SAFECARE® Multi-Drug Urine Test Dip Card is competitive binding, lateral flow immunochromatographic assays for qualitative and simultaneous detection of Amphetamine, Oxazepam, Methamphetamine, Morphine, Oxycodone, Secobarbital, Buprenorphine, Methylenedioxy-methamphetamine, Phencyclidine, Methadone, Nortriptyline d-Propoxyphene and 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine (EDDP) in human urine at the cutoff concentrations listed. The test may yield positive results for the prescription drugs Buprenorphine, 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. The tests are intended for over-the-counter use.

SAFECARE® Multi-Drug Urine Test Cup is 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 d-Propoxyphene and 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine (EDDP) in human urine at the cutoff concentrations listed. 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. The tests are intended for over-the-counter use.

Device Description

The SAFECARE® Dip Card Tests and SAFECARE® Cup Tests are immunochromatographic assays that use a lateral flow system for the qualitative detection of Amphetamine, Oxazepam, Cocaine, Cannabinoids, Methamphetamine, Morphine, Secobarbital, Methadone, Methylenedioxymethamphetamine, Oxycodone, Buprenorphine, Phencyclidine, Nortriptyline, Propoxyphen and 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine (target analytes) in human urine. The products are single-use in vitro diagnostic devices, which come in the formats of Dip Cards or Cups. Each test kit contains a Test Device (in one of the two formats), a package insert and a urine cup for sample collection. Each test device is sealed with a desiccant in an aluminum pouch.

AI/ML Overview

The provided text describes the performance characteristics of the SAFECARE® Multi-Drug Urine Test Dip Card and SAFECARE® Multi-Drug Urine Test Cup. The document details analytical performance (precision, linearity, stability, interference, specificity, effect of specific gravity and pH) and comparison studies (method comparison and lay-user study).

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for each analytical performance characteristic are implicitly defined by the successful results reported in the study. The study aims to demonstrate that the device performs as expected according to its intended use and analytical specifications.

Precision:
- Acceptance Criteria for -100% to -25% Cut-off: All samples should test negative.
- Acceptance Criteria for +25% to +100% Cut-off: All samples should test positive.
- Acceptance Criteria for Cut-off (nominal concentration): Approximately 50% positive and 50% negative results (reflecting the nature of the cut-off).
- Reported Device Performance (for 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine as an example):
  - Dip Card (Lot 1, 2, 3):
    - -100% Cut-off to -25% Cut-off: 50-/0+ (All negative)
    - +25% Cut-off to +100% Cut-off: 50+/0- (All positive)
    - Cut-off: 24-/26+, 25-/25+, 26-/24+ (Split between positive and negative, as expected)
  - Cup (Lot 1, 2, 3):
    - -100% Cut-off to -25% Cut-off: 50-/0+ (All negative)
    - +25% Cut-off to +100% Cut-off: 50+/0- (All positive)
    - Cut-off: 27-/23+, 24-/26+, 26-/24+ (Split between positive and negative, as expected)
Interference:
- Acceptance Criteria: No interference from common physiological or pathological substances at specified concentrations.
- Reported Device Performance: No interference observed for a comprehensive list of compounds at 100ug/mL (except albumin at 100mg/dL and ethanol at 1% volume).
Specificity (Cross-Reactivity):
- Acceptance Criteria: Related compounds should either not cross-react or cross-react at concentrations significantly higher than the cut-off, as defined by medical relevance.
- Reported Device Performance (for 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine as an example):
  - Methadone: Positive at 300000 ng/mL (0.1% cross-reactivity)
  - EMDP: Positive at 300000 ng/mL (0.1% cross-reactivity)
  - Doxylamine, Disopyramide, LAAM HCl, Alpha Methadol: Positive at >100,000 ng/mL (<0.3% cross-reactivity)
Effect of Urine Specific Gravity and Urine pH:
- Acceptance Criteria: Reliable results (positive above cut-off, negative below cut-off) across a specified range of specific gravity and pH.
- Reported Device Performance: All samples at and above +25% Cut-Off were positive, and all samples at and below -25% Cut-Off were negative, for specific gravity from 1.000 to 1.035 and pH 4 to 9.
Method Comparison Study (Clinical Samples):
- Acceptance Criteria: High agreement (minimal discordant results) between the device results and LC/MS (Liquid Chromatography/Mass Spectrometry) results, especially for samples near the cut-off.
- Reported Device Performance (for 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine as an example):
  - Dip Card: High concordance with LC/MS, with few discordant results (e.g., Viewer A: 1 false positive at 291 ng/mL; Viewer B: 1 false negative at 309 ng/mL).
  - Cup: High concordance with LC/MS, with few discordant results (e.g., Viewer A: 1 false positive at 285 ng/mL; Viewer B: 1 false negative at 372 ng/mL).
Lay-user Study:
- Acceptance Criteria: High percentage of correct results for samples well below and well above the cut-off, and reasonable performance for samples near the cut-off, when interpreted by lay users. Ease of understanding instructions.
- Reported Device Performance (for specific drugs like Amphetamine (AMP), Cocaine (COC), THC, BAR, BZO, MET, MTD, MDMA, OXY, OPI, BUP, PCP, TCA, PPX, EDDP as examples):
  - For samples at -100% to -50% Cut-off and +50% to +75% Cut-off: 100% correct results across all drugs.
  - For samples at -25% Cut-off: generally 90-95% correct negative results (some false positives).
  - For samples at +25% Cut-off: generally 85-95% correct positive results (some false negatives).
  - All lay users indicated the device instructions were easy to follow (Flesch-Kincaid Grade Level 7).

