For in vitro diagnostic use in the quantitative determination of carbon dioxide in human serum and plasma on ADVIA Chemistry Systems. Such measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance.

Device Description

The ADVIA Chemistry Carbon Dioxide reagent is a solution containing buffer (pH 7.6 at 25°C), 12.5 mmol/L PEP, ≥ 400 U/L PEPC (microbial), ≥ 4100 U/L malate dehydrogenase (mammalian), 0.6 mmol/L NADH analog, activators, stabilizers, a surfactant, and a preservative.

AI/ML Overview

The provided text describes a 510(k) summary for the ADVIA® Chemistry Carbon Dioxide Liquid (CO2 L) Reagent, demonstrating its substantial equivalence to a predicate device. The information focuses on the device's performance characteristics.

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

Preamble: This document does not describe an AI/ML powered device, therefore some of the requested information (like MRMC study, AI assistance, training set details) is not applicable. The device is an in-vitro diagnostic reagent and its acceptance criteria are based on analytical performance compared to a predicate device, not on diagnostic accuracy involving human interpretation.

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

The document does not explicitly state pre-defined acceptance criteria in numerical terms for each performance characteristic. Instead, it states that "All of the evaluation studies gave acceptable results compared to the predicate device" and concludes with a "substantial equivalence" claim. However, we can infer the performance metrics reported.

Performance Characteristic	Acceptance Criteria (Implied / Comparator)	Reported Device Performance (ADVIA CO2 L Assay)
Imprecision	Acceptable precision for clinical use
- Within Run (Level 1)	(Not explicitly stated)	Mean: 16.1 mmol/L; SD: 0.19; CV: 1.2%
- Within Run (Level 2)	(Not explicitly stated)	Mean: 25.9 mmol/L; SD: 0.17; CV: 0.7%
- Within Run (Level 3)	(Not explicitly stated)	Mean: 34.6 mmol/L; SD: 0.33; CV: 1.0%
- Total (Level 1)	(Not explicitly stated)	Mean: 16.1 mmol/L; SD: 0.56; CV: 3.5%
- Total (Level 2)	(Not explicitly stated)	Mean: 25.9 mmol/L; SD: 0.92; CV: 3.5%
- Total (Level 3)	(Not explicitly stated)	Mean: 34.6 mmol/L; SD: 1.21; CV: 3.5%
Linearity/Reportable Range	Comparable to predicate device's range (2.9-50.0 mmol/L) and clinically appropriate	10 to 40 mmol/L (mEq/L)
Limit of Detection (LoD)	Clinically appropriate (Implied < 2 mmol/L for predicate)	<2 mmol/L (mEq/L)
Method Comparison (Correlation)	High correlation (e.g., >0.95) with predicate device	Correlation Coefficient: 0.995
Method Comparison (Regression)	Slope close to 1, intercept close to 0 compared to predicate	Equation: This method = 1.07 (predicate) + 0.75 mmol/L
Analytical Specificity (Interference)	<10% variance from control	- Lipemia: No significant interference at Intralipid levels from 0-500 mg/dL (in 22.2 mmol/L CO2 sample)
- Icterus	(Not explicitly stated)	- Unconjugated Bilirubin: No significant interference from 0-25 mg/dL (in 21.7 mmol/L CO2 sample)
		- Bilirubin: 10.3% variance from 0-25 mg/dL (in 21.9 mmol/L CO2 sample) Note: This is >10%, but the text states "with acceptable results" with hemoglobin, and "no significant interference" for unconjugated. This specific bilirubin result is slightly ambiguous in its acceptability within the " >10% variance from the control" significance criterion for icterus.
- Hemolysis	(Not explicitly stated)	- Hemoglobin: Acceptable results from 0-500 mg/dL (in 22.6 mmol/L CO2 sample)

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

Imprecision: Assayed two control sera. Each sample was assayed 2 times per run, 2 runs per day, for at least 10 days. The 'N' column in the table refers to the number of replicates (40 for each level). This is a prospective lab-based study using control materials.
Linearity/Assay Reportable Range: Established based on calculations from the limit of detection and linearity studies. No specific sample size of patient samples is given for the linearity study itself.
Limit of Detection: 40 replicates of 0.9% saline and 40 replicates of a Low Sample, using one lot of reagent. Data obtained from a 10-day precision study. This is a prospective lab-based study.
Method Comparison: Sixty-two (62) serum samples. The provenance (country of origin, retrospective/prospective) is not specified, but it's implied to be a prospective comparison of the new and predicate methods.
Analytical Specificity: Interference studies used samples spiked with interferents (Intralipid, unconjugated bilirubin, hemoglobin). Specific sample sizes for each interference study are not given, but they refer to specific CO2 sample concentrations (e.g., 22.2 mmol/L CO2 sample). This is a controlled lab-based study using spiked samples.

Data Provenance (General): Not explicitly stated, but these are typical studies performed in a lab setting, likely in the US, during product development.

