Reagent: for in vitro diagnostic use in the quantitative determination of β2-microglobulin in human serum or plasma (lithium heparin and potassium EDTA) on ADVIA® 1650 Chemistry systems. The ADVIA 1650 Chemistry 32-Microglobulin (B2M) assay aids in the diagnosis of active rheumatoid arthritis and kidney disease.

Calibrators: for in vitro diagnostic use in the calibration of ADVIA® Chemistry systems for the ADVIA Chemistry β2-Microglobulin method.

Device Description

The ADVIA 1650 Chemistry 32-Microglobulin (B2M) assay sample is diluted and reacted with a buffer that contains latex particles coated with antibody specific for ß2microglobulin. The formation of the antibody-antigen complex during the reaction results in an increase in turbidity, the extent of which is measured as the amount of light absorbed at 545 nm. The ß2-Microglobulin concentration in a sample is determined by constructing a standard curve from the absorbance of a reagent blank and a single-level calibrator.

The ADVIA Chemistry B2-Microglobulin Calibrator is a single analyte, lyophilized, buffer based product containing bovine serum albumin and human ß2-Microglobulin. The kit consists of 3 vials of a single level calibrator. The calibrator requires reconstitution with 1 mL of distilled water prior to use.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and study for the ADVIA Chemistry β2-Microglobulin reagent:

Acceptance Criteria and Device Performance

The document does not explicitly state pre-defined acceptance criteria in a dedicated section. However, the "Performance" section (Section 5, 6, 7, 8) outlines the studies conducted and their results, implying that these results met the criteria for substantial equivalence to the predicate device.

Based on the studies described, the implied acceptance criteria and reported device performance are summarized below:

Performance Characteristic	Implied Acceptance Criteria (relative to predicate)	Reported Device Performance (ADVIA 1650 Chemistry β2-Microglobulin assay)
Analytical Sensitivity (LoD)	Limit of Detection (LoD) should be adequate for intended use and comparable to predicate.	LoD = 0.25 mg/L
Analytical Sensitivity (LoB)	Limit of Blank (LoB) should be adequate for intended use and comparable to predicate.	LoB = 0.20 mg/L
Imprecision (Total CV%)	Within acceptable biological and analytical variability for the analyte, and comparable to predicate.	Levels: 0.74 mg/L (3.3%), 1.77 mg/L (2.6%), 3.68 mg/L (2.4%), 12.52 mg/L (2.1%)
Interfering Substances	No significant interference (NSI) for common interferents at specified concentrations, defined as a percentage effect ≤ 10%.	NSI for most tested substances at specified levels. Exceptions: Ascorbic Acid at 100 mg/dL (-15.3%) and 200 mg/dL (-13.4%).
Method Comparison (Correlation)	Strong correlation (high 'r' value) and good agreement (slope close to 1, y-intercept close to 0) with the predicate device.	n=88, r=0.99, Slope=1.03, Y-int=-0.38 (vs. Siemens N Latex β2-Microglobulin)
Serum/Plasma Equivalency	No significant differences between different sample tube types (serum vs. potassium EDTA, serum vs. lithium heparin).	Potassium EDTA: N=57, y = 1.00x - 0.04, Sy.x=0.19, r=0.99Lithium Heparin: N=57, y = 1.01x + 0.01, Sy.x=0.21, r=0.99(No significant differences observed)

