The ADVIA® Chemistry Myoglobin assay is for in vitro diagnostic use in the quantitative measurement of myoglobin in human serum or plasma on the ADVIA® Chemistry systems. Measurement of myoglobin aids in the rapid diagnosis of heart or renal disease.

The ADVIA Chemistry Myoglobin calibrator is for in vitro diagnostic use in the calibration of ADVIA® Chemistry system for Myoglobin assay.

Device Description

The Myoglobin reagents are ready-to-use liquid reagents packaged for use on the automated ADVIA 1650 Chemistry system. They are supplied as a 100 tests/wedge, 2 wedges/kit. ADVIA Chemistry Myoglobin calibrator is a single analyte, human serum based product containing myoglobin derived from human heart source. The kit consists of 1 vial each of 4 calibrator levels which are lyophilized. The target concentrations of these calibrators are 50, 100, 200, and 720 ng/mL. The volume per vial (after reconstitution with deionized water) is 1.0 mL. Deionized water is recommended to be used as a zero calibrator.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance:

The document describes several performance characteristics and the results obtained for the ADVIA® 1650 Chemistry Myoglobin Assay. Since this is a submission for substantial equivalence to a predicate device, the "acceptance criteria" are implicitly the performance levels of the predicate device or generally accepted clinical laboratory standards as guided by CLSI documents. The reported performance of the new device is compared to these.

Performance Characteristic	Acceptance Criteria (Implicit/Guidance)	Reported Device Performance (ADVIA® 1650 Chemistry Myoglobin Assay)
Precision	As per CLSI EP05-A2 guidance	Within-run SD/CV: 0.70-4.22 SD, 0.5-0.8% CV (depending on sample/concentration)Total SD/CV: 1.41-10.23 SD, 1.8-6.2% CV (depending on sample/concentration)
Linearity/Assay Reportable Range	Linear range typically defined by predicate device or clinical needs	Linear/measuring range: 22 to 680 ng/mL
Limit of Blank (LoB)	As per CLSI EP17-A guidance	12 ng/mL
Limit of Detection (LoD)	As per CLSI EP17-A guidance	21 ng/mL
Limit of Quantitation (LoQ)	As per CLSI EP17-A guidance	22 ng/mL
Method Comparison (Serum)	Good correlation with predicate device (ADVIA Centaur Myoglobin assay)	Correlation coefficient: 0.99Slope: 0.96 (95% CI: 0.95-0.98)Intercept: 12.5 ng/mL (95% CI: 8.3-16.7)Range tested: 19.9 - 684.0 ng/mL
Matrix Comparison (Plasma)	Good correlation with predicate device (ADVIA Centaur Myoglobin assay)	Correlation coefficient: 0.99Slope: 0.98 (95% CI: 0.96-1.00)Intercept: 14.1 ng/mL (95% CI: 8.1-20.1)Range tested: 18.9 - 624.1 ng/mL
Analytical Specificity (Interference)	< 10% variance from control in presence of interferents	No significant interference found at specified levels for unconjugated bilirubin, conjugated bilirubin, Intralipid, hemoglobin, total protein, and rheumatoid factor. Hemolysed samples should not be used.
Reference Range	Substantial equivalence to predicate device	< 110.0 ng/mL

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

Precision:
- Serum Pool 1: 40 replicates (assayed over 5 days)
- Control 1, Control 2, Control 3: 80 replicates each (assayed over 20 days)
- Serum Pool 2, Serum Pool 3, Serum Pool 4: 80 replicates each (assayed over 20 days)
- Data Provenance: Not explicitly stated, but typically these types of studies are prospective lab studies conducted internally or by contract research organizations (CROs) for the manufacturer. The document doesn't mention country of origin or if samples were from specific patient populations, implying a general laboratory setting for assay validation.
Linearity/Assay Reportable Range: Nine intermediate levels were created from low and high serum pools, plus two additional low levels. The total number of samples is not explicitly given but would be at least 11.
- Data Provenance: Not explicitly stated, but likely laboratory-prepared serum pools.
Limit of Blank, Limit of Detection, Limit of Quantitation:
- LoB: 160 replicates of "zero" serum pool.
- LoD/LoQ: Several serum pools with myoglobin concentration up to 4 x LOD level. (Exact number not specified for these pools).
- Data Provenance: Not explicitly stated, likely laboratory-prepared or confirmed serum pools.
Method Comparison (Serum): 71 serum samples. One sample was removed.
- Data Provenance: Not explicitly stated, but typically these are human patient samples. The country of origin is not specified, and it's not stated whether they were retrospective or prospectively collected for the study, but typically for method comparison, they would be prospectively selected from a relevant patient population.
Matrix Comparison (Plasma): 64 plasma samples.
- Data Provenance: Similar to serum comparison, likely human patient samples. Country/retrospective/prospective not specified.
Analytical Specificity (Interference): Test samples at specific myoglobin concentrations (50, 100, 400 ng/mL) were spiked with various interferents. The number of samples for each interferent type and concentration is not explicitly given but implies multiple measurements.
- Data Provenance: Not explicitly stated, likely laboratory-prepared spiked samples using various concentrations of human physiological interferents.

