LZI COCAINE METABOLITE HOMOGENEOUS ENZYME IMMUNOASSAY,CALIBRATORS,CONTROLS

{0}------------------------------------------------ # 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. # 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 (408) 732-3849 Fax: e-mail: bclin@lin-zhi.com Contact: Bernice Lin, Ph.D. VP Operations # Device Name and Classification | Classification Name: | Enzyme Immunoassay, Cocaine<br>Class II, DIO (91 Toxicology),<br>21 CFR 862.3250<br><br>Drug Specific Calibrators,<br>Class II, DLJ (91 Toxicology),<br>21 CFR 862.3200<br><br>Drug Specific Controls,<br>Class I, LAS (91 Toxicology),<br>21 CFR 862.3280 | |----------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Common Name: | Homogeneous Cocaine Enzyme Immunoassay | | Proprietary Name: | Cocaine Metabolite Enzyme Immunoassay,<br>Cocaine Metabolite Drugs of Abuse (DAU) Calibrators<br>Cocaine Metabolite Drugs of Abuse (DAU) Controls | {1}------------------------------------------------ # Legally Marketed Predicate Device(s) The Cocaine Metabolite Enzyme Immunoassay (EIA) at a cutoff of 150 ng/mL is substantially equivalent to the Cocaine Metabolite Enzyme Immunoassay (k020763), Calibrators and Controls for Hitachi 717 Systems (k020769) manufactured by Lin-Zhi International, Inc with a cutoff of 300 ng/mL. The Cocaine Metabolite Enzyme Immunoassay is identical or similar to its predicate in terms of intended use, method principle, device components, and clinical performance. ## Device Description The Cocaine Metabolite 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, benzoylecgonine-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 benzoylecgonine-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 Cocaine Metabolite Enzyme Immunoassay is a kit comprised of two reagents, an R, and R2 which are bottled separately but sold together within the kit. The Ri solution contains a mouse monoclonal anti-benzoylecgonine 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 benzoylecgonine in buffer with sodium azide (0.09%) as preservative. The Cocaine Metabolite Enzyme Immunoassay calibrators and controls designated for use at the 150 ng/mL cutoff contain 0, 75, 112.5, 150, 187.5, 300, and 1000 ng/mL of benzoylecgonine in human urine with sodium azide (0.09%) as preservative. These five calibrators and two controls are sold as individual bottles. {2}------------------------------------------------ ## Intended Use The Cocaine Metabolite Enzyme Immunoassay is intended for the qualitative and semiquantitative determination of benzoylecgonine in human urine, at a cutoff value of 150 ng/mL. The assay is designed for professional 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 or (2) permitting laboratories to establish quality control procedures. The Cocaine Metabolite Drugs of Abuse (DAU) Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the Cocaine Metabolite Enzyme Immunoassay at a cutoff value of 150 ng/mL. The Cocaine Metabolite Drugs of Abuse (DAU) Controls are for use as assayed quality control materials to monitor the precision of the Cocaine Metabolite Enzyme Immunoassay at a cutoff value of 150 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 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. {3}------------------------------------------------ # Comparison to Predicate Device The Lin-Zhi International, Inc. Cocaine Metabolite Enzyme Immunoassay used at the 150 ng/mL cutoff is substantially equivalent to the Lin-Zhi International, Inc. Cocaine Metabolite Enzyme Immunoassay, Calibrators and Controls for Hitachi 717 Systems cleared by the FDA under the premarket notification k020763 and k020769 for its stated intended use. The