(265 days)
The Snap-Top Split Key Cup for use with the GenPrime Drugs of Abuse (DOA) Reader System is for in vitro diagnostic use and is intended for prescription use in laboratories, point-of-care and workplaces by trained users. The test is not intended for over-the-counter use. The test cannot be read visually and must be used with the GenPrime DOA Reader. The Snap-Top Split Key Cup qualitatively detects drug classes in human urine at the cutoff concentrations shown below:
- Test/ Calibrated to /Cutoff Amphetamines/ d-Amphetamine/ 500 ng/mL Barbiturates/ Secobarbital/ 300 ng/mL Benzodiazepines/ Oxazapam/ 300 ng/mL Cocaine/ Benzoylecgonine/ 150 ng/mL Methamphetamine/ d-Methamphetamine/ 500 ng/mL Methadone/ Methadone/ 300 ng/mL Morphine/ Morphine/ 300 ng/mL Morphine 2000/ Morphine/ 2000 ng/mL Oxycodone/ Oxycodone/ 100 ng/mL Phencyclidine/ Phencyclidine/ 25 ng/mL Marijuana/ Delta-9-THC-COOH/ 50 ng/mL
Configurations of the Snap-Top Split Key Cup may consist of any combination of the above listed drug analytes. The Snap-Top Split Key Cup provides only a preliminary analytical result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography / mass spectrometry (GC/MS), high performance liquid chromatography (HPLC) or liquid chromatography/tandem mass spectrometry (LC/MS/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are obtained.
The GenPrime Drugs of Abuse (DOA) Reader System consists of a small, portable high resolution flatbed scanner, customized GenPrime DOA Reader Software, and lateral flow tests that are intended for use in the system. The scanner has a custom Scanner Lid with an opening for the test device, and a Scanner Stand, which places the scanner bed at the appropriate angle for running and reading the test devices. The System is intended for use with the Snap-Top Split Key Cup, which is a rapid, single use, disposable immunochromatographic test for the qualitative detection of drugs of abuse in human urine (K130082). This description is limited to the Snap-Top Split Key Cup (SK Cup), with 3 additional drugs being added, giving 11 total drugs.
The Snap-Top SK cup contains up to five (5) test strips embedded in a urine sample cup, containing a total of up to 11 drug test lines (between one and four drug test lines per test strip). Different drug configurations may be used. Each test strip has an internal control line to confirm validity of the test results.
The Snap-Top SK Cup Drugs of Abuse Test devices are run in the GenPrime DOA Reader System according to their specific instructions for use. At the conclusion of the test (5 minutes) an image is captured and the software algorithm determines whether the colored test lines for each analyte are above or below the threshold associated with a negative or positive result. The software also confirms the validity of the results by verifying the presence of control lines. The results are recorded and logged into a database along with an image of the test, patient and operator information and the time of image capture. The results can be viewed, printed, or sent to a recipient via email or other electronic method. The GenPrime DOA Reader is for in vitro diagnostic use and is intended for use in laboratories, point-of-care sites and workplaces by trained users. The test is not intended for over-the-counter use. The GenPrime DOA Reader System test devices cannot be read visually.
All analytes on the Snap-Top SK Cup for use with the GenPrime DOA Reader System were previously cleared (K130082) except for the drug tests for benzodiazepines, cocaine and barbiturates.
Here's a summary of the acceptance criteria and study details for the Snap-Top Split Key Cup, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the precision studies, which show the percentage of correct classifications at various concentrations relative to the cutoff. For accuracy, the agreement with reference methods is presented.
| Drug Analyte | Cutoff (ng/mL) | Acceptance Criteria (Implied by study results) | Reported Device Performance (Summary from tables) |
|---|---|---|---|
| Precision Studies | |||
| BAR | 300 | 100% Negative at 0-50% of cutoff | 100% Negative at 0%, 25%, 50% |
| 100% Positive at 150-200% of cutoff | 100% Positive at 150%, 175%, 200% | ||
| BZO | 300 | 100% Negative at 0-50% of cutoff | 100% Negative at 0%, 25% (96% at 50%) |
| 100% Positive at 150-200% of cutoff | 100% Positive at 150%, 175%, 200% (96% at 125%) | ||
| COC | 150 | 100% Negative at 0-50% of cutoff | 100% Negative at 0%, 25%, 50% |
| 100% Positive at 150-200% of cutoff | 100% Positive at 150%, 175%, 200% (97.8% at 125%) | ||
| Clinical Accuracy (Agreement with Reference Method) | |||
| BAR | 300 | High agreement for positive and negative samples | 100% for positive, 96.0% for negative |
| BZO | 300 | High agreement for positive and negative samples | 100% for positive, 95.2% for negative |
| COC | 150 | High agreement for positive and negative samples | 100% for positive, 100% for negative |
| All Drugs | N/A | High agreement for positive and negative samples | 100% (96.9-100% CI) for positive, 97.0% (92.5-98.8% CI) for negative |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size (Precision Study):
- For each drug (BAR, BZO, COC) at specific % of cutoff concentrations (0%, 25%, 50%, 75%, 125%, 150%, 175%, 200%), the number of tests (N) ranged from 45 to 50 samples.
