK (1 discordant positive). Near Cutoff Negative (0.5-0.9 ng/mL LC-MS/MS): 20 positive, 3 negative by ARK (23 total). Near Cutoff Positive (1.0-1.5 ng/mL LC-MS/MS): 12 positive, 0 negative by ARK (12 total). |
| Calibration Curve Stability | Maintain effectiveness for a specified period. | Effective up to at least 15 days. |
2. Sample size used for the test set and the data provenance
- Precision Test Set: Not explicitly stated as a separate "test set" but 160 analyses were performed for each of 9 fentanyl concentration levels, totaling 1440 analyses.
- Analytical Specificity / Interference Test Set: Concentrations of various compounds were spiked into drug-free, negative human urine. The number of individual urine samples used is not specified, but the testing was performed on Beckman Coulter AU680.
- Method Comparison Test Set: A total of 150 unaltered clinical urine specimens.
- Data Provenance: The document states "human urine" was used for testing, and for the method comparison, it specifies "unaltered clinical urine specimens that are not individually identifiable." No specific country of origin is mentioned, but the context implies it was likely conducted in the US, given the FDA submission. The studies appear to be prospective as they were specifically designed and conducted to evaluate the device's performance for this submission.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This section is not applicable as the device is an in-vitro diagnostic (IVD) immunoassay for detecting a chemical (fentanyl) in urine, not an image-based AI device requiring expert interpretation of medical images. The "ground truth" for the method comparison was established by a laboratory-based confirmatory method, LC-MS/MS (Liquid Chromatography/tandem Mass Spectrometry).
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
This is not applicable for this type of IVD device. Adjudication methods like "2+1" or "3+1" are typically used in medical imaging studies where human readers provide interpretations that need to be reconciled to establish a consensus ground truth. Here, the ground truth is an analytical measurement (LC-MS/MS).
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
This is not applicable. The device is an automated immunoassay, which does not involve human readers for interpretation, nor is it an AI-assisted diagnostic tool. Its performance is compared against a gold-standard laboratory method (LC-MS/MS).
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the studies presented (Precision, Analytical Specificity, Interference, and Method Comparison) represent the standalone performance of the ARK Fentanyl Assay, as it is an automated immunoassay performed on clinical chemistry analyzers, without human intervention for result interpretation beyond the machine's output. The device itself is the "algorithm only" in this context.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The ground truth for the method comparison study was established by LC-MS/MS (Liquid Chromatography/tandem Mass Spectrometry), which is considered a definitive confirmatory chemical method for fentanyl detection.
8. The sample size for the training set
This information is not provided in the document. The document describes performance validation studies for the device, but it does not detail the internal development or "training" process (if any, in the context of an immunoassay optimization rather than machine learning). Immunoassays are biochemically developed systems, not typically "trained" on data sets in the same way an AI algorithm is.
9. How the ground truth for the training set was established
As the document does not describe a "training set" in the context of machine learning, this information is not applicable. The development of an immunoassay involves extensive biochemical research, optimization, and validation using well-characterized samples, rather than a data-driven "training" process with a ground truth dataset in the AI sense. The calibrators and controls used are prepared by volumetric dilution of high purity fentanyl traceable to HPLC into drug-free human urine.
{0}------------------------------------------------
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA text logo on the right. The FDA text logo is in blue and includes the letters "FDA" followed by the words "U.S. FOOD & DRUG ADMINISTRATION".
June 6, 2018
ARK Diagnostics, Inc. Cherry Mun Manager, Quality and Regulatory Affairs 48089 Fremont Boulevard Fremont, CA 94538
Re: K180427
Trade/Device Name: ARK Fentanyl Assay Regulation Number: 21 CFR 862.3650 Regulation Name: Opiate test system Regulatory Class: Class II Product Code: DJG Dated: May 3, 2018 Received: May 4, 2018
Dear Cherry Mun:
We have reviewed vour 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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR
{1}------------------------------------------------
803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely, Kellie B. Kelm -S
for Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
{2}------------------------------------------------
Indications for Use
510(k) Number (if known) K180427
Device Name ARK Fentanyl Assay
Indications for Use (Describe)
Form Approved: OMB No. 0910-0120 Expiration Date: 06/30/2020 See PRA Statement below.
The ARK Fentanyl Assay is an immunoasay intended for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL. The assay is intended for use in laboratories with automated clinical chemistry analyzers. This in vitro diagnostic device is for prescription use only.
