ROCHE COBAS INTEGRA REAGENT CASSETTES & ANCILLARY REAGENTS

• K Number: K972250
• Device Name: ROCHE COBAS INTEGRA REAGENT CASSETTES & ANCILLARY REAGENTS
• Manufacturer: ROCHE DIAGNOSTIC SYSTEMS, INC.
• Date Cleared: 1997-08-12 ( 57 days)
• Product Code: JFJ , CDQ , CDT , CET , CFR , CGX , CHH , DLB , DLJ , JIF , JQB , LAS , LFM
• Regulation Number: 862.1070
• Type: Traditional
• Panel: Clinical Chemistry
• Reference & Predicate Devices: K954992 , K961824 , K963292 , K964457 , K913124 , K951595 , K842280
• Predicate For: K031856 , K061048 , K062239 , K111753 , K132031 , K980996

Intended Use

COBAS INTEGRA Ammonia (NH3): contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the ammonia concentration in plasma (test NH3, 0-045).

COBAS INTEGRA aAmylase EPS (AMYLL): contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the catalytic activity of amylase in serum, plasma (test AMY-L, 0998) and urine (test AMY-UL 0-999).

COBAS INTEGRA Cholesterol (CHOLL): contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of total cholesterol (test CHOLL, 0-001) and HDL cholesterol concentration in serum and plasma in clinical laboratories.

COBAS INTEGRA HDL Cholesterol Application (HDLL): contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of total cholesterol and HDL - cholesterol (test HDLL, 0-002) concentration in serum and plasma in clinical laboratories.

COBAS INTEGRA Creatinine Enzymatic (CREAE): contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the creatinine concentration in serum (test CREAE, 0-014), and urine (test CREEU, 0-114).

COBAS INTEGRA Digitoxin (DIGIT): contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of digitoxin in serum or heparinized plasma (test DIGIT 0-259).

COBAS INTEGRA Gamma Glutamyltransferase (GGTL): 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; y-glutamyl peptide: amino acid y-glutamyltransferase) in serum and plasma (test GGTL, 0-599).

COBAS INTEGRA Glucose HK Liquid (GLUCL): contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the glucose concentration in serum, plasma (test GLUL, 0-991), urine (test GLULU, 0-992), and cerebrospinal fluid (test GLULC, 0-993).

COBAS INTEGRA Lipase (LIPL): contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the catalytic activity of lipase in serum and plasma (test LIPL, 0-200).

COBAS INTEGRA Lysergic acid diethylamide (LSD) contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the qualitative determination of lysergic acid diethylamide (LSD) in urine (test LSD, 0-001)

COBAS INTEGRA Urea/BUN (UREAL): contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the urea/BUN (blood urea nitrogen), in serum, plasma (test UREL, 0-003) and urine (test URELU, 0-004).

Roche TDM OnLine Digitoxin Calibrators: are intended for use with the Roche reagents for Digitoxin and the COBAS Chemistry systems for the quantitative determination of digitoxin in serum and plasma.

Roche TDM OnLine Digitoxin Controls: are quality control samples intended for use on COBAS chemistry systems with Roche reagents and calibrators for the quantitative determination of digitoxin assays.

Device Description

The COBAS INTEGRA test applications contained in this submission are intended for use with the COBAS INTEGRA Analyzer. The COBAS INTEGRA Analyzer and COBAS INTEGRA Reagent cassettes together provide an integrated system for in vitro diagnostic testing. The COBAS INTEGRA Analyzer utilizes three measuring principles, i.e., absorbance, fluorescence polarization and ion-selective electrodes. The analyzer has a throughput of up to 600 tests per hour with STAT samples prioritized and tested immediately. Random sample access, robotics and a user interface optimize time management and streamline workflow. The COBAS INTEGRA can store up to 68 COBAS INTEGRA Reagent Cassettes on board, 24 hours a day at 2-8℃. The COBAS INTEGRA Reagent Cassettes are compact and preparation-free with the added convenience of long term on-board stability. Barcode readers are used to identify newly loaded reagent cassettes, samples for patient identification, and rack inserts and to read calibration and control data from the cassette label. COBAS INTEGRA tests include chemistry, drugs of abuse, immunology, ion selective electrodes, therapeutic drug monitoring, and hematology reagents. Through this submission, it is the intention of Roche Diagnostic Systems to gain clearance for an additional 4 COBAS INTEGRA Reagent Cassettes and 2 ancillary reagents as well as modifications to 7 previously cleared COBAS INTEGRA Reagent Cassettes. These reagents have been modified from granulate to liquid form.

AI/ML Overview

The provided 510(k) summary (K972250) describes the acceptance criteria and study results for several Roche COBAS INTEGRA Reagent Cassettes and ancillary reagents. The studies are primarily focused on demonstrating substantial equivalence to predicate devices, rather than establishing de novo performance criteria against a fixed clinical standard. Consequently, the "acceptance criteria" are implied by the results of the comparative studies to be within acceptable analytical performance limits for equivalent devices.

Here's a breakdown of the requested information for each reagent, based on the provided text:

---

Roche COBAS® INTEGRA Reagent Cassettes & Ancillary Reagents (K972250)

The acceptance criteria are generally implied by the strong correlation and similar performance characteristics (assay range, precision, sensitivity, accuracy/linearity) when compared to the legally marketed predicate devices. The study's goal was to demonstrate substantial equivalence, meaning the new device performs comparably to the predicate.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for these in vitro diagnostic devices are demonstrated through a comparison of their performance characteristics (Assay Range, Precision, Sensitivity, Accuracy/Correlation Coefficient, and Linear Regression) against legally marketed predicate devices. The "reported device performance" is the performance of the COBAS INTEGRA (Liquid) reagents. The "acceptance criteria" are implied to be within comparable ranges to the predicate devices, indicating substantial equivalence.

Note: For each test, the predicate device's performance is presented alongside the new device's performance, and the linear regression typically shows correlation against the predicate. This comparative approach is the core of the acceptance criteria.

---

Ammonia (NH3)

Performance Characteristic	Acceptance Criteria (Predicate)	Reported Device Performance (COBAS INTEGRA Ammonia Liquid)
Assay Range	0 - 700 U/L (0-2800 U/L with postdilution)	0 - 700 µmol/L (0-1190 ug/dL)
Precision (Level 1)	Mean: ૯દિવ; %CV (within run): 5.7; %CV (total): 8.8	Mean: 48.8 µmol/L; %CV (w/r): 3.1; %CV (total): 5.2
Precision (Level 2)	Mean: 211; %CV (within run): 1.9; %CV (total): 5.9	Mean: 226 µmol/L; %CV (w/r): 2.0; %CV (total): 2.5
Sensitivity	0.0009 AA per µmol/L	0.76 AA per µmol/L
Accuracy (n=164)	Corr. Coefficient (r): 0.992	Corr. Coefficient (r): 0.997
Lin. Regression	1.02x + 3.2 µmol/L	1.03x - 2.8 µmol/L vs. Roche Reagent for Ammonia

---

Creatinine (CREAE) - Serum and Plasma

Performance Characteristic	Acceptance Criteria (Predicate: COBAS INTEGRA Creatinine (Kinetic, Jaffé))	Reported Device Performance (COBAS INTEGRA Creatinine (Enzymatic, PAP))
Assay Range	0 - 1300 µmol/L (0-13000 µmol/L with post dilution)	0 - 2000 µmol/L (0-20000 µmol/L with post dilution)
Precision (Level 1)	Mean: 85.5 µmol/L; %CV (w/r): 1.5; %CV (total): 1.9	Mean: 99.4 µmol/L; %CV (w/r): 1.6; %CV (total): 2.2
Precision (Level 2)	Mean: 624 µmol/L; %CV (w/r): 1.1; %CV (total): 1.5	Mean: 535 µmol/L; %CV (w/r): 0.88; %CV (total): 1.5
Sensitivity	8.0 X 10^-5 ΔA/min per µmol/L	2.2 X 10^-4 ΔA per µmol/L
Accuracy (n=238)	Corr. Coefficient (r): 0.999	Corr. Coefficient (r): 0.999
Lin. Regression	0.87x - 2 µmol/L	1.08x - 30.6 µmol/L vs. COBAS INTEGRA Creatinine (Jaffé)

