(30 days)
Not Found
No
The device description details a standard immunoassay technique based on enzyme activity and spectrophotometric measurement. There is no mention of AI or ML in the device description, intended use, or performance studies. The analysis of clinical specimens and performance studies are based on traditional statistical methods and comparisons to a confirmatory method (LC-MS/MS).
No.
This device is an in vitro diagnostic assay intended for the qualitative detection of fentanyl in human urine, which provides analytical results rather than direct treatment or diagnosis.
Yes
The "Intended Use / Indications for Use" section explicitly states, "This in vitro diagnostic device is for prescription use only." This directly classifies the device as diagnostic.
No
The device description clearly states it is an immunoassay technique involving reagents and enzyme activity measured spectrophotometrically, indicating a physical, chemical, and optical process, not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicitly stated in the Intended Use: The document clearly states, "This in vitro diagnostic device is for prescription use only."
- Intended Use aligns with IVD definition: The assay is intended for the qualitative detection of fentanyl in human urine, which is a biological specimen. This analysis is performed in vitro (outside the body) to provide information about a person's health status (in this case, the presence of fentanyl).
- Device Description supports IVD nature: The description details a laboratory-based immunoassay technique using reagents to analyze a sample. This is characteristic of an IVD.
- Intended User/Care Setting: The device is intended for use in "laboratories with automated clinical chemistry analyzers," which are typical settings for performing IVD tests.
- Performance Studies: The document describes performance studies (precision, analytical specificity, method comparison) conducted to evaluate the device's performance in analyzing human urine samples, which is standard for IVD devices.
N/A
Intended Use / Indications for Use
The ARK Fentanyl II 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 II Assay provides only a preliminary analytical result. A more specific alternative chemical method must be used in order to obtain a confirmed positive 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.
Product codes (comma separated list FDA assigned to the subject device)
DJG
Device Description
The ARK Fentanyl II 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 related 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 serum G6PDH does not interfere because the coenzyme NAD functions only with the bacterial enzyme used in the assay.
The ARK Fentanyl II Assay consists of reagents R1 anti-fentanyl monoclonal antibodies with substrate and R2 fentanyl derivative labeled with bacterial recombinant G6PDH enzyme.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
laboratories with automated clinical chemistry analyzers. This in vitro diagnostic device is for prescription use only.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
A total of one hundred forty seven (147) unaltered clinical urine specimens that are not individually identifiable were analyzed for fentanyl with the ARK Fentanyl II 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 II Assay in single replicates on a Beckman Coulter AU680 analyzer and compared to results obtained by LC-MS/MS. Groups of up to 31 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.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
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). Result summary:
At 1.00 ng/mL (Cutoff), there were 84 Negative and 76 Positive results out of 160.
At 0.00, 0.25, 0.50, 0.75 ng/mL, all results were Negative (160 each).
At 1.25, 1.50, 1.75, 2.00 ng/mL, all results were Positive (160 each).
Analytical Specificity: Cross-reactivity of Norfentanyl was 7% (15 ng/mL). Other metabolites and structural analogs showed varying cross-reactivity from 90.91% (Acetyl fentanyl, Isobutyryl fentanyl) down to 1.5 ng/mL by LC-MS/MS): 62 ARK Positive, 0 ARK Negative.
Discordant Results (ARK Immunoassay Positive, LC-MS/MS Fentanyl
§ 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).
0
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health and Human Services logo on the left and the FDA logo on the right. The FDA logo features the letters 'FDA' in a blue box, followed by the words 'U.S. FOOD & DRUG ADMINISTRATION' in blue text.
