ADVIA Chemistry Enzyme 1 Calibrator is intended for in vitro diagnostic use in the calibration of Gamma-Glutamyl Transferase (GGT), Lactate Dehydrogenase P-L (LDPL), Lactate Dehvdrogenase L-P (LDLP), Cholinesterase (CHE), and Lipase (LIP) assays on the ADVIA Chemistry systems.

ADVIA® Chemistry Enzyme 2 Calibrator is intended for in vitro diagnostic use in the calibration of Alanine Aminotransferase (ALT); Alanine Aminotransferase, Concentrated Reagents (ALT c); Alanine Aminotransferase (P5P) (ALTP5P); Alanine Aminotransferase (P5P), Concentrated Reagents (ALTP c); Aspartate Aminotransferase (AST); Aspartate Aminotransferase, Concentrated Reagents (AST_c); Aspartate Aminotransferase (PSP)(ASTP5P); and Aspartate Aminotransferase (P5P), Concentrated Reagents (ASTP_c) assays on the ADVIA Chemistry systems.

Device Description

The ADVIA® Chemistry Enzyme 1 Calibrator and Enzyme 2 Calibrator are liquid, multianalyte, bovine serum albumin based products. Enzyme 1 Calibrator kit consists of six vials of the same calibrator which is ready for use (no preparation is required). The volume per vial is 2.5 mL. Enzyme 2 Calibrator kit consists of six vials of calibrator of the same level which is ready for use (no preparation is required). The volume per vial is 1.5 mL.

AI/ML Overview

The provided document describes the Siemens ADVIA® Chemistry Enzyme 1 and Enzyme 2 Calibrators, which are intended for in vitro diagnostic use in the calibration of various enzyme assays. The document is a 510(k) summary, which aims to demonstrate substantial equivalence to previously cleared predicate devices.

Here's an analysis of the acceptance criteria and the study information based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document explicitly states: "Acceptance criteria is the mean concentration should be within ±15% of the target value." This acceptance criterion is applied during the verification of the commercial calibrator lot.

Performance Metric	Acceptance Criteria (ADVIA Chemistry Enzyme 1 & 2 Calibrators)	Reported Device Performance
Commercial Calibrator Lot Verification	Mean concentration within ±15% of the target value	"the concentration of each analyte is verified to be within acceptable range by using an instrument calibrated with Master Lot Calibrators." (Implies acceptance criteria were met)
Stability (Shelf-life)	Not explicitly stated, but "acceptance criteria were met."	"minimum 6 months at 2-8°C at launch" (Enzyme 1 & 2 Calibrator)
Stability (Open-vial)	Not explicitly stated, but "acceptance criteria were met."	"30 days at 2-8°C" (Enzyme 1 & 2 Calibrator)

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

For the commercial calibrator lot value assignment:

Sample Size: "Each instrument is calibrated using the Masterpool. The calibrators are run as unknowns with n=20 replicates." This indicates a sample size of 20 replicates for each analyte on each of the two instruments. The total number of calibrator vials used was three.
Data Provenance: The data is prospective, generated during the manufacturing and verification process of the new calibrator lots. The country of origin is not explicitly stated but is implied to be where Siemens Healthcare Diagnostics Inc. (Tarrytown, NY) conducts its manufacturing and testing.

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

This information is not applicable in the context of calibrator performance. The "ground truth" for calibrators is their assigned target concentration based on reference materials and established methods, not clinical interpretation by experts.

4. Adjudication Method for the Test Set

This is not applicable as the "test set" involves quantitative measurements against target values, not subjective interpretations requiring adjudication.

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

No. This type of study is for comparing human reader performance, typically in diagnostic imaging or similar fields. This document is about calibrator performance in a laboratory setting.

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

Yes, in a sense. The core "performance" described is the ability of the calibrator lots to meet their target concentration specifications when measured on the ADVIA Chemistry systems, without direct human cognitive input influencing the measurement results. The setup involves instruments measuring the calibrators as "unknowns," which is a form of standalone performance measurement for the calibrator's assigned values.

