(34 days)
CR3 Keyless Split Sample Cup Amphetamine-Cocaine is a rapid test for the qualitative detection of d-Amphetamine (major metabolite of Amphetamine) and Benzoylecgonine (major metabolite of Cocaine) in human urine at a cutoff concentration of 1000ng/mL and 300ng/mL, respectively.
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 is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.
For in vitro diagnostic use only. It is intended for over-the-counter and for prescription use.
The CR3 Keyless Split Sample Cup Amphetamine-Cocaine test uses immunochromatographic assays for amphetamine and cocaine. The test is a lateral flow, one step system for the qualitative detection of d-Amphetamine (major metabolite of Amphetamine) and Benzoylecgonine (major metabolite of Cocaine) in human urine.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Acceptance Criteria and Device Performance for CR3 Keyless Split Sample Cup Amphetamine-Cocaine
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly present a formal table of "acceptance criteria" with specific thresholds for sensitivity, specificity, accuracy, etc., that the device must meet. Instead, the performance characteristics section describes the results of various studies, implying that these results are considered acceptable for demonstrating substantial equivalence.
Here's a summary of the reported device performance for Amphetamine (AMP) and Cocaine (COC) testing, based on the precision, cut-off verification, and comparison studies:
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (AMP) | Reported Device Performance (COC) |
|---|---|---|---|
| Precision (Cut-off) | Consistent and expected results around the cut-off. | For cut-off (1000 ng/mL), 42-43 out of 50 tests were positive across 3 lots (84-86% positive). | For cut-off (300 ng/mL), 41-43 out of 50 tests were positive across 3 lots (82-86% positive). |
| Precision (+25% Cut-off) | All positive at +25% of cut-off. | 50/50 positive across 3 lots (100%). | 50/50 positive across 3 lots (100%). |
| Precision (-25% Cut-off) | All negative at -25% of cut-off. | 50/50 negative across 3 lots (100%). | 50/50 negative across 3 lots (100%). |
| Cut-off Verification | All positive at +25% and +50% cut-off; all negative at -25% and -50% cut-off. | Pass: All positive at +25% & +50%; all negative at -25% & -50%. | Pass: All positive at +25% & +50%; all negative at -25% & -50%. |
| Interference | No interference from common substances at 100 ug/mL. | Wide range of listed substances showed no interference. | Wide range of listed substances showed no interference. |
| Specificity (Cross-reactivity) | Detailed cross-reactivity for related compounds with % values. | d-Amphetamine: 100%, l-Amphetamine: 2%, d,l-Amphetamine: 33%, MDA: 20%, Phentermine: 33%, others <1%. | Benzoylecgonine: 100%, Cocaine HCl: 40%, Cocaethylene: 2.4%, Ecgonine: <1%. |
| Effect of Urinary Density & pH | No effect on device performance across specified ranges. | Device performance not affected by varying urine density (1.000-1.035) and pH (4.00-9.00). | Device performance not affected by varying urine density (1.000-1.035) and pH (4.00-9.00). |
| Comparison to GC/MS (Overall Accuracy) | High agreement with GC/MS, especially for high positive/low negative samples. | Viewer A: 37/40 positive (+), 37/40 negative (-). Total 74/80 (92.5%). Viewer B: 35/40 positive (+), 36/40 negative (-). Total 71/80 (88.75%). Viewer C: 36/40 positive (+), 37/40 negative (-). Total 73/80 (91.25%). | Viewer A: 36/40 positive (+), 35/40 negative (-). Total 71/80 (88.75%). Viewer B: 37/40 positive (+), 36/40 negative (-). Total 73/80 (91.25%). Viewer C: 35/40 positive (+), 36/40 negative (-). Total 71/80 (88.75%). |
| Lay-user study agreement with GC/MS at ±25% cut-off | Reasonable agreement to demonstrate usability by lay-users. | d-Amphetamine: 80% at -25% cut-off; 85% at +25% cut-off. | Benzoylecgonine: 85% at -25% cut-off; 80% at +25% cut-off. |
| Lay-user study agreement with GC/MS at ±50%, ±75%, -free | Very high agreement. | 100% agreement for drug-free, -75%, -50%, +50%, +75%. | 100% agreement for -75%, -50%, +50%, +75%. |
2. Sample Size and Data Provenance
-
Sample size for the test set:
- Precision Studies: For each of the 9 concentration levels (for both AMP and COC), 50 tests were performed per concentration (2 runs/day for 25 days). This results in a total of 9 concentration levels * 50 tests/level = 450 tests per drug (AMP/COC).