- For the "All Drugs" summary in the precision studies, the total N at each % of cutoff ranged from 135 to 142.
- Test Set Sample Size (Clinical Accuracy Study):
- For each drug (BAR, BZO, COC), a minimum of 40 unaltered positive and 40 unaltered negative clinical samples were assessed.
- Data Provenance:
- The precision studies were performed at three sites representative of laboratory, workplace, and point-of-care (POC) settings, suggesting prospective data collection in a controlled environment.
- The clinical accuracy studies used "blind coded clinical urine samples," implying prospective or retrospectively collected clinical samples with unknown status to the test operators.
- The country of origin is not explicitly stated, but the submission is to the U.S. FDA, suggesting the studies were likely conducted in the USA or adhering to international standards acceptable to the FDA.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
- Precision Studies Ground Truth: The ground truth for the precision studies was established chemically. "GC/MS and/or LC/MS/MS were performed to confirm the concentration of calibrator drug in each test solution." No human experts were involved in establishing this ground truth directly.
- Clinical Accuracy Study Ground Truth: The ground truth for clinical samples was determined by "GC/MS or LC/MS/MS." Negative samples were initially screened by EIA, with 10% also confirmed by GC/MS or LC/MS/MS. Again, this points to instrumental analysis rather than human expert consensus for ground truth.
4. Adjudication Method for the Test Set
- No specific adjudication method by human experts (like 2+1 or 3+1) is mentioned in the document. The determination of "positive" or "negative" from the reference methods (GC/MS or LC/MS/MS) serves as the definitive ground truth for both precision and clinical studies. Discrepancies between the device and the reference standard were simply reported as "discordant results."
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No MRMC comparative effectiveness study was done to assess how much human readers improve with AI vs. without AI assistance. The device is for in vitro diagnostic use, and the "Reader System" refers to an automated instrument that interprets the results, not human readers.
6. Standalone Performance Study (Algorithm Only)
- Yes, a standalone performance study was done. The document explicitly states: "The test devices cannot be read visually." and "the software algorithm determines whether the colored test lines for each analyte are above or below the threshold associated with a negative or positive result." This indicates that the GenPrime DOA Reader System (which includes the software algorithm) operates as a standalone device to interpret the results without human interpretation of the test lines.
7. Type of Ground Truth Used
- Chemical/Instrumental Analysis (Gold Standard): The primary ground truth for both precision and clinical studies was established using highly accurate chemical analysis methods: Gas Chromatography / Mass Spectrometry (GC/MS) or Liquid Chromatography / Tandem Mass Spectrometry (LC/MS/MS). These are considered gold standard methods for drug concentration confirmation.
8. Sample Size for the Training Set
- The document does not specify a separate "training set" for the device's algorithm. The precision and clinical studies described appear to be validation studies rather than data used for initial algorithm development or training. Immunochromatographic tests typically rely on pre-defined thresholds and chemical reactions rather than machine learning algorithms that require explicit training sets. The "software algorithm" likely operates on fixed parameters derived from extensive research and development rather than a dynamic training process described for AI.
9. How the Ground Truth for the Training Set Was Established
- As a training set is not explicitly mentioned or implied for a machine learning-based algorithm, how its ground truth was established is not detailed. For typical immunochromatographic tests with an automated reader, the 'training' process involves calibrating the reader to accurately detect the visual signal (colored lines) produced by known concentrations of analytes, which would have been established through controlled experimental protocols using chemically verified samples (similar to how the test set ground truth was established by GC/MS/LC/MS/MS).
{0}------------------------------------------------
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized symbol that resembles three human profiles facing to the right, with flowing lines that suggest movement or connection.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
December 8, 2014
GENPRIME, INC MAUREEN GARNER PRESIDENT 1983 HAZELWOOD ROAD TOMS RIVER NJ 08753
Re: K140665
Trade/Device Name: Snap-Top Split Key Cup for use with the GenPrime Drugs of Abuse Reader System Regulation Number: 21 CFR 862.3150 Regulation Name: Barbiturate test system Regulatory Class: II Product Code: DIS, JXM, DIO Dated: December 2, 2014 Received: December 3, 2014
Dear Ms. Maureen Garner:
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 electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
{1}------------------------------------------------
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Katherine Serrano -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) K140665
Device Name
Snap-Top Split Key Cup for use with the GenPrime Drugs of Abuse Reader System
Indications for Use (Describe)
The Snap-Top Split Key Cup for use with the GenPrime Drugs of Abuse (DOA) Reader System is for in vitro diagnostic use and is intended for prescription use in laboratories, point-of-care and workplaces by trained users. The test is not intended for over-the-counter use. The test cannot be read visually and must be used with the GenPrime DOA Reader. The Snap-Top Split Key Cup qualitatively detects drug classes in human urine at the cutoff concentrations shown below:
- Test/ Calibrated to /Cutoff Amphetamines/ d-Amphetamine/ 500 ng/mL Barbiturates/ Secobarbital/ 300 ng/mL Benzodiazepines/ Oxazapam/ 300 ng/mL Cocaine/ Benzoylecgonine/ 150 ng/mL Methamphetamine/ d-Methamphetamine/ 500 ng/mL Methadone/ Methadone/ 300 ng/mL Morphine/ Morphine/ 300 ng/mL Morphine 2000/ Morphine/ 2000 ng/mL Oxycodone/ Oxycodone/ 100 ng/mL Phencyclidine/ Phencyclidine/ 25 ng/mL Marijuana/ Delta-9-THC-COOH/ 50 ng/mL
Configurations of the Snap-Top Split Key Cup may consist of any combination of the above listed drug analytes. The Snap-Top Split Key Cup provides only a preliminary analytical result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography / mass spectrometry (GC/MS), high performance liquid chromatography (HPLC) or liquid chromatography/tandem mass spectrometry (LC/MS/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are obtained.