7. Type of Ground Truth Used

The ground truth for the calibrator's value assignment is based on:

Reference Materials: For several analytes (LDLP, GGT, ALT, AST), the ground truth is traceable to IFCC Reference materials or IFCC Reference methods.
Molar Extinction Coefficient: For CHE and LDPL, the ground truth relies on the molar extinction coefficient of the reaction product or NADH, respectively.
Internal Standard: For LIP, an internal standard is used.
Master Lot Assigned Bottle Values: Initially, the stock solution concentration is determined by comparison to Master Lot assigned bottle values, which themselves would be traceable to the aforementioned reference standards/methods.

8. Sample Size for the Training Set

This product is a calibrator, not an algorithm that requires a "training set" in the machine learning sense. The concept of a training set is not applicable here.

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

As explained above, there is no "training set" as this is not an AI/ML algorithm. The "ground truth" for the calibrators' assigned values is established through traceability to international reference materials, molar extinction coefficients, and internal standards, as detailed in point 7.

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

SIEMENS HEALTHCARE DIAGNOSTICS, INC. KIRA GORDON SR. REGULATORY AFFAIRS SPECIALIST 511 BENEDICT AVENUE TARRYTOWN NY 10591

December 18, 2015

Re: K153365

Trade/Device Name: ADVIA® Chemistry Enzyme 1 Calibrator, ADVIA® Chemistry Enzyme 2 Calibrator Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: II Product Code: JIX Dated: November 19, 2015 Received: November 20, 2015

Dear Kira 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Katherine Serrano -S

For : Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K153365

Device Name ADVIA® Chemistry Enzyme 1 Calibrator

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

*DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW."

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

510(k) Number (if known) K153365

Device Name ADVIA® Chemistry Enzyme 2 Calibrator

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

2 Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW .

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

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510(k) Summary of Safety and Effectiveness for the ADVIA® Chemistry Enzyme 1 Calibrator and ADVIA® Chemistry Enzyme 2 Calibrator

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.

1. 510(k) Number: K153365

2. Applicant:

Contact: Kira Gordon, PhD Sr. Regulatory Affairs Specialist Siemens Healthcare Diagnostics Inc Address: 511 Benedict Ave, Tarrytown, NY 10591 (914) 524-2996 Phone: (914) 524-3579 (FAX)

1. Date: November 19, 2015

4. Proprietary and Established Names:

ADVIA® Chemistry Enzyme 1 Calibrator ADVIA® Chemistry Enzyme 2 Calibrator

5. Regulatory Information:

Regulation section: 21 CFR $862.1150, calibrator, multi-analyte mixture Classification: Class II Product Code: JIX Panel: Clinical Chemistry

6. Predicate Device:

Device Name: Dimension® Vista ENZ 1 CAL; Dimension® Vista ENZ 2 CAL 510(k) Number: K061923; K103612 Manufacturer: Siemens Healthcare Diagnostics Inc.

7. Intended Use:

See Indications for Use

8. Indications for Use:

ADVIA® Chemistry Enzyme 1 Calibrator is for in vitro diagnostic use in the calibration of Gamma-Glutamyl Transferase (GGT), Lactate Dehydrogenase P-L (LDPL), Lactate Dehydrogenase L-P (LDLP), Cholinesterase (CHE), and Lipase (LIP) assays on the ADVIA Chemistry systems

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ADVIA® Chemistry Enzyme 2 Calibrator is for in vitro diagnostic use in the calibration of Alanine Aminotransferase (ALT); Alanine Aminotransferase, Concentrated Reagents (ALT_c); Alanine Aminotransferase (ALTP5P); Alanine Aminotransferase (P5P), Concentrated Reagents (ALTP_c); Aspartate Aminotransferase (AST); Aspartate Aminotransferase, Concentrated Reagents (AST c); Aspartate Aminotransferase (PSP) (ASTP5P); and Aspartate Aminotransferase (P5P), Concentrated Reagents (ASTP c) assays on the ADVIA Chemistry systems