---

Creatinine (CREAE) - Urine

Performance Characteristic	Acceptance Criteria (Predicate: COBAS INTEGRA Creatinine (Kinetic, Jaffé))	Reported Device Performance (COBAS INTEGRA Creatinine (Enzymatic, PAP))
Assay Range	0 - 32.5 mmol/L (0-130 mmol/L with post dilution)	0 - 40 mmol/L (0-200 mmol/L with post dilution)
Precision (Level 1)	Mean: 5.3 mmol/L; %CV (w/r): 1.5	Mean: 4.1 mmol/L; %CV (w/r): 0.88; %CV (total): 1.1
Precision (Level 2)	Mean: 19 mmol/L; %CV (w/r): 1.0	Mean: 14.0 mmol/L; %CV (w/r): 0.87; %CV (total): 0.93
Sensitivity	Not specified in labeling	5.7 X 10^-3 ΔA per mmol/L
Accuracy (n=116)	Not specified in labeling	Corr. Coefficient (r): 0.999
Lin. Regression	Not specified in labeling	0.99x - 0.28 mmol/L vs. COBAS INTEGRA Creatinine (Jaffé)

---

Digitoxin (DIGIT)

Performance Characteristic	Acceptance Criteria (Predicate: Abbott TDx/TDxFLx Digitoxin)	Reported Device Performance (COBAS INTEGRA Digitoxin)
Assay Range	2.0 - 80 ng/mL	2.0 - 65 ng/mL
Precision (Level 1)	Mean: 7.5 ng/mL; %CV (w/r): 7.05; %CV (total): 10.61	Mean: 10.4 ng/mL; %CV (w/r): 6.0; %CV (total): 7.4
Precision (Level 2)	Mean: 15.0 ng/mL; %CV (w/r): 4.87; %CV (total): 7.19	Mean: 19.5 ng/mL; %CV (w/r): 3.9; %CV (total): 4.5
Precision (Level 3)	Mean: 35.0 ng/mL; %CV (w/r): 4.72; %CV (total): 8.46	Mean: 37.1 ng/mL; %CV (w/r): 3.6; %CV (total): 3.7
Sensitivity	2.0 ng/mL	2.0 ng/mL
Accuracy (n=232)	Corr. Coefficient (r): 0.967	Corr. Coefficient (r): 0.973
Lin. Regression	1.060 + 0.729 ng/mL	0.945x + 1.19 ng/mL vs. Abbott TDx/TDxFLx Digitoxin

---

Lysergic acid diethylamide (LSD)

Performance Characteristic	Acceptance Criteria (Predicate: Roche Abuscreen RIA for LSD)	Reported Device Performance (COBAS INTEGRA LSD)
Assay Range	0 - 1 ng/mL	0 - 1 ng/mL
Precision (Level 1)	Mean: 0.0; %CV (w/r): 0.6	Mean (O.D.): 0.978; %CV (w/r): N/A
Precision (Level 2)	Mean: 0.25; %CV (w/r): 1.3	Mean (O.D.): 0.913; %CV (w/r): N/A
Precision (Level 3)	Mean: 0.5; %CV (w/r): 1.6	Mean (O.D.): 0.870; %CV (w/r): N/A
Sensitivity	0.25 ng/mL of LSD at > 99% confidence	0.10 ng/mL of LSD at > 95% confidence
Accuracy	Positive Samples (GC/MS): 21/0; Positive Samples (RIA): 21/0	Positive Samples (GC/MS): 39/0; Positive Samples (RIA): 39/0

Note: For LSD, precision is presented in Optical Density (O.D.) for the new device vs. ng/mL for the predicate, making direct comparison of mean values challenging. However, the %CV for within-run are similar.

---

α-Amylase (AMYLL) - Serum and Plasma

Performance Characteristic	Acceptance Criteria (Predicate: COBAS INTEGRA α-Amylase (Granulate))	Reported Device Performance (COBAS INTEGRA α-Amylase EPS (Liquid))
Assay Range	0 - 2000 U/L (0-20000 U/L with post dilution)	0 - 2000 U/L (0-10000 U/L with post dilution)
Precision (Level 1)	Mean: 143 U/L; %CV (w/r): 1.6; %CV (total): 1.6	Mean: 76 U/L; %CV (w/r): 1.6; %CV (total): 2.3
Precision (Level 2)	Mean: 277 U/L; %CV (w/r): 1.1; %CV (total): 2.0	Mean: 498 U/L; %CV (w/r): 1.3; %CV (total): 2.6
Sensitivity	1.5 X 10^-4 ΔA/min per U/L	1.9 X 10^-4 ΔA/min per U/L
Accuracy (n=114)	Corr. Coefficient (r): 0.992	Corr. Coefficient (r): 0.996
Lin. Regression	0.98x - 19 U/L	0.43x + 4 U/L vs. COBAS INTEGRA α-Amylase (granulate)

---

α-Amylase (AMYLL) - Urine

Performance Characteristic	Acceptance Criteria (Predicate: COBAS INTEGRA α-Amylase (Granulate))	Reported Device Performance (COBAS INTEGRA α-Amylase EPS (Liquid))
Assay Range	0 - 2000 U/L (0-20000 U/L with post dilution)	0 - 2000 U/L (0-10000 U/L with post dilution)
Precision (Level 1)	Mean: 22 U/L; %CV (w/r): 2.5	Mean: 183 U/L; %CV (w/r): 1.3; %CV (total): 1.7
Precision (Level 2)	Mean: 302 U/L; %CV (w/r): 0.56	Mean: 603 U/L; %CV (w/r): N/A; %CV (total): 1.6
Sensitivity	Not specified in labeling	1.9 X 10^-4 ΔA/min per U/L
Accuracy (n=150)	Not specified in labeling	Corr. Coefficient (r): 0.988
Lin. Regression	Not specified in labeling	0.44x + 0 U/L vs. COBAS INTEGRA α-Amylase (granulate)

---

Cholesterol (CHOLL)

Performance Characteristic	Acceptance Criteria (Predicate: COBAS INTEGRA Cholesterol (Granulate))	Reported Device Performance (COBAS INTEGRA Cholesterol (Liquid))
Assay Range	0 - 20.7 mmol/L (0-8000 mg/dL with post dilution)	0 - 18.1 mmol/L (0-7000 mg/dL with post dilution)
Precision (Level 1)	Mean: 5.0 mmol/L; %CV (w/r): 1.3; %CV (total): 1.1	Mean: 5.3 mmol/L; %CV (w/r): 1.3; %CV (total): 2.2
Precision (Level 2)	Mean: 6.3 mmol/L; %CV (w/r): 1.0; %CV (total): 1.2	Mean: 6.7 mmol/L; %CV (w/r): 1.1; %CV (total): 2.5
Precision (Level 3)	Mean: 8.0 mmol/L; %CV (w/r): 2.0; %CV (total): 1.5	N/A
Sensitivity	6.4 X 10^-2 ΔA per mmol/L	8.8 X 10^-2 ΔA per mmol/L
Accuracy (n=214)	Corr. Coefficient (r): 0.995	Corr. Coefficient (r): 0.998
Lin. Regression	1.04x + 0.1 mmol/L	0.99x + 0.0 mmol/L vs. COBAS INTEGRA Cholesterol (granulate)

---

HDL-Cholesterol Application (HDLL)

Performance Characteristic	Acceptance Criteria (Predicate: COBAS INTEGRA HDL - Cholesterol Application (granulate))	Reported Device Performance (COBAS INTEGRA HDL - Cholesterol Application (liquid))
Assay Range	0 - 5.0 mmol/L (0-193 mg/dL)	0 - 5.0 mmol/L (0-193 mg/dL)
Precision (Level 1)	Mean: 0.82 mmol/L; %CV (w/r): 1.2; %CV (total): 2.7	Mean: 0.20 mmol/L; %CV (w/r): 1.51.3*; %CV (total): 3.0
Precision (Level 2)	Mean: 1.42 mmol/L; %CV (w/r): 0.85; %CV (total): 5.5	Mean: 1.91 mmol/L; %CV (w/r): 0.26; %CV (total): 1.6
Sensitivity	6.4 X 10^-2 ΔA per mmol/L	8.8 X 10^-2 ΔA per mmol/L
Accuracy (n=240)	Corr. Coefficient (r): 0.998	Corr. Coefficient (r): 0.999
Lin. Regression	0.99x - 0.05 mmol/L	0.99x + 0.03 mmol/L vs. COBAS INTEGRA HDL - Cholesterol Application (granulate)

Note: There seems to be a typo for %CV (within run) in Level 1 of the HDLL liquid reagent (1.51.3).