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}------------------------------------------------
- APPLICANT'S INFORMATION: 1. GenPrime, Inc. 502 W. Riverside Avenue, #101 Spokane. WA 99201 PH: 866-624-9855 FX: 509-462-2847 E-mail: dmclean@genprime.com Internet: www.genprime.com Establishment Registration No.: 10046367
-
- SUBMITTER'S INFORMATION Maureen Garner President New World Requlatory Solutions. Inc. P.O. Box 5374 Toms River, NJ 08754 PH: 732-779-7422 Fax: 732-270-4829 E-mail: NWRSinc@gmail.com Internet: www.newworldreg.com
- DATE PREPARED: 3. December 5, 2014
- DEVICE INFORMATION 4.
| DEVICE NAME: | Snap-Top Split Key Cup for use with the GenPrime Drugs of |
|---|---|
| Abuse Reader System |
- Classification Panel: Clinical Toxicology (91)
Classification Names: Regulatory information applicable to the test system is provided below:
| CFR Section | Product Code |
|---|---|
| 862.3150, Barbiturate Test System | DIS |
| 862.3170, Benzodiazepine Test System | JXM |
| 862.3250, Cocaine and cocaine metabolite Test System | DIO |
DEVICE CLASSIFICATION: Class II
- PREDICATE DEVICE: PROFILE®-V MEDTOXScan® Drugs of Abuse Test System, 5. (K080635)
-
- DEVICE DESCRIPTION:
The GenPrime Drugs of Abuse (DOA) Reader System consists of a small, portable high resolution flatbed scanner, customized GenPrime DOA Reader Software, and lateral flow tests that are intended for use in the system. The scanner has a custom Scanner Lid with an opening for the test device, and a Scanner Stand, which places the scanner bed at the appropriate angle for running and reading the test devices. The System is intended for use with the Snap-Top Split Key Cup, which is a rapid, single use, disposable immunochromatographic test for the qualitative detection of drugs of abuse in human urine (K130082). This description is limited to the Snap-Top Split Key Cup (SK Cup), with 3 additional drugs being added, giving 11 total drugs.
{4}------------------------------------------------
The Snap-Top SK cup contains up to five (5) test strips embedded in a urine sample cup, containing a total of up to 11 drug test lines (between one and four drug test lines per test strip). Different drug configurations may be used. Each test strip has an internal control line to confirm validity of the test results.
The Snap-Top SK Cup Drugs of Abuse Test devices are run in the GenPrime DOA Reader System according to their specific instructions for use. At the conclusion of the test (5 minutes) an image is captured and the software algorithm determines whether the colored test lines for each analyte are above or below the threshold associated with a negative or positive result. The software also confirms the validity of the results by verifying the presence of control lines. The results are recorded and logged into a database along with an image of the test, patient and operator information and the time of image capture. The results can be viewed, printed, or sent to a recipient via email or other electronic method. The GenPrime DOA Reader is for in vitro diagnostic use and is intended for use in laboratories, point-of-care sites and workplaces by trained users. The test is not intended for over-the-counter use. The GenPrime DOA Reader System test devices cannot be read visually.
All analytes on the Snap-Top SK Cup for use with the GenPrime DOA Reader System were previously cleared (K130082) except for the drug tests for benzodiazepines, cocaine and barbiturates.
The GenPrime DOA Reader System detects drug classes at the following cutoff concentrations for the Snap-Top SK Cup device:
| Test | Drug (Calibrator) | Cutoff |
|---|---|---|
| AMP | Amphetamine (d-Amphetamine) | 500 ng/mL |
| BAR | Barbiturates (Secobarbital) | 300 ng/mL |
| BZO | Benzodiazepines (Oxazapam) | 300 ng/mL |
| COC | Cocaine (Benzoylecgonine) | 150 ng/mL |
| MTD | Methadone (Methadone) | 300 ng/mL |
| MET | Methamphetamine (d-Methamphetamine) | 500 ng/mL |
| MOP 300 | Morphine | 300 ng/mL |
| MOP 2000 | Morphine | 2000 ng/mL |
| OXY | Oxycodone (Oxycodone) | 100 ng/mL |
| PCP | Phencyclidine (Phencyclidine) | 25 ng/mL |
| THC | Marijuana (Delta-9-THC-COOH) | 50 ng/mL |
Configurations of the Snap-Top SK Cup may consist of any combination of the above listed drug analytes. Refer to specific product labeling for the combination of drug tests included in that test device.
