Healgen Propoxyphene Test is an immunochromatographic assay for the qualitative determination of Propoxyphene in human urine at a Cut-Off concentration of 300 ng/mL. The test is available in a Strip format, a Dip Card format and a Cup format.

The test may yield preliminary positive results even when the prescription drug Propoxyphene is ingested, at prescribed doses; it is not intended to distinguish between prescription use or abuse of this drug. There is no uniformly recognized cutoff concentration level for Propoxyphene in urine. 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 prefered 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 prescription and for over-the-counter use.

Healgen Nortriptyline Test is an immunochromatographic assay for the qualitative determination of Nortriptyline in human urine at a Cut-Off concentration of 1000 ng/mL. The test is available in a Strip format, a Dip Card format and a Cup format.

The test may yield preliminary positive results even when the prescription is ingested, at prescribed doses, it is not intended to distinguish between prescription use or abuse of this drug. There is no uniformly recognized cutoff concentration level for Nortriptyline in urine. 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 prefered 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 prescription and for over-the-counter use.

Healgen EDDP (Methadone Metabolite) Test is an immunochromatographic assay for the qualitative determination of EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine) in human urine at a Cut-Off concentration of 300 ng/mL. The test is available in a Strip format, a Cassette format, a Dip Card format and a Cup format.

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 prescription and for over-the-counter use.

Device Description

Healgen Propoxyphene Test, Healgen Nortriptyline Test and Healgen EDDP (Methadone Metabolite) Test are immunochromatographic assays for Propoxyphene, Nortriptyline and EDDP. Each assay test is a lateral flow system for the qualitative detection of Propoxyphene, Nortriptyline and EDDP (target analyte) in human urine. The products are in vitro diagnostic devices, which come in the form of: Strips, Cassettes, DipCards, or Cups. Each product contains a Test Device (in one of the four formats), and a package insert. Each test device is sealed with a desiccant in an aluminum pouch.

AI/ML Overview

The provided document describes the performance characteristics of the Healgen Propoxyphene Test, Healgen Nortriptyline Test, and Healgen EDDP (Methadone Metabolite) Test, which are immunochromatographic assays for the qualitative determination of these substances in human urine. The acceptance criteria and the studies performed to demonstrate the device meets these criteria are detailed.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" as a separate, quantified threshold for each performance characteristic. Instead, it presents the results of various analytical and comparison studies, implying that the observed performance meets the manufacturer's internal standards for claiming substantial equivalence to a predicate device. For the purpose of this response, I will interpret the reported performance in the precision and cut-off studies as the de facto acceptance criteria demonstrated by the manufacturer.

The key acceptance criterion for qualitative drug tests is typically the ability to correctly classify samples as positive or negative relative to a defined cut-off concentration. For samples precisely at or near the cut-off, some variability is expected.

Implicit Acceptance Criteria and Reported Performance (Based on "Precision" and "Cut-off" Studies):

Performance Characteristic	Acceptance Criteria (Implicit)	Reported Device Performance
Precision	Consistent and accurate classification of samples at various concentrations around the cut-off, with expected variability at the exact cut-off. Ideally, 100% agreement for samples sufficiently below and above the cut-off. For samples at the cut-off, results should be approximately 50% positive and 50% negative.	Propoxyphene (All formats): Samples at -100%, -75%, -50%, -25% cut-off consistently yielded 50-/0+ (negative) results across all three lots for each format. Samples at +25%, +50%, +75%, +100% cut-off consistently yielded 50+/0- (positive) results across all three lots for each format. At the cut-off, results varied (e.g., Strip: 25-/25+, 21-/29+, 27-/23+; Cassette: 27-/23+, 22-/28+, 22-/28+; Dip Card: 26-/24+, 26-/24+, 23-/27+; Cup: 25-/25+, 21-/29+, 29-/21+). This indicates appropriate performance at and around the cut-off. Nortriptyline (All formats): Samples at -100%, -75%, -50%, -25% cut-off consistently yielded 50-/0+ (negative) results. Samples at +25%, +50%, +75%, +100% cut-off consistently yielded 50+/0- (positive) results. At the cut-off, results varied (e.g., Strip: 20-/30+, 24-/26+, 21-/29+; Cassette: 20-/30+, 22-/28+, 18-/32+; Dip Card: 22-/28+, 26-/24+, 18-/32+; Cup: 26-/24+, 24-/26+, 21-/29+). This also indicates appropriate performance at and around the cut-off. EDDP (All formats): Samples at -100%, -75%, -50%, -25% cut-off consistently yielded 50-/0+ (negative) results. Samples at +25%, +50%, +75%, +100% cut-off consistently yielded 50+/0- (positive) results. At the cut-off, results varied (e.g., Strip: 27-/23+, 23-/27+, 28-/22+; Cassette: 28-/22+, 20-/30+, 23-/27+; Dip Card: 21-/29+, 26-/24+, 22-/28+; Cup: 29-/21+, 24-/26+, 18-/32+). This demonstrates appropriate performance at and around the cut-off.
Cut-off Verification	100% correct classification of samples at +/- 25% of the cut-off, within a specified margin of error.	For Propoxyphene, Nortriptyline, and EDDP, results were all positive at and above +25% cut-off and all negative at and below -25% cut-off. This confirms the accuracy of the stated cut-off values.
Interference	No significant interference from common exogenous or endogenous substances found in urine.	A comprehensive list of compounds (e.g., Acetophenetidin, Ascorbic Acid, Caffeine, etc.) showed no interference at a concentration of 100µg/mL in drug-free urine or urine spiked with target drugs at 25% above cut-off levels. This was consistent across all formats.
Specificity	Demonstrate cross-reactivity with structurally similar compounds and no significant cross-reactivity with unrelated analytes.	Propoxyphene: Positive at 300 ng/mL (100% cross-reactivity) for Propoxyphene and Norpropoxyphene (metabolite). Nortriptyline: Positive at 1000 ng/mL (100% cross-reactivity) for Nortriptyline. Shows cross-reactivity with related tricyclic antidepressants (e.g., Amitriptyline 67%, Desipramine 20%, Imipramine 10%). EDDP: Positive at 300 ng/mL (100% cross-reactivity) for EDDP. Cross-reactivity with EMDP (60%). No cross-reactivity with Methadone, LAAM, Alpha Methadol, Doxylamine at 100000 ng/mL (<0.3%).
Effect of Specific Gravity & pH	Consistent results across a physiological range of urine specific gravity and pH.	Urine samples with specific gravity 1.000 to 1.035 and pH 4 to 9, spiked at 25% below and 25% above cut-off, showed all positive results above +25% cut-off and all negative results below -25% cut-off. This confirms insensitivity to physiological variations in urine.
Method Comparison (Clinical Samples)	High agreement (concordance) with a validated confirmatory method (GC/MS) for clinical samples, especially for samples significantly separating from the cutoff. Close to the cut-off, some discordance is expected due to the nature of qualitative assays and instrumental variation.	Propoxyphene, Nortriptyline, EDDP (All formats): High overall concordance with GC/MS. For all drug tests and formats:- All "Negative" and "Low Negative by GC/MS (less than -50%)" samples were correctly identified as Negative (e.g., 10 negative + 15 low negative = 25 negative test results by device).- All "High Positive by GC/MS (greater than +50%)" samples were correctly identified as Positive (24 positive test results by device).- For "Near Cutoff Negative by GC/MS (between -50% and cut-off)", all samples were correctly identified as Negative (15 negative test results by device).- For "Near Cutoff Positive by GC/MS (between the cut-off and +50%)", a small number of discordant results were observed, where GC/MS positive samples (e.g., 301 ng/mL, 304 ng/mL for Propoxyphene) were reported as negative by the device. This is expected due to the qualitative nature of the rapid test and the variability around the cut-off. The clinical significance of these low-level discordant results is mitigated by the recommendation for confirmatory testing.
Lay-User Performance	High percentage of correct results by lay users demonstrating ease of use and interpretability of the device and instructions.	Propoxyphene, Nortriptyline, EDDP (All formats): Percentage of correct results by lay persons was consistently 90-100% for concentrations at +/- 25% of the cutoff and beyond. Specifically: - 100% correct for -100%, -75%, -50% cut-off samples (negative). - 90-95% correct for -25% cut-off samples. - 90-95% correct for +25% cut-off samples. - 100% correct for +50%, +75% cut-off samples (positive). All lay users indicated ease of understanding the instructions (Flesch-Kincaid Grade Level 7).