Special Conditions for Use Statement(s): For prescription use only

9. Device Description:

10. Test Principle

ADVIA® Chemistry Enzyme 1 Calibrator is intended for in vitro diagnostic use in the calibration of Chemistry Gamma-Glutamy] Transferase (GGT), Lactate Dehydrogenase (LDPL and LDLP), Cholinesterase (CHE), and Lipase (LIP) assays on the ADVIA® Chemistry systems

ADVIA® Chemistry Enzyme 2 Calibrator is intended for in vitro diagnostic use in the calibration of Alanine Aminotransferase (ALT, ALT_c, ALTP5P, ALTP_c) Assays and Aspartate Aminotransferase (AST, AST_c, ASTP5P, ASTP_c) Assays on the ADVA® Chemistry systems

11. Substantial Equivalence Information:

Predicate device name: Dimension® Vista Enzyme 1 Calibrator Predicate K number: K061923 Comparison with Predicate:

Item	New Device:	Predicate Device:
Intended Use	for in vitro diagnostic use in thecalibration of Gamma-Glutamyl Transferase (GGT),Lactate Dehydrogenase P-L (LDPL), Lactate Dehydrogenase L-P (LDLP),Cholinesterase (CHE), and Lipase (LIP) assays on the ADVIA Chemistry systems	in vitro diagnostic product for thecalibration of Amylase (AMY),Gamma-Glutamyl Transferase (GGT),Lactate Dehydrogenase (LDH), Lipase (LIPL), and Pseudocholinesterase (PCHE) methods
Instrument	ADVIA Chemistry Systems	Dimension Vista Clinical Chemistry System
MeasuredAnalytes (valueassigned)	Gamma-Glutamyl Transferase,Lactate Dehydrogenase,Lipase,Cholinesterase (Pseudocholinesterase)	Gamma-Glutamyl Transferase,Lactate Dehydrogenase,Lipase,PseudocholinesteraseAmylase
Form	Liquid	Same

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Matrix	bovine serum albumin based product	Same
Analyte source	gamma-glutamyl transferase (bovinekidney)lactate dehydrogenase (chicken heart)lipase (porcine pancreas)pseudocholinesterase (horse serum)	gamma-glutamyl transferase (bovinekidney)lactate dehydrogenase (chicken heart)lipase (porcine pancreas)pseudocholinesterase (horse serum)amylase (human saliva)
Number of levels	One	Two
Targetconcentrations(U/L)	Gamma-glutamyl transferase - 840Lactate dehydrogenase L-P - 350Lactate dehydrogenase P-L - 780Lipase - 100Cholinesterase – 14200Amylase – N/A	Gamma-glutamyl transferase – 0, 840Lactate dehydrogenase – 0, 350Lipase - 0, 1612Cholinesterase - 0, 14700Amylase – 0, 682
Fill Volume	2.5 mL	Same
Stability	Shelf-life – minimum 6 months at 2-8°Cat launchOpen-vial - 30 days at 2-8°C	Shelf-life – 12 months at 2-8°COpen-vial – 30 days at 2-8°C

Dimension® Vista Enzyme 2 Calibrator Predicate device name:
Predicate K number: K103612 Comparison with Predicate:

Item	New Device:	Predicate Device:
Intended Use	for in vitro diagnostic use in thecalibration of Alanine Aminotransferase(ALT); Alanine Aminotransferase,Concentrated Reagents (ALT_c); AlanineAminotransferase (ALTP5P); AlanineAminotransferase (P5P), ConcentratedReagents (ALTP_c); AspartateAminotransferase (AST); AspartateAminotransferase, ConcentratedReagents (AST_c); AspartateAminotransferase (P5P) (ASTP5P); andAspartate Aminotransferase (P5P),Concentrated Reagents (ASTP_c) assayson the ADVIA Chemistry systems	Is an in vitro diagnostic product forthe calibration of alanineaminotransferase (ALT and ALTI)and aspartate aminotransferase (AST)methods
Instrument	ADVIA Chemistry Systems	Dimension Vista Clinical ChemistrySystem
MeasuredAnalytes (valueassigned)	Alanine aminotransferase and aspartateaminotransferase	Same
Form	Liquid	Same
Matrix	bovine serum albumin based product	Same
Analyte source	alanine aminotransferase (porcine heart)aspartate aminotransferase (porcineheart)	Same

