For in vitro diagnostic use in the quantitative determination of glucose in human serum, plasma, urine and CSF on the ADVIA Chemistry systems. Such measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia, and insulin overdose.

Device Description

The ADVIA Chemistry Glucose Hexokinase 3 (GLUH 3) method uses a two-component reagent. Sample is added to Reagent 1, which contains the buffer, ATP, and NAD. Absorbance readings of the sample in Reagent 1 are taken and are used to correct for interfering substances in the sample. Reagent 2 is added, which initiates the conversion of glucose and the development of absorbance at 340/410 nm. The difference between the absorbance in Reagent 1 and Reagent 2 is proportional to the glucose concentration.

AI/ML Overview

1. Acceptance Criteria and Device Performance

Acceptance Criteria (Predicate Device K101854 - using serum, Li-Heparin plasma, K-EDTA plasma)	Reported Device Performance (New Device - K120681, specifically for Na-Fluoride/K-Oxalate plasma)
Regression Equation: Y = 1.001x + 0.3 (Serum), Y = 1.001x + 0.2 (Li-Heparin), Y = 1.002x - 0.0 (K-EDTA)	Regression Equation: Y = 1.011x + 0.8 (Na-Fluoride/K-Oxalate plasma)
Correlation Coefficient (r): 1.000 (Serum, Li-Heparin, K-EDTA)	Correlation Coefficient (r) for Na-Fluoride/K-Oxalate plasma: 0.999
(Implicitly similar slopes and intercepts to show substantial equivalence for existing plasma types)	Slope 95% CI: 1.003 to 1.019 (contains 1, suggesting good linearity)
	Intercept 95% CI: -1.18 to 2.73 (contains 0, suggesting minimal bias)
	Sample Range: 2-601 mg/dL (covering clinically relevant range)

The acceptance criteria for the new device (specifically for the Na-Fluoride/K-Oxalate plasma type) are implicitly based on demonstrating substantial equivalence to the predicate device's performance with other plasma types. The reported performance for the new plasma type shows a strong correlation (r=0.999) and a regression equation very close to ideal (slope near 1, intercept near 0), indicating good agreement with the serum measurements using the existing GLUH_3 assay.

2. Sample Size and Data Provenance for Test Set

Sample Size for Test Set: 82 data-points were included in the calculations. This was derived from 56 matched serum and plasma (Sodium Fluoride/Potassium Oxalate) samples, with some samples being spiked and/or diluted to achieve a wider range of concentrations.
Data Provenance: Not explicitly stated, but based on the context of a 510(k) submission by Siemens Healthcare Diagnostics Inc., the data is likely from internal studies conducted in a controlled laboratory environment. It is a prospective study as it involves new testing for the expanded sample type.

3. Number of Experts and Qualifications for Ground Truth (Test Set)

Number of Experts: Not applicable. This study is a method comparison for an in vitro diagnostic device, not an interpretation of images or clinical cases by experts.
Qualifications of Experts: N/A

4. Adjudication Method (Test Set)

Adjudication Method: Not applicable. Ground truth for this type of device comparison is established by reference measurement methods or the predicate device's results, not through expert adjudication of subjective interpretations.

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

MRMC Study: No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typically performed for image-based diagnostic devices where human interpretation plays a significant role.
Effect Size of AI Improvement: N/A

6. Standalone Performance Study

Standalone Performance: Yes, a standalone performance study was done for the algorithm (the ADVIA Chemistry GLUH_3 assay) using the new Na-Fluoride/K-Oxalate plasma type. The study compared the results obtained with this new plasma type against results obtained from serum samples using the predicate device's established method. The reported regression equation and correlation coefficient demonstrate the standalone performance of the device with the new sample type.

7. Type of Ground Truth Used

Type of Ground Truth: The ground truth for the comparison study was established by the results obtained from serum samples using the predicate ADVIA Chemistry GLUH_3 assay (K101854). This is a common approach for method comparison studies for IVD devices, treating the established method (here, using serum) as the reference or "ground truth" to determine the performance of the new application (using Na-Fluoride/K-Oxalate plasma).

8. Sample Size for Training Set

Sample Size for Training Set: Not explicitly mentioned as a separate "training set" in the context of this 510(k) summary. For in vitro diagnostic assays, the development and initial validation (which might be analogous to "training") typically involve numerous experiments and data points to optimize the reagent formulation and assay parameters. The submitted data focuses on the verification and validation of the new sample type's performance against the established method.

9. How Ground Truth for Training Set was Established

How Ground Truth for Training Set was Established: As noted above, a distinct "training set" with established ground truth is not typically described in this manner for IVD assay submissions. The development of the ADVIA Chemistry GLUH_3 reagen itself (prior to this modification) would have involved extensive analytical studies, including:
- Using certified reference materials.
- Comparing results to established reference methods (e.g., isotope dilution mass spectrometry, enzymatic reference methods).
- Correlation with clinically validated predicate devices.
For this particular modification, the existing, cleared GLUH_3 reagent used with serum (and other plasma types) serves as the reference, and the new plasma type's performance is evaluated against this established performance.

Summary

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K120681

510(k) Summary

MAY 1 5 2012

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.

Submitter's Name:	Kira GordonSiemens Healthcare Diagnostics Inc.511 Benedict Ave,Tarrytown, NY 10591
Date of Preparation:	May 10, 2012
Name of Product:	ADVIA® Chemistry Glucose Hexokinase_3 (GLUH_3) reagen
FDA Classification Name:	Glucose test system.