Detailed Study Information:

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

Precision Test Set:
- For each drug (Propoxyphene, Nortriptyline, EDDP) and each of the four formats (Strip, Cassette, Cup, Dip Card):
  - 9 different concentrations were tested (-100%, -75%, -50%, -25%, Cut-off, +25%, +50%, +75%, +100% of cut-off).
  - Each concentration was tested 50 times (2 runs/day for 25 days) for each of 3 different lots.
  - Total precision samples per drug: 9 concentrations * 50 tests/concentration * 3 lots * 4 formats = 5400 tests.
- Data Provenance: Samples were prepared by spiking known concentrations of drugs into negative urine samples. The origin of the negative urine itself is not specified but is implied to be human. The study was conducted "in-house" (Healgen Scientific LLC). These are prospective analytical studies.
Cut-off Verification Test Set:
- For each drug (Propoxyphene, Nortriptyline, EDDP) and for all formats (implicitly, as "different lots of each device" and "all formats" are mentioned in the interference study which follows this section):
  - 150 samples were used, equally distributed at -50% cut-off, cut-off, +25% cut-off, +50% cut-off concentrations. This means 37-38 samples per concentration.
  - Tested using three different lots of each device.
- Data Provenance: Samples were prepared by spiking known concentrations of drugs into negative samples. Prospective analytical studies.
Interference Test Set:
- Not explicitly stated, but common interfering compounds (listed in pages 11-14) were tested at 100µg/mL in drug-free urine and in target drug urine (at 25% above cut-off).
- Tested using three batches of each device for all formats.
- Data Provenance: Prepared samples. Prospective analytical studies.
Specificity (Cross-reactivity) Test Set:
- Not explicitly stated, but drug metabolites and other components were tested.
- Tested using three batches of each device for all formats. Lowest detectable concentration used to calculate cross-reactivity.
- Data Provenance: Prepared samples. Prospective analytical studies.
Effect of Urine Specific Gravity and Urine pH Test Set:
- Urine samples with specific gravity 1.000 to 1.035 and pH 4 to 9.
- Spiked with target drugs at 25% below and 25% above cut-off levels.
- Tested using three batches of each device for all formats.
- Data Provenance: Prepared samples. Prospective analytical studies.
Method Comparison (Clinical Samples) Test Set:
- For each drug (Propoxyphene, Nortriptyline, EDDP) and each format (Strip, Cassette, Cup, Dip Card):
  - 80 unaltered clinical urine samples were used (40 negative and 40 positive).
  - Total samples for method comparison = 3 drugs * 4 formats * 80 samples = 960 samples.
- Data Provenance: "unaltered clinical samples" (implies human origin, retrospective or prospective collection not specified but usually retrospective for samples with confirmed status). The studies were performed "in-house."
Lay-User Study Test Set:
- For each drug (Propoxyphene, Nortriptyline, EDDP) and each format (Strip, Cassette, Cup, Dip Card):
  - 7 concentrations were evaluated: -100%, -75%, -50%, -25%, +25%, +50%, +75% of cut-off.
  - Each concentration was tested with 20 samples.
  - Total samples per drug/format: 7 concentrations * 20 samples/concentration = 140 samples.
  - Total samples across all drugs and implicitly all formats for lay user study (the table heading states "Propoxyphene Strip" but the preamble says "560 lay persons testing each of the Propoxyphene, the Nortriptyline and the EDDP devices." and then gives data for Strip, Cassette, DipCard, Cup formats. It is most logical that each lay person tests one sample of one format for one drug.) So, if each of 560 lay persons tested one sample for propoxyphene, 560 for nortriptyline, and 560 for EDDP (total 1680 individuals), the sample numbers in the tables would represent a subset or a summary of this. The tables show 20 samples per concentration level. It's more plausible that the lay users tested 140 different samples per drug, one sample per lay user, for each format specifically.
  - The tables specify "Number of samples" as 20 for each concentration level. If the tables represent the total combined results across all lay users, then the total number of distinct samples tested for each drug/format combination would be 7 concentrations * 20 samples/concentration = 140 samples * 4 formats (assuming tables were just representative) = 560 samples.
- Data Provenance: Urine samples were prepared by spiking drugs into drug-free pooled urine specimens. The concentrations were confirmed by GC/MS. The study was performed at "three intended user sites." Prospective study design with prepared samples.

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

Ground Truth Method: Gas Chromatography/Mass Spectrometry (GC/MS) was used as the confirmatory method for all studies involving quantitative drug concentrations, including precision, cut-off verification, and method comparison with clinical samples, and lay-user studies.
Number/Qualifications of Experts: The document details the use of "three different operators" for precision studies and "three different laboratory assistants" for method comparison studies. It does not mention experts establishing GC/MS ground truth, as GC/MS is an objective analytical method. The results were confirmed by GC/MS, implying that qualified personnel performed these tests, but no specific number or qualifications are given for the GC/MS operators.

4. Adjudication Method for the Test Set:

Analytical Studies (Precision, Cut-off, Interference, Specificity, Specific Gravity/pH): No explicit adjudication method is mentioned. The results are quantitative (GC/MS confirmation for preparation) or directly interpreted by operators judging the presence/absence of a line on the qualitative test. For precision, the results are aggregates (e.g., "50-/0+"), indicating consensus or direct reading rather than an adjudication process between human readers.
Method Comparison (Clinical Samples): "Operators ran 80 (40 negative and 40 positive) unaltered clinical samples...compared to GC/MS results." "Three different laboratory assistants" interpreted the test results of the devices. The individual results from each viewer (Viewer A, B, C) are presented. GC/MS served as the definitive ground truth, so the comparison is directly between the device's output (as read by an operator) and the GC/MS result. Discrepancies are listed, highlighting where an operator's reading differed from GC/MS. No formal adjudication among the three laboratory assistants is described; their individual results are reported and compared to the GC/MS ground truth.
Lay-User Study: Lay persons tested the device and results were compared to GC/MS. No adjudication among lay users is mentioned.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and the effect size of how much human readers improve with AI vs without AI assistance:

No MRMC study or AI: The device is a qualitative immunochromatographic assay (rapid test strip/cassette/cup/dip card), not an AI-powered diagnostic device. Therefore, a multi-reader multi-case (MRMC) comparative effectiveness study comparing human readers with and without AI assistance was not applicable and not performed. The studies involved human readers (laboratory assistants, lay users) interpreting the results of the rapid tests directly.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:

No standalone algorithm: As stated above, this is a rapid diagnostic test, not an AI or algorithm-based device. Performance is inherently tied to human visual interpretation of the test line. Therefore, a standalone (algorithm-only) performance study was not applicable and not performed. The "device performance" refers to the entire system including the physical test and its visual interpretation.

7. The Type of Ground Truth Used:

GC/MS (Gas Chromatography/Mass Spectrometry): This was the primary method used to establish ground truth for all samples with known drug concentrations (prepared samples for precision, cut-off, interference, specificity, specific gravity/pH, and lay-user studies) and for the "unaltered clinical samples" used in the method comparison study. GC/MS is a highly sensitive and specific analytical technique considered the gold standard for confirmatory drug testing in urine.