- Cut-off Verification: 125 amphetamine samples and 125 cocaine samples (equally distributed across 5 concentrations: -50%, -25%, at cut-off, +25%, +50%). Each tested using 3 lots by 3 operators.
- Interference & Specificity (Cross-reactivity): Substances were added to drug-free urine and urine containing drugs at ±25% cut-off. These were tested using 3 batches by 3 operators. The exact number of samples for each interfering substance or cross-reactant isn't specified, but implies multiple samples per substance.
- Effect of Urinary Density and pH: 12 urine samples (density) and an aliquot of negative urine pool adjusted to 6 pH ranges. Each spiked with drugs at ±25% cut-off. Tested using 3 batches by 3 operators.
- Comparison Studies: 80 clinical samples (40 negative and 40 positive) for each drug (AMP and COC). Therefore, 80 * 2 = 160 clinical samples in total.
- Lay-user Study: 260 lay persons. 20 for drug-free samples, 120 for d-Amphetamine samples, 120 for benzoylecgonine samples. Each individual tested one sample.
-
Data Provenance:
- Clinical Samples (Comparison Studies): "unaltered clinical samples." The geographic origin (country) is not explicitly stated, but the submission is from Guangzhou, P.R. China.
- Other Studies (Precision, Cut-off, Interference, Specificity, Density/pH, Lay-user): Samples were likely prepared in-house (e.g., drug-free pooled urine spiked with drugs). The "clinical samples" mentioned only in the Comparison Study section suggest the others used prepared samples.
- Retrospective or Prospective: Not explicitly stated. The description of preparing and testing samples suggests a prospective setup for most analytical performance studies and the lay-user study. The "unaltered clinical samples" for the comparison study could be retrospective or prospectively collected for the study.
3. Number of Experts and Qualifications for Ground Truth
-
For Analytical and Comparison Studies:
- Comparison Study: The ground truth for the 80 clinical samples (40 negative, 40 positive for each drug) was established using GC/MS (Gas Chromatography/Mass Spectrometry). This is a highly accurate and widely accepted reference method for drug testing, often considered the "gold standard." These were then compared to the device's results as interpreted by "three laboratory assistants."
- Cut-off, Precision, Lay-user Studies: The ground truth for these studies was established by spiking known concentrations of d-Amphetamine or benzoylecgonine into drug-free urine, with concentrations confirmed by GC/MS. The "person who prepared them" (cut-off study) was masked from the testing, ensuring blinding.
-
Number of Experts:
- For the analytical performance studies (Precision, Cut-off, Interference, Specificity, Density/pH), results were read by "three different operators." Their qualifications are not specified beyond being "operators" or "laboratory assistants."
- For the comparison studies, the device results were viewed by "three laboratory assistants." Their specific qualifications (e.g., experience level, professional certification) are not detailed.
- For the lay-user study, 260 "lay persons" interpreted the results themselves without expert intervention, as the intent was to evaluate usability by the general public.
4. Adjudication Method for the Test Set
- No explicit adjudication method (e.g., 2+1, 3+1) is mentioned for the interpretation of the device's results in the analytical or comparison studies. Each of the three operators' results is presented separately for the comparison study, and discordance tables show individual viewer discrepancies with GC/MS. This suggests that the operators made independent interpretations, and their individual results were compared to the GC/MS ground truth.
- In the lay-user study, each lay person interpreted their own single test device.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, an MRMC comparative effectiveness study where human readers improve with AI vs. without AI assistance was not done.
- The study described is a comparison of the device's performance against a reference method (GC/MS) when read by individual "laboratory assistants" (human readers). There is no AI component or a comparison of human performance with vs. without AI assistance.
6. Standalone Performance Study (Algorithm only)
- Yes, a standalone performance study was implicitly done. The device itself is a qualitative rapid test, effectively an "algorithm" (immunochromatographic assay producing a visual result) that produces a "positive" or "negative" outcome. The "Performance Characteristics" section details the device's intrinsic analytical capabilities:
- Precision: How consistently the device performs with known concentrations.
