The One Step EDDP (Methadone Metabolite) Test Strip is a rapid immunochromatographic assay for the qualitative detection of 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrolidine (EDDP), an inactive metabolite of methadone, at a designated cutoff concentration of 300 ng/mL. This product is used to obtain a visual, qualitative result and is intended for professional use and professionals at point of care sites.

This assay provides only a preliminary result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method.

Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are indicated.

Device Description

The One Step EDDP (Methadone Metabolite) Test is an immunoassay based on the principle of competitive binding. Drugs which may be present in the urine specimen compete against the drug conjugate for binding sites on the antibody. During testing, a urine specimen migrates upward by capillary action. EDDP, if present in the urine specimen below 300 ng/mL, will not saturate the binding sites of antibody-coated particles in the test. The antibody-coated particles will then be captured by immobilized EDDP 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 EDDP level exceeds 300 ng/mL because it will saturate all the binding sites of anti-EDDP antibodies. A drug-positive urine specimen will not generate a colored line in the test line region because of drug competition, while a drug-negative urine specimen containing a drug concentration less than the cut-off will generate a line in the test line region. To serve as a procedural control, a colored line will always appear at the control line region. This confirms sufficient specimen volume, adequate membrane wicking and correct

AI/ML Overview

Here's a summary of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Implicit from Study)	Reported Device Performance
Overall Agreement with GC/MS Analysis (% Agreement)	98% (538/5549) with a 95% Confidence Interval of (96% - 99%)
Accuracy at 50% below cut-off (150 ng/mL EDDP)	>99% (90/90 negative results in spiked samples)
Accuracy at 50% above cut-off (450 ng/mL EDDP)	>99% (90/90 positive results in spiked samples)

Note: The document does not explicitly state "acceptance criteria" with numerical targets. Instead, the "Accuracy" and "Analytical Sensitivity" sections describe the performance that was evaluated and found acceptable. The "Overall Agreement with GC/MS Analysis" of 98% is the primary performance metric for accuracy.

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

Sample Size for Accuracy Study (Clinical Study): 549 specimens across three clinical sites (183 specimens per site).
Sample Size for Analytical Sensitivity Study (Spiked Samples): 630 tests (90 tests at each of 7 different EDDP concentrations).
Data Provenance: The text does not specify the country of origin of the data. The clinical study was performed at "three external clinical study sites," suggesting prospective collection for the purpose of this evaluation. The analytical sensitivity study used "drug-free urine pool[s] spiked with EDDP," indicating laboratory-controlled, prospective data generation.

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

Number of Experts: The document states that the testing for the accuracy study was performed by "3 different employees performing the testing" at the clinical sites for the One Step EDDP Test Strip. However, the ground truth was established by Gas Chromatography/Mass Spectrometry (GC/MS). Therefore, the "experts" in this context would be the technicians or analysts operating the GC/MS.
Qualifications of Experts: The document does not specify the qualifications of the personnel operating the GC/MS.

4. Adjudication Method for the Test Set

The document implies a direct comparison of the One Step EDDP Test Strip results to the GC/MS results. There is no mention of an "adjudication method" involving multiple human readers for either the test device results or the GC/MS results. The GC/MS is presented as the reference method ("preferred confirmatory method"), suggesting its results were considered definitive for ground truth.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, a multi-reader multi-case (MRMC) comparative effectiveness study comparing human readers with and without AI assistance was not done. This device is a diagnostic test strip, not an AI-assisted diagnostic tool for interpretation by human readers.

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

Yes, the performance data presented is for the "One Step EDDP (Methadone Metabolite) Test Strip" itself, without human interpretation influencing the reported accuracy against GC/MS. The test is designed to provide a "visual, qualitative result," which is then compared to the GC/MS. While a human reads the test strip, the reported accuracy reflects the strip's ability to correctly indicate the presence or absence of EDDP at the cutoff, rather than a human's ability to interpret complex images or data. The "Analytical Sensitivity" section, especially with spiked samples, is a clear standalone performance evaluation.