8. The Sample Size for the Training Set:

Not applicable: These are immunochromatographic assays, not machine learning or AI models. There is no "training set" in the context of developing a learning algorithm. The device's performance is determined by its chemical and biological components and manufacturing quality, not trained data.

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

Not applicable: As there is no training set for an AI/ML algorithm, this question does not apply. The ground truth for evaluating the device's performance (i.e., for the test sets) was established using GC/MS, as detailed in point 7.

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

August 18, 2015

HEALGEN SCIENTIFIC LLC C/O JOE XIA BUSINESS DIRECTOR 504 EAST DIAMOND AVE. SUITE I GAITHERSBURG MD 20877

Re: K151348

Trade/Device Name: Healgen Propoxyphene Test (Strip, Cassette, Cup, Dip Card), Healgen Nortriptyline Test (Strip, Cassette, Cup, Dip Card), Healgen EDDP (Methadone Metabolite) Test (Strip, Cassette, Cup, Dip Card) Regulation Number: 21 CFR 862.3910 Regulation Name: Tricyclic antidepressant drugs test system Regulatory Class: II Product Code: LFG, DJR, JXN Dated: July 6, 2015 Received: July 9, 2015

Dear Mr. Xia:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA), You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the

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electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

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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Indications for Use

510(k) Number (if known) K151348

Device Name

Healgen Propoxyphene Test (Strip, Cassette, Cup, Dip Card) Healgen Nortriptyline Test (Strip, Cassette, Cup, Dip Card) Healgen EDDP (Methadone Metabolite) Test (Strip, Cassette, Cup, Dip Card)

Indications for Use (Describe)

For in vitro diagnostic use only. It is intended for prescription and for over-the-counter use.

Type of Use (Select one or both, as applicable)

X Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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1. Date: July 6, 2015
1. Submitter: HEALGEN SCIENTIFIC LLC 5213 Maple St Bellaire, TX 77401
1. Contact person: Jianqiu Fang HEALGEN SCIENTIFIC LLC 5213 Maple St Bellaire, TX 77401 Telephone: 713-733-8088 Fax: 713-733-8088 Email: bryan@healgen.com
1. Device Name: Healgen Propoxyphene Test (Strip, Cassette, Cup, Dip Card) Healgen Nortriptyline Test (Strip, Cassette, Cup, Dip Card) Healgen EDDP (Methadone Metabolite) Test (Strip, Cassette, Cup, Dip Card)

Classification: Class II

Product Code	CFR #	Panel
JXN	21 CFR, 862.3700 Propoxyphene Test System	Toxicology
DJR	21 CFR, 862.3620 Methadone Test System	Toxicology
LFG	21 CFR, 862.3910 Tricyclic antidepressant drugs test system Test System	Toxicology

1. Predicate Devices:

K140748

Co-Innovation Biotech One Step Single/Multi-drug Test.

1. Intended Use / Indications for Use
  Healgen Propoxyphene Test is an immunochromatographic assay for the qualitative determination of Propoxyphene in human urine at a Cut-Off concentration of 300 ng/mL. The test is available in a Strip format, a Cassette format, a Dip Card format and a Cup format.

The test may yield preliminary positive results even when the prescription drug Propoxyphene is ingested, at prescribed doses; it is not intended to distinguish between prescription use or abuse of this drug. There is no uniformly recognized cutoff concentration level for Propoxyphene in urine. 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 is the preferred confirmatory method. Clinical consideration and

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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 prescription and for over-the-counter use.

The test may yield preliminary positive results even when the Nortriptyline is ingested, at prescribed doses; it is not intended to distinguish between prescription use or abuse of this drug. There is no uniformly recognized cutoff concentration level for Nortriptyline in urine. 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 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 prescription and for over-the-counter use.

Healgen EDDP (Methadone Metabolite) Test is an immunochromatographic assay for the qualitative determination of EDDP (2-ethylidene-1,5-dimethyl-3,3- diphenylpyrrolidine) in human urine at a Cut-Off concentration of 300 ng/mL. The test is available in a Strip format, a Cassette format, a Dip Card format and a Cup format.

For in vitro diagnostic use only. It is intended for prescription and for over-the-counter use.

7. Device Description

8. Substantial Equivalence Information

A summary comparison of features of the Healgen Propoxyphene Test, Healgen Nortriptyline Test and Healgen EDDP (Methadone Metabolite) Test and the predicate device is provided in Table 1, Table 2 and Table 3.

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Table 1: Features Comparison of Healgen Propoxyphene Test and the Predicate Device

Item	Device	Predicate -K140748
Intended Use	For the qualitative determination ofPropoxyphene in human urine.	Same
Drug Analyte	Propoxyphene	Same
Methodology	Competitive binding, lateral flowimmunochromatographic assays based onthe principle of antigen antibodyimmunochemistry.	Same
Specimen Type	Human Urine	Same
Cut-Off Values	300 ng/mL	Same
IntendedPopulation	For over-the-counter and prescriptionSameuses.
Configurations	Strip, Cassette, Cup, Dip Card	Cup

Table 2: Features Comparison of Healgen Nortriptyline Test and the Predicate Device

Item	Device	Predicate – K140748
Intended Use	For the qualitative determination ofNortriptyline in human urine.	Same
Drug Analyte	Nortriptyline	Same
Methodology	Competitive binding, lateral flowimmunochromatographic assays basedon the principle of antigen antibodyimmunochemistry.	Same
Specimen Type	Human Urine	Same
Cut-Off Values	1000 ng/mL	Same
IntendedPopulation	For over-the-counter and prescriptionuses.	Same
Configurations	Strip, Cassette, Cup, Dip Card	Cup

Table 3: Features Comparison of Healgen EDDP (Methadone Metabolite)Test and the Predicate Device

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Item	Device	Predicate – K140748
Intended Use	For the qualitative determination of EDDP in human urine.	Same
Drug Analyte	EDDP	Same
Methodology	Competitive binding, lateral flow immunochromatographic assays based on the principle of antigen antibody immunochemistry.	Same
Specimen Type	Human Urine	Same
Cut-Off Values	300 ng/mL	Same
Intended Population	For over-the-counter and prescription uses.	Same
Configurations	Strip, Cassette, Cup, Dip Card	Cup

9. Test Principle

Healgen Propoxyphene Test, Healgen Nortriptyline Test and Healgen EDDP (Methadone Metabolite) Test are rapid tests for the qualitative detection of Propoxyphene, Nortriptyline and EDDP in urine samples. Each assay test is a lateral flow chromatographic immunoassay. During testing, a urine specimen migrates upward by capillary action. If target drugs are present in the urine specimen below its cut-off concentration, it will not saturate the binding sites of its specific antibody (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 cut-off concentration because it will saturate all the binding sites of the antibody coated on the particles. A band should form in the control region of the devices regardless of the presence of drug or metabolite in the sample to indicate that the test has been performed properly.

