Reagent: For in vitro diagnostic use in the quantitative determination of Cystatin-C (CYSC) in human serum or plasma (lithium heparin, potassium EDTA) on the ADVIA Chemistry systems. Measurement of Cystatin C aids in the diagnosis and treatment of renal disease.

Calibrator: For in vitro diagnostic use in the calibration of Cystatin C method on ADVIA Chemistry systems.

Device Description

The CYSC latex reagent is a suspension of uniform latex particles coated with anticystatin-C antibody. When serum or plasma containing cystatin C is mixed with the latex reagent, agglutination takes place resulting in an increase in turbidity. This turbidity is measured at 571 and 805 nm. The cystatin C concentration in serum or plasma is determined from a calibration curve that is generated with the calibrators.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and supporting study for the ADVIA® Chemistry Cystatin C Method:

1. Table of Acceptance Criteria and Reported Device Performance

The provided text does not contain explicit, quantitative acceptance criteria for device performance. Instead, it relies on demonstrating substantial equivalence to an existing predicate device (Dade Behring N Latex Cystatin C and Dade Behring N Protein Standard UY). The "performance" is implicitly deemed acceptable if it closely matches or is considered equivalent to the predicate device in various aspects.

Therefore, the table below reflects the comparative information provided rather than explicit acceptance criteria.

Feature / Performance Aspect	Predicate Device Performance / Characteristic	Device Performance / Characteristic (ADVIA® Chemistry Cystatin C)
Intended Use (Reagent)	For quantitative determination of cystatin C in human serum and heparinized plasma; aids in diagnosis/treatment of renal disease.	For quantitative determination of Cystatin C in human serum or plasma (lithium heparin, potassium EDTA); aids in diagnosis/treatment of renal disease.
Intended Use (Calibrator)	For preparing reference curves for immunonephelometric determinations of a-1-micorglobulin and Cystatin C using BN systems.	For calibration of Cystatin C method on ADVIA Chemistry systems.
Antibody	Rabbit Polyclonal antibodies to human Cystatin C	Rabbit Polyclonal antibodies to human Cystatin C
Format	Liquid	Liquid
Use of Calibrators	Yes	Yes
Traceability	Internal standard of highly purified human cystatin C	Internal standard of highly purified human cystatin C
Reference Range	0.53 - 0.95 mg/L	0.56 - 0.95 mg/L
Sample Matrix	Serum or Heparinized Plasma	Serum, Heparinized Plasma, EDTA plasma
Reagents	Three: (1) latex coated with anti-cystatin C antibody, (2) Supplementary A (rabbit antibody), (3) Supplementary B (polyethylene glycol).	Two: R1 (buffer), R2 (latex coated with anti-cystatin C antibody from rabbit).
Technology / Methodology	Particle enhanced immunonephelometric assay	Latex enhanced turbidimetric assay
Number of Calibrators	1 (diluted on system to 6 levels)	6 (5 provided in package and zero-calibrator - DI water)
Calibrators	Urinary proteins of human origin, polygeline and preservatives (lyophilized).	Recombinant Cystatin C in human serum base (liquid).
Reportable Range	0.05 - 8.0 mg/L	0.1 - 8.0 mg/L

2. Sample Size Used for the Test Set and Data Provenance

The document states: "Comparative testing described in the protocol included in this submission demonstrates substantial equivalent performance."

Sample Size for Test Set: The specific sample size for the comparative testing (test set) is not explicitly mentioned in the provided text.
Data Provenance: The country of origin and whether the data was retrospective or prospective is not explicitly mentioned. Given it's a submission to the FDA in the US, it's highly probable that some or all of the data generation occurred in the US or under US regulatory guidelines.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This type of information (experts, qualifications) is typically related to diagnostic imaging or clinical interpretation where human judgment is a critical component of ground truth. For an in vitro diagnostic (IVD) like a Cystatin C blood test, the "ground truth" for the test set would be established by reference methods or validated laboratory results, not by human experts interpreting clinical data in the same way a radiologist would interpret an image.

Therefore, this information is not applicable in the context of this device and is not mentioned in the document.

4. Adjudication Method for the Test Set

Similar to point 3, adjudication methods (like 2+1, 3+1) are for resolving discrepancies in human expert interpretations. For an IVD, the "adjudication" would involve technical verification of reference methods and statistical comparison of analytical results.

