LZI ORAL FLUID 6-ACETYLMORPHINE ENZYME IMMUNOASSAY, LZI ORAL FLUID 6-ACETYLMORPHINE CALIBRATORS (5 ML), LZI ORAL FLUID 6

Q: Who is the manufacturer of LZI ORAL FLUID 6-ACETYLMORPHINE ENZYME IMMUNOASSAY, LZI ORAL FLUID 6-ACETYLMORPHINE CALIBRATORS (5 ML), LZI ORAL FLUID 6?

Lin-Zhi International, Inc. filed the 510(k) submission for LZI ORAL FLUID 6-ACETYLMORPHINE ENZYME IMMUNOASSAY, LZI ORAL FLUID 6-ACETYLMORPHINE CALIBRATORS (5 ML), LZI ORAL FLUID 6 (K141205).

Q: What is the FDA product code for LZI ORAL FLUID 6-ACETYLMORPHINE ENZYME IMMUNOASSAY, LZI ORAL FLUID 6-ACETYLMORPHINE CALIBRATORS (5 ML), LZI ORAL FLUID 6?

DJG. It is classified under 21 CFR 862.3650 as a Class 2 device in the Clinical Toxicology panel.

Q: What is the regulatory pathway for LZI ORAL FLUID 6-ACETYLMORPHINE ENZYME IMMUNOASSAY, LZI ORAL FLUID 6-ACETYLMORPHINE CALIBRATORS (5 ML), LZI ORAL FLUID 6?

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

Q: Who can help prepare an FDA 510(k) submission like LZI ORAL FLUID 6-ACETYLMORPHINE ENZYME IMMUNOASSAY, LZI ORAL FLUID 6-ACETYLMORPHINE CALIBRATORS (5 ML), LZI ORAL FLUID 6?

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.

K141205 · Lin-Zhi International, Inc. · DJG · Feb 13, 2015 · Clinical Toxicology

Device Facts

Record ID	K141205
Device Name	LZI ORAL FLUID 6-ACETYLMORPHINE ENZYME IMMUNOASSAY, LZI ORAL FLUID 6-ACETYLMORPHINE CALIBRATORS (5 ML), LZI ORAL FLUID 6
Applicant	Lin-Zhi International, Inc.
Product Code	DJG · Clinical Toxicology
Decision Date	Feb 13, 2015
Decision	SESE
Submission Type	Traditional
Regulation	21 CFR 862.3650
Device Class	Class 2

Intended Use

The LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay is intended for the qualitative and semi-quantitative determination of 6-Acetylmorphine in neat human oral fluid, collected into the LZI Oral Fluid Collector, at the cutoff value of 4 ng/mL. The assay is designed for prescription use with a number of 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 GCMS and LCMS or (2) permitting laboratories to establish quality control procedures. The LZI Oral Fluid 6-Acetylmorphine Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay at the cutoff value of 4 ng/mL. The LZI Oral Fluid 6-Acetylmorphine Controls are for use as assayed quality control materials to monitor the precision of the LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay at the cutoff value of 4 ng/mL. The assay provides only a preliminary analytical result. A more specific alternative chemical 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.

Device Story

Homogeneous enzyme immunoassay (EIA) for 6-Acetylmorphine detection in oral fluid. Input: neat human oral fluid collected via LZI Oral Fluid Collector. Principle: competitive binding between sample drug and G6PDH-labeled drug for fixed antibody; enzyme activity inhibited when antibody binds labeled drug; free drug in sample displaces labeled drug, increasing enzyme activity. Output: spectrophotometric absorbance change at 340 nm, proportional to drug concentration. Used in clinical laboratories; operated by trained technicians on automated chemistry analyzers (e.g., Beckman AU400e). Results are preliminary; require confirmation via GC/MS or LC/MS. Clinical decision-making relies on professional judgment following screening. Benefits: rapid screening for 6-Acetylmorphine in oral fluid samples.

Clinical Evidence

Bench testing only. Precision studies (n=80 per concentration) evaluated total and within-run performance across 0-8 ng/mL range. Analytical recovery showed 96.7-120% accuracy. Clinical correlation study (n=150) compared immunoassay results against GC/MS. Semi-quantitative mode showed 99.0% agreement; qualitative mode showed 98.0% agreement. Interference testing identified Ascorbic Acid (>3 mg/mL) as a source of false-negatives.