Study Details

Sample sizes used for the test set and the data provenance:
- Analytical Sensitivity (LoD/LoB): 60 replicates of a blank sample, 60 replicates of a low serum sample.
- Imprecision: 4 serum-based samples, tested 2 times per run, 2 runs per day, for at least 20 days (resulting in n=80 per level).
- Interfering Substances: Multiple concentrations of β2-microglobulin (approx. 1, 3, and 11 mg/L) tested with various concentrations of interferents.
- Method Comparison: 88 serum samples.
- Serum/Plasma Equivalency: 57 matched specimens (serum, potassium EDTA plasma, lithium heparin plasma).
Data Provenance: The document does not explicitly state the country of origin for the data or whether it was retrospective or prospective. It implies the studies were conducted by Siemens Healthcare Diagnostics. Given the context of a 510(k) submission, these would typically be controlled prospective studies conducted in a laboratory setting to demonstrate analytical performance.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This is a laboratory assay for quantitative determination of β2-microglobulin. The "ground truth" for such assays is established through analytical methods and verification against reference materials or established predicate devices, not via expert consensus or clinical adjudication as would be for diagnostic imaging or clinical decision support systems. Therefore, the concept of "experts" to establish ground truth in the traditional sense doesn't apply here. The accuracy of the analytical measurements and the comparison to a legally marketed predicate device (Siemens N Latex β2-Microglobulin) serve as the basis for performance evaluation.
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
Not applicable to a laboratory diagnostic assay of this type. Adjudication is typically used in clinical studies or for subjective interpretations (e.g., radiology reads) where multiple human readers are involved. This study evaluates the quantitative performance of an automated assay.
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 is a study for an in vitro diagnostic assay, not an AI-assisted diagnostic tool involving human readers.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
Yes, the studies described are for the standalone analytical performance of the ADVIA 1650 Chemistry β2-Microglobulin assay. It's an automated process performed on an instrument, and the results presented represent the algorithm's (assay's) performance. There is no human-in-the-loop described in these performance evaluations.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The "ground truth" for this in vitro diagnostic assay is primarily:
- Reference materials/standards: For analytical sensitivity (LoD/LoB) and potentially for calibrator values (traceability to WHO 1st International Standard is mentioned for the calibrator).
- Measurements from a legally marketed predicate device: For method comparison (correlation study).
- Known concentrations in spiked samples: For interfering substances studies.
The sample size for the training set:
Not applicable. This is an in vitro diagnostic assay, not a machine learning model that requires a separate training set. The assay's parameters would have been developed and validated internally by the manufacturer through R&D, but there isn't a "training set" in the context of typical AI/ML studies.
How the ground truth for the training set was established:
Not applicable, as there is no training set mentioned or implied in the context of an AI/ML model for this type of IVD device. The assay development involves chemical and biological principles, calibration, and optimization based on known analytical standards and performance targets.

Summary

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

K110874

510(k) Summary

JAN 2 0 2012

Submitter informationContact person:	Neil ParkerSenior Regulatory Affairs Specialist
Address:	Siemens Healthcare Diagnostics511 Benedict AvenueTarrytown, NY 10591
Phone:	914-524-2477914-524-2500 (fax)

Date summary prepared: March 28, 2011

Device Trade or Proprietary Names:

ADVIA Chemistry β2-Microglobulin reagent ADVIA Chemistry β2-Microglobulin calibrator

Device Common/Usual Name or Classification Name:

Beta-2-Microglobulin Immunological Test System Calibrator

Classification Number / Class:

21 CFR 866.5630 - Beta-2-Microglobulin Immunological Test System Class II 21 CFR 862.1150 - Calibrator - Class II

Product code:

JZG - Beta-2-Microglobulin Immunological Test System JIT - Calibrator, Secondary

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

This 510/k) summary of safety and effectiveness is being submitted in accordance with the requirements of 21 CFR 807.92.

The assigned 510(k) number is:

Assay Predicate Device:

	Predicate Device
Device Name	Siemens N Latex β2 – Microglobulin (N B2M)
Common name	Beta-2-Microglobulin Immunological TestSystem – Class II
510(k) Number	K002731
Manufacturer	Siemens (formerly Dade Behring, Inc)

Calibrator Predicate Device

	Predicate Device
Device Name	Siemens N-protein standard SL
Common name	Calibrator, multi-analyte mixture
510(k) Number	K052788
Manufacturer	Siemens (formerly Dade Behring, Inc)

Device Description:

Siemens Healthcare Diagnostics ADVIA 1650 Chemistry ß2-Microglobulin 510(k) Summary

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

Statements of Intended Use:

Calibrators: for in vitro diagnostic use in the calibration of ADVIA® Chemistry systems for the ADVIA Chemistry β2-Microglobulin method.

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

Comparisons to the Predicate Devices: Assay Similarities

Items	ADVIA 1650 Chemistry β2-Microglobulin (B2M) assay	Siemens N Latex β2 -Microglobulin (N B2M)(Predicate Device) K002731
Intended Use/Indication foruse	for in vitro diagnostic use in thequantitative determination of β2-microglobulin in human serum orplasma (lithium heparin andpotassium EDTA) on ADVIA®1650 Chemistry systems. TheADVIA 1650 Chemistry β2-Microglobulin (B2M) assay aidsin the diagnosis of activerheumatoid arthritis and kidneydisease.	SimilarThe Siemens N Latex β2 -Microglobulin (N B2M) isIn vitro diagnostic reagent forthe quantitative determinationof β2-microglobulin in humanserum, plasma (EDTA andheparinized), as well as inurine by means of particle-enhanced immuno-nephelometry on the BNSystems. This assay aids inthe diagnosis of renaldysfunction.
Measurement	Quantitative	Same
Reagent storage temperature	2-8°C	Same
Format	Liquid	Same
Use of Calibrators	Yes	Same
Reference Range	1.0 to 2.4 mg/L	Similar1.09 to 2.53 mg/L

