LZI Methadone Metabolite Enzyme Immunoassay, LZI Methadone Metabolite (100 and 300) Calibrators

Q: Who is the manufacturer of LZI Methadone Metabolite Enzyme Immunoassay, LZI Methadone Metabolite (100 and 300) Calibrators?

Lin-Zhi International, Inc. filed the 510(k) submission for LZI Methadone Metabolite Enzyme Immunoassay, LZI Methadone Metabolite (100 and 300) Calibrators (K170416).

Q: What is the FDA product code for LZI Methadone Metabolite Enzyme Immunoassay, LZI Methadone Metabolite (100 and 300) Calibrators?

DJR. It is classified under 21 CFR 862.3620 as a Class 2 device in the Clinical Toxicology panel.

Q: What is the regulatory pathway for LZI Methadone Metabolite Enzyme Immunoassay, LZI Methadone Metabolite (100 and 300) Calibrators?

510(k) clearance (submission type: Traditional).

Q: Who can help prepare an FDA 510(k) submission like LZI Methadone Metabolite Enzyme Immunoassay, LZI Methadone Metabolite (100 and 300) Calibrators?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA 510(k) submissions. See https://innolitics.com/services/510ks/ or contact https://innolitics.com/contact.

K170416 · Lin-Zhi International, Inc. · DJR · Jun 26, 2017 · Clinical Toxicology

Device Facts

Record ID	K170416
Device Name	LZI Methadone Metabolite Enzyme Immunoassay, LZI Methadone Metabolite (100 and 300) Calibrators
Applicant	Lin-Zhi International, Inc.
Product Code	DJR · Clinical Toxicology
Decision Date	Jun 26, 2017
Decision	SESE
Submission Type	Traditional
Regulation	21 CFR 862.3620
Device Class	Class 2

Intended Use

The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay is an in vitro diagnostic test intended for the qualitative and semi-quantitative determination of Methadone Metabolite in human urine. The cutoff for both the qualitative and semi-quantitative modes of the assay are 100 ng/mL and 300 ng/mL for methadone metabolite. The assay is designed for prescription use on automated clinical chemistry analyzers. The semi-quantitative mode is for purposes of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as gas or liquid chromatography/mass spectrometry (GC/MS or LC/MS) or (2) permitting laboratories to establish quality control procedures. The assay provides only a preliminary analytical result. A more specific alternative analytical chemistry method must be used in order to obtain a confirmed analytical result. Gas or liquid chromatography/mass spectrometry (GC/MS or LC/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 test result is positive. The LZI Methadone Metabolite (EDDP) (100 and 300) Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the LZI Methadone Metabolite (EDDP) Enzyme Immunoassay at the cutoff values of 100 ng/mL and 300 ng/mL.

Device Story

Homogeneous enzyme immunoassay; detects Methadone Metabolite (EDDP) in human urine. Input: urine sample; Reagents: mouse monoclonal anti-methadone metabolite antibody, G6P, NAD, and G6PDH-labeled EDDP conjugate. Principle: competitive binding between sample EDDP and enzyme-labeled EDDP for fixed antibody; active G6PDH enzyme activity proportional to EDDP concentration; enzyme converts NAD to NADH; absorbance measured spectrophotometrically at 340 nm. Used in clinical laboratories; operated by trained personnel on automated clinical chemistry analyzers (e.g., Beckman Coulter AU480). Output: qualitative (positive/negative) or semi-quantitative (concentration estimate) result. Clinical utility: preliminary screening for methadone metabolite; results require confirmation by GC/MS or LC/MS; aids clinical decision-making regarding drug use.

Clinical Evidence

Bench testing only. Precision evaluated over 22 days (N=88) on Beckman Coulter AU480. Linearity/recovery confirmed via LC/MS. Analytical specificity tested against structurally related compounds and common interfering substances (pH 3-11, specific gravity 1.004-1.025). Method comparison performed on 87 clinical samples (100 ng/mL cutoff) and 84 clinical samples (300 ng/mL cutoff) against LC/MS reference method.

Technological Characteristics

Homogeneous enzyme immunoassay; reagents include mouse monoclonal anti-methadone metabolite antibody, G6P, NAD, and G6PDH-labeled EDDP. Spectrophotometric detection at 340 nm. Automated clinical chemistry analyzer platform. Storage 2-8°C. Calibrators prepared from EDDP standard in synthetic urine matrix.