- Cut-off: Verification of the detection limit.
- Interference & Specificity: How the device reacts to other substances.
- Effect of Urinary Density and pH: Stability across different urine conditions.
- While human "operators" or "laboratory assistants" read the visual results, the studies establish the inherent capability of the test mechanism (the "device" or "algorithm") to detect the analytes at specified cut-offs and react appropriately to various conditions. The "Comparison Studies" further validate this by comparing the device's output (as read by humans) directly to GC/MS.
7. Type of Ground Truth Used
- The primary ground truth used for validation was GC/MS (Gas Chromatography/Mass Spectrometry).
- For the comparison studies, "unaltered clinical samples" had their ground truth established by GC/MS.
- For the precision, cut-off, interference, specificity, density/pH, and lay-user studies, known concentrations of target drugs were spiked into drug-free urine, and these spiked concentrations were confirmed by GC/MS. This ensures that the true concentration of the target analyte was known for these prepared samples.
8. Sample Size for the Training Set
- The document describes a submission for a medical device (a rapid diagnostic test), not a machine learning model. Therefore, there is no explicit "training set" in the context of typical AI/ML development.
- The device's underlying "learning" or "calibration" would have occurred during its initial design, manufacturing process development, and internal R&D validation (e.g., optimizing antibody concentrations, membrane properties), which typically isn't detailed as a "training set" in a regulatory submission.
9. How Ground Truth for the Training Set Was Established
- As explained above, since this is a rapid diagnostic test and not an AI/ML device, the concept of a "training set" in the machine learning sense does not apply directly.
- The "ground truth" during the device's development (analogous to how a training set might be used) would have been established through a combination of:
- Known concentrations of pure drug analytes or their metabolites.
- Reference laboratory methods (like GC/MS) to verify concentrations of prepared samples or evaluate early prototypes.
- Chemical and biological assays to optimize the components (antibodies, conjugates, membranes) for specific binding and detection characteristics.
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510(k) SUMMARY
JUL 1 4 2014
- Date: July 11, 2014 Submitter: Guangzhou Wondfo Biotech Co., Ltd. 2. No.8 Lizhishan Road, Science City, Luogang District, Guangzhou, P.R. China 510663 3. Contact person: Joe Shia LSI International Inc. 504 East Diamond Ave., Suite F Gaithersburg, MD 20878
Telephone: 240-505-7880 Fax: 301-916-6213 Email:shiajl@yahoo.com
-
- Device Name: CR2 Keyless Split Sample Cup Amphetamine-Cocaine
Classification:
- Device Name: CR2 Keyless Split Sample Cup Amphetamine-Cocaine
| Product | |
|---|---|
| Code | CFR # |
| DKZ | 21CFR 862.3100 |
| DIO | 21CFR 862.3250 |
-
- Predicate Devices: K130665 Wondfo Multi-Drug Urine Test Cup Wondfo Multi-Drug Urine Test Panel
-
- Intended Use
CR3 Keyless Split Sample Cup Amphetamine-Cocaine is a rapid test for the qualitative detection of d-Amphetamine (major metabolite of Amphetamine) and Benzoylecgonine (major metabolite of Cocaine) in human urine at a cutoff concentration of 1000ng/mL and 300ng/mL, respectively.
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 is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.
For in vitro diagnostic use only. It is intended for over-the-counter and for prescription use.
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-
- Device Description
Split Sample Cup Amphetamine-Cocaine Keyless test uses The CR3 immunochromatographic assays for amphetamine and cocaine. The test is a lateral flow, one step system for the qualitative detection of d-Amphetamine (major metabolite of Amphetamine) and Benzoylecgonine (major metabolite of Cocaine) in human urine.
