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.

Device Description

Not Found

AI/ML Overview

The provided document describes the performance characteristics of various assays on the Bayer ADVIA IMS Systems, not an AI device. Therefore, several requested fields, such as "Multi-reader multi-case (MRMC) comparative effectiveness study," "Effect size of human readers improvement," "Standalone algorithm performance," "Number of experts for ground truth," "Qualifications of experts," "Adjudication method," and "Sample size for training set," are not applicable as they pertain to AI/ML device studies.

The document presents information comparing the performance of the ADVIA IMS assays to predicate devices. The acceptance criteria for these devices are implicitly demonstrated by showing comparable or superior performance to the legally marketed predicate devices, which is the basis for 510(k) clearance for in-vitro diagnostic devices, establishing substantial equivalence.

Acceptance Criteria and Device Performance (for each assay)

The acceptance criteria are generally demonstrated by showing strong correlation, comparable precision, and acceptable interference profiles relative to the predicate device.

1. Amylase (AMY) Method for the ADVIA IMS Systems (Section 0, 1)

Acceptance Criteria Category	Acceptance Criteria (Implied by Predicate)	Reported Device Performance (ADVIA IMS)
Analytical Range	10 to 3400 U/L (RA-XT)	0 to 1500 U/L
Precision (Total)	Serum: 51 U/L: 2.2% CV; 179 U/L: 1.0% CV; 373 U/L: 0.6% CV (RA-XT)	Serum: 56 U/L: 2.5% CV; 113 U/L: 2.1% CV; 430 U/L: 1.5% CV
	Urine: 57 U/L: 3.4% CV; 172 U/L: 1.3% CV; 510 U/L: 1.3% CV (RA-XT)	Urine: 50 U/L: 1.3% CV; 218 U/L: 1.1% CV; 493 U/L: 1.6% CV
Correlation (Serum)	Strong correlation to RA-XT	y = 1.01x - 5.7 (r = 0.999, Sy.x = 11.9)
Correlation (Plasma equiv.)	Strong correlation to serum (reference method)	y = 1.00x - 0.2 (r = 0.999, Sy.x = 1.0)
Correlation (Urine)	Strong correlation to RA-XT	y = 1.01x - 5.7 (Note: discrepancy - original table shows range, not equation. This might be a typo in the original document, as the serum equation is repeated but with urine range criteria)
Interference (Serum)	Minimal effect (e.g., within a few % change)	Hemoglobin: +2%; Bilirubin (conj): -4%; Bilirubin (unconj): -2%; Lipemia: +3%
Interference (Urine)	Minimal effect (e.g., within a few % change)	Ascorbic Acid: 1%; Acetaminophen: -1%; Salicylate: -2%

2. Cortisol Method for Bayer ADVIA® IMS™ (Section 2)

Acceptance Criteria Category	Acceptance Criteria (Implied by Predicate)	Reported Device Performance (ADVIA Cortisol)
Minimum Detectable Conc.	0.2 µg/dL (Immuno 1)	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% (Immuno 1)	4.4 µg/dL: 6.0%; 17.3 µg/dL: 5.0%; 37.5 µg/dL: 3.8%
Correlation	Strong correlation to Immuno 1	y = 1.013 x - 0.142 (r = 0.996, Syx = 0.961 µg/dL)
Interference	Minimal effect (e.g., within a few % change)	Hemoglobin: -4.8%; Lipids: -4.5%; Bilirubin: -1.9%; Urea Nitrogen: -4.4%

3. Iron Method for the Bayer ADVIA Integrated Modular System (IMS) (Section 3, 4)

Acceptance Criteria Category	Acceptance Criteria (Implied by Predicate)	Reported Device Performance (ADVIA IMS Iron)
Analytical Range	0 to 1200 ug/dL (CHEM 1)	0 to 800 ug/dL
Precision (Total)	96 ug/dL: 1.9%; 211 ug/dL: 1.3%; 383 ug/dL: 1.2% (CHEM 1)	50.7 ug/dL: 2.8%; 230.1 ug/dL: 1.1%; 438.3 ug/dL: 0.7%
Correlation	Strong correlation to CHEM 1	Y=0.93X+10.8 ug/dL (r=0.998, Sy.x=9.75 ug/dL)
Plasma/Serum Equivalence	Strong correlation to serum (reference method)	Y=0.98X+0.46 ug/dL (r=0.99, Sy.x=3.12 ug/dL)
Interference	Minimal effect (e.g., within a few % change)	Bilirubin (unconj): 7.0%; Bilirubin (conj): -1.0%; Hemoglobin: 44.0%; Lipemia: -20.0%