{5}------------------------------------------------
INDICATIONS FOR USE: 7.
The Snap-Top Split Key Cup for use with the GenPrime Drugs of Abuse (DOA) Reader System is for in vitro diagnostic use and is intended for prescription use in laboratories, point-of-care and workplaces by trained users. The test is not intended for over-thecounter use. The test cannot be read visually and must be used with the GenPrime DOA Reader. The Snap-Top Split Key Cup qualitatively detects drug classes in human urine at the cutoff concentrations shown below:
| Test | Calibrated to | Cutoff |
|---|---|---|
| Amphetamines | d-Amphetamine | 500 ng/mL |
| Barbiturates | Secobarbital | 300 ng/mL |
| Benzodiazepines | Oxazepam | 300 ng/mL |
| Cocaine | Benzoylecgonine | 150 ng/mL |
| Methamphetamine | d-Methamphetamine | 500 ng/mL |
| Methadone | Methadone | 300 ng/mL |
| Morphine | Morphine | 300 ng/mL |
| Morphine 2000 | Morphine | 2000 ng/mL |
| Oxycodone | Oxycodone | 100 ng/mL |
| Phencyclidine | Phencyclidine | 25 ng/mL |
| Marijuana | Delta-9-THC-COOH | 50 ng/mL |
Configurations of the Snap-Top Split Key Cup may consist of any combination of the above listed drug analytes.
The Snap-Top Split Key Cup provides only a preliminary analytical result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography / mass spectrometry (GC/MS), high performance liguid chromatography (HPLC) or liquid chromatography/tandem mass spectrometry (LC/MS/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are obtained.
Special conditions for use statement(s):
The device is for in vitro diagnostic prescription use.
The GenPrime DOA Reader System test devices cannot be read visually.
The GenPrime DOA Reader System only provides a preliminary analytical result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS), high performance liquid chromatography (HPLC) or liquid chromatography/tandem mass spectrometry (LC/MS/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are obtained.
The test is not intended for over-the-counter use.
{6}------------------------------------------------
Special instrument requirements:
- The GenPrime DOA Reader is required.
- · The GenPrime DOA Reader Software must be loaded onto a PC, laptop computer or Windows compatible device meeting the following minimum requirements:
GenPrime DOA Reader Software System Requirements
Operating System
- MS Windows® XP with Service Pack 3, MS Windows® Vista, MS Windows® 7 or MS ● Windows® 8
Hardware
- Minimum Processor: Intel® Pentium® 4 1.5 GHz or equivalent ●
- . Minimum RAM: 1 GB
- Free hard disc space: minimum of 50 MB at Installation, needs additional disc space while operating; an additional 850 MB necessary for installation of MS .NET Framework 4.0
- . Mouse for optimal interaction with user interface (e.g. IntelliMouse / Microsoft®)
- Standard keyboard with cursor kevs. Num-Pad and Insert-. Delete-. Page up/down keys. . Recommended with cable.
- Minimum: 1 USB 2.0-compatible port .
External Software
- PDF-Compatible viewing application, i.e. Adobe Reader ●
8. DISCUSSION OF TECHNOLOGICAL CHARACTERISTICS:
Similarities and differences to predicate device
Both the candidate and the predicate test systems are used to detect the presence of drugs of abuse and their metabolites in human urine. In both systems, a urine sample is added to the test device and allowed to react for a specified period of time, after which an instrument is used to read the test device and interpret and display the test result. Both the candidate and predicate test device are rapid single use disposable devices that use immunochromatographic lateral flow technology. Both the candidate and predicate test utilize gold-conjugated reagents to generate reddish-purple test and control lines, which are read by the instrument. Both devices are competitive assays where concentration of drug is inversely related to the signal detected by the instrument. The candidate device measures line intensities using image analysis algorithms and then performs the analysis and outputs the results via a Windows compatible computer. The predicate device uses a CIS (contact imaging sensor) to measure line intensity and performs the analysis and outputs results using an embedded operating system and display. The candidate device requires that the operator manually time test development (5 minutes) and then operate the instrument, while the predicate instrument internally times test strip development (10 minutes) and then scans the test cassette.
