SAFECARE Fentanyl Urine Test Cassette is a competitive binding, lateral flow immunochromatographic assay for qualitative detection of fentanyl in human urine at the cutoff concentrations of 1 ng/mL. 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 test is intended for over-the-counter use and for in vitro diagnostic use only.

Device Description

The SAFECARE Fentanyl Urine Tests are immunoassays intended for the qualitative detection of fentanyl in human urine. Each SAFECARE Fentanyl Urine Test device consists of a Test Cassette, a Dropper and a package insert. Each Test Cassette is sealed with sachets of desiccant in an aluminum pouch.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the SAFECARE Fentanyl Urine Test Cassette, based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" percentages (e.g., "must achieve X% sensitivity"). Instead, it presents performance data that implies the device met sufficient standards for clearance. The "performance" column below summarizes the key findings.

Category	Description of Performance (Implicit Acceptance Criteria)	Reported Device Performance
Precision	Demonstrate consistent and accurate results across different concentrations relative to the cutoff, ideally showing 100% agreement for concentrations significantly below or above the cutoff, and a mix around the cutoff.	Lot 1: 100% negative for -100%, -75%, -50% cutoff; 98% negative (1 positive) for -25% cutoff; 52% positive/48% negative for cutoff; 100% positive for +25%, +50%, +75%, +100% cutoff. Lot 2: 100% negative for -100%, -75%, -50% cutoff; 98% negative (1 positive) for -25% cutoff; 50% positive/50% negative for cutoff; 100% positive for +25%, +50%, +75%, +100% cutoff. Lot 3: 100% negative for -100%, -75%, -50% cutoff; 96% negative (2 positive) for -25% cutoff; 54% positive/46% negative for cutoff; 100% positive for +25%, +50%, +75%, +100% cutoff.
Stability	Device must remain functional and accurate for a specified shelf life under defined storage conditions.	Devices are stable for 24 months at 36-86°F based on accelerated stability studies.
Interference	No interference from a list of common physiological, pathological, or drug substances at specified concentrations when fentanyl is absent or at known concentrations (50% below/above cutoff).	No interference observed from a comprehensive list of compounds (e.g., Acetaminophen, Albumin, Glucose, Ibuprofen, Nicotine) at 100µg/mL or specified concentrations when fentanyl was at ±50% cutoff levels.
Specificity (Cross-Reactivity)	Minimal to no cross-reactivity with structurally similar compounds or other common opioids/drugs, especially for compounds listed as "no cross-reactivity." For fentanyl analogs, a defined cross-reactivity profile.	Detected various fentanyl analogs with varying cross-reactivity percentages (e.g., Acetyl fentanyl: 100%, Ocfentanil: 40%). Showed no cross-reactivity for a list of over 30 opioid compounds (e.g., Codeine, Morphine, Buprenorphine) tested at 100 µg/mL.
Effect of Urine Specific Gravity & pH	Device performance should not be significantly affected by variations in urine specific gravity (1.000-1.035) or pH (4-9) at critical fentanyl concentrations (50% below and 50% above cutoff).	All results were positive for samples at and above +50% Cut-Off and all negative for samples at and below -50% Cut-Off, regardless of specific gravity or pH within the tested ranges.
Method Comparison (Clinical Samples)	Demonstrated agreement with a confirmatory method (LC/MS) for both negative and positive clinical urine samples across a range of fentanyl concentrations, including those near the cutoff. A low number of discordant results is expected, especially near the cutoff.	Operator 1: - 39/40 (97.5%) agreement for Negative/Low Negative/Near Cutoff Negative. - 38/40 (95%) agreement for Near Cutoff Positive/High Positive. - Discordant (1 positive at 0.985 ng/mL LC/MS; 2 negative at 1.055 and 1.097 ng/mL LC/MS). Operator 2: - 40/40 (100%) agreement for Negative/Low Negative/Near Cutoff Negative. - 39/40 (97.5%) agreement for Near Cutoff Positive/High Positive. - Discordant (2 positive at 0.954 and 0.993 ng/mL LC/MS; 1 negative at 1.055 ng/mL LC/MS). Operator 3: - 40/40 (100%) agreement for Negative/Low Negative/Near Cutoff Negative. - 39/40 (97.5%) agreement for Near Cutoff Positive/High Positive. - Discordant (2 positive at 0.980 and 0.985 ng/mL LC/MS; 1 negative at 1.055 ng/mL LC/MS).
Lay-User Study	High percentage of correct results by lay users when following instructions, particularly for concentrations clearly below or above the cutoff. User instructions should be easily understood.	Correct result percentages: 100% for -100%, -75%, -50% cutoff; 95% for -25% cutoff; 100% for +25%, +50%, +75% cutoff. All lay users indicated instructions were easily followed. Flesch-Kincaid score indicated reading grade level < 7.

