For in vitro diagnostic use in the quantitative determination of glucose in human serum, plasma, urine and CSF on the ADVIA 1650 Chemistry system. 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 1650 Chemistry Glucose Hexokinase 3 (GLUH 3) method uses a twocomponent 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

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Device: ADVIA® 1650 Chemistry Glucose Hexokinase 3 (GLUH 3) method

1. Table of Acceptance Criteria and Reported Device Performance

Category	Acceptance Criteria (Predicate Device K042015)	Reported Device Performance (ADVIA® GLUH 3)
Intended Use	Quantitative determination of glucose in human serum, plasma, urine, and CSF, for diagnosis and treatment of carbohydrate metabolism disorders.	Quantitative determination of glucose in human serum, plasma, urine, and CSF, for diagnosis and treatment of carbohydrate metabolism disorders (Same).
Sample Type	human serum, plasma (Li Heparin), urine, CSF	human serum, plasma (Li Heparin and K EDTA), urine, CSF
Instrument	ADVIA 1650 Chemistry	ADVIA 1650 Chemistry (Same)
Method Principle	Based on the method by Slein using hexokinase and glucose-6-phosphate dehydrogenase enzymes.	Same
Calibrators	Siemens Healthcare Diagnostics Chemistry Calibrator REF 09784096	Same
Reportable Range	0 - 700 mg/dL	4 - 700 mg/dL (Slightly narrower low end, but the overall range overlaps significantly with the predicate.)
Traceability	Standard reference material 965a from NIST	Same
Format	Concentrate	Liquid
Reagents	Three: R1, R2, and R2 mix	Two: R1 and R2
Interfering Substances (NSI)	Bilirubin-NSI to 25 mg/dL at glucose level of 80 mg/dL.Hemoglobin-NSI up to 500 mg/dL at glucose level of 80 mg/dL.Lipemia (Intralipid)-NSI to 500 mg/dL at glucose level of 80 mg/dL.	Bilirubin-NSI to 30 mg/dL at glucose level of 54 mg/dL.Hemoglobin-NSI up to 1000 mg/dL at glucose level of 52 mg/dL.Lipemia (Intralipid)-NSI to 1000 mg/dL. (Improved interference tolerance for Bilirubin, Hemoglobin, and Lipemia).
Precision (Total)	Serum: 2.2% at 74.7 mg/dL, 2.0% at 247.6 mg/dL.Urine: 4.1% at 45.8 mg/dL, 3.6% at 266.7 mg/dL.CSF: 3.1% at 36.9 mg/dL, 2.7% at 60.2 mg/dL.	Serum: 0.8% at 87 mg/dL, 0.7% at 297 mg/dL.Urine: 1.1% at 49 mg/dL, 1.9% at 301 mg/dL.CSF: 1.0% at 56 mg/dL, 0.8% at 97 mg/dL. (Significantly improved precision across all sample types and concentrations).
Accuracy / Correlation	Serum: Y = 1.02x - 1.84 (N=194, r=0.998) vs. ADVIA 1650 (ADVIA glucose-single reagent).Plasma (Li Heparin): Y = 1.00x - 0.09 (N=35, r=1.000).CSF: Y = 1.03x - 1.25 (N=55, r=0.987).Urine: Y = 0.97x - 7.44 (N=99, r=0.999).	Serum: Y = 1.001x + 0.3 (N=99, r=1.000) vs. ADVIA 1650 (ADVIA GLUH reagent).Plasma (Li-Heparin): Y = 1.001x + 0.2 (N=88, r=1.000).Plasma (K-EDTA): Y = 1.002x - 0.0 (N=87, r=1.000).CSF: Y = 1.005x - 0.1 (N=113, r=1.000).Urine: Y = 0.989x - 0.3 (N=51, r=1.000). (Shows very strong correlation with the predicate, with regression lines close to ideal Y=X and correlation coefficients very close to 1).

Study Proving Acceptance Criteria:

The study proving the device meets the acceptance criteria is a comparative testing study demonstrating substantial equivalence to the predicate device (ADVIA Chemistry Glucose Hexokinase II reagent, cleared under K042015). This is typical for a 510(k) submission where the new device is compared against a legally marketed predicate device.