2. Sample Sizes Used for the Test Set and the Data Provenance

Precision Study: For each drug and concentration, two runs per day for 25 days per device (Dip Card and Cup), implying a total of 50 tests per concentration per lot. With 3 lots, this is 150 tests per concentration per format. There were 9 concentrations tested. So 150*9 = 1350 tests per drug per format.
Interference Study: Not explicitly stated, but tests were performed on "three batches of each device" for various interfering substances spiked into drug-free and drug-spiked urine samples.
Specificity Study: Not explicitly stated how many tests per compound, but "three batches of each device" were used.
Effect of Urine Specific Gravity and Urine pH Study: "three lots of each device" were used for samples spiked with target drugs at +/- 25% Cut-Off levels across the range of specific gravity and pH.
Method Comparison Study: 80 "unaltered clinical samples" for each drug (40 negative and 40 positive relative to cut-off). This was conducted "in-house." The provenance of the clinical samples is not specified beyond being "clinical samples."
Lay-user Study: 310 lay persons for each device format. The samples were prepared by spiking drugs into "drug free-pooled urine specimens." The concentrations were confirmed by LC/MS. Thus, the samples were prepared and not naturally occurring clinical samples.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts

For the Precision, Interference, Specificity, and Effect of Urine Specific Gravity and Urine pH Studies: The ground truth was established by precise laboratory preparation of samples where drug concentrations were known and confirmed by LC/MS. There were no human experts classifying these samples for ground truth.
For the Method Comparison Study: The ground truth was established by LC/MS results. LC/MS is a highly accurate and definitive analytical method. The text does not mention human experts establishing ground truth for these samples; it was based on the objective chemical analysis. The "three laboratory assistants" were operators performing the device tests, not establishing ground truth.
For the Lay-user Study: The ground truth was the known drug concentration of the prepared urine samples, confirmed by LC/MS.

4. Adjudication Method for the Test Set

Precision, Interference, Specificity, and Effect of Urine Specific Gravity and Urine pH Studies: No human adjudication was mentioned as the ground truth was based on precisely prepared samples with known concentrations.
Method Comparison Study: The device results were compared directly to LC/MS results. There was no adjudication mentioned involving human experts to reconcile discrepancies between device and LC/MS. Discrepancies were simply reported as "discordant results."
Lay-user Study: Comparisons were made against the known LC/MS confirmed concentrations of the prepared samples. No human adjudication was mentioned.