4. T4 Method for the Bayer ADVIA® IMS Systems (Section 5, 6)

Acceptance Criteria Category	Acceptance Criteria (Implied by Predicate)	Reported Device Performance (ADVIA IMS T4)
Minimum Det. Conc.	0.4 µg/dL (Immuno 1)	0.25 µg/dL
Precision (Total)	4.7 µg/dL: 3.6%; 8.2 µg/dL: 2.6%; 15.7 µg/dL: 2.5% (Immuno 1)	3.5µg/dL: 6.0%; 7.9 µg/dL: 5.1%; 14.9 µg/dL: 4.7%
Correlation (SERUM)	Strong correlation to Immuno 1	y = 1.06 x +0.11 (r = 0.994, Syx = 0.65 µg/dL)
Correlation (PLASMA)	Strong correlation to serum (reference method)	y = 0.98X + 0.06 (r = 0.977, Syx = 0.36)
Interference	Minimal effect (e.g., within a few % change)	Bilirubin (unconj): 0%; Bilirubin (conj): -2%; Hemoglobin: -3%; Lipemia: +3%

5. Free T4 Assay for Bayer ADVIA® Integrated Modular System (Section 7)

Acceptance Criteria Category	Acceptance Criteria (Implied by Predicate)	Reported Device Performance (ADVIA FREE T4 Assay)
Minimum Detectable Conc.	0.10 ng/dL (Immuno 1)	0.05 ng/dL
Precision (Total CV)	0.94 ng/dL: 4.9%; 1.76 ng/dL: 3.5%; 4.68 ng/dL: 2.2% (Immuno 1)	0.85 ng/dL: 4.5%; 1.46 ng/dL: 4.8%; 3.04 ng/dL: 3.0%
Correlation	Strong correlation to Immuno 1	y = 0.998 x + 0.2179 (r = 0.9928, Syx = 0.1368 ng/dL)
Interference	Minimal effect (e.g., within a few % change)	Hemoglobin: 3.8%; Lipids: 2.2%; Bilirubin: 0.6%; Urea Nitrogen: 1.1%

6. Total T3 Assay for Bayer ADVIA® Integrated Modular System (Section 8)

Acceptance Criteria Category	Acceptance Criteria (Implied by Predicate)	Reported Device Performance (ADVIA T3 Assay)
Minimum Detectable Conc.	0.06 ng/mL (Immuno 1)	0.13 ng/mL
Precision (Total CV)	0.46 ng/mL: 13.3%; 1.34 ng/mL: 6.0%; 3.43 ng/mL: 3.9% (Immuno 1)	0.67 ng/mL: 10.3%; 1.74 ng/mL: 4.9%; 2.89 ng/mL: 3.6%
Correlation	Strong correlation to Immuno 1	y = 1.014x + 0.1368 (r = 0.996)
Interference	Minimal effect (e.g., within a few % change)	Hemoglobin: 3.7%; Lipids: 5.5%; Bilirubin: 3.0%; Urea Nitrogen: (data partially illegible but likely similar minimal effect)

7. Free T3 Assay for Bayer ADVIA® Integrated Modular System (Section 9)

Acceptance Criteria Category	Acceptance Criteria (Implied by Predicate)	Reported Device Performance (ADVIA Free T3 Assay)
Minimum Detectable Conc.	0.3 pg/mL (Immuno 1)	0.4 pg/mL
Precision (Total CV)	1.8 pg/mL: 8.5%; 5.4 pg/mL: 3.8%; 10.8 pg/mL: 2.9% (Immuno 1)	2.0 pg/mL: 10.0%; 4.88 pg/mL: 5.0%; 9.35 pg/mL: 4.1%
Correlation	Strong correlation to Immuno 1	y = 0.97x + 0.41 (r = 0.998, Syx = 0.427 pg/mL)
Interference	Minimal effect (e.g., within a few % change)	Hemoglobin: 6.4% (value partially illegible/corrupted); Lipids: 9.4% (value partially illegible/corrupted); Bilirubin: -3.4%; Urea Nitrogen: 2.1%

8. T-Uptake Assay for Bayer ADVIA® Integrated Modular System (Section 10)

Acceptance Criteria Category	Acceptance Criteria (Implied by Predicate)	Reported Device Performance (ADVIA T-Uptake Assay)
Precision (Total CV)	0.71: 2.8%; 1.03: 2.6%; 1.41: 2.4% (Immuno 1)	0.96: 3.2%; 0.89: 2.6%; 1.14: 2.3%
Correlation	Strong correlation to Immuno 1	y = 0.96x + 0.0003 (r = 0.987)
Interference	Minimal effect (e.g., within a few % change)	Hemoglobin: 0.88%; Lipids: 0.90%; Bilirubin: 1.74%; Urea Nitrogen: 0.91%

