(46 days)
BIOEASY Multi-Drug Test Cup Tests are competitive binding, lateral flow immunochromatographic assays for qualitative and simultaneous detection of Amphetamine, Oxazepam, Marijuana, Methamphetamine, Morphine, Oxycodone, Secobarbital, Buprenorphine, Methylenedioxy-methamphetamine, Phencyclidine, Methadone, Nortriptyline and d-Propoxyphene in human urine at the cutoff concentrations of:
| Drug(Identifier) | Cut-off level |
|---|---|
| Amphetamine | 1000 ng/mL |
| Oxazepam | 300 ng/mL |
| Cocaine | 300 ng/mL |
| Marijuana | 50 ng/mL |
| Methamphetamine | 1000 ng/mL |
| Morphine | 300 ng/mL or 2000 ng/mL |
| Oxycodone | 100 ng/mL |
| Secobarbital | 300 ng/mL |
| Buprenorphine | 10 ng/mL |
| Methylenedioxy-methamphetamine | 500 ng/mL |
| Phencyclidine | 25 ng/mL |
| Methadone | 300 ng/mL |
| Nortriptyline | 1000 ng/mL |
| d-Propoxyphene | 300 ng/mL |
Configuration of the BIOEASY Multi-Drug Test Cup tests can consist of any combination of the above listed drug analytes.
The test may yield positive results for the prescription drugs Buprenorphine, Nortriptyline, Oxazepam, Secobarbital, Propoxyphene and Oxycodone when taken at or above prescribed doses. It is not intended to distinguish between prescription use or abuse of these drugs. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. The test provides only preliminary test results. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method.
For in vitro diagnostic use only.
The BIOEASY Multi-Drug Test Cup tests are immunochromatographic assays that use a lateral flow system for the qualitative detection of Amphetamine, Oxazepam, Cocaine, Marijuana, Methamphetamine, Morphine, Oxycodone, Secobarbital, Buprenorphine, Methylenedioxymethamphetamine, Phencyclidine, Methadone, Nortriptyline and Propoxyphene (target analytes) in human urine. The products are single-use in vitro diagnostic devices. Each test kit contains a Test Device, a package insert and a urine cup for sample collection. Each test device is sealed with a desiccant in an aluminum pouch
The provided document describes the performance of the BIOEASY Multi-Drug Test Cup, an in-vitro diagnostic device for qualitative and simultaneous detection of various drugs in human urine. Here's a breakdown of the acceptance criteria and study details:
1. A table of acceptance criteria and the reported device performance
The document doesn't explicitly state "acceptance criteria" in a separate table. However, the performance is demonstrated through precision studies and lay-user studies, showing the device's ability to correctly identify drug presence/absence at specific concentrations relative to the defined cutoff levels. The implicit acceptance criteria appear to be high percentages of correct results, particularly at and beyond the +/- 25% cutoff concentrations. For the lay user study, 90-100% correct results were generally achieved across different drug panels and concentrations close to the cutoff, with 100% correct results for samples far from the cutoff.
Here's an aggregated summary of the performance for each drug panel from the lay user study, which serves as a key indicator of device performance in the hands of intended users:
| Drug Panel (Cut-off) | % Correct Results (-100% Cutoff) | % Correct Results (-75% Cutoff) | % Correct Results (-50% Cutoff) | % Correct Results (-25% Cutoff) | % Correct Results (+25% Cutoff) | % Correct Results (+50% Cutoff) | % Correct Results (+75% Cutoff) |
|---|---|---|---|---|---|---|---|
| Amphetamine (1000 ng/mL) | 100% | 100% | 100% | 95% | 100% | 100% | 100% |
| Secobarbital (300 ng/mL) | 100% | 100% | 100% | 95% | 95% | 100% | 100% |
| Cocaine (300 ng/mL) | 100% | 100% | 100% | 95% | 95% | 100% | 100% |
| Buprenorphine (10 ng/mL) | 100% | 100% | 100% | 95% | 90% | 100% | 100% |
| Methamphetamine (1000 ng/mL) | 100% | 100% | 100% | 95% | 95% | 100% | 100% |
| Methadone (300 ng/mL) | 100% | 100% | 100% | 95% | 95% | 100% | 100% |
| Morphine (2000 ng/mL) | 100% | 100% | 100% | 100% | 95% | 100% | 100% |
| Oxycodone (100 ng/mL) | 100% | 100% | 100% | 95% | 95% | 100% | 100% |
| Phencyclidine (25 ng/mL) | 100% | 100% | 100% | 95% | 100% | 100% | 100% |
| Marijuana (50 ng/mL) | 100% | 100% | 100% | 90% | 95% | 100% | 100% |
| Oxazepam (300 ng/mL) | 100% | 100% | 100% | 95% | 95% | 100% | 100% |
| MDMA (500 ng/mL) | 100% | 100% | 100% | 95% | 95% | 100% | 100% |
| Nortriptyline (1000 ng/mL) | 100% | 100% | 100% | 95% | 95% | 100% | 100% |
| Propoxyphene (300 ng/mL) | 100% | 100% | 100% | 95% | 95% | 100% | 100% |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Precision Studies: For each drug concentration point tested (-100% cut off, -75% cut off, -50% cut off, -25% cut off, +25% cut off, +50% cut off, +75% cut off, and +100% cut off), tests were performed for 25 days per device, with two runs per day for each drug. This means 50 runs per concentration for each drug across three lots (total of 150 runs per concentration per drug across lots). The samples were prepared in-house by spiking drugs into negative samples. The data provenance is implied to be from the manufacturer's lab, likely Shenzhen, China, where the submitter is located. This appears to be a prospective internal study.