following table compares LZI's Cocaine Metabolite Enzyme Immunoassay at the 150 ng/mL cutoff with the predicate device. | Device<br>Characteristics | Subject Device | Predicate Device (k020763 & k020769) | |---------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Intended Use | The Cocaine Metabolite Enzyme<br>Immunoassay, when used in conjunction<br>with Hitachi 717 automated clinical<br>system analyzers, is intended for the<br>qualitative and semi-quantitative<br>determination of benzoylecgonine in<br>human urine, at a cutoff value of 150<br>ng/mL. The assay is designed for<br>professional use with a number of<br>automated clinical chemistry analyzers.<br><br>This assay provides a rapid screening procedure<br>for determining the presence of Benzoylecgonine<br>in urine. The assay provides only a preliminary<br>analytical result. A more specific alternative<br>chemical method must be used in order to obtain a<br>confirmed analytical result. Gas or liquid<br>chromatography/mass spectrometry (GC/MS or<br>LC/MS) is the preferred confirmatory method.<br>Clinical consideration and professional judgment<br>should be exercised with any drug of abuse test<br>result, particularly when the preliminary test result<br>is positive. | The Cocaine Metabolite Enzyme<br>Immunoassay from Lin-Zhi International,<br>Inc., when used in conjunction with<br>Hitachi 717 automated clinical system<br>analyzers, is intended for the qualitative<br>and semi-quantitative determination of<br>benzoylecgonine in human urine, at a<br>cutoff value of 300 ng/mL. The assay is<br>designed for professional use with a<br>number of automated clinical chemistry<br>analyzers.<br><br>This assay provides a rapid screening procedure<br>for determining the presence of Benzoylecgonine<br>in urine. The assay provides only a preliminary<br>analytical result. A more specific alternative<br>chemical method must be used in order to obtain a<br>confirmed analytical result. Gas or liquid<br>chromatography/mass spectrometry (GC/MS or<br>LC/MS) is the preferred confirmatory method.<br>Clinical consideration and professional judgment<br>should be exercised with any drug of abuse test<br>result, particularly when the preliminary test result<br>is positive. | | Analyte | Benzoylecgonine | Benzoylecgonine | | Cutoff | 150 ng/ml | 300 ng/mL | | Matrix | Urine | Urine | | Calibrators<br>Level | 5 Levels<br>(0, 75, 150, 300, 1000 ng/mL) | 5 Levels<br>(0, 150, 300, 1000, 3000 ng/mL) | | Controls Level | 2 Levels<br>(112.5 ng/mL, 187.5 ng/mL) | 2 Levels<br>(225 ng/mL, 375 ng/mL) | | Storage | 2-8 °C until expiration date | 2-8 °C until expiration date | {4}------------------------------------------------ # Performance Characteristics Summary: Hitachi 717 Analyzer Precision: Precision: Semi-Quantitative, ng/mL | N=88<br>(ng/mL) | Within Run | | | Total Precision | | | |-----------------|------------|-----|------|-----------------|------|-------| | | Mean | SD | % CV | Mean | SD | % CV | | 0 ng/mL | 1.7 | 2.2 | n/a | 1.7 | 2.7 | 156.9 | | 37.5 ng/mL | 40.4 | 3.8 | 9.3 | 40.4 | 4.4 | 10.8 | | 75 ng/mL | 76.9 | 4.2 | 5.4 | 76.9 | 5.7 | 7.4 | | 112.5 ng/mL | 111.6 | 4.1 | 3.7 | 111.6 | 4.8 | 4.3 | | 150 ng/mL | 146.2 | 5.9 | 4.1 | 146.2 | 6.8 | 4.7 | | 187.5 ng/mL | 185.1 | 6.3 | 3.4 | 185.1 | 7.5 | 4.0 | | 225 ng/mL | 224.0 | 9.0 | 4.0 | 224.0 | 9.1 | 4.1 | | 267.5 ng/mL | 263.4 | 7.8 | 3.0 | 263.4 | 8.9 | 3.4 | | 300 ng/mL | 301.9 | 9.4 | 3.1 | 301.9 | 11.2 | 3.7 | # Semi-Quantitative Precision Analysis Summary: Qualitative Results : | N=88 | (ng/mL) | Within Run | | Total Precision | | |------|-------------|------------|----------------------|-----------------|----------------------| | | | Mean | Qualitative Response | Mean | Qualitative Response | | | 0 ng/mL | 1.7 | - | 1.7 | - | | | 37.5 ng/mL | 40.4 | - | 40.4 | - | | | 75 ng/mL | 76.9 | - | 76.9 | - | | | 112.5 ng/mL | 111.6 | - | 111.6 | - | | | 150 ng/mL | 146.2 | - | 146.2 | - | | | 187.5 ng/mL | 185.1 | + | 185.1 | + | | | 225 ng/mL | 224.0 | + | 224.0 | + | | | 267.5 ng/mL | 263.4 | + | 263.4 | + | | | 300 ng/mL | 301.9 | + | 301.9 | + | # Semi-Quantitative Positive/Negative Results: | 150 ng/mL Cutoff Result: | | Within Run | | Total Precision | | |--------------------------|-------------|----------------------------|-----------------------|----------------------------|-----------------------| | Sample<br>Concentration | % of Cutoff | Number of<br>Determination | Immunoassay<br>Result | Number of<br>Determination | Immunoassay<br>Result | | 0 ng/mL | -100.0% | 22 | 22 Negative | 88 | 88 Negative | | 37.5 ng/mL | -75.0% | 22 | 22 Negative | 88 | 88 Negative | | 75 ng/mL | -50.0% | 22 | 22 Negative | 88 | 88 Negative | | 112.5 ng/mL | -25.0% | 22 | 22 Negative | 88 | 88 Negative | | 150 ng/mL | 0% | 22 | 3 Pos/19 Neg | 88 | 29 Pos/ 59 Neg | | 187.5 ng/mL | +25.0% | 22 | 22 Positive | 88 | 88 Positive | | 225 ng/mL | +50.0% | 22 | 22 Positive | 88 | 88 Positive | | 267.5 ng/mL | +75.0% | 22 | 22 Positive | 88 | 88 Positive | | 300 ng/mL | +100.0% | 22 | 22 Positive | 88 | 88 Positive | {5}------------------------------------------------ # Performance Characteristics Summary: continued Hitachi 717 Analyzer | N=88 | Within Run | | | Total Precision | | | |-------------|------------|-----|------|-----------------|-----|------| | (mA/min) | Mean | SD | % CV | Mean | SD | % CV | | 0 ng/mL | 373.5 | 3.1 | 0.8 | 373.5 | 5.0 | 1.3 | | 37.5 ng/mL | 407.2 | 2.8 | 0.7 | 407.2 | 3.8 | 0.9 | | 75 ng/mL | 437.2 | 3.3 | 0.7 | 437.2 | 4.6 | 1.1 | | 112.5 ng/mL | 462.6 | 2.8 | 0.6 | 462.6 | 4.5 | 1.0 | | 150 ng/mL | 486.0 | 3.7 | 0.8 | 486.0 | 4.6 | 0.9 | | 187.5 ng/mL | 509.6 | 3.0 | 0.6 | 509.6 | 4.3 | 0.9 | | 225 ng/mL | 528.9 | 4.5 | 0.9 | 528.9 | 5.0 | 0.9 | | 267.5 ng/mL | 544.8 | 3.4 | 0.6 | 544.8 | 4.6 | 0.8 | | 300 ng/mL | 560.8 | 3.6 | 0.6 | 560.8 | 4.7 | 0.8 | #### Precision: Qualitative, mA/min ### Qualitative Positive/Negative Results: | 150 ng/mL Cutoff Result: | | Within Run | | Total Precision | | |--------------------------|-------------|----------------------------|-----------------------|----------------------------|-----------------------| | Sample<br>Concentration | % of Cutoff | Number of<br>Determination | Immunoassay<br>Result | Number of<br>Determination | Immunoassay<br>Result | | 0 ng/mL | -100.0% | 22 | 22 Negative | 88 | 88 Negative | | 37.5 ng/mL | -75.0% | 22 | 22 Negative | 88 | 88 Negative | | 75 ng/mL | -50.0% | 22 | 22 Negative | 88 | 88 Negative | | 112.5 ng/mL | -25.0% | 22 | 22 Negative | 88 | 88 Negative | | 150 ng/mL | 0% | 22 | 3 Pos/19 Neg | 88 | 15 Pos/73 Neg | | 187.5 ng/mL | +25.0% | 22 | 22 Positive | 88 | 88 Positive | | 225 ng/mL | +50.0% | 22 | 22 Positive | 88 | 88 Positive | | 267.5 ng/mL | +75.0% | 22 | 22 Positive | 88 | 88 Positive | | 300 ng/mL | +100.0% | 22 | 22 Positive | 88 | 88 Positive | # Linearity: Hitachi 717 Instrument: 0 - 1000 ng/mL When comparing the result (y) and target (x) value, using the least squares regression technique, the regression equation and correlation are as follow: y = 1.0488x -0.5229, r4=0.9992 # Method Comparison - Clinical Samples: From a total of eighty (80) clinical unaltered samples Semi-Quantitative Data: 90% agreement with positive, 98% agreement with negative samples Qualitative Data: 90% agreement with positive, 95% agreement with negative samples # Endogenous Compound