---

Gamma-Glutamyltransferase (GGTL)

Performance Characteristic	Acceptance Criteria (Predicate: COBAS INTEGRA GGT (Granulate))	Reported Device Performance (COBAS INTEGRA GGTL (Liquid))
Assay Range	0 - 700 U/L (0-7000 U/L with post dilution)	0 - 600 U/L (0-6000 U/L with post dilution)
Precision (Level 1)	Mean: 37.9 U/L; %CV (w/r): 0.67; %CV (total): 1.2	Mean: 21 U/L; %CV (w/r): 0.83; %CV (total): 2.8
Precision (Level 2)	Mean: 345 U/L; %CV (w/r): 0.46; %CV (total): 1.4	Mean: 428 U/L; %CV (w/r): 0.54; %CV (total): 1.5
Sensitivity	5.0 X 10^4 ΔA/min per U/L	6.8 X 10^4 ΔA/min per U/L
Accuracy (n=196)	Corr. Coefficient (r): 0.998	Corr. Coefficient (r): 0.999
Lin. Regression	1.00x + 0 U/L	1.00x - 1.2 U/L vs. COBAS INTEGRA GGTL (granulate)

---

Glucose (GLUCL) - Serum and Plasma

Performance Characteristic	Acceptance Criteria (Predicate: COBAS INTEGRA Glucose (Granulate))	Reported Device Performance (COBAS INTEGRA Glucose (Liquid))
Assay Range	0 - 40 mmol/L (0-400 mmol/L with post dilution)	0 - 40 mmol/L (0-400 mmol/L with post dilution)
Precision (Level 1)	Mean: 5.6 mmol/L; %CV (w/r): 1.2; %CV (total): 1.1	Mean: 5.3 mmol/L; %CV (w/r): 1.7; %CV (total): 2.6
Precision (Level 2)	Mean: 19.7 mmol/L; %CV (w/r): 0.97; %CV (total): 0.89	Mean: 33.2 mmol/L; %CV (w/r): 0.72; %CV (total): 1.5
Sensitivity	9.3 X 10^-2 ΔA per mmol/L	5.4 X 10^-2 ΔA per mmol/L
Accuracy (n=220)	Corr. Coefficient (r): 0.997	Corr. Coefficient (r): 0.999
Lin. Regression	0.98x + 0.1 mmol/L	1.05x - 0.2 mmol/L vs. COBAS INTEGRA Glucose (granulate)

---

Glucose (GLUCL) - Urine

Performance Characteristic	Acceptance Criteria (Predicate: COBAS INTEGRA Glucose (Granulate))	Reported Device Performance (COBAS INTEGRA Glucose (Liquid))
Assay Range	0 - 16 mmol/L (0-160 mmol/L with post dilution)	0 - 40 mmol/L (0-400 mmol/L with post dilution)
Precision (Level 1)	Mean: 0.27 mmol/L; %CV (w/r): 2.0	Mean: 1.7 mmol/L; %CV (w/r): 1.7; %CV (total): 4.3
Precision (Level 2)	Mean: 0.48 mmol/L; %CV (w/r): 0.99	Mean: 37.1 mmol/L; %CV (w/r): 1.8; %CV (total): 2.9
Sensitivity	2.2 X 10^1 ΔA per mmol/L	5.4 X 10^2 ΔA per mmol/L
Accuracy (n=120)	Not specified in labeling	Corr. Coefficient (r): 0.999
Lin. Regression	Not specified in labeling	1.01x - 0.02 mmol/L vs. COBAS INTEGRA Glucose (granulate)

---

Glucose (GLUCL) - CSF

Performance Characteristic	Acceptance Criteria (Predicate: COBAS INTEGRA Glucose (Granulate))	Reported Device Performance (COBAS INTEGRA Glucose (Liquid))
Assay Range	0 - 20 mmol/L (0-360 mmol/L with post dilution)	0 - 40 mmol/L (0-400 mmol/L with post dilution)
Precision (Level 1)	Mean: 4.7 mmol/L; %CV (w/r): 0.57	Mean: 1.7 mmol/L; %CV (w/r): 1.6; %CV (total): 2.3
Precision (Level 2)	Mean: 10.3 mmol/L; %CV (w/r): 0.23	Mean: 3.3 mmol/L; %CV (w/r): 1.8; %CV (total): 1.9
Sensitivity	1.8 X 10^1 ΔA per mmol/L	5.4 X 10^2 ΔA per mmol/L
Accuracy (n=212)	Not specified in labeling	Corr. Coefficient (r): 0.999
Lin. Regression	Not specified in labeling	1.02x - 0.17 mmol/L vs. COBAS INTEGRA Glucose (granulate)

---

Lipase (LIPL)

Performance Characteristic	Acceptance Criteria (Predicate: COBAS INTEGRA Lipase (Granulate))	Reported Device Performance (COBAS INTEGRA Lipase (Liquid))
Assay Range	0 - 700 U/L (0-3500 U/L with post dilution)	0 - 600 U/L (0-3000 U/L with post dilution)
Precision (Level 1)	Mean: 116 U/L; %CV (w/r): 1.7; %CV (total): 4.6	Mean: 126 U/L; %CV (w/r): 1.9; %CV (total): 3.1
Precision (Level 2)	Mean: 550 U/L; %CV (w/r): 2.1; %CV (total): 3.7	Mean: 515 U/L; %CV (w/r): 1.3; %CV (total): 2.9
Sensitivity	5.6 X 10^-5 ΔA/min per U/L	6.4 X 10^-5 ΔA/min per U/L
Accuracy (n=198)	Corr. Coefficient (r): 0.976	Corr. Coefficient (r): 0.976
Lin. Regression	1.06x - 7 U/L	0.82x + 16 U/L vs. COBAS INTEGRA Lipase (granulate)

---

Urea/BUN (UREAL) - Serum and Plasma

Performance Characteristic	Acceptance Criteria (Predicate: COBAS INTEGRA Urea/BUN (Granulate))	Reported Device Performance (COBAS INTEGRA Urea/BUN (Liquid))
Assay Range	0 - 55 mmol/L (0-550 mmol/L with post dilution)	0 - 40 mmol/L (0-400 mmol/L with post dilution)
Precision (Level 1)	Mean: 6.9 mmol/L; %CV (w/r): 0.85; %CV (total): 2.0	Mean: 4.1 mmol/L; %CV (w/r): 2.3; %CV (total): 3.9
Precision (Level 2)	Mean: 19.9 mmol/L; %CV (w/r): 1.0; %CV (total): 2.3	Mean: 31.0 mmol/L; %CV (w/r): 0.89; %CV (total): 2.8
Sensitivity	6.8 X 10^-3 ΔA/min per mmol/L	2.2 X 10^-2 ΔA/min per mmol/L
Accuracy (n=236)	Corr. Coefficient (r): 0.999	Corr. Coefficient (r): 0.999
Lin. Regression	1.01x + 0.30 mmol/L	1.00x + 0.1 mmol/L vs. COBAS INTEGRA Urea/BUN (granulate)

---

Urea/BUN (UREAL) - Urine

Performance Characteristic	Acceptance Criteria (Predicate: COBAS INTEGRA Urea/BUN (Granulate))	Reported Device Performance (COBAS INTEGRA Urea/BUN (Liquid))
Assay Range	0 - 2200 mmol/L (0-5500 mmol/L with post dilution)	0 - 2000 mmol/L (0-6000 mmol/L with post dilution)
Precision (Level 1)	Mean: 73 mmol/L; %CV (w/r): 0.99	Mean: 421 mmol/L; %CV (w/r): 1.3; %CV (total): 1.8
Precision (Level 2)	Mean: 345 mmol/L; %CV (w/r): 0.6	Mean: 679 mmol/L; %CV (w/r): 1.2; %CV (total): 1.8
Sensitivity	Not specified in labeling	2.0 X 10^-2 ΔA/min per mmol/L
Accuracy (n=120)	Not specified in labeling	Corr. Coefficient (r): 0.999
Lin. Regression	Not specified in labeling	1.0X + 1.3 mmol/L vs. COBAS INTEGRA Urea/BUN (granulate)

---

2. Sample sizes used for the test set and data provenance

The sample sizes for accuracy/correlation studies are provided in the tables above under "Sample size (n)". These values range from 114 to 240 for quantitative assays and 39 (positive) for LSD.