The ARK Fentanyl Assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/tandem Mass Spectrometry (LC-MS/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug test result, particularly when the prelininary test result is positive.
Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
{3}------------------------------------------------
510(k) SUMMARY
This 510(k) Summary of Safety and Effectiveness information is being submitted in accordance with the requirements of Safe Medical Device Act of 1990 and 21 CFR 807.92.
The assigned 510(k) number is K180427.
| 807.92 (a)(1): Name: | ARK Diagnostics, Inc. |
|---|---|
| Address: | 48089 Fremont BlvdFremont, CA 94538 USA |
| Owner Operator Number: | 10027663 |
| Establishment Registration: | 3005755244 |
| Phone: | (510) 270-6270 |
| FAX: | (510) 270-6298 |
| Contact: | Cherry Mun – (510) 270-6288Manager of Quality and Regulatory Affairs |
Date Prepared: May 03, 2018
807.92 (a)(2): Device Name – Trade Name, Common Name, and Classification
| Trade Name: | ARK™ Fentanyl Assay |
|---|---|
| Common Name: | Homogeneous Enzyme Immunoassay, Opiate Test System |
Classification:
| Product Code | Classification | Regulation Section | Panel |
|---|---|---|---|
| DJG | Class II | 21 CFR 862.3650Opiate Test System | Toxicology(91) |
807.92 (a)(3): Identification of the Legally Marketed Predicate Device
Immunalysis SEFRIA™ Fentanyl Urine Enzyme Immunoassay K161216
{4}------------------------------------------------
807.92 (a)(4): Device Description
The ARK Fentanyl Assay is a homogeneous enzyme immunoassay technique used for the analysis of a specific compound in human urine. The assay is based on competition between drug in the specimen and drug labeled with recombinant glucose-6-phosphate dehydrogenase (rG6PDH) for antibody binding sites. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly proportional to the drug concentration. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH in the presence of glucose-6-phosphate (G6P), resulting in an absorbance change that is measured spectrophotometrically. Endogenous G6PDH does not interfere because the coenzyme NAD functions only with the bacterial enzyme used in the assay.
The ARK Fentanyl Assay consists of reagents R1 anti-fentanyl polyclonal antibody with substrate and R2 fentanyl derivative labeled with bacterial recombinant G6PDH enzyme.
807.92 (a)(5): Intended Use / Indications for Use
ARK Fentanyl Assay
The ARK Fentanyl Assay is an immunoassay intended for the qualitative detection of fentanyl in human urine at a cutoff concentration of 1.0 ng/mL. The assay is intended for use in laboratories with automated clinical chemistry analyzers. This in vitro diagnostic device is for prescription use only.
The ARK Fentanyl Assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/tandem Mass Spectrometry (LC-MS/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug test result, particularly when the preliminary test result is positive.
{5}------------------------------------------------
807.92 (a)(6): Technological Similarities and Differences to the Predicate
SUBSTANTIAL EQUIVALENCE COMPARATIVE TABLE
Comparison between the Immunalysis SEFRIA™ Fentanyl Urine Enzyme Immunoassay and the ARK™ Fentanyl Assay
| Characteristic | Predicate DeviceImmunalysis SEFRIA™ Fentanyl UrineEnzyme Immunoassay (K161216) | Candidate DeviceARK™ Fentanyl Assay |
|---|---|---|
| Similarities | ||
| Test System | Homogenous enzyme immunoassay(EIA) | Same |
| Intended Use | For the qualitative determination offentanyl in human urine at a cutoffconcentration of 1.0 ng/mL. | Same |
| Sample Matrix | Human urine | Same |
| User Environment | Clinical laboratories; Prescription useonly | Same |
| Mass SpectrometryConfirmation | Required to confirm preliminary positiveanalytical results | Same |
| Platform Required | Automated clinical chemistry analyzer | Same |
| Reagents Form | Liquid - Ready to use | Same |
| Reagent Materials | Two (2) reagent system:Antibody/substrate reagent and enzymelabeled conjugateSodium azide preservative | Same |
| Storage | 2-8°C until expiration date | Same |
| Measured Analyte | Fentanyl | Same |
| Antibody | Rabbit antibodies to fentanyl | Same |
| Cutoff Level | 1.0 ng/mL | Same |
| Characteristic | Predicate DeviceImmunalysis SEFRIA™ Fentanyl UrineEnzyme Immunoassay (K161216) | Candidate DeviceARK™ Fentanyl Assay |
|---|---|---|
| Differences | ||
| Detection | Absorbance change measuredspectrophotometrically at 570 nm. | Absorbance change measuredspectrophotometrically at 340 nm. |
{6}------------------------------------------------
807.92 (b)(1) and 807.92 (b)(2): Brief Description of Nonclinical and Clinical Data
The following performance characteristics were obtained on the Beckman Coulter AU680® automated clinical chemistry analyzer.