Overall performance and characteristics of the Snap-Top SK Cup GenPrime DOA Reader System and the predicate device, the MEDTOXScan® are summarized in Table 1 below:
{7}------------------------------------------------
| Similarities | ||
|---|---|---|
| Item | Device | Predicate |
| Intended Use | Determines qualitative positive or negative resultfrom drugs of abuse immunoassay screens usingan instrument reader. | Same |
| Single-UseTest Device | Produces colored lines on device. | Same |
| Assay Type | Competitive assay where concentration of drug isinversely related to the visible signal detected bythe instrument. | Same |
| SystemProcedure | Sample is added to a single use test device, whichis then read by instrument. Instrument is designedto read multiple single use test devices, one at atime. | Same |
| MeasurementMethod | Scans the single-use test device to detect a signal. | Same |
| Differences | ||
| Item | Device | Predicate |
| Test DeviceFormat | Reads multiple formats of single-use test devicesin different cup formats. | Reads a single-use testcassette. |
| Test Time andTimingMethod | Operator manually times test development for 5minutes and then operates the instrument. | Instrument internally times teststrip development for 10 minutesand then scans the test cassette. |
| DetectionMethod | Measures density of visible lines againstbackground on single-use test device. | Measures reflectance of visiblelines on single use test cassette. |
| Output | Outputs "presumptive positive", "negative", and"invalid" test results on a graphic user interfacedisplayed on a computer screen and automaticallystores results along with test information. Operatorhas ability to print and/or export results. | Outputs "positive,” “negative,”and “invalid” test results onpaper printout or LCD screen;stores and uploads results. |
| Cutoff values | BAR cutoff is 300ngBZO cutoff is 300ngMTD cutoff is 300ngMOP cutoff is 300ng | BAR cutoff is 200ngBZO cutoff is 150ngMTD cutoff is 200ngMOP cutoff is 100ng |
| PowerRequirements | AC power only | AC or battery power |
| AdditionalRequirements | Windows®-based computer and cable accessories | None. |
Table 1. Similarities and Differences between the GenPrime DOA Reader System and predicate system.
The manufacturer believes that the technological characteristics of the Snap-Top SK Cup are substantially similar to those of the predicate device.
DISCUSSION OF NON-CLINICAL TESTS PERFORMED FOR DETERMINATION OF 9. SUBSTANTIAL EQUIVALENCE:
Laboratory performance studies were conducted to determine the substantial equivalence of the Snap-Top SK Cup to the predicate system. Testing was only conducted for BAR, BZO and COC since the other analytes of the device have been previously cleared under K130082. These studies are as follows:
Sensitivity/Precision/Distribution of Random Error
The precision studies were performed in the hands of the intended users at three sites representative of laboratory, workplace, and POC settings. The studies were performed with an intended use operator at each site. The operators performed the tests following the instructions for use, which are included with the GenPrime DOA Reader.
Precision studies were performed with the target analytes at 0%, 25%, 50%, 75%, 125%, 150%, 175%, and 200% of the cutoff. Urine test solutions were created with human urine
{8}------------------------------------------------
GC/MS and/or LC/MS/MS were performed to confirm the and calibrator drugs. concentration of calibrator drug in each test solution. The identity of the samples was masked from the operator, and they were tested in random order. Each urine specimen was labeled with a unique alpha-numeric sample ID prior to delivery to the POC sites.
Performance of the Snap-Top SK Cup was evaluated for each drug analyte by testing each drug at the stated concentration using a minimum of 10 tests per operator. Each of the operators used a different GenPrime DOA Reader. Results for this study are summarized in Table 2 below:
| BAR (300 ng/mL) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| % of Cutoff | ng/mL | N | # NEG | # POS | Precision | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| NEG | 0 | 45 | 45 | 0 | 100% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 25% | 75 | 45 | 45 | 0 | 100% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 50% | 150 | 46 | 46 | 0 | 100% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 75% | 225 | 45 | 39 | 6 | 86.7% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 125% | 375 | 45 | 0 | 45 | 100% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 150% | 450 | 45 | 0 | 45 | 100% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 175% | 525 | 45 | 0 | 45 | 100% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 200% | 600 | 46 | 0 | 46 | 100% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BZO (300 ng/mL) | % of Cutoff | ng/mL | N | # NEG | # POS | Precision | NEG | 0 | 45 | 45 | 0 | 100% | 25% | 75 | 50 | 50 | 0 | 100% | 50% | 150 | 50 | 48 | 2 | 96.0% | 75% | 225 | 50 | 29 | 21 | 58.0% | 125% | 375 | 50 | 2 | 48 | 96.0% | 150% | 450 | 49 | 0 | 49 | 100% | 175% | 525 | 49 | 0 | 49 | 100% | 200% | 600 | 49 | 0 | 49 | 100% | COC (150 ng/mL) | % of Cutoff | ng/mL | N | # NEG | # POS | Precision | NEG | 0 | 45 | 45 | 0 | 100% | 25% | 37.5 | 45 | 45 | 0 | 100% | 50% | 75 | 46 | 46 | 0 | 100% | 75% | 112.5 | 45 | 28 | 17 | 62.2% | 125% | 187.5 | 45 | 1 | 44 | 97.8% | 150% | 225 | 46 | 0 | 46 | 100% | 175% | 262.5 | 46 | 0 | 46 | 100% | 200% | 300 | 47 | 0 | 47 | 100% | ||||||||||
| BZO (300 ng/mL) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| % of Cutoff | ng/mL | N | # NEG | # POS | Precision | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| NEG | 0 | 45 | 45 | 0 | 100% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 25% | 75 | 50 | 50 | 0 | 100% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 50% | 150 | 50 | 48 | 2 | 96.0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 75% | 225 | 50 | 29 | 21 | 58.0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 125% | 375 | 50 | 2 | 48 | 96.0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 150% | 450 | 49 | 0 | 49 | 100% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 175% | 525 | 49 | 0 | 49 | 100% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 200% | 600 | 49 | 0 | 49 | 100% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COC (150 ng/mL) | % of Cutoff | ng/mL | N | # NEG | # POS | Precision | NEG | 0 | 45 | 45 | 0 | 100% | 25% | 37.5 | 45 | 45 | 0 | 100% | 50% | 75 | 46 | 46 | 0 | 100% | 75% | 112.5 | 45 | 28 | 17 | 62.2% | 125% | 187.5 | 45 | 1 | 44 | 97.8% | 150% | 225 | 46 | 0 | 46 | 100% | 175% | 262.5 | 46 | 0 | 46 | 100% | 200% | 300 | 47 | 0 | 47 | 100% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| COC (150 ng/mL) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| % of Cutoff | ng/mL | N | # NEG | # POS | Precision | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| NEG | 0 | 45 | 45 | 0 | 100% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 25% | 37.5 | 45 | 45 | 0 | 100% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 50% | 75 | 46 | 46 | 0 | 100% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 75% | 112.5 | 45 | 28 | 17 | 62.2% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 125% | 187.5 | 45 | 1 | 44 | 97.8% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 150% | 225 | 46 | 0 | 46 | 100% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 175% | 262.5 | 46 | 0 | 46 | 100% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 200% | 300 | 47 | 0 | 47 | 100% |
Table 2. Sensitivity/Precision/Distribution of Random Error
Table 2. Sensitivity/Precision/Distribution of Random Error, continued
| All Drugs (95% CI) | ||||
|---|---|---|---|---|
| % of Cutoff | N | # NEG | # POS | Precision |
| NEG | 135 | 135 | 0 | 100% (97.2-100) |
| 25% | 140 | 140 | 0 | 100% (97.3-100) |
| 50% | 142 | 140 | 2 | 98.6% (95.0-99.6) |
| 75% | 140 | 96 | 44 | 68.6% (60.5-75.7) |
| 125% | 140 | 3 | 137 | 97.9% (93.9-99.3) |
| 150% | 140 | 0 | 140 | 100% (97.3-100) |
| 175% | 140 | 0 | 140 | 100% (97.3-100) |
| 200% | 142 | 0 | 142 | 100% (97.4-100) |
{9}------------------------------------------------
Related Compounds and Cross Reactants
Analytical specificity studies were performed to determine whether drugs and drug metabolites within the same class of drugs or with similar molecular structures cross-react in the test system. Results are expressed as the minimum concentration required to produce a positive result in the indicated assay.
Reference standards for the various metabolites and compounds were prepared at 100 ug/mL in pooled negative human urine samples. Compounds that tested positive were serially diluted until a negative result was observed. Results shown are expressed as the minimum concentration producing a positive result in the indicated assay. A list of these compounds and their level of cross reactivity is shown in Table 3 below.
| Related Compound or Cross-Reactant | Result | % CrossReactive |
|---|---|---|
| Barbiturate (BAR) (Secobarbital) (300 ng/mL) | ||
| Butabarbital | Positive at 75 ng/mL | 400% |