February 26, 2020
ARK Diagnostics, Inc. Thomas Houts, Ph.D. Director, Quality, Regulatory and Planning 48089 Fremont Boulevard Fremont, CA 94538
Re: K200197
Trade/Device Name: ARKTM Fentanyl II Assay Regulation Number: 21 CFR 862.3650 Regulation Name: Opiate Test System Regulatory Class: Class II Product Code: DJG Dated: January 24, 2020 Received: January 27, 2020
Dear Thomas Houts:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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
- for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
Marianela Perez-Torres, M.T., Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K200197
Device Name ARKTM Fentanyl II Assay
Indications for Use (Describe)
The ARK Fentanyl II 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 II Assay provides only a preliminary analytical result. A more specific alternative chemical method must be used in order to obtain a confirmed positive 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.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| X Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
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 K200197.
| 807.92 (a)(1): Name: | ARK Diagnostics, Inc. | ||
|---|---|---|---|
| Address: | 48089 Fremont Blvd | ||
| Fremont, CA 94538 USA | |||
| Owner Operator Number: | 10027663 | ||
| Establishment Registration: | 3005755244 | ||
| Phone: | (510) 270-6270 | ||
| FAX: | (510) 270-6298 | ||
| Contact: | Thomas Houts, Ph.D. – (510) 270-6296 | ||
| Director, Quality, Regulatory and Planning |
Date Prepared: February 25, 2020
807.92 (a)(2): Device name – trade name and common name, and classification
| Trade Name: | ARKTM Fentanyl II Assay |
|---|---|
| Common Name: | Homogeneous Enzyme Immunoassay, Opiate Test System |
Classification:
| Product Code | Classification | Regulation Section | Panel |
|---|---|---|---|
| DJG | Class II | 21 CFR 862.3650 | |
| Opiate Test System | Toxicology | ||
| (91) |
807.92 (a)(3): Identification of the legally marketed predicate device
ARK™ Fentanyl Assay - K180427
4
807.92 (a)(4): Device Description
The ARK Fentanyl II 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 related 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 serum G6PDH does not interfere because the coenzyme NAD functions only with the bacterial enzyme used in the assay.
The ARK Fentanyl II Assay consists of reagents R1 anti-fentanyl monoclonal antibodies with substrate and R2 fentanyl derivative labeled with bacterial recombinant G6PDH enzyme.
807.92 (a)(5): Intended Use / Indications for Use
ARK Fentanyl II Assay
The ARK Fentanyl II 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 II Assay provides only preliminary analytical result. A more specific alternative chemical method must be used in order to obtain a confirmed positive 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 ARK™ Fentanyl Assay and the ARK™ Fentanyl II Assay
| Characteristic | Predicate Device
ARK™ Fentanyl Assay (K180427) | Candidate Device
ARK™ Fentanyl II Assay |
|--------------------------------------|--------------------------------------------------------------------------------------------------------------------|--------------------------------------------|
| Similarities | | |
| Test System | Homogenous enzyme immunoassay
(EIA) | Same |
| Intended Use | For the qualitative detection of fentanyl
in human urine at a cutoff concentration
of 1.0 ng/mL | Same |
| Sample Matrix | Human urine | Same |
| Detection | Absorbance change measured
spectrophotometrically at 340 nm. | Same |
| User Environment | Clinical laboratories; Prescription use
only | Same |
| Mass
Spectrometry
Confirmation | Required to confirm preliminary
positive analytical 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
enzyme labeled conjugate
