COBAS INTEGRA REAGENT CASSETTES & ANCILLARY REAGENTS
Device Facts
| Record ID | K963292 |
|---|---|
| Device Name | COBAS INTEGRA REAGENT CASSETTES & ANCILLARY REAGENTS |
| Applicant | Roche Diagnostic Systems, Inc. |
| Product Code | CIC · Clinical Chemistry |
| Decision Date | Oct 31, 1996 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1145 |
| Device Class | Class 2 |
Indications for Use
The COBAS INTEGRA Cassette for Antithrombin III (AT III) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of human antithrombin III activity in plasma. The COBAS INTEGRA Cassette for Ferritin contains an in vitro diagnostic reagent system intended for the quantitative immunological determination of human ferritin in serum. The COBAS INTEGRA Cassette for Myoglobin contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative immunological determination of human myoglobin in serum and plasma. The COBAS INTEGRA Cassette for Rheumatoid Factors contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative immunological determination of human rheumatoid factors in serum. Plasmachrom Calibrator is intended for use as a calibrator in quantitative kinetic antithrombin III activity assays. Plasmachrom Control N is an assayed control intended for use to monitor the accuracy and precision at normal concentration levels in quantitative kinetic colorimetric tests for antithrombin III activity assays. Plasmachrom Control P is an assayed control intended for use to monitor the accuracy and precision at pathological concentration levels in quantitative kinetic colorimetric tests for antithrombin III activity assays. MYO T Standard is intended for use as a calibrator in quantitative determinations of human myoglobin. FERR T Standard is intended for use as a calibrator in quantitative determinations of human ferritin. FERR/MYO T Control is intended for use as a quality control material to monitor accuracy and precision in quantitative determinations of human ferritin and myoglobin. RF T Standard is intended for use as a calibrator in quantitative determinations of human rheumatoid factor.
Device Story
COBAS INTEGRA Reagent Cassettes are preparation-free, barcoded, on-board storage reagents for the COBAS INTEGRA Analyzer; system performs quantitative in vitro diagnostic testing. Analyzer uses absorbance, fluorescence polarization, and ion-selective electrodes to measure analytes. Barcode labels provide lot number, expiration, and test count to the analyzer. Cassettes are stored at 2-8°C. Healthcare providers use quantitative results to assess patient status for AT III, ferritin, myoglobin, and rheumatoid factors. System includes ancillary calibrators and controls to monitor accuracy and precision. Modification to Calcium cassette improves performance via updated instrument parameters.
Clinical Evidence
Clinical performance evaluated via method comparison studies against predicate devices. Sample sizes ranged from N=188 to N=244. Correlation coefficients (R) ranged from 0.70 to 0.987. Precision (day-to-day or within-run) reported for all assays, with CVs generally <10%. Analytical sensitivity and assay ranges provided for each analyte.
Technological Characteristics
Reagent cassettes for automated analyzer; methodologies include kinetic colorimetric and immunoturbidimetric tests. Reagents utilize buffers (glycine, TRIS), latex particles, and specific antibodies/enzymes. Connectivity via barcoded cassettes for automated information transfer. System uses absorbance, fluorescence polarization, and ion-selective electrodes.
Indications for Use
Indicated for quantitative determination of human antithrombin III activity in plasma, human ferritin in serum, human myoglobin in serum/plasma, and human rheumatoid factors in serum. Used for diagnostic testing in clinical settings.
Regulatory Classification
Identification
A calcium test system is a device intended to measure the total calcium level in serum. Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).
Predicate Devices
- COBAS INTEGRA Calcium (K951595)
- Boehringer Mannheim Calcium Reagent (K850281)
- Berichrom Antithrombin III Reagent (K933125)
- Behring N Latex Ferritin Reagent (K950707)
- Behring N Latex Myoglobin Reagent (K902154)
- Behring N Latex RF Reagent (K942328)
- Behring N Protein Standard Plasma (K883662)
- N/T Protein Control Py (K951012)
- Behring N Ferritin Standard (K950707)
- Behring N Ferritin Controls (K950707)
- Behring N Myoglobin Controls (K902154)
- Behring N Myoglobin Standard (K902154)
- Behring N RF Standard (K942328)
Submission Summary (Full Text)
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K963292
Roche
Roche Diagnostic Systems
A Member of the Roche Group
OCT 31 1996
Roche Diagnostic Systems, Inc.