- Method Comparison Studies: 80 (40 negative and 40 positive) unaltered clinical samples for each drug were used. The samples were blind labeled. These appear to be retrospective clinical samples, but the country of origin is not specified.
- Lay-user Study: 300 lay persons participated. Urine samples were prepared at varying concentrations: negative, +/-75%, +/-50%, +/-25% of the cutoff. Each participant received one blind-labeled sample and one device. The number of samples tested at each concentration varied per drug, as shown in the tables (e.g., 20 samples for -100% cutoff, 160 for -50% cutoff, 40 for +50% cutoff). These were likely prepared in-house or externally for the study, making it a prospective study, though the country of origin for the lay users is not specified (but likely related to the submitter's regions of operation or intended market).
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
- Precision and Lay-user Studies: The "ground truth" for the urine samples in these studies was established by LC/MS (Liquid Chromatography/Mass Spectrometry) or LC/MS/MS, which is a gold standard analytical method for drug concentration determination. The number or qualifications of the individuals performing the LC/MS analysis are not specified, but it's presumed to be trained laboratory personnel.
- Method Comparison Studies: The ground truth for the 80 clinical samples was also established by LC/MS. The number or qualifications of the individuals performing the LC/MS analysis are not specified.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
- Precision Studies: The document doesn't explicitly state an adjudication method. "All sample aliquots were blindly labeled by the person who prepared the samples and didn't take part in the sample testing." The results presented are counts of "positive" and "negative" outcomes.
- Method Comparison Studies: The studies were performed in-house with three laboratory assistants for each device. The results are summarized by "Viewer A," "Viewer B," and "Viewer C." This indicates a multi-reader approach. However, there's no mention of an adjudication process (e.g., 2+1, 3+1) if their readings disagreed. The discordant results table lists individual discrepancies.
- Lay-user Study: Each participant tested one device and recorded their results. The assessment of whether their result was "correct" was based on the LC/MS confirmed concentration of the sample they received. No adjudication among lay users is mentioned or appropriate for this type of study.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
No, a multi-reader multi-case (MRMC) comparative effectiveness study focusing on human readers improving with AI vs. without AI assistance was not done. This device is a lateral flow immunoassay, a point-of-care test that human users (including lay users) interpret visually. It is not an AI-assisted diagnostic device.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
No, a standalone algorithm-only performance study was not done, as this device does not incorporate an AI algorithm. Its performance is based on the chemical reaction and visual interpretation.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The ground truth used for validating the device's performance was primarily analytical confirmation by LC/MS or LC/MS/MS. This is considered a highly accurate and quantitative laboratory diagnostic method for determining drug concentrations.
8. The sample size for the training set
The document does not describe a "training set" in the context of an AI/ML algorithm. This device is a lateral flow immunoassay and does not employ machine learning or AI that would require a separate training dataset. The studies described are for analytical and clinical validation of the immunoassay.
9. How the ground truth for the training set was established
As there is no AI/ML component mentioned and thus no "training set," this question is not applicable to the information provided.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. Underneath the square are the words "U.S. FOOD & DRUG ADMINISTRATION" in blue.
January 31, 2020
Shenzhen Bioeasy Biotechnology Co., Ltd. % Joe Shia Director LSI 504E Diamond Ave., Suite I Gaithersburg, MD 20877
Re: K193480
Trade/Device Name: BIOEASY Multi-Drug Test Cup Regulation Number: 21 CFR 862.3650 Regulation Name: Opiate test system Regulatory Class: Class II Product Code: NGL, NGI, NFW, NFY, NGG, NFT, NFV, PTH, NGM, PTG, QAW, QBF Dated: December 11, 2019 Received: December 16, 2019
Dear Joe Shia:
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
{1}------------------------------------------------
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 803) 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 medical devices and radiation-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
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Indications for Use
510(k) Number (if known) K193480
Device Name BIOEASY Multi-Drug Test Cup
Indications for Use (Describe)
BIOEASY Multi-Drug Test Cup Tests are competitive binding, lateral flow immunochromatographic assays for qualitative and simultaneous detection of Amphetamine, Oxazepam, Marijuana, Methamphetamine, Morphine, Oxycodone, Secobarbital, Buprenorphine, Methylenedioxy-methamphetamine, Phencyclidine, Methadone, Nortriptyline and d-Propoxyphene in human urine at the cutoff concentrations of:
| Drug(Identifier) | Cut-off level |
|---|---|
| Amphetamine | 1000 ng/mL |
| Oxazepam | 300 ng/mL |
| Cocaine | 300 ng/mL |
| Marijuana | 50 ng/mL |
| Methamphetamine | 1000 ng/mL |
| Morphine | 300 ng/mL or 2000 ng/mL |
| Oxycodone | 100 ng/mL |
| Secobarbital | 300 ng/mL |
| Buprenorphine | 10 ng/mL |
| Methylenedioxy-methamphetamine | 500 ng/mL |
| Phencyclidine | 25 ng/mL |
| Methadone | 300 ng/mL |
| Nortriptyline | 1000 ng/mL |
| d-Propoxyphene | 300 ng/mL |
Configuration of the BIOEASY Multi-Drug Test Cup tests can consist of any combination of the above listed drug analytes.
