Predicate Devices

Not Found

Reference Devices

Not Applicable

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes standard in vitro diagnostic assays and their performance characteristics, with no mention of AI, ML, or related technologies.

Therapeutic

No
The device is an in vitro diagnostic device used to measure various substances in human bodily fluids, which aids in the diagnosis and treatment of conditions, but it does not directly treat or prevent a disease.

Diagnostic

Yes
The "Intended Use / Indications for Use" section explicitly states that the various assays within the Bayer ADVIA IMS system are "in vitro diagnostic device[s]" intended to measure analytes for "aid in the diagnosis and treatment" of various conditions.

SaMD (Software as a Medical Device)

No

The device is described as an in vitro diagnostic device intended to measure analytes in human samples, which implies the use of physical reagents and instrumentation, not solely software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

The "Intended Use / Indications for Use" section explicitly states for each assay that it is an "in vitro diagnostic device". This is the primary indicator that the device falls under the IVD classification.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The Bayer ADVIA IMS Amylase assay is an in vitro diagnostic device intended to measure amylase activity in human serum, plasma or urine. Such measurements are used as an aid primarily in the diagnosis and treatment of pancreatitis (inflammation of the pancreas).

The Bayer ADVIA IMS Cortisol assay is an in vitro diagnostic device intended to quantitatively measure cortisol in human serum. Measurements of cortisol are used as an aid in the diagnosis and treatment of disorders of the adrenal gland.

The Bayer ADVIA IMS Iron assay is an in vitro diagnostic device intended to measure iron in human serum of plasma. Measurements of iron are used as an aid in the diagnosis, monitoring and treatment of a variety of diseases including iron deficiency anemias, hemochromatosis, hemosiderosis from excessive iron intake, and hemolytic anemias.

The Baver ADVIA IMS Thyroxine assay is an in vitro diagnostic device intended to measure thyroxine (T4), both protein bound and free, in human serum and plasma. Measurements of T4 are used as an aid in the diagnosis and treatment of thyroid diseases.

The Baver ADVIA IMS Free Thyroxine (FT4) assay is an in vitro diagnostic device intended to quantitatively measure free thyroxine in human serum. Measurements of free thyroxine in conjunction with other thyroid tests and clinical indicators are used as an aid in the diagnostic discrimination and assessment of thyroid diseases.

The Bayer ADVIA IMS Triiodothyronine (T3) assay is an in vitro diagnostic device intended to quantitatively measure triiodothyronine (T3) in human serum. Measurements of triiodothyronine, in conjunction with other thyroid tests and clinical indicators, are used as an aid in the diagnostic discrimination and assessment of thyroid diseases.

The Bayer ADVIA IMS Free Triiodothyronine (FT3) assay is an in vitro diagnostic device intended to quantitatively measure free triiodothyronine in human serum. Measurements of free triodothyronine, in conjunction with other first-line thyroid tests such as Thyroid Stimulating Hormone (TSH) and Free Thyroxine (Free T4), as well as other clinical indicators, are used as an aid in the diagnostic discrimination and assessment of thyroid diseases.

The Bayer ADVIA IMS T Uptake (TUP) assay is an in vitro diagnostic device intended to quantitatively measure the total amount of available binding sites for thyroid hormone on the thyroxine-binding proteins, globulin, pre-albumin, and albumin in human serum. Measurements of T Uptake, in conjunction with other thyroid tests and clinical indicators, are used as an aid in the diagnostic discrimination and assessment of thyroid diseases.

The Bayer ADVIA IMS Urea Nitrogen (BUN) method is an in vitro diagnostic device intended to measure urea nitrogen in human serum, plasma and urine. Such measurements are used as an aid in the diagnosis and treatment of certain renal and metabolic diseases.

Product codes (comma separated list FDA assigned to the subject device)

CIJ

Device Description

Not Found

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Amylase (AMY) Method for the ADVIA IMS Systems

Study Type: Comparison of performance with a similar device granted clearance of substantial equivalence (Bayer RA-XT Amylase method).
Key Results:
- Analytical Range: ADVIA IMS: 0 to 1500 U/L; RA-XT: 10 to 3400 U/L.
- Precision (Total):
  - Serum: ADVIA IMS: 2.5% CV at 56 U/L, 2.1% CV at 113 U/L, 1.5% CV at 430 U/L. RA-XT: 2.2% CV at 51 U/L, 1.0% CV at 179 U/L, 0.6% CV at 373 U/L.
  - Urine: ADVIA IMS: 1.3% CV at 50 U/L, 1.1% CV at 218 U/L, 1.6% CV at 493 U/L. RA-XT: 3.4% CV at 57 U/L, 1.3% CV at 172 U/L, 1.3% CV at 510 U/L.
- Regression Equation (serum): y = 1.01x - 5.7 (where y = ADVIA IMS, x = RA-XT); n = 72, r = 0.999, Sy.x = 11.9, range = 19 to 1318 U/L.
- Regression Equation (plasma qualification): y = 1.00x - 0.2 (where y = plasma, x = serum); n = 60, r = 0.999, Sy.x = 1.0, range = 18 to 106 U/L.
- Regression Equation (urine): y = ADVIA IMS, x = RA-XT; n = 72, r = 0.999, Sy.x = 9.7, range = 17 to 1465 U/L.
- Interference (serum): Hemolysis (500 mg/dL): +2% change; Bilirubin (conjugated, 20 mg/dL): -4% change; Bilirubin (unconjugated, 25 mg/dL): -2% change; Lipemia (500 mg/dL): 3% change.
- Interference (urine): Ascorbic Acid (400 mg/dL): 1% change; Acetaminophen (50 mg/dL): -1% change; Salicylate (500 mg/dL): -2% change.