| Aprobarbital | Positive at 200 ng/mL | 150% |
| Barbital | Positive at 250 ng/mL | 120% |
| Butethal | Positive at 250 ng/mL | 120% |
| Phenobarbital | Positive at 250 ng/mL | 120% |
| Pentobarbital | Positive at 300 ng/mL | 100% |
| Alphenal | Positive at 600 ng/mL | 50% |
| Cyclopentobarbital | Positive at 600 ng/mL | 50% |
| Amobarbital | Positive at 850 ng/mL | 35% |
| Allobarbital | Positive at 1000 ng/mL | 30% |
| Butalbital | Positive at 5000 ng/mL | 6% |
| Mephobarbital | Positive at 50000 ng/mL | 1% |
| Barbituric Acid | Negative at 100000 ng/mL | N/A |
| Glutethimide | Negative at 100000 ng/mL | N/A |
| Hexobarbital | Negative at 100000 ng/mL | N/A |
| Phenytoin (diphenylhydantoin) | Negative at 100000 ng/mL | N/A |
| Thiopental | Negative at 100000 ng/mL | N/A |
| Benzodiazepine (BZO) (Oxazepam) 300 ng/mL | ||
| Temazepam glucuronide | Positive at 50 ng/mL | 600% |
| Clobazam | Positive at 98 ng/mL | 306% |
| N-Desmethylflunitrazepam | Positive at 100 ng/mL | 300% |
| Nitrazepam | Positive at 100 ng/mL | 300% |
| Oxazepam glucuronide | Positive at 100 ng/mL | 300% |
| Temazepam | Positive at 125 ng/mL | 240% |
| RS-Lorazepam glucuronide | Positive at 150 ng/mL | 200% |
| Diazepam | Positive at 195 ng/mL | 154% |
| Flunitrazepam | Positive at 195 ng/mL | 154% |
| Clorazepate | Positive at 200 ng/mL | 150% |
| Alprazolam | Positive at 250 ng/mL | 120% |
| Desalkylflurazepam | Positive at 390 ng/mL | 77% |
| Nordiazepam | Positive at 390 ng/mL | 77% |
| Clonazepam | Positive at 400 ng/mL | 75% |
| Bromazepam | Positive at 1000 ng/mL | 30% |
| Estazolam | Positive at 1250 ng/mL | 24% |
| Alprazolam-OH (α-Hydroxyalprazolam) | Positive at 1262 ng/mL | 24% |
| Lorazepam (d,l) | Positive at 1500 ng/mL | 20% |
| Triazolam | Positive at 2500 ng/mL | 12% |
| Chlordiazepoxide | Positive at 3125 ng/mL | 10% |
| Norchlordiazepoxide (N-Desmethylchlordiazepoxide) | Positive at 6250 ng/mL | 5% |
| Midazolam | Positive at 12500 ng/mL | 2% |
| Triazolam, 1-hydroxy | Positive at 50000 ng/mL | N/A |
| Related Compound or Cross-Reactant | Result | % CrossReactive |
| Sertraline | Negative at 100000 ng/mL | N/A |
| 7-Aminoclonazepam | Negative at 100000 ng/mL | N/A |
| 7-Aminoflunitrazepam | Negative at 100000 ng/mL | N/A |
| Flurazepam | Negative at 100000 ng/mL | N/A |
| Cocaine (COC) (Benzoylecgonine) 150 ng/mL | ||
| Cocaine | Positive at 2000 ng/mL | 8% |
| Cocaethylene | Positive at 9325 ng/mL | 2% |
| Ecgonine | Positive at 30000 ng/mL | 1% |
| Ecgonine Methyl Ester | Negative at 100000 ng/mL | N/A |
Table 3. Snap-Top Split Key Cup Related Compounds and Cross-Reactants
{10}------------------------------------------------
Interference Data
Endogenous Compounds
The Snap-Top Split Key Cup was tested for interference with 15 endogenous compounds. The compounds were dissolved in appropriate solvents at a concentration of at least 1.0 mg/mL. Each compound was further diluted to 100 ug/mL in contrived specimens containing 50% of each assay cut-off and 150% of each assay cut-off. None of the compounds listed below showed interference at 100 µg/mL.
- 1-Thvroxine (d) Creatinine Epinephrine Acetaldehyde Acetone Albumin, Human Bilirubin Cholesterol
Glucose, Standard Hemoglobin, Human Sodium Chloride Uric Acid B-Estradiol Estriol Tetrahydrocortisone-3-acetate
pH and Specific Gravity
The Snap-Top SK Cup was assayed with pH values of 3.0, 4.0, 7.0 and 9.0 ± 0.1. Each sample was assayed in triplicate. The pH samples were fortified with drug concentrations at 50% (negative) and 150% (positive) of cutoff. All four pH samples gave negative results in the 50% of cutoff level for each drug, and all gave positive results at the 150% of cutoff level for each drug.
The Snap-Top SK Cup was assayed in triplicate with specific gravity values of 1.003, 1.015 and 1.030 ± 0.001. The specific gravity samples were fortified with drug concentrations as described above for pH to give strong negative and strong positive results. All three specific gravity samples gave negative results when fortified to the maximum strong negative level for each drug, and all gave positive results when fortified to the minimum strong positive level for each drug.
{11}------------------------------------------------
Prescription Drugs
A study was conducted to determine the cross-reactivity of the device with compounds spiked into either weak-positive or weak-negative urine containing Barbiturates, Benzodiazepines, and Cocaine. The following compounds demonstrated no cross-reactivity when tested with the Snap Top Split Key Cup at a concentration of 25 µg/mL (unless otherwise noted).