Indications for Use

Indicated for the qualitative and semi-quantitative determination of Methadone Metabolite (EDDP) in human urine for prescription use on automated clinical chemistry analyzers. Intended for use as a preliminary screening test; requires confirmation by GC/MS or LC/MS.

Regulatory Classification

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.

Special Controls

*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).

Predicate Devices

Lin-Zhi International, Inc. Methadone Metabolite (EDDP) Enzyme Immunoassay (k031797)

Related Devices

K023317 — METHADONE ENZYME IMMUNOASSAY · Lin-Zhi International, Inc. · Dec 12, 2002
K023617 — DRI METHADONE METABOLITE ENZYME IMMUNOASSAY · Microgenics Corp. · Aug 27, 2003
K031797 — METHADONE METABOLITE (EDDP) ENZIME IMMUNOASSAY, CAT. NO. 190 (500 TEST KIT), NO. 191 (5000 TEST KIT) · Lin-Zhi International, Inc. · Oct 10, 2003
K151395 — Immunalysis EDDP Specific Urine Enzyme Immunoassay, Immunalysis EDDP Urine Calibrators, Immunalysis EDDP Urine Control Sets · Immunalysis Corporation · Jul 24, 2015
K192433 — LZI Methadone II Enzyme Immunoassay · Lin-Zhi International, Inc. · Oct 4, 2019

Submission Summary (Full Text)