The data provenance is not explicitly stated as "country of origin" or "retrospective/prospective." However, given the context of a 510(k) submission for in vitro diagnostic reagents by Roche Diagnostic Systems, Inc. (located in Somerville, New Jersey, USA), it is highly likely these studies were conducted in a clinical laboratory setting in the USA. The studies are presented as direct comparisons between the new liquid reagents and existing granulate reagents or other legally marketed devices, implying they are prospective comparative studies assessing analytical performance.

3. Number of experts used to establish the ground truth for the test set and qualifications of those experts

For these chemical assays (e.g., ammonia, creatinine, cholesterol) and therapeutic drug monitoring (digitoxin), "ground truth" is typically established by the quantitative results of the predicate device or a reference method. The document does not mention "experts" in the sense of human readers adjudicating results, as these are quantitative in vitro diagnostic tests. The ground truth is the measured concentration or activity of the analyte as determined by the accepted reference method or predicate device functionality.

For LSD, which involves qualitative detection, the "ground truth" against which the COBAS INTEGRA LSD was compared appears to be GC/MS (Gas Chromatography/Mass Spectrometry), which is a gold standard analytical method for drug detection. The document does not specify the qualifications of individuals performing these GC/MS analyses or interpreting the results, but they would be trained laboratory personnel.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set

No adjudication method is mentioned. For these types of quantitative and qualitative analytical tests, "adjudication" by experts in the context of diagnostic imaging or pathology interpretation is not applicable. The comparison is based on numerical results compared to an established method or predicate.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, if so, what was the effect size of how much human readers improve with AI vs without AI assistance

No MRMC study was conducted. This type of study is relevant for medical imaging or pathology devices where human interpretation is a key component, often assisted by AI. The submitted devices are reagents for automated clinical analyzers, where the output is a numerical value or a qualitative positive/negative result, not an image requiring human interpretation. Therefore, there's no mention of AI assistance or human reader improvement.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done

Yes, the studies presented are effectively standalone performance evaluations of the reagent-analyzer system. These are not "algorithm-only" studies in the modern AI sense, but rather a direct assessment of the analytical performance of the new liquid reagent format on the COBAS INTEGRA Analyzer. The results (e.g., assay range, precision, accuracy) reflect the performance of the integrated system without direct human-in-the-loop interpretation impacting the primary measurement.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The type of ground truth used varies slightly based on the assay, but generally involves:

• Quantitative Assays (Ammonia, Creatinine, Cholesterol, HDL-Cholesterol, GGT, Glucose, Lipase, Urea/BUN): The ground truth for these assays is the quantitative result obtained from the predicate device method. The accuracy is assessed by correlating the results of the new liquid reagents with the predicate (often the granulate version of the same Roche COBAS INTEGRA reagents or another established method like Abbott TDx/TDxFLx for Digitoxin). Linear regression analysis is used to demonstrate agreement.
• Qualitative Assay (LSD): The ground truth for LSD detection is established by a more definitive analytical method, specifically Gas Chromatography/Mass Spectrometry (GC/MS).

8. The sample size for the training set

The document does not explicitly delineate a "training set" in the context of machine learning or AI development. For these chemical assays, the development of the reagents and their formulation would involve extensive R&D and optimization, which could be considered an iterative development process, but it's not described as a distinct "training set" with separate ground truth establishment. The data presented in the tables are for validation or verification of the final product.

9. How the ground truth for the training set was established

As there is no explicitly defined "training set" in the submitted documentation related to AI/ML, there is no description of how ground truth for such a set was established. The development of reagents relies on established chemical and biochemical principles, and performance characteristics are determined through standard analytical validation procedures using reference materials and comparative studies against predicate methods.

Summary

{0}------------------------------------------------

912250

Roche

AUG 1 2 1997

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.

Identification of 510(k) Sponsor: I.

Roche Diagnostic Systems, Inc. a subsidiary of Hoffmann-La Roche, Inc. Branchburg Township 1080 U.S. Highway 202 Somerville, New Jersey 08876-3771

510(k) Submission dated June 13, 1997

Maria Feijoo Contact: Regulatory Affairs Associate Phone: [phone] [phone] Fax:

{1}------------------------------------------------

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	Regulation Number
COBAS INTEGRA...
Ammonia	Ammonia test system,Enzymatic method	JIF	862.1065
αAmylase EPS	Amylase test system,Catalytic method	JFJ	862.1070
Cholesterol	Cholesterol test system,Enzymatic esterase - oxidasemethod	CHH	862.1175
HDL-Cholesterol	Lipoprotein test system,Phosphotungstic acid method	N/A	862.1475
Creatinine	Creatinine test system,Enzymatic method	JFY	862.1225
Digitoxin	Digitoxin test system,Kinetic interaction ofmicroparticles in solution method	DKQ	862.3300
Gamma-Glutamyltransferase (GGT)	Gamma-glutamyl transpeptidase and isoenzymes test system,Kinetic method	JQB	862.1360
Glucose HK	Glucose test system,Enzymatic method	CFR	862.1345
Lipase	Lipase test system,Turbidimetric method	CET	862.1465
Lysergic acid diethylamide (LSD)	Lysergic acid diethylamide (LSD) test system,Kinetic interaction ofmicroparticles in solution method	N/A	862.3580
Urea	Urea nitrogen test system,Kinetic urease method	CDQ	862.1770
Roche TDM OnLine...
Digitoxin Calibrators	Clinical toxicology calibrator,Drug specific	DLJ	862.3200
Digitoxin Controls	Clinical toxicology controlmaterial,Drug specific	LAS	862.3280

ableœ5
----------------	--

{2}------------------------------------------------

1

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 ofsubstantialequivalence
COBAS INTEGRA...
Ammonia	Roche Reagent for Ammonia	K913124	8/12/91
αAmylase EPS (Liquid)	COBAS INTEGRA αAmylase (Granulate,CL-PNP-G, method)	K951595	9/8/95
Cholesterol (Liquid)	COBAS INTEGRA Cholesterol (Granulate)	K951595	9/8/95
HDL - Cholesterol (Liquid)	COBAS INTEGRAHDL - Cholesterol(Granulate)	K951595	9/8/95
Creatinine (Enzymatic)	COBAS INTEGRA Creatinine (KineticJaffe)	K951595	9/8/95
Digitoxin	Abbott Diagnostics, TDX / TDX FlexDigitoxin Reagent	K842280	8/16/84
Gamma-Glutamyltransferase (GGT)	COBAS INTEGRA Lipase (Granulate)	K951595	9/8/95
Glucose HK	COBAS INTEGRA Glucose HK (Granulate)	K951595	9/8/95
Lipase	COBAS INTEGRA Lipase (Granulate)	K951595	9/8/95
Lysergic acid diethylamide (LSD)
Urea	COBAS INTEGRA Urea (Granulate)	K951595	9/8/95
Roche TDM OnLine ...
Digitoxin Calibrators	Abbott Diagnostics, TDX / TDX FlexDigitoxin Calibrators	K842280	8/16/84
Digitoxin Controls	Abbott Diagnostics, TDX / TDX FlexDigitoxin Controls	K842280	8/16/84

11C	ablાર	1

IV. Description of the Device/Statement of Intended Use:

The COBAS INTEGRA test applications contained in this submission are intended for use with the COBAS INTEGRA Analyzer. The COBAS INTEGRA Analyzer and COBAS INTEGRA Reagent cassettes together provide an integrated system for in vitro diagnostic testing. The COBAS INTEGRA Analyzer along with 96 other Roche COBAS INTEGRA Reagent Cassettes were previously cleared on September 8, 1995 (K951595); January 25, 1996 (K954992); July 23, 1996 (K961824); October 31, 1996 (K963292); and January 21, 1997 (K964457).