9. Urea Nitrogen method for ADVIA® 400 (Section 11, 12)

Acceptance Criteria Category	Acceptance Criteria (Implied by Predicate)	Reported Device Performance (ADVIA 400 Urea Nitrogen)
Analytical Range	(Not explicitly stated for CHEM 1, assumed to cover relevant clinical range)	Serum/Plasma: 0 to 150 mg/dL; Urine: 2 to 1030 mg/dL
Imprecision (SERUM)	21 mg/dL: 3%; 54 mg/dL: 3%; 97 mg/dL: 3% (CHEM 1)	7.3 mg/dL: 4.3%; 17 mg/dL: 2.5%; 52 mg/dL: 1.6%
Imprecision (URINE)	478 mg/dL: 2.6%; 648 mg/dL: 2.5% (CHEM 1)	69 mg/dL: 3.9%; 212 mg/dL: 2.1%; 404 mg/dL: 2.0%
Correlation (Serum)	Strong correlation to CHEM 1	Y=1.03X-0.6 (r=0.997, Syx=2.8 mg/dL)
Correlation (Plasma equiv.)	Strong correlation to serum (reference method)	Y=0.96X+0.6 (r=0.975, Syx=1.1)
Correlation (Urine)	Strong correlation to CHEM 1	Y=1.08X-8.9 (r=0.997, Syx=22.5)
Interference	Minimal effect (e.g., within a few % change)	Bilirubin: -4.0%; Hemoglobin: +4.4%; Lipids: +23.0%; Ascorbic Acid: +3.2%; Salicylate: -2.4%; Glucose: +9.5%; Acetominophen: +4.5%

Study Details

This document describes a series of performance studies for multiple in-vitro diagnostic assays on the Bayer ADVIA IMS Systems. The studies aim to demonstrate "substantial equivalence" to predicate devices, which is a regulatory pathway for marketing these devices.

2. Sample size used for the test set and the data provenance:

AMY Method:
- Serum Correlation: n = 72
- Plasma Qualification: n = 60
- Urine Correlation: n = 72
- Provenance: Not explicitly stated, but typically these studies are conducted with clinical samples from various sources (e.g., hospitals, labs) within the country where the manufacturer is seeking clearance or where R&D is conducted. It's retrospective in the sense that samples are collected and then analyzed.
Cortisol Method:
- Correlation: n = 57
- Provenance: Not explicitly stated.
Iron Method:
- Correlation: n = 65
- Plasma/Serum Equivalence: n = 56
- Provenance: Not explicitly stated.
T4 Method:
- Serum Correlation: n = 72
- Plasma Correlation: n = 24
- Provenance: Not explicitly stated.
Free T4 Assay:
- Correlation: n = 50
- Provenance: Not explicitly stated.
Total T3 Assay:
- Correlation: n = 50
- Provenance: Not explicitly stated.
Free T3 Assay:
- Correlation: n = 56
- Provenance: Not explicitly stated.
T-Uptake Assay:
- Correlation: n = 51
- Provenance: Not explicitly stated.
Urea Nitrogen Method:
- Serum Correlation: n = 50
- Plasma (y), Serum (x) Correlation: n = 58
- Urine Correlation: n = 53
- Provenance: Not explicitly stated.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
Not applicable. These are in-vitro diagnostic tests for quantitative measurement of analytes. "Ground truth" is established by laboratory reference methods or predicate devices, not human expert interpretation.

4. Adjudication method for the test set:
Not applicable. Ground truth for quantitative chemical assays is determined by analytical methods, not human adjudication.

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:
Not applicable. This document is for in-vitro diagnostic assays, not AI/ML devices requiring human reader studies.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Not applicable. These are automated laboratory assays, and their performance is inherently "standalone" in a laboratory setting, meaning the instrument and reagents produce a result without human interpretation of raw data points, beyond quality control and review of final numerical results.

7. The type of ground truth used:
For each assay, the "ground truth" (or reference method) for analytical performance comparison is the predicate device (e.g., Bayer RA-XT Amylase method, Immuno 1 Cortisol assay, Technicon CHEM 1 Iron-II method, etc.) or a well-established reference method (e.g., serum for plasma equivalence studies). The performance is assessed by comparison (correlation, regression) against results obtained from these predicate devices on the same samples.

8. The sample size for the training set:
Not applicable. These are traditional IVD assays, not machine learning models that require a separate training set. The "development" of the assay involves optimizing reagents and instrument parameters, not training on a dataset in the AI sense.

9. How the ground truth for the training set was established:
Not applicable. As there is no training set in the AI/ML sense, no ground truth was established for it.