Technological Characteristics

Homogeneous enzyme immunoassay. Reagents: mouse monoclonal anti-6-Acetylmorphine antibody, G6PDH-labeled 6-Acetylmorphine, G6P, NAD, stabilizers, 0.09% sodium azide. Matrix: synthetic oral fluid for calibrators/controls. Detection: spectrophotometric (340 nm). Form factor: liquid reagents, calibrators, and controls. Connectivity: compatible with automated clinical chemistry analyzers. Storage: 2-8°C.

Indications for Use

Indicated for the qualitative and semi-quantitative determination of 6-Acetylmorphine in neat human oral fluid at a 4 ng/mL cutoff. Intended for prescription use in clinical laboratories using automated chemistry analyzers to screen for drug presence.

Regulatory Classification

Identification

An opiate test system is a device intended to measure any of the addictive narcotic pain-relieving opiate drugs in blood, serum, urine, gastric contents, and saliva. An opiate is any natural or synthetic drug that has morphine-like pharmocological actions. The opiates include drugs such as morphine, morphine glucoronide, heroin, codeine, nalorphine, and meperedine. Measurements obtained by this device are used in the diagnosis and treatment of opiate use or overdose and in monitoring the levels of opiate administration to ensure appropriate therapy.

Special Controls

*Classification.* Class II (special controls). An opiate test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (*e.g.,* programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).

Predicate Devices

Lin-Zhi International, Inc. 6-Acetylmorphine Enzyme Immunoassay, Calibrators and Controls for Hitachi 717 Systems (k101195)

Related Devices

K101195 — 6-ACETYLMORPHINE ENZYME IMMUNOASSAY WITH 6-ACETYLMORPHINE CALIBRATORS AND CONTROLS · Lin-Zhi International, Inc. · Jul 6, 2010
K120761 — LZI OPIATE 2000 HOMOGENEOUS ENZYME IMMUNOASSAY, LZI OPIATE 2000 CALIBRATORS, LZI OPIATE 2000 CONTROLS · Lin-Zhi International, Inc. · May 8, 2012
K231007 — CEDIA Heroin Metabolite (6-AM) Assay · Microgenics Corporation · Sep 27, 2023
K050988 — OPIATE ORAL FLUID HOMOGENEOUS ENZYME IMMUNOASSAY, CALIBRATORS AND CONTROLS · Lin-Zhi International, Inc. · Apr 6, 2006

