ROCHE COBAS IBTEGRA REAGENT CASSETTES

{0} JAN 13 1997 K964457 Roche Diagnostic Systems A Member of the Roche Group Roche Diagnostic Systems, Inc. Branchburg Township 1080 U.S. Highway 202 Somerville, New Jersey 08876-3771 Direct Dial Fax # 510(k) Summary Roche COBAS® INTEGRA Reagent Cassettes In accordance with the Safe Medical Devices Act of 1990, a 510(k) summary as outlined in 21 CFR 807.92 is provided herewith. ## I. Identification of 510(k) Sponsor: Roche Diagnostic Systems, Inc. a subsidiary of Hoffmann-La Roche, Inc. Branchburg Township 1080 US Highway 202 Somerville, NJ 08876-3771 510(k) Submission dated November 5, 1996 1 024 {1} 1 025 ## II. Device Name The device name, including both the trade/proprietary name and the classification name are provided in the table below. | Proprietary Name | Classification Name | Product Code | CFR Reference Number | | --- | --- | --- | --- | | COBAS INTEGRA... | | | | | Gamma-Glutamyltransferase - IFCC | Gamma-glutamyl transpeptidase Isoenzymes, Kinetic Method | JQB | 862.1360 | | Lactate Dehydrogenase - IFCC | Lactate Dehydrogenase, NAD Reduction / NADH Oxidation | CFJ | 862.1440 | | Total Protein - urine and CSF | Total Protein, Biuret (Colorimetric) | CEK | 862.1635 | | Lactate | Lactic Acid, Enzymatic Method | KHP | 862.1450 | | Tobramycin | Tobramycin, Fluorescence Polarization Immunoassay | LFW | 862.3900 | | Immunoglobulin A | Immunoglobulins (G, A, M), Nephelometric Method | CFN | 862.1330 | | Immunoglobulin G | Immunoglobulins (G, A, M), Nephelometric Method | CFN | 862.1330 | | Immunoglobulin M | Immunoglobulins (G, A, M), Nephelometric Method | CFN | 862.1330 | ## III. Identification of the legally marketed device to which the 510(k) sponsor claims equivalence: The following table identifies the legally marketed devices to which Roche Diagnostic Systems, Inc. claims equivalence. | Product Name | Predicate Product Name | K number | date of substantial equivalence | | --- | --- | --- | --- | | COBAS INTEGRA... | | | | | Gamma-Glutamyltransferase - IFCC | Roche COBAS INTEGRA, GGT (TRIS) | K951595 | 9/8/95 | | Lactate Dehydrogenase - IFCC | Roche COBAS INTEGRA, LD (Lactate - Pyruvate) | K954992 | 1/25/96 | | Total Protein - urine and CSF | SIGMA Diagnostics, Microprotein-PR | K853681 | 10/28/95 | | Lactate | Boehringer Mannheim, Lactate | K780563 | 4/18/78 | | Tobramycin | Abbott Diagnostics, TDX / TDX Flex Tobramycin | K802668 | 11/24/80 | | Immunoglobulin A | Behring Diagnostics, N and NA Reagents | K860894 | 4/15/86 | | Immunoglobulin G | BehringDiagnostics, N and NA Reagents | K860894 | 4/15/86 | | Immunoglobulin M | Behring Diagnostics, N and NA Reagents | K860894 | 4/15/86 | {2} 1 026 # IV. Description of the Device/Statement of Intended Use: Through this submission it is the intention of Roche to gain clearance of an additional 5 new COBAS INTEGRA Reagent Cassettes and a modified version of 3 previously cleared reagent cassettes. All of the COBAS INTEGRA Reagent Cassettes contained in this submission are intended for use with the COBAS INTEGRA Analyzer. The new Reagent Cassettes are: - COBAS INTEGRA Gamma- Glutamyltransferase - IFCC: contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the catalytic activity of GGT, (EC 2.3.2.2; γ-glutamyl peptide: amino acid γ-glutamyltransferase) in serum and plasma (test GGTI, 0-562). - COBAS INTEGRA Lactate Dehydrogenase - IFCC: contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the catalytic activity of LDH (EC 1.1.1.27; L-lactate: NAD⁺ oxidoreductase) in serum and plasma (test LDHI, 0-181). - COBAS INTEGRA Total Protein - urine and CSF: contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the total protein concentration in urine and cerebrospinal fluid (tests TPU, 0-123 and TPC, 0-223). - COBAS INTEGRA Lactate: contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the lactate concentration in plasma and cerebrospinal fluid (tests LACT, 0-22 and LACTC, 0-122). - COBAS INTEGRA Tobramycin: contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of tobramycin in serum or heparinized plasma (test TOBR, 0-92). The modified Reagent Cassettes are: - COBAS INTEGRA Immunoglobulin A: contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the immunological determination of human immunoglobulin A in serum. In addition to the standard application (test IGA, 0-075), the sensitive application (test IGAP, 0-175) is designed for the quantitative determination of low IgA concentrations in e.g. pediatric samples. {3} - COBAS INTEGRA Immunoglobulin G: contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the immunological determination of human immunoglobulin G in serum. In addition to the standard application (test IGG, 0-076), the sensitive application (test IGGP, 0-176) is designed for the quantitative determination of low IgG concentrations in e.g. pediatric samples. - COBAS INTEGRA Immunoglobulin M: contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the immunological determination of human immunoglobulin M in serum. In addition to the standard application (test IGM, 0-077), the sensitive application (test IGMP, 0-177) is designed for the quantitative determination of low IgM concentrations in e.g. pediatric samples. The Analyzer provides quantitative measurement of these analytes via three measuring principles, i.e., absorbance, fluorescence polarization and ion-selective electrodes. The COBAS INTEGRA Reagent Cassettes are compact and preparation-free. Sixty-eight COBAS INTEGRA Reagent Cassettes can be stored on board, 24 hours a day at 2-8°C. Each cassette is barcoded. This barcode label provides the analyzer with specific reagent information such as the lot number, the expiration date and the number of tests. V. Summary of the technological characteristics of the new device in comparison to those of the predicate. Tables 1 through 8 in the following section of this summary outline the technological characteristics (methodologies) of the COBAS INTEGRA Reagent Cassettes in comparison to those of legally marketed products. V. Brief discussion of the clinical and nonclinical tests relied on for a determination of substantial equivalence: The following tables 1 through 8 demonstrate the results of clinical and nonclinical studies performed using the COBAS INTEGRA Reagent Cassettes. The significant performance characteristics relied upon for a determination of substantial equivalence are summarized in this chart. This information concludes that the performance of these devices are essentially equivalent to other legally marketed devices of a similar kind. {4} Table 1 - Gamma-Glutamyltransferase IFCC | | COBAS INTEGRA GGT - IFCC | COBAS INTEGRA GGT - (TRIS) | | --- | --- | --- | | Intended Use | quantitative determination of the catalytic activity of GGT | quantitative determination of the catalytic activity of GGT | | Sample type | serum and plasma | serum and plasma | | Methodology | kinetic method - International Federation of Clinical Chemistry (IFCC) | kinetic method - Szasz-Persjun | | Reagents | R1: Buffer granulate R2: L-γ-glutamyl-3-carboxy-4-nitroanilide granulate with preservative | R1: Buffer granulate R2: L-γ-glutamyl-3-carboxy-4-nitroanilide granulate with preservative | | Calibrator | Roche Calibrator (human) | Roche Calibrator (human) | | Controls | Roche Control Serum N and P (human) | Roche Control Serum N and P (human) | | Performance Characteristics: | | | | Assay Range | 0 - 1,200 U/L 0 - 12,000 U/L with post dilution | 0 - 700 U/L 0 - 2,800 U/L with postdilution | | Precision: Mean (U/L) %CV (within run) %CV (total) | Level 1 Level 2 28 546 1.0 1.1 