For in vitro diagnostic use in the calibration of Phenobarbital 2 (PHNB 2), Phenytoin 2 (PHNY_2), and Theophylline_2 (THEO_2) methods on the ADVIA Chemistry Systems .

Device Description

ADVIA Chemistry DRUG Calibrator I is a multi-analyte, liquid, human serum based product containing multiple analytes. The kit consists of 2 vials each of 5 calibrator levels which are ready for use (no preparation is required). The volume per vial is 3.0 mL. Phenobarbital, Phenytoin, and Theophylline are value assigned for ADVIA Chemistry systems. In addition DRUG Calibrator I also contains Lithium and Digoxin with no specific value assignment on ADVIA Chemistry systems at this time.

AI/ML Overview

The provided document is a 510(k) summary for the ADVIA® Chemistry DRUG Calibrator I, which is a calibrator device used in laboratory settings. This type of device does not typically involve the acceptance criteria, study designs, and human reader performance metrics that are common for diagnostic imaging or AI-driven decision support tools. Instead, the "acceptance criteria" for a calibrator are primarily related to its ability to accurately calibrate specific assays and its substantial equivalence to a predicate device.

Here's an analysis based on the information provided, framed to address your questions where applicable, but noting limitations for others given the device type:

1. A table of acceptance criteria and the reported device performance

For a calibrator like the ADVIA® Chemistry DRUG Calibrator I, the primary "acceptance criterion" for 510(k) clearance is demonstrated substantial equivalence to a legally marketed predicate device. This is achieved by showing that the new device has the same intended use, technological characteristics, and performs as well as or better than the predicate device without raising new questions of safety or effectiveness.

The study presented focuses on justifying substantial equivalence rather than reporting a specific performance metric against a numerical acceptance criterion in the way an AI-driven diagnostic device might.

Acceptance Criterion (Implicit for Substantial Equivalence)	Reported Device Performance (Comparison with Predicate)
Intended Use: Same as predicate.	"for in vitro diagnostic use in the calibration of Phenobarbital_2 (PHNB_2), Phenytoin_2 (PHNY_2), and Theophylline_2 (THEO_2) methods on the ADVIA Chemistry Systems." This is largely the same as the predicate, though the new device is specified for ADVIA systems, and the predicate listed more analytes for calibration. However, the measured (value-assigned) analytes are identical.
Formulation/Analytes Present: Similar composition.	Both devices contain Digoxin, Phenobarbital, Phenytoin, Theophylline, and Lithium.
Measured Analytes (Value Assigned): Same analytes calibrated.	Both devices calibrate for Phenobarbital, Phenytoin, and Theophylline. (Predicate also calibrated Digoxin and Lithium)
Physical Form: Same.	Both are "Liquid".
Traceability: Same standard.	Both are "USP" (United States Pharmacopeia) traceable.
Matrix: Same.	Both use "Human Serum".
Number of Levels: Same.	Both have "five" levels.
Packaging: Similar.	Both have "Ten vials: two vials at five levels (3.0 mL each)".
Stability: Same.	Both have "18 months - shelf-life" and "90 days open vial" stability.

Summary of Acceptance: The device was accepted because it was found to be "substantially equivalent" to the predicate device, meaning it meets the regulatory requirements for safety and effectiveness for its intended use as a calibrator. All compared parameters were either identical or very similar, supporting this conclusion.

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

This type of information (sample size for a test set, data provenance, retrospective/prospective) is typically for studies evaluating the diagnostic performance of a device on patient samples. For a calibrator, the "study" is a comparison to a predicate device and verification of its intrinsic characteristics (e.g., stability, traceability, composition). The document does not describe patient-level data or a "test set" in the traditional sense. The "sample" here refers to the calibrator product itself, and its characteristics were evaluated. No country of origin for "data" is relevant as it's about product properties.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

Not applicable. This calibrator device does not involve expert interpretation or ground truth establishment in the context of diagnostic performance on patient cases. Its "ground truth" (or accurate values) would be established through a rigorous metrological traceability chain, often to primary reference materials, as indicated by "USP traceability."

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable. There is no diagnostic "test set" or human judgment requiring adjudication for a calibrator.

5. 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 not a diagnostic device involving human readers or AI assistance.