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 MRMC comparative effectiveness study was done. This device is a rapid diagnostic test (lateral flow immunoassay) for drug detection, where the "reading" is a visual interpretation of lines by a user (or laboratory assistant in the method comparison study). It does not appear to involve AI or sophisticated image analysis where human readers would be "assisted" by AI. The "lay-user study" involved multiple readers (310 lay persons), but it was designed to assess the ease of use and accuracy of the device itself by untrained individuals, not to compare human performance with and without AI assistance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done

This device is a lateral flow immunoassay intended for visual interpretation. It does not have an "algorithm only" component in the sense of a software-based AI system. Its performance inherently involves a "human-in-the-loop" to view and interpret the test lines.

7. The Type of Ground Truth Used

The primary ground truth used throughout the studies (precision, interference, specificity, method comparison, and lay-user study) was LC/MS (Liquid Chromatography/Mass Spectrometry), which is a definitive analytical method for confirming drug concentrations in urine samples. For analytical studies, ground truth was also established by careful preparation of samples with known drug concentrations.

8. The Sample Size for the Training Set

This document describes performance studies for an immunochromatographic assay, which is a chemical/biological test, not a machine learning or AI model. Therefore, there is no "training set" in the context of AI model development. The assays are "trained" during their manufacturing and chemical formulation processes to react at specific cut-off levels.

9. How the Ground Truth for the Training Set Was Established

As stated above, this device is not an AI/ML product and thus does not have a "training set" with ground truth in that context. The "training" of the assay refers to its inherent chemical design to react to certain drug concentrations, which relies on established analytical chemistry principles and known drug properties.

Summary

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May 27, 2020

Safecare Biotech (Hangzhou) Co., Ltd. % Joe Shia Manager LSI International 504 E Diamond Ave., Suite I Gaithersburg, MD 20877

Re: K201120

Trade/Device Name: SAFECARE® Multi-Drug Urine Test Dip Card SAFECARE® Multi-Drug Urine Test Cup Regulation Number: 21 CFR 862.3100 Regulation Name: Amphetamine Test System Regulatory Class: Class II Product Code: NFT, NFW, NFY, NGG, NGI, NFV, NGL, PTH, NGM, PTG, QAW, QBF Dated: April 23, 2020 Received: April 27, 2020

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

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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, 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

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Indications for Use

510(k) Number (if known) K201120

Device Name

SAFECARE® Multi-Drug Urine Test Dip Card SAFECARE® Multi-Drug Urine Test Cup

Indications for Use (Describe)

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	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
2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine	300 ng/mL

Configuration of SAFECARE® Multi-Drug Urine Test Dip Card can consist of any combination of the above listed drug analytes.

The test may yield positive results for the prescription drugs Buprenorphine, 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. The tests are intended for over-the-counter use.

Drug(Identifier)	Cut-off level
Amphetamine	1000 ng/mL
Oxazepam	300 ng/mL
FORM FDA 3881 (7/17)	Page 1 of 2

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Cocaine	300 ng/mL
Marijuana	50 ng/mL
Methamphetamine	1000 ng/mL
Morphine	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
2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine	300 ng/mL

Configuration of SAFECARE® Multi-Drug Urine Test Cup 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.

The tests are intended for over-the-counter use.

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)

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510(k) SUMMARY

510(k) Number: K201120

May 27, 2020 1. Date: Safecare Biotech (Hangzhou) Co. Ltd. 2. Submitter: 18 Haishu Road, Yuhang District Hangzhou, China 3. Contact person: Joe Shia LSI International Inc. 504E Diamond Ave., Suite I
Email: shiajl@yahoo.com SAFECARE® Multi-Drug Urine Test Dip Card 4. Device Name: SAFECARE® Multi-Drug Urine Test Cup

Gaithersburg, MD 20877 Telephone: 240-505-7880

Classification:

Class 2

Product Code	Classification	Regulation Section	Panel
NFTAmphetamine	II	21 CFR § 862.3100, Amphetamine Test System	Toxicology (91)
NFWCannabinoids	II	21 CFR § 862.3870, Cannabinoids Test System	Toxicology (91)
NFYCocaine	II	21 CFR § 862.3250, Cocaine and Cocaine Metabolites Test System	Toxicology (91)
NGGMethamphetamine	II	21 CFR § 862.3610, Methamphetamine Test System	Toxicology (91)
NGIMorphine	II	21 CFR § 862.3640, Morphine Test System	Toxicology (91)
NFVOxazepam	II	21 CFR § 862.3170, Benzodiazepine Test System	Toxicology (91)
NGLOxycodone	II	21 CFR § 862.3650, Opiate Test System	Toxicology (91)
PTHSecobarbital	II	21 CFR § 862.3150, Barbiturate Test 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 Immunoassay Phencyclidine	Toxicology (91)
PTGMethadone	II	21 CFR § 862.3620, Methadone Test System	Toxicology (91)
QAWNortriptyline	II	21 CFR, 862.3910 Tricyclic Antidepressant Drugs Test System	Toxicology (91)
QBFPropoxyphene	II	21 CFR, 862.3700 Propoxyphene Test System	Toxicology (91)

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Product Code	Classification	Regulation Section	Panel
PTG2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine	II	21 CFR § 862.3620, Methadone Test System	Toxicology(91)

1. Predicate Device
  The SAFECARE® Multi-Drug Urine Test Dip Card and SAFECARE® Multi-Drug Urine Test Cup (K182654)
1. Intended Use
  SAFECARE® Multi-Drug Urine Test Dip Card is 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 d-Propoxyphene and 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine (EDDP) 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	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
2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine	300 ng/mL

Configuration of SAFECARE® Multi-Drug Urine Test Dip Card 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. The tests are intended for over-the-counter use.

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Propoxyphene and 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine (EDDP) 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	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
2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine	300 ng/mL

Configuration of SAFECARE® Multi-Drug Urine Test Cup 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. The tests are intended for over-the-counter use.

7. Device Description

8. Substantial Equivalence Information

A summary comparison of features of the SAFECARE® Dip Card Tests and SAFECARE® Cup Tests and the predicate devices is provided in following tables.

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Table 1: Features Comparison of SAFECARE® Dip Card Tests and the Predicate Device

Item	Device	Predicate - K182654
Indication(s)for Use	For the qualitative determination of drugs ofabuse in human urine.	Same (but the number ofdrugs detected isdifferent)
	Similarities
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	Dip Card	Same
	Differences
Calibrator and Cut-OffValues	Amphetamine (AMP): 1,000 ng/mlOxazepam (BZO):300 ng/mlCocaine (COC): 300 ng/ml11-Nor-△9-Tetrahydrocannabinol-9-COOH(THC):50 ng/mlMethamphetamine (MET): 1,000 ng/mlMorphine (OPI): 2000ng/mlSecobarbital (BAR): 300 ng/mlMethadone (MTD): 300 ng/mlMethylenedioxymethamphetamine(MDMA): 500 ng/mlOxycodone (OXY): 100 ng/mlBuprenorphine (BUP): 10 ng/mlPhencyclidine (PCP): 25 ng/mlNortriptyline (TCA): 1000 ng/mlPropoxyphene (PPX): 300 ng/ml2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine (EDDP): 300 ng/mL	Same as candidate devicewith exclusion of 2-ethylidene-1, 5-dimethyl-3,3-diphenylpyrrolidine(EDDP): 300 ng/mL

Table 2: Features Comparison of SAFECARE® Cup Tests and the Predicate Devices

Item	Device	Predicate - K182654
Indication(s)for Use	For the qualitative determination ofdrugs of abuse in human urine.	Same (but the number ofdrugs detected is different)
Similarities