7. The Type of Ground Truth Used

The primary ground truth used was Gas Chromatography/Mass Spectrometry (GC/MS) analysis. GC/MS is described as the "preferred confirmatory method" and the "reference method" against which the device's accuracy was compared.

8. The Sample Size for the Training Set

The document does not provide details on a separate "training set" or its sample size. This type of immunoassay device typically does not involve a machine learning algorithm that requires a "training set" in the conventional sense. Its performance is based on the chemical and immunological properties built into the strip. The studies described are for validation/testing.

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

As there's no mention of a traditional "training set" for a machine learning algorithm, this question is not applicable. The device's performance is inherently linked to its design and manufacturing specifications.

Summary

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

5. 510(k) Summary

APR 1 9 2010

This summary of safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The Assigned 510(k) number is:_K092048

Submitter:

Biosite, Inc. 9975 Summers Ridge Road San Diego, California 92121 Tel.: 858-805-2278 Fax: 858-695-7100

Date:

April 12, 2010

Contact Person:

Lisa Chicorka

Product Names:

One Step EDDP (Methadone Metabolite) Test Strip

Common Name:	Immunochromatographic Test for the 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in urine
Regulation Name:	Methadone Test System
Product Code:	DJR
Regulatory Class:	Class II
Classification Regulation:	21 CFR 862.3620

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

Intended Use

Step EDDP (Methadone Metabolite) Test Strip is a rapid The One immunochromatographic immunoassay for the qualitative detection of 2-ethylidene-1,5dimethyl-3.3-diphenylpyrrolidine (EDDP), an inactive metabolite of methadone, at a designated cutoff concentration of 300 ng/mL. This product is used to obtain a visual, qualitative result and is intended for professional use and professionals at point of care sites.

Clinical consideration and professional judgment should be applied to any drug of abuse test result. particularly when preliminary positive results are indicated.

Description:

Comparison to a Predicate Device:

The predicate devices, ACON MTD One Step Methadone Test Strip and ACON MTD One Step Methadone Test Device (K012595) are intended for the detection of Methadone in urine with a cutoff of 300 ng/mL. The One Step EDDP (Methadone Metabolite) Test Strip is to be used for the detection of the Methadone Metabolite EDDP at a cutoff of 300 ng/mL. The same test principle and technology of these rapid diagnostic tests enables substantial equivalence. Another predicate device, the DRI Methadone Metabolite Enzyme Assay (K023617), is a Liquid Homogeneous Enzyme Assay which detects EDDP with results being obtained spectrophotometrically. Although the test principle differs, the same metabolite is to be detected at the same cut-off (300 ng/mL) as does the One Step EDDP (Methadone Metabolite) Test Strip. Therefore, the DRI Methadone Metabolite Enzyme Assay is also used in the substantial equivalence discussion.

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

A predicate device with identical technology is K081378 -Bionexia™ Single and Multi-Strip Cassette/Dipstick DOA Screen Panels., which are rapid immunochromatographic immunoassays for the qualitative detection of 2-ethylidene-1,5-dimethyl-3,3diphenylpyrrolidine with a cutoff of 100 ng/mL (EDDP) (and other drugs). The submitter is Applied DNA Technologies Inc. BioClinical Performance Data of the One Step EDDP (Methadone Metabolite) Test Strip was compared with the reference method GC/MS and the DRI® Methadone Metabolite Assay (cutoff 300 ng/mL) manufactured by Microgenics, Inc.

Performance Characteristics

The One Step EDDP (Methadone Metabolite) Test Strip was evaluated to determine the performance characteristics of the test. Various studies were performed to determine the Analytical Sensitivity, Cross Reactivity, Interference Substances, Urinary pH, Urinary Specific Gravity, Reading Time Flexibility, Sample Flexibility, Temperature Flexibility, Specimen Storage, Recovery, Stability, POL Study and Clinical Study.