1080 U.S. Highway 202
Branenburg, New Jersey 08876-1760
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 is provided as outlined in 21 CFR 807.92.
### I. Identification of 510(k) Sponsor:
Roche Diagnostic Systems, Inc.
a subsidiary of Hoffmann-La Roche, Inc.
Branenburg Township
1080 U.S. Highway 202
Somerville, New Jersey 08876-3771
510(k) Submission dated August 20, 1996
Contact:
Andrea Casper
Sr. Manager Regulatory and Clinical Affairs
Phone: (908) 253-7332
Fax: (908) 253-7547
### II. Device Name:
The device name, including both the trade/proprietary name and the classification name are provided in the table below.
Table 1
| Product Name | Classification Name | Regulatory Class | CFR Classification Number | Predicate Product Name | Date Predicate Cleared | Predicate 510(k) Number |
| --- | --- | --- | --- | --- | --- | --- |
| Chemistry Panel | | | | | | |
| COBAS INTEGRA Calcium (modification) | Calcium test system | Class II | 862.1145 | COBAS INTEGRA Calcium
Boehringer Mannheim Calcium Reagent | 9/5/95
1/23/85 | K951595
K850281 |
| Immunology Panel | | | | | | |
| COBAS INTEGRA Antithrombin III | Antithrombin III assay | Class II | 866.7060 | Berichrom Antithrombin III Reagent | 4/19/94 | K933125 |
{1}
Roche Diagnostic Systems, Inc.
Somerville, New Jersey 08876
August 1996
COBAS® INTEGRA Reagent Cassettes & Ancillary Reagents
510(k) Premarket Notification
Summary
| COBAS INTEGRA Ferritin | Ferritin immunological test system | Class II | 866.5340 | Behring N Latex Ferritin Reagent | 3/27/95 | K950707 |
| --- | --- | --- | --- | --- | --- | --- |
| COBAS INTEGRA Myoglobin | Myoglobin immunological test system | Class II | 866.5680 | Behring N Latex Myoglobin Reagent | 6/01/96 | K902154 |
| COBAS INTEGRA Rheumatoid Factors | Rheumatoid factor immunological test system | Class II | 866.5775 | Behring N Latex RF Reagent | 10/20/94 | K942328 |
| Plasmachrom Calibrator | Calibrator | Class II | 862.1150 | Behring N Protein Standard Plasma | 4/7/88 | K883662 |
| Plasmachrom Controls | Quality control material (assayed and unassayed) | Class I | 862.1660 | N/T Protein Control Py | 4/17/96 | K951012 |
| Roche FERR T Standard | Calibrator | Class II | 862.1150 | Behring N Ferritin Standard | 3/27/95 | K950707 |
| Roche FERR/MYO T Control | Quality control material (assayed and unassayed) | Class I | 862.1660 | Behring N Ferritin Controls
Behring N Myoglobin Controls | 3/27/95
6/01/96 | K950707
K902154 |
| Roche MYO T Standard | Calibrator | Class II | 862.1150 | Behring N Myoglobin Standard | 6/01/96 | K902154 |
| Roche RF T Standard | Calibrator | Class II | 862.1150 | Behring N RF Standard | 10/20/94 | K942328 |
III. Identification of the legally marketed device to which the 510(k) sponsor claims equivalence:
Table 1, presented above, identifies the legally marketed devices to which Roche Diagnostic Systems, Inc. claims equivalence.
IV. Description of the Device/Statement of Intended Use:
The COBAS INTEGRA Analyzer and COBAS INTEGRA Reagent Cassettes together provide an integrated system for in vitro diagnostic testing. The COBAS INTEGRA Reagent Cassettes are comprised of chemistry, drugs of abuse, immunology, therapeutic drug monitoring, and hematology assay systems. The COBAS INTEGRA 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 with the added convenience of long term on-board stability. 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.
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{2}
Roche Diagnostic Systems, Inc.