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

Precision Studies:
- Test Set Size: For each of 3 lots, 50 tests were performed at each of 9 concentrations (-100%, -75%, -50%, -25%, cutoff, +25%, +50%, +75%, +100%). This totals 3 lots * 9 concentrations * 50 tests/concentration = 1350 tests.
- Data Provenance: Samples were prepared by spiking fentanyl into negative samples. The document does not specify the origin of the "negative samples." It states the fentanyl concentration was confirmed by LC/MS.
Interference & Specificity Studies:
- Test Set Size: Not explicitly stated as a number of individual tests, but each interfering substance/cross-reactant was tested using "three batches of each device" with drug-free urine and target drug fentanyl urine (at ±50% cutoff).
- Data Provenance: Samples were prepared by spiking test substances into drug-free urine or urine containing fentanyl.
Effect of Urine Specific Gravity and Urine pH:
- Test Set Size: Not explicitly stated as an exact number of tests, but samples within specific gravity (1.000-1.035) and pH (4-9) ranges were spiked with fentanyl at 50% below and 50% above cutoff. These were then tested using "three lots of device."
- Data Provenance: Samples were prepared by altering the specific gravity/pH and spiking fentanyl into urine.
Method Comparison (Clinical Samples):
- Test Set Size: 80 unaltered clinical samples (40 negative and 40 positive).
- Data Provenance: "Unaltered clinical samples" - implies naturally occurring samples from a clinical population. The country of origin is not specified, but it's generally understood to be within the scope of where such tests would be used.
Lay-user Study:
- Test Set Size: 140 lay persons, each testing one blind-labeled sample. A total of 140 tests were performed. The samples themselves were 20 for each of 7 concentrations (-100%, -75%, -50%, -25%, +25%, +50%, +75% cutoff), so 7 * 20 = 140 unique prepared samples were used.
- Data Provenance: Samples were prepared by spiking fentanyl into "drug free-pooled urine specimens."

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

Method Comparison (Clinical Samples): The ground truth was established by LC/MS (Liquid Chromatography/Mass Spectrometry), which is a highly accurate and routinely used laboratory method for drug confirmation. This is a scientific instrument, not an "expert" in the human sense. The operators running the LC/MS would be trained laboratory personnel.
Precision, Interference, Specificity, Effect of Urine Specific Gravity & pH, Lay-User Study: For these studies, the "ground truth" was established by spiking known concentrations of fentanyl (or other substances) into urine samples and confirming by LC/MS. This process relies on the accuracy of the LC/MS method and the precision of the spiking process.

4. Adjudication Method for the Test Set

Method Comparison (Clinical Samples): The document states samples were "blind labeled" and compared directly to "LC/MS results." This implies a direct comparison without an explicit adjudication process involving multiple human readers beyond the initial device reading by each of the three operators. Discordant results were simply listed for each operator.
Lay-user Study: Samples were "blind-labeled and randomized." Each participant provided a result, which was then compared to the known LC/MS-confirmed concentration. There was no mention of an adjudication process among lay users or reviewers.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No MRMC comparative effectiveness study was done comparing human performance with and without AI assistance.
This device is a rapid diagnostic test (lateral flow immunoassay), not an AI-powered diagnostic imaging or interpretation system. Therefore, an MRMC study in the context of AI assistance is not applicable. The study involved three operators for the method comparison and 140 lay users for usability, but these were for direct device performance and ease of use, not AI-assisted interpretation.

6. Standalone Performance

Yes, a standalone (algorithm only without human-in-the-loop) performance study was done implicitly. This device is the standalone "algorithm" (the immunoassay itself). The precision, interference, and specificity studies evaluate the inherent performance of the device without a human interpreting a complex image or data set. The human involvement is limited to performing the test procedure and reading a clear positive/negative line, which is a direct output of the device's chemistry.

7. The Type of Ground Truth Used

LC/MS (Liquid Chromatography/Mass Spectrometry): This was the primary method used to establish the ground truth for all studies involving fentanyl concentrations (precision, method comparison, lay-user study, and confirming spiked concentrations for interference/specificity/pH/SG studies). LC/MS is a highly accurate and quantitative analytical chemistry technique considered the "gold standard" for confirming drug concentrations in toxicology.