{0}------------------------------------------------ Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes entwined around it, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES-USA" arranged in a circular pattern around the symbol. The caduceus is a common symbol associated with healthcare and medicine. Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002 June 26, 2017 LIN-ZHI INTERNATIONAL, INC. BERNICE LIN VP OPERATIONS 2945 OAKMEAD VILLAGE COURT SANTA CLARA CA 95051 Re: k170416 Trade/Device Name: LZI Methadone Metabolite (EDDP) Enzyme Immunoassay, LZI Methadone Metabolite (EDDP) (100 And 300) Calibrators Regulation Number: 21 CFR 862.3620 Regulation Name: Methadone test system Regulatory Class: II Product Code: DJR, DJR, DLJ Dated: May 24, 2017 Received: May 25, 2017 Dear Ms. Lin: 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 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 {1}------------------------------------------------ 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 {2}------------------------------------------------ ### Indications for Use 510(k) Number (if known) k170416 #### Device Name LZI Methadone Metabolite (EDDP) Enzyme Immunoassay The LZI Methadone Metabolite (EDDP) (100 and 300) Calibrators #### Indications for Use (Describe) The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay is an in vitro diagnostic test intended for the qualitative and semi-quantitative determination of Methadone Metabolite in human urine. The cutoff for both the and semi-quantitative modes of the assay are 100 ng/mL for methadone metabolite. The assay is designed for prescription use on automated clinical chemistry analyzers. The semi-quantitative mode is for purposes of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as gas or liquid chromatography/mass spectrometry (GC/MS or LC/MS) or (2) permitting laboratories to establish quality control procedures. The assay provides only a preliminary analytical result. A more specific alternistry method must be used in order to obtain a confirmed analytical result. Gas or liquid chromatography/mass spectrometry (GC/MS or LC/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 test result is positive. The LZI Methadone Metabolite (EDDP) (100 and 300) Calibrators are for use as calibrators in the qualitative and semiquantitative calibration of the LZI Methadone Metabolite (EDDP) Enzyme Immunoassay at the cutoff values of 100 ng/mL and 300 ng/mL. Type of Use (Select one or both, as applicable) | <input checked="true" type="checkbox"/> Prescription Use (Part 21 CFR 801 Subpart D) | |----------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | <input type="checkbox"/> 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 of Safety and Effectiveness This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92. ## Submitted On February 9, 2017 ## Last Updated On June 26, 2017 ## Introduction According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence. ## Submitter Name, Address, and Contact: Lin-Zhi International, Inc. 2945 Oakmead Village Court Santa Clara, CA 95051 Phone: (408) 970-8811 (408) 970-9030 Fax: e-mail: bclin@lin-zhi.com Bernice Lin, Ph.D. Contact: VP Operations ### Device Name and Classification | Classification Name: | Enzyme Immunoassay, Methadone Metabolite Class II, DJR (91 Toxicology), 21 CFR 862.3620 | | |-----------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--| | | Drug Specific Calibrators, Class II, DLJ (91 Toxicology), 21 CFR 862.3200 | | | Common Name: Proprietary Name: | Homogeneous Methadone Metabolite Enzyme Immunoassay LZI Methadone Metabolite (EDDP) Enzyme Immunoassay, LZI Methadone Metabolite (EDDP) (100 and 300) Calibrator | | {4}------------------------------------------------ # Legally Marketed Predicate Device(s) The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay (EIA) is substantially equivalent to the Lin-Zhi International, Inc. Methadone Metabolite (EDDP) Enzyme Immunoassay (k031797) manufactured by Lin-Zhi International, Inc. The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay is identical or similar to its predicate in terms of intended use, method principle, device components, and clinical performance. # Device Description The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay is a homogeneous enzyme immunoassay with ready-to-use liquid reagents. The assay is based on competition between EDDP in the sample and EDDP labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. Enzyme activity decreases upon binding to the antibody, and the EDDP concentration in the sample is measured in terms of enzyme activity. In the absence of EDDP in the sample, EDDP-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free EDDP is present in the sample, antibody would bind to free EDDP; the unbound EDDP-labeled G6PDH then exhibits its maximal enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that