Somerville, New Jersey 08876
August 1996
COBAS® INTEGRA Reagent Cassettes & Ancillary Reagents
510(k) Premarket Notification
Summary
Through this submission, it is the intention of Roche to gain clearance of an additional 4 COBAS Reagent Cassettes and 6 ancillary reagents. These are the COBAS INTEGRA Cassette for Antithrombin III, COBAS INTEGRA Cassette for Ferritin, COBAS INTEGRA Cassette for Myoglobin, COBAS INTEGRA Cassette for Rheumatoid Factors, Roche Plasmachrom Calibrator, Roche Plasmachrom N & P Controls, Roche FERR T Standard, Roche FERR/MYO T Control, Roche MYO T Standard, and Roche RF Standard II. The COBAS INTEGRA Cassette for Antithrombin III (AT III) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of human antithrombin III activity in plasma. The COBAS INTEGRA Cassette for Ferritin contains an in vitro diagnostic reagent system intended for the quantitative immunological determination of human ferritin in serum. The COBAS INTEGRA Cassette for Myoglobin contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative immunological determination of human myoglobin in serum and plasma. The COBAS INTEGRA Cassette for Rheumatoid Factors contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative immunological determination of human rheumatoid factors in serum. Plasmachrom Calibrator is intended for use as a calibrator in quantitative kinetic antithrombin III activity assays. Plasmachrom Control N is an assayed control intended for use to monitor the accuracy and precision at normal concentration levels in quantitative kinetic colorimetric tests for antithrombin III activity assays. Plasmachrom Control P is an assayed control intended for use to monitor the accuracy and precision at pathological concentration levels in quantitative kinetic colorimetric tests for antithrombin III activity assays. MYO T Standard is intended for use as a calibrator in quantitative determinations of human myoglobin. FERR T Standard is intended for use as a calibrator in quantitative determinations of human ferritin. FERR/MYO T Control is intended for use as a quality control material to monitor accuracy and precision in quantitative determinations of human ferritin and myoglobin. RF T Standard is intended for use as a calibrator in quantitative determinations of human rheumatoid factor.
This submission also contains a modification to the previously cleared COBAS INTEGRA Reagent Cassette for Calcium. The performance of the COBAS INTEGRA Reagent Cassette for Calcium has been improved due to the use of new instrument parameters.
V. Summary of the technological characteristics of the new device in comparison to those of the predicate.
Tables 2-6 attached to this summary outline the technological characteristics (methodologies) of the COBAS INTEGRA Reagents in comparison to those of legally marketed predicate products.
VI. Brief discussion of the clinical and nonclinical tests relied on for a determination of substantial equivalence:
Tables 2-6 attached to this summary 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 this device is essentially equivalent to other legally marketed devices of a similar kind.
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Roche Diagnostic Systems, Inc.
Somerville, New Jersey 08876
August 1996
COBAS® INTEGRA Reagent Cassettes & Ancillary Reagents
510(k) Premarket Notification
Summary
Table 2
COBAS INTEGRA Cassette for AT III
| | COBAS INTEGRA Cassette for Antithrombin III | Berichrom AT III (A) |
| --- | --- | --- |
| Methodology | Kinetic colorimetric test | Kinetic colorimetric test |
| Sample type | Plasma (citrate) | Plasma |
| Reported measuring units | % | % |
| Calibrator | Plasmachrom Calibrator (lyophilized human plasma)
Calibrator value: 102% | Behring N Protein Standard Plasma (lyophilized human plasma)
Calibrator Value: 87% |
| Controls | Plasmachrom N & P Controls (lyophilized human plasma)
Control N: 99.4%
Control P: 61.1% | N/T Protein Control Py (lyophilized human plasma)
Control N: 92%
Control P: 34% |
| Reagent (active ingredients) | TRIS
NaCl
Citrate
BSA
Heparin
Thrombin
D-phenylalanyl-prolyl-arginyl-4-acetylanilide | Thrombin
tos-gly-pro-arg-ANBA-IPA
TRIS |
| Performance Characteristics: | | |
| Assay range | 0-150% | 0-140% |
| Precision (Day-to-day) | 4.1% at 51.9%
2.8% at 105.7% | Normal plasma -1.0-2.5%
Pathological plasma-1.5-3.0% |
| Accuracy | N = 200
R = 0.973 vs. Berichrom Reagent | R = > 0.95 |
| Sensitivity (Analytical) | 1.6 X 10-3 ΔA/min per %
change in AT III activity | Not specified in labeling |
{4}
Roche Diagnostic Systems, Inc.