The test may yield positive results for the prescription drugs Buprenorphine, Nortriptyline, Oxazepam, Secobarbital, Propoxyphene and Oxycodone when taken at or above prescribed doses. It is not intended to distinguish between prescription use or abuse of these drugs. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. The test provides only preliminary test results. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method.
For in vitro diagnostic use only.
Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)
X Over-The-Counter Use (21 CFR 801 Subpart C)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
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K193480 510(k) SUMMARY
- January 27, 2020 1. Date: Shenzhen Bioeasy Biotechnology Co., Ltd. 2. Submitter: No.2-1, Liuxian 1st Road Baoan District Shenzhen, China 518101
- Joe Shia 3. Contact person: LSI International Inc. 504 East Diamond Ave. Gaithersburg, MD 20877 Telephone: 240-505-7880 Email: shiajl@yahoo.com
-
- Device Name: BIOEASY Multi-Drug Test Cup
| Classification: | Class 2 | ||
|---|---|---|---|
| Product Code | Classification | Regulation Section | Panel |
| NFTAmphetamine | II | 21 CFR § 862.3100, AmphetamineTest System | Toxicology (91) |
| NFWCannabinoids | II | 21 CFR § 862.3870, CannabinoidsTest System | Toxicology (91) |
| NFYCocaine | II | 21 CFR § 862.3250, Cocaine andCocaine Metabolites Test System | Toxicology (91) |
| NGGMethamphetamine | II | 21 CFR § 862.3610,Methamphetamine Test System | Toxicology (91) |
| NGIMorphine | II | 21 CFR § 862.3640, MorphineTest System | Toxicology (91) |
| NFVOxazepam | II | 21 CFR § 862.3170,Benzodiazepine Test System | Toxicology (91) |
| NGLOxycodone | II | 21 CFR § 862.3650, Opiate TestSystem | Toxicology (91) |
| PTHSecobarbital | II | 21 CFR § 862.3150, BarbiturateTest System | Toxicology (91) |
| NGLBuprenorphine | II | 21 CFR § 862.3650,Opiate Test System | Toxicology (91) |
| NGGMethylenedioxy-methamphetamine | II | 21 CFR § 862.3610,Methamphetamine Test System | Toxicology (91) |
| NGMPhencyclidine | unclassified | Enzyme ImmunoassayPhencyclidine | Toxicology (91) |
| PTGMethadone | II | 21 CFR § 862.3620, MethadoneTest System | Toxicology (91) |
| QAWNortriptyline | II | 21 CFR, 862.3910 TricyclicAntidepressant Drugs Test System | Toxicology (91) |
| QBFPropoxyphene | II | 21 CFR, 862.3700 PropoxypheneTest System | Toxicology (91) |
-
- Predicate Devices: K182530
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The Shenzhen Bioeasy Biotechnology's BIOEASY Multi-Drug Test Cup
-
- Indications for Use
BIOEASY Multi-Drug Test Cup Tests are competitive binding, lateral flow immunochromatographic assays for qualitative and simultaneous detection of Amphetamine, Oxazepam, Cocaine, Marijuana, Methamphetamine, Morphine, Oxycodone, Secobarbital, Buprenorphine, Methylenedioxy-methamphetamine, Phencyclidine, Methadone, Nortriptyline and d-Propoxyphene in human urine at the cutoff concentrations of:
- Indications for Use
| Drug (Identifier) | Cut-off level |
|---|---|
| Amphetamine | 1000 ng/mL |
| Oxazepam | 300 ng/mL |
| Cocaine | 300 ng/mL |
| Marijuana | 50 ng/mL |
| Methamphetamine | 1000 ng/mL |
| Morphine | 300 ng/mL or 2000 ng/mL |
| Oxycodone | 100 ng/mL |
| Secobarbital | 300 ng/mL |
| Buprenorphine | 10 ng/mL |
| Methylenedioxy-methamphetamine | 500 ng/mL |
| Phencyclidine | 25 ng/mL |
| Methadone | 300 ng/mL |
| Nortriptyline | 1000 ng/mL |
| d-Propoxyphene | 300 ng/mL |
Configuration of the BIOEASY Multi-Drug Test Cup tests can consist of any combination of the above listed drug analytes.