Assay Differences

Items	ADVIA 1650 Chemistry β2-Microglobulin (B2M) assay	Siemens N Latex β2 -Microglobulin (N B2M)(Predicate Device) K002731
Differences
Platform	ADVIA 1650 Chemistry System	BN system
Assay principle	turbidimetric	nephelometric
On Board stability	21 days	Minimum 5 days
Sample Type	Serum, plasma	Serum, plasma, urine
Assay Range	0.25 - 18.0 mg/L	0.7 - 23.0 mg/L(serum/plasma)
Antibody Source	goat	mouse

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

Calibrator Similarities

Items	ADVIA Chemistry β2-Microglobulin Calibrator	Siemens N Protein Standard SL (Predicate Device) K052788
Similarities
Intended Use/Indication for use	for in vitro diagnostic use the calibration of ADVIA® Chemistry systems for the ADVIA Chemistry β2-Microglobulin method.	SimilarFor in vitro diagnostic use for establishment of reference curves for the determination of 27 analytes including β2-Microglobulin on the BN Systems.
Number of calibrators	1	Same
Calibrator storage temperature	2-8°C	Same
Fill volume	1.0mL	Same
Traceability	WHO 1st International Standard	Same

Calibrator Differences

Items	ADVIA Chemistry β2-MicroglobulinCalibrator	Siemens N Protein StandardSL (Predicate Device)K052788
Differences
Analyte	Single	Multi
Format	Lyophilized - buffer based	Liquid - serum based
Stability	30 days after reconstitution	14 days after opening
Instrument	ADVIA 1650 Chemistry System	BN Systems

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

Performance:

Substantial equivalence for the ADVIA 1650 Chemistry ß2-Microglobulin assay to the predicate device was demonstrated by testing several method performance characteristics including analytical sensitivity, linearity, imprecision, method comparison and interfering substances. The following information summarize the analytical sensitivity, linearity, precision (total), interfering substances, serum / plasma equivalency and method comparison results.

All of the evaluation studies gave acceptable results compared to the predicate device. These studies support that the ADVIA 1650 Chemistry ß2-Microglobulin assay is substantially equivalent to the Siemens N Latex ß2 -Microglobulin (N B2M) that is currently marketed.

Analytical Sensitivity

The Limit of Detection (LoD) and Limit of Blank (LoB) were determined by following CLSI quideline EP-17A. The study was performed by running 60 replicates of a blank (serum sample with a low concentration of ß2-Microglobulin at < 0.20 mg/L) and 60 replicates of a low serum sample (serum sample with approximate concentration of 0.74mg/L). The following results were obtained:

LoB = 0.20 mg/L LoD = 0.25 mg/L

Imprecision

Imprecision was assessed by assaying 4 serum based samples 2 times per run, 2 runs per day, for at least 20 days. Precision estimates were calculated according to CLSI document EP5-A2. The following results were obtained.

Table 1 - summary of Precision for the ADVIA 1650 Chemistry (32-Microglobulin (B2M) assav

ADVIA 1650 Chemistry β2-Microglobulin (B2M) assay
Level (mg/L)	Total CV (%)
	n = 80
0.74	3.3
1.77	2.6
3.68	2.4
12.52	2.1

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

Interfering Substances

Interfering substances were tested at ß2-microglobulin concentrations of approximately 1, 3 and 11 mg/L on the ADVIA 1650 chemistry ß2-microglobulin assay. Table 2 summarizes the data for biliirubin (conjugated and unconjugated), hemolysis, lipemia (from intralipid), rheumatoid factor and ascorbic acid. Table 3 summarizes the data for acetone, cholesterol, creatinine, ethanol, glucose, IgG, IgM, riboflavin, total protein, urea, and uric acid.

Interferent	Interferent Level	β₂-Microglobulin SampleConcentration	Interference
Bilirubin	60 mg/dL	1.14 mg/L	NSI*
(conjugated andunconjugated)	(1026 µmol/L)	10.95 mg/L	NSI*
Hemolysis	1000 mg/dL	1.27 mg/L	NSI*
(hemoglobin)	(10.0 g/L)	11.00 mg/L	NSI*
Lipemia**	1000 mg/dL	1.20 mg/L	NSI*
(from Intralipid)	(11.3 mmol/L)	11.03 mg/L	NSI*
Rheumatoid Factor (RF)	2500 IU/mL	1.16 mg/L	NSI*
		10.30 mg/L	NSI*
Ascorbic Acid	50 mg/dL	1.21 mg/L	NSI*
	100 mg/dL	1.21 mg/L	-15.3%
	150 mg/dL	10.73 mg/L	NSI*
	200 mg/dL	10.73 mg/L	-13.4%

Table 2

*NSI = No Significant Interference. A percentage effect > 10% is considered a significant interference.