8. The Sample Size for the Training Set

This document describes performance studies for a finished medical device (an immunoassay rapid test). Immunochromatographic assays do not have a "training set" in the machine learning sense. Their performance is inherent to their design, reagents, and manufacturing process. Therefore, there is no training set mentioned or applicable for this type of device.

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

As there is no "training set" for this type of device, this question is not applicable. The "ground truth" (LC/MS confirmation) is used for validation of the device's performance, not for training it.

Summary

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left, there is a symbol representing the Department of Health & Human Services USA. To the right of the symbol, there is the FDA logo in blue, with the words "U.S. FOOD & DRUG" stacked on top of the word "ADMINISTRATION."

Safecare Biotech (Hangzhou) Co., Ltd. % Joe Shia Director LSI International Inc 504E Diamond Ave., Suite H Gaithersburg, Maryland 20877

Re: K240654

Trade/Device Name: SAFECARE Fentanyl Urine Test Cassette; SAFECARE FYL Urine Test Cassette Regulation Number: 21 CFR 862.3650 Regulation Name: Opiate test system Regulatory Class: Class II Product Code: NGL Dated: March 2, 2024 Received: March 7, 2024

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 (the 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 available 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming

{1}------------------------------------------------

product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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.

Joseph A.
Kotarek -S

Digitally signed by Joseph A. Kotarek -S Date: 2024.04.10 16:06:14 -04'00'

Joseph Kotarek Branch Chief for Toxicology Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

Indications for Use

510(k) Number (if known) K240654

Device Name SAFECARE Fentanyl Urine Test Cassette SAFECARE FYL Urine Test Cassette

Indications for Use (Describe)

SAFECARE FYL Urine Test Cassette is a competitive binding, lateral flow immunochromatographic assay for qualitative detection of fentanyl in human urine at the cutoff concentrations of 1 ng/mL.

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.

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.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

510(k) SUMMARY K240654

1. Date:	April 8, 2024
2. Submitter:	Safecare Biotech (Hangzhou) Co. Ltd.18 Haishu Road, Yuhang DistrictHangzhou, China
3. Contact person:	Joe ShiaLSI International Inc.504E Diamond Ave., Suite HGaithersburg, MD 20877Telephone: 240-505-7880Email: shiajl@yahoo.com
4. Device Names:	SAFECARE Fentanyl Urine Test CassetteSAFECARE FYL Urine Test Cassette

Classification:	Class 2
Product Code	Classification	Regulation Section	Panel
NGL	II	21 CFR § 862.3650Opiate Test System	Toxicology (91)

1. Predicate Devices:
  AllTest Fentanyl Urine Test Cassette (K233417)
1. Indications for Use
  SAFECARE Fentanyl Urine Test Cassette is a competitive binding, lateral flow immunochromatographic assay for qualitative detection of fentanyl in human urine at the cutoff concentrations of 1 ng/mL.

The test is intended for over-the-counter use and for in vitro diagnostic use only.

SAFECARE FYL Urine Test Cassette is a competitive binding, lateral flow immunochromatographic assay for qualitative detection of fentanyl in human urine at the cutoff concentrations of 1 ng/mL.

1. Device Description
  The SAFECARE Fentanyl Urine Tests are immunoassays intended for the qualitative detection of fentanyl in human urine. Each SAFECARE Fentanyl Urine Test device consists of a Test Cassette, a Dropper and a package insert. Each Test Cassette is sealed with sachets of desiccant in an aluminum pouch.
1. Substantial Equivalence Information

{4}------------------------------------------------

A summary comparison of features of the SAFECARE Fentanyl Test and the predicate devices is provided in following table.

Item	Device	Predicate – K233417
Indication(s)for Use	For the qualitative determination offentanyl in human urine.	Same
Calibrator and Cut-OffValues	Fentanyl (FTY)1 ng/ml	Same
Methodology	Competitive binding, lateral flowimmunochromatographic assays basedon the principle of antigen antibodyimmunochemistry.	Same
Type of Test	Qualitative	Same
Specimen Type	Human Urine	Same
Intended Use	For OTC use	Same
Configurations	Cassette	Same
Storage	4-30°C	Same

Table 1: Features Comparison of SAFECARE Fentanyl Urine Test and the Predicate Device

9. Test Principle

The SAFECARE Fentanyl Urine Tests are immunoassays based on the principle of competitive binding.

During testing, a urine specimen migrates upward by capillary action. Fentanyl, if present in the urine specimen below 1 ng/mL, will not saturate the binding sites of antibody-coated particles in the test device. The antibody-coated particles will then be captured by immobilized fentanyl 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 fentanyl level exceeds 1 ng/mL because it will saturate all the binding sites of anti-fentanyl antibodies.