| N-Acetylprocainamide | Fenoprofen | Niacinamide | Sulfamethazine |
|---|---|---|---|
| Amoxicillin | Furosemide | Nifedipine | Sulindac |
| Ampicillin | Hydralazine | Noscapine | Tetracycline |
| I-Ascorbic Acid | Hydrochlorothiazide | Oxolinic acid | Tetrahydrocortisone 3-acetate |
| Atropine | Hydrocortisone | Oxymetazoline | Tetrahydrozoline |
| Chlorothiazide* | o-Hydroxyhippuric acid | Papaverine | Thiamine |
| Chlorpromazine | Ketamine | Penicillin-G | Thioridazine |
| Clonidine | Ketoprofen | Perphenazine | Tolbutamide |
| I-Cotinine | Labetalol | Phenelzine | Triamterene |
| Cortisone | Loperamide | Prednisone | Trifluoperazine |
| Diclofenac | Meprobamate | d,I-Propranolol | Trimethoprim |
| Diflunisal | Methoxyphenamine | Quinine | d,I-Tryptophan |
| Digoxin | Methylphenidate | Quinidine | Verapamil |
| Diphenhydramine | Nalidixic acid | Serotonin | Zomepirac |
| Erythromycin |
Table 4. Prescription Drugs
*tested at 12.5 µg/mL
Common Drugs
Drug free urine samples were spiked with drug concentrations that were at 50% (negative) and 150% (positive) of cutoff. Concentrations of 100,000 ng/mL of the common drugs were then added to the preparation and assayed by the GenPrime DOA Reader System. If a common compound name is followed by the drug abbreviation (e.q., "BAR"), then it has expected reactivity in the specified drug test (see Related Compounds and Cross Reactants) and was not assayed for interference in that drug test. Samples were evaluated in triplicate by in-house operators. None of the common drugs affected the expected results for the Split Key Cup (Table 4):
| Acetylsalicylic Acid | Chlorpheniramine | Morphine |
|---|---|---|
| Acetaminophen | Cocaine - COC | Phenobarbital – BAR |
| Brompheniramine maleate | Dextromethorphan | Phenytoin (Diphenylhydantoin)-BAR |
| Caffeine | Doxylamine | d-Pseudoephedrine |
| Carbamazepine | Ibuprofen | Salicylic Acid |
Table 5. Common Drugs Evaluated with the GenPrime DOA Reader System Split Key Cup
Discussion of Clinical Tests Performed for Determination of Substantial Equivalence
The accuracy of the Snap-Top SK Cup was evaluated at three sites representative of laboratory, workplace, and POC settings with blind coded clinical urine samples that contained varying concentrations of drugs as determined by GC/MS or LC/MS/MS. For each drug, a minimum of 40 unaltered positive and 40 unaltered negative clinical samples were assessed. Negative samples were screened negative by EIA, 10% of which were also confirmed by GC/MS or LC/MS/MS. Results were stratified to give values of 0%, 0-50%, 50-100%, 100-150% and >150% of cutoff. Results summaries are provided below in Table 5, for all sites combined. Discordant results and the drug levels detected by GC/MS or LC/MS/MS are provided in Table 6 below.
{12}------------------------------------------------
| Table 5. Summary of method comparison data for the Split Key Cup (all sites combined) | |||||||
|---|---|---|---|---|---|---|---|
| DRUG(cutoff) | GenPrimeTestSystemSK Cup | NoDrug | Relative to Cutoff | AgreementwithReference | |||
| Negative(<50%) | Near CutoffNegative(50-100%) | Near CutoffPositive(100-150%) | Positive(>150%) | ||||
| BAR(300) | Positive | 0 | 0 | 2 | 4 | 36 | 100% |
| BAR(300) | Negative | 42 | 3 | 3 | 0 | 0 | 96.0% |
| BZO(300) | Positive | 0 | 0 | 2 | 4 | 36 | 100% |
| BZO(300) | Negative | 36 | 2 | 2 | 0 | 0 | 95.2% |
| COC(150) | Positive | 0 | 0 | 0 | 4 | 36 | 100% |
| COC(150) | Negative | 36 | 0 | 4 | 0 | 0 | 100% |
| AllDrugs | Positive(95% CI) | 0 | 0 | 4 | 12 | 108 | 100%(96.9-100) |
| Negative(95% CI) | 114 | 5 | 9 | 0 | 0 | 97.0%(92.5-98.8) |
Summary of method comparison data for the Split Kev Cun (all sites combined) Tohlo
Table 6. Discordant Results for the Split Key Cup
| CutoffValue(ng/mL) | Drug | GenPrime DOAReader System | GC/MS or LC/MS/MS Value |
|---|---|---|---|
| 300 | BAR | Presumptive Positive | Phenobarbital at 160 ng/mL (=192 ng/mL BAR equiv) |
| 300 | BAR | Presumptive Positive | Butalbital at 4788 ng/mL (=287 ng/mL BAR equiv) |
| 300 | BZO | Presumptive Positive | Oxazepam at 271 ng/mL |
| Presumptive Positive | Oxazepam at 235 ng/mL |
10. CONCLUSION
The Snap-Top SK Cup has the same intended use, similar technological characteristics and equivalent precision, interference, cross-reactivity and clinical accuracy as the predicate device. The data demonstrate that the addition of three new drugs to the test menu do not raise any new issues of safety or effectiveness. GenPrime believes that the Snap-Top SK Cup is substantially equivalent to the predicate device.
§ 862.3150 Barbiturate test system.
(a)
Identification. A barbiturate test system is a device intended to measure barbiturates, a class of hypnotic and sedative drugs, in serum, urine, and gastric contents. Measurements obtained by this device are used in the diagnosis and treatment of barbiturate use or overdose and in monitoring levels of barbiturate to ensure appropriate therapy.(b)
Classification. Class II (special controls). A barbiturate 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).