- Device Description
| Item | Device | Predicate |
|---|---|---|
| Indication(s)for use | For the qualitative determination ofAmphetamine and Cocaine inhuman urine | Same, but alsodetects other drugs inhuman urine |
| Methodology | Competitive binding, lateral flowimmunochromatographic assaysbased on the principle of antigenantibody immunochemistry. | Same |
| Results | Qualitative | Same |
| SpecimenType | Human urine | Same |
| Cut Off Values | Amphetamine: 1000ng/mlCocaine: 300ng/ml | Same forAmphetamine andCocaine |
| Configurations | Cup | Cup, Panel |
| Conditions forUse | Over-the-Counter & PrescriptionUse | Same |
-
- Substantial Equivalence Information
9. Test Principle
The CR3 Keyless Split Sample Cup Amphetamine-Cocaine test is a rapid test for the qualitative detection of d-Amphetamine and benzoylecgonine in urine samples and contains lateral flow chromatographic immunoassays for amphetamine and cocaine. Each assay uses a mouse monoclonal anti-drug antibody-dye conjugate, fixed drug-protein conjugates, and anti-mouse IgG polyclonal antibodies coated on the test membranes. When the absorbent end of the test is immersed into a urine sample, the urine is absorbed into the device by capillary action and mixes with the antibody-dye conjugate, flowing across the pre-coated membrane. At analyte concentrations below the target cut-off, antibody-dye conjugates bind to the drug-protein conjugate immobilized in the Test Region (T) of the device. This produces a colored test line that indicates a negative result. When analyte concentration is above the cut-off, analyte molecules bind to the antibody-dye conjugate, preventing the antibody-dye conjugate from binding to the drug-protein conjugate immobilized in the Test Region (T) of the device. No colored band shows in the test region, indicating a potentially
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positive result. A band should form in the control region (C) of the device regardless of the presence of drug or metabolite in the sample.
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, at the cut-off, +25% cut-off, +50% cut-off , +75% cut-off and +100% cut-off. For each concentration, tests were performed two runs per day for 25 days. All sample aliquots were masked and randomized. The results obtained are summarized in the following tables:
| ResultAMP | -100%cut-off | -75%cut-off | -50%cut-off | -25%cut-off | +25%cut-off | +50%cut-off | +75%cut-off | +100%cut-off |
|---|---|---|---|---|---|---|---|---|
| W11710501CU5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 42+/8- | 50+/0- | 50+/0- | 50+/0- |
| W11710502CU5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 43+/7- | 50+/0- | 50+/0- | 50+/0- |
| W11710503CU5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 43+/7- | 50+/0- | 50+/0- | 50+/0- |
A. For Amphetamine (AMP) testing
B. For Cocaine (COC) testing
| Result | -100%cut-off | -75%cut-off | -50%cut-off | -25%cut-off | cut-off | +25%cut-off | +50%cut-off | +75%cut-off | +100%cut-off |
|---|---|---|---|---|---|---|---|---|---|
| W11710501CU5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 41+/9- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| W11710502CU5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 43+/7- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| W11710503CU5 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 42+/8- | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
-
b. Linearity
Not applicable. -
c. Stability
The CR3 Keyless Split Sample Cup Amphetamine-Cocaine is stable at 4-30°C for 18 months as determined by conducting accelerated and real-time stability testing.
Control materials are not provided with the device. The labeling provides information on how to obtain control materials.
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- d. Cut-off
A total of 125 amphetamine samples and 125 cocaine samples equally distributed at concentrations of -50%, -25%, at the cut-off, +25%, +50% of their respective cut-offs were labeled by a person who prepared them and would not participate in the sample testing. These samples were tested using three different lots by three different operators. Results were all positive at +25% and +50% cut-off and all negative at -25% and -50% cut-off for both cocaine and amphetamine. The following cut-off values for the test devices have been verified.
| Test | Calibrator | Cut-off (ng/ml) |
|---|---|---|
| Amphetamine(AMP) | d-Amphetamine | 1000 |
| Cocaine(COC) | Benzoylecgonine | 300 |
- Interference e.