can be measured spectrophotometrically at 340 nm. The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit. The Ri solution contains mouse monoclonal anti-methadone metabolite antibody, glucose-6phosphate (G6P) nicotinamide adenine dinucleotide (NAD), stabilizers, and sodium azide (0.09 %) as a preservative. The R2 solution contains glucose-6-phosphate dehydrogenase (G6PDH) labeled with methadone metabolite in buffer with sodium azide (0.09 %) as a preservative. The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay calibrators and controls designated for use at the 100 ng/mL cutoff contain 0, 50, 75, 100, 125, 250, 500 ng/mL of methadone metabolite (EDDP) in human urine with sodium azide (0.09 %) as a preservative. These five calibrators and two controls are sold as individual bottles. The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay calibrators and controls designated for use at the 300 ng/mL cutoff contain 0, 150, 225, 300, 375, 600, and 1000 ng/mL of methadone metabolite (EDDP) in human urine with sodium azide (0.09 %) as a preservative. These five calibrators and two controls are sold as individual bottles. {5}------------------------------------------------ # Intended Use The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay is an in vitro diagnostic test intended for the qualitative and semi-quantitative determination of Methadone Metabolite in human urine. The cutoff for both the qualitative and semi-quantitative modes of the assay are 100 ng/mL and 300 ng/mL for methadone metabolite. The assay is designed for prescription use on automated clinical chemistry analyzers. The semi-quantitative mode is for purposes of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as gas or liquid chromatography/mass spectrometry (GCMS or (2) permitting laboratories to establish quality control procedures. The assay provides only a preliminary analytical result. A more specific alternative analytical chemistry method must be used in order to obtain a confirmed analytical result. Gas or liguid chromatography/mass spectrometry (GC/MS or LC/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 test result is positive. The LZI Methadone Metabolite (EDDP) (100 and 300) Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the LZI Methadone Metabolite (EDDP) Enzyme Immunoassay at the cutoff values of 100 ng/mL and 300 ng/mL. {6}------------------------------------------------ # Comparison to Predicate Device The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay is substantially equivalent to the Lin-Zhi International, Inc. Methadone Metabolite Enzyme Immunoassay, Calibrators and Controls cleared by the FDA under the premarket notification k031797 for its stated intended use. The following table compares LZI's Methadone Metabolite (EDDP) Enzyme Immunoassay with the predicate device. | Device Characteristics | Subject Device (k170416) LZI Methadone Metabolite (EDDP) Enzyme Immunoassay and Methadone Metabolite (EDDP) (100 and 300) Calibrators | Predicate Device (k031797) LZI Methadone Metabolite (EDDP) Enzyme Immunoassay, Calibrators and Controls | |---------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Intended Use | The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay is an in vitro diagnostic test intended for the qualitative and semi-quantitative determination of Methadone Metabolite in human urine. The cutoff for the qualitative and semi- quantitative modes of the assay are 100 ng/mL and 300 ng/mL for methadone metabolite. The assay is designed for prescription use on automated clinical chemistry analyzers. The assay provides only a preliminary analytical | The Lin-Zhi International, Inc. (LZI) Methadone Metabolite (EDDP) Enzyme Immunoassay is intended for the qualitative and semi-quantitative determination of methadone metabolite in human urine at a cutoff value of 300 ng/mL. The assay is designed for professional use with a number of automated clinical chemistry analyzers. This assay provides a rapid screening procedure for determining the presence of methadone metabolite in urine. The assay provides only a | | | result. A more specific alternative analytical chemistry method must be used in order to obtain a confirmed analytical result. Gas or liquid chromatography/mass spectrometry (GC/MS or LC/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 test result is positive. | preliminary analytical result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas or liquid chromatography/mass spectrometry (GC/MS or LC/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 test result is positive. | | Analyte | Methadone Metabolite (EDDP) | Methadone Metabolite (EDDP) | | Cutoff | 100 and 300 ng/ml | 300 ng/mL | | Matrix | Urine | Urine | | Calibrators Level | 100 ng/mL Cutoff: 5 Levels 0, 50, 100, 250, and 500 ng/mL 300 ng/mL Cutoff: 5 Levels 0, 150, 300, 600, and 1000 ng/mL | 0, 150, 300, 600, and 