Sodium azide preservative | Same |
| Storage | 2-8°C until expiration date | Same |
| Measured Analyte | Fentanyl | Same |
| Cutoff Level | 1.0 ng/mL | Same |
| Characteristic | Predicate Device
ARKTM Fentanyl Assay (K180427) | Candidate Device
ARKTM Fentanyl II Assay |
|----------------|----------------------------------------------------|---------------------------------------------|
| Differences | | |
| Antibody | Rabbit polyclonal antibodies to
fentanyl | Rabbit monoclonal antibodies to
fentanyl |
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 | Qualitative
Precision
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 | 84 Negative;
76 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 and evaluated by dose-response to determine the approximate equivalence 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 / Concentration approximately equivalent to the 1.0 ng/mL cutoff) 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 | Concentration
Tested
(ng/mL) | Percent
Crossreactivity
(%) |
|--------------------------------|------------------------------------|-----------------------------------|
| Norfentanyl (Major Metabolite) | 15 | 7 |
Other Metabolites and Structural Analogs of Fentanyl
| Compound | Concentration
Approximately
Equivalent to
the Cutoff
(ng/mL) | Percent
Crossreactivity
(%) |
|-------------------------------------|--------------------------------------------------------------------------|-----------------------------------|
| Acetyl fentanyl | 1.1 | 90.91 |
| Isobutyryl fentanyl | 1.1 | 90.91 |
| ω-1-Hydroxyfentanyl | 1.2 | 83.33 |
| Acrylfentanyl | 1.3 | 76.90 |
| Butyryl fentanyl | 1.4 | 71.43 |
| Furanyl fentanyl | 1.5 | 66.67 |
| Para-fluoro fentanyl | 1.5 | 66.67 |
| Ocfentanil | 1.6 | 62.50 |
| 4-Fluoro-isobutyryl fentanyl | 1.9 | 52.63 |
| Para-fluorobutyryl fentanyl (p-FBF) | 1.9 | 52.63 |
| Valeryl fentanyl | 2.3 | 43.48 |
| β-hydroxyfentanyl | 9.5 | 10.53 |
| Acetyl norfentanyl | 12.1 | 8.26 |
| (±) β-hydroxythiofentanyl | 32.7 | 3.06 |
| (±)-3-cis-methyl fentanyl | 144.1 | 0.69 |
| Carfentanil | 448.2 | 0.22 |
| Despropionyl fentanyl (4-ANPP) | 471.8 | 0.21 |
| Sufentanil | 2,362 | 0.04 |
| Remifentanil | 10,000 | 1.5 ng/mL
by LC-
MS/MS) |
| Positive | 1 * | 21 | 11 | 62 |
| Negative | 50 | 2 | 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) | Norfentanyl
(ng/mL by LC-
MS/MS) |
|---------------------|---------------------------|-------------------------------------|----------------------------------------|
| 052* | Positive | 0.4 | 7.6 |
| 065 | Positive | 0:5 | 5.2 |
| 058 | Positive | 0:5 | 7.9 |
| 069 | Positive | 0:5 | 31.2 |
| 060 | Positive | 0:5 | 425.4 |
| 056 | Positive | 0.6 | 3.7 |
| 072 | Positive | 0.6 | 13.8 |
| 062 | Positive | 0.6 | 14.5 |
| 074 | Positive | 0.6 | 14.6 |
| 0રર | Positive | 0.6 | 16.9 |
12
| Sample ID
Number | ARK Immunoassay
Result | Fentanyl
(ng/mL by LC-
MS/MS) | Norfentanyl
(ng/mL by LC-
MS/MS) |
|---------------------|---------------------------|-------------------------------------|----------------------------------------|
| 071 | Positive | 0.6 | 19.0 |
| 070 | Positive | 0.6 | 161.7 |
| 051 | Positive | 0.7 | 2.1 |
| 066 | Positive | 0.7 | 3.1 |
| 064 | Positive | 0.8 | 15.9 |
| 073 | Positive | 0.8 | 45.8 |
| 063 | Positive | 0.9 | 2.2 |
| 061 | Positive | 0.9 | 6.5 |
| 057 | Positive | 0.9 | 12.3 |
| 053 | Positive | 0.9 | 14.0 |
| 059 | Positive | 0.9 | 62.6 |
| 054 | Positive | 0.9 | 63.4 |
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 II Assay on the Beckman Coulter AU680 automated clinical chemistry analyzer, calibrated with the ARK Fentanyl Calibrator.
807.92 (b)(3): Conclusions from Nonclinical Testing
As summarized above, the ARK Fentanyl II Assay system was shown to be substantially equivalent to the legally marketed predicate device, ARK Fentanyl Assay system: K180427.