10. Performance Characteristics

1. Analytical Performance
- a. Precision

Precision studies were carried out for samples with concentrations of -100% cut-off, -50% cut-off, -25% cut-off, at the cut-off, +25% cut-off, +75% 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 GC/MS. All sample aliquots were blind labeled and randomized by the person who prepared samples and did not take part in the sample testing. For each concentration, tests were performed two runs per day for 25 days by three different operators for each format of devices. Different set of operators tested each format. The results obtained are summarized in the following tables:

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Propoxyphene

Strip Format

	-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
Drug
Lot 1	50-/0+	50-/0+	50-/0+	50-/0+	25-/25+	50+/0-	50+/0-	50+/0-	50+/0-
Lot 2	50-/0+	50-/0+	50-/0+	50-/0+	21-/29+	50+/0-	50+/0-	50+/0-	50+/0-
Lot 3	50-/0+	50-/0+	50-/0+	50-/0+	27-/23+	50+/0-	50+/0-	50+/0-	50+/0-

Cassette Format

	-100%Cut-off	-75%Cut-off	-50%Cut-off	-25%Cut-off	+25%Cut-off	+50%Cut-off	+75%Cut-off	+100%Cut-off
Drug
Lot 1	50-/0+	50-/0+	50-/0+	50-/0+	27-/23+	50+/0-	50+/0-	50+/0-
Lot 2	50-/0+	50-/0+	50-/0+	50-/0+	22-/28+	50+/0-	50+/0-	50+/0-
Lot 3	50-/0+	50-/0+	50-/0+	50-/0+	22-/28+	50+/0-	50+/0-	50+/0-

Dip Card Format

Drug	Result	Cut-off				Cut-off	Cut-off
		-100%	-75%	-50%	-25%		+25%	+50%	+75%	+100%
Lot 1	50-/0+	50-/0+	50-/0+	50-/0+	50-/0+	26-/24+	50+/0-	50+/0-	50+/0-	50+/0-
Lot 2	50-/0+	50-/0+	50-/0+	50-/0+	50-/0+	26-/24+	50+/0-	50+/0-	50+/0-	50+/0-
Lot 3	50-/0+	50-/0+	50-/0+	50-/0+	50-/0+	23-/27+	50+/0-	50+/0-	50+/0-	50+/0-

CUP Format

Drug	Result	-100%Cut-off	-75%Cut-off	-50%Cut-off	-25%Cut-off	+25%Cut-off	+50%Cut-off	+75%Cut-off	+100%Cut-off
Lot 1	50-/0+	50-/0+	50-/0+	50-/0+	25-/25+	50+/0-	50+/0-	50+/0-	50+/0-
Lot 2	50-/0+	50-/0+	50-/0+	50-/0+	21-/29+	50+/0-	50+/0-	50+/0-	50+/0-
Lot 3	50-/0+	50-/0+	50-/0+	50-/0+	29-/21+	50+/0-	50+/0-	50+/0-	50+/0-

Nortriptyline

Strip Format

	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
Drug	Lot 1	50-/0+	50-/0+	50-/0+	50-/0+	20-/30+	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+	21-/29+	50+/0-	50+/0-	50+/0-	50+/0-

Cassette Format

{9}------------------------------------------------

	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
Drug	Lot 1	50-/0+	50-/0+	50-/0+	50-/0+	20-/30+	50+/0-	50+/0-	50+/0-	50+/0-
	Lot 2	50-/0+	50-/0+	50-/0+	50-/0+	22-/28+	50+/0-	50+/0-	50+/0-	50+/0-
	Lot 3	50-/0+	50-/0+	50-/0+	50-/0+	18-/32+	50+/0-	50+/0-	50+/0-	50+/0-

Dip Card Format

	-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
Drug
Lot 1	50-/0+	50-/0+	50-/0+	50-/0+	22-/28+	50+/0-	50+/0-	50+/0-	50+/0-
Lot 2	50-/0+	50-/0+	50-/0+	50-/0+	26-/24+	50+/0-	50+/0-	50+/0-	50+/0-
Lot 3	50-/0+	50-/0+	50-/0+	50-/0+	18-/32+	50+/0-	50+/0-	50+/0-	50+/0-

CUP Format

	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
Drug	Lot 1	50-/0+	50-/0+	50-/0+	50-/0+	26-/24+	50+/0-	50+/0-	50+/0-	50+/0-
	Lot 2	50-/0+	50-/0+	50-/0+	50-/0+	24-/26+	50+/0-	50+/0-	50+/0-	50+/0-
	Lot 3	50-/0+	50-/0+	50-/0+	50-/0+	21-/29+	50+/0-	50+/0-	50+/0-	50+/0-

EDDP

Strip Format

	-100%Cut-off	-75%Cut-off	-50%Cut-off	-25%Cut-off	+25%Cut-off	+50%Cut-off	+75%Cut-off	+100%Cut-off
Drug
Lot 1	50-/0+	50-/0+	50-/0+	50-/0+	27-/23+	50+/0-	50+/0-	50+/0-
Lot 2	50-/0+	50-/0+	50-/0+	50-/0+	23-/27+	50+/0-	50+/0-	50+/0-
Lot 3	50-/0+	50-/0+	50-/0+	50-/0+	28-/22+	50+/0-	50+/0-	50+/0-

Cassette Format

Drug	-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
Lot 1	50-/0+	50-/0+	50-/0+	50-/0+	28-/22+	50+/0-	50+/0-	50+/0-	50+/0-
Lot 2	50-/0+	50-/0+	50-/0+	50-/0+	20-/30+	50+/0-	50+/0-	50+/0-	50+/0-
Lot 3	50-/0+	50-/0+	50-/0+	50-/0+	23-/27+	50+/0-	50+/0-	50+/0-	50+/0-

Dip Card Format

Drug	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
Lot 1		50-/0+	50-/0+	50-/0+	50-/0+	21-/29+	50+/0-	50+/0-	50+/0-	50+/0-
Lot 2		50-/0+	50-/0+	50-/0+	50-/0+	26-/24+	50+/0-	50+/0-	50+/0-	50+/0-

{10}------------------------------------------------

Drug	Result	-100%Cut-off	-75%Cut-off	-50%Cut-off	-25%Cut-off	+25%Cut-off	+50%Cut-off	+75%Cut-off	+100%Cut-off
Lot 3		50-/0+	50-/0+	50-/0+	50-/0+	22-/28+	50+/0-	50+/0-	50+/0-

CUP Format

Drug	-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
Lot 1	50-/0+	50-/0+	50-/0+	50-/0+	29-/21+	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+	18-/32+	50+/0-	50+/0-	50+/0-	50+/0-

b. Linearity

Not applicable.

c. Stability
The devices are stable at 4-30°C for 24 months based on the accelerated stability study at 45°C and real time stability determination at both 4 ℃ and 30℃.

Control materials are not provided with the device. The labeling provides information on how to obtain control materials.

d. Cut-off
A total of 150 samples equally distributed at concentrations of -50% cut-off; cutoff; +25% cut-off; +50% cut-off were tested using three different lots of each device by three different operators. Results were all positive at and above +25% cut-off and all negative at and below -25% cut-off for Propoxyphene, Nortriptyline and EDDP. The following cut-off values for the test devices have been verified.

Test	Calibrator	Cut-off(ng/mL)
Propoxyphene Test	Propoxyphene	300
Nortriptyline Test	Nortriptyline	1000
EDDP Test	EDDP	300

e. Interference

Potential interfering substances found in human urine of physiological conditions were added to drug-free urine and target drugs urine with concentration at 25% above cut-off levels. These urine samples were tested using three batches of each device for all formats.

{11}------------------------------------------------

Compounds that showed no interference at a concentration of 100µg/mL are summarized in the following tables. There were no differences observed for different formats.