Predicate Device:

The following table describes the predicate devices, device classification, regulation and product code associated with this pre-market notification:

New Product	Predicate Device	510(k) number	Device Class	Regulation	Product Code
ADVIA®ChemistryGLUH_3 Reagent(additionalplasma type)	ADVIA®ChemistryGLUH_3 Reagent	K101854	Class II	862.1345	CFR

Device Description: 1

Intended Use:

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Comparison to Predicate Device:

A comparison of the important features of the devices are provided in the following table:

Item	New Device	Predicate Device
Analyte	Glucose	Same
Intended Use	For in vitro diagnostic use in thequantitative determination of glucose inhuman serum, plasma, urine and CSF onthe ADVIA Chemistry systems. Suchmeasurements are used in the diagnosisand treatment of carbohydratemetabolism disorders including diabetesmellitus, neonatal hypoglycemia,idiopathic hypoglycemia, and insulinoverdose	Same
Sample type	human serum, plasma, urine and CSF	Same
Plasma type	Li-Heparin, K-EDTA andNa-Fluoride/K-Oxalate	Li-Heparin, K-EDTA
Instrument tobe used	ADVIA Chemistry	Same
MethodPrinciple	based on the method by Slein usinghexokinase and glucose-6-phosphatedehydrogenase enzymes.	Same
Calibrators	Siemens Healthcare DiagnosticsChemistry Calibrator REF 09784096	Same
Assay range	4 -700 mg/dL	Same
Accuracy /Correlation	Serum:$Y = 1.001x + 0.3$ ; N=99 r=1.000Plasma (Li-Heparin):$Y = 1.001x + 0.2$ , N=88; r=1.000Plasma (K-EDTA)$Y = 1.002x - 0.0$ , N=87; r=1.000Plasma (Na Fluoride/Potassium Oxalate)$Y = 1.011x + 0.8$ , N=82; r=0.999CSF:$Y = 1.005x - 0.1$ , N=113; r=1.000Urine:	Serum:SamePlasma (Li-Heparin):samePlasma (K-EDTA)SamePlasma (Na Fluoride/Potassium Oxalate)noneCSF:SameUrine:Same

Comments on Substantial Equivalence:

Analytical performance:

a. Precision/Reproducibility:
Not applicable for this modification.

b. Linearity/assay reportable range:

Not applicable for this modification.

c. Traceability (controls, calibrators, or method): Not applicable for this modification.

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d. Detection limit (functional sensitivity):

Not applicable for this modification.

e. Analytical specificity:
Not applicable for this modification.
f. Assay cut-off:
Not applicable.

2. Comparison studies: ·

a. Method comparison with predicate device:

Not applicable for this modification.

b. Matrix comparison: .

56 matched serum and plasma (Sodium Fluoride/Potassium Oxalate) samples were evaluated. Some of these samples were spiked and/or diluted. There were a total of 82 data-points included in calculations. Matrix

Comparison between serum and Na FI plasma tubes using the ADVIA 1650 Chemistry GLUH_3 assay gave the following correlation statistics using the
linear regression calculations:

x - serum, y -Sodium Fluoride/Potassium Oxalate plasma

Regression Equation			Sample Range
v=1.011 * x + 0.8
Slope 95% CI: 1.003 to 1.019	6.13	0.999	ર-601
Intercept 95% Cl: -1.18 to 2.73

Clinical studies:

a. Clinical sensitivity:

Not applicable for this submission.

b. Clinical specificity:

Not applicable for this submission.

1. Clinical cut-off:
  Not applicable for this submission.

Expected values/Reference range:

Not applicable for this modification.

Conclusion:

Comparative testing of the ADVIA 1650 Chemistry Glucose Hexokinase 3 reagent using Sodium Fluoride/Potassium Oxalate plasma type demonstrates substantially equivalent performance to the GLUH_3 reagent using serum as a plasma type cleared under K101854.

Kira Gordon Regulatory Affairs & Compliance May 10, 2012

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Image /page/3/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three stripes forming its body and wing. The eagle faces left. Encircling the eagle is the text "DEPARTMENT OF HEALTH & HUMAN SERVICES-USA" in all capital letters.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration

10903 New Hampshire Avenue Silver Spring, MD 20993

Siemens Healthcare Diagnostics Inc. c/o Kira Gordon 511 Benedict Ave Tarrytown, N.Y. 10509

MAY 1 5 2012

Re: K120681

Trade Name: Advia® Chemistry GLUH 3 Reagent Regulation Number: 21 CFR §862.1345 Regulation Name: Glucose test system Regulatory Class: Class II Product Codes: CFR Dated: March 2, 2012 Received: March 6, 2012

Dear Ms 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); 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).

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Page 2

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), 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 postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/Medical

Devices/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) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm

Sincerely yours,

N. Kim, Ph.D.

Couriney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indication for Use

510(k) Number (if known):

Device Name:

ADVIA® Chemistry GLUH 3 Reagent

Indication For Use:

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 (OVD)

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

510(k) R 120681

Page 1 of 1

Regulation Number and Section

§ 862.1345 Glucose test system.

(a)
Identification. A glucose test system is a device intended to measure glucose quantitatively in blood and other body fluids. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.(b)
Classification. Class II (special controls). The device, when it is solely intended for use as a drink to test glucose tolerance, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.