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 circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of a caduceus, which is a symbol often associated with healthcare and medicine. Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002 February 13, 2015 LIN-ZHI INTERNATIONAL, INC. BERNICE LIN, PH.D. VP OF OPERATIONS 670 ALMANOR AVE SUNNYVALE CA 94085 Re: K141205 Trade/Device Name: LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay LZI Oral Fluid 6-Acetylmorphine Calibrators LZI Oral Fluid 6-Acetylmorphine Controls Regulation Number: 21 CFR 862.3650 Regulation Name: Opiate test system Regulatory Class: II Product Code: DJG, DKB, DIF Dated: February 2, 2015 Received: February 4, 2015 Dear Dr. Bernice 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 (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/ResourcesforYou/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, Stayce Beck -S For: 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) k141205 Device Name LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay LZI Oral Fluid 6-Acetylmorphine Calibrators LZI Oral Fluid 6-Acetylmorphine Controls Indications for Use (Describe) The LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay is intended for the qualitative and semi-quantitative determination of 6-Acetylmorphine in neat human oral fluid, collected into the LZI Oral Fluid Collector, at the cutoff value of 4 ng/mL. The assay is designed for prescription use with a number of 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 GCMS and LCMS or (2) permitting laboratories to establish quality control procedures. The LZI Oral Fluid 6-Acetylmorphine Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay at the cutoff value of 4 ng/mL. The LZI Oral Fluid 6-Acetylmorphine Controls are for use as assayed quality control materials to monitor the precision of the LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay at the cutoff value of 4 ng/mL. The assay provides only a preliminary analytical result. A more specific alternative chemical 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. 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}------------------------------------------------ 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. ## 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. 670 Almanor Avenue Sunnyvale, CA 94085 Phone: (408) 732-3856 Fax: (408) 732-3849 e-mail: bclin@lin-zhi.com | Contact: | Bernice Lin, Ph.D. | |----------|--------------------| | | VP Operations | #### Preparation Date February 12, 2015 #### Device Name and Classification | Classification Name: | Enzyme Immunoassay, Opiates | |----------------------|------------------------------------------------------------| | | Class II, DJG (91 Toxicology), | | | 21 CFR 862.3650 | | | Drug Specific Calibrators, | | | Class II, DLJ (91 Toxicology), | | | 21 CFR 862.3200 | | | Drug Specific Controls, | | | Class I, LAS (91 Toxicology), | | | 21 CFR 862.3280 | | Common Name: | Homogeneous Oral Fluid 6-Acetylmorphine Enzyme Immunoassay | | Proprietary Name: | LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay, | | | LZI Oral Fluid 6-Acetylmorphine Calibrators | | | LZI Oral Fluid 6-Acetylmorphine Controls | {4}------------------------------------------------ ## Legally Marketed Predicate Device(s) The LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay (EIA) (k141205) is substantially equivalent to the Lin-Zhi International, Inc. 6-Acetylmorphine Enzyme Immunoassay, Calibrators and Controls for Hitachi 717 Systems (k101195) manufactured by Lin-Zhi International. Inc. The LZI Oral Fluid 6-Acetylmorphine 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 Oral Fluid 6-Acetylmorphine assay is a homogeneous enzyme immunoassay with ready-to-use liquid reagent. The assay is based on competition between drug in the sample and drug 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 drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, 6-Acetylmorphine-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free drug is present in the sample, antibody would bind to free drug, the unbound 6-Acetylmorphine-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 Oral Fluid 6-Acetylmorphine Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit. The R1 solution contains mouse monoclonal anti-6-Acetylmorphine 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 6-Acetylmorphine in buffer with sodium azide (0.09%) as preservative. The LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay calibrators and controls designated for use at the 4 ng/mL cutoffs contain 0, 2, 4, 6, 10, and 20 ng/mL of 6-Acetylmorphine in synthetic oral fluid matrix with sodium azide (0.09%) as preservative. These five calibrators and two controls are sold as individual bottles. {5}------------------------------------------------ ## Intended Use The LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay is intended for the qualitative and