Interference & Specificity & Cross-Reactivity: No significant undesired cross reactants or endogenous substance interference was observed. {6}------------------------------------------------ # Performance Characteristics Summary: continued Hitachi 717 Analyzer # Summary: The information provided in this pre-market notification demonstrates that the Cocaine Metabolite Enzyme Immunoassay at a cutoff value of 150 ng/mL 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 chromatography/mass spectrometry (GC/MS or LC/MS), an independent analytical method. The information supplied in this premarket notification provides reasonable assurance that the Cocaine Metabolite Enzyme Immunoassay at a cutoff value of 150 ng/mL is safe and effective for its stated intended use. {7}------------------------------------------------ Image /page/7/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with its wings spread, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged in a circle around the eagle. The eagle is depicted in a simple, abstract style, with flowing lines suggesting movement. The text is in a sans-serif font and is evenly spaced around the circle. #### DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993 Image /page/7/Picture/4 description: The image shows a date, "NOV 22 2011". The month is November, the day is the 22nd, and the year is 2011. The text is in a bold, sans-serif font. The text is black against a white background. LIN-ZHI INTERNATIONAL, INC c/o Bernice Lin. PHD VP Operations 670 Almanor Ave Sunnyvale, California 94085 . Re: k113139 > Trade Name: LZI Cocaine Metabolite Homogeneous Enzyme Immunoassay, Cocaine Metabolite Drugs of Abuse Calibrators and Controls Regulation Number: 21 CFR §862.3250 Regulation Name: Cocaine and cocaine metabolite test system Regulatory Class: Class II Product Codes: DIO, DLJ, LAS Dated: October 21, 2011 Received: October 24, 2011 Dear 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. 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 (OS) regulation (21 CFR Part 820). {8}------------------------------------------------ Page 2 - If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Viro 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/MedicalDevicesforYou/Industry/default.htm. Sincerely yours, signature Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health Enclosure {9}------------------------------------------------ #### Indications for Use Statement #### 510(k) Number (if known): k113139 ### Device Name: Cocaine Metabolite Enzyme Immunoassay Cocaine Metabolite Calibrators and Controls #### Indications for Use: The Cocaine Metabolite Enzyme Immunoassay is intended for the qualitative and semiquantitative determination of benzoylecgonine in human urine, at the cutoff value of 150 ng/mL. The assay is designed for professional 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 or (2) permitting laboratories to establish quality control procedures. The Cocaine Metabolite Drugs of Abuse (DAU) Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the Cocaine Metabolite Enzyme Immunoassay at a cutoff value of 150 ng/mL. The Cocaine Metabolite Drugs of Abuse (DAU) Controls are for use as assayed quality control materials to monitor the precision of the Cocaine Metabolite Enzyme Immunoassay at a cutoff value of 150 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 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 Prescription Use __ \__ AND/OR Over-The-Counter Use _ (Part 21 CFR 801 Subpart D) (21 CFR 807 Subpart C) Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD) (Per 21 CFR 801.109) Signature Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety 510(k) K113134