Cortisol Method for Bayer ADVIA® IMSTM

Study Type: Comparison of performance with a similar device granted clearance of substantial equivalence (Immuno 1 Cortisol assay).
Key Results:
- Minimum Detectable Conc.: Immuno 1: 0.2 µg/dL; ADVIA Cortisol: 0.1 µg/dL.
- Precision (Total CV%):
  - Immuno 1: 7.9% at 3.2 µg/dL, 4.5% at 20.1 µg/dL, 4.7% at 33.3 µg/dL.
  - ADVIA Cortisol: 6.0% at 4.4 µg/dL, 5.0% at 17.3 µg/dL, 3.8% at 37.5 µg/dL.
- Correlation: y = 1.013 x - 0.142 (where y = Bayer ADVIA Modular System, x = Bayer Immuno 1 System); n = 57, r = 0.996, Syx = 0.961 µg/dL.
- Interference: Hemoglobin (10 g/L): -4.8% effect; Lipids (11.3 mmol/L): -4.5% effect; Bilirubin (171 µmol/L): -1.9% effect; Urea Nitrogen (71.4 mmol/L): -4.4% effect.

Iron Method for the Bayer ADVIA Integrated Modular System (IMS)

Study Type: Comparison of performance with a similar device granted clearance of substantial equivalence (Technicon CHEM 1 Iron-II method).
Key Results:
- Analytical Range: ADVIA IMS: 0 to 800 ug/dL; CHEM 1: 0 to 1200 ug/dL.
- Precision (Total):
  - ADVIA IMS: 2.8% at 50.7 ug/dL, 1.1% at 230.1 ug/dL, 0.7% at 438.3 ug/dL.
  - CHEM 1: 1.9% at 96 ug/dL, 1.3% at 211 ug/dL, 1.2% at 383 ug/dL.
- Correlation: Y=0.93X+10.8 ug/dL (Where Y=ADVIA IMS, X=CHEM 1); N=65, r=0.998, Sy.x=9.75 ug/dL.
- Plasma/Serum Equivalence: Y=0.98X+0.46 ug/dL (Where Y = plasma, X= Serum); N = 56, r = 0.99, Sy.x = 3.12 ug/dL.
- Interfering Substances: Bilirubin (unconjugated 25 mg/dL): 7.0% effect change @ 215 ug/dL Fe; Bilirubin (conjugated 25 mg/dL): -1.0% effect change @ 221 ug/dL Fe; Hemoglobin (hemolysate 500 mg/dL): 44.0% effect change @ 217 ug/dL Fe; Lipemia (Triglycerides 500 mg/dL): -20.0% effect change @ 207 ug/dL Fe.

T4 Method for the Bayer ADVIA® IMS Systems

Study Type: Comparison of performance with a similar device granted clearance of substantial equivalence (Technicon Immuno 1® method).
Key Results:
- Minimum Det. Conc. ADVIA IMS: 0.25 µg/dL; Immuno 1: 0.4 µg/dL.
- Precision (Total):
  - ADVIA IMS: 6.0% at 3.5µg/dL, 5.1% at 7.9 µg/dL, 4.7% at 14.9 µg/dL.
  - Immuno 1: 3.6% at 4.7 µg/dL, 2.6% at 8.2 µg/dL, 2.5% at 15.7 µg/dL.
- Correlation (SERUM): y = 1.06 x +0.11 (where y = ADVIA IMS, x = Immuno 1); n = 72, r = 0.994, Syx = 0.65 µg/dL.
- Correlation (PLASMA): y = 0.98X + 0.06 (Where y = Serum (ADVIA IMS), x = Plasma (ADVIA IMS)); n = 24, r = 0.977, Syx = 0.36.
- Interference: Bilirubin (unconjugated 25 mg/dL): 0% change; Bilirubin (conjugated 20 mg/dL): -2% change; Hemoglobin (600 mg/dL): -3% change; Lipemia (Triglycerides 1000 mg/dL): +3% change.

Free T4 Assay for Bayer ADVIA® Integrated Modular System

Study Type: Comparison of performance with a similar device granted clearance of substantial equivalence (Bayer Immuno 1 FREE T4 Assay).
Key Results:
- Minimum Detectable Conc.: ADVIA FREE T4 Assay: 0.05 ng/dL; Immuno 1 FREE T4 Assay: 0.10 ng/dL.
- Precision (Total CV):
  - ADVIA FREE T4 Assay: 4.5% at 0.85 ng/dL, 4.8% at 1.46 ng/dL, 3.0% at 3.04 ng/dL.
  - Immuno 1 FREE T4 Assay: 4.9% at 0.94 ng/dL, 3.5% at 1.76 ng/dL, 2.2% at 4.68 ng/dL.
- Correlation: y = 0.998 x + 0.2179 (where y = ADVIA FREE T4 Assay, x = Immuno 1 FREE T4 Assay); n = 50, r = 0.9928, S = 0.1368 ng/dL.
- Interfering Substances: Hemoglobin (10 g/L): 3.8% effect; Lipids (11.3 mmol/L): 2.2% effect; Bilirubin (428 umol/L): 0.6% effect; Urea Nitrogen (71.4 mmol/L): 1.1% effect.