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

Accuracy/Correlation Test Sets:
- Serum: N=99
- Plasma (Li-Heparin): N=88
- Plasma (K-EDTA): N=87
- CSF: N=113
- Urine: N=51
Precision Test Sets: The text provides precision percentages at different glucose levels for serum, urine, and CSF, but does not explicitly state the number of individual samples or replicates used for these tests. It's common for precision studies to involve multiple measurements of control materials or pooled patient samples over several days.
Interference Test Sets: The text indicates the maximum concentrations of interfering substances where "No Significant Interference" (NSI) was observed. It does not specify the number of samples used for these interference studies.
Data Provenance: The document does not explicitly state the country of origin of the data or whether the data was retrospective or prospective. However, given that Siemens Healthcare Diagnostics Inc. is based in Tarrytown, NY, and the submission is to the FDA, it is highly probable that the studies were conducted in the US and followed standard industry practices for in vitro diagnostic device validation. Assumed to be prospective validation studies as part of the device development process.

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

The concept of "experts" and "ground truth" as typically defined in imaging or diagnostic AI studies (e.g., radiologists interpreting images) is not directly applicable here. For an in vitro diagnostic device like a glucose assay, the "ground truth" is established by a reference method.

Reference Method: The predicate device itself (ADVIA 1650 (ADVIA GLUH reagent)) served as the reference method for the accuracy/correlation studies. This means the new device's readings were compared against the established, cleared method. In this context, the "qualification" of the predicate method is its prior FDA clearance (K042015) based on its own validation against accepted standards and potentially reference methods like isotope dilution mass spectrometry (IDMS) which are often traceable to NIST.

4. Adjudication Method for the Test Set:

Not applicable in the context of this type of in vitro diagnostic device study. Adjudication methods like "2+1" or "3+1" are typically used when there are subjective human interpretations (e.g., by multiple radiologists) that need to be resolved to establish ground truth for a diagnostic aid. For a quantitative chemistry analyzer, the output is a numerical value, and agreement is determined by statistical correlation and bias against a reference method.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done, and what was the effect size of how much human readers improve with AI vs without AI assistance:

Not applicable. This device is an in vitro diagnostic chemistry analyzer, not a diagnostic imaging AI tool designed to assist human readers. Therefore, an MRMC study and analysis of human reader improvement with AI assistance are not relevant.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

Yes, a standalone performance evaluation was done. The reported performance metrics (precision, accuracy/correlation, interference) are characteristics of the device itself, providing quantitative results directly from the instrument. While human operators are involved in running the analyzer and preparing samples, the core measurement and output are solely from the device's chemical reactions and detection system, without a human interpretation loop like in imaging diagnostics.

7. The Type of Ground Truth Used:

The ground truth for the comparative studies was established by comparison to the established, legally marketed predicate device (ADVIA 1650 (ADVIA GLUH reagent)). This is a common and accepted method for demonstrating substantial equivalence for 510(k) submissions in in vitro diagnostics. The "ground truth" of the predicate itself would have been established through correlation with recognized reference methods (e.g., standard reference materials from NIST, or other highly accurate laboratory methods) during its own clearance process.

8. The Sample Size for the Training Set:

The document does not specify a separate "training set" size. For traditional in vitro diagnostic devices like chemical reagents, there isn't typically an "algorithm training" phase in the same way there is for machine learning models. The development and optimization of the reagent formulation and assay parameters are guided by chemical and analytical principles, and then validated through analytical performance studies (like the ones presented). If there were any internal development studies that could be considered "training", their details are not provided in this 510(k) summary.

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

As there's no explicitly defined "training set" in the machine learning sense for this type of device, the concept of establishing ground truth for it doesn't directly apply. The method development likely involved iterative testing to achieve desired performance characteristics (e.g., sensitivity, specificity, linearity, interference profile) against known concentrations of glucose and interfering substances, often using reference materials or established laboratory methods as benchmarks during the development phase.

Summary

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MAR - 7 2011

510(k) Summary of Safety and Effectiveness for the

ADVIA® 1650 Chemistry Glucose Hexokinase 3 (GLUH 3) method

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: July 26, 2010

C. Proprietary and Established Names:

ADVIA® 1650 Chemistry Glucose Hexokinase 3 (GLUH 3) reagent

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 1650 Chemistry Glucose Hexokinase 3 Reagent

1. Regulation section: 21 CFR & 862.1345 Glucose test system.
1. Classification: Class II
1. Product Code: CFR. Hexokinase, Glucose
1. Panel: Clinical Chemistry

F. Predicate Device:

ADVIA 1650 Chemistry Glucose Hexokinase 3 reagent is substantially equivalent to the ADVIA Chemistry Glucose Hexokinase II reagent cleared under K042015

G. Device Description:

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H. Intended Use:

I. Substantial Equivalence Information:

The new device (Glucose Hexokinase 3 reagent) and the predicate device (Glucose Hexokinase II reagent) were compared. A comparison of the important features between the new device and the predicate device is provided in the following table:

Item	Device	Predicate
Analyte	Glucose	Same
Intended Use	For in vitro diagnostic use in thequantitative determination of glucose inhuman serum, plasma, urine and CSF onthe ADVIA 1650 Chemistry system.Such measurements are used in thediagnosis and treatment of carbohydratemetabolism disorders including diabetesmellitus, neonatal hypoglycemia,idiopathic hypoglycemia, and insulinoverdose	Same
Sample type	human serum, plasma, urine and CSF(plasma - Li Heparin and K EDTA)	human serum, plasma, urine and CSF(plasma – Li Heparin)
Instrument tobe used	ADVIA 1650 Chemistry	ADVIA 1650 Chemistry
MethodPrinciple	based on the method by Slein usinghexokinase and glucose-6-phosphatedehydrogenase enzymes.	Same
Calibrators	Siemens Healthcare DiagnosticsChemistry Calibrator REF 09784096	Same
Reportablerange	4 -700 mg/dL	0 -700 mg/dL
Traceability	Standard reference material 965a fromNIST	Same
Format	Liquid	Concentrate
Reagents	Two: R1 and R2	Three: R1, R2 and R2 mix
InterferingSubstances *	Bilirubin-NSI to 30 mg/dL at glucoselevel of 54 mg/dLHemoglobin-NSI up to 1000 mg/dL atglucose level of 52 mg/dLLipemia (Intralipid)-NSI to 1000 mg/dL	Bilirubin-NSI to 25 mg/dL at glucoselevel of 80 mg/dLHemoglobin-NSI up to 500 mg/dL atglucose level of 80 mg/dLLipemia (Intralipid)-NSI to 500 mg/dLat glucose level of 80 mg/dL

Precision(total)	0.8% at 87 mg/dL (serum)0.7% at 297 mg/dL (serum)1.1% at 49 mg/dL (urine)1.9% at 301 mg/dL (urine)1.0% at 56 mg/dL (CSF)0.8% at 97 mg/dL (CSF)	2.2% at 74.7 mg/dL (serum)2.0% at 247.6 mg/dL (serum)4.1% at 45.8 mg/dL (urine)3.6% at 266.7 mg/dL (urine)3.1% at 36.9 mg/dL (CSF)2.7% at 60.2 mg/dL (CSF)
Accuracy /Correlation	Serum:$Y = 1.001x + 0.3$ ; N=99 r=1.000 (vs.ADVIA 1650 (ADVIA GLUH reagent)Plasma (Li-Heparin):$Y = 1.001x + 0.2$ , N=88; r=1.000Plasma (K-EDTA)$Y = 1.002x - 0.0$ , N=87; r=1.000CSF:$Y = 1.005x - 0.1$ , N=113; r=1.000Urine:$Y = 0.989x - 0.3$ , N=51; r=1.000	Serum:$Y = 1.02x - 1.84$ ; N=194 r=0.998 (vs.ADVIA 1650 (ADVIA glucose-singlereagent formulation))Plasma (Li Heparin):$Y = 1.00x - 0.09$ , N=35; r=1.000CSF:$Y = 1.03x - 1.25$ , N=55; r=0.987Urine:$Y = 0.97x - 7.44$ , N=99; r=0.999

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

J. Conclusion:

Comparative testing of the ADVIA 1650 Chemistry Glucose Hexokinase_3 reagent demonstrates substantially equivalent performance to the ADVIA Chemistry Glucosc Hexokinasc II reagent cleared under K042015.

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Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002

HAR 0 7 2011

Siemens Healthcare Diagnostics, Inc. c/o Kira Gordon Senior Regulatory Affairs Specialist 511 Benedict Avenue. Tarrytown, NY. 10591. USA

Re: K101854

Trade/Device Name: ADVIA Chemistry Glucose Hexokinase (GLUH_3) Reagent Regulation Number: 21 CFR 862.1345 Regulation Name: Glucose Test System Regulatory Class: Class II Product Code: CFR Dated: February 23, 2011 Received: February 24, 2011

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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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.

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

Sincerely yours.

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

Enclosure

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Indication for Use

KIDI854 510(k) Number (if known):

Device Name:

ADVIA® Chemistry GLUH_3 Reagent

Indication For Use:

Prescription Use V _ (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)

Carol C. Benett

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K101854

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.