The test may yield positive results for the prescription drugs Buprenorphine, Nortriptyline, Oxazepam, Secobarbital, Propoxyphene and Oxycodone when taken at or above prescribed doses. It is not intended to distinguish between prescription use or abuse of these drugs. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only.
-
- Device Description
The BIOEASY Multi-Drug Test Cup tests are immunochromatographic assays that use a lateral flow system for the qualitative detection of Amphetamine, Oxazepam, Cocaine, Marijuana, Methamphetamine, Morphine, Oxycodone, Secobarbital, Buprenorphine, Methylenedioxymethamphetamine, Phencyclidine, Methadone, Nortriptyline and Propoxyphene (target analytes) in human urine. The products are single-use in vitro diagnostic devices. Each test kit contains a Test Device, a package insert and a urine cup for sample collection. Each test device is sealed with a desiccant in an aluminum pouch
- Device Description
-
- Substantial Equivalence Information
A summary comparison of features of the BIOEASY Multi-Drug Test Cup tests and the predicate devices is provided in following table.
- Substantial Equivalence Information
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Table 1: Features Comparison of BIOEASY Multi-Drug Test Cup tests and the Predicate Devices
| Item | Device | Predicate - K182530 |
|---|---|---|
| Indication(s)for Use | For the qualitative determination ofdrugs of abuse in human urine. | Same |
| Calibrator and Cut-OffValues | Amphetamine (AMP): 1,000 ng/mlOxazepam (BZO):300 ng/mlCocaine(COC): 300 ng/mlMarijuana (THC):50 ng/mlMethamphetamine (MET): 1,000 ng/mlMorphine (MOP): 300ng/ml or 2000ng/mLOxycodone(OXY) : 100 ng/mlSecobarbital (BAR): 300 ng/mlBuprenorphine (BUP): 10 ng/mlMethylenedioxy-methamphetamine(MDMA): 500 ng/mlPhencyclidine (PCP): 25 ng/mlMethadone (MTD): 300 ng/mlNortriptyline (TCA): 1000 ng/mlPropoxyphene (PPX): 300 ng/ml | Same except formorphine 2000 ng/mL |
| Methodology | Competitive binding, lateral flowimmunochromatographic assays based onthe principle of antigen antibodyimmunochemistry. | Same |
| Type of Test | Qualitative | Same |
| Specimen Type | Human Urine | Same |
| Intended Use | For over-the-counter | Same |
| Configurations | Cup | Same |
9. Test Principle
The BIOEASY Multi-Drug Test Cup tests are rapid tests for the qualitative detection of Amphetamine, Oxazepam, Cocaine, Marijuana, Methamphetamine, Morphine, Oxycodone, Secobarbital, Buprenorphine, Methylenedioxy-methamphetamine, Phencyclidine, Methadone, Nortriptyline and Propoxyphene in urine samples. The tests are lateral flow chromatographic immunoassays. During testing, a urine specimen migrates upward by capillary action. If target drugs present in the urine specimen are below the cut-off concentration, it will not saturate the binding sites of its specific monoclonal mouse antibody coated on the particles. The antibodycoated particles will then be captured by immobilized drug-conjugate and a visible colored line will show up in the test line region. The colored line will not form in the test line region if the target drug level exceeds its cutoff-concentration because it will saturate all the binding sites of the antibody coated on the particles. A band should form in the control region of the devices regardless of the presence of drug or metabolite in the sample to indicate that the tests have been
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performed properly.
10. Performance Characteristics
-
- Analytical Performance
- a. Precision
Precision studies were carried out for samples with concentrations of -100% cut off, -75% cut off, -50% cut off, -25% cut off, +25% cut off, +50% cut off , +75% cut off and +100% cut off. These samples were prepared by spiking drug in negative samples. Each drug concentration was confirmed by LC/MS. All sample aliquots were blindly labeled by the person who prepared the samples and didn't take part in the sample testing. For each concentration, tests were performed two runs per day for 25 days per device in a randomized order. The results obtained are summarized in the following table for Morphine 2000 ng/mL. The data for Amphetamine, Oxazepam, Cocaine, Marijuana, Methamphetamine, Morphine, Oxycodone, Secobarbital, Buprenorphine, Methylenedioxy-methamphetamine, Phencyclidine, Methadone, Nortriptyline and Propoxyphene were reported in K182530.
| Lot Number | -100% cut off | -75% cut off | -50% cut off | -25% cutoff | +25% cut off | +50% cut off | +75% cut off | +100% cut off | |
|---|---|---|---|---|---|---|---|---|---|
| Lot 1 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 26-/24+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot 2 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 29-/21+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot 3 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 24-/26+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
Morphine 2000 ng/mL
c. Stability
The devices are stable at 4-30 ℃ for 24 months based on the real time stability studies at both 4 ℃ and 30 ℃.