2.7 2.5 | Level 1 Level 2 37.9 345 0.67 0.46 1.2 1.4 | | Accuracy | y = 1.27x - 0.9 U/L r = 0.999 n = 202 vs. COBAS INTEGRA GGT (TRIS) | y = 1.02x + 0 U/L r = 0.998 n = 238 | {5} Table 2 - Lactate Dehydrogenase - IFCC | | COBAS INTEGRA LDH - IFCC | COBAS INTEGRA LDH - (L - P) | | --- | --- | --- | | Intended Use | quantitative determination of the catalytic activity of LDH | quantitative determination of the catalytic activity of LDH | | Sample type | serum and plasma | serum | | Methodology | kinetic method - lactate to pyruvate International Federation of Clinical Chemistry (IFCC) | kinetic method - lactate to pyruvate Gay, McComb, and Bowers | | Reagents | R1: Substrate R2: Coenzyme - NADH in TRIS buffer with preservatives and stabilizer | R1: Substrate R2: Coenzyme - NAD | | Calibrator | Roche Calibrator (human) | Roche Calibrator (human) | | Controls | Roche Control Serum N and P (human) | Roche Control Serum N and P (human) | | Performance Characteristics: | | | | Assay Range | 0 - 1,200 U/L 0 - 12,000 U/L with post dilution | 0 - 1,000 U/L 0 - 10,000 U/L with postdilution | | Precision: Mean (U/L) %CV (within run) %CV (total) | Level 1 Level 2 214 339 0.65 0.65 2.6 1.9 | Level 1 Level 2 141 439 1.3 0.99 2.8 1.5 | | Accuracy | y = 1.07x + 0.4 U/L r = 0.999 n = 106 vs. COBAS INTEGRA LD (L - P) | y = 0.95x - 14.3 U/L r = 0.999 n = 190 vs. Boehringer Mannheim | 1 029 {6} Table 3 Total Protein - Urine and CSF | | COBAS INTEGRA Total Protein - Urine / CSF | | | Sigma Diagnostics Microprotein - PR | | | | --- | --- | --- | --- | --- | --- | --- | | Intended Use | quantitative determination of total protein | | | quantitative determination of total protein | | | | Sample type | urine and cerebrospinal fluid | | | urine and cerebrospinal fluid | | | | Methodology | colorimetric method using pyrogallol-red molybdate complex | | | colorimetric method using pyrogallol-red molybdate complex | | | | Reagents | R1: Pyrogallol red and sodium molybdate in buffer with detergents and stabilizer | | | 1. Pyrogallol red and sodium molybdate in buffer with chelating agent, stabilizer, surfactant and preservative | | | | Calibrator | Roche Calibrator (human) | | | Sigma Protein Standard Solution | | | | Controls | recommended : Biorad Lyphocheck Urine Controls | | | Sigma urine and CSF Controls | | | | Performance Characteristics: | | | | | | | | Assay Range | 1 - 250 mg/dL 1 - 250 mg/dL with post dilution | | | 1 - 200 mg/dL | | | | Precision ( Urine): Mean (mg/dL) %CV (total) | Level 1 17.4 8.2 | Level 2 57.4 2.9 | Level 3 107.6 2.4 | Level 1 7.69 9.37 | Level 2 26.96 6.42 | Level 3 135.49 2.57 | | Precision ( CSF): Mean (mg/dL) %CV (total) | Level 1 28.9 1.3 | Level 2 951 0.80 | | Level 1 37.87 3.47 | Level 2 69.86 2.65 | Level 3 121.25 2.29 | | Accuracy (Urine) | y = 0.89x + 0 mg/L r = 0.992 n = 274 vs. Sigma | | | y = 1.005x +0.458 r = 0.997 n = 95 vs. similar commercially available method | | | 1 030 {7} Table 4 - Lactate | | COBAS INTEGRA Lactate | Boehringer Mannheim Lactate - on Hitachi 911 Analyzer | | --- | --- | --- | | Intended Use | quantitative determination of lactate | quantitative determination of lactate | | Sample type | plasma and cerebrospinal fluid | plasma and cerebrospinal fluid | | Methodology | colorimetric (LOX/PAP) with lactate oxidase and 4-aminoantipyrine | colorimetric - lactate to pyruvate (NAD Reduction/NADH Oxidation) | | Reagents | R1: Lactate oxidase (microbial) in TRIS buffer with stabilizer and preservative | R1: NAD in carbonate buffer with preservatives R2: LD (porcine muscle) and ALT (porcine heart) | | Calibrator | Roche Calibrator (human) | BM Standard 1 | | Controls | Roche Control Serum N and P (human) | Precitrol - N and A Control Serum | | Performance Characteristics: | | | | Assay Range | 0 - 180 mmol/L 0 - 