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Number of levels	One	Two
Targetconcentrations(U/L)	AST, AST_c, ASTP5P, ASTP_c – 500ALT, ALT_c, ALTP5P, ALTP_c – 500	AST – 0, 1050ALT – 0, 1050
Fill Volume	1.5 mL	Same
Stability	Shelf-life – min 6 months at 2-8°C atlaunchOpen-vial - 30 days at 2-8°C	Shelf-life – 12 months at 2-8°COpen-vial - 30 days at 2-8°C

12. Standard/Guidance Document Reference

The following recognized standard and guidance documents were used:

CEN 13640 Stability Testing of In Vitro Diagnostic Reagents ●
Guidance for Industry Abbreviated 510(k) Submissions for In Vitro Diagnostic ● Calibrators

13. Performance Characteristics

The following studies are not applicable for the purpose of this submission:

Precision/Reproducibility ●
- Linearity/Assay Reportable Range .
- Detection limit ●
- Method and Matrix Comparison Studies
- Analytical Specificity
- Assay cut-off
- Expected Values/Reference Interval ●

Stability:

Real-time stability studies for shelf-life and open-vial claims have been conducted and acceptance criteria were met.

ADVIA Chemistry Enzyme 1 Calibrator is to be stored at 2-8°C until the expiration date printed on each carton. ADVIA Chemistry Enzyme 2 Calibrator is to be stored at 2-8℃ until the expiration date printed on each carton. Real-time stability studies for shelf-life are ongoing. The final shelf life claims will be based on the completed real-time study results. For opened products, once the cap is removed, assigned values are stable for 30 days when recapped immediately after use and stored at 2-8℃.

Traceability and Value Assignment

To manufacture calibrator, a stock solution is prepared by gravimetrically adding quantities of analytes to bovine serum albumin base to the target concentrations. The stock solution concentration is determined by comparing the recovery of the stock solution versus the Master Lot assigned bottle values. Calculated quantities of the stock solution are added to the bovine serum albumin base to the target concentrations to produce the commercial calibrator lot. The concentration of each analyte is verified to be within acceptable range by using an instrument calibrated with Master Lot Calibrators.

Production lot calibrator value assignments are completed using two ADVIA 1800 Chemistry systems, two reagents lots, and three vials of calibrator. Each instrument is

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calibrated using the Masterpool. The calibrators are run as unknowns with n=20 replicates. Acceptance criteria is the mean concentration should be within ±15% of the target value. Traceability: The assigned values of the Enzyme 1 Calibrator and Enzyme 2 Calibrator are traceable as listed in the following table:

Product	Analyte	Traceability
Enzyme 1	CHE	molar extinction coefficient of the reaction product
Calibrator	LDLP	IFCC Reference material (IFCC-453)
	LDPL	extinction coefficient of the NADH
	LIP	Internal Standard
	GGT	IFCC Reference material (IFCC-452)
Enzyme 2	ALT (ALT, ALT_c,ALTP5P, ALTP_c)	IFCC Reference material (IFCC-454)
Calibrator	AST (AST, AST_c,ASTP5P, ASTP_c)	IFCC Reference method

14. Conclusions

The ADVIA Chemistry Enzyme 1 Calibrator is substantially equivalent to the Siemens Dimension Vista ENZ 1 Calibrator cleared under K061923. Based on the testing and the comparisons with the predicate device, the ADVIA Chemistry Enzyme 1 Calibrator is substantially equivalent to the Dimension Vista ENZ 1 Calibrator.

The ADVIA Chemistry Enzyme 2 Calibrator is substantially equivalent to the Siemens Healthcare Diagnostics Dimension Vista ENZ 2 Calibrator cleared under K103612. Based on the testing and the comparisons with the predicate device, the ADVIA Chemistry Enzyme 2 Calibrator is substantially equivalent to the Dimension Vista ENZ 2 Calibrator.

Regulation Number and Section

§ 862.1150 Calibrator.

(a)
Identification. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. (See also § 862.2 in this part.)(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 § 862.9.