1000 ng/mL | | Storage | 2-8°C until expiration date | 2-8°C until expiration date | {7}------------------------------------------------ ## Performance Characteristics Summary: Beckman Coulter AU480 Analyzer ## Precision: 100 ng/mL Cutoff ### Semi-Quantitative Precision Analysis Summary: Qualitative Results | Methadone Metabolite (EDDP) Concentration | Within Run (N=22) | Total Precision (N=88) | |----------------------------------------------------|----------------------|---------------------------| | 0 ng/mL | - | - | | 25 ng/mL | - | - | | 50 ng/mL | - | - | | 75 ng/mL | - | - | | 100 ng/mL | - | - | | 125 ng/mL | + | + | | 150 ng/mL | + | + | | 175 ng/mL | + | + | | 200 ng/mL | + | + | #### Semi-Quantitative Positive/Negative Results: | 100 ng/mL Cutoff Result: | | Within Run (N=22) | | Total Precision (N=88) | | |----------------------------------------------------|-------------|-------------------|---------------|------------------------|---------------| | Methadone Metabolite (EDDP) Concentration | % of Cutoff | # of Samples | EIA Result | # of Samples | EIA Result | | 0 ng/mL | 0.0 % | 22 | 22 Negative | 88 | 88 Negative | | 25 ng/mL | 25.0 % | 22 | 22 Negative | 88 | 88 Negative | | 50 ng/mL | 50.0 % | 22 | 22 Negative | 88 | 88 Negative | | 75 ng/mL | 75.0 % | 22 | 22 Negative | 88 | 88 Negative | | 100 ng/mL | 100.0 % | 22 | 11 Neg/11 Pos | 88 | 40 Pos/48 Neg | | 125 ng/mL | 125.0 % | 22 | 22 Positive | 88 | 88 Positive | | 150 ng/mL | 150.0 % | 22 | 22 Positive | 88 | 88 Positive | | 175 ng/mL | 175.0 % | 22 | 22 Positive | 88 | 88 Positive | | 200 ng/mL | 200.0 % | 22 | 22 Positive | 88 | 88 Positive | #### Qualitative Positive/Negative Results: | 100 ng/mL Cutoff Result: | Within Run (N=22) | | Total Precision (N=88) | | | |----------------------------------------------------|-------------------|--------------|------------------------|--------------|---------------| | Methadone Metabolite (EDDP) Concentration | % of Cutoff | # of Samples | EIA Result | # of Samples | EIA Result | | 0 ng/mL | 0.0 % | 22 | 22 Negative | 88 | 88 Negative | | 25 ng/mL | 25.0 % | 22 | 22 Negative | 88 | 88 Negative | | 50 ng/mL | 50.0 % | 22 | 22 Negative | 88 | 88 Negative | | 75 ng/mL | 75.0 % | 22 | 22 Negative | 88 | 88 Negative | | 100 ng/mL | 100.0 % | 22 | 13 Neg/ 9 Pos | 88 | 54 Neg/34 Pos | | 125 ng/mL | 125.0 % | 22 | 22 Positive | 88 | 88 Positive | | 150 ng/mL | 150.0 % | 22 | 22 Positive | 88 | 88 Positive | | 175 ng/mL | 175.0 % | 22 | 22 Positive | 88 | 88 Positive | | 200 ng/mL | 200.0 % | 22 | 22 Positive | 88 | 88 Positive | {8}------------------------------------------------ ## Performance Characteristics Summary, continued: Beckman Coulter AU480 Analyzer #### Precision: 300 ng/mL Cutoff #### Semi-Quantitative Precision Analysis Summary: Qualitative Results | Methadone Metabolite (EDDP) Concentration | Within Run (N=22) | Total Precision (N=88) | |----------------------------------------------------|----------------------|---------------------------| | 0 ng/mL | - | - | | 75 ng/mL | - | - | | 150 ng/mL | - | - | | 225 ng/mL | - | - | | 300 ng/mL | + | + | | 375 ng/mL | + | + | | 450 ng/mL | + | + | | 525 ng/mL | + | + | | 600 ng/mL | + | + | #### Semi-Quantitative Positive/Negative Results: | 300 ng/mL Cutoff Result: | | | Within Run (N=22) | Total Precision (N=88) | | |----------------------------------------------------|-------------|--------------|-------------------|------------------------|----------------| | Methadone Metabolite (EDDP) Concentration | % of Cutoff | # of Samples | EIA Result | # of Samples | EIA Result | | 0 ng/mL | 0.0 % | 22 | 22 Negative | 88 | 88 Negative | | 75 ng/mL | 25.0 % | 22 | 22 Negative | 88 | 88 Negative | | 150 ng/mL | 50.0 % | 22 | 22 Negative | 88 | 88 Negative | | 225 ng/mL | 75.0 % | 22 | 22 Negative | 88 | 88 Negative | | 300 ng/mL | 100.0 % | 22 | 6 Neg/ 16 Pos | 88 | 36 Neg/ 52 Pos | | 375 ng/mL | 125.0 % | 22 | 22 Positive | 88 | 88 Positive | | 450 ng/mL | 150.0 % | 22 | 22 Positive | 88 | 88 Positive | | 525 ng/mL | 175.0 % | 22 | 22 Positive | 88 | 88 Positive | | 600 ng/mL | 200.0 % | 22 | 22 Positive | 88 | 88 Positive | #### Qualitative Positive/Negative Results: | 300 ng/mL Cutoff Result: | | Within Run (N=22) | | Total Precision (N=88) | | |-----------------------------------|-------------|-------------------|--------------|------------------------|---------------| | Methadone Metabolite (EDDP) | % of Cutoff | # of Samples | EIA Result | # of Samples | EIA Result | | Concentration | | | | | | | 0 ng/mL | 0.0 % | 22 | 22 Negative | 88 | 88 Negative | | 75 ng/mL | 25.0 % | 22 | 22 Negative | 88 | 88 Negative | | 150 ng/mL | 50.0 % | 22 | 22 Negative | 88 | 88 Negative | | 225 ng/mL | 75.0 % | 22 | 22 Negative | 88 | 88 Negative | | 300 ng/mL | 100.0 % | 22 | 7 Neg/15 Pos | 88 | 33 Neg/55 Pos | | 375 ng/mL | 125.0 % | 22 | 22 Positive | 88 | 88 Positive | | 