{3}------------------------------------------------

The COBAS INTEGRA Analyzer utilizes three measuring principles, i.e., absorbance, fluorescence polarization and ion-selective electrodes. The analyzer has a throughput of up to 600 tests per hour with STAT samples prioritized and tested immediately. Random sample access, robotics and a user interface optimize time management and streamline workflow. The COBAS INTEGRA can store up to 68 COBAS INTEGRA Reagent Cassettes on board, 24 hours a day at 2-8℃. The COBAS INTEGRA Reagent Cassettes are compact and preparation-free with the added convenience of long term on-board stability. Barcode readers are used to identify newly loaded reagent cassettes, samples for patient identification, and rack inserts and to read calibration and control data from the cassette label. COBAS INTEGRA tests include chemistry, drugs of abuse, immunology, ion selective electrodes, therapeutic drug monitoring, and hematology reagents. For additional information on the COBAS INTEGRA Analyzer and its constituent modules, please refer to the Operator's Manual in Volumes 1 through 2, pages 92-703, of the original 510(k) submission (K951595).

Through this submission, it is the intention of Roche Diagnostic Systems to gain clearance for an additional 4 COBAS INTEGRA Reagent Cassettes and 2 ancillary reagents as well as modifications to 7 previously cleared COBAS INTEGRA Reagent Cassettes. These reagents have been modified from granulate to liquid form.

The new Reagent Cassettes and ancillary reagents are:

COBAS INTEGRA Ammonia (NH3):

contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the ammonia concentration in plasma (test NH3, 0-045).

COBAS INTEGRA Creatinine Enzymatic (CREAE):

contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the creatinine concentration in serum (test CREAE, 0-014), and urine (test CREEU, 0-114).

COBAS INTEGRA Digitoxin (DIGIT):

contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of digitoxin in serum or heparinized plasma (test DIGIT 0-259).

Roche TDM OnLine Digitoxin Calibrators:

are intended for use with the Roche reagents for Digitoxin and the COBAS Chemistry systems for the quantitative determination of digitoxin in serum and plasma.

{4}------------------------------------------------

Roche Diagnostic Systems, Inc. Somerville, New Jersey 08876 June 1997

Roche TDM OnLine Digitoxin Controls:

are quality control samples intended for use on COBAS chemistry systems with Roche reagents and calibrators for the quantitative determination of digitoxin assays.

COBAS INTEGRA Lysergic acid diethylamide (LSD):

contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the qualitative determination of lysergic acid diethylamide (LSD) in urine (test LSD, 0-001)

The modified Reagent Cassettes are:

COBAS INTEGRA aAmylase EPS (AMYLL):

contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the catalytic activity of amylase in serum, plasma (test AMY-L, 0998) and urine (test AMY-UL 0-999).

COBAS INTEGRA Cholesterol (CHOLL):

contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of total cholesterol (test CHOLL, 0-001) and HDL - cholesterol concentration in serum and plasma in clinical laboratories.

COBAS INTEGRA HDL - Cholesterol Application (HDLL):

contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of total cholesterol and HDL - cholesterol (test HDLL, 0-002) concentration in serum and plasma in clinical laboratories.

COBAS INTEGRA Gamma - Glutamyltransferase (GGTL):

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; y-glutamyl peptide: amino acid y-glutamyltransferase) in serum and plasma (test GGTL, 0-599).

COBAS INTEGRA Glucose HK Liquid (GLUCL):

contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the glucose concentration in serum, plasma (test GLUL, 0-991), urine (test GLULU, 0-992), and cerebrospinal fluid (test GLULC, 0-993).

COBAS INTEGRA Lipase (LIPL):

contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the catalytic activity of lipase in serum and plasma (test LIPL, 0-200).

{5}------------------------------------------------

COBAS INTEGRA Urea/BUN (UREAL):

contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the urea/BUN (blood urea nitrogen), in serum, plasma (test UREL, 0-003) and urine (test URELU, 0-004).

The clinical utility and methodology of each reagent cassette are further described in the test specific COBAS INTEGRA Method Manual sheets, contained in the test specific sections of this submission.

V. Summary of the technological characteristics of the new device in comparison to those of the predicate.

Tables 3-13 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 3-13 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.

{6}------------------------------------------------

・

, de

Table 3 - Ammonia (NH3)

	COBAS INTEGRA Ammonia		Roche Reagent for Ammonia
Intended Use	quantitative determination of the		quantitative determination of the
	ammonia concentration		ammonia concentration
Sample type	plasma		plasma
Methodology	enzymatic, with glutamate		enzymatic, with glutamate
	dehydrogenase		dehydrogenase
Reagents	R1: Enzyme (liquid)		R1: Enzyme (liquid)
	R2: Coenzyme (liquid)		R2: Coenzyme (liquid)
Calibrator	Roche Ammonia/Ethanol/CO,		Roche Ammonia/Ethanol/CO.
	Calibrator		Calibrator
Controls	Roche Ammonia/Ethanol Controls		Roche Ammonia/Ethanol Controls
Performance Characteristics:
Assay Range	0 - 700 umol/L (0 - 1190 ug/dL )		0 - 700 U/L
			0 - 2,800 U/L with postdilution
Precision:	Level 1	Level 2	Level 1 2	Level 2
Mean (umol/L)	48.8	226	ર્દિવ	211
	(83.0 ug/dL)	(384 ug/dL)
%CV (within run)	3.1	2.0	5.7	1.9
%CV (total)	5.2	2.5	8.8	5.9
Sensitivity	0.76 AA per umol/L		0.0009 AA per umol/L
Accuracy:
Sample size (n)	164		વેરૂ
Corr. Coefficient (r)	0.997		0.992
Lin. Regression	1.03x - 2.8 umol/L vs. Roche		1.02x + 3.2 umol/L
	Reagent for Ammonia

{7}------------------------------------------------

Table 4 - Creatinine (CREAE)

	COBAS INTEGRA Creatinine(Enzymatic, PAP)	COBAS INTEGRA Creatinine(Kinetic, Jaffé)
Intended Use	quantitative determination of the catalyticactivity of a amylase	quantitative determination of the catalyticactivity of a amylase
Sample type	serum, plasma and urine	serum, plasma and urine
Methodology	enzymatic colorimetric method (PAP)	Jaffé, buffered, kinetic method
Reagents	R1: Enzyme (liquid)R2: Substrate (liquid)	R1: Alkaline buffer (liquid)R2: Picric acid (liquid)
Calibrator	Roche Calibrator (human)	Roche Calibrator (human)
Controls	Roche Control Serum N and P (human)	Roche Control Serum N and P (human)

Performance Characteristics for serum and plasma:

Assay Range	0 - 2000 µmol/L (0-22.6 mg/dL)0 - 20000 µmol/L (0-226 mg/dL) with post dilution	0 - 1300 µmol/L (0-15 mg/dL)0 - 13000 µmol/L (0-1470 mg/dL) with post dilution
Precision:	Level 1	Level 2	Level 1	Level 2
Mean (µmol/L)	99.4(1.1mg/dL)	535(6.0 mg/dL)	85.5(0.97mg/dL)	624(7.1 mg/dL)
%CV (within run)	1.6	0.88	1.5	1.1
%CV (total)	2.2	1.5	1.9	1.5
Sensitivity	2.2 X 10-4 ΔA per µmol/L(1.9 X 10-4 ΔA per mg/dL)		8.0 X 10-5 ΔA/min per µmol/L(1.7 X 10-3 ΔA/min per mg/dL)
Accuracy:
Sample size (n)	238		256
Corr. Coefficient (r)	0.999		0.999
Lin. Regression	1.08x - 30.6 µmol/L vs. COBASINTEGRA Creatinine (Jaffé)		0.87x - 2 µmol/L

Performance Characteristics for urine:

Assay Range	0 - 40 mmol/L (0-450 mg/dL)0 - 200 mmol/L (0-2260 mg/dL) with postdilution	0 - 32.5 mmol/L (0-367 mg/dL)0 - 130 mmol/L (0-1470 mg/dL) with postdilution
Precision:	Level 1	Level 2	Level 1	Level 2
Mean (mmo/L)	4.1(46.7 mg/dL)	14.0(159 mg/dL)	5.3(60 mg/dL)	19(216 mg/dL)
%CV (within run)	0.88	0.87	1.5	1.0
%CV (total)	1.1	0.93
Sensitivity	$5.7 X 10^{-3}$ ΔA per mmol/L( $5.1 X 10^{-2}$ ΔA per mg/dL)	Not specified in labeling
Accuracy:
Sample size (n)	116	Not specified in labeling
Corr. Coefficient (r)	0.999
Lin. Regression	0.99x -0.28 mmol/L vs. COBASINTEGRA Creatinine (Jaffé)

{8}------------------------------------------------

Lin. Regression

く

1.060 + 0.729 ng/mL

Table 5 - Digitoxin Reagent, Calibrators, and Controls (DIGIT)