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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	Cup
	Differences
Calibrator and Cut-OffValues	Amphetamine (AMP): 1,000 ng/mlOxazepam (BZO):300 ng/mlCocaine (COC): 300 ng/ml11-Nor-△9-Tetrahydrocannabinol-9-COOH(THC):50 ng/mlMethamphetamine (MET): 1,000 ng/mlMorphine (OPI): 2000ng/mLSecobarbital (BAR): 300 ng/mlMethadone (MTD): 300 ng/mlMethylenedioxymethamphetamine(MDMA): 500 ng/mlOxycodone (OXY): 100 ng/mlBuprenorphine (BUP): 10 ng/mlPhencyclidine (PCP): 25 ng/mlNortriptyline (TCA): 1000 ng/ml	Same as candidate devicewith exclusion of 2-ethylidene-1, 5-dimethyl-3,3-diphenylpyrrolidine(EDDP): 300 ng/mL
	Propoxyphene (PPX): 300 ng/ml2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine (EDDP): 300ng/mL

9. Test Principle

The SAFECARE® Dip Card Tests, and SAFECARE® Cup Tests are rapid tests for the qualitative detection of Amphetamine, Oxazepam, Cocaine, Cannabinoids, Methamphetamine, Morphine, Secobarbital, Methadone, Methylenedioxymethamphetamine, Oxycodone, Buprenorphine, Phencyclidine, Nortriptyline, Propoxyphen and 2-ethylidene-1, 5-dimethyl-3, 3diphenylpyrrolidine 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 antibody-coated 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

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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 performed properly.

1. Performance Characteristics
- 1. 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. 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 tables for 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine. Please refer to K182654 for precision data for Methylenedioxy-Methamphetamine, Oxycodone, Buprenorphine, Phencyclidine, Nortriptyline and Propoxyphene, and to K181968 for precision data for Oxazepam, Methamphetamine, Morphine, Secobarbital and Methadone, and to K153646 for precision data for Amphetamine, Cocaine, and Cannabinoids.

Dip Card
ResultsLot Number	-100% Cut-off	-75% Cut-off	-50% Cut-off	-25% Cut-off	Cut-off	Cut-off +25%	Cut-off +50%	Cut-off +75%	Cut-off +100%
Lot 1	50-/0+	50-/0+	50-/0+	50-/0+	24-/26+	50+/0-	50+/0-	50+/0-	50+/0-
Lot 2	50-/0+	50-/0+	50-/0+	50-/0+	25-/25+	50+/0-	50+/0-	50+/0-	50+/0-
Lot 3	50-/0+	50-/0+	50-/0+	50-/0+	26-/24+	50+/0-	50+/0-	50+/0-	50+/0-

2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine

Cup
Results
LotNumber	-100%Cut-off	-75%Cut-off	-50%Cut-off	-25%Cut-off	Cut-off	Cut-off+25%	Cut-off+50%	Cut-off+75%	Cut-off+100%
Lot 1	50-/0+	50-/0+	50-/0+	50-/0+	27-/23+	50+/0-	50+/0-	50+/0-	50+/0-
Lot 2	50-/0+	50-/0+	50-/0+	50-/0+	24-/26+	50+/0-	50+/0-	50+/0-	50+/0-
Lot 3	50-/0+	50-/0+	50-/0+	50-/0+	26-/24+	50+/0-	50+/0-	50+/0-	50+/0-

The cut-off value of 300 ng/mL for 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine is verified.

b. Linearity

Not applicable.

c. Stability
The devices are stable at 4-30 ℃ for 24 months based on the accelerated stability study at 50 °C and real time stability studies at 4°C and 30 °C.
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 each device. Compounds that showed no interference at a concentration

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of 100ug/mL. with the exception of albumin with no interference at a concentration of 100mg/dL and ethanol at 1% volume, are summarized in the following tables. There were no differences observed between the SAFECARE® Cup and Dip Card formats.