Total T3 Assay for Bayer ADVIA® Integrated Modular System

Study Type: Comparison of performance with a similar device granted clearance of substantial equivalence (Bayer Immuno 10 T3 Assay).
Key Results:
- Minimum Detectable Conc.: ADVIA T3 Assay: 0.13 ng/mL; Immuno 1 T3 Assay: 0.06 ng/mL.
- Precision (Total CV):
  - ADVIA T3 Assay: 10.3% at 0.67 ng/mL, 4.9% at 1.74 ng/mL, 3.6% at 2.89 ng/mL.
  - Immuno 1 T3 Assay: 13.3% at 0.46 ng/mL, 6.0% at 1.34 ng/mL, 3.9% at 3.43 ng/mL.
- Correlation: y = 1.014x + 0.1368 (where y = ADVIA T3 Assay, x = Immuno 1 T3 Assay); n = 50, r = 0.996.
- Interfering Substances: Hemoglobin (10 g/L): 3.7% effect; Lipids (11.3 mmol/L): 5.5% effect; Bilirubin (428 umol/L): 3.0% effect.

Free T3 Assay for Bayer ADVIA® Integrated Modular System

Study Type: Comparison of performance with a similar device granted clearance of substantial equivalence (Bayer Immuno 1ª Free T3 Assay).
Key Results:
- Minimum Detectable Conc.: ADVIA Free T3 Assay: 0.4 pg/mL; Immuno 1 Free T3 Assay: 0.3 pg/mL.
- Precision (Total CV):
  - ADVIA Free T3 Assay: 10.0% at 2.0 pg/mL, 5.0% at 4.88 pg/mL, 4.1% at 9.35 pg/mL.
  - Immuno 1 Free T3 Assay: 8.5% at 1.8 pg/mL, 3.8% at 5.4 pg/mL, 2.9% at 10.8 pg/mL.
- Correlation: y = 0.97x + 0.41 (where y = ADVIA Free T3 Assay, x = Immuno 1 Free T3 Assay); n = 56, r = 0.998, Syx = 0.427 pg/mL.
- Interfering Substances: Hemoglobin (10 g/L): 6.4% effect; Lipids (11.3 mmol/L): 9.4% effect; Bilirubin (428 umol/L): -3.4% effect; Urea Nitrogen (153.1 mmol/L): 2.1% effect.

T-Uptake Assay for Bayer ADVIA® Integrated Modular System

Study Type: Comparison of performance with a similar device granted clearance of substantial equivalence (Bayer Immuno 19 T-Uptake Assay).
Key Results:
- Minimum Detectable Conc.: N/A for both devices.
- Precision (Total CV):
  - ADVIA T-Uptake Assay: 3.2% at 0.96, 2.6% at 0.89, 2.3% at 1.14.
  - Immuno 1 T-Uptake Assay: 2.8% at 0.71, 2.6% at 1.03, 2.4% at 1.41.
- Correlation: y = 0.96x + 0.0003 (where y = ADVIA T-Uptake Assay, x = Immuno 1 T-Uptake Assay); n = 51, r = 0.987.
- Interfering Substances: Hemoglobin (10 g/L): 0.88% effect; Lipids (11.3 mmol/L): 0.90% effect; Bilirubin (428 µmol/L): 1.74% effect; Urea Nitrogen (71.4 mmol/L): 0.91% effect.

SUMMARY OF SAFETY AND EFFECTIVENESS Urea Nitrogen method for ADVIA® 400

Study Type: Comparison of performance with a similar device granted clearance of substantial equivalence (Technicon CHEM 1 " Urea Nitrogen).
Key Results:
- Imprecision (SERUM):
  - ADVIA 400: 4.3% CV at 7.3 mg/dL, 2.5% CV at 17 mg/dL, 1.6% CV at 52 mg/dL.
  - CHEM 1: 3% CV at 21 mg/dL, 3% CV at 54 mg/dL, 3% CV at 97 mg/dL.
- Imprecision (URINE):
  - ADVIA 400: 3.9% CV at 69 mg/dL, 2.1% CV at 212 mg/dL, 2.0% CV at 404 mg/dL.
  - CHEM 1: 3.6% CV at 478 mg/dL, 3.7% CV at 648 mg/dL.
- Correlation:
  - Serum: Y=1.03X-0.6 (Y=ADVIA 400, X=CHEM 1); N=50, Syx=2.8 mg/dL, R=0.997, Sample Range=5-124 mg/dL.
  - Plasma(y), Serum(x): Y=0.96X+0.6 (Y=ADVIA 400, X=ADVIA 400); N=58, Syx=1.1, R=0.975, Sample Range=6-32 mg/dL.
  - Urine: Y=1.08X-8.9 (Y=ADVIA 400, X=CHEM 1); N=53, Syx=22.5, R=0.997, Sample Range=70-1010 mg/dL.
- Interfering Substances: Bilirubin (33 mg/dL): -4.0% change; Hemoglobin (500 mg/dL): +4.4% change; Lipids (Triglycerides 500 mg/dL): +23.0% change; Ascorbic Acid (400 mg/dL): +3.2% change; Salicylate (500 mg/dL): -2.4% change; Glucose (500 mg/dL): +9.5% change; Acetominophen (40 mg/dL): +4.5% change.
- Analytical Range: Serum/Plasma: 0 to 150 mg/dL; Urine: 2 to 1030 mg/dL.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Not Found. Precision and Correlation metrics provided.

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

Bayer RA-XT Amylase method, Immuno 1 Cortisol assay, Technicon CHEM 1 Iron-II method, Technicon Immuno 1® method, Bayer Immuno 1 FREE T4 Assay, Bayer Immuno 10 T3 Assay, Bayer Immuno 1ª Free T3 Assay, Bayer Immuno 19 T-Uptake Assay, Technicon CHEM 1 " Urea Nitrogen

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

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.

Summary

0

Amylase (AMY) Method for the ADVIA IMS Systems

Listed below is a comparison of the performance of the Bayer ADVIA Amylase (AMY) method and a similar device that was granted clearance of substantial equivalence (Bayer RA-XT Amylase method). The information was extracted from the Bayer ADVIA AMY method and Bayer RA-XT Amylase method sheet.

INTENDED USE

The Bayer ADVIA IMS Amylase (AMY) assay is an in-vitro diagnostic device intended to measure AMY in human serum, plasma or urine. Such measurements are used in the diagnosis and treatment of acute pancreatitis. This diagnostic method is not intended for -use on any other diagnostic system .- - -

AMY METHOD:	ADVIA IMS		RA-XT
Part Number:	Reagents B41-3721-23		T01-3508-01
Analytical Range:	0 to 1500 U/L		10 to 3400 U/L
Precision (Total):	mean
(U/L)	% CV	mean
(U/L)	% CV
	56	2.5	51	2.2
	113	2.1	179	1.0
	430	1.5	373	0.6
Regression Equation:
(serum)	y = 1.01x - 5.7
	where: y	= ADVIA IMS
	x	= RA-XT
	n	= 72
	r	= 0.999
	Sy.x	= 11.9
	range	= 19 to 1318 U/L
Regression Equation:
(plasma qualification)	y = 1.00x - 0.2
	where: y	= plasma
	x	= serum
	n	= 60
	r	= 0.999
	Sy.x	= 1.0
	range	= 18 to 106 U/L

1

Interference

| | Interfering Substance
Concentration | AMY
(U/L) | Effect
% Change |
|--------------------------|----------------------------------------|--------------|--------------------|
| Hemolysis (Hemoglobin) | 500 mg/dL | 112 | +2 |
| Bilirubin (conjugated) | 20 mg/dL | 113 | -4 |
| Bilirubin (unconjugated) | 25 mg/dL | 112 | -2 |
| Lipemia (Triglycerides) | 500 mg/dL | 113 | 3 |

Urine Samples:

1

AMY METHOD:	ADVIA IMS	RA-XT
Part Number:	Reagents B41-3721-23	T01-3508-01
Analytical Range:	0 to 1500 U/L	10 to 3400 U/L
Precision (Total):	mean (U/L)	% CV	mean (U/L)	% CV
	50	1.3	57	3.4
	218	1.1	172	1.3
	493	1.6	510	1.3

(urine)

where:	y	= ADVIA IMS
	x	= RA-XT
	n	= 72
	r	= 0.999
	Sy.x	= 9.7
	range	= 17 to 1465 U/L

Interference

:

| | Interfering Substance
Concentration | AMY
(U/L) | Effect
% Change |
|---------------|----------------------------------------|--------------|--------------------|
| Ascorbic Acid | 400 mg/dL | 115 | 1 |
| Acetaminophen | 50 mg/dL | 116 | -1 |
| Salicylate | 500 mg/dL | 116 | -2 |

Rqm. Jr. RA
5/21/99

2

Cortisol Method for Bayer ADVIA® IMSTM

Listed below is a comparison of the performance between the ADVIA Cortisol method and a similar device that was granted clearance of substantial equivalence (Immuno 1 Cortisol assay). The information used in the Summary of Safety and Effectiveness was extracted from the ADVIA Cortisol method sheet and the Immuno 1 Cortisol method sheet.

INTENDED USED

This in viro method is intended to quantitatively measure cortisol, a hormone secreted by the human adrenal gland, in human serum using Bayer cortisol reagents on a Bayer ADVIA Modular System. Measurements of cortisol are used as a direct indicator of adrenal status or an indirect monitor of pituitary function.

| METHOD | | Immuno 1 Cortisol
(predicate device) | ADVIA Cortisol |
|--------------------------|--|---------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------|
| Part No. | | Reagents T01-2910-01
Calibrators T03-3252-01 | Reagents B42-3899-21
Calibrators B43-3931-01 |
| Minimum Detectable Conc. | | 0.2 µg/dL | 0.1 µg/dL |
| Precision (Total CV%) | | 3.2 µg/dL 7.9%
20.1 µg/dL 4.5%
33.3 µg/dL 4.7% | 4.4 µg/dL 6.0%
17.3 µg/dL 5.0%
37.5 µg/dL 3.8% |
| Correlation | | y = 1.013 x - 0.142

where
y = Bayer ADVIA Modular System
x = Bayer Immuno 1 System
n = 57
r = 0.996
Syx = 0.961 µg/dL | |

| Interfering
Substance | Interfering Substance
Concentration | | Analyte
Concentration | | Effect |
|--------------------------|----------------------------------------|---------|--------------------------|---------|--------|
| | SI Units | (mg/dL) | (nmol/L) | (µg/dL) | (%) |
| Hemoglobin | 10.0 g/L | 1000 | 466.4 | 16.9 | -4.8 |
| Lipids (Triglycerides) | 11.3 mmol/L | 1000 | 463.7 | 16.8 | -4.5 |
| Bilirubin | 171 µmol/L | 25 | 469.2 | 17.0 | -1.9 |
| Urea Nitrogen | 71.4 mmol/L | 200 | 554.8 | 20.1 | -4.4 |

Interforing Subotanco

Gabriel J. Muncey, Jr.

Gabriel J. Muraca, Jr. Manager Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, New York 10591-5097

5/21/99
Date

Date

3

Iron Method for the Bayer ADVIA Integrated Modular System (IMS)

Listed below is a comparison of the performance between the Bayer ADVIA IMS Iron method and a similar device that was granted clearance of substantial equivalence (Technicon CHEM 1 Iron-II method). The information used in the Summary of Safety and Effectiveness was extracted from the Bayer ADVIA IMS Iron method sheet and the CHEM 1 Iron-II method sheet.

INTENDED USE

This in vitro method is intended to quantitatively measure iron (Fe) in human serum and plasma on the Bayer ADVIA IMS. Measurements of iron are used in the diagnosis, monitoring and treatment of a variety of diseases including iron deficiency anemias, hemochromatosis, hemosiderosis from excessive iron intake, and hemolytic anemias.

METHOD	ADVIA IMS	CHEM 1
Part No.	Reagents
B41-3735-43
Calibrators
T03-1291-62	T01-3328-53
T03-1291-62
Analytical Range	0 to 800 ug/dL	0 to 1200 ug/dL
Precision (Total)	2.8% @ 50.7 ug/dL
1.1% @ 230.1 ug/dL
0.7% @ 438.3 ug/dL	1.9% @ 96 ug/dL
1.3% @ 211 ug/dL
1.2% @ 383 ug/dL
Correlation	Y=0.93X+10.8 ug/dL
Where
Y=ADVIA IMS
X=CHEM 1
N=65
r=0.998
Sy.x=9.75 ug/dL
Plasma/Serum Equivalence	Y=0.98X+0.46 ug/dL
Where
Y = plasma
X= Serum
N = 56
r = 0.99
Sy.x = 3.12 ug/dL

Gabriel J. Murea, Jr. 5/21/99

4

Interfering Substances

Bilirubin (unconjugated) 25 mg/dL	7.0%	effect change @ 215 ug/dL Fe
Bilirubin (conjugated) 25 mg/dL	-1.0%	effect change @ 221 ug/dL Fe
Hemoglobin (hemolysate) 500 mg/dL	44.0%	effect change @ 217 ug/dL Fe
Lipemia (Triglycerides) 500 mg/dL	-20.0%	effect change @ 207 ug/dL Fe

Gabriel J. Murace, Jr.

Gabriel J. Muraca, Jr. Manager Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, New York 10591-5097

5/21/99

Date

5

T4 Method for the Bayer ADVIA® IMS Systems

·

Listed below is a comparison of the performance between the Bayer ADVIA IMS T4 method and a similar device that was granted clearance of substantial equivalence (Technicon Immuno 1® method). The information used in the Summary of Safety and Effectiveness was extracted from the ADVIA IMS T4 method sheet and the Immuno 1 method sheet.

INTENDED USE

This in vitro method is intended to quantitatively measure T4 in human serum and plasma on the Bayer ADVIA IMS systems. Measurements of T4 are used to aid in the diagnosis and treatment of thyroid diseases.

METHOD		ADVIA IMS	Immuno 1
` Part No.	Reagents	B41-3855-42
B41-3855-43	T01-3260-51
	Calibrators	B46-4092-01	T03-3174-01
Minimum Det. Conc.		0.25 µg/dL	0.4 µg/dL
Precision (Total)		6.0% @ 3.5µg/dL
5.1% @ 7.9 µg/dL
4.7% @14.9 µg/dL	3.6% @ 4.7 µg/dL
2.6% @ 8.2 µg/dL
2.5% @ 15.7 µg/dL
Correlation	SERUM	y = 1.06 x +0.11
where
y = ADVIA IMS
x = Immuno 1
n = 72
r = 0.994
Syx = 0.65 µg/dL
	PLASMA	y = 0.98X + 0.06
Where
y = Serum (ADVIA IMS)
x = Plasma (ADVIA IMS)
n = 24
r = 0.977
Syx = 0.36

6

| Interference
Substance | Interfering
Substance
Concentration | Thyroxine
Concentration,
ug/dL | Effect
% Change |
|-----------------------------|-------------------------------------------|--------------------------------------|--------------------|
| Bilirubin
(unconjugated) | 25 mg/dL | 15.3 | 0 |
| Bilirubin
(conjugated) | 20 mg/dL | 15.2 | -2 |
| Hemoglobin | 600 mg/dL | 15.2 | -3 |
| Lipemia
(Triglycerides) | 1000 mg/dL | 15.0 | +3 |

RgM, Jr.
5/24/95

7

Free T4 Assay for Bayer ADVIA® Integrated Modular System

Listed below is a comparison of the performance between the ADVIA FREE T4 (Free Thyroxine) method, and a similar device that was granted clearance of substantial equivalence (Bayer Immuno 1 FREE T4 Assay). The information used in the Summary of Safety and Effectiveness was extracted from the ADVIA FREE T4 insert and the Immuno 1 FREE T4 Assay method sheet.

INTENDED USED

This in vitro method is intended to quantitatively measure the unbound FREE T4 in human serum by using the ADVA FREE T4 Assay on the Bover ADVIA® Interrated Modular System. Less than 0.05% of the Total T4 is unbound to the serum proteins and it is this Free T4 fraction that directly regulates metabolic activity. Thus Free T4 measurements are generally used in the direct or first line diagnosis of thyroid disorders.

| METHOD | ADVIA FREE T4 Assay | | | Immuno 1 FREE T4 Assay
(predicate Device) | | |
|--------------------------|------------------------------------------------------------------------------------------------------------------------------------|-------------------------|--|----------------------------------------------|-------------------|--|
| Part No. | Reagents | B42-3905-41 (100 tests) | | Reagents | T01-3360-57 | |
| | Reagents | B42-3905-42 (250 tests) | | Calibrators | T03-3401-07 | |
| | Calibrators | B43-3936-01 | | | | |
| Minimum Detectable Conc. | 0.05 ng/dL | | | 0.10 ng/dL | | |
| Precision (Total CV) | 4.5% @ 0.85 ng/dL | 4.8% @ 1.46 ng/dL | | 4.9% @ 0.94 ng/dL | 3.5% @ 1.76 ng/dL | |
| | 3.0% @ 3.04 ng/dL | | | 2.2% @ 4.68 ng/dL | | |
| Correlation | y = 0.998 x + 0.2179
where
y = ADVIA FREE T4 Assay
x = Immuno 1 FREE T4 Assay
n = 50
r = 0.9928
S = 0.1368 ng/dL | | | | | |

Interfering Substances

Interfering	Interfering Substance		Analyte		Effect
Substance	Concentration		Concentration, uIU/mL
	SI Units -	- (mg/dL) -	I - Expected	Observed	(%)
Hemoglobin	10 g/L	1000	1.83	1.76	3.8
Lipids (Triglycerides)	11.3 mmol/L	1000	1.84	1.88	2.2
Bilirubin	428 umol/L	25	1.78	1.79	0.6
Urea Nitrogen	71.4 mmol/L	200	1.83	1.81	1.1

Gabriel J. Muraca, Jr.

Gabriel J. Muraca, Jr. Manager Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, New York 10591-5097

5/21/99

8

Total T3 Assay for Bayer ADVIA® Integrated Modular System

Listed below is a companison of the performance between the ADVIA T3 (Trilodothyronine) method, and a similar device that was granted clearance of substantial equivalence (Bayer Immuno 10 T3 Assay). The Summary of Safety and Effectiveness was extracted from the ADVIA T3 insert and the Immuno 1 T3 Assay method sheet.

INTENDED USED

This in vitro method is intended to quantitatively measure T3 in human serum using ADVIA T3 Assay on a Bayer ADVIA Integrated Modular System. Measurements of T3 are used in the diagnosis and treatment of thyroid disorders such as hyperthyroidism.

| METHOD | ADVIA T3 Assay | | Immuno 1 T3 Assay
(predicate Device) | |
|--------------------------|--------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------|-----------------------------------------|--------------------------|
| Part No. | Reagents
Reagents
Calibrators | B42-3916-41 (100 tests)
B42-3916-42 (250 tests)
B43-3943-01 | Reagents
Calibrators | T01-2942-0
T03-2872-0 |
| Minimum Detectable Conc. | 0.13 ng/mL | 0.06 ng/mL | | |
| Precision (Total CV) | 10.3% @ 0.67 ng/mL
4.9% @ 1.74 ng/mL
3.6% @ 2.89 ng/mL | 13.3% @ 0.46 ng/mL
6.0% @ 1.34 ng/mL
3.9% @ 3.43 ng/mL | | |
| Correlation | y = 1.014x + 0.1368
where
y = ADVIA T3 Assay
x = Immuno 1 T3 Assay
n = 50
r = 0.996
| | | |

Interfering Substances

| Interfering
Substance | Interfering Substance
Concentration | | Analyte
Concentration, ng/mL | | Effect | |
|--------------------------|----------------------------------------|------|---------------------------------|----------|---------|--|
| | SI Units (mg/dL) | | Expected | Observed | · (%) | |
| Hemoglobin | 10 g/L | 1000 | 1.85 | 1.91 | 3.7 | |
| Lipids (Triglycerides) | 11.3 mmol/L | 1000 | 1.85 | ાં તેરે | 5.5 | |
| Bilirubin | 428 umol/L | 25 | I '85 | 1.90 | 3.0 | |
| Urea Nitrogen | 71.4 mmol/L | 200 | I જર | 1.95 | રેંદર્ભ | |

Gabriel J. Murray Jr.

Syx =

Gabriel J. Muraca, Jr. Manager Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, New York 10591-5097

5721/99

9

Free T3 Assay for Bayer ADVIA® Integrated Modular System

Listed below is a companison of the performance between the ADVIA Free T3 Assay method and a similar device that was granted clearance of substantial equivalence (Bayer Immuno 1ª Free T3 Assay). The information used in the Summary of Safety and Effectiveness was extracted from the ADVIA Free T3 insert and the Immuno 1 " Free T3 Assay method sheet.

INTENDED USED

This in vitro method is intended to quantitatively measure Free T3, in human serven using ADVIA Free T3 Assay on a Bayer ADVIA® Integrated Modular System. Measurements of Free T3 are used in the diagnosis of thyroid or pituitary disorders.

| METHOD | ADVIA Free T3 Assay | | Immuno 1 Free T3 Assay
(predicate Device) | |
|--------------------------|--------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------|----------------------------------------------|-----------------------------------------------------------|
| Part No. | Reagents
Calibrators | B42-3904-42
B43-3935-01 | Reagents
Calibrators | T01-3662-57
T03-3663-02 |
| Minimum Detectable Conc. | | 0.4 pg/mL | | 0.3 pg/mL |
| Precision (Total CV) | | 10.0% @ 2.0 pg/mL
5.0% @ 4.88 pg/mL
4.1% @ 9.35 pg/mL | | 8.5% @ 1.8 pg/mL
3.8% @ 5.4 pg/mL
2.9% @ 10.8 pg/mL |
| Correlation | y = 0.97x + 0.41
where
y = ADVIA Free T3 Assay
x = Immuno 1 Free T3 Assay
n = 56
r = 0.998
Syx = 0.427 pg/mL | | | |