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)

This is not applicable to an in-vitro diagnostic assay. The "ground truth" for this type of device is established by the analytical reference methods or reference materials themselves, or by comparison to a legally marketed predicate device which serves as the comparative standard. There are no human experts "reading" or interpreting the results in a diagnostic imaging sense.

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

This is not applicable. Adjudication methods like 2+1 or 3+1 are used in studies where human experts interpret data (e.g., radiology images) and a consensus is needed to establish ground truth or resolve discrepancies. For an in-vitro diagnostic, the measurements are quantitative chemical analyses, not subjective interpretations.

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

This is not applicable. The device is a laboratory reagent, not an AI-powered diagnostic tool that assists human readers.

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

The device itself is a "standalone" analytical system in that it chemically quantifies CO2. Its performance is entirely "algorithm only" in the sense of the chemical reactions and spectrophotometric measurements. There is no human interpretation of an image or signal that the device is intending to aid or replace.

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

The "ground truth" for this type of device is established by:

Reference Methods/Materials: For imprecision, linearity, and LoD, the device measures against established control materials or standard concentrations.
Predicate Device: For method comparison, the Genzyme Carbon Dioxide L3K® Assay (K042362) serves as the "ground truth" or reference for comparison, based on its established performance and market history. The goal is to show agreement with this predicate.

8. The sample size for the training set

This is not applicable. This is an IVD reagent developed through chemical and assay optimization, not a machine learning model that requires a "training set" in the context of AI.

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

This is not applicable as there is no training set for an AI model. The development of the reagent involves standard chemical and analytical validation processes.

Summary

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MAY 1 0 2010

510(k) Summary of Safety and Effectiveness for the ADVIA® Chemistry Carbon Dioxide Liquid (CO2 L) Reagent

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: K100289

B. Date of Preparation: May 6, 2010

C. Proprietary and Established Names: ADVIA® Chemistry Carbon Dioxide Liguid (CO2_L) Assay

D. Applicant

Contact:	Sandra D. White, MS, RACSr. Regulatory Technical Specialist
Address:	Siemens Healthcare Diagnostics, Inc333 Coney StreetEast Walpole, MA 02032
Phone:	(508) 660-4553(508) 660-4591 (fax)

E. Requiatory Information:

1. Regulation section: 21 CFR §862.1160 Bicarbonate/carbon dioxide test system, (Enzymatic, Carbon Dioxide)
1. Classification: Class II
1. Product Code: KHS
1. Panel: 75 - Chemistry

F. Predicate Device:

1. Device Name: Genzyme/DCL Carbon Dioxide L3K® Assay
1. Common Name: Carbon Dioxide-L3K Assay
1. 510(k) Number:
K042362
1. Manufacturer:

Genzyme Diagnostics P.E.I. Inc. (formerly Diagnostic Chemicals Limited)

G. Intended Use:

The ADVIA Chemistry Carbon Dioxide Liquid (CO2 L) assay is for in vitro diagnostic use in the quantitative determination of carbon dioxide in human serum and plasma on ADVIA Chemistry systems. Such measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance.

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H. Device Description:

l. Test Principle:

The ADVIA® Chemistry Carbon Dioxide Liquid (CO2 L) Assay is based on enzymatic reactions. Phosphoenolpyruvate carboxylase (PEPC) catalyzes the first reaction which generates oxaloacetate. In the presence of MDH, the NADH analog is oxidized by oxaloacetate to NAD+ analog. The oxidation of NADH analog is measured by the decreased absorbance at 410/478 nm, which is proportional to the amount of CO2 in the sample.

J. Substantial Equivalence Information:

1. Predicate device name: Genzyme (formerly DCL) Carbon Dioxide L3K Assay
1. Predicate K number: K042362
1. Comparison with predicate:

Similarities
Item	ADVIA Chemistry Carbon Dioxide Liquid (New Device)	Genzyme (formerly DCL) Carbon Dioxide L3K® Assay (Predicate Device)
Intended Use	For the in vitro quantitative measurement of carbon dioxide concentration in serum and plasma.	Same
Sample Type	Serum and Plasma	Same
Test Principle	Enzymatic
Reagents	A solution containing buffer, 12.5 mmol/L PEP, >400 U/L PEPC (microbial), >4100 U/L malate dehydrogenase (mammalian), 0.6 mmol/L NADH analog, activators, stabilizers, a surfactant, and a preservative.	Same
Format	Liquid, ready for use	Same
Reagent Storage Temperature	2-8°C	Same

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Item	ADVIA Chemistry CarbonDioxide Liquid(New Device)	Genzyme (formerly DCL)Carbon Dioxide L3K®Assay(Predicate Device)
MeasurementWavelength	410 nm or 478 nm	405 nm or 415 nm
Calibrators	Siemens ADVIA Chemistry CO2Calibrator/Diluent	Genzyme CO2 Calibrator
CalibrationFrequency	Daily	The frequency of calibration,if necessary, using anautomated system isdependent on the systemand the parameters used.
Reportable range	10 to 40 mmol/L (mEq/L)	2.9 to 50.0 mmol/L (mEq/L)