Therefore, an adjudication method in this sense is not applicable and is not mentioned.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

An MRMC study is relevant for devices where multiple human readers interpret results, and the device's main benefit is to improve human reader performance (e.g., CAD for radiology). For an in vitro diagnostic like a Cystatin C assay, the device directly measures a biomarker; there is no "human reader" in the sense of interpreting complex diagnostic images or clinical scenarios.

Therefore, an MRMC study was not performed and is not applicable to this device type.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes, a standalone performance assessment was effectively done. The entire premise of this 510(k) submission is to demonstrate the analytical performance of the ADVIA Chemistry Cystatin C Method as a standalone assay, comparing its analytical characteristics (e.g., intended use, antibody, format, traceability, reference range, reportable range) directly against the predicate device. The performance data would primarily be objective analytical measurements from the device itself.

7. Type of Ground Truth Used

For this in vitro diagnostic device, the "ground truth" would be established by:

Reference methods: Highly accurate and precise laboratory methods for measuring Cystatin C.
Established analytical performance characteristics: The predicate device itself serves as a benchmark for "ground truth" in terms of expected analytical performance and clinical utility. The new device demonstrates substantial equivalence to these established characteristics.
Internal standards of highly purified human cystatin C: Used for traceability and calibration, indicating a defined chemical standard as part of establishing the truth for concentration measurements.

8. Sample Size for the Training Set

The document does not specify the sample size used for the training set. For an IVD, "training" typically refers to the development of calibration curves and optimization of the assay parameters rather than a classical machine learning training set with labeled data in the same way an AI model is trained.

9. How the Ground Truth for the Training Set Was Established

For an IVD like this, the "ground truth" for developing or "training" the assay (e.g., establishing calibration curves, optimizing reagents) would likely be established through:

Known concentrations of purified Cystatin C: Used to create calibration standards (as hinted by "internal standard of highly purified human cystatin C").
Standard laboratory methods: Validated methods to assign target values to control materials and calibrators.
Clinical panels: Samples from individuals with known physiological states (e.g., healthy controls, patients with renal disease at various stages) might be used during development to assess clinical correlation, though the analytical ground truth comes from quantitative measures.

The document directly mentions the use of "internal standard of highly purified human cystatin C" for traceability of calibrators, which is a key aspect of establishing ground truth for the quantitative measurement.

Summary

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510(k) Summary of Safety and Effectiveness for the

ADVIA® Chemistry Cystatin C Method

MAR 1 1 2009

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

A. 510(k) Number:

B. Date of Preparation: December 22, 2008

C. Proprietary and Established Names:

ADVIA® Chemistry Cystatin C Reagent ADVIA® Chemistry Cystatin C Calibrator

D. Applicant:

Siemens Healthcare Diagnostics Inc., 511 Benedict Ave, Tarrytown, NY 10591

Kira Gordon, Sr. Regulatory Affairs Specialist

Office: (914) 524-2996 Fax: (914) 524-2500

E. Regulatory Information:

ADVIA Chemistry Cystatin C Reagent

1. Regulation section: 21 CFR § 862.1225 Creatinine, test system.
1. Classification: Class II
1. Product Code: NDY, Test, Cystatin C
1. Panel: Clinical Chemistry

ADVIA Chemistry Cystatin C Calibrator

1. Regulation section: 21 CFR § 862.1150 Calibrator
1. Classification: Class II
1. Product Code: JIT, calibrator secondary
1. Panel: Clinical Chemistry

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F. Predicate Device:

ADVIA Chemistry Cystatin C reagent is substantially equivalent to the Dade Behring N Latex Cystatin C reagent cleared under K041878

ADVIA Chemistry Cystatin C calibrator is substantially equivalent to the Dade Behring N Protein Standard UY cleared under K003501.

G. Device Description:

H. Intended Use:

Reagent: For in vitro diagnostic use in the quantitative determination of Cystatin C (CYSC) in human serum or plasma on the ADVIA Chemistry systems. Measurement of Cystatin C aids in the diagnosis and treatment of renal disease.

Calibrator: For in vitro diagnostic use in the calibration of Cystatin C method on ADVIA Chemistry systems.