- d. Interference
Potential interfering substances found in human urine of physiological or pathological conditions were added to drug-free urine and target drugs urine with concentrations at 25% below and 25% above Cut-Off levels. These urine samples were tested using three batches of the device. Compounds that showed no interference at a concentration of 100ug/mL (albumin was tested at 100 mg/dL, ethanol at 1%) are summarized in the following tables.
| Acetaminophen | ß-Estradiol | Oxalic acid |
|---|---|---|
| Acetophenetidin | Erythromycin | Oxolinic acid |
| N-Acetylprocainamide | Ethanol | Oxymetazoline |
| Acetylsalicylic acid | Fenoprofen | Papaverine |
| Albumin (100 mg/dL) | Furosemide | Penicillin G |
| Aminopyrine | Gentisic acid | Perphenazine |
| Amoxicillin | Hemoglobin | Phenelzine |
| Ampicillin | Hydralazine | Prednisone |
| Apomorphine | Hydrochlorothiazide | (±)-Propranolol |
| Ascorbic acid | Hydrocortisone | Pseudoephedrine |
| Aspartame | O-Hydroxyhippuric acid | Quinine |
| Atropine | 3-Hydroxytyramine | Ranitidine |
| Benzilic acid | Ibuprofen | Salicylic acid |
| Benzoic acid | Isoproterenol | Serotonin (5- Hydroxytyramine) |
| Bilirubin | Isoxsuprine | Sulfamethazine |
| Chloral hydrate | Ketamine | Sulindac |
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| Chloramphenicol | Ketoprofen | Tetrahydrocortisone 3-(β-Dglucuronide) |
|---|---|---|
| Chlorothiazide | Labetalol | Tetrahydrocortisone 3-acetate |
| Chlorpromazine | Loperamide | Tetrahydrozoline |
| Cholesterol | Meperidine | Thiamine |
| Clonidine | Meprobamate | Thioridazine |
| Cortisone | Methoxyphenamine | Triamterene |
| (-)-Cotinine | Nalidixic acid | Trifluoperazine |
| Creatinine | Naloxone | Trimethoprim |
| Deoxycorticosterone | Naltrexone | DL-Tryptophan |
| Dextromethorphan | Naproxen | Tyramine |
| Diclofenac | Niacinamide | DL-Tyrosine |
| Diflunisal | Nifedipine | Uric acid |
| Digoxin | Norethindrone | Verapamil |
| Diphenhydramine | Noscapine | Zomepirac |
| Ecgonine methyl ester | (±)-Octopamine |
e. Specificity
To test specificity, drug metabolites and other components that are likely to interfere in urine samples were tested using three batches of each device. The lowest concentration that caused a positive result for each compound are listed below for Morphine 2000 ng/mL cut-off. The data for Amphetamine, Oxazepam, Cocaine, Marijuana. Methamphetamine. Morphine, Oxycodone, Secobarbital, Buprenorphine, Methylenedioxy-methamphetamine, Phencyclidine, Methadone, Nortriptyline and Propoxyphene were reported in K182530
| Morphine, Cut-off=2000 ng/mL | Result | %Cross-Reactivity |
|---|---|---|
| Morphine | Positive at 2000 ng/mL | 100% |
| Codeine | Positive at 200 ng/mL | 1000% |
| Ethylmorphine | Positive at 2500 ng/mL | 80% |
| Hydrocodone | Negative at 100000 ng/mL | <2% |
| Hydromorphone | Positive at 4000 ng/mL | 50% |
| Levorphanol | Negative at 100000 ng/mL | <2% |
| 6-Acetylmorphine | Positive at 3000 ng/mL | 67% |
| Morphine-3- β -D-glucuronide | Positive at 6000 ng/mL | 33% |
| Normorphine | Negative at 100000 ng/mL | <2% |
| Oxycodone | Negative at 100000 ng/mL | <2% |
| Oxymorphone | Negative at 100000 ng/mL | <2% |
| Procaine | Negative at 100000 ng/mL | <2% |
| Thebaine | Negative at 100000 ng/mL | <2% |
| Heroin | Positive at 3500 ng/mL | 57% |
f. Effect of Urine Specific Gravity and Urine pH
To investigate the effect of urine specific gravity and urine pH, urine samples, with 1.000 to 1.035 specific gravity or urine samples with pH 4 to 9 were spiked with target drugs at 25% below and 25% above Cut-Off levels. These samples were tested using three lots of each device. Results were all positive for samples at and above +25% Cut-Off and all negative for samples at and below -25% Cut-Off. There were no differences observed for different devices.