K. Performance Characteristics

Substantial equivalence was demonstrated by testing several performance characteristics including imprecision, method comparison, interfering substances, serum/plasma equivalency, and analytical range. All of the evaluation studies gave acceptable results compared to the predicate device. These studies support that the ADVIA Chemistry Carbon Dioxide Liquid assay is substantially equivalent to the Genzyme Carbon Dioxide L3K® assay that is currently marketed.

l. Imprecision

Within run and Total Precision were established by assaying two control sera. Each sample was assayed 2 times per run, 2 runs per day, for at least 10 days. Precision estimates were computed according to CLSI document EP05-A2, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline.

Sample	Meanmmol/L(mEq/L)	Standard Deviationmmol/L(mEq/L)	Coefficientof Variation%	N
Within Run Imprecision
Level 1	16.1	0.19	1.2	40
Level 2	25.9	0.17	0.7	40
Level 3	34.6	0.33	1.0	40
Total Imprecision
Level 1	16.1	0.56	3.5	40
Level 2	25.9	0.92	3.5	40
Level 3	34.6	1.21	3.5	40

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II. Linearity/assay reportable range:

Linear/measuring range of the assay is 10-40 mmol/L (mEq/L). The low end of the assay range is calculated based on the Limit of Detection. The high end of the assav range is based on the linearity calculation.

111. Limit of detection

The estimations of the Limit of Blank (LoB) and Limit of Detection (LoD) were performed by running 40 replicates of 0.9% saline and 40 replicates of a Low Sample, using one lot of reagent. Data were obtained from a 10-day precision study. The LoD for the CO2 assays is <2mmol/L (mEq/L).

IV. Method comparison with predicate device:

The performance of this method (y) on a ADVIA 1650 was compared with performance of Genzyme carbon dioxide L3K® method (x) on a Hitachi 717. Sixty-two (62) serum samples tested ranging from 12.8 - 40.0 mmol/L (mEg/L) gave a correlation coefficient of 0.995. Linear regression analysis gave the following equation:

This method = 1.07 (predicate device) + 0.75 mmol/L (mEq/L).

V. Analytical specificity

Interferences from icterus, lipemia, and hemolysis were evaluated for this carbon dioxide method on an ADVIA 1650 analyzer using a significance criterion of >10% variance from the control. No significant lipemia interference was found at Intralipid levels from 0-500 mg/dL in a 22.2 mmol/L (mEg/L) carbon dioxide sample. No significant interference was found at unconjugated bilirubin levels from 0-25 mg/dL in a 21.7 mmol/L (mEg/L) carbon dioxide sample. Hemoglobin levels of 0-500 mg/dL were studied with acceptable results to a level of a 22.6 mmol/L (mEg/L) carbon dioxide sample. Billirubin levels from 0-25 mg/dL in a 21.9 mmol/L (mEq/L) carbon dioxide sample was 10.3%.

L. Conclusion:

The ADVIA Chemistry Carbon Dioxide Liquid (CO2 L) assay is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed Genzyme (formerly Diagnostics Chemicals Limited) Carbon Dioxide L3K® Assay (K042362).

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Image /page/4/Picture/0 description: The image shows the text "DEPARTMENT OF HEALTH & HUMAN SERVICES". The text is in all caps and is in a sans-serif font. The text is centered in the image and is the only element in the image. The text is likely the name of a government agency.

Image /page/4/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States of America. The seal features an abstract eagle design, with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged in a circular pattern around the eagle. The text is in all caps and is evenly spaced around the circle.

Food & Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993

Siemens Healthcare Diagnostics c/o Sandra D. White, Sr. Manager Regulatory Affairs 333 Coney Street Walpole, MA 02032

MAY 1 0 2010

Re: K100289

Trade Name: ADVIA Chemistry Systems Carbon Dioxide Liquid (CO2 L) Assay Regulation Number: 21 CFR 8862.1160 Regulation Name: Bicarbonate/carbon dioxide test system Regulatory Class: Class II Product Codes: KHS Dated: April 1, 2010 Received: April 2, 2010

Dear Ms. White:

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/ResourcesforYou/Industry/default.htm.

Sincerely yours,

CAC

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

510(k) Number (if known): __k100289

Device Name: ADVIA® Chemistry Carbon Dioxide Liquid (CO2 L) Assay

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 (OIVD)

Signature

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

510(k) K100289

Regulation Number and Section

§ 862.1160 Bicarbonate/carbon dioxide test system.

(a)
Identification. A bicarbonate/carbon dioxide test system is a device intended to measure bicarbonate/carbon dioxide in plasma, serum, and whole blood. Bicarbonate/carbon dioxide measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance.(b)
Classification. Class II.