Potential interfering substances found in human urine of physiological or pathological conditions were added to drug-free urine and to urine containing target drugs (d-amphetamine or benzoylecgonine) at 25% below and 25% above the cut-off. These urine samples were tested using three batches of the CR3Keyless Split Sample Cup Amphetamine-Cocaine by three different operators. Compounds that showed no interference at a concentration of 100ug/mL are summarized below:
d-Amphetamine
| 4-Acetamidophenol | (-) Y Ephedrine | Penicillin-G |
|---|---|---|
| Acetophenetidin | Erythromycin | Pentazocaine |
| N-Acetylprocainamide | β-Estradiol | Pentobarbital |
| Acetylsalicylic acid | Estrone-3-sulfate | Perphenazine |
| Aminopyrine | Ethyl-p-aminobenzoate | Phencyclidine |
| Amitryptyline | Fenfluramine | Phenelzine |
| Amobarbital | Fenoprofen | Phendimetrazine |
| Amoxicillin | Furosemide | Phenobarbital |
| Ampicillin | Gentisic acid | Phetoin |
| Ascorbic acid | Hemoglobin | L-Phenylephrine |
| Apomorphine | Hydralazine | β-Phenylethlamine |
| Aspartame | Hydrochlorothiazide | Phenylpropanolamine |
| Atropine | Hydrocodone | Prednisolone |
| Benzilic acid | Hydrocortisone | Prednisone |
| Benzoic acid | O-Hydroxyhippuric acid | Procaine |
| Benzoylecgonine | 3-Hydroxytyramine | Promazine |
| Bilirubin | Ibuprofen | Promethazine |
| Brompheniramine | Imipramine | D,L-Propanolol |
| Caffeine | (-) Isoproterenol | Propiomazine |
| Cannabidiol | Isoxsuprine | D-Propoxyphene |
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Cannabinol Chloralhydrate Chloramphenicol Chlordiazepoxide Chlorothiazide (±) Chlorpheniramine Chlorpromazine Chlorquine Cholesterol Clomipramine Clonidine Cocaine hydrochloride Codeine Cortisone (-) Cotinine Creatinine Deoxycorticosterone Dextromethorphan Diazepam Diclofenac Diflunisal Digoxin Diphenhydramine Doxylamine Ecgonine hydrochloride Ecgonine methylester (IR,2S)-(-)-Ephedrine L-Ephedrine
Benzoylecgonine
Acetominophen Acetophenetidin N-Acetylprocainamide Acetylsalicylic acid Aminopyrine Amitryptyline Amobarbital Amoxicillin Ampicillin L-Ascorbic acid DL-Amphetamine Sulfate Apomorphine Aspartame Atropine Benzilic acid
Ketamine Ketoprofen Labetalol Levorphanol Loperamide Maprotiline Meperidine Meprobamate Methadone Methylphenidate Morphine-3-Dglucuronide Nalidixic acid Naloxone Naltrexone Naproxen Niacinamide Nifedipine Norcodein Norethindrone D-Norpropoxyphene Noscapine D.L-Octopamine Oxalic acid Oxazepam Oxolinic acid
Oxycodone Oxymetazoline Papaverine
Estrone-3-sulfate Ethyl-p-aminobenzoate Fenoprofen Furosemide Gentisic acid Hemoglobin Hydralazine Hydrochlorothiazide Hydrocodone Hydrocortisone O-Hydroxyhippuric acid p-Hydroxymethamphetamine 3-Hydroxytyramine Ibuprofen Imipramine
Quinidine Quinine Ranitidine Salicylic acid Secobarbital Serotonin Sulfamethazine Sulindac Temazepam Tetracycline Tetrahydrocortisone Tetrahydrozoline A9-THC-COOH Thebaine Thiamine Thioridazine D.L-Thyroxine Tolbutamine Triamterene Trifluoperazine Trimethoprim Trimipramine Tryptamine D, L-Tyrosine Uric acid
Verapamil Zomepirac
Papaverine Penicillin-G Pentobarbital Perphenazine Phencyclidine Phenelzine Phenobarbital Phentermine L-Phenylephrine ß-Phenylethylamine Phenylpropanolamine Prednisolone Prednisone Procaine Promazine