To serve as a procedural control, a colored line will always appear at the control line region indicating that proper volume of specimen has been added and membrane wicking has occurred.

10. Performance Characteristics

1. Analytical Performance
- Precision a.

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 fentanyl in negative samples. Each fentanyl 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 tests per day for 25 days per device lot in a randomized order.

{5}------------------------------------------------

LotNumber	-100%cut off	-75%cut off	-50%cut off	-25%cutoff	cut off	+25%cut off	+50%cut off	+75%cut off	+100%cut off
Lot 1	50-/0+	50-/0+	50-/0+	49-/1+	26+/24-	50+/0-	50+/0-	50+/0-	50+/0-
Lot 2	50-/0+	50-/0+	50-/0+	49-/1+	25+/25-	50+/0-	50+/0-	50+/0-	50+/0-
Lot 3	50-/0+	50-/0+	50-/0+	48-/2+	27+/23-	50+/0-	50+/0-	50+/0-	50+/0-

c. Stability

The devices are stable at 36-86F for 24 months based on the accelerate stability study.

d. Interference

Potential interfering substances found in human urine of physiological or pathological conditions were added to drug-free urine and target drug fentanyl urine with concentrations at 50% below and 50% above Cut-Off levels. These urine samples were tested using three batches of each device. Compounds that showed no interference at a concentration of 100µg/mL or specified concentrations are summarized in the following tables.

Acetaminophen	Doxepin	Nortriptyline
Acetone (1000 mg/dL)	Ecgonine methyl ester	Noscapine
Acetophenetidin	Ephedrine	O-Hydroxyhippuric acid
Acetylsalicylic acid	Erythromycin	Octopamine
Albumin (100 mg/dL)	Ethanol (1%)	Oxalic acid (100 mg/dL)
Albuterol	Fenoprofen	Oxazepam
Aminopyrine	Fluphenazine	Oxolinic acid
Amitriptyline	Furosemide	Oxymetazoline
Amobarbital	Galactose (10 mg/dL)	Papaverine
Amoxicillin	Gamma globulin (500 mg/dL)	Penicillin G
Ampicillin	Gentisic acid	Perphenazine
Apomorphine	Glucose (3000 mg/dL)	Phencyclidine
Ascorbic Acid	Hemoglobin	Phenelzine
Aspartame	Hydralazine	Phenobarbital
Atropine	Hydrochlorothiazide	Prednisone
Benzilic acid	Hydrocortisone	Propoxyphene
Benzoic acid	Hydroxytyramine	Propranolol
Benzoylecgonine	Ibuprofen	Pseudoephedrine
Bilirubin	Imipramine	Quinine
Boric acid (1% w/v)	Isoproterenol	Ranitidine
Bupropion	Isoxsuprine (10ug/mL)	Riboflavin (10 mg/dL)
Caffeine	Ketamine	Salicylic acid
Carbamazepine	Ketoprofen	Secobarbital
Chloral hydrate	Labetalol	Serotonin (5-hydroxytyramine)
Chloramphenicol	Lidocaine	Sulfamethazine
Chlorothiazide	Loperamide	Sulindac
Chlorpromazine	Maprotiline	Tetrahydrocortisone 3-(β-Dglucuronide)
Cholesterol	Meperidine	Tetrahydrocortisone 3-acetate
Clomipramine	Meprobamate	Tetrahydrozoline
Clonidine	Methapyrilene	Thiamine
Cortisone	Methaqualone	Thioridazine
Cotinine	Methoxyphenamine	Triamterene
Creatinine	Metronidazole (300 ug/mL)	Trifluoperazine

{6}------------------------------------------------

Cyclobenzaprine	N-Acetylprocainamide	Trimethoprim
Deoxycorticosterone	NaCl (4000 mg/dL)	Tyramine
Desipramine	Nalidixic acid	Urea (2000 mg/dL)
Dextromethorphan	Naloxone	Uric acid
Diclofenac	Naltrexone	Valproic acid (250 ug/mL)
Diflunisal	Naproxen	Venlafaxine
Digoxin	Niacinamide	Verapamil
Diphenhydramine	Nicotine	Zomepirac
DL-Tryptophan	Nifedipine	B-Estradiol
DL-Tyrosine	Norethindrone

e. Specificity

To test specificity, drug metabolites and other components that are likely to interfere in urine samples were tested using three batches of device. The lowest concentration that caused a positive result for each compound are listed below.