Somerville, New Jersey 08876
August 1996
COBAS® INTEGRA Reagent Cassettes & Ancillary Reagents
510(k) Premarket Notification
Summary
Table 3
COBAS INTEGRA Cassette for Ferritin
| | COBAS INTEGRA Cassette for Ferritin | Behring N Latex Ferritin Reagent on Behring Nephelometer |
| --- | --- | --- |
| Methodology | Immunoturbidimetric test for Ferritin | Immunoturbidimetric test for Ferritin |
| Sample type | Serum | Serum |
| Reported measuring units | ug/L | ug/L |
| Calibrator | Roche FERR T Standard (human sourced)
0, 12.5, 50, 100, 200, & 300 ug/L | Behring N Ferritin Standard (human sourced)
344 ug/L |
| Controls | Roche FERR/MYO T Control (lyophilized human serum w/added BSA)
Ferritin: 126 ± 13 ug/L
Myoglobin: 115 ± 12 ug/L | Behring N Ferritin Controls (human sourced)
Control 1: 20.2 ug/L
Control 2: 153 ug/L |
| Reagent (active ingredients) | R1. Glycine buffer
R2. Latex particles coated with anti-human ferritin (rabbit) in glycine buffer | R1. Freeze dried polystyrene particles coated with rabbit anti-human ferritin
R2. Buffered solution of rabbit serum
R3. buffered solution of detergents |
| Performance Characteristics: | | |
| Assay range | 0-300 ug/L
0-3000 ug/L w/postdilution | 5-320 ug/L |
| Precision (Within-run) | 9.9 % at 19 ug/L
1.2% at 260 ug/L | 3.8% at 5 ug/L
1.5% at 15 ug/L
1.3% at 30 ug/L
1.5% at 50 ug/L
0.9% at 200 ug/L |
| Accuracy | N = 188
y = 0.80x + 2.9 ug/L vs.
Behring N Latex Ferritin Reagent | N = 44
y = 1.01x - 0.37 ug/L vs.
enzyme immunoassay |
| Sensitivity (Analytical) | < 10 ug/L | 5 ug/L |
{5}
Roche Diagnostic Systems, Inc.
Somerville, New Jersey 08876
August 1996
COBAS® INTEGRA Reagent Cassettes & Ancillary Reagents
510(k) Premarket Notification
Summary
# Table 4
## COBAS INTEGRA Cassette for Myoglobin
| | COBAS INTEGRA Cassette for Myoglobin | Behring N Latex Myoglobin Reagent |
| --- | --- | --- |
| Methodology | Immunoturbidimetric test for Myoglobin | Immunoturbidimetric test for Myoglobin |
| Sample type | Serum and plasma (heparin, EDTA, & fluoride) | Serum and plasma |
| Reported measuring units | ug/L | ug/L |
| Calibrator | Roche MYO T Standard (sourced from human skeletal muscle in liquid form)
0, 62.5, 125, 250, & 500 ug/L | Behring N Myoglobin Standard (lyophilized human serum)
785 ng/mL |
| Controls | Roche FERR/MYO T Control (lyophilized human serum w/added BSA)
Ferritin: 126 ± 13 ug/L
Myoglobin: 115 ± 12 ug/L | Behring N Myoglobin Control (lyophilized human serum)
106 ng/mL |
| Reagent (active ingredients) | R1. Glycine buffer w/ BSA and immunoglobulins (rabbit)
R2. Latex particles in glycine buffer coated w/ anti-myoglobin (rabbit) | R1. lyophilisate of polystyrene particles coated with rabbit anti-human myoglobin
R2. buffered rabbit serum soln.
R3. detergent soln. |
| Performance Characteristics: | | |
| Assay range | 0-500 ug/L
0-5000 IU/mL w/postdilution | 25-400 ug/L |
| Precision (Day-to-day) | 1.4% at 46 ug/L
0.6% at 312 ug/L | 4.8% at 85 ug/L
4.2% at 160 ug/L
5.0% at 310 ug/L |
| Accuracy | N = 230
y = 0.91x + 15 ug/L vs.
Behring N Latex Myoglobin Reagent | N = 117
y = 0.95X - 4.33 vs.
radioimmunoassay |
| Sensitivity (Analytical) | 3 ug/L | 25 ug/L |
{6}
Roche Diagnostic Systems, Inc.