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

Not applicable. This is not an algorithm or AI device.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

For a calibrator, the "ground truth" for the analytes within it is established through a chain of traceability to reference materials and/or established reference methods. The document states "Traceability: USP," meaning the values assigned to the analytes (Phenobarbital, Phenytoin, Theophylline) in the calibrator are traceable to standards set by the United States Pharmacopeia, which ensures their accuracy and consistency.

8. The sample size for the training set

Not applicable. This is not a machine learning or AI device that requires a training set.

9. How the ground truth for the training set was established

Not applicable. As above, there is no training set for this device.

Summary

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510(k) Summary of Safety and Effectiveness for the

ADVIA® Chemistry DRUG Calibrator I

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: K093732

B. Date of Preparation: December 03, 2009

C. Proprietary and Established Names:

MAR 2 2 2010

ADVIA® Chemistry DRUG Calibrator I

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 DRUG Calibrator I

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

F. Predicate Device:

ADVIA Chemistry DRUG Calibrator I is substantially equivalent to the (formerly) Dade Behring Dimension Drug Calibrator (DC22B) cleared under K011035.

G. Device Description:

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Chemistry systems. In addition DRUG Calibrator I also contains Lithium and Digoxin with no specific value assignment on ADVIA Chemistry systems at this time.

H. Intended Use:

The ADVIA Chemistry DRUG Calibrator I is for in vitro diagnostic use in the calibration of Phenobarbital (PHNB_2), Phenytoin (PHNY_2), and Theophylline (THEO 2) methods on the ADVIA Chemistry Systems

I. Substantial Equivalence Information:

The ADVIA Chemistry DRUG Calibrator I and Dimension Drug Calibrator I were compared in the following table.

Item	New Device - The ADVIAChemistry DRUG Calibrator I	Predicate Device - (formerly) DadeBehring Dimension Drug Calibrator(DC22B)
Intended Use	for in vitro diagnostic use in thecalibration of Phenobarbital_2(PHNB_2), Phenytoin_2 (PHNY_2),and Theophylline_2 (THEO_2)methods on the ADVIA ChemistrySystems .	DRUG CAL is an in vitro diagnosticproduct intended to be used to calibratedigoxin, lithium, phenobarbital,phenytoin and theophylline methods onthe Dimension System
Formulation /analytes present	DigoxinPhenobarbitalPhenytoinTheophyllineLithium	DigoxinPhenobarbitalPhenytoinTheophyllineLithium
MeasuredAnalytes (valueassigned)	PhenobarbitalPhenytoinTheophylline	DigoxinPhenobarbitalPhenytoinTheophyllineLithium
Form	Liquid	Liquid
Traceability	USP	USP
Matrix	Human Serum	Human Serum
Number ofLevels	five	five
Packaging	Ten vials: two vials at five levels (3.0mL each)	Ten vials: two vials at five levels (3.0mL each)
Stability	18 months - shelf-life90 days open vial	18 months - shelf-life90 days open vial

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J. Conclusion:

The multi-analyte, five level, human serum based ADVIA Chemistry DRUG Calibrator I is substantially equivalent to the Dimension DRUG Calibrator. They are identical in composition and both used in calibration of TDM methods on Chemistry systems.

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Image /page/3/Picture/0 description: The image shows the logo for the Department of Health & Human Services USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is an image of an eagle with its wings spread, which is a common symbol of the United States. The eagle is stylized and simplified, with only a few lines used to create its form.

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

Siemens Healthcare Diagnostics c/o Kira Gordon 511 Benedict Ave Tarrytown, NY 10591

K093732 Re:

Trade Name: Advia Chemistry Drug Calibrator I Regulation Number: 21 CFR §862.1150 Regulation Name: Calibrator Regulatory Class: Class II Product Codes: JIX Dated: February 5, 2010 Received: February 12, 2010

MAR 2 2 2010

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/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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Indications for Use

K093732 510(k) Number (if known):

Device Name: ADVIA® Chemistry DRUG Calibrator I

Indications For Use:

For in vitro diagnostic use in the calibration of Phenobarbital 2 (PHNB 2), Phenytoin 2 (PHNY_2), and Theophylline_2 (THEO_2) methods on the ADVIA Chemistry Systems .

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)

Carol C. Benson

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

K 093732

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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.