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2. Comparison Studies
Method comparison studies for the BIOEASY Multi-Drug Test Cup tests were performed inhouse with three laboratory assistants for each device. Operators ran 80 (40 negative and 40 positive) unaltered clinical samples for each drug. The samples were blind labeled and compared to LC/MS results. The results obtained are summarized in the following table for Morphine 2000 ng/mL. The data for Amphetamine, Oxazepam, Cocaine, Marijuana, Methamphetamine, Morphine, Oxycodone, Secobarbital, Buprenorphine, Methylenedioxy-methamphetamine, Phencyclidine, Methadone, Nortriptyline and Propoxyphene were reported in K182530.
Morphine 2000 ng/mL
| Negative | LowNegative byLC/MS(less than-50%) | Near CutoffNegative byLC/MS(Between-50% andcutoff) | Near CutoffPositive byLC/MS(Between thecutoff and+50%) | High Positiveby LC/MS(greater than+50%) | ||
|---|---|---|---|---|---|---|
| Viewer | Positive | 0 | 0 | 2 | 20 | 18 |
| A | Negative | 7 | 15 | 16 | 2 | 0 |
| Viewer | Positive | 0 | 0 | 2 | 21 | 18 |
| B | Negative | 7 | 15 | 16 | 1 | 0 |
| Viewer | Positive | 0 | 0 | 2 | 21 | 18 |
| C | Negative | 7 | 15 | 16 | 1 | 0 |
Discordant Results
| Viewer | Sample Number | LC/MS Result | BIOEASY CupViewer Results |
|---|---|---|---|
| Viewer A | OPIC341 | 1920 | Positive |
| Viewer A | OPIC335 | 1870 | Positive |
| Viewer B | OPIC450 | 1860 | Positive |
| Viewer B | OPIC335 | 1870 | Positive |
| Viewer C | OPIC341 | 1920 | Positive |
| Viewer C | OPIC450 | 1860 | Positive |
| Viewer A | OPIC475 | 2150 | Negative |
| Viewer A | OPIC408 | 2100 | Negative |
| Viewer B | OPIC408 | 2100 | Negative |
| Viewer C | OPIC475 | 2150 | Negative |
Lay-user study
A lay user study was performed at three intended user sites with 300 lay persons for the device. The lay users had diverse educational and professional backgrounds and ranged in age from 18 to > 50 years. Urine samples were prepared at the following concentrations; negative, +/-75%, +/-50%, +/-25% of the cutoff by spiking drugs into drug free-pooled urine specimens. The concentrations of the samples were confirmed by LC/MS. Each sample was aliquoted into individual containers and blind-labeled. Each participant was provided with the package insert, 1 blind labeled sample and a device. Each device was tested. Summary results are shown below.
The results summary for AMP:
| % of Cutoff | Number of | Drug Concentration | Lay person Results | The percentage of |
|---|---|---|---|---|
| ------------- | ----------- | -------------------- | -------------------- | ------------------- |
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| samples | by LC/MS/MS(ng/mL) | No. ofPositive | No. ofNegative | correct results (%) | |
|---|---|---|---|---|---|
| -100% Cutoff | 20 | 0 | 0 | 20 | 100 |
| -75% Cutoff | 20 | 261 | 0 | 20 | 100 |
| -50% Cutoff | 160 | 507 | 0 | 160 | 100 |
| -25% Cutoff | 20 | 771 | 1 | 19 | 95 |
| +25% Cutoff | 20 | 1290 | 20 | 0 | 100 |
| +50% Cutoff | 40 | 1560 | 40 | 0 | 100 |
| +75% Cutoff | 20 | 1870 | 20 | 0 | 100 |
The results summary for BAR:
| % of Cutoff | Number ofsamples | Drug ConcentrationbyLC/MS/MS(ng/mL) | Lay person Results | The percentage ofcorrect results(%) | |
|---|---|---|---|---|---|
| No. ofPositive | No. ofNegative | ||||
| -100% Cutoff | 20 | 0 | 0 | 20 | 100 |
| -75% Cutoff | 20 | 75.9 | 0 | 20 | 100 |
| -50% Cutoff | 160 | 150 | 0 | 160 | 100 |
| -25% Cutoff | 20 | 220 | 1 | 19 | 95 |
| +25% Cutoff | 20 | 360 | 19 | 1 | 95 |
| +50% Cutoff | 40 | 429 | 40 | 0 | 100 |