Acetophenetidin	Ethyl-p-aminobenzoate	Perphenazine
N-Acetylprocainamide	Fenoprofen	Phencyclidine
Acetylsalicylic Acid(Aspirin)	Furosemide	Phenelzine
Aminopyrine	Gentisic acid	Phenobarbital
Amitriptyline	Hemoglobin	Phentermine
Amoxicillin	Hydralazine	Phenylephrine-L
Amobarbital	(+/-)-4-HydroxyamphetamineHCL	Phenylethylamine
D-Amphetamine	Hydrochlorothiazide	Phenylpropanolamine
L-Amphetamine	Hydrocodone	Prednisolone Acetate
Amphetamine Sulfate	Hydrocortisone	Prednisone
Ampicinine(Ampicillin)	a -Hydroxyhippuric acid	Procaine(Novocaine)
Apomorphine	p-Hydroxymethamphetamine	Promazine
L-Ascorbic Acid	Ibuprofen	Promethazine
Aspartame	Imipramine	Propranolol
Atropine	Isoxsuprine	Pseudoephedrine HCL
Benzilic acid	Isoproterenol-(+/-)	Quinidine
Benzphetamine	Ketamine	Quinine
Benzoic Acid	Labetalol	Ranitidine(Zantac)
Bilirubin	Levorphanol	Salicylic Acid
Caffeine	Loperamide	Secobarbital
Chloramphenicol	Maprotiline	Serotonin
Chlordiazepoxide HCL	Meprobamate	Sulfamethazine
Chloroquine	Methadone	Sulindac
Chlorothiazide	Methoxyphenamine	Temazepam
Chlorpheniramine	(+/-)- Methylenedioxyamphetamine(MDA)	11-Nor-A9-Tetrahydrocannabinol
Chlorpromazine	Methylphenidate	Tetracycline
Cholesterol	Nalbuphine	Tetrahydrozoline
Clomipramine	Nalidixic acid	Thiamine
Clonidine hydrochloride	Naloxone hydrochloride	L-Thyroxine
Cortisone	Naltrexone hydrochloride	Thioridazine Hydrochloride
Cotinine(-)	Naproxen	Triamterene
Creatinine	Niacinamide	TriflupromazineHydrochloride
Deoxyepinephrine	Nifedipine	Trimethoprim
Dextromethorphan	Norethindrone	Trimipramine
Diazepam	Noscapine	Tryptamine
Diflunisal	Oxazepam	DL-Tryptophan
Digoxin	Oxymetazoline	Tyramine
Doxylamine	Papaverine	D/L-Tyrosine
Ecgonine methylester	Penicillin	Uric Acid
R(-)-Epinephrine	Pentobarbital	Verapamil
Erythromycin	Perphenazine	Zomepirac
Estrone-3-sulfate	Phencyclidine

{12}------------------------------------------------

Nortriptyline

Acetophenetidin	Ethyl-p-aminobenzoate	Phencyclidine
N-Acetylprocainamide	Fenoprofen	Phenelzine
Acetylsalicylic Acid	Furosemide	Phenobarbital
(Aspirin)
Aminopyrine	Gentisic acid	Phentermine
Amoxicillin	Hemoglobin	Phenylephrine-L
Amobarbital	Hydralazine	Phenylethylamine
D-Amphetamine	(+/-)-4-HydroxyamphetamineHCL	Phenylpropanolamine
L-Amphetamine	Hydrochlorothiazide	Prednisolone Acetate
Amphetamine Sulfate	Hydrocodone	Prednisone
Ampicinine(Ampicillin)	Hydrocortisone	Procaine(Novocaine)
Apomorphine	a -Hydroxyhippuric acid	Propoxyphene,d-
L-Ascorbic Acid	p-Hydroxymethamphetamine	Propranolol
Aspartame	Ibuprofen	Pseudoephedrine HCL
Atropine	Isoxsuprine	Quinidine
Benzilic acid	Isoproterenol-(+/-)	Quinine
Benzphetamine	Ketamine	Ranitidine(Zantac)
Bezoic Acid	Labetalol	Salicylic Acid
Bilirubin	Levorphanol	Secobarbital
Caffeine	Loperamide	Serotonin
Chloramphenicol	Meprobamate	Sulfamethazine
Chlordiazepoxide HCL	Methadone	Sulindac
Chloroquine	Methoxyphenamine	Temazepam
Chlorothiazide	(+/-)-	11-Nor-Δ9-Tetrahydrocannabinol
	Methylenedioxyamphetamine(MDA)
Chlorpheniramine	Methylphenidate	Tetracycline

{13}------------------------------------------------

Chlorpromazine	Nalbuphine	Tetrahydrozoline
Cholesterol	Nalidixic acid	Thiamine
Clonidine hydrochloride	Naloxone hydrochloride	L-Thyroxine
Cortisone	Naltrexone hydrochloride	ThioridazineHydrochloride
Cotinine(-)	Naproxen	Triamterene
Creatinine	Niacinamide	TriflupromazineHydrochloride
Deoxyepinephrine	Nifedipine	Trimethoprim
Dextromethorphan	Norethindrone	Tryptamine
Diazepam	Norpropoxyphene	DL-Tryptophan
Diflunisal	Noscapine	Tyramine
Digoxin	Oxazepam	D/L-Tyrosine
Doxylamine	Oxymetazoline	Uric Acid
Ecgonine methylester	Papaverine	Verapamil
R(-)-Epinephrine	Penicillin	Zomepirac
Erythromycin	Pentobarbital
Estrone-3-sulfate	Perphenazine

EDDP

Acetophenetidin	Ethyl-p-aminobenzoate	Phencyclidine
N-Acetylprocainamide	Fenoprofen	Phenelzine
Acetylsalicylic Acid(Aspirin)	Furosemide	Phenobarbital
Aminopyrine	Gentisic acid	Phentermine
Amitriptyline	Hemoglobin	Phenylephrine-L
Amoxicillin	Hydralazine	Phenylethylamine
Amobarbital	(+/-)-4-HydroxyamphetamineHCL	Phenylpropanolamine
D-Amphetamine	Hydrochlorothiazide	Prednisolone Acetate
L-Amphetamine	Hydrocodone	Prednisone
Amphetamine Sulfate	Hydrocortisone	Procaine(Novocaine)
Ampicinine(Ampicillin)	a -Hydroxyhippuric acid	Promazine
Apomorphine	p-Hydroxymethamphetamine	Promethazine
L-Ascorbic Acid	Ibuprofen	Propoxyphene,d-
Aspartame	Imipramine	Propranolol
Atropine	Isoxsuprine	Pseudoephedrine HCL
Benzilic acid	Isoproterenol-(+/-)	Quinidine
Benzphetamine	Ketamine	Quinine
Benzoic Acid	Labetalol	Ranitidine(Zantac)

{14}------------------------------------------------

Bilirubin	Levorphanol	Salicylic Acid
Caffeine	Loperamide	Secobarbital
Chloramphenicol	Maprotiline	Serotonin
Chlordiazepoxide HCL	Meprobamate	Sulfamethazine
Chloroquine	Methadone	Sulindac
Chlorothiazide	Methoxyphenamine	Temazepam
Chlorpheniramine	(+/-)- Methylenedioxyamphetamine(MDA)	11-Nor-Δ9-Tetrahydrocannabinol
Chlorpromazine	Methylphenidate	Tetracycline
Cholesterol	Nalbuphine	Tetrahydrozoline
Clomipramine	Nalidixic acid	Thiamine
Clonidine hydrochloride	Naloxone hydrochloride	L-Thyroxine
Cortisone	Naltrexone hydrochloride	ThioridazineHydrochloride
Cotinine(-)	Naproxen	Triamterene
Creatinine	Niacinamide	TriflupromazineHydrochloride
Deoxyepinephrine	Nifedipine	Trimethoprim
Dextromethorphan	Norethindrone	Trimipramine
Diazepam	Norpropoxyphene	Tryptamine
Diflunisal	Noscapine	DL-Tryptophan
Digoxin	Oxazepam	Tyramine
Doxylamine	Oxymetazoline	D/L-Tyrosine
Ecgonine methylester	Papaverine	Uric Acid
R(-)-Epinephrine	Penicillin	Verapamil
Erythromycin	Pentobarbital	Zomepirac
Estrone-3-sulfate	Perphenazine

f. Specificity
To test the specificity, drug metabolites and other components that are likely to interfere in urine samples were tested using three batches of each device for all formats. The obtained lowest detectable concentration was used to calculate the cross-reactivity. There were no differences observed for different formats.