COBAS INTEGRA Digitoxin &Roche - TDM OnLine DigitoxinCalibrators & Controls			Abbott TDx/TDxFLx DigitoxinReagent, Calibrators & Controls
Intended Use	quantitative determination of digitoxin		quantitative determination of digitoxin
Sample type	serum and heparinized plasma		serum and plasma
Methodology	kinetic interaction of microparticles insolution (KIMS)		fluorescence polarization (FPIA)
Reagents	R1: Anti-digitoxin monoclonal antibody(mouse) in buffer (liquid)R2: Conjugated digitoxin derivativemicroparticles in buffer (liquid)		R1: Digitoxin Antiserum (Rabbit) inbufferR2: Digitoxin Fluorescein tracer in buffer
Calibrator Levels(in human serum)	0, 7.5, 15, 30, 45, 65 ng/mL		0, 5.0, 10.0, 20.0, 40.0, 80.0 ng/mL
Controls Levels(ng/mL)(in human serum)	Level 112.0 - 18.0	Level 224.0 - 36.0	Level 336.0 - 54.0	Level 15.4- 9.6	Level 212.0- 18.0	Level 326.5 - 43.5
Performance Characteristics:
Assay Range	2.0 - 65 ng/mL		2.0 - 80 ng/mL
Precision:	Level 1	Level 2	Level 3	Level 1	Level 2	Level 3
Mean (ng/mL)	10.4	19.5	37.1	7.5	15.0	35.0
% CV (within run)	6.0	3.9	3.6	7.05	4.87	4.72
%CV (total)	7.4	4.5	3.7	10.61	7.19	8.46
Sensitivity	2.0 ng/mL			2.0 ng/mL
Accuracy:Sample size (n)	232			178
Corr. Coefficient (r)	0.973			0.967

0.945x + 1.19 ng/mL vs. Abbott

TDx/TDxFLx Digitoxin

1 039

{9}------------------------------------------------

Table 6 - Lysergic acid diethylamide (LSD)

	COBAS INTEGRA LSD	Roche Abuscreen RIA for LSD
Intended Use	qualitative detection of LSD and itsmetabolites	detection of LSD and its metabolites
Sample type	urine	urine
Methodology	kinetic interaction of microparticles insolution (KIMS)	competitive binding to antibody of ¹²⁵I-radiolabeled antigen and unlabeledantigen
Cutoff	0.5 ng/mL	0.5 ng/mL
Reagents	R1: BufferR2: conjugated LSD derivativemicroparticles in bufferR3: LSD polyclonal antibody (goat) inbuffer	R1: LSD polyclonal (rabbit) antibody inbufferR2: ¹²⁵I-LSD in bufferR3: Anti-rabbit immunoglobulin serum(goat) in buffer
Calibrator	Roche Abuscreen Calibration Standard	Roche Abuscreen Calibration Standard
Controls	Roche Abuscreen Reference Controlsand Calibrator	Roche Abuscreen Reference Controlsand Calibrator

Performance Characteristics:

ે છ

Assay Range	0 - 1 ng/mL			0 - 1 ng/mL
Precision:	Level 1	Level 2	Level 3	L1ng/mL	L2ng/mL	L3ng/mL	L4ng/mL
Mean	O.D.	O.D.	O.D.	0.0	0.25	0.5	1.0
%CV (within run)	0.978	0.913	0.870	0.6	1.3	1.6	1.8
Sensitivity	0.10 ng/mL of LSD at > 95% confidence				0.25 ng/mL of LSD at > 99% confidence
Accuracy:
Positive Samples	INTEGRA	GC/MS	RIA		GC/MS		RIA
	+39-0	390	390	+	21		210

{10}------------------------------------------------

Table 7 - α- Amylase (AMYLL)

	COBAS INTEGRA α - AmylaseEPS (Liquid)	COBAS INTEGRA α - Amylase(Granulate)
Intended Use	quantitative determination of thecatalytic activity of α amylase	quantitative determination of thecatalytic activity of α amylase
Sample type	serum, plasma and urine	serum, plasma and urine
Methodology	enzymatic colorimetric methodusing the substrate 4,6-ethylidene-p-nitrophenyl-α,D-maltoheptaoside	enzymatic colorimetric method with 2-chloro -4-nitrophenyl-β-D-maltoheptaoside
Reagents	R1: Enzyme (liquid)R2: Substrate (liquid)	R1: Enzyme (granulate)R2: Substrate (granulate)
Calibrator	Roche Calibrator (human)	Roche Calibrator (human)
Controls	Roche Control Serum N and P(human)	Roche Control Serum N and P(human)
Performance Characteristics for serum and plasma:
Assay Range	0 - 2000 U/L0 - 10000 U/L with post dilution	0 - 2000 U/L0 - 20000 U/L with post dilution
Precision:Mean (U/L)	Level 176	Level 2498
	Level 1143	Level 2277

Mean (U/L)	76	498	143	277
%CV (within run)	1.6	1.3	1.6	1.1
%CV (total)	2.3	2.6	1.6	2.0
Sensitivity	1.9 X 10-4 ΔA/min per U/L		1.5 X 10-4 ΔA/min per U/L
Accuracy:
Sample size (n)	114		212
Corr. Coefficient (r)	0.996		0.992
Lin. Regression	0.43x + 4 U/L vs. COBAS		0.98x - 19 U/L
	INTEGRA α - Amylase (granulate)

Performance Characteristics for urine:

Assay Range	0 - 2000 U/L0 - 10000 U/L with post dilution		0 - 2000 U/L0 - 20000 U/L with post dilution
Precision:	Level 1	Level 2	Level 1	Level 2
Mean (U/L)	183	603	22	302
%CV (within run)	1.3		2.5	0.56
%CV (total)	1.7	1.6
Sensitivity	1.9 X 10-4 ΔA/min per U/L		Not specified in labeling
Accuracy:
Sample size (n)	150		Not specified in labeling
Corr. Coefficient (r)	0.988
Lin. Regression	0.44x + 0 U/L vs. COBASINTEGRA α - Amylase (granulate)

{11}------------------------------------------------

Table 8 - Cholesterol (CHOLL)

	COBAS INTEGRA Cholesterol(Liquid)	COBAS INTEGRA Cholesterol(Granulate)
Intended Use	quantitative determination of totalcholesterol & HDL cholesterol	quantitative determination of totalcholesterol & HDL cholesterol
Sample type	serum and plasma	serum and plasma
Methodology	enzymatic, colorimetric methodusing cholesterol esterase,cholesterol oxidase and 4-aminoantipyrine	enzymatic, colorimetric method usingcholesterol esterase, cholesterol oxidaseand 4-aminoantipyrine
Reagents	R: Cholesterol esterase, cholesteroloxidase and 4-aminoantipyrine(liquid)	R: Cholesterol esterase, cholesteroloxidase and 4-aminoantipyrine (granulate)
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 - 18.1 mmol/L (0 - 700 mg/dL)0 - 181 mmol/L (0 - 7000 mg/dL)with post dilution	0 - 20.7 mmol/L (0 - 800 mg/dL)0 - 207 mmol/L (0 - 8000 mg/dL)with post dilution
Precision:Mean (mmol/L)	Level 1      Level 25.3            6.7(205 mg/dL)   (259 mg/dL)	Level 1      Level 2      Level 35.0            6.3            8.0(94 mg/dL)   (242 mg/dL)   (309 mg/dL)
%CV (within run)	1.3            1.1	1.3            1.0            2.0
%CV (total)	2.2            2.5	1.1            1.2            1.5
Sensitivity	$8.8 X 10^{-2}$ ΔA per mmol/L( $2.3 X 10^{-3}$ ΔA per mg/dL)	$6.4 X 10^{-2}$ ΔA per mmol/L( $1.7 X 10^{-3}$ ΔA per mg/dL)
Accuracy:
Sample size (n)	214	240
Corr. Coefficient (r)	0.998	0.995
Lin. Regression	0.99x + 0.0 mmol/L vs. COBASINTEGRA Cholesterol (granulate)	1.04x + 0.1 mmol/L

,可以在

juund

{12}------------------------------------------------

ાં છે. -ﮧ

	Table 9 - HDL - Cholesterol Application (HDLL)
--	------------------------------------------------	--