Precision
Precision studies were performed using CLSI EP05-A3 as a guideline. Drug-free, negative human urine was supplemented with fentanyl (0.00 to 2.00 ng/mL). Each level was assayed in quadruplicate twice a day for 20 days (N=160). Results are summarized in the table below.
| Human Urine(ng/mL) | Relative %Cutoff | # of Results | Results |
|---|---|---|---|
| 0.00 | -100 | 160 | 160 Negative |
| 0.25 | -75 | 160 | 160 Negative |
| 0.50 | -50 | 160 | 160 Negative |
| 0.75 | -25 | 160 | 160 Negative |
| 1.00 | Cutoff | 160 | 97 Negative;63 Positive |
| 1.25 | +25 | 160 | 160 Positive |
| 1.50 | +50 | 160 | 160 Positive |
| 1.75 | +75 | 160 | 160 Positive |
| 2.00 | +100 | 160 | 160 Positive |
Analytical Specificity
All compounds tested were added to drug-free, negative human urine.
The cross-reactivity of the following metabolites and structural analogs of fentanyl was evaluated by spiking these compounds into drug-free, negative human urine to determine the minimum concentration that would give a positive result approximately equivalent to the 1.0 ng/mL fentanyl cutoff. These concentrations were used to determine the percent cross-reactivity according to the formula:
% Cross-reactivity = (Cutoff concentration / Lowest concentration of cross-reactant causing a positive result) X 100
For the compounds Alfentanil and Remifentanil that did not produce a positive result, the highest concentration tested was used to calculate percent cross-reactivity.
{7}------------------------------------------------
Cross-reactivity
Norfentanyl (Major Metabolite)
| Compound | ConcentrationTested(ng/mL) | Percent Cross-reactivity (%) |
|---|---|---|
| Norfentanyl(Major Metabolite) | 2.5 | 10 |
| 300 | 0.33 |
Other Metabolites and Structural Analogs of Fentanyl
| Compound | LowestConcentrationTested ThatProduced aResponseApproximatelyEquivalent to theCutoff(ng/mL) | Percent Cross-reactivity (%) |
|---|---|---|
| Acetyl fentanyl | 1.20 | 83.33 |
| Acrylfentanyl | 1.20 | 83.33 |
| ω-1-Hydroxyfentanyl | 1.20 | 83.33 |
| Isobutyryl fentanyl | 1.50 | 66.67 |
| Ocfentanil | 1.50 | 66.67 |
| Butyryl fentanyl | 1.60 | 62.50 |
| Furanyl fentanyl | 1.75 | 57.14 |
| Valeryl fentanyl | 2.50 | 40.00 |
| (±) β-hydroxythiofentanyl | 2.80 | 35.71 |
| 4-Fluoro-isobutyrylfentanyl | 3.00 | 33.33 |
| Para-fluorobutyrylfentanyl (p-FBF) | 3.00 | 33.33 |
| Para-fluoro fentanyl | 3.00 | 33.33 |
| (±)-3-cis-methylfentanyl | 5.00 | 20.00 |
| Despropionylfentanyl (4-ANPP) | 75.00 | 1.33 |
| Carfentanil | 500 | 0.20 |
| Sufentanil | 625 | 0.16 |
| Norcarfentanil | 5,000 | <0.02 |
| Acetyl norfentanyl | 10,000 | 0.01 |
| Remifentanil | 10,000 | <0.01 |
| Alfentanil | 100,000 | <0.001 |
{8}------------------------------------------------
The following opioids, structurally similar compounds, and functional analogs were negative at the concentrations tested with the ARK Fentanyl Assay.