| +75% Cutoff | 20 | 501 | 20 | 0 | 100 |
The results summary for COC:
| % of Cutoff | Number ofsamples | Drug ConcentrationbyLC/MS/MS(ng/mL) | Lay person Results | The percentage ofcorrect results(%) | |
|---|---|---|---|---|---|
| No. ofPositive | No. ofNegative | ||||
| -100% Cutoff | 20 | 0 | 0 | 20 | 100 |
| -75% Cutoff | 20 | 81.5 | 0 | 20 | 100 |
| -50% Cutoff | 160 | 151 | 0 | 160 | 100 |
| -25% Cutoff | 20 | 225 | 1 | 19 | 95 |
| +25% Cutoff | 20 | 395 | 19 | 1 | 95 |
| +50% Cutoff | 40 | 455 | 40 | 0 | 100 |
| +75% Cutoff | 20 | 520 | 20 | 0 | 100 |
The results summary for BUP:
| % of Cutoff | Number of samples | Drug Concentration by LC/MS/MS(ng/mL) | Lay person Results | The percentage of correct results (%) | |
|---|---|---|---|---|---|
| -100% Cutoff | 20 | 0 | 0 | 20 | 100 |
| -75% Cutoff | 20 | 2.57 | 0 | 20 | 100 |
| -50% Cutoff | 160 | 5.14 | 0 | 160 | 100 |
| -25% Cutoff | 20 | 6.76 | 1 | 19 | 95 |
| +25% Cutoff | 20 | 12.8 | 18 | 2 | 90 |
| +50% Cutoff | 40 | 15.1 | 40 | 0 | 100 |
| +75% Cutoff | 20 | 17.2 | 20 | 0 | 100 |
The results summary for MET:
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| % of Cutoff | Number of samples | Drug Concentration by LC/MS/MS(ng/mL) | Lay person Results | The percentage of correct results (%) | |
|---|---|---|---|---|---|
| No. of Positive | No. of Negative | ||||
| -100% Cutoff | 20 | 0 | 0 | 20 | 100 |
| -75% Cutoff | 20 | 268 | 0 | 20 | 100 |
| -50% Cutoff | 160 | 526 | 0 | 160 | 100 |
| -25% Cutoff | 20 | 769 | 1 | 19 | 95 |
| +25% Cutoff | 20 | 1270 | 19 | 1 | 95 |
| +50% Cutoff | 40 | 1560 | 40 | 0 | 100 |
| +75% Cutoff | 20 | 1780 | 20 | 0 | 100 |
The results summary for MTD:
| % of Cutoff | Number ofsamples | Drug ConcentrationbyLC/MS/MS(ng/mL) | Lay person Results | The percentage ofcorrect results(%) | |
|---|---|---|---|---|---|
| No. ofPositive | No. ofNegative | ||||
| -100% Cutoff | 20 | 0 | 0 | 20 | 100 |
| -75% Cutoff | 20 | 76.8 | 0 | 20 | 100 |
| -50% Cutoff | 160 | 147 | 0 | 160 | 100 |
| -25% Cutoff | 20 | 226 | 1 | 19 | 95 |
| +25% Cutoff | 20 | 375 | 19 | 1 | 95 |
| +50% Cutoff | 40 | 441 | 40 | 0 | 100 |
| +75% Cutoff | 20 | 504 | 20 | 0 | 100 |
The results summary for Morphine:
| % of Cutoff | Number ofsamples | Drug ConcentrationbyLC/MS/MS(ng/mL) | Lay person Results | The percentage ofcorrect results(%) | |
|---|---|---|---|---|---|
| No. ofPositive | No. ofNegative | ||||
| -100% Cutoff | 20 | 0 | 0 | 20 | 100 |
| -75% Cutoff | 20 | 535 | 0 | 20 | 100 |
| -50% Cutoff | 160 | 1010 | 0 | 160 | 100 |
| -25% Cutoff | 20 | 1580 | 0 | 20 | 100 |
| +25% Cutoff | 20 | 2600 | 19 | 1 | 95 |
| +50% Cutoff | 40 | 3050 | 40 | 0 | 100 |
| +75% Cutoff | 20 | 3240 | 20 | 0 | 100 |
The results summary for OXY:
| % of Cutoff | Number of samples | Drug Concentration by LC/MS/MS(ng/mL) | Lay person Results | The percentage of correct results (%) | |
|---|---|---|---|---|---|
| No. of Positive | No. of Negative | ||||
| -100% Cutoff | 20 | 0 | 0 | 20 | 100 |
| -75% Cutoff | 20 | 24.5 | 0 | 20 | 100 |
| -50% Cutoff | 160 | 49.3 | 0 | 160 | 100 |
| -25% Cutoff | 20 | 71.1 | 1 | 19 | 95 |
| +25% Cutoff | 20 | 118 | 19 | 1 | 95 |
| +50% Cutoff | 40 | 147 | 40 | 0 | 100 |
| +75% Cutoff | 20 | 169 | 20 | 0 | 100 |
The results summary for PCP:
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| % of Cutoff | Number ofsamples | Drug ConcentrationbyLC/MS/MS(ng/mL) | Lay person Results | The percentage ofcorrect results(%) | |
|---|---|---|---|---|---|
| No. ofPositive | No. ofNegative | ||||
| -100% Cutoff | 20 | 0 | 0 | 20 | 100 |
| -75% Cutoff | 20 | 6.27 | 0 | 20 | 100 |