450 ng/mL | 150.0 % | 22 | 22 Positive | 88 | 88 Positive | | 525 ng/mL | 175.0 % | 22 | 22 Positive | 88 | 88 Positive | | 600 ng/mL | 200.0 % | 22 | 22 Positive | 88 | 88 Positive | {9}------------------------------------------------ ## Performance Characteristics Summary, continued: Beckman Coulter AU480 Analyzer ## Method Comparison - Clinical Samples: 100 ng/mL Cutoff From a total of eighty-seven (87) clinical unaltered samples, Semi-Quantitative & Qualitative Data: | 100 ng/mL Cutoff | Neg | < 50 % of the cutoff | Near Cutoff Neg | Near Cutoff Pos | High Pos | |---------------------|-----|-------------------------|-----------------------|-----------------------|-------------| | Positive | 0 | 0 | 0 | 2 | 40 | | Negative | 23 | 11 | 9 | 2* | 0 | Qualitative Accuracy Study: The following table summarizes the result for the two discordant samples: | 100 ng/mL Cutoff | Assay Result: | | LC/MS (ng/mL) | |---------------------|---------------|---------|---------------| | | LC/MS | LZI EIA | | | Sample #45 | + | - | 103.1 | | Sample #46 | + | - | 126.0 | Concentration for the discrepant samples are based on the absorbance rate from a single point calibration. Semi-Quantitative Accuracy Study: | 100 ng/mL Cutoff | Neg | < 50 % of the cutoff | Near Cutoff Neg | Near Cutoff Pos | High Pos | |---------------------|-----|-------------------------|-----------------------|-----------------------|-------------| | Positive | 0 | 0 | 0 | 2 | 40 | | Negative | 23 | 11 | 9 | 2* | 0 | The following table summarizes the result for the two discordant samples: | 100 ng/mL Cutoff | Assay Result: | | LC/MS (ng/mL) | |---------------------|---------------|---------|---------------| | | LC/MS | LZI EIA | | | Sample #45 | + | - | 103.1 | | Sample #46 | + | - | 126.0 | {10}------------------------------------------------ ## Method Comparison - Clinical Samples: 300 ng/mL Cutoff From a total of eighty-four (84) clinical unaltered samples, Semi-Quantitative & Qualitative Qualitative Accuracy Study: | 300 ng/mL Cutoff | Neg | < 50 % of the cutoff | Near Cutoff Neg | Near Cutoff Pos | High Pos | |---------------------|-----|-------------------------|-----------------------|-----------------------|-------------| | Positive | 0 | 0 | 0 | 4 | 38 | | Negative | 21 | 15 | 6 | 0 | 0 | Semi-Quantitative Accuracy Study: | 300 ng/mL Cutoff | Neg | < 50 % of the cutoff | Near Cutoff Neg | Near Cutoff Pos | High Pos | |---------------------|-----|-------------------------|-----------------------|-----------------------|-------------| | Positive | 0 | 0 | 0 | 4 | 38 | | Negative | 21 | 15 | 6 | 0 | 0 | ## Cross-reactivity: 100 ng/mL Cutoff Methadone Metabolite and Structurally Related Compounds for 100 ng/mL Cutoff: | Cross-reactant | Spiked [] (ng/mL) | EIA [] (ng/mL) | % Cross Reactivity | |-------------------------------------------|----------------------|-------------------|-----------------------| | EDDP | 100 | Pos | 100 % | | EMDP | 100,000 | Neg | <0.1 % | | Methadone | 300,000 | Neg | <0.1 % | | LAAM HCl | 500,000 | Neg | <0.1 % | | (±)-α-Methadol | 300,000 | Neg | <0.1 % | | (-)-Isomethadone HCl | 60,000 | Neg | <0.2 % | | (-)-α-Noracetylmethadol (Nor-LAAM) HCl | 300,000 | Neg | <0.1 % | ## Cross-reactivity: 300 ng/mL Cutoff Methadone Metabolite and Structurally Related Compounds for 100 ng/mL Cutoff: | Cross-reactant | Spiked [](ng/mL) | EIA (ng/mL) | % Cross Reactivity | |-------------------------------------------|---------------------|----------------|-----------------------| | EDDP | 300 | Pos | 100 % | | EMDP | 100,000 | Neg | <0.1 % | | Methadone | 500,000 | Neg | <0.1 % | | LAAM HCl | 500,000 | Neg | <0.1 % | | (±)-α-Methadol | 300,000 | Neg | <0.1 % | | (-)-Isomethadone HCl | 200,000 | Neg | <0.1 % | | (-)-α-Noracetylmethadol (Nor-LAAM) HCl | 300,000 | Neg | <0.1 % | {11}------------------------------------------------ ## Endogenous Compound Interference & Specific Gravity: No significant undesired cross-reactants or endogenous substance interference was observed. ## Performance Characteristics Summary, continued: Beckman Coulter AU480 Analyzer ## Summary: The information provided in this pre-market notification demonstrates that the LZI Methadone Metabolite (EDDP) Enzyme Immunoassay and LZI Methadone Metabolite (EDDP) (100 and 300) Calibrators are substantially equivalent to the legally marketed predicate device for its general intended use. Substantial equivalence was demonstrated through comparison of intended use and physical properties to the commercially available predicate device as confirmed by chromatography/mass spectrometry (LC/MS), an independent analytical chemistry method. The information supplied in this pre-market notification provides reasonable assurance that the LZI Methadone Metabolite (EDDP) Enzyme Immunoassay and LZI Methadone Metabolite (EDDP) (100 and 300) Calibrators are safe and effective for its stated intended use.