Fentanyl (Cutoff=1ng/mL)	Minimumconcentration requiredto obtain a positiveresult (ng/mL)	% Cross-Reactivity
Acetyl fentanyl	1	100
Acrylfentanyl	10	10
ω-1-Hydroxyfentanyl	20000	0.005
Isobutyryl fentanyl	10	10
Ocfentanil	2.5	40
Butyryl fentanyl	10	10
Furanyl fentanyl	10	10
Valeryl fentanyl	10	10
(±) β-hydroxythiofentanyl	6	16.7
4-Fluoro-isobutyrylfentanyl	50	2
Para-fluorobutyryl fentanyl	20	5
Para-fluoro fentanyl	3	33.3
(±)-3-cis-methyl fentanyl	50	2
Carfentanil	2	50
Sufentanil	7.5	13.3
Alfentanil	500	0.2
Despropionyl fentanyl (4-ANPP)	2500	0.04
Remifentanil	100	1
Norfentanyl	2000	0.05
Acetyl norfentanyl	>100000	/
Norcarfentanil	>100000	/
Trazodone	>100000	/

The following opioids compounds were tested at a concentration of 100ug/mL. Negative results were obtained for all these compounds. There is no cross-reactivity for these compounds using the SAFECARE Fentanyl Test.

6-Acetyl morphine	Naltrexone
Amphetamine	Norbuprenorphine
Buprenorphine	Norcodeine

{7}------------------------------------------------

Buprenorphineglucuronide	Norketamine
Codeine	Normeperidine
Dextromethorphan	Normorphine
Dihydrocodeine	Noroxycodone
EDDP	Oxycodone
EMDP	Oxymorphone
Fluoxetine	Pentazocine (Talwin)
Heroin	Pipamperone
Hydrocodone	Risperidone
Hydromorphone	Tapentadol
Ketamine	Thioridazine
Levorphanol	Tilidine
Meperidine	Tramadol
Methadone	Tramadol-O-Desmethyl
Morphine	Tramadol-N-Desmethyl
Morphine-3-glucuronide
Naloxone

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 fentanyl at 50% below and 50% above Cut-Off levels. These samples were tested using three lots of device. Results were all positive for samples at and above +50% Cut-Off and all negative for samples at and below -50% Cut-Off.

2. Comparison Studies

Method comparison studies for the SAFECARE Fentanyl Urine Test were performed by three different operators. Operators ran 80 (40 negative and 40 positive) unaltered clinical samples. The samples were blind labeled and compared to LC/MS results. The results are presented in the tables below.

		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%)
Operator	Positive	0	0	1	18	20
1	Negative	10	10	19	2	0
Operator	Positive	0	0	2	19	20
2	Negative	10	10	18	1	0
Operator	Positive	0	0	2	19	20
3	Negative	10	10	18	1	0

Discordant Results
Operator	Sample ID	LC/MS Result (ng/mL)	Rapid Test Result
Operator 1	FM157	0.985	Positive
Operator 1	FM152	1.055	Negative

{8}------------------------------------------------

Operator 1	FM212	1.097	Negative
Operator 2	FM083	0.954	Positive
Operator 2	FM024	0.993	Positive
Operator 2	FM152	1.055	Negative
Operator 3	FM179	0.980	Positive
Operator 3	FM157	0.985	Positive
Operator 3	FM152	1.055	Negative

3. Lay-user study

A lay user study was performed at three testing sites with 140 lay persons. They had diverse educational and professional backgrounds and ranged in age from 20 to >50 years. Urine samples were prepared at the following concentrations; -100%, +/-50%, +/-50%, +/-25% of the cut-off by spiking fentanyl into drug free-pooled urine specimens. The concentrations of the samples were confirmed by LC/MS. Each sample was aliquoted into individual containers, blind-labeled and randomized. Each participant was provided with the package insert, 1 blind labeled sample and a device. The results are summarized below:

% of Cutoff	Numberofsamples	Fentanyl Concentrationby LC/MS(ng/mL)	Lay person results		Thepercentage of
			No. ofPositive	No. ofNegative	correct results(%)
-100% Cutoff	20	0	0	20	100
-75% Cutoff	20	0.24	0	20	100
-50% Cutoff	20	0.46	0	20	100
-25% Cutoff	20	0.71	1	19	95
+25% Cutoff	20	1.31	20	0	100
+50% Cutoff	20	1.58	20	0	100
+75% Cutoff	20	1.77	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 the package insert and the score revealed a reading grade level of less than 7.

4. 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 a substantial equivalence decision.

Regulation Number and Section

§ 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).