Propoxyphene(Cut-off=300 ng/mL)	Result	% Cross-Reactivity
Propoxyphene	Positive at 300 ng/mL	100%
Norpropoxyphene	Positive at 300 ng/mL	100%

{15}------------------------------------------------

Nortriptyline(Cut-off=1000 ng/mL)	Result	% Cross-Reactivity
Nortriptyline	Positive at 1000 ng/mL	100%
Amitriptyline	Positive at 1500 ng/mL	67%
Clomipramine	Positive at 50000 ng/mL	2%
Desipramine	Positive at 5000 ng/mL	20%
Doxepine	Positive at 10000 ng/mL	10%
Imipramine	Positive at 10000 ng/mL	10%
Maprotiline	Positive at 100000 ng/mL	1%
Nordoxepin	Positive at 10000 ng/mL	10%
Promazine	Positive at 50000 ng/mL	2%
Promethazine	Positive at 2500 ng/mL	40%
Trimipramine	Positive at 50000 ng/mL	2%
Cyclobenzaprine Hydrochloride	Positive at 5000 ng/mL	20%
Norclomipramine	Positive at 50000 ng/mL	2%

EDDP(Cut-off=300 ng/mL)	Result	% Cross-Reactivity
EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine)	Positive at 300 ng/mL	100%
EMDP (2-Ethyl-5-methyl-3,3-diphenylpyrroline)	Positive at 500 ng/mL	60%
Disopyramide	Positive at 50000 ng/mL	1%
Methadone	Negative at 100000	<0.3
LAAM (Levo-alpha-acetylmethadol) HCl	Negative at 100000	<0.3
Alpha Methadol	Negative at 100000	<0.3
Doxylamine	Negative at 100000	<0.3

g. Effect of Urine Specific Gravity and Urine pH
To investigate the effect of urine specific gravity and urine pH, urine samples with of 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 batches of each device for all formats. Results were all positive for samples at and above +25% cut-off and all negative for samples at and below -25% Cut-Off. There were no differences observed for different formats.

2. Comparison Studies

The method comparison studies for the Propoxyphene Test, the Nortriptyline Test and the EDDP Test were performed in-house with three different laboratory assistants for each format of the device.

{16}------------------------------------------------

Operators ran 80 (40 negative and 40 positive) unaltered clinical samples were blind labeled and compared to GC/MS results. The results are presented in the tables below:

Propoxyphene
Stripformat		Negative	LowNegativeby GC/MS(less than -50%)	Near CutoffNegative byGC/MS(Between50% andcut-off)	NearCutoffPositive byGC/MS(Betweenthe cut-offand +50%)	HighPositive byGC/MS(greaterthan +50%)
Viewer A	Positive	0	0	0	14	24
	Negative	10	15	15	2	0
Viewer B	Positive	0	0	0	15	24
	Negative	10	15	15	1	0
Viewer C	Positive	0	0	0	14	24
	Negative	10	15	15	2	0

Discordant Results of Propoxyphene Strip

Viewer	Sample Number	GC/MS Result	Strip FormatViewer Results
Viewer A	PPX67	301	Negative
Viewer A	PPX66	304	Negative
Viewer B	PPX67	301	Negative
Viewer C	PPX67	301	Negative
Viewer C	PPX66	304	Negative

Cassette format		Negative	Low Negative by GC/MS (less than -50%)	Near Cutoff Negative by GC/MS (Between -50% and cut-off)	Near Cutoff Positive by GC/MS (Between the cut-off and +50%)	High Positive by GC/MS (greater than +50%)
Viewer A	Positive	0	0	0	14	24
	Negative	10	15	15	2	0
Viewer B	Positive	0	0	0	15	24
	Negative	10	15	15	1	0
Viewer C	Positive	0	0	0	14	24
	Negative	10	15	15	2	0

Discordant Results of Propoxyphene Cassette

{17}------------------------------------------------

Viewer	Sample Number	GC/MS Result	Cassette FormatViewer Results
Viewer A	PPX67	301	Negative
Viewer A	PPX66	304	Negative
Viewer B	PPX67	301	Negative
Viewer C	PPX67	301	Negative
Viewer C	PPX66	304	Negative

Cup format		Negative	Low Negative by GC/MS (less than - 50%)	Near Cutoff Negative by GC/MS (Between - 50% and cut-off)	Near Cutoff Positive by GC/MS (Between the cut-off and +50%)	High Positive by GC/MS (greater than +50%)
Viewer A	Positive	0	0	0	14	24
	Negative	10	15	15	2	0
Viewer B	Positive	0	0	0	14	24
	Negative	10	15	15	2	0
Viewer C	Positive	0	0	0	14	24
	Negative	10	15	15	2	0

Discordant Results of Propoxyphene Cup

Viewer	Sample Number	GC/MS Result	Cup Format Viewer Results
Viewer A	PPX67	301	Negative
Viewer A	PPX66	304	Negative
Viewer B	PPX67	301	Negative
Viewer B	PPX66	304	Negative
Viewer C	PPX67	301	Negative
Viewer C	PPX66	304	Negative

Dip Cardformat		Negative	Low Negativeby GC/MS(less than -50%)	Near CutoffNegative byGC/MS(Between -50% and cut-off)	Near CutoffPositive byGC/MS(Betweenthe cut-offand +50%)	HighPositive byGC/MS(greaterthan+50%)
Viewer A	Positive	0	0	0	14	24
	Negative	10	15	15	2	0
Viewer B	Positive	0	0	0	14	24

{18}------------------------------------------------

	Negative	10	ﮯ ﻟﻠ	ﮯ ﻟﻠ
Viewer C	Positive				24
	Negative		ﺎﺕ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟ	ﻟﻠ

Discordant Results of Propoxyphene Dip Card

Viewer	Sample Number	GC/MS Result	Dip Card FormatViewer Results
Viewer A	PPX67	301	Negative
Viewer A	PPX66	304	Negative
Viewer B	PPX67	301	Negative
Viewer B	PPX66	304	Negative
Viewer C	PPX67	301	Negative
Viewer C	PPX66	304	Negative

Nortriptyline

Stripformat		Negative	LowNegativeby GC/MS(less than -50%)	Near CutoffNegative byGC/MS(Between -50% and cut-off)	Near CutoffPositive byGC/MS(Betweenthe cut-offand +50%)	HighPositive byGC/MS(greaterthan+50%)
Viewer A	Positive	0	0	0	15	24
	Negative	10	15	15	1	0
Viewer B	Positive	0	0	0	14	24
	Negative	10	15	15	2	0
Viewer C	Positive	0	0	0	14	24
	Negative	10	15	15	2	0

Discordant Results of Nortriptyline Strip

Viewer	Sample Number	GC/MS Result	Strip FormatViewer Results
Viewer A	TCA27	1011	Negative
Viewer B	TCA51	1025	Negative
Viewer B	TCA27	1011	Negative
Viewer C	TCA51	1025	Negative
Viewer C	TCA27	1011	Negative

{19}------------------------------------------------

Cassetteformat		Negative	LowNegativeby GC/MS(less than -50%)	Near CutoffNegative byGC/MS(Between -50% and cut-off)	Near CutoffPositive byGC/MS(Betweenthe cut-offand +50%)	HighPositive byGC/MS(greaterthan+50%)
Viewer A	Positive	0	0	0	13	24
	Negative	10	15	15	3	0
Viewer B	Positive	0	0	0	14	24
	Negative	10	15	15	2	0
Viewer C	Positive	0	0	0	13	24
	Negative	10	15	15	3	0

Discordant Results of Nortriptyline Cassette

Viewer	Sample Number	GC/MS Result	Cassette FormatViewer Results
Viewer A	TCA51	1025	Negative
Viewer A	TCA34	1232	Negative
Viewer A	TCA52	1123	Negative
Viewer B	TCA51	1025	Negative
Viewer B	TCA34	1232	Negative
Viewer C	TCA51	1025	Negative
Viewer C	TCA34	1232	Negative
Viewer C	TCA52	1123	Negative