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Benzoic acid Iproniazid Benzphetamine (±) - Isoproterenol Isoxsuprine Bilirubin (±) -Brompheniramine Ketamine Caffeine Ketoprofen Cannabidiol Labetalol Cannabinol Levorphanol Chloralhydrate Loperamide Chloramphenicol Maprotiline Chlordiazepoxide Meperidine Chlorothiazide Meprobamate (±) -Chlorpheniramine Methadone Chlorpromazine (土) Chlorquine (主 Cholesterol Clomipramine Clonidine Morphine Sulfate Codeine Nalidixic acid Cortisone Naloxone (-) Cotinine Naltrexone Creatinine Naproxen Deoxycorticosterone Niacinamide Dextromethorphan Nifedipine Diazepam Norcodein Diclofenac Norethindrone Diflunisal Digoxin Noscapine Diphenhydramine DL-Octopamine Doxylamine Oxalic acid Ecgonine methylester Oxazepam (-) - Y-Ephedrine Oxolinic acid Erythromycin Oxycodone B-Estradiol Oxymetazoline
Methoxyphenamine 4-Methvlene dioxyamphetamine nydrochloride -Methylene vmethamphetamine Morphine-3-B-D glucuronide D-Norpropoxyphene
Promethazine DL-Propranolol D-Propoxyphene D-Pseudoephedrine Quinidine Quinine Ranitidine Salicylic acid Secobarbital Serotonin Sulfamethazine Sulindac Temazepam Tetracycline Tetrahydrocortisone, 3-Acetate Tetrahydrocortisone glucuronide) Tetrahydrozoline Thebaine Thiamine Thioridazine DL-Tyrosine Tolbutamide Triamterene Trifluoperazine Trimethoprim Trimipramine Tryptamine DL-Tryptophan Tyramine Uric acid Verapamil Zomepirac
- f. Specificity
To test the specificity, drug metabolites and other components that are likely to be present in urine samples were tested. The target drug (d-Amphetamine or Benzoylecgonine), its drug metabolites and the related compounds were studied. These samples were tested using three batches of the CR3Kevless Split Sample Cup Amphetamine-Cocaine by three different operators. The drug metabolites and other components were tested at different concentrations. The obtained lowest detectable concentration was used to calculate the cross-reactivity. Results are shown in the following tables.
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| AMP (Amphetamine)(d-Amphetamine,Cut-off=1000 ng/mL) | Result | % Cross-Reactivity |
|---|---|---|
| d-Amphetamine | Positive at 1,000ng/mL | 100% |
| l-Amphetamine | Positive at 50,000ng/mL | 2% |
| d,l-Amphetamine | Positive at 3,000ng/mL | 33% |
| (+/-) 3,4-methylenedioxyamphetamine(MDA) | Positive at 5,000ng/mL | 20% |
| Phentermine | Positive at 3,000ng/mL | 33% |
| d-Methamphetamine | >100,000 ng/mL | <1% |
| l-Methamphetamine | >100,000 ng/mL | <1% |
| Ephedrine | >100,000 ng/mL | <1% |
| 3,4-Methylenedioxyethylamphetamine(MDEA) | >100,000 ng/mL | <1% |
| COC(Cocaine)(Benzoylecgonine,Cut-off=300 ng/mL) | Result | % Cross-Reactivity |
|---|---|---|
| Benzoylecgonine | Positive at 300 ng/mL | 100% |
| Cocaine HCl | Positive at 750 ng/mL | 40% |
| Cocaethylene | Positive at 12,500ng/mL | 2.4% |
| Ecgonine | Positive at 32,000ng/mL | <1% |
Effect of Urinary Density and pH g.
Twelve urine samples of normal, high, and low specific density ranges (1.000 to 1.035) were collected and spiked with either d-Amphetamine or benzoylecgonine at 25% below and 25% above the corresponding cut-off level. These samples were tested using three batches of the CR3Keyless Split Sample Cup Amphetamine-Cocaine by three different operators.
The pH of an aliquot negative urine pool was adjusted to pH ranges of 4.00 to 9.00 in 1 pH unit increments and spiked with d-Amphetamine or benzoylecgonine at 25% below and 25% above the corresponding cut-off levels. These samples were tested using three batches of the CR3Keyless Split Sample Cup Amphetamine-Cocaine by three different operators.
The device performance was found not affected by varying urine density and pH.