I. Substantial Equivalence Information:

The ADVIA Chemistry Cystatin C Method and (formerly) Dade Behring, Inc., N Latex Cystatin C methods were compared. A comparison of the important similarities and differences between the devices and the predicates is provided in the following tables:

.LA CAR SHEARsimilarities	A B = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = =.A REAL PRODUCT CONNUMBER	------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 4 - 4 - 4 - 4 - 4 - 4 - 4 - 4 - 4 - 4 - 4 - 4 - 4 - 4 - 4 - 4 - 4 - 4 - 4 - 4 - 4 - 4 - 4 - 4 - 4 - 4 - 4 - 4 -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
.called in the same may was	And Concession of Canadian Company of Children14-14-11-14a· · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·	1 12 65 511/2/11Property------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
A 46-44-4844na Vit	44-4-4-448-1-800-.	Company Control Concession Company of Children.

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Intended Use	Reagent: for in vitro diagnosticuse in the quantitativedetermination of cystatin C inhuman serum and plasma on theADVIA Chemistrysystems.Measurement of cystatinC aids in the diagnosis andtreatment of renal diseases.Calibrator: For in vitro diagnosticuse in the calibration of theCystatin C method on ADVIAChemistry systems.	Reagent: N Latex CYSC method isan in vitro diagnostic kit for thequantitative determination ofcystatin C in human serum andheparinized plasma. Cystatin Cmeasurements are used in thediagnosis and treatment of renaldiseases.Calibrator: For preparing referencecurves for theimmunonephelometricdeterminations of a-1-micorglobulinand Cystatin C using the BNsystems.
Antibody	Rabbit Polyclonal antibodies tohuman Cystatin C	Rabbit Polyclonal antibodies tohuman Cystatin C
Format	Liquid	Liquid
Use ofCalibrators	Yes	Yes
Traceability	internal standard of highly purifiedhuman cystatin C	internal standard of highly purifiedhuman cystatin C
Referencerange	0.56-0.95 mg/L	0.53 -0.95 mg/L
Differences
Item	Device	Predicate
SampleMatrix	Serum , Heparinized Plasma,EDTA plasma	Serum or Heparinized Plasma
Reagents	Two: R1 (buffer), R2 (latex coatedwith anti-cystatin C antibody fromrabbit) contained in systemspecific packaging	Three: (1) latex coated with anti-cystatin C antibody from rabbit, (2)Supplementary A (rabbit antibody),(3) Supplementary B (polyethyleneglycol) in system specific packaging
Technology /Methodology	Latex enhancedturbidimetric assay	Particle enhancedimmunonephelometric assay
Number ofCalibrators	6 (5 provided in package andzero-calibrator - DI water)	1 (diluted on system to 6 levels)
Calibrators	Recombinant Cystatin C in humanserum base (liquid)	Urinary proteins of human originpolygeline and preservatives(lyophilized)
Reportablerange	0.1 - 8.0 mg/L	0.05 - 8.0 mg/L

and the state of the states and

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J. Conclusion:

The ADVIA Chcmistry Cystatin C Method is substantially equivalent to the A Dade Behring, Inc., N Latex Cystatin C method cleared under K041878. Comparative testing described in the protocol included in this submission demonstrates substantial equivalent performance.

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Image /page/4/Picture/1 description: The image shows the seal for the Department of Health & Human Services. The seal is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES. USA" around the edge. In the center of the seal is an abstract image of an eagle.

MAR 1 1 2009

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Siemens Healthcare Diagnostics c/o Dr. Kira Gordon 511 Benedict Avenue Tarrytown, New York 10591

Re: K083906 Trade/Device Name: ADVIA Chemistry Cystatin C Reagent Regulation Number: 21CFR 862.1225 Regulation Name: Creatinine, test system Regulatory Class: Class II Product Code: NDY, JIT Dated: December 23, 2008 Received: December 30, 2008

Dear Dr. Gordon:

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 either class II (Special Controls) or class III (PMA), 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page - 2

This letter 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Corg C. He

Courtney C. Harper, Ph.D. Acting Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

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Indication for Use

510(k) Number (if known): K083906

Device Name:

ADVIA® Chemistry Cystatin C Reagent

ADVIA® Chemistry Cystatin C Calibrator

Indication For Use:

Calibrator: For in vitro diagnostic use in the calibration of Cystatin C method on ADVIA Chemistry systems.

Prescription Use
(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)

Rute Chealer

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

510(k) K 083906

Regulation Number and Section

§ 862.1225 Creatinine test system.

(a)
Identification. A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.(b)
Classification. Class II.