Somerville, New Jersey 08876
August 1996
COBAS® INTEGRA Reagent Cassettes & Ancillary Reagents
510(k) Premarket Notification
Summary
Table 5
COBAS INTEGRA Cassette for Rheumatoid Factors
| | COBAS INTEGRA Cassette for Rheumatoid Factors | Behring N Latex RF Reagent on Behring Nephelometer |
| --- | --- | --- |
| Methodology | Immunoturbidimetric test for RF | Immunoturbidimetric test for RF |
| Sample type | Serum | Serum |
| Reported measuring units | IU/mL | IU/mL |
| Calibrator | Roche RF T Standard II (liquid human serum) 10, 20, 40, 80, &160 IU/mL | Behring N RF Standard (lyophilized human serum) 73 IU/mL |
| Controls | Roche RF/ASO T Control II (K954992) | Behring N Rheumatology SL Controls |
| Reagent (active ingredients) | R1. Accelerator polyethylene glycol in glycine buffer with bovine serum albumin
R2. Latex particles coated with human IgG in glycine buffer | R1. lyophilisate of polystyrene particles coated with antigen-antibody complex of human gamma-globulin/ anti-human gamma-globulin from sheep
R2. aqueous solution of polyethylene glycol |
| Performance Characteristics: | | |
| Assay range | 10-120 IU/mL
10-600 IU/mL w/postdilution | 10-600 IU/mL |
| Precision (Day-to-day) | 8.0% at 32 IU/mL
5.0% at 125 IU/mL | 9.3% at 92 IU/mL
6.2% at 155 IU/mL
6.6% at 306 IU/mL |
| Accuracy | N = 244
y = 0.70x + 12 IU/mL vs.
Behring N Latex RF Reagent | N = 72
y = 0.99 x - 20 IU/mL vs.
enzyme immunoassay |
| Sensitivity (Analytical) | 10 IU/mL | 10 IU/mL |
{7}
Roche Diagnostic Systems, Inc.
Somerville, New Jersey 08876
August 1996
COBAS® INTEGRA Reagent Cassettes & Ancillary Reagents
510(k) Premarket Notification
Summary
Table 6
COBAS INTEGRA Cassette for Calcium
| | COBAS INTEGRA Cassette for Calcium (Modified) | COBAS INTEGRA Cassette for Calcium (Cleared) | Boehringer Mannheim Calcium on Hitachi 911 |
| --- | --- | --- | --- |
| Methodology | Colorimetric o-Cresolphthalein complexone | Colorimetric o-cresolphthalein complexone | Colorimetric o-cresolphthalein complexone |
| Sample type | Serum, heparinized plasma and urine | Serum, heparinized plasma and urine | Serum, heparinized plasma and urine |
| Calibrator | Roche Calibrator (K942706) | Roche Calibrator (K942706) | Boehringer Mannheim Precial Calibrato r Serum |
| Reagent (active ingredients) | 1. o-Cresolphthalein complexone
2. 8-Hydroxyquinoline
3. CAPS
4. NaOH | 1. o-Cresolphthalein complexone
2. 8-Hydroxyquinoline
3. CAPS
4. NaOH | 1. 4-Aminobutyric acid
2. o-Cresolphthalein complexone
3. 8-Hydroxyquinoline
4. HCl |
| Performance Characteristics: | | | |
| Assay range | Serum, plasma: 0-20 mg/dL
Urine: 0-28 mg/dL
0-140 mg/dL
w/postdilution | Serum, plasma: 0-20 mg/dL
Urine: 0-100 mg/dL | Serum, plasma: 0-15 mg/dL
0-24.9 w/postdilution
Urine: 0-15 mg/dL
0-60 mg/dL
w/postdilution |
| Precision (Total) | Serum, plasma: 3.5% at 9.2 mg/dL
3.1% at 13.6 mg/dL
Urine: 0.91% at 5.6 mg/dL
1.1% at 23.7 mg/dL | Serum, plasma: 2.1% at 7.9 mg/dL
1.8% at 10.2 mg/dL
Urine: 2.8% at 3.9 mg/dL
0.77% at 18 mg/dL | Serum, plasma: 1.6% at 8.9 mg/dL
1.2% at 9.7 mg/dL
1.3% at 12.5 mg/dL
Urine: 2.2% at 2.9 mg/dL
1.7% at 7.8 mg/dL
1.4% at 36.7 mg/dL |
| Accuracy | N = 196
R = 0.987 vs. BM
Hitachi 911 | N = 240
R = 0.960 vs. BM
Hitachi 911 | N = 53
R = 0.997 vs. BM
Hitachi 717 |
| Sensitivity (Analytical) | 4.0 X 10⁻⁴ ΔA per mg/dL of calcium | 3.2 X 10⁻⁴ ΔA per mg/dL of calcium | Not specified in labeling |