| Compound | ConcentrationTested(µg/mL) | Compound | ConcentrationTested(µg/mL) |
|---|---|---|---|
| 6-Acetyl morphine | 10 | Naltrexone | 50 |
| Amphetamine | 100 | Norbuprenorphine | 50 |
| Buprenorphine | 100 | Norcodeine | 50 |
| Buprenorphineglucuronide | 50 | Norketamine | 100 |
| Codeine | 100 | Normeperidine | 100 |
| Dextromethorphan | 100 | Normorphine | 50 |
| Dihydrocodeine | 100 | Noroxycodone | 100 |
| EDDP | 100 | Oxycodone | 100 |
| EMDP | 50 | Oxymorphone | 50 |
| Fluoxetine | 50 | Pentazocine(Talwin) | 10 |
| Heroin | 30 | Pipamperone | 100 |
| Hydrocodone | 100 | Risperidone | 2 |
| Hydromorphone | 100 | Tapentadol | 50 |
| Ketamine | 100 | Thioridazine | 50 |
| Levorphanol | 50 | Tilidine | 50 |
| Meperidine | 100 | Tramadol | 100 |
| Methadone | 100 | Tramadol-O-Desmethyl | 100 |
| Morphine | 100 | Tramadol-N-Desmethyl | 100 |
| Morphine-3-glucuronide | 50 | Trazodone | 10 |
| Naloxone | 50 |
{9}------------------------------------------------
Interference – Structurally Unrelated Compounds
High concentrations of the following structurally unrelated compounds were added into fentanylspiked urine (± 50% of the cutoff concentration). The substances listed below did not yield a false result relative to the cutoff.
| Compound | ConcentrationTested(µg/mL) | 0.5 ng/mL(-50% Cutoff) | 1.5 ng/mL(+50% Cutoff) |
|---|---|---|---|
| Acetaminophen | 500 | Negative | Positive |
| Acetylsalicylic acid | 1000 | Negative | Positive |
| Albuterol | 100 | Negative | Positive |
| Amitriptyline | 35 | Negative | Positive |
| Amobarbital | 100 | Negative | Positive |
| Benzoylecgonine | 100 | Negative | Positive |
| Bupropion | 50 | Negative | Positive |
| Caffeine | 100 | Negative | Positive |
| Carbamazepine | 100 | Negative | Positive |
| Chlorpromazine | 50 | Negative | Positive |
| Clomipramine | 50 | Negative | Positive |
| Cyclobenzaprine | 10 | Negative | Positive |
| Desipramine | 50 | Negative | Positive |
| Doxepin | 50 | Negative | Positive |
| Ecgonine | 100 | Negative | Positive |
| Ephedrine | 100 | Negative | Positive |
| Fluphenazine | 100 | Negative | Positive |
| Ibuprofen | 500 | Negative | Positive |
| Imipramine | 30 | Negative | Positive |
| Lidocaine | 50 | Negative | Positive |
| Maprotiline | 50 | Negative | Positive |
| Methapyrilene | 10 | Negative | Positive |
| Methaqualone | 50 | Negative | Positive |
| Metronidazole | 300 | Negative | Positive |
| Nicotine | 10 | Negative | Positive |
| Nortriptyline | 25 | Negative | Positive |
| Oxazepam | 100 | Negative | Positive |
| Phencyclidine | 100 | Negative | Positive |
| Phenobarbital | 100 | Negative | Positive |
| Propoxyphene | 50 | Negative | Positive |
| Ranitidine | 100 | Negative | Positive |
| Secobarbital | 100 | Negative | Positive |
| Valproic acid | 250 | Negative | Positive |
| Venlafaxine | 100 | Negative | Positive |
{10}------------------------------------------------
Interference – Endogenous Substances
Interference studies were performed using CLSI EP07-A2 as a guideline. High concentrations of the following endogenous substances were added into fentanyl-spiked urine (± 50% of the cutoff concentration). No interference was observed when tested with the ARK Fentanyl Assay.
| Compound | ConcentrationTested(mg/dL) | 0.5 ng/mL(-50% Cutoff) | 1.5 ng/mL(+50% Cutoff) |
|---|---|---|---|
| Acetone | 1000 | Negative | Positive |
| Ascorbic Acid | 560 | Negative | Positive |
| Bilirubin | 2 | Negative | Positive |
| Creatinine | 500 | Negative | Positive |
| Ethanol | 1000 | Negative | Positive |
| Galactose | 10 | Negative | Positive |
| Gamma Globulin | 500 | Negative | Positive |
| Glucose | 3000 | Negative | Positive |
| Hemoglobin | 500 | Negative | Positive |
| Human Albumin | 500 | Negative | Positive |
| Oxalic Acid | 100 | Negative | Positive |
| Riboflavin | 7.5 | Negative | Positive |
| Sodium Chloride | 4000 | Negative | Positive |
| Urea | 2000 | Negative | Positive |
Interference – Specific Gravity and pH
Urine samples with specific gravity values from 1.001 to 1.030 and pH values ranging from 3.0 to 11.0 were tested in the presence of the two levels of fentanyl at ± 50% of the cutoff concentration. No interference was observed when tested with the ARK Fentanyl Assay.