Acetominophen (4-Acetamidophenol)	Ecgonine methyl ester	D,L-Octopamine
Acetophenetidin	Erythromycin	Oxalic acid
N-Acetylprocainamide	ẞ-Estradiol	Oxolinic acid
Acetylsalicylic acid	Ethanol (1% vol)	Oxymetazoline
Albumin (100mg/dL)	Fenoprofen	Papaverine
Aminopyrine	Furosemide	Penicillin-G
Amoxicillin	Gentisic acid	Perphenazine
Ampicillin	Hemoglobin	Phenelzine
Apomorphine	Hydralazine	Prednisone
Ascorbic acid	Hydrochlorothiazide	DL-Propranolol
Aspartame	Hydrocortisone	D-Pseudoephedrine
Atropine	O-Hydroxyhippuric acid	Quinine
Benzilic acid	3-Hydroxytyramine	Ranitidine
Benzoic acid	Ibuprofen	Salicylic acid
Bilirubin	D,L-Isoproterenol	Serotonin (5- Hydroxytyramine)
Chloralhydrate	Isoxsuprine	Sulfamethazine
Chloramphenicol	Ketamine	Sulindac
Chlorothiazide	Ketoprofen	Tetrahydrocortisone, 3-acetate
Chlorpromazine	Labetalol	Tetrahydrocortisone 3-(β-Dglucuronide)
Cholesterol	Loperamide	Tetrahydrozoline
Clonidine	Meperidine	Thiamine
Cortisone	Meprobamate	Thioridazine
(-) Cotinine	Methoxyphenamine	Triamterene
Creatinine	Nalidixic acid	DL-Tyrosine
Deoxycorticosterone	Naloxone	Trifluoperazine
Dextromethorphan	Naltrexone	Trimethoprim
Diclofenac	Naproxen	D,L-Tryptophan
Diflunisal	Niacinamide	Tyramine
Digoxin	Nifedipine	Uric acid
Diphenhydramine	Norethindrone	Verapamil
Disopyramide	Noscapine	Zomepirac

e. Specificity

To test specificity, drug metabolites and other structure related compounds that are likely to cross-react 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 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine. The rest of the data were in K182654 for for Methylenedioxy-Methamphetamine, Oxycodone, reported Buprenorphine, Phencyclidine, Nortriptyline and Propoxyphene, and K181968 for Amphetamine, Oxazepam, Cocaine, Cannabinoids, Methamphetamine, Morphine, Secobarbital and Methadone. There were no differences observed between the SAFECARE® Cup and Dip Card formats.

Compounds	ResultPositive at(ng/ml)	% Cross-Reactivity
Methadone	300000	0.1%

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EMDP	300000	0.1%
Doxylamine	>100,000	<0.3%
Disopyramide	>100,000	<0.3%
LAAM (Levo-alpha-acetylmethadol) HCl	>100,000	<0.3%
Alpha Methadol	>100,000	<0.3%

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 between the SAFECARE® Cup and Dip Card formats.

2. Comparison Studies

Method comparison studies for the SAFECARE® Dip Card Tests and the SAFECARE® Cup Tests were performed in-house 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 are presented in the tables below for 2ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine (EDDP). The rest data were reported in K182654 for Methylenedioxy-Methamphetamine, Oxycodone, Buprenorphine, Phencyclidine, Nortriptyline and Propoxyphene, and in K181968 for Amphetamine, Oxazepam, Cocaine, Cannabinoids, Methamphetamine, Morphine, Secobarbital and Methadone.

DipCard		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%)
ViewerA	Positive	0	0	1	20	20
	Negative	10	10	19	0	0
ViewerB	Positive	0	0	0	19	20
	Negative	10	10	20	1	0
ViewerC	Positive	0	0	0	20	20
	Negative	10	10	20	0	0

EDDP

Discordant Results

Viewer	Sample Number	LC/MS Result	Dip Card Viewer Results
Viewer A	CM2632	291	Positive
Viewer B	CM9474	309	Negative

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Cup		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	1	20	20
A	Negative	10	10	19	0	0
Viewer	Positive	0	0	0	19	20
B	Negative	10	10	20	1	0
Viewer	Positive	0	0	0	20	20
C	Negative	10	10	20	0	0

Discordant Results

Viewer	Sample Number	LC/MS Result	CupViewer Results
Viewer A	CM1684	285	Positive
Viewer B	CM2850	372	Negative

Lay-user study:

A lay user study was performed at three intended user sites with 310 lay persons for each device format. 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. Typical results are shown below.