semi-quantitative determination of 6-Acetylmorphine in neat human oral fluid, collected into the LZI Oral Fluid Collector, at the cutoff value of 4 ng/mL. The assay is designed for prescription use with a number of 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 GC/MS or (2) permitting laboratories to establish quality control procedures. The LZI Oral Fluid 6-Acetylmorphine Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay at the cutoff value of 4 ng/mL. The LZI Oral Fluid 6-Acetylmorphine Controls are for use as assayed quality control materials to monitor the precision of the LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay at the cutoff value of 4 ng/mL. The assay provides only a preliminary analytical result. A more specific alternative 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 exercised with any drug of abuse test result, particularly when the preliminary test result is positive. {6}------------------------------------------------ # Comparison to Predicate Device The LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay (k141205) is substantially equivalent to the Lin-Zhi International, Inc. 6-Acetylmorphine Enzyme Immunoassay, Calibrators and Controls for Hitachi 717 Systems cleared by the FDA under the premarket notification k101195 for its stated intended use. The following table compares LZI's Oral Fluid 6-Acetylmorphine Enzyme Immunoassay with the predicate device. | Device Characteristics | Subject Device (k141205) LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay, Calibrators and Controls | Predicate Device (k101195) LZI 6-Acetylmorphine Enzyme Immunoassay, Calibrators and Controls | |---------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Intended Use | The LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay, when used in conjunction with the Beckman AU400e automated clinical system analyzers, is intended for the qualitative and semi- quantitative determination of 6- Acetylmorphine in neat human oral fluid, collected into the LZI Oral Fluid Collector, at the cutoff value 4 ng/mL. The assay is designed for prescription use with a number of automated clinical chemistry analyzers. This assay provides a rapid screening procedure for determining the presence of 6-Acetylmorphine in oral fluid. The assay provides only a preliminary analytical result. A more specific alternative 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 exercised with any drug of abuse test result, particularly when the preliminary test result is positive. | The LZI 6-Acetylmorphine Enzyme Immunoassay, when used in conjunction with Hitachi 717 automated clinical system analyzers, is intended for the qualitative and semi-quantitative determination of 6-Acetylmorphine in human urine, at a cutoff value of 10 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 6-Acetylmorphine in urine. The assay provides only a 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 | 6-Acetylmorphine | 6-Acetylmorphine | | Cutoff | 4 ng/ml | 10 ng/mL | | Matrix | Oral fluid | Urine | | Calibrator | 5 Levels | 5 Levels | | Levels | (0, 2, 4, 10, 20 ng/mL) | (0, 5, 10, 20, 40 ng/mL) | | Control Levels | 2 Levels | 2 Levels | | | (2 ng/mL, 6 ng/mL) | (7.5 ng/mL, 12.5 ng/mL) | | Storage | 2-8 ℃ until expiration date | 2-8 ℃ until expiration date | {7}------------------------------------------------ # Performance Characteristics Summary: Beckman AU400e Analyzer # Precision: | 4 ng/mL Cutoff Result: | | | | | | |------------------------|-------------|-------------------------|--------------------|-------------------------|--------------------| | Sample Concentration | % of Cutoff | Total Precision | | Within Run Precision | | | | | Number of Determination | Immunoassay Result | Number of Determination | Immunoassay Result | | 0 ng/mL | -100.0% | 80 | 80 Negative | 20 | 20 Negative | | 1 ng/mL | -75.0% | 80 | 80 Negative | 20 | 20 Negative | | 2 ng/mL | -50.0% | 80 | 80 Negative | 20 | 20 Negative | | 3 ng/mL | -25.0% | 80 | 80 Negative | 20 | 20 Negative | | 4 ng/mL | 100.0% | 80 | 32 Pos/48 Neg | 20 | 8 Pos/12 Neg | | 5 ng/mL | +25.0% | 80 | 80 Positive | 20 | 20 Positive | | 6 ng/mL | +50.0% | 80 | 80 Positive | 20 | 20 Positive | | 7 ng/mL | +75.0% | 80 | 80 Positive | 20 | 20 Positive | | 8 ng/mL | +100.0% | 80 | 80 Positive | 20 | 20 Positive | ## Semi-Quantitative Positive/Negative Results: ## Qualitative (ΔΟD Value) Positive/Negative Results: | | 4 ng/mL Cutoff Result: | | Total Precision | | Within Run Precision | | |-------------------------|------------------------|----------------------------|-----------------------|----------------------------|-----------------------|--| | Sample Concentration | % of Cutoff | Number of Determination | Immunoassay Result | Number of Determination | Immunoassay Result | | | 0 ng/mL | -100.0% | 80 | 80 Negative | 20 | 20 Negative | | | 1 ng/mL | -75.0% | 80 | 80 Negative | 20 | 20 Negative | | | 2 ng/mL | -50.0% | 80 | 80 Negative | 20 | 20 Negative | | | 3 ng/mL | -25.0% | 80 | 80 Negative | 20 | 20 Negative | | | 4 ng/mL | 100.0% | 80 | 18 Pos/62 Neg | 20 | 4 Pos/16 Neg | | | 5 ng/mL | +25.0% | 80 | 80 Positive | 20 | 20 Positive | | | 6 ng/mL | +50.0% | 80 | 80 Positive | 20 | 20 Positive | | | 7 ng/mL | +75.0% | 80 | 80 Positive | 20 | 20 Positive | | | 8 ng/mL | +100.0% | 80 | 80 Positive | 20 | 20 Positive | | ## Analytical Recovery: | Expected Value (ng/mL) | Observed Value (ng/mL) | % Recovery | |---------------------------|---------------------------|------------| | 1 | 1.2 | 120.0 | | 2 | 2.2 | 110.0 | | 4 | 4.3 | 107.5 | | 6 | 5.8 | 96.7 | | 8 | 8.1 | 101.3 | | 10 | 10.1 | 101.0 | | 12 | 12.1 | 100.8 | | 14 | 15.0 | 107.1 | | 16 | 16.8 | 105.0 | | 18 | 18.8 | 104.4 | | 20 | 20.6 | 103.0 | {8}------------------------------------------------ # Method Comparison: Clinical Samples From a total of one-hundred-fifty (150) clinical unaltered samples #### Clinical Samples Correlation Results: Semi-Quantitative Accuracy Study | 4 ng/mL Cutoff | Negative | < 50 % of the cutoff concentration by GC/MS analysis | Near Cutoff Negative (Between 50 % below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50 % above the cutoff concentration) | High Positive (Greater than 50 % above the cutoff concentration) | % Agreement | |-------------------|----------|------------------------------------------------------------------|--------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------|----------------| | Positive | 0 | 0 | 0 | 10 | 89 | 99.0% | | Negative | 20 | 14 | 16 | 1 * | 0 | 100.0% | Discrepant samples determined as compared to the Estimated GC/MS Total Value | Discrepant Sample # | GC/MS 6AM (ng/mL) | Pos/ Neg Result | AU400e Immunoassay Semi- Quantitative Result (ng/mL) | Pos/ Neg Result | |---------------------------|-------------------------|-----------------------|------------------------------------------------------------------|-----------------------| | 51* | 4.2 | + | 3.5 | - | #### Clinical Samples Correlation Results: Qualitative Accuracy Study (ΔΟD, mAu) | 4 ng/mL Cutoff | Negative | < 50 % of the cutoff concentration by GC/MS analysis | Near Cutoff Negative (Between 50 % below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50 % above the cutoff concentration) | High Positive (Greater than 50 % above the cutoff concentration) | % Agreement | |-------------------|----------|------------------------------------------------------------------|--------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------|----------------| | Positive | 0 | 0 | 0 | 9 | 89 | 98.0% | | Negative | 20 | 14 | 16 | 2* | 0 | 100.0% | | Discrepant Sample # | GC/MS 6AM (ng/mL) | Pos/ Neg Result | AU400e Immunoassay Qualitative Result (mAu) | Cutoff ΔOD (mAu) | Pos/ Neg Result | |---------------------------|-------------------------|-----------------------|------------------------------------------------------|------------------------|-----------------------| | 51* | 4.2 | + | 662.9 | 678.6 | - | | 52* | 4.4 | + | 675.3 | 701.6 | - | # Endogenous Compound Interference and Specificity - Cross-Reactivity: No significant undesired cross reactants or endogenous substance interference was observed at physiologically relevant concentrations. Ascorbic Acid concentrations above 3 mg/mL cause false-negative results. See product insert for list of compounds tested. ## Shipping/Recovery Stability Study: No significant sample degradation occurred following real-time and accelerated stability studies up to 72 hours. All sample shipments are based on the assumption of a 24 hour priority overnight delivery. {9}------------------------------------------------ #### Sample Storage Stability Study: No significant sample degradation occurred following real-time stability studies. Based on realtime studies, samples can be stored at 2-8 ℃ for up to 15 Days. Based on real-time studies, samples can be stored at -20 ℃ for up to 113 Days. Real-time stability studies are on-going. ### Open (and re-capped) vial Stability for Reagent and Calibrator/Control: Real time (2-8°C) and accelerated stability studies (at room temperature. ~25°C and 30°C) were performed. Results indicated that opened and recapped calibrators and controls are stable for 6 months when stored at (2-8℃). #### Closed vial Stability for Calibrator/Control: Real time (2-8°C) stability studies were performed. Results indicated that unopened calibrators and controls are stable for 6 months when stored at 2-8℃. ## Summary: The information provided in this pre-market notification demonstrates that the LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay is 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 gas chromatography/mass spectrometry (GC/MS), an independent analytical method. The information supplied in this pre-market notification provides reasonable assurance that the LZI Oral Fluid 6-Acetylmorphine Enzyme Immunoassay is safe and effective for its stated intended use.