	COBAS INTEGRA HDL -		COBAS INTEGRA HDL -
	Cholesterol Application (for use		Cholesterol Application (for use
	with COBAS INTEGRA Cholesterol		with COBAS INTEGRA
	Liquid Reagent)		Cholesterol Granulate Reagent)
Intended Use	quantitative determination HDLcholesterol		quantitative determination HDLcholesterol
Sample type	serum and plasma		serum and plasma
Methodology	Phosphotungstic acid pretreatment		Phosphotungstic acid pretreatment
Reagents	Roche Separating Reagent for HDL -Cholesterol used with COBASINTEGRA Cholesterol liquid reagent		Roche Separating Reagent for HDL -- Cholesterol used with COBASINTEGRA Cholesterol granulatereagent
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 - 5.0 mmol/L (0 - 193 mg/dL)		0 - 5.0 mmol/L (0 - 193 mg/dL)
Precision:	Level 1	Level 2	Level 1	Level 2
Mean (mmol/L)	0.20(7.7 mg/dL)	1.91(73.8mg/dL)	0.82(31.7 mg/dL)	1.42(54.9 mg/dL)
%CV (within run)	1.51.3	0.26	1.2	0.85
%CV (total)	3.0	1.6	2.7	5.5
Sensitivity	$8.8 X 10^{-2}$ ΔA per mmol/L(2.3 X $10^{-3}$ ΔA per mg/dL)		$6.4 X 10^{-2}$ ΔA per mmol/L(1.7 X $10^{-3}$ AA per mg/dL)
Accuracy:
Sample size (n)	240		232
Corr. Coefficient (r)	0.999		0.998
Lin. Regression	0.99x + 0.03 mmol/L vs. COBASINTEGRA HDL - CholesterolApplication (granulate)		0.99x - 0.05 mmol/L

043 1

{13}------------------------------------------------

	COBAS INTEGRA GGTL(Liquid)	COBAS INTEGRA GGT(Granulate)
Intended Use	quantitative determination of thecatalytic activity of GGT	quantitative determination of thecatalytic activity of GGT
Sample type	serum and plasma	serum and plasma
Methodology	kinetic method - Szasz-Persjun	kinetic method - Szasz-Persjun
Reagents	R1: Buffer (liquid)R2: L-γ-glutamyl-3-carboxy-4-nitroanilide (liquid)	R1: Buffer (granulate)R2: L-γ-glutamyl-3-carboxy-4-nitroanilide (granulate)
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 - 600 U/L0 - 6000 U/L with post dilution	0 - 700 U/L0 - 7000 U/L with post dilution
Precision:	Level 1 Level 2	Level 1 Level 2
Mean (U/L)	21 428	37.9 345
%CV (within run)	0.83 0.54	0.67 0.46
%CV (total)	2.8 1.5	1.2 1.4
Sensitivity	$6.8 X 10^4 ΔA/min per U/L$	$5.0 X 10^4 ΔA/min per U/L$
Accuracy:
Sample size (n)	196	238
Corr. Coefficient (r)	0.999	0.998
Lin. Regression	1.00x - 1.2 U/L vs. COBAS	1.00x + 0 U/L
	INTEGRA GGTL (granulate)

Table 10 - Gamma-Glutamyltransferase (GGTL)

{14}------------------------------------------------

• 14

Table 11 - Glucose (GLUCL)

	COBAS INTEGRA Glucose(Liquid)	COBAS INTEGRA Glucose(Granulate)
Intended Use	quantitative determination ofglucose	quantitative determination of glucose
Sample type	serum, plasma, urine andCerebrospinal fluid (CSF)	serum, plasma, urine andCerebrospinal fluid (CSF)
Methodology	enzymatic reference method withhexokinase	enzymatic reference method withhexokinase
Reagents	R: Enzyme (liquid)	R1: Buffer (granulate)R2: Enzyme (granulate)
Calibrator	Roche Calibrator (human)	Roche Calibrator (human)
Controls	Roche Control Serum N and P(human)	Roche Control Serum N and P(human)

Performance Characteristics for serum and plasma:

Assay Range	0 - 40 mmol/L (0-720 mg/dL)0 - 400 mmol/L (0-7200 mg/dL) withpost dilution		0 - 40 mmol/L (0-720 mg/dL)0 - 400 mmol/L (0-7200 mg/dL) withpost dilution
Precision:	Level 1	Level 2	Level 1	Level 2
Mean (mmol/L)	5.3	33.2	5.6	19.7
	(96 mg/dL)	(598 mg/dL)	(101mg/dL)	(355 mg/dL)
%CV (within run)	1.7	0.72	1.2	0.97
%CV (total)	2.6	1.5	1.1	0.89
Sensitivity	5.4 X 10-2 ΔA per mmol/L		9.3 X 10-2 ΔA per mmol/L
	(3.0 x 10-3 ΔA per mg/dL)		(5.2 X 10-3 ΔA per mg/dL)
Accuracy:
Sample size (n)	220		254
Corr. Coefficient (r)	0.999		0.997
Lin. Regression	1.05x - 0.2 mmol/L vs. COBASINTEGRA Glucose (granulate)		0.98x + 0.1 mmol/L

{15}------------------------------------------------

Table 11 - Glucose - Continued

Performance Characteristics for urine:
Assay Range	0 - 40 mmol/L (0-720 mg/dL)0~ 400 mmol/L (0-7200 mg/dL) withpost dilution		0 - 16 mmol/L (0-288 mg/dL)0 - 160 mmol/L (0-2880 mg/dL) withpost dilution
Precision:	Level 1	Level 2	Level 1	Level 2
Mean (mmol/L)	1.7(31 mg/dL)	37.1(668 mg/dL)	0.27(4.9 mg/dL)	0.48(8.6 mg/dL)
%CV (within run)	1.7	1.8	2.0	0.99
%CV (total)	4.3	2.9
Sensitivity	$5.4 X 10^2$ ΔA per mmol/L(3.0 x $10^{-3}$ ΔA per mg/dL)		$2.2 X 10^1$ ΔA per mmol/L(1.3 X $10^2$ ΔA per mg/dL)
Accuracy:
Sample size (n)	120	Not specified in labeling
Corr. Coefficient (r)	0.999
Lin. Regression	1.01x -0.02 mmol/L vs. COBASINTEGRA Glucose (granulate)
Performance Characteristics for CSF:
Assay Range	0 - 40 mmol/L (0-720 mg/dL)0 - 400 mmol/L (0-7200 mg/dL) withpost dilution		0 - 20 mmol/L (0-360 mg/dL)0 - 360 mmol/L (0-3600 mg/dL) withpost dilution
Precision:	Level 1	Level 2	Level 1	Level 2
Mean (mmol/L)	1.7(31 mg/dL)	3.3(59 mg/dL)	4.7(85 mg/dL)	10.3(186 mg/dL)
%CV (within run)	1.6	1.8	0.57	0.23
%CV (total)	2.3	1.9
Sensitivity	$5.4 X 10^2$ ΔA per mmol/L(3.0 x $10^{-3}$ ΔA per mg/dL)		$1.8 X 10^1$ ΔA per mmol/L(1.0 x $10^2$ ΔA per mg/dL)
Accuracy:
Sample size (n)	212	Not specified in labeling
Corr. Coefficient (r)	0.999
Lin. Regression	1.02x -0.17 mmol/L vs. COBASINTEGRA Glucose (granulate)

{16}------------------------------------------------

, (4)

Table 12 - Lipase (LIPL)

	COBAS INTEGRA Lipase(Liquid)	COBAS INTEGRA Lipase(Granulate)
Intended Use	quantitative determination of thecatalytic activity of lipase	quantitative determination of thecatalytic activity of lipase
Sample type	serum and plasma	serum and plasma
Methodology	turbidimetric method with triolein	turbidimetric method with triolein
Reagents	R: triolein and colipase (liquid)	R: triolein and colipase (granulate)
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 - 600 U/L0 - 3000 U/L with post dilution	0 - 700 U/L0 - 3500 U/L with post dilution
Precision:	Level 1      Level 2	Level 1      Level 2
Mean (U/L)	126          515	116          550
%CV (within run)	1.9          1.3	1.7          2.1
%CV (total)	3.1          2.9	4.6          3.7
Sensitivity	6.4 X 10-5 ΔA/min per U/L	5.6 X 10-5 ΔA/min per U/L
Accuracy:
Sample size (n)	198	262
Corr. Coefficient (r)	0.976	0.976
Lin. Regression	0.82x + 16 U/L vs. COBASINTEGRA Lipase (granulate)	1.06x - 7 U/L