% of Cutoff	Number ofsamples	DrugConcentration byLC/MS (ng/mL)	Lay person Results	No. ofPositive
-100% Cutoff	20	0	0	20	100
-75% Cutoff	20	253	0	20	100
-50% Cutoff	170	496	0	170	100
-25% Cutoff	20	753	2	18	90
+25% Cutoff	20	1249	17	3	85
+50% Cutoff	40	1498	40	0	100
+75% Cutoff	20	1758	20	0	100

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COC:

% of Cutoff	Number ofsamples	DrugConcentration byLC/MS(ng/mL)	Lay person Results		The percentageof correctresults (%)
			No. ofPositive	No. ofNegative
-100% Cutoff	20	0	0	20	100
-75% Cutoff	20	76	0	20	100
-50% Cutoff	170	147	0	170	100
-25% Cutoff	20	226	1	19	95
+25% Cutoff	20	372	18	2	90
+50% Cutoff	40	449	40	0	100
+75% Cutoff	20	524	20	0	100

THC:

% of Cutoff	Number ofsamples	DrugConcentration byLC/MS(ng/mL)	Lay person Results		The percentage
			No. ofPositive	No. ofNegative	of correct results(%)
-100% Cutoff	20	0	0	20	100
-75% Cutoff	20	12	0	20	100
-50% Cutoff	170	24	0	170	100
-25% Cutoff	20	36	1	19	95
+25% Cutoff	20	63	18	2	90
+50% Cutoff	40	75	40	0	100
+75% Cutoff	20	88	20	0	100

BAR:

% of Cutoff	Number ofsamples	DrugConcentration byLC/MS(ng/mL)	Lay person Results		The percentageof correct results(%)
			No. ofPositive	No. ofNegative
-100% Cutoff	20	0	0	20	100
-75% Cutoff	20	76	0	20	100
-50% Cutoff	170	147	0	170	100
-25% Cutoff	20	225	1	19	95
+25% Cutoff	20	374	18	2	90
+50% Cutoff	40	449	40	0	100
+75% Cutoff	20	524	20	0	100

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% of Cutoff	Number ofsamples	DrugConcentration byLC/MS(ng/mL)	Lay person Results		The percentageof correct results(%)
			No. ofPositive	No. ofNegative
-100% Cutoff	20	0	0	20	100
-75% Cutoff	20	76	0	20	100
-50% Cutoff	170	147	0	170	100
-25% Cutoff	20	227	1	19	95
+25% Cutoff	20	374	19	1	95
+50% Cutoff	40	450	40	0	100
+75% Cutoff	20	526	20	0	100

BZO:

MET:

% of Cutoff	Number ofsamples	DrugConcentration byLC/MS(ng/mL)	Lay person Results		The percentage
			No. ofPositive	No. ofNegative	of correct results(%)
-100% Cutoff	20	0	0	20	100
-75% Cutoff	20	248	0	20	100
-50% Cutoff	170	497	0	170	100
-25% Cutoff	20	749	1	19	95
+25% Cutoff	20	1251	18	2	90
+50% Cutoff	40	1499	40	0	100
+75% Cutoff	20	1754	20	0	100

MTD:

% of Cutoff	Number ofsamples	DrugConcentration byLC/MS(ng/mL)	Lay person Results		The percentage
			No. ofPositive	No. ofNegative	of correct results(%)
-100% Cutoff	20	0	0	20	100
-75% Cutoff	20	76	0	20	100
-50% Cutoff	170	147	0	170	100
-25% Cutoff	20	223	1	19	95
+25% Cutoff	20	374	17	3	85
+50% Cutoff	40	450	40	0	100
+75% Cutoff	20	526	20	0	100

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% of Cutoff	Number of samples	Drug Concentration by LC/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	501	0	20	100
-50% Cutoff	170	999	0	170	100
-25% Cutoff	20	1501	1	19	95
+25% Cutoff	20	2499	19	1	95
+50% Cutoff	40	2999	40	0	100
+75% Cutoff	20	3501	20	0	100