Dip Card format		Negative	Low Negative by GC/MS (less than - 50%)	Near Cutoff Negative by GC/MS (Between - 50% and cut-off)	Near Cutoff Positive by GC/MS (Between the cut-off and +50%)	High Positive by GC/MS (greater than +50%)
Viewer A	Positive	0	0	0	14	24
	Negative	10	15	15	2	0
Viewer B	Positive	0	0	0	14	24
	Negative	10	15	15	2	0
Viewer C	Positive	0	0	0	14	24
	Negative	10	15	15	2	0

Discordant Results of Nortriptyline Dip Card

{20}------------------------------------------------

Viewer	Sample Number	GC/MS Result	Dip Card FormatViewer Results
Viewer A	TCA51	1025	Negative
Viewer A	TCA27	1011	Negative
Viewer B	TCA51	1025	Negative
Viewer B	TCA27	1011	Negative
Viewer C	TCA51	1025	Negative
Viewer C	TCA27	1011	Negative

Cup format		Negative	Low Negative by GC/MS (less than - 50%)	Near Cutoff Negative by GC/MS (Between - 50% and cut-off)	Near Cutoff Positive by GC/MS (Between the cut-off and +50%)	High Positive by GC/MS (greater than +50%)
Viewer A	Positive	0	0	0	13	24
	Negative	10	15	15	3	0
Viewer B	Positive	0	0	0	13	24
	Negative	10	15	15	3	0
Viewer C	Positive	0	0	0	13	24
	Negative	10	15	15	3	0

Discordant Results of Nortriptyline Cup

Viewer	Sample Number	GC/MS Result	Cup FormatViewer Results
Viewer A	TCA51	1025	Negative
Viewer A	TCA27	1011	Negative
Viewer A	TCA38	1097	Negative
Viewer B	TCA51	1025	Negative
Viewer B	TCA27	1011	Negative
Viewer B	TCA38	1097	Negative
Viewer C	TCA51	1025	Negative
Viewer C	TCA27	1011	Negative
Viewer C	TCA38	1097	Negative

EDDP

Strip format	Negative	Low Negative by GC/MS(less than - 50%)	Near Cutoff Negative by GC/MS(Between - 50% and cut-off)	Near Cutoff Positive by GC/MS(Between the cut-off and +50%)	High Positive by GC/MS(greater than +50%)
--------------	----------	--------------------------------------------	--------------------------------------------------------------	-----------------------------------------------------------------	-----------------------------------------------

{21}------------------------------------------------

Viewer A	Positive	0	0	0	13	24
	Negative	10	15	15	3	0
Viewer B	Positive	0	0	0	14	24
	Negative	10	15	15	2	0
Viewer C	Positive	0	0	0	13	24
	Negative	10	15	15	3	0

Discordant Results of EDDP Strip

Discordant Results of EDDP Strip
Viewer	Sample Number	GC/MS Result	Strip FormatViewer Results
Viewer A	EDDP28	308	Negative
Viewer A	EDDP02	302	Negative
Viewer A	EDDP72	303	Negative
Viewer B	EDDP02	302	Negative
Viewer B	EDDP72	303	Negative
Viewer C	EDDP28	308	Negative
Viewer C	EDDP02	302	Negative
Viewer C	EDDP72	303	Negative

Cassette format		Negative	Low Negative by GC/MS (less than - 50%)	Near Cutoff Negative by GC/MS (Between - 50% and cut-off)	Near Cutoff Positive by GC/MS (Between the cut-off and +50%)	High Positive by GC/MS (greater than +50%)
Viewer A	Positive	0	0	0	13	24
	Negative	10	15	15	3	0
Viewer B	Positive	0	0	0	14	24
	Negative	10	15	15	2	0
Viewer C	Positive	0	0	0	14	24
	Negative	10	15	15	2	0

Discordant Results of EDDP Cassette

Viewer	Sample Number	GC/MS Result	Cassette FormatViewer Results
Viewer A	EDDP28	308	Negative
Viewer A	EDDP02	302	Negative
Viewer A	EDDP72	303	Negative
Viewer B	EDDP02	302	Negative
Viewer B	EDDP72	303	Negative
Viewer C	EDDP02	302	Negative

{22}------------------------------------------------

Viewer	Sample Number GC/MS Result		Cassette FormatViewer Results
Viewer C	EDDP72	303	Negative

Dip Cardformat		Negative	LowNegativeby GC/MS(less than -50%)	Near CutoffNegative byGC/MS(Between -50% and cut-off)	Near CutoffPositive byGC/MS(Betweenthe cut-offand +50%)	HighPositive byGC/MS(greaterthan+50%)
Viewer A	Positive	0	0	0	14	24
	Negative	10	15	15	2	0
Viewer B	Positive	0	0	0	13	24
	Negative	10	15	15	3	0
Viewer C	Positive	0	0	0	14	24
	Negative	10	15	15	2	0

Discordant Results of EDDP Dip Card

Viewer	Sample Number	GC/MS Result	Dip Card Format Viewer Results
Viewer A	EDDP02	302	Negative
Viewer A	EDDP72	303	Negative
Viewer B	EDDP28	308	Negative
Viewer B	EDDP02	302	Negative
Viewer B	EDDP72	303	Negative
Viewer C	EDDP02	302	Negative
Viewer C	EDDP72	303	Negative

Cupformat		Negative	LowNegativeby GC/MS(less than -50%)	Near CutoffNegative byGC/MS(Between -50% and cut-off)	Near CutoffPositive byGC/MS(Betweenthe cut-offand +50%)	HighPositive byGC/MS(greaterthan+50%)
Viewer A	Positive	0	0	0	14	24
	Negative	10	15	15	2	0
Viewer B	Positive	0	0	0	14	24
	Negative	10	15	15	2	0
Viewer C	Positive	0	0	0	14	24
	Negative	10	15	15	2	0

{23}------------------------------------------------

Viewer	Sample Number	GC/MS Result	Cup FormatViewer Results
Viewer A	EDDP02	302	Negative
Viewer A	EDDP72	303	Negative
Viewer B	EDDP02	302	Negative
Viewer B	EDDP72	303	Negative
Viewer C	EDDP02	302	Negative
Viewer C	EDDP72	303	Negative

Discordant Results of EDDP Cup

Lay-user study

A lay user study was performed at three intended user sites with 560 lay persons testing each of the Propoxyphene, the Nortriptyline and the EDDP devices. Total of 1680 individuals performed the study. A total of 204 females and 356 males tested the Propoxyphene samples, 213 females and 347 males tested the Nortriptyline samples and 209 females and 351 males tested the EDDP 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; negative, +/-75%, +/-25% of the cutoff by spiking drugs into drug free-pooled urine specimens. The concentrations of the samples were confirmed by GC/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. The results are summarized below.

	Numberofsamples	PropoxypheneConcentration by GC/MS(ng/mL)	Lay person results		The
% of Cutoff			No. ofPositive	No. ofNegative	percentage ofcorrect results(%)
-100%Cutoff	20	0	0	20	100%
-75%Cutoff	20	75	0	20	100%
-50% Cutoff	20	150	0	20	100%
-25% Cutoff	20	225	1	19	95%
+25% Cutoff	20	375	18	2	90%
+50% Cutoff	20	450	20	0	100%
+75% Cutoff	20	525	20	0	100%

Comparison between GC/MS and Lay Person Results (Propoxyphene Strip)

Comparison between GC/MS and Lay Person Results (Propoxyphene Cassette)

% of Cutoff	Numberofsamples	PropoxypheneConcentration by GC/MS(ng/mL)	Lay person results		Thepercentage ofcorrect results(%)
			No. ofPositive	No. ofNegative
-100%Cutoff	20	0	0	20	100%
-75%Cutoff	20	75	0	20	100%