1 047

{17}------------------------------------------------

Table 13 -Urea/BUN (UREAL)

	COBAS INTEGRA UREA/BUN(Liquid)	COBAS INTEGRA UREA/BUN(Granulate)
Intended Use	quantitative determination of urea/BUN	quantitative determination of urea/BUN
Sample type	serum, plasma and urine	serum, plasma and urine
Methodology	kinetic test with urease and glutamatedehydrogenase	kinetic test with urease and glutamatedehydrogenase
Reagents	R: urease and glutamate dehydrogenase (liquid)	R: urease and glutamate dehydrogenase (granulate)
Calibrator	Roche Calibrator (human)	Roche Calibrator (human)
Controls	Roche Control Serum N and P (human)	Roche Control Serum N and P (human)

Performance Characteristics for serum and plasma:

Assay Range	0 - 40 mmol/L (0-12 mg/dL)0 - 400 mmol/L (0-2400 mg/dL) with postdilution		0 - 55 mmol/L (0-330 mg/dL)0 - 550 mmol/L (0-3300 mg/dL) with postdilution
Precision:	Level 1	Level 2	Level 1	Level 2
Mean (mmol/L)	4.1(24.6 mg/dL)	31.0(186 mg/dL)	6.9(41.4 mg/dL)	19.9(119 mg/dL)
%CV (within run)	2.3	0.89	0.85	1.0
%CV (total)	3.9	2.8	2.0	2.3
Sensitivity	$2.2 X 10^{-2}$ ΔA/min per mmol/L( $3.3 X 10^{-3}$ ΔA/min per mg/dL)		$6.8 X 10^{-3}$ ΔA/min per mmol/L( $1.1 X 10^{-3}$ ΔA/min per mg/dL)
Accuracy:
Sample size (n)	236		234
Corr. Coefficient (r)	0.999		0.999
Lin. Regression	1.00x + 0.1 mmol/L vs. COBASINTEGRA Urea/BUN (granulate)		1.01x + 0.30 mmol/L

Performance Characteristics for urine:

Assay Range	0 - 2000 mmol/L (0-12 g/dL)0 - 6000 mmol/L (0-36 g/dL) with postdilution		0 - 2200 mmol/L (0-13.2 g/dL)0 - 5500 mmol/L (0-33 g/dL) with postdilution
Precision:Mean (mmo/L)%CV (within run)	Level 1421(2.53 g/dL)1.3	Level 2679(4.08 g/dL)1.2	Level 173(438 mg/dL)0.99	Level 2345(2072 mg/dL)0.6
%CV (total)Sensitivity	1.81.82.0 X 10-2 ΔA/min per mmol/L(3.3 X 10-2 ΔA/min per g/dL)		Not specified in labeling
Accuracy:Sample size (n)Corr. Coefficient (r)Lin. Regression	1200.9991.0X + 1.3 mmol/L vs. COBAS INTEGRAUrea/BUN (granulate)		Not specified in labeling

{18}------------------------------------------------

Image /page/18/Picture/1 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 words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" are arranged in a circle around the eagle. The logo is black and white and has a simple, clean design. The eagle is facing to the right.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

AUG 12 1997

Ms. Maria Feijoo Regulatory Affairs Associate Roche Diagnostic Systems, Inc. 1080 U.S. Highway 202 Somerville, NJ 08876-3771

Re: K972250 Roche COBAS® INTEGRA Reagent Cassettes & Ancillary Reagents Regulatory Class: II JFJ, CDQ, CDT, CET, CFR, CGX, CHH, LAS, DLJ, Product Code: DLB, JIF, JQB, LFM June 13, 1997 Dated: Received: June 16, 1997

Dear Ms. Feijoo:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). You may, therefore, market the device, subject to the general controls provisions The general controls provisions of the Act 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 (Premarket Approval), it may be subject to such additional controls. Existing major requlations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (QS) for Medical General requlation (21 CFR Part 820) and that, Devices: through periodic (QS) inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP requlation may result in regulatory In addition, FDA may publish further announcements action. concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal Laws or Requlations.

{19}------------------------------------------------

Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at [phone].

This letter will allow you to begin marketing your device as described in your 510 (k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number [phone] or [phone] or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".

Sincerely yours,
Steven Litman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

{20}------------------------------------------------

Page 1 of 4

510(k) Number (if known)

Device Name: Roche COBAS® INTEGRA Reagent Cassettes for:

• l. Ammonia
• 2. xAmylase EPS (liquid reagent)
• 3. Cholesterol (liquid reagent)
• 4. HDL Cholesterol Application
• 5. Creatinine (enzymatic)
• 6. Digitoxin
• 7. Gamma-Glutamyltransferaste (liquid reagent)
• 8. Glucose HK (liquid reagent)
• 9. Lipase (liquid reagent)
• 10. Lysergic acid diethylamide (LSD)
• 11. Urea (liquid reagent)

Ancillary Reagents:

• 12. Roche TDM OnLine Digitoxin Calibrators
• 13. Roche TDM OnLine Digitoxin Controls

Indications for Use:

COBAS INTEGRA Ammonia (NH3): !.

contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the ammonia concentration in plasma (test NH3, 0-045).

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109)

ision Sign-Off)

• of Clinical Laboratory Devices

Educator

OR

{21}------------------------------------------------

Page 2 of 4

510(k) Number (if known)

Indications for Use (continued):

• COBAS INTEGRA aAmylase EPS (AMYLL): 2. contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the catalytic activity of amylase in serum, plasma (test AMY-L, 0998) and urine (test AMY-UL 0-999).
• COBAS INTEGRA Cholesterol (CHOLL): 3. દ્ધ contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of total cholesterol (test CHOLL, 0-001) and HDL cholesterol concentration in serum and plasma in clinical laboratories.
• COBAS INTEGRA HDL Cholesterol Application (HDLL): 4. contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of total cholesterol and HDL - cholesterol (test HDLL, 0-002) concentration in serum and plasma in clinical laboratories.
• ડ. COBAS INTEGRA Creatinine Enzymatic (CREAE): contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the creatinine concentration in serum (test CREAE, 0-014), and urine (test CREEU, 0-114).

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109)

OR

{22}------------------------------------------------

Page 3 of 4

510(k) Number (if known)

Indications for Use (continued):

• COBAS INTEGRA Digitoxin (DIGIT): 6. contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of digitoxin in serum or heparinized plasma (test DIGIT 0-259).
• COBAS INTEGRA Gamma Glutamyltransferase (GGTL): 7. 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; y-glutamyl peptide: amino acid y-glutamyltransferase) in serum and plasma (test GGTL, 0-599).
• COBAS INTEGRA Glucose HK Liquid (GLUCL): 8.

contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the glucose concentration in serum, plasma (test GLUL, 0-991), urine (test GLULU, 0-992), and cerebrospinal fluid (test GLULC, 0-993).

COBAS INTEGRA Lipase (LIPL): contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the catalytic activity of lipase in serum and plasma (test LIPL, 0-200).

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH. Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109)

OR

{23}------------------------------------------------

Page 4 of of a イ

510(k) Number (if known)

Indications for Use (continued):

• COBAS INTEGRA Lysergic acid diethylamide (LSD) 10. contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the qualitative determination of lysergic acid diethylamide (LSD) in urine (test LSD, 0-001)
• COBAS INTEGRA Urea/BUN (UREAL): 11. contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA for the quantitative determination of the urea/BUN (blood urea nitrogen), in serum, plasma (test UREL, 0-003) and urine (test URELU, 0-004).
• Roche TDM OnLine Digitoxin Calibrators: 12. are intended for use with the Roche reagents for Digitoxin and the COBAS Chemistry systems for the quantitative determination of digitoxin in serum and plasma.
• 13. Roche TDM OnLine Digitoxin Controls: are quality control samples intended for use on COBAS chemistry systems with Roche reagents and calibrators for the quantitative determination of digitoxin assays.

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109)

OR

Regulation Number and Section

§ 862.1070 Amylase test system.

(a)
Identification. An amylase test system is a device intended to measure the activity of the enzyme amylase in serum and urine. Amylase measurements are used primarily for the diagnosis and treatment of pancreatitis (inflammation of the pancreas).(b)
Classification. Class II.