Accuracy

The performance of the One Step EDDP (Methadone Metabolite) Test Strip was evaluated and compared to GC/MS by three external clinical study sites, with 3 different employees performing the testing.

Method	Specimen Cut-off Range by GC/MS Analysis					% Agreement with GC/MS Analysis
		Negative	Low negative (<-50% cutoff)	Near cutoff negative (-50% cutoff to cutoff)	Near cutoff positive (cutoff to +50% cutoff)	High positive (>+50% cutoff)
Clinical Site	Positive	0	0	3	8	70	98% (180/183)
	Negative	100	1	1	0	0	(95% - 100%)*
EDDP Test Strip	Clinical Site	Positive	0	0	4	8	70	98% (179/183)
		Negative	100	1	0	0	0	(94% - 99%)*
		Positive	0	0	4	8	70	98% (179/183)
	Clinical Site	Negative	100	1	0	0	0	(90% - 97%)*
Over All Agreement With GC/MS Analysis							98% (538/5549)(96% - 99%)*

Table 1			One Step EDDP (Methadone Metabolite) Test Strip vs. GC/MS Analysis

Denotes 95% confidence intervals Overall % Agreement with GC/MS is 98%.

Analytical Sensitivity

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

A drug-free urine pool was spiked with EDDP at the following concentrations: 0 ng/mL, 150 ng/mL, 225 ng/mL, 300 ng/mL, 375 ng/mL, 450 ng/mL and 900 ng/mL. The results demonstrate >99% accuracy at 50% above and 50% below the cut-off concentration. The data are summarized below:

EDDPConcentration(ng/mL)	Percent ofCut-off	n	Visual Result
			Negative	Positive
0	0%	90	90	0
150	-50%	90	90	0
225	-25%	90	90	0
300	Cut-off	90	51	39
375	+25%	90	14	76
450	+50%	90	0	90
900	+300%	90	0	90

			Table 2 One Step EDDP (Methadone Metabolite) Test Strip
--	--	--	---------------------------------------------------------	--	--

Risk Analysis

Risk analysis was performed on the One Step EDDP (Methadone Metabolite) Test Strip and results were found acceptable.

Conclusion:

The One Step EDDP (Methadone Metabolite) Test Strip is a rapid chromatographic immunoassay for detection of Methadone Metabolite in human urine at a designated cutoff concentration of 300 ng/mL. The EDDP Test Strip is used to provide only a preliminary analytical result. All positive test results obtained with this device must be confirmed by another test method, preferably GC/MS. It is intended for healthcare professionals including professionals at point-of-care sites to assist in the determination of drug compliance.

!..

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

Image /page/4/Picture/0 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States of America. The seal features a stylized eagle with three lines forming its body and wings, symbolizing health, services, and human aspects. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged in a circular pattern around the eagle.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Biosite, Inc. c/o Lisa Chicorka 9975 Summers Ridge Road San Diego, CA 92121

K092048

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002

APR 1 9 2010

Trade Name: One Step EDDP (Methadone Metabolite) Test Strip Regulation Number: 21 CFR §862.3620 Regulation Name: Methadone test system Regulatory Class: Class II Product Codes: DJR Dated: April 12, 2010 Received: April 13, 2010

Dear Ms. Chicorka:

Re:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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

Page 2

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. 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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or ( 301 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Signature

Courtney C. Harper, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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

Indications for Use Statement

Indications for Use

510(k) Number (if known): K092048

Device Name: One Step EDDP (Methadone Metabolite) Test Strip

Intended Use

Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are indicated.

Prescription Use X (21 CFR Part 801 Subpart D)

Over the

. . . . . . . . . . . . . .

Over the Counter Use _________________________________________________________________________________________________________________________________________________________ (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

And/Or

Division Sign Off

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K092048

Regulation Number and Section

§ 862.3620 Methadone test system.

(a)
Identification. A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by this device are used in the diagnosis and treatment of methadone use or overdose and to determine compliance with regulations in methadone maintenance treatment.(b)
Classification. Class II (special controls). A methadone 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).