510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k153596 B. Purpose for Submission: New Device C. Measurand: Oxcarbazepine Metabolite D. Type of Test: Homogenous enzyme immunoassay E. Applicant: ARK Diagnostics, Inc. F. Proprietary and Established Names: ARK Oxcarbazepine Metabolite Assay G. Regulatory Information: Product Classification Regulation Section Panel Code POX II 862.3645 - Neuroleptic drugs 91 - Toxicology radioreceptor assay test system. DLJ II 862.3200 - Clinical toxicology 91 - Toxicology calibrator LAS I, reserved 862.3280 - Clinical toxicology 91 - Toxicology control material H. Intended Use: 1. Intended use(s): See indications for use. 1 2. Indication(s) for use: The ARK Oxcarbazepine Metabolite Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of Oxcarbazepine Metabolite in human serum on automated clinical chemistry analyzers. The measurements obtained are used in monitoring levels of Oxcarbazepine Metabolite to help ensure appropriate therapy. The ARK Oxcarbazepine Metabolite Calibrator is intended for use in calibration of the ARK Oxcarbazepine Metabolite Assay. The ARK Oxcarbazepine Metabolite Control is an assayed quality control material intended for use in quality control of the ARK Oxcarbazepine Metabolite Assay. 3. Special conditions for use statement(s): For prescription use only 4. Special instrument requirements: The assay was validated on the Beckman Coulter AU480 automated clinical chemistry analyzer. I. Device Description: The ARK Oxcarbazepine Metabolite Assay is a homogeneous immunoassay based on competition between drug in the specimen and Oxcarbazepine Metabolite labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for binding to the antibody reagent. The ARK Oxcarbazepine Metabolite Assay consists of reagents R1 (anti-Oxcarbazepine Metabolite polyclonal antibody with substrate) and R2 (Oxcarbazepine Metabolite labeled with bacterial G6PDH enzyme). ARK Oxcarbazepine Metabolite Calibrator is comprised of a synthetic protein matrix and consists of a six-level set to calibrate the assay. The ARK Oxcarbazepine Metabolite Control is comprised of a synthetic protein matrix and consists of a three level set used for quality control of the assay. J. Substantial Equivalence Information: 1. Predicate device name(s): Emit 2000 Carbamazepine Assay, ARK Topiramate Calibrator, ARK Topiramate Control 2. Predicate 510(k) number(s): k010814 (assay); k083799 (calibrator and control) 2 3. Comparison with predicate: Assay Similarities Item Candidate Device (ARK Predicate Device (Emit Oxcarbazepine Assay) 2000 Carbamazepine Assay, k010814) Intended Use/Indications The ARK Oxcarbazepine The Emit® 2000 for Use Metabolite Assay is Carbamazepine Assay is a intended for the quantitative homogeneous enzyme determination of immunoassay intended for Oxcarbazepine Metabolite use in the quantitative in human serum on analysis of carbamazepine automated clinical in human serum or plasma. chemistry analyzers. The The results obtained helps measurements obtained are physicians individualize used in monitoring levels of dosage regimens. Oxcarbazepine Metabolite to help ensure appropriate therapy. Sample Type Serum Serum or plasma Methodology Homogenous enzyme Same immunoassay (EIA) Reagent components Two (2) reagent system: Two (2) reagent system: Anti- Oxcarbazepine Antibody/Substrate Metabolite Reagent (R1) containing Antibody/Substrate Reagent mouse monoclonal (R1) containing rabbit antibodies to polyclonal antibodies to carbamazepine, glucose-6- Oxcarbazepine Metabolite, phosphate, nicotinamide glucose-6- phosphate, adenine dinucleotide. nicotinamide adenine dinucleotide, bovine serum Enzyme Reagent (R2) albumin, sodium azide, and containing carbamazepine stabilizers labeled with bacterial G6PDH, buffer. Enzyme Reagent (R2) containing Oxcarbazepine Sodium azide, buffer, Metabolite labeled with preservatives, and bacterial G6PDH, buffer, stabilizers bovine serum albumin, sodium azide, and stabilizers Testing environment Routine clinical laboratory Same Reagent condition and Liquid, 2-8°C Same 3 Assay Similarities Item Candidate Device (ARK Predicate Device (Emit Oxcarbazepine Assay) 2000 Carbamazepine Assay, k010814) storage Assay Differences Item Candidate Device (ARK Predicate Device (ARK Oxcarbazepine Assay) Topiramate Assay, k083799) Analyte Oxcarbazepine metabolite Carbamazepine Controls: Similarities and Differences Item Candidate Device (ARK Predicate Device (ARK Oxcarbazepine Control) Topiramate Control; k083799) Intended Use/Indications The ARK Oxcarbazepine The ARK Topiramate for Use Metabolite control is an Control is intended for use assayed quality control in quality control of the material intended for use in ARK Topiramate Assay. quality control of the ARK Oxcarbazepine Metabolite Assay. Matrix Synthetic protein matrix Same (buffer, bovine serum albumin, preservatives) Levels 3 (LOW, MID, HIGH) Same Calibrators: Similarities and Differences Item Candidate Device (ARK Predicate Device (ARK Oxcarbazepine Topiramate Calibrator; Calibrator) k083799) Intended Use/Indications ARK Oxcarbazepine The ARK Topiramate for Use Metabolite Calibrator is Calibrator is intended for intended for use in use in calibration of the calibration of the ARK ARK Topiramate Assay. Oxcarbazepine Metabolite Assay. Matrix Synthetic protein matrix Same (buffer, bovine serum albumin, preservatives) Levels 6 Same 4 K. Standard/Guidance Document Referenced (if applicable): · Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline- Third Edition (EP05-A3) · Interference Testing in Clinical Chemistry; Approved Guideline - Second Edition (EP07-A2) · Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline - Third Edition (EP09-A3) · Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline (EP6-A) · Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline - Second Edition (EP17-A2) L. Test Principle: The ARK Oxcarbazepine Metabolite Assay is a homogeneous immunoassay based on competition between drug in the specimen and Oxcarbazepine Metabolite labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for binding to the antibody reagent. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly proportional to the drug concentration. Active enzyme converts the coenzyme nicotinamide adenine dinucleotide (NAD) to NADH that is measured spectrophotometrically as a rate of change in absorbance. Endogenous serum G6PDH does not interfere with the results because the coenyzme NAD functions only with the bacterial enzyme used in the assay. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Data for the precision evaluation studies (total and within-laboratory precision) were collected on a single Beckman Coulter AU480 automated clinical chemistry analyzer. Each level of control and patient sample was assayed in quadruplicate twice a day over twenty non-consecutive days. A total of 160 determinations were made for each sample. One calibration was performed during this interval. A total of 6 samples (3 levels of human serum pooled specimens containing Oxcarbazepine Metabolite, and 3 levels of ARK Oxcarbazepine Metabolite controls) were used in the study. Mean oxcarbazepine metabolite, standard deviation (SD) and coefficients of variation (%CVs) were calculated for within-run, between-day, and total precision. 5 Sample N Mean Within Run Between Day Total ( g/mL) SD CV SD CV SD CV (%) (%) (%) ARK Control LOW 160 3.0 0.12 4.0 0.12 4.1 0.17 5.7 MID 160 10.1 0.37 3.6 0.33 3.2 0.48 4.8 HIGH 160 30.2 0.99 3.3 1.19 3.9 1.54 5.1 Human Serum LOW 160 3.1 0.12 3.9 0.12 4.0 0.17 5.5 MID 160 10.1 0.38 3.8 0.36 3.6 0.55 5.5 HIGH 160 30.4 1.10 3.6 1.11 3.7 1.55 5.1 b. Linearity/assay reportable range: Linearity was evaluated according to the CLSI EP6-A standard. A series of 8 concentrations (1.00, 3.00, 5.00, 10.00, 20.00, 30.00, 40.00, and 50.00 g/mL) in human serum were prepared by proportionally diluting a spiked high Oxcarbazepine Metabolite concentration serum sample pool with a negative serum pool. Two analytical runs of three replicates of each sample (6 replicates total) were measured for each concentration, and the mean of the measured concentration was compared to the theoretical expected Oxcarbazepine Metabolite concentrations based on the first order and second order linear regression analysis. The linear regression results using the sample concentrations listed above are: Analyzer Slope Intercept R2 AU480 1.0388 -0.0693 0.9994 This evaluation supports linearity within the claimed measuring range of 1.0 to 37.0 g/mL. Recovery An analytical recovery study was conducted on the Beckman Coulter AU480 to determine the effect of differing ratios of Oxcarbazepine Metabolite enantiomers (S- or R- enantiomer; ratio hereafter S:R) on recovery by spiking Oxcarbazepine Metabolite into human serum negative for Oxcarbazepine Metabolite. The results are as follows: 6 Mean Recovered Concentration ( g/mL) Theoretical S:R 1:1 S:R 4:1 S:R 9:1 S:R 19:1 Concentration ( g/mL) 1.0 0.77 0.93 0.98 0.95 4.0 3.78 3.92 3.94 3.86 8.0 7.47 8.18 8.16 7.82 15.0 14.10 15.80 14.91 15.42 20.0 19.03 21.69 19.81 21.02 35.0 33.74 34.71 33.52 36.16 45.0 42.89 46.88 44.63 49.46 c.