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

This device is a quantitative immunological test system for measuring myoglobin. The "ground truth" for the test set is established by the predicate device (ADVIA Centaur Myoglobin Assay), which is itself a legally marketed device. There is no explicit mention of human experts establishing a "ground truth" for individual patient samples in the way it might be done for an imaging device (e.g., radiologists). The performance is assessed against an established analytical reference method (the predicate).

4. Adjudication Method:

Not applicable in the typical sense for a diagnostic imaging or clinical decision support device where human experts adjudicate. For analytical assays, the "adjudication" is inherent in the analytical method comparison and statistical analysis against the predicate device.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for diagnostic imaging or interpretation systems where human readers are making diagnoses. This device is an in vitro diagnostic (IVD) assay that provides a quantitative measurement, not an interpretation by a human reader.

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

Yes, the entire performance evaluation described (precision, linearity, LoB/LoD/LoQ, method comparison, interference) is a standalone (algorithm only) performance study. The ADVIA® 1650 Chemistry Myoglobin assay is an automated system that performs the measurement without direct human interaction in the analytical process after sample loading.

7. Type of Ground Truth Used:

The primary "ground truth" used for evaluating the new device's performance is the results obtained from the predicate device (ADVIA Centaur Myoglobin Assay) and, for basic analytical characteristics like LoB/LoD/LoQ, established analytical methodologies and industry standards (CLSI guidelines). For interference, the ground truth is the absence of interfering substances, and deviations are measured against that.

8. Sample Size for the Training Set:

This 510(k) summary is for an in vitro diagnostic (IVD) assay, not a machine learning or AI model in the typical sense that requires explicit "training data" in the submission. The methods (e.g., latex-particle-enhanced immunoturbidimetric) are based on established chemical and immunological principles. Therefore, there is no specific "training set" sample size mentioned or generally applicable in the context of such an IVD submission. The assay's parameters would have been optimized during its development phase, but these aren't typically documented as a "training set" in a 510(k).

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

As there is no "training set" specified in the context of an AI/ML model for this IVD assay, this question is not applicable. The "ground truth" for developing and optimizing such an assay would be based on fundamental chemical/immunological principles and experiments to ensure accurate and precise measurement of myoglobin concentrations.

Summary

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510(k) Summary of Safety and Effectiveness for the ADVIA® 1650 Chemistry Myoglobin Assay

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: 08/24/2012

C. Proprietary and Established Names:

ADVIA® Chemistry Myoglobin (MYO) Assay ADVIA® Chemistry Myoqlobin Calibrator

D. Applicant

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

E. Regulatory Information:

Reagent

1. Regulation section: 21 CFR §866.5680, Myoglobin immunological test system
1. Classification: Class II
1. Product Code: DDR
1. Panel: Immunology

Calibrator

1. Requlation section: 21 CFR §862.1150, Calibrator, secondary
1. Classification: Class II ·
1. Product Code: JIT
1. Panel: Clinical Chemistry

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F. Predicate Device:

Reagent

1. Device Name: ADVIA Centaur Myoglobin Reagent
1. Common Name: ADVIA Centaur Myoglobin Reagent
1. 510(k) Number: K974325 and K041133
1. Manufacturer: Siemens Healthcare Diagnostics Inc. Calibrator
1. Device Name: Dimension Clinical Chemistry System Myoglobin Calibrator
1. Common Name: Dimension Clinical Chemistry System Myoglobin Calibrator
1. 510(k) Number: K984193
1. Manufacturer: Siemens Healthcare Diagnostics Inc.

G. Intended Use:

The ADVIA® Chemistry Myoqlobin assay is for in vitro diagnostic use in the quantitative measurement of myoglobin in human serum or plasma on the ADVIA® Chemistry systems. Measurement of myoglobin aids in the rapid diagnosis of heart or renal disease.

The ADVIA Chemistry Myoglobin calibrator is for in vitro diagnostic use in the calibration of ADVIA® Chemistry system for Myoqlobin assay.

H. Device Description:

