The Bayer ADVIA IMS alkaline phosphatase (ALP) assay is an in-vitro diagnostic device intended to measure ALP in human serum or plasma. Such measurements are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases. This diagnostic method is not intended for use on any other diagnostic system.

This in vitro method is intended to quantitatively measure calcium in human serum and plasma on the Bayer ADVIA IMS. Measurements of calcium are used in the diagnosis, monitoring and treatment of a variety of diseases including parathyroid disease, a variety of bone diseases, chronic renal disease and tetany.

The Bayer ADVIA IMS Glucose assay is an in vitro diagnostic device intended to measure glucose in human serum or plasma. Such measurements are used in the diagnosis, monitoring and treatment of carbohydrate metabolism disorders, including diabetes mellitus and neonatal hypoglycemia. This diagnostic method is not intended for use on any other diagnostic system.

The Bayer ADVIA IMS Ferritin assay is an in vitro diagnostic device intended to quantitatively measure ferritin (an iron-storage protein) in human serum. Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency. This diagnostic method is not intended for use on any other diagnostic system.

This in viro method is intended to quantitatively measure hCG, human chorionic gonadotropin, in human serum using ADVIA hCG Assay on a Bayer ADVIA® Integrated Modular System. Measurements of hCG are used in the detection of pregnancy. This diagnostic method is not intended for use on any other diagnostic system.

This in viro method is intended to quantitatively measure TSH, Thyroid Stimulating Hormone, in human serum using ADVIA 3d Generation TSH Assay on a Bayer ADVIA® Integrated Modular System. This assay allows the determination of TSH with 3d generation sensitivity of less than 20% total coefficient of variation (CV) at 0.02 µIU/mL, as defined by the American Thyroid Association. Measurements thyroid stimulating hormone are used in the diagnosis of thyroid or pituitary disorders. This diagnostic method is not intended for use on any other diagnostic system.

Device Description

Not Found

AI/ML Overview

Here's an analysis of the provided text, outlining the acceptance criteria and study details for each assay method on the Bayer ADVIA IMS System. Please note that the document primarily focuses on demonstrating substantial equivalence to a predicate device, which means the "acceptance criteria" are largely implied by the performance of the predicate device and direct comparison studies. There are no explicit, pre-defined acceptance criteria listed as pass/fail thresholds in the provided text, but rather observed performance values used for comparison.

General Observations:

Device Type: This document describes in-vitro diagnostic devices (assays) for measuring various analytes in human serum or plasma.
Study Type: The studies described are primarily method comparison studies (correlation, regression) and precision studies, along with interference studies. These are standard for demonstrating substantial equivalence for IVDs.
Ground Truth: For these types of quantitative assays, the "ground truth" is generally established by the reference method (the predicate device) or by highly controlled laboratory measurements. There isn't an "expert consensus" or "pathology" in the typical sense for these quantitative measurements.
Human-in-the-loop/MRMC: These concepts are not applicable to the performance evaluation of a quantitative, automated in-vitro diagnostic assay. The device performs the measurement; it's not an AI assisting a human reader in interpretation.
Data Provenance: The data is implicitly retrospective as it compares the new device's performance to an already cleared predicate. No specific country of origin is mentioned, but Bayer Corporation has its headquarters in the US.
Ground Truth for Training Set: Since these are largely traditional chemical/immunoassay methods and not AI/ML algorithms in the modern sense (which require a distinct training phase), the concept of a "training set" for an algorithm and how its ground truth was established is not directly applicable. The "development" of such assays involves optimizing reagents and protocols.

1. Alkaline Phosphatase (ALP) Method

Acceptance Criteria (Implied by Predicate Performance)	Reported Device Performance (ADVIA IMS)
Analytical Range: 0 to 2250 U/L (Chem 1)	0 to 2800 U/L
Precision (Total %CV):
- At ~65 U/L: 3.8% (Chem 1)	- At 74 U/L: 3.6%
- At ~263 U/L: 3.3% (Chem 1)	- At 160 U/L: 2.9%
- At ~547 U/L: 3.2% (Chem 1)	- At 420 U/L: 2.1%
Regression (vs. Chem 1): (Implied close correlation)	y = 0.96x + 2.0 (r = 0.999, Sy.x = 11.2)
Plasma Qualification (vs. Serum): (Implied close correlation)	y = 1.06x - 0.9 (r = 0.999, Sy.x = 0.93)
Interference (% Change): (Implied acceptable levels)
- Hemoglobin (500mg/dL): 9%
- Bilirubin (conjugated, 20mg/dL): 8%
- Bilirubin (unconjugated, 25mg/dL): 1%
- Lipemia (Triglycerides, 1000mg/dL): 3%

Study Details:

Sample sizes for test set:
- Regression (serum comparison): n = 74
- Regression (plasma qualification): n = 59
- Interference: Not explicitly stated per interfering substance, but done at specific analyte concentrations.
- Data Provenance: Not specified, but likely samples collected from a clinical laboratory setting, retrospective for the purpose of comparison.
Number of experts and qualifications: Not applicable. These are quantitative chemical assays, not image interpretation.
Adjudication method: Not applicable. Direct quantitative measurements.
MRMC comparative effectiveness study: Not applicable.
Standalone performance: Yes, the performance data provided (analytical range, precision, interference) represents the standalone performance of the ADVIA IMS ALP method. The regression studies compare its standalone performance to another standalone device.
Type of ground truth: The "ground truth" for the comparative studies is the measurement obtained from the predicate device (Bayer Chem 1 ALP(AMP) method). For interference studies, it is the measurement of the sample without the interfering substance ("neat concentration") or at a known baseline.
Sample size for training set: Not applicable for this type of IVD (not an AI/ML algorithm requiring a training set).
Ground truth for training set: Not applicable.

2. Calcium Method

Acceptance Criteria (Implied by Predicate Performance)	Reported Device Performance (ADVIA IMS)
Analytical Range: 1 to 15 mg/dL (Chem 1)	0 to 14.0 mg/dL
Precision (Total):
- @ 8.4 mg/dL: 2.3% (Chem 1)	- @ 8.4 mg/dL: 1.1%
- @ 10.6 mg/dL: 2.5% (Chem 1)	- @ 10.4 mg/dL: 2.2%
- @ 13.4 mg/dL: 2.2% (Chem 1)	- @ 13.6 mg/dL: 0.9%
Correlation (vs. Chem 1): (Implied close correlation)	y = 0.96 - 0.8 mg/dL (n=48, r=0.996, Sy.x=0.01 mg/dL)
Plasma/Serum Equivalence: (Implied minimal difference)	0.00 difference at 8.4 mg/dL, 0.75% Within-run CV for plasma vs. 0.73% for serum
Interference (% Effect Change): (Implied acceptable levels)
- Bilirubin (unconjugated, 25mg/dL): 1.1%
- Hemoglobin (1000mg/dL): 3.0%
- Triglycerides (500mg/dL): 3.0%

Study Details:

Sample sizes for test set:
- Correlation: n = 48
- Plasma/Serum Equivalence: Not explicitly stated, but includes a specific concentration (8.4 mg/dL).
- Interference: Not explicitly stated per interfering substance, but done at specific analyte concentrations.
- Data Provenance: Not specified, likely retrospective clinical samples.
Number of experts and qualifications: Not applicable.
Adjudication method: Not applicable.
MRMC comparative effectiveness study: Not applicable.
Standalone performance: Yes, performance data reflects standalone operation, with correlation against a predicate.
Type of ground truth: Measurements from the predicate device (Technicon CHEM 1 Calcium method) for correlation. Known baseline or reference values for precision and interference.
Sample size for training set: Not applicable.
Ground truth for training set: Not applicable.

3. Glucose Method

Acceptance Criteria (Implied by Predicate Performance)	Reported Device Performance (ADVIA IMS)
Analytical Range: 0 to 675 mg/dL (Chem 1)	0 to 800 mg/dL
Precision (Total %CV):
- At ~87 mg/dL: 2.7% (Chem 1)	- At 48 mg/dL: 3.66%
- At ~262 mg/dL: 2.9% (Chem 1)	- At 97 mg/dL: 3.03%
- At ~305 mg/dL: 2.3% (Chem 1)	- At 293 mg/dL: 1.80%
- At ~562 mg/dL: 1.3% (Chem 1)
Regression (serum vs. Chem 1): (Implied close correlation)	y = 1.03x + 0.71 (n=58, r=0.993, Sy.x=11.4)
Regression (plasma qualification vs. serum): (Implied close correlation)	y = 0.97x + 4.12 (n=60, r=0.943, Sy.x=4.1)
Interference (% Change): (Implied acceptable levels)
- Hemoglobin (1000mg/dL): 0.5%
- Bilirubin (conjugated, 25mg/dL): 0.5%
- Bilirubin (unconjugated, 25mg/dL): 1.3%
- Lipemia (Triglycerides, 500mg/dL): 9.5%

Study Details:

Sample sizes for test set:
- Regression (serum comparison): n = 58
- Regression (plasma qualification): n = 60
- Interference: Not explicitly stated per interfering substance, but done at specific analyte concentrations.
- Data Provenance: Not specified, likely retrospective clinical samples.
Number of experts and qualifications: Not applicable.
Adjudication method: Not applicable.
MRMC comparative effectiveness study: Not applicable.
Standalone performance: Yes, performance data reflects standalone operation, with correlation against a predicate.
Type of ground truth: Measurements from the predicate device (Bayer Technicon Chem 1 Glucose method) for correlation. Known baseline or reference values for precision and interference.
Sample size for training set: Not applicable.
Ground truth for training set: Not applicable.

4. Ferritin Method

Acceptance Criteria (Implied by Predicate Performance)	Reported Device Performance (ADVIA Ferritin)
Minimum Detectable Conc.: 0.3 ng/mL (Immuno 1)	0.06 ng/mL
Precision (Total CV%):
- At 21 ng/mL: 7.1% (Immuno 1)	- At 28 ng/mL: 4.1%
- At 148 ng/mL: 5.0% (Immuno 1)	- At 108 ng/mL: 4.8%
- At 344 ng/mL: 5.0% (Immuno 1)	- At 245 ng/mL: 5.0%
Correlation (vs. Immuno 1): (Implied close correlation)	y = 1.040x - 6.132 (n=50, r=0.993, Syx=57.50 ng/mL)
Interference (% Change): (Implied acceptable levels)
- Hemoglobin (1000mg/dL): 0.8%
- Bilirubin (27.5mg/dL): 3.5%
- Urea Nitrogen (200mg/dL): 3.8%
- Lipemia (Triglycerides, 1110mg/dL): 4.5%

Study Details:

Sample sizes for test set:
- Correlation: n = 50
- Interference: Not explicitly stated per interfering substance, but done at specific analyte concentrations.
- Data Provenance: Not specified, likely retrospective clinical samples.
Number of experts and qualifications: Not applicable.
Adjudication method: Not applicable.
MRMC comparative effectiveness study: Not applicable.
Standalone performance: Yes, performance data reflects standalone operation, with correlation against a predicate.
Type of ground truth: Measurements from the predicate device (Immuno 1 Ferritin assay) for correlation. Known baseline or reference values for precision and interference.
Sample size for training set: Not applicable.
Ground truth for training set: Not applicable.

5. Human Chorionic Gonadotropin (hCG) Method

Acceptance Criteria (Implied by Predicate Performance)	Reported Device Performance (ADVIA hCG Assay)
Minimum Detectable Conc.: 0.5 mIU/mL (Immuno 1)	0.1 mIU/mL
Precision (Total CV):
- @ 18.3 mIU/mL: 4.0% (Immuno 1)	- @ 12.1 mIU/mL: 4.2%
- @ 55.7 mIU/mL: 3.7% (Immuno 1)	- @ 23.9 mIU/mL: 4.5%
- @ 198.1 mIU/mL: 3.7% (Immuno 1)	- @ 198.1 mIU/mL: 5.5%
Correlation (vs. Immuno 1): (Implied close correlation)	y = 0.99x + 1.96 (n=40, r=1.0, Syx=17.5 mIU/mL)
Interference (% Effect): (Implied acceptable levels)
- Hemoglobin (1000 mg/dL): -2.3%
- Lipids (Triglycerides, 1000 mg/dL): -8.7%
- Bilirubin (25 mg/dL): -6.1%
- Urea Nitrogen (200 mg/dL): -7.6%

Study Details:

Sample sizes for test set:
- Correlation: n = 40
- Interference: Not explicitly stated per interfering substance, but done at specific analyte concentrations.
- Data Provenance: Not specified, likely retrospective clinical samples.
Number of experts and qualifications: Not applicable.
Adjudication method: Not applicable.
MRMC comparative effectiveness study: Not applicable.
Standalone performance: Yes, performance data reflects standalone operation, with correlation against a predicate.
Type of ground truth: Measurements from the predicate device (Bayer Immuno 1 hCG Assay) for correlation. Known baseline or reference values for precision and interference.
Sample size for training set: Not applicable.
Ground truth for training set: Not applicable.

6. Thyroid Stimulating Hormone (TSH) Method

Acceptance Criteria (Implied by Predicate Performance and ATA definition)	Reported Device Performance (ADVIA TSH Assay)
Minimum Detectable Conc.: 0.03 µIU/mL (Immuno 1)	0.005 µIU/mL
Precision (Total CV): Less than 20% CV at 0.02 µIU/mL	13.2% @ 0.02 µIU/mL
Precision (Total CV) (from Immuno 1):
- @ 1.3 µIU/mL: 6.3% (Immuno 1)	- @ 0.52 µIU/mL: 2.9%
- @ 9.0 µIU/mL: 2.0% (Immuno 1)	- @ 4.95 µIU/mL: 2.3%
- @ 22.5 µIU/mL: 1.8% (Immuno 1)	- @ 31.10 µIU/mL: 2.6%
Correlation (vs. Immuno 1): (Implied close correlation)	y = 0.98x - 0.357 (n=50, r=0.997, Syx=1.48 µIU/mL)
Interference (% Effect): (Implied acceptable levels)
- Hemoglobin (1000 mg/dL): 1.8%
- Lipids (Triglycerides, 1000 mg/dL): -0.9%
- Bilirubin (28 mg/dL): (Value missing in document)
- Urea Nitrogen (200 mg/dL): -1.5%

Study Details:

Sample sizes for test set:
- Correlation: n = 50
- Interference: Not explicitly stated per interfering substance, but done at specific analyte concentrations.
- Data Provenance: Not specified, likely retrospective clinical samples.
Number of experts and qualifications: Not applicable.
Adjudication method: Not applicable.
MRMC comparative effectiveness study: Not applicable.
Standalone performance: Yes, performance data reflects standalone operation, with correlation against a predicate.
Type of ground truth: Measurements from the predicate device (Bayer Immuno 1 TSH Assay) for correlation. Known baseline or reference values for precision and interference. The acceptance criterion for sensitivity is also tied to the American Thyroid Association standard.
Sample size for training set: Not applicable.
Ground truth for training set: Not applicable.

Summary

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

Alkaline Phosphatase (AMP) Method for the ADVIA IMS Systems

Listed below is a comparison of the performance of the Bayer ADVIA Alkaline Phosphatase (AMP) method and a similar device that was granted clearance of substantial equivalence (Bayer Chem 1 ALP(AMP) method). The information was extracted from the Bayer ADVIA ALP(AMP) method and Bayer Chem 1 method sheet.

INTENDED USE

ALP(AMP) METHOD:	ADVIA IMS	CHEM 1
Part Number:	Reagents B41-3718-23	T01-1459-53
Analytical Range:	0 to 2800 U/L	0 to 2250 U/L
Precision (Total):	mean (U/L)	% CV	mean (U/L)	% CV
	74	3.6	65	3.8
	160	2.9	263	3.3
	420	2.1	547	3.2
Regression Equation: (serum)	$y = 0.96x + 2.0$
where:	y = ADVIA IMSx = Chem 1n = 74r = 0.999Sy.x = 11.2range = 36 to 1599 U/L
Regression Equation: (plasma qualification)	$y = 1.06x - 0.9$
where:	y = plasmax = serumn = 59r = 0.999Sy.x = 0.93range = 33 to 111 U/L

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

Interference

	Interfering SubstanceConcentration	ALP(AMP)	Effect% Change
Hemoglobin	500 mg/dL	97 U/L	9
Bilirubin (conjugated)	20 mg/dL	100 U/L	8
Bilirubin (unconjugated)	25 mg/dL	107 U/L	1
Lipemia (Triglycerides)	1000 mg/dL	110 U/L	3

Gabriel J. Muracy Jr.
Gabriel J. Muraco, Jr.

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

6/30/98
Date

Date

00168

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

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

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

INTENDED USE

METHOD		ADVIA IMS	CHEM 1
Part No.	ReagentsCalibrators	B41-3725-25T03-1291-62	T01-1614-01T03-1291-62
Analytical Range		0 to 14.0 mg/dL	1 to 15 mg/dL
Precision (Total)		1.1% @ 8.4 mg/dL2.2% @ 10.4 mg/dL0.9% @ 13.6 mg/dL	2.3% @ 8.4 mg/dL2.5% @10.6 mg/dL2.2% @ 13.4 mg/dL
Correlation		y=0.96-0.8 mg/dLwherey=ADVIA IMSx=CHEM 1n=48r=0.996Sy.x=0.01 mg/dL

Plasma/Serum Equivalence	Plasma	Serum	Difference
	8.4 mg/dL	8.4 mg/dL	0.00
Within-run CV	0.75%	0.73%	0.02%

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

Interfering Substances

Bilirubin (unconjugated) 25 mg/dL	1.1% effect change @ 9.0 mg/dL Ca
Hemoglobin 1000 mg/dL	3.0% effect change @ 8.9 mg/dL Ca
Triglycerides 500 mg/dL	3.0% effect change @ 9.1 mg/dL Ca

Gabriel J. Muraca Jr.

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

6/30/98
__
Date

Date

000170

ﻪ ﻣﺴ

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

Glucose Method for the ADVIA IMS Systems

Listed below is a comparison of the performance of the Bayer ADVIA IMS Glucose method and a similar device that was granted clearance of substantial equivalence (Bayer Technicon Chem 1 Glucose method). The information was extracted from the Bayer ADVIA IMS Glucose method sheet.

INTENDED USE

GLUCOSE METHOD:	ADVIA IMS		CHEM 1
Part Number:	Reagents B41-3732-26		T01-1460-53
	Calibrators T03-1291-62		T03-1291-62
Analytical Range:	0 to 800 mg/dL		0 to 675 mg/dL
Precision (Total):	mean(mg/dL)	% CV	mean(mg/dL)	% CV
	48	3.66	87	2.7
	97	3.03	262	2.9
	293	1.80	305	2.3
			562	1.3
Regression Equation:(serum)	y = $1.03x + 0.71$
where:	y	= ADVIA IMS
	x	= Chem 1
	n	= 58
	r	= 0.993
	Sy.x	= 11.4
	range	= 51 to 534 mg/dL
Regression Equation:(plasma qualification)	y = $0.97x + 4.12$
where:	y	= plasma
	x	= serum
	n	= 60
	r	= 0.943
	Sy.x	= 4.1

range = 58 to 174 mg/dL

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

Interference

	Interfering SubstanceConcentration	GlucoseConcentration	Effect% Change
Hemoglobin	1000 mg/dL	297 mg/dL	0.5
Bilirubin (conjugated)	25 mg/dL	288 mg/dL	0.5
Bilirubin (unconjugated)	25 mg/dL	271 mg/dL	1.3
Lipemia (Triglycerides)	500 mg/dL	274 mg/dL	9.5

Gabriel J. Munoz, Jr.

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

6/30/98

Date

00172

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

Ferritin Method for Bayer ADVIA™ MODULAR SYSTEM

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

INTENDED USED

This in vitro method is intended to quantitatively measure ferritin, an iron storage protein, in human serum using Bayer Immuno 1 ferritin reagents on a Bayer ADVIA Modular System. Measurements of ferritin are used in the diagnosis and treatment of iron deficiency or iron overload disease states.

METHOD	Immuno 1 Ferritin(predicate device)		ADVIA Ferritin
Part No.	Reagents	T01-2863-51Calibrators T03-3251-01	Reagents	B42-3902-2Calibrators B43-3933-0
Minimum Detectable Conc.	0.3 ng/mL		0.06 ng/mL
Precision (Total CV%)	21 ng/mL	7.1%	28 ng/mL	4.1%
	148 ng/mL	5.0%	108 ng/mL	4.8%
	344 ng/mL	5.0%	245 ng/mL	5.0%

Correlation

y = 1.040 x - 6.132

where
y =	Bayer ADVIA Modular System
x =	Bayer Immuno 1 System
n =	50
r =	0.993
Syx =	57.50 ng/mL

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

Interference

	Interfering SubstanceConcentration	Ferritinconcentration	Ferritin (Neatconcentration)	Effect% Change
Hemoglobin	1000 mg/dL	179.8 ng/mL	178.3 ng/mL	0.8
Bilirubin	27.5 mg/dL	34.74 ng/mL	36.01ng/mL	3.5
Urea Nitrogen	200 mg/dL	175.1 ng/mL	182.0 ng/ml	3.8
Lipemia (Triglycerides)	1110 mg/dL	212.6 ng/mL	222.6 ng/ml	4.5

Gabriel J. Muraca, Jr.

Manager Regulatory Affairs
Bayer Corporation 511 Benedict Avenue Tarrytown, New York 10591-5097

6/30/98

Date

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

hCG Assay for Bayer ADVIA® Integrated Modular System

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

INTENDED USED

METHOD	ADVIA hCG Assay	Immuno 1 hCG Assay(predicate Device)
Part No.	Reagents B42-3907-43Calibrators B43-3941-01	Reagents T01-2966-5Calibrators T03-3148-0
Minimum Detectable Conc.	0.1 mIU/mL	0.5 mIU/mL
Precision (Total CV)	4.2% @ 12.1 mIU/mL4.5% @ 23.9 mIU/mL5.5% @ 198.1 mIU/mL	4.0% @ 18.3 mIU/mL3.7% @ 55.7 mIU/mL3.7% @ 198.1 mIU/mL
Correlation	y = 0.99x + 1.96wherey = ADVIA hCG Assayx = Immuno 1 hCG Assayn = 40r = 1.0Syx = 17.5 mIU/mL

Interfering Substances

InterferingSubstance	Interfering SubstanceConcentration		AnalyteConcentration, mIU/mL		Effect
	SI Units	(mg/dL)	Expected	Observed	(%)
Hemoglobin	1.0 g/L	1000	17.2	16.8	-2.3
Lipids (Triglycerides)	11.3 mmol/L	1000	17.2	15.7	-8.7
Bilirubin	428 $\mu$ mol/L	25	16.5	15.5	-6.1
Urea Nitrogen	71.4 mmol/L	200	17.2	15.9	-7.6

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

Gabriel J. Menaca Jr.

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

6/30/98

Date

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

3rd Generation TSH Assay for Bayer ADVIA® Integrated Modular System

Listed below is a comparison of the performance between the ADVIA 3d Generation TSH method and a similar device that was granted clearnice of substantial equivalence (Bayer Immuno 19 TSH Assay). The information used in the Summary of Safety and Effectiveness was extracted from the ADVIA 3ª Generation TSH insert and the Immuno 1 TSH Assay method sheet.

INTENDED USED

This in viro method is intended to quantitatively measure TSH, Thyroid Stimulating Hormone, in human serum using ADVIA 3d Generation TSH Assay on a Bayer ADVIA® Integrated Modular System. Measurements of TSH are used in the diagnosis of thyroid or pituitary disorders. This assay allows the determination of TSH with 3d generation sensitivity of less than 20% total coefficient of variation (CV) at 0.02 µIU/mL, as defined by the American Thyroid Association.

METHOD	ADVIA TSH Assay		Immuno 1 TSH Assay(predicate Device)
Part No.	Reagents	B42-3921-43Calibrators B43-3948-01	Reagents	T01-2942-51Calibrators T03-3568-01
Minimum Detectable Conc.	0.005 µIU/mL		0.03 µIU/mL
Precision (Total CV)		13.2% @ 0.02 µIU/mL2.9% @ 0.52 µIU/mL2.3% @ 4.95 µIU/mL2.6% @ 31.10 µIU/mL		6.3% @ 1.3 µIU/mL2.0% @ 9.0 µIU/mL1.8% @ 22.5 µIU/mL
Correlation	y = 0.98x - 0.357wherey = ADVIA TSH Assayx = Immuno 1 TSH Assayn = 50r = 0.997Syx = 1.48 µIU/mL

Interfering Substances

Interfering	Interfering Substance		Analyte		Effect
Substance	Concentration		Concentration, ulU/mL
	SI Units	(mg/dL)	Expected	Observed	(%)
Hemoglobin	1.0 g/L	1000	3.32	3.38	1.8
Lipids (Triglycerides)	11.3 mmol/L	1000	3.49	3.45	-0.9
Bilirubin	428 umol/L	ટર્ડ	3.25	3.30	ાં રે
Urea Nitrogen	71.4 mmol/L	200	3.30	3.31	-1.5

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

Gabriel J. Muraca, Jr.

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

6/30/98
Date

Date

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

JAN 2 9 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

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

K982328 Re: Trade Name: Bayer ADVIA® IMS™ System Regulatory Class: II Product Code: CJO, CFR, CIC, CJO, DHA, JLW, JMG Dated: November 12, 1998 Received: November 19, 1998

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 Requlations, 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.

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

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/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Butman

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

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

510(k) Number (if known):___

Device Name: Bayer ADVIA™ Integrated Module System (IMS™)

Indications For Use:

ALKALINE PHOSPHATASE (ALP)

Intended Use:

The Bayer ADVIA IMS alkaline phosphatase (ALP) assay is an in vitro diagnostic device intended to measure ALP in human serum or plasma. Such measurements are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases. This diagnostic method is not intended for use on any other diagnostic system.

CALCIUM (CA)

Intended Use:

The Bayer ADVIA IMS Calcium assay is an in vitro diagnostic device intended to measure calcium in human serum or plasma. Measurements of calcium are used in the diagnosis, monitoring and treatment of a variety of diseases including parathyroid disease, a variety of bone diseases, chronic renal disease, and tetany. This diagnostic method is not intended for use on any other diagnostic system.

GLUCOSE (GLU)

Intended Use:

(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)

Over-The-Counter Use

Optional Format 1-2-96)

000252

Page 1 of 2

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

510(k) Number (if known): A4893238

Device Name: Bayer ADVIA™ Integrated Module System (IMS™)

Indications For Use:

FERRITIN (FERR)

Intended Use:

HUMAN CHORIONIC GONDADOTROPIN (hCG)

Intended Use:

The Bayer ADVIA IMS hCG assay is an in vitro diagnostic device intended to quantitatively measure total beta (8) in human chorionic gonadotropin (hcG) in human serum. Measurements of human chorionic gonadotropin are used in the detection of pregnancy. This diagnostic method is not intended for use on any other diagnostic system.

THYROID STIMULATING HORMONE (TSH)

Intended Use:

"، "ﺍﻷﻣ

The Bayer ADVIA IMS TSH assay is an in vitro diagnostic device intended to quantitatively measure thyroid stimulating hormone (TSH)in human serum. This assay allows the determination of TSH with 3d generation sensitivity of less than 20% total coefficient variation (CV) at 0.01 to 0.02 mIUL or uiU/mL, as defined by the American Thyroid Association. Measurements thyroid stimulating hormone are used in the diagnosis of thyroid or pituitary disorders. This diagnostic method is not intended for use on any other diagnostic system.

(PLEASE DO NOT WRITE BELOW THIS LINE -

(Division Sign-Off)
Division of Clinical Laboratory Devices

NEEDED)

ANOTHER PAGE IF

Division of Clinica 510(k) Number -

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use (Per 21 CFR 801.109) OR

Over-The-Counter Use

000253 Optional Format 1-2-96)

Regulation Number and Section

§ 862.1050 Alkaline phosphatase or isoenzymes test system.

(a)
Identification. An alkaline phosphatase or isoenzymes test system is a device intended to measure alkaline phosphatase or its isoenzymes (a group of enzymes with similar biological activity) in serum or plasma. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.(b)
Classification. Class II.