Interfering Substances

| Interfering
Substance | Interfering Substance
Concentration | | Analyte
Concentration, pg/mL | | Effect | |
|--------------------------|----------------------------------------|---------|---------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------|--|
| | SI Units | (mg/dL) | Expected | Observed | (%) | |
| Hemoglobin --- | 10 g/L | 1000 | 4.66 | રું રેણે રેણવાડી તેમ જ દૂધની ડેરી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામનાં પ્રાથમિક શાળા, આંગણવાડી તેમ જ દૂધની ડેરી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામનાં છે. આ ગામનાં પ્રાથમિક | 6:4 | |
| Lipids (Triglycerides) | l 1.3 mmol/L | 1000 | 4.80 | રું 30 | 9.4 | |
| Bilirubin | 428 umol/L | 25 | 4.66 | 4.50 | -3.4 | |
| Urea Nitrogen | 153.1mmol/L | 429 | 4.66 | 4.76 | 2.1 | |

Gabriel J. Munoz, Jr.

Gabriel J. Muraca, Jr. Manager Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, New York 10591-5097

5/2/99

10

T-Uptake Assay for Bayer ADVIA® Integrated Modular System

Listed below is a comparison of the performance between the ADVIA T-Uptake method, and a similar device that was granted clearance of substantial equivalence (Bayer Immuno 19 T-Uptake Assay). The information used in the Summary of Safety and Effectiveness was extracted from the ADVIA T-Uptake insert and the Immuno 1 T-Uptake Assay method sheet.

INTENDED USED

This in vitro method is intended to quantiatively measure the total amount of binding thyroid hormone on the thyroxine-binding proteins, thyroxine-binding prealbuning prealburnin, and albumin in human serum using the ADVIA T-Untake Assay on the Boyer ADVIA® Integrated Modular System. Measurements of T-Uptake are used in the diagnosis and treatment of thyroid disorders.

METHOD	ADVIA T-Uptake Assay	Immuno 1 T-Uptake Assay (predicate Device)
Part No.	Reagents
Calibrators	B42-3915-41 (100 tests)
B43-3994-01	Reagents
Calibrators	T01-3036-51
T03-3076-01
Minimum Detectable Conc.	N/A		N/A
Precision (Total CV)	3.2% @ 0.96
2.6% @ 0.89
2.3% @ 1.14		2.8% @ 0.71
2.6% @ 1.03
2.4% @ 1.41
Correlation	y = 0.96x + 0.0003
where
y = ADVIA T-UptakeAssay
x = Immuno 1 T-Uptake Assay
n = 51
r = 0.987

Interfering Substances

| Interfering
Substance | Interfering Substance
Concentration | Analyte
Concentration, ratio | Effect | | |
|--------------------------|----------------------------------------|---------------------------------|----------|----------|------|
| | SI Units | (mg/dL) | Expected | Observed | (%) |
| Hemoglobin | 10 g/L | 1000 | 1.13 | 1.14 | 0.88 |
| Lipids (Triglycerides) | 11.3 mmol/L | 1000 | 1.11 | 1.11 | 0.90 |
| Bilirubin | 428 $\mu$ mol/L | 25 | 1.15 | 1.17 | 1.74 |
| Urea Nitrogen | 71.4 mmol/L | 200 | 1.10 | 1.11 | 0.91 |

Gabriel J. Munoz Jr.

Gabriel J. Muraca, Jr. Manager Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, New York 10591-5097

5/21/99

11

510(k) SUMMARY OF SAFETY AND EFFECTIVENESS Urea Nitrogen method for ADVIA® 400

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.

The assigned 510(k) number is: _______________________________________________________________________________________________________________________________________________

1. Intended Use

This in vitro diagnostic method to measure urea nitrogen (an end product of nitrogen metabolism) in human serum, plasma or urine on the Bayer ADVIA 400 system

2. Predicate Device

Product Name		Reagent Part # Calibrator Part #
Technicon CHEM 1 " Urea	IT01-1452-53 T03-1291-62
Nitrogen · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

3. Device / Method

Product Name	Reagent Part #	Calibrator Part #
ADVIA 400 Urea Nitrogen	B41-3745-26	T03-1291-62

Imprecision(SERUM)

ADVIA 400		CHEM 1
Level
(mg/dL)	Total
CV(%)	Level
(mg/dL)	Total
CV(%)
7.3	4.3	21	3
17	2.5	54	3
52	1.6	97	3

B. Imprecision(URINE)

ADVIA 400		CHEM
Level
(mg/dL)	Total
CV(%)	Level
(mg/dL)
69	3.9	478
212	2.1	648
404	2.0

CHEM 1
Level
(mg/dL)	Total
CV(%)
478	2.6
648	2.5

Total CV(%) 3.6 3.7 3.4

Correlation (Y=ADVIA 400, X=comparison system)

Specimen type	Comparison System (X)	N	Regression Equation	Syx (mg/dL)	R	Sample Range (mg/dL)
Serum	CHEM 1	50	Y=1.03X-0.6	2.8	0.997	5-124
Plasma(y), Serum(x)	ADVIA 400	58	Y=0.96X+0.6	1.1	0.975	6-32
Urine	CHEM 1	53	Y=1.08X-8.9	22.5	0.997	70-1010

Gabriel J. Murray Jr. 7/21/99

.