Interference – Boric Acid
One percent (1%) w/v of boric acid was added into fentanyl-spiked urine (± 50% of the cutoff concentration). Results are provided in the table below.
| Compound | ConcentrationTested | 0.5 ng/mL(-50% Cutoff) | 1.5 ng/mL(+50% Cutoff) |
|---|---|---|---|
| Boric Acid | 1% w/v | Negative | Negative |
{11}------------------------------------------------
Method Comparison
A total of one hundred fifty (150) unaltered clinical urine specimens that are not individually identifiable were analyzed for fentanyl with the ARK Fentanyl Assay and by LC-MS/MS. The LC-MS/MS confirmatory method was performed by a licensed reference laboratory and used a fentanyl cutoff of 0.2 ng/mL.
Specimens were tested with the ARK Fentanyl Assay in single replicates on a Beckman Coulter AU680 analyzer and compared to results obtained by LC-MS/MS. Groups of around 10-30 specimens were assayed per run. Each run was verified by assaying the bi-level ARK Fentanyl Controls (0.5 ng/mL and 1.5 ng/mL) as quality control samples with values above the assay range (>10.0 ng/mL) were diluted with negative urine calibrator (ARK Fentanyl Calibrator A) and retested.
Results are summarized as follows:
| ARK Result | Low NegativeLess than50% belowthe Cutoff | Near CutoffNegativeBetween 50%below theCutoff and theCutoff | Near CutoffPositiveBetween theCutoff and50% abovethe Cutoff | High PositiveGreater than50% abovethe Cutoff |
|---|---|---|---|---|
| (< 0.5 ng/mLby LC-MS/MS) | (0.5 - 0.9ng/mL by LC-MS/MS) | (1.0 - 1.5ng/mL by LC-MS/MS) | (> 1.5 ng/mLby LC-MS/MS) | |
| Positive | 1* | 20 | 12 | 64 |
| Negative | 50 | 3 | 0 | 0 |
Discordant Results
*Norfentanyl was detected in this discordant sample (Sample ID #052) and contributed to the positive result obtained with the ARK Fentanyl Assay for this sample.
| Sample ID Number | ARK Immunoassay Result | Fentanyl(ng/mL by LC-MS/MS) |
|---|---|---|
| 051 | Positive | 0.7 |
| 052* | Positive | 0.4 |
| 053 | Positive | 0.9 |
| 054 | Positive | 0.9 |
| 055 | Positive | 0.6 |
| 056 | Positive | 0.6 |
| 057 | Positive | 0.9 |
| 058 | Positive | 0.5 |
| 059 | Positive | 0.9 |
| 060 | Positive | 0.5 |
| 061 | Positive | 0.9 |
| 062 | Positive | 0.6 |
| 063 | Positive | 0.9 |
{12}------------------------------------------------
| Sample ID Number | ARK Immunoassay Result | Fentanyl(ng/mL by LC-MS/MS) |
|---|---|---|
| 064 | Positive | 0.8 |
| 065 | Positive | 0.5 |
| 066 | Positive | 0.7 |
| 069 | Positive | 0.5 |
| 070 | Positive | 0.6 |
| 072 | Positive | 0.6 |
| 073 | Positive | 0.8 |
| 074 | Positive | 0.6 |
Traceability and Value Assignment
ARK Fentanyl Calibrators and Controls are prepared by volumetric dilution of high purity fentanyl (certified solution traceable to HPLC) into non-sterile, processed human urine free of fentanyl. Testing is performed with the ARK Fentanyl Assay on the Beckman Coulter AU680 automated clinical chemistry analyzer, calibrated with the ARK Fentanyl Calibrator.
Calibration Curve Stability
A stored calibration curve was effective up to at least 15 days based on supporting data. Calibration curve stability may depend on individual laboratory performance.
807.92 (b)(3): Conclusions from Nonclinical Testing
As summarized above, the ARK Fentanyl Assay is substantially equivalent to the legally marketed predicate device, Immunalysis SEFRIA™ Fentany] Urine Enzyme Immunoassay (K161216).
§ 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).