{24}------------------------------------------------

-50% Cutoff	20	150		20	100%
-25% Cutoff	20	225	2	18	90%
+25% Cutoff	20	375	19		તે તે જે જે જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામનાં લોકોનો મુખ્ય વ્યવસાય ખેતી, ખેતમજૂરી તેમ જ પશુપાલન છે. આ ગામમાં પ્રાથમિક શાળા, પંચાયતઘર, આંગણવાડી તેમ જ દૂધની ડેરી જેવી સવલત
+50% Cutoff	20	450	20		100%
+75% Cutoff	20	525	20		100%

Comparison between GC/MS and Lay Person Results (Propoxyphene DipCard)

% of Cutoff	Number of samples	Propoxyphene Concentration by GC/MS (ng/mL)	Lay person results		The percentage of correct results (%)
-100% Cutoff	20	0	0	20	100%
-75% Cutoff	20	75	0	20	100%
-50% Cutoff	20	150	0	20	100%
-25% Cutoff	20	225	1	19	95%
+25% Cutoff	20	375	18	2	90%
+50% Cutoff	20	450	20	0	100%
+75% Cutoff	20	525	20	0	100%

Comparison between GC/MS and Lay Person Results (Propoxyphene Cup)

% of Cutoff	Numberofsamples	PropoxypheneConcentration by GC/MS(ng/mL)	Lay person results		Thepercentage ofcorrect results(%)
			No. ofPositive	No. ofNegative
-100% Cutoff	20	0	0	20	100%
-75% Cutoff	20	75	0	20	100%
-50% Cutoff	20	150	0	20	100%
-25% Cutoff	20	225	1	19	95%
+25% Cutoff	20	375	19	1	95%
+50% Cutoff	20	450	20	0	100%
+75% Cutoff	20	525	20	0	100%

Comparison between GC/MS and Lay Person Results (Nortriptyline Strip)

% of Cutoff	Numberofsamples	NortriptylineConcentration by GC/MS(ng/mL)	Lay person results		Thepercentage ofcorrect results(%)
			No. ofPositive	No. ofNegative
-100% Cutoff	20	0	0	20	100%
-75% Cutoff	20	250	0	20	100%
-50% Cutoff	20	500	0	20	100%
-25% Cutoff	20	750	2	18	90%

{25}------------------------------------------------

+25% Cutoff	20	1250	18	2	90%
+50% Cutoff	20	1500	20	0	100%
+75% Cutoff	20	1750	20	0	100%

Comparison between GC/MS and Lay Person Results (Nortriptyline Cassette)

	Number	NortriptylineConcentration by GC/MS(ng/mL)	Lay person results		The
% of Cutoff	ofsamples		No. ofPositive	No. ofNegative	percentage ofcorrect results(%)
-100% Cutoff	20	0	0	20	100%
-75% Cutoff	20	250	0	20	100%
-50% Cutoff	20	500	0	20	100%
-25% Cutoff	20	750	1	19	95%
+25% Cutoff	20	1250	19	1	95%
+50% Cutoff	20	1500	20	0	100%
+75% Cutoff	20	1750	20	0	100%

Comparison between GC/MS and Lay Person Results (Nortriptyline DipCard)

% of Cutoff	Numberofsamples	NortriptylineConcentration by GC/MS(ng/mL)	Lay person results		Thepercentage ofcorrect results(%)
-100% Cutoff	20	0	0	20	100%
-75% Cutoff	20	250	0	20	100%
-50% Cutoff	20	500	0	20	100%
-25% Cutoff	20	750	2	18	90%
+25% Cutoff	20	1250	18	2	90%
+50% Cutoff	20	1500	20	0	100%
+75% Cutoff	20	1750	20	0	100%

Comparison between GC/MS and Lay Person Results (Nortriptyline Cup)

% of Cutoff	Numberofsamples	NortriptylineConcentration by GC/MS(ng/mL)	Lay person results		Thepercentage ofcorrect results(%)
			No. ofPositive	No. ofNegative
-100% Cutoff	20	0	0	20	100%
-75% Cutoff	20	250	0	20	100%
-50% Cutoff	20	500	0	20	100%
-25% Cutoff	20	750	2	18	90%
+25% Cutoff	20	1250	18	2	90%

{26}------------------------------------------------

+50% Cutoff	20	1500	20	0	100%
+75% Cutoff	20	1750	20	0	100%

Comparison between GC/MS and Lay Person Results (EDDP Strip)

% of Cutoff	Numberofsamples	EDDP Concentration byGC/MS(ng/mL)	Lay person results		Thepercentage ofcorrect results(%)
			No. ofPositive	No. ofNegative
-100% Cutoff	20	0	0	20	100%
-75% Cutoff	20	75	0	20	100%
-50% Cutoff	20	150	0	20	100%
-25% Cutoff	20	225	2	18	90%
+25% Cutoff	20	375	18	2	90%
+50% Cutoff	20	450	20	0	100%
+75% Cutoff	20	525	20	0	100%

Comparison between GC/MS and Lay Person Results (EDDP Cassette)

	Numberofsamples	EDDP Concentration byGC/MS(ng/mL)	Lay person results		The
% of Cutoff			No. ofPositive	No. ofNegative	percentage ofcorrect results(%)
-100% Cutoff	20	0	0	20	100%
-75% Cutoff	20	75	0	20	100%
-50% Cutoff	20	150	0	20	100%
-25% Cutoff	20	225	2	18	90%
+25% Cutoff	20	375	19	1	95%
+50% Cutoff	20	450	20	0	100%
+75% Cutoff	20	525	20	0	100%

Comparison between GC/MS and Lay Person Results (EDDP DipCard)

% of Cutoff	Numberofsamples	EDDP Concentration byGC/MS(ng/mL)	Lay person results		Thepercentage ofcorrect results(%)
			No. ofPositive	No. ofNegative
-100% Cutoff	20	0	0	20	100%
-75% Cutoff	20	75	0	20	100%
-50% Cutoff	20	150	0	20	100%
-25% Cutoff	20	225	1	19	95%
+25% Cutoff	20	375	19	1	95%
+50% Cutoff	20	450	20	0	100%

{27}------------------------------------------------

+75% Cutoff	20	525	20	0	100%
-------------	----	-----	----	---	------

% of Cutoff	Number	EDDP Concentration byGC/MS(ng/mL)	Lay person results		The
	ofsamples		No. ofPositive	No. ofNegative	percentage ofcorrect results(%)
-100%Cutoff	20	0	0	20	100%
-75%Cutoff	20	75	0	20	100%
-50% Cutoff	20	150	0	20	100%
-25% Cutoff	20	225	1	19	તે તે જે જ જીરી તેમ જ દૂધની ડેરી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામમાં પ્રાથમિક શાળા, પંચાયતઘર, આંગણવાડી તેમ જ દૂધની ડેરી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામનાં લોકોનો મુખ્ય
+25% Cutoff	20	375	19	1	તે તે જે જ જીરી તેમ જ દૂધની ડેરી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામમાં પ્રાથમિક શાળા, પંચાયતઘર, આંગણવાડી તેમ જ દૂધની ડેરી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામનાં લોકોનો મુખ્ય
+50% Cutoff	20	450	20	0	100%
+75% Cutoff	20	રેટર	20	0	100%

Comparison between GC/MS and Lav Person Results (EDDP Cup)

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 and method comparison of the devices, it's concluded that the Healgen Propoxyphene Test, Healgen Nortriptyline Test and Healgen EDDP (Methadone Metabolite) Test are substantially equivalent to the predicate.

Regulation Number and Section

§ 862.3910 Tricyclic antidepressant drugs test system.

(a)
Identification. A tricyclic antidepressant drugs test system is a device intended to measure any of the tricyclic antidepressant drugs in serum. The tricyclic antidepressant drugs include imipramine, desipramine, amitriptyline, nortriptyline, protriptyline, and doxepin. Measurements obtained by this device are used in the diagnosis and treatment of chronic depression to ensure appropriate therapy.(b)
Classification. Class II (special controls). A tricyclic antidepressant drugs 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).