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

Table	3
-------	---

Substance in Serum	Concentration Tested	Interference
Acetone	up to 250 mg/dL	NSI*
Cholesterol	up to 500 mg/dL	NSI*
Creatinine	up to 125 mg/dL	NSI*
Ethanol	up to 1000 mg/dL	NSI*
Glucose	up to 2000 mg/dL	NSI*
Immunoglobulin G	up to 5000 mg/dL	NSI*
Immunoglobulin M	up to 1600 mg/dL	NSI*
Riboflavin	up to 15 mg/dL	NSI*
Total protein	up to 12 g/dL	NSI*
Urea	up to 60 mg/dL	NSI*
Uric acid	up to 12 mg/dL	NSI*

*NSI = No Significant Interference. A percentage effect ≥ 10% is considered a significant interference.

Correlation

A total of 88 samples serum samples were analyzed on the ADVIA 1650 Chemistry system using ß2-Microglobulin reagent and on the Siemens N Latex ß2 -Microglobulin (predicate device), in parallel on the same day to demonstrate the equivalence of the two methods.

Table 4 summarizes the data.

Table 4 - ADVIA 1650 Chemistry ß2-microglobulin assay vs. Siemens N Latex ß2 -Microglobulin (N B2M) method

Siemens N Latex β2 -Microglobulin vs ADVIA 1650 Chemistry B2MAssay
X Axis	Y Axis	n	r	Slope	Y-int
Siemens NLatex β2 -Microglobulin	ADVIA 1650ChemistryB2M	88	0.99	1.03	-0.38

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

Serum / Plasma (lithium heparin and EDTA)

The ADVIA 1650 Chemistry Centaur (32-microglobulin assay was evaluated using different sample tube collection types. A matrix study was performed using matched specimens drawn in different tube types. potassium EDTA and lithium heparin. 82microglobulin values ranged from 0.97 to 17.75 mg/L. Linear regression analysis was performed using the following:

· serum (x) vs. potassium EDTA (v1)

· serum (x) vs. lithium heparin (y2)

No significant differences between tube types was observed. The following results were obtained:

Table 5

SpecimenType	Comparison Assay(x)	N	RegressionEquation	Sy.x r	Sample Range
Plasma(K,EDTA)	ADVIA 1650/1800B2M Reagent	57	$y = 1.00x - 0.04$	0.19 0.99	0.97-17.75 mg/L
Plasma(LithiumHeparin)	ADVIA 1650/1800B2M Reagent	57	$y = 1.01x + 0.01$	0.21 0.99	0.97-17.75 mg/L

Conclusions:

The Siemens Healthcare Diagnostics ADVIA 1650 Chemistry Centaur 02-microglobulin assay ADVIA is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed Siemens N Latex ß2 -Microglobulin (N B2M) K002731.

The Siemens Healthcare Diagnostics ADVIA Chemistry β2-Microglobulin calibrator is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed Siemens N Protein Standard SL K052788.

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

Image /page/9/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 words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. Inside the circle is an abstract image of an eagle or other bird-like figure.

Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993

Siemens Healthcare Diagnostics, Inc. c/o Mr. Neil Parker Sr. Regulatory Affairs Specialist 511 Benedict Ave Tarrytown, NY 10591

JAN 2 0 2012

Re: K110874

ADVIA® Chemistry ß2-Microglobulin Reagent Regulation Number: 21 CFR §866.5630 Regulation Name: Beta-2-Microglobulin Immunological Test System Regulatory Class: II Product Code: JZG, JIT Dated: January 10, 2012 Received: January 12, 2012

Dear Mr. Parker:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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) that do not require approval of a premarket approval application (PMA). 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 class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter

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

Page 2 – Mr. Neil Parker

will allow you to begin marketing your device as described in your Section 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 Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Reeva Philip

C 0%

Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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

Indication for Use

K 110874 510(k) Number (if known): Device Name: ADVIA 1650 Chemistry ß2-microglobulin (B2M) method Indication for Use:

Reagent: for in vitro diagnostic use in the quantitative determination of ß2-microglobulin in human serum or plasma (lithium heparin and potassium EDTA) on ADVIA 1650 Chemistry systems. The ADVIA 1650 Chemistry ß2-Microglobulin (B2M) assay aids in the diagnosis of active rheumatoid arthritis and kidney disease.

Calibrator: for in vitro diagnostic use in the calibration of ADVIA® Chemistry systems for the ADVIA Chemistry ß2-Microglobulin method

Prescription Use X_ (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

KII0874 510(k)

Page 1 of 1 __

Regulation Number and Section

§ 866.5630

Beta -2-microglobulin immunological test system.(a)
Identification. Abeta -2-microglobulin immunological test system is a device that consists of the reagents used to measure by immunochemical techniquesbeta -2-microglobulin (a protein molecule) in serum, urine, and other body fluids. Measurement ofbeta -2-microglobulin aids in the diagnosis of active rheumatoid arthritis and kidney disease.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.