| -50% Cutoff | 160 | 12.5 | 0 | 160 | 100 |
| -25% Cutoff | 20 | 17.9 | 1 | 19 | 95 |
| +25% Cutoff | 20 | 30.8 | 20 | 0 | 100 |
| +50% Cutoff | 40 | 36.4 | 40 | 0 | 100 |
| +75% Cutoff | 20 | 42.8 | 20 | 0 | 100 |
The results summary for THC:
| % of Cutoff | Number ofsamples | Drug ConcentrationbyLC/MS/MS(ng/mL) | Lay person Results | The percentage ofcorrect results(%) | |
|---|---|---|---|---|---|
| No. ofPositive | No. ofNegative | ||||
| -100% Cutoff | 20 | 0 | 0 | 20 | 100 |
| -75% Cutoff | 20 | 13 | 0 | 20 | 100 |
| -50% Cutoff | 160 | 25.3 | 0 | 160 | 100 |
| -25% Cutoff | 20 | 41 | 2 | 18 | 90 |
| +25% Cutoff | 20 | 65 | 19 | 1 | 95 |
| +50% Cutoff | 40 | 79 | 40 | 0 | 100 |
| +75% Cutoff | 20 | 93 | 20 | 0 | 100 |
The results summary for BZO:
| % of Cutoff | Number ofsamples | DrugConcentration byLC/MS/MS(ng/mL) | Lay person Results | The percentage ofcorrect results(%) | |
|---|---|---|---|---|---|
| No. ofPositive | No. ofNegative | ||||
| -100% Cutoff | 20 | 0 | 0 | 20 | 100 |
| -75% Cutoff | 20 | 70.8 | 0 | 20 | 100 |
| -50% Cutoff | 160 | 148 | 0 | 160 | 100 |
| -25% Cutoff | 20 | 224 | 1 | 19 | 95 |
| +25% Cutoff | 20 | 390 | 19 | 1 | 95 |
| +50% Cutoff | 40 | 452 | 40 | 0 | 100 |
| +75% Cutoff | 20 | 504 | 20 | 0 | 100 |
The results summary for MDMA:
| % of Cutoff | Number ofsamples | Drug ConcentrationbyLC/MS/MS(ng/mL) | Lay person Results | The percentage ofcorrect results(%) | |
|---|---|---|---|---|---|
| No. ofPositive | No. ofNegative | ||||
| -100% Cutoff | 20 | 0 | 0 | 20 | 100 |
| -75% Cutoff | 20 | 137 | 0 | 20 | 100 |
| -50% Cutoff | 160 | 250 | 0 | 160 | 100 |
| -25% Cutoff | 20 | 351 | 1 | 19 | 95 |
| +25% Cutoff | 20 | 600 | 19 | 1 | 95 |
| +50% Cutoff | 40 | 745 | 40 | 0 | 100 |
| +75% Cutoff | 20 | 925 | 20 | 0 | 100 |
The results summary for TCA:
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| % of Cutoff | Number ofsamples | Drug ConcentrationbyLC/MS/MS(ng/mL) | Lay person Results | The percentage ofcorrect results(%) | |
|---|---|---|---|---|---|
| No. ofPositive | No. ofNegative | ||||
| -100% Cutoff | 20 | 0 | 0 | 20 | 100 |
| -75% Cutoff | 20 | 273 | 0 | 20 | 100 |
| -50% Cutoff | 160 | 509 | 0 | 160 | 100 |
| -25% Cutoff | 20 | 809 | 1 | 19 | 95 |
| +25% Cutoff | 20 | 1190 | 19 | 1 | 95 |
| +50% Cutoff | 40 | 1510 | 40 | 0 | 100 |
| +75% Cutoff | 20 | 1680 | 20 | 0 | 100 |
The results summary for PPX:
| % of Cutoff | Number ofsamples | Drug ConcentrationbyLC/MS/MS(ng/mL) | Lay person Results | The percentage ofcorrect results(%) | |
|---|---|---|---|---|---|
| No. ofPositive | No. ofNegative | ||||
| -100% Cutoff | 20 | 0 | 0 | 20 | 100 |
| -75% Cutoff | 20 | 77.4 | 0 | 20 | 100 |
| -50% Cutoff | 160 | 150 | 0 | 160 | 100 |
| -25% Cutoff | 20 | 227 | 1 | 19 | 95 |
| +25% Cutoff | 20 | 351 | 19 | 1 | 95 |
| +50% Cutoff | 40 | 420 | 40 | 0 | 100 |
| +75% Cutoff | 20 | 492 | 20 | 0 | 100 |
Lay-users were also given surveys on the ease of understanding the package insert instructions. All lay users indicated that the device instructions can be easily followed. A Flesch-Kincaid reading analysis was performed on each package insert and the scores revealed a reading Grade Level of 7.
3. Clinical Studies
Not applicable.
11. Conclusion
Based on the test principle and acceptable performance characteristics including precision, cut-off, interference, specificity, method comparison, and lay-user studies of the device, it's concluded that the BIOEASY Multi-Drug Test Cup tests are substantially equivalent to the predicate.
§ 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).