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 SubstanceConcentration	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:

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 SubstanceConcentration	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 T01-2910-01Calibrators T03-3252-01	Reagents B42-3899-21Calibrators 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 - 0.142wherey = Bayer ADVIA Modular Systemx = Bayer Immuno 1 Systemn = 57r = 0.996Syx = 0.961 µg/dL

InterferingSubstance	Interfering SubstanceConcentration		AnalyteConcentration		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.	ReagentsB41-3735-43CalibratorsT03-1291-62	T01-3328-53T03-1291-62
Analytical Range	0 to 800 ug/dL	0 to 1200 ug/dL
Precision (Total)	2.8% @ 50.7 ug/dL1.1% @ 230.1 ug/dL0.7% @ 438.3 ug/dL	1.9% @ 96 ug/dL1.3% @ 211 ug/dL1.2% @ 383 ug/dL
Correlation	Y=0.93X+10.8 ug/dLWhereY=ADVIA IMSX=CHEM 1N=65r=0.998Sy.x=9.75 ug/dL
Plasma/Serum Equivalence	Y=0.98X+0.46 ug/dLWhereY = plasmaX= SerumN = 56r = 0.99Sy.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	B41-3855-42B41-3855-43	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/dL5.1% @ 7.9 µg/dL4.7% @14.9 µg/dL	3.6% @ 4.7 µg/dL2.6% @ 8.2 µg/dL2.5% @ 15.7 µg/dL
Correlation	SERUM	y = 1.06 x +0.11wherey = ADVIA IMSx = Immuno 1n = 72r = 0.994Syx = 0.65 µg/dL
	PLASMA	y = 0.98X + 0.06Wherey = Serum (ADVIA IMS)x = Plasma (ADVIA IMS)n = 24r = 0.977Syx = 0.36

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

InterferenceSubstance	InterferingSubstanceConcentration	ThyroxineConcentration,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 + 0.2179wherey = ADVIA FREE T4 Assayx = Immuno 1 FREE T4 Assayn = 50r = 0.9928S = 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.	ReagentsReagentsCalibrators	B42-3916-41 (100 tests)B42-3916-42 (250 tests)B43-3943-01	ReagentsCalibrators	T01-2942-0T03-2872-0
Minimum Detectable Conc.	0.13 ng/mL	0.06 ng/mL
Precision (Total CV)	10.3% @ 0.67 ng/mL4.9% @ 1.74 ng/mL3.6% @ 2.89 ng/mL	13.3% @ 0.46 ng/mL6.0% @ 1.34 ng/mL3.9% @ 3.43 ng/mL
Correlation	y = 1.014x + 0.1368wherey = ADVIA T3 Assayx = Immuno 1 T3 Assayn = 50r = 0.996

Interfering Substances

InterferingSubstance	Interfering SubstanceConcentration		AnalyteConcentration, 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.	ReagentsCalibrators	B42-3904-42B43-3935-01	ReagentsCalibrators	T01-3662-57T03-3663-02
Minimum Detectable Conc.		0.4 pg/mL		0.3 pg/mL
Precision (Total CV)		10.0% @ 2.0 pg/mL5.0% @ 4.88 pg/mL4.1% @ 9.35 pg/mL		8.5% @ 1.8 pg/mL3.8% @ 5.4 pg/mL2.9% @ 10.8 pg/mL
Correlation	y = 0.97x + 0.41wherey = ADVIA Free T3 Assayx = Immuno 1 Free T3 Assayn = 56r = 0.998Syx = 0.427 pg/mL

Interfering Substances

InterferingSubstance	Interfering SubstanceConcentration		AnalyteConcentration, 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.	ReagentsCalibrators	B42-3915-41 (100 tests)B43-3994-01	ReagentsCalibrators	T01-3036-51T03-3076-01
Minimum Detectable Conc.	N/A		N/A
Precision (Total CV)	3.2% @ 0.962.6% @ 0.892.3% @ 1.14		2.8% @ 0.712.6% @ 1.032.4% @ 1.41
Correlation	y = 0.96x + 0.0003wherey = ADVIA T-UptakeAssayx = Immuno 1 T-Uptake Assayn = 51r = 0.987

Interfering Substances

InterferingSubstance	Interfering SubstanceConcentration	AnalyteConcentration, 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)	TotalCV(%)	Level(mg/dL)	TotalCV(%)
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)	TotalCV(%)	Level(mg/dL)
69	3.9	478
212	2.1	648
404	2.0

CHEM 1
Level(mg/dL)	TotalCV(%)
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

InterferingSubstance	Interfering Sub.Conc. (mg/dL)	Urea NitrogenConc. (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:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use ﮯ (Per 21 CFR 801.109) OR

Over-The-Counter Use

(Optional Format 1-2-96)

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

510(k) Number (if known):

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

Indications For Use:

(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:

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)

Over-The-Counter Use

(Optional Format 1-2-96)

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.