1,800 mmol/L with post dilution | Up to 100 mg/dL Up to 199 mg/dL with postdilution | | Precision (Control Sera): Mean (mg/dL) %CV (within run) %CV (total) | Level 1 Level 2 12.6 47.7 0.92 0.62 1.2 1.1 | Level 1 Level 2 Level 3 7.7 23.5 55.1 2.7 1.1 0.7 3.8 1.3 0.9 | | Precision (CSF): Mean (mg/dL) %CV (within run) | Level 1 Level 2 20.7 74.7 0.90 0.89 | | | Accuracy | y = 1.00x - 0.1 mmol/L r = 0.999 n = 224 vs. Boehringer Mannheim 911 | y = 0.985x - 0.09 r = 0.999 n = 57 vs. Boehringer Mannheim 717 | {8} Table 5 - Tobramycin | | COBAS INTEGRA Tobramycin | | | Abbott TDX/TDX Flex Tobramycin | | | | --- | --- | --- | --- | --- | --- | --- | | Intended Use | quantitative determination of tobramycin | | | quantitative determination of tobramycin | | | | Sample type | serum and heparinized plasma | | | serum and plasma | | | | Methodology | fluorescence polarization | | | fluorescence polarization | | | | Calibrators | 0, 1, 2, 4, 7, 10 μg/mL | | | 0, 0.5, 1.5, 3.0, 6.0, 10.0 μg/mL | | | | Reagents: | R1: Anti-tobramycin monoclonal antibody (mouse) in buffer R2: Fluorescein labeled tobramycin derivative in buffer | | | R1: Tobramycin Antiserum (sheep) in buffer R2: Fluorescein tracer in buffer | | | | Performance Characteristics: | | | | | | | | Assay Range | 0.04 - 10 μg/mL | | | 0.18 - 10.0 μg/mL | | | | Precision: Mean (mg/dL) %CV (total) | Level 1 1.4 6.0 | Level 2 3.5 4.5 | Level 3 7.5 4.0 | Level 1 0.98 5.18 | Level 2 4.02 4.45 | Level 3 8.15 4.62 | | Accuracy | y = 0.854 +0.015 r = 0.996 n = 196 vs. Abbott TDX | | | y = 0.934 +0.248 μg/mL r = 0.951 n = 170 vs. enzyme immunoassay | | | | Sensitivity | 0.04 μg/mL | | | 0.18 μg/mL | | | 1 032 {9} Table 6 - Immunoglobulin A | | COBAS INTEGRA IgA (modified) | COBAS INTEGRA IgA (currently marketed) | Behringer N and NA Reagents | | --- | --- | --- | --- | | Intended Use | quantitative determination of human IgA, and a sensitive application for quantitative determination of low IgA concentrations (pediatric) | quantitative determination of human IgA | quantitative determination of human serumproteins | | Sample type | serum | serum | serum, umbilical cord serum or cerebrospinal fluid | | Methodology | Immunoturbidimetric | Immunoturbidimetric | Immunoturbidimetric | | Reagents | R1: Anti-IgA T antiserum (rabbit) specific for human IgM in phosphate buffer R2: IgA in diluted serum (human) with stabilizer | R1: Anti-IgA T antiserum (rabbit) specific for human IgM in phosphate buffer R2: IgA in diluted serum (human) with stabilizer | 1. Antiserum to human IgA 2. Phosphate-buffered saline | | Calibrator | Roche Serumproteins T Standard | Roche Serumproteins T Standard | Behringer N Protein Standard | | Controls | Roche Serumproteins T Control | Roche Serumproteins T Control | Behringer N/T Protein Control Serum (human) | | Performance Characteristics: | | | | | Assay Range | 0.11 - 3.54 g/L 0.04 - 10.6 g/L with rerun | 0.95 - 15.2 g/L 0.32 - 36.5 g/L with rerun | not specified in labeling | | Precision (standard application: Mean (g/mL) %CV (within run) %CV (total) | Level 1 Level 2 2.3 3.5 1.4 0.81 2.8 1.8 | Level 1 Level 2 2.3 3.5 1.4 0.81 2.8 1.8 | not specified in labeling | | Precision (Pediatric application): Mean (mg/dL) %CV (within run) %CV (total) | Level 1 Level 2 1.17 3.28 1.1 0.96 3.0 1.0 | not applicable | not specified in labeling | | Accuracy (standard application) | y = 0.97x -0.05 g/L r = 0.989 n = 400 vs. Behringer | y = 0.97x -0.05 g/L r = 0.989 n = 400 vs. Behringer | not specified in labeling | | Accuracy (pediatric application) | y = 1.01x + 0.01 g/L r = 0.996 n = 204 vs. Behringer | not applicable | not specified in labeling | {10} Table 7 - Immunoglobulin G | | COBAS INTEGRA IgG (modified) | COBAS INTEGRA IgG (currently marketed) | Behringer N and NA Reagents | | --- | --- | --- | --- | | Intended Use | quantitative determination of human IgG, and a sensitive application for quantitative determination of low IgG concentrations (pediatric) | quantitative determination of human IgG | quantitative determination of human serumproteins | | Sample type | serum | serum | serum, umbilical cord serum or cerebrospinal fluid | | Methodology | Immunoturbidimetric | Immunoturbidimetric | Immunoturbidimetric | | Reagents | R1: Anti-IgG T antiserum (rabbit) specific for human IgM in phosphate buffer R2: IgG in diluted serum (human) with stabilizer | R1: Anti-IgG T antiserum (rabbit) specific for human IgM in phosphate buffer R2: IgG in diluted serum (human) with stabilizer | 1. Antiserum to human IgG 2. Phosphate-buffered saline | | Calibrator | Roche Serumproteins T Standard | Roche Serumproteins T Standard | Behringer N Protein Standard | | Controls | Roche Serumproteins T Control | Roche Serumproteins T Control | Behringer N/T Protein Control Serum (human) | | Performance Characteristics: | | | | | Assay Range | 4.0 - 63.8 g/L 1.0 - 153 g/L with rerun | 4.7 - 75 g/L 1.2 - 180 g/L with rerun | not specified in labeling | | Precision (standard application: Mean (g/mL) %CV (within run) %CV (total) | Level 1 Level 2 12.9 25.5 2.0 1.4 2.9 1.9 | Level 1 Level 2 12.9 25.5 2.0 1.4 2.9 1.9 | not specified in labeling | | Precision (Pediatric application): Mean (mg/dL) %CV (within run) %CV (total) | Level 1 Level 2 7.1 16.9 0.81 0.83 3.0 1.3 | not applicable | not specified in labeling | | Accuracy (standard application) | y = 1.02x - 0.9 g/L r = 0.996 n = 244 vs. Behringer | y = 1.02x - 0.9 g/L r = 0.996 n = 244 vs. Behringer | not specified in labeling | | Accuracy (pediatric application) | y = 0.93x + 0.30 g/L r = 0.986 n = 212 vs. Behringer | not applicable | not specified in labeling | {11} Table 8 - Immunoglobulin M | | COBAS INTEGRA IgA (modified) | COBAS INTEGRA IgA (currently marketed) | Behringer N and NA Reagents | | --- | --- | --- | --- | | Intended Use | quantitative determination of human IgM, and a sensitive application for quantitative determination of low IgM concentrations (pediatric) | quantitative determination of human IgM | quantitative determination of human serumproteins | | Sample type | serum | serum | serum, umbilical cord serum or cerebrospinal fluid | | Methodology | Immunoturbidimetric | Immunoturbidimetric | Immunoturbidimetric | | Reagents | R1: Anti-IgM T antiserum (rabbit) specific for human IgM in phosphate buffer R2: IgM in diluted serum (human) with stabilizer | R1: Anti-IgM T antiserum (rabbit) specific for human IgM in phosphate buffer R2: IgM in diluted serum (human) with stabilizer | 1. Antiserum to human IgM 2. Phosphate-buffered saline | | Calibrator | Roche Serumproteins T Standard | Roche Serumproteins T Standard | Behringer N Protein Standard | | Controls | Roche Serumproteins T Control | Roche Serumproteins T Control | Behringer N/T Protein Control Serum (human) | | Performance Characteristics: | | | | | Assay Range | 0.31 - 5.0 g/L 0.11 - 12.1 g/L with rerun | 0.47 - 7.5 g/L 0.16 - 18 g/L with rerun | not specified in labeling | | Precision (standard application): Mean (g/mL) %CV (within run) %CV (total) | Level 1 Level 2 0.6 1.9 2.6 2.0 3.1 2.2 | Level 1 Level 2 0.6 1.9 2.6 2.0 3.1 2.2 | not specified in labeling | | Precision (Pediatric application): Mean (mg/dL) %CV (within run) %CV (total) | Level 1 Level 2 0.44 1.08 1.9 1.6 4.9 2.1 | not applicable | not specified in labeling | | Accuracy (standard application) | y = 1.12x - 0.06 g/L r = 0.994 n = 400 vs. Behringer | y = 1.12x - 0.06 g/L r = 0.994 n = 400 vs. Behringer | not specified in labeling | | Accuracy (pediatric application) | y = 1.17x - 0.03 g/L r = 0.984 n = 214 vs. Behringer | not applicable | not specified in labeling |