MDMA:

% of Cutoff	Number ofsamples	DrugConcentration byLC/MS(ng/mL)	Lay person Results		The percentageof correct results(%)
			No. ofPositive	No. ofNegative
-100% Cutoff	20	0	0	20	100
-75% Cutoff	20	126	0	20	100
-50% Cutoff	170	248	0	170	100
-25% Cutoff	20	375	1	19	95
+25% Cutoff	20	624	18	2	90
+50% Cutoff	40	748	40	0	100
+75% Cutoff	20	877	20	0	100

OXY:

% of Cutoff	Number ofsamples	DrugConcentration byLC/MS(ng/mL)	Lay person Results		The percentageof correct results(%)
			No. ofPositive	No. ofNegative
-100% Cutoff	20	0	0	20	100
-75% Cutoff	20	25	0	20	100
-50% Cutoff	170	48	0	170	100
-25% Cutoff	20	74	1	19	95
+25% Cutoff	20	126	18	2	90
+50% Cutoff	40	150	40	0	100
+75% Cutoff	20	176	20	0	100

OPI:

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BUP:

% of Cutoff	Number ofsamples	DrugConcentration byLC/MS(ng/mL)	Lay person Results		The percentageof correct results(%)
			No. ofPositive	No. ofNegative
-100% Cutoff	20	0	0	20	100
-75% Cutoff	20	3	0	20	100
-50% Cutoff	170	5	0	170	100
-25% Cutoff	20	8	2	18	90
+25% Cutoff	20	13	18	2	90
+50% Cutoff	40	15	40	0	100
+75% Cutoff	20	18	20	0	100

PCP:

% of Cutoff	Number ofsamples	DrugConcentration byLC/MS(ng/mL)	Lay person Results		The percentageof correct results(%)
			No. ofPositive	No. ofNegative
-100% Cutoff	20	0	0	20	100
-75% Cutoff	20	6	0	20	100
-50% Cutoff	170	12	0	170	100
-25% Cutoff	20	19	2	18	90
+25% Cutoff	20	32	18	2	90
+50% Cutoff	40	37	40	0	100
+75% Cutoff	20	43	20	0	100

TCA:

% of Cutoff	Number ofsamples	DrugConcentration byLC/MS(ng/mL)	Lay person Results		The percentageof correct results(%)
			No. ofPositive	No. ofNegative
-100% Cutoff	20	0	0	20	100
-75% Cutoff	20	250	0	20	100
-50% Cutoff	170	497	0	170	100
-25% Cutoff	20	750	1	19	95
+25% Cutoff	20	1249	18	2	90
+50% Cutoff	40	1500	40	0	100
+75% Cutoff	20	1749	20	0	100

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% of Cutoff	Number ofsamples	DrugConcentration byLC/MS(ng/mL)	Lay person Results		The percentageof correct results(%)
			No. ofPositive	No. ofNegative
-100% Cutoff	20	0	0	20	100
-75% Cutoff	20	76	0	20	100
-50% Cutoff	170	148	0	170	100
-25% Cutoff	20	223	3	17	85
+25% Cutoff	20	374	18	2	90
+50% Cutoff	40	448	40	0	100
+75% Cutoff	20	525	20	0	100

PPX:

EDDP:

% of Cutoff	Number ofsamples	DrugConcentration byLC/MS(ng/mL)	Lay person Results		The percentage
			No. ofPositive	No. ofNegative	of correct results(%)
-100% Cutoff	20	0	0	20	100
-75% Cutoff	20	76	0	20	100
-50% Cutoff	170	152	0	170	100
-25% Cutoff	20	226	1	19	95
+25% Cutoff	20	375	18	2	90
+50% Cutoff	40	452	40	0	100
+75% Cutoff	20	526	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.

1. 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 devices, it's concluded that the SAFECARE® Dip Card Tests and SAFECARE® Cup Tests are substantially equivalent to the predicate.

Regulation Number and Section

§ 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).