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2. Comparison Studies
The method comparison for the CR3 Keyless Split Sample Cup Amphetamine-Cocaine was performed in-house with three laboratory assistants. Operators ran 80 (40 negative and 40 positive) unaltered clinical samples. The samples were masked and randomized. The obtained test results are compared to GC/MS results. The results are presented in the table below:
| Amphetamine | ||||||
|---|---|---|---|---|---|---|
| GroupOperators | Negative | LowNegative byGC/MS(less than-50%) | Near CutoffNegative byGC/MS(Between-50% andcutoff) | Near CutoffPositive byGC/MS(Betweenthe cutoffand +50%) | HighPositive byGC/MS(greaterthan +50%) | |
| Viewer A | Positive | 0 | 0 | 3 | 17 | 20 |
| Negative | 10 | 18 | 9 | 3 | 0 | |
| Viewer B | Positive | 0 | 0 | 4 | 15 | 20 |
| Negative | 10 | 18 | 8 | 5 | 0 | |
| Viewer C | Positive | 0 | 0 | 3 | 16 | 20 |
| Negative | 10 | 18 | 9 | 4 | 0 |
Discordant table:
| Viewer | Sample number | GC/MS result | Viewer result |
|---|---|---|---|
| Viewer A | AMPC1035 | 811 | positive |
| Viewer A | AMPC1062 | 945 | positive |
| Viewer A | AMPC1065 | 987 | positive |
| Viewer A | AMPC1061 | 1033 | negative |
| Viewer A | AMPC1063 | 1002 | negative |
| Viewer A | AMPC1064 | 1014 | negative |
| Viewer B | AMPC1032 | 781 | positive |
| Viewer B | AMPC1035 | 811 | positive |
| Viewer B | AMPC1062 | 945 | positive |
| Viewer B | AMPC1065 | 987 | positive |
| Viewer B | AMPC1061 | 1033 | negative |
| Viewer B | AMPC1063 | 1002 | negative |
| Viewer B | AMPC1064 | 1014 | negative |
| Viewer B | AMPC1092 | 1185 | negative |
| Viewer B | AMPC1094 | 1312 | negative |
| Viewer C | AMPC1033 | 702 | positive |
| Viewer C | AMPC1035 | 811 | positive |
| Viewer C | AMPC1065 | 987 | positive |
| Viewer C | AMPC1061 | 1033 | negative |
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| Viewer C | AMPC1063 | 1002 | negative |
|---|---|---|---|
| Viewer C | AMPC1091 | 1212 | negative |
| Viewer C | AMPC1093 | 1296 | negative |
Cocaine
| GroupOperators | Negative | Low Negative byGC/MS(less than-50%) | Near Cutoff Negative byGC/MS(Between-50% andcutoff) | Near Cutoff Positive byGC/MS(Betweenthe cutoffand +50%) | High Positive byGC/MS(greaterthan +50%) | |
|---|---|---|---|---|---|---|
| Viewer A | Positive | 0 | 0 | 4 | 16 | 20 |
| Negative | 10 | 15 | 11 | 4 | 0 | |
| Viewer B | Positive | 0 | 0 | 4 | 17 | 20 |
| Negative | 10 | 15 | 11 | 3 | 0 | |
| Viewer C | Positive | 0 | 0 | 4 | 15 | 20 |
| Negative | 10 | 15 | 11 | 5 | 0 |
Discordant table:
| Viewer | Sample number | GC/MS result | viewer results |
|---|---|---|---|
| Viewer A | COCC1031 | 231 | positive |
| Viewer A | COCC1033 | 229 | positive |
| Viewer A | COCC1034 | 232 | positive |
| Viewer A | COCC1062 | 293 | positive |
| Viewer A | COCC1061 | 302 | negative |
| Viewer A | COCC1064 | 314 | negative |
| Viewer A | COCC1065 | 306 | negative |
| Viewer A | COCC1091 | 351 | negative |
| Viewer B | COCC1031 | 231 | positive |
| Viewer B | COCC1032 | 219 | positive |
| Viewer B | COCC1035 | 221 | positive |
| Viewer B | COCC1062 | 293 | positive |
| Viewer B | COCC1061 | 302 | negative |
| Viewer B | COCC1063 | 325 | negative |
| Viewer B | COCC1065 | 306 | negative |
| Viewer C | COCC1032 | 219 | positive |
| Viewer C | COCC1033 | 229 | positive |
| Viewer C | COCC1034 | 232 | positive |
| Viewer C | COCC1062 | 293 | positive |
| Viewer C | COCC1061 | 302 | negative |
| Viewer C | COCC1063 | 325 | negative |
| Viewer C | COCC1064 | 314 | negative |
| Viewer C | COCC1065 | 306 | negative |
| Viewer C | COCC1095 | 378 | negative |
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Lay-user study
A lay user study was performed at three intended user sites with 260 lay persons, of which, 20 tested for drug-free samples, 120 for d-Amphetamine samples, 120 for benzoylecgonine samples. They had diverse educational and professional backgrounds and ranged in age from 21 to >50 years. Urine samples were prepared at the following concentrations; -100%, +1-75%, +/-50%, +/-25% of the cut-off by spiking drug(s) into drug free-pooled urine specimens. The concentrations of the samples were confirmed by GC/MS. Each sample was aliquoted into individual containers, blind-labeled and randomized. Each participant was provided with the package insert, I blind labeled sample and a device. The results are summarized below:
| Cup format | Numberofsamples | OTC user | %AgreementWithGC/MS | ||
|---|---|---|---|---|---|
| Drug | Concentration | Negative | Positive | ||
| Drug -free | -100% | 20 | 20 | 0 | 100% |
| d-Amphetamine | -75% | 20 | 20 | 0 | 100% |
| -50% | 20 | 20 | 0 | 100% | |
| -25% | 20 | 16 | 4 | 80% | |
| +25% | 20 | 3 | 17 | 85% | |
| +50% | 20 | 0 | 20 | 100% | |
| +75% | 20 | 0 | 20 | 100% | |
| Benzoylecgonine | -75% | 20 | 20 | 0 | 100% |
| -50% | 20 | 20 | 0 | 100% | |
| -25% | 20 | 17 | 3 | 85% | |
| +25% | 20 | 4 | 16 | 80% | |
| +50% | 20 | 0 | 20 | 100% | |
| +75% | 20 | 0 | 20 | 100% |
Data analysis shows that all lay persons have carried out the test correctly and the results show good accuracy compared to theGC/MS. Also, a Flesch-Kincaid reading analysis was performed on both drug's package inserts (AMP and COC) and the score revealed a reading grade level of less than 7.
-
- Clinical Studies
Not applicable
- Clinical Studies
11. Conclusion
Based on the test principle and performance characteristics of the device, it's concluded that CR3 Keyless Split Sample Cup Amphetamine-Cocaine is substantially equivalent to the predicate.
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Image /page/10/Picture/0 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized eagle with three stripes extending from its body, representing people. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the eagle.
Public Health Service
Food and Orig Administration 10903 New Hampshire Avenue Document Comrol Center - WO66-G609 Silver Spring, MD 20993-0002
July 14, 2014
GUANGZHOU WONDFO BIOTECH CO., LTD. C/O JOE SHIA LSI INTERNATIONAL INC 504 EAST DIAMOND AVE. SUITE F GAITHERSBURG MD 20878
Re: K141532
Trade/Device Name: CR3 Keyless Split Sample Cup Amphetamine-Cocaine Regulation Number: 21 CFR 862.3100 Regulation Name: Amphetamine test system Regulatory Class: II Product Code: DKZ, DIO Dated: June 6, 2014 Received: June 10, 2014
Dear Mr. 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. 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 (sec 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 cquivalence 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.
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Page 2-Mr. Shia
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/Industrv/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/ReportalProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours.
Courtney H. Lias -S
Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement befow.
510(k) Number (if known) K141532
Device Name
CR3 Keyless Split Sample Cup Amphetamine-Cocaine
Indications for Use (Describe)
CR3 Kevless Split Sample Cup Amphetamine-Cocaine is a rapid test for the qualitative detection of d-Amphetamine (major metabolite of Amphetamine) and Benzoylecgonine (major metabolite of Cocaine) in human urine at a cutoff concentration of 1000ng/mL and 300ng/mL, respectively.
The test provides only preliminary test results. A more specific alternical method must be used in order to obtain a confirmed analytical result. GCMS is the preferred confirmatory method. Clinical consideration and professional iudement should be exercised with any drug of abuse test result, particularly when the presult is positive.
For in vitro diagnostic use only. It is intended for over-the-counter and for prescription use.
Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)
2 Over-The-Counter Use (21 CFR 801 Subpart C)
PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.
FOR FDA USE ONLY
Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)
Denise Johnson-lyles -S
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*DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW."
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FORM FDA 3881 (1/14)
Page 1 of 1
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§ 862.3100 Amphetamine test system.
(a)
Identification. An amphetamine test system is a device intended to measure amphetamine, a central nervous system stimulating drug, in plasma and urine. Measurements obtained by this device are used in the diagnosis and treatment of amphetamine use or overdose and in monitoring levels of amphetamine to ensure appropriate therapy.(b)
Classification. Class II (special controls). An amphetamine 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).