12

Interfering Substances

| Interfering
Substance | Interfering Sub.
Conc. (mg/dL) | Urea Nitrogen
Conc. (mg/dL) | Effect
(% change) |
|--------------------------|-----------------------------------|--------------------------------|----------------------|
| Bilirubin | 33 | 17.6 | -4.0 |
| Hemoglobin | 500 | 36.1 | +4.4 |
| Lipids (Triglycerides) | 500 | 30.5 | +23.0 |
| Ascorbic Acid | 400 | 58.5 | +3.2 |
| Salicylate | 500 | 66.3 | -2.4 |
| Glucose | 500 | 61.9 | +9.5 |
| Acetominophen | 40 | 52.9 | +4.5 |

.

Analytical Range

: 上

Serum/Plasma: 0 to 150 mg/dL Urine: 2 to 1030 mg/dL 1

Ядт. Jr.
SYMBA

13

Image /page/13/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol resembling a stylized caduceus or a bird-like figure with three parallel lines forming the body and a wavy line representing the tail or base.

JUL 22 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Gabriel J. Muraca, Jr. Manager Regulatory Affairs Bayer Corporation Business Group Diagnostics 511 Benedict Avenue Tarrytown, New York 10591-5097

Re: K991817

Trade Name: Additional IMS Assays for the Bayer ADVIA® IMS™System Regulatory Class: II Product Code: CIJ Dated: May 21, 1999 Received: May 27, 1999

Dear Mr. Muraca:

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 legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations 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 requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements 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 regulations.

14

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 (770) 488-7655.

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 (301) 594-4588. Additionally, for questions on the promotion and advertising of your device. please contact the Office of Compliance at (301) 594-4639. 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 (800) 638-2041 or (301) 443-6597, or at its internet address "http://www.fda.gov/cdrl/dsma/dsmamain.html".

Sincerely yours,

Steven Sutman

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

15

Page 1 of 3

510(k) Number (if known): K991817

Device Name: Bayer ADVIA® Integrated Modular System (IMS)

Indications For Use:

The Bayer ADVIA IMS Amylase assay is an in vitro diagnostic device intended to measure amylase activity in human serum, plasma or urine. Such measurements are used as an aid primarily in the diagnosis and treatment of pancreatitis (inflammation of the pancreas).

The Bayer ADVIA IMS Cortisol assay is an in vitro diagnostic device intended to quantitatively measure cortisol in human serum. Measurements of cortisol are used as an aid in the diagnosis and treatment of disorders of the adrenal gland.

The Bayer ADVIA IMS Iron assay is an in vitro diagnostic device intended to measure iron in human serum of plasma. Measurements of iron are used as an aid in the diagnosis, monitoring and treatment of a variety of diseases including iron deficiency anemias, hemochromatosis, hemosiderosis from excessive iron intake, and hemolytic anemias.

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

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Over-The-Counter Use

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16

510(k) Number (if known):

Device Name: Bayer ADVIA® Integrated Modular System (IMS)

Indications For Use:

The Baver ADVIA IMS Thyroxine assay is an in vitro diagnostic device intended to measure thyroxine (T4), both protein bound and free, in human serum and plasma. Measurements of T4 are used as an aid in the diagnosis and treatment of thyroid diseases.

The Baver ADVIA IMS Free Thyroxine (FT4) assay is an in vitro diagnostic device intended to quantitatively measure free thyroxine in human serum. Measurements of free thyroxine in conjunction with other thyroid tests and clinical indicators are used as an aid in the diagnostic discrimination and assessment of thyroid diseases.

The Bayer ADVIA IMS Triiodothyronine (T3) assay is an in vitro diagnostic device intended to quantitatively measure triiodothyronine (T3) in human serum. Measurements of triiodothyronine, in conjunction with other thyroid tests and clinical indicators, are used as an aid in the diagnostic discrimination and assessment of thyroid diseases.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use L (Per 21 CFR 801.109) OR

Over-The-Counter Use ..

(Optional Format 1-2-96)

..............................................................................................................................................................................

17

510(k) Number (if known):

Device Name: Bayer ADVIA® Integrated Modular System (IMS)

Indications For Use:

The Bayer ADVIA IMS Free Triiodothyronine (FT3) assay is an in vitro diagnostic device intended to quantitatively measure free triiodothyronine in human serum. Measurements of free triodothyronine, in conjunction with other first-line thyroid tests such as Thyroid Stimulating Hormone (TSH) and Free Thyroxine (Free T4), as well as other clinical indicators, are used as an aid in the diagnostic discrimination and assessment of thyroid diseases.

The Bayer ADVIA IMS T Uptake (TUP) assay is an in vitro diagnostic device intended to quantitatively measure the total amount of available binding sites for thyroid hormone on the thyroxine-binding proteins, globulin, pre-albumin, and albumin in human serum. Measurements of T Uptake, in conjunction with other thyroid tests and clinical indicators, are used as an aid in the diagnostic discrimination and assessment of thyroid diseases.

The Bayer ADVIA IMS Urea Nitrogen (BUN) method is an in vitro diagnostic device intended to measure urea nitrogen in human serum, plasma and urine. Such measurements are used as an aid in the diagnosis and treatment of certain renal and metabolic diseases.

Alan Cooper

(Division Sign-Off) Division of Clinical Laboratory Devices 1991811 510(k) Number _

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

1-Prescription Use (Per 21 CFR 801.109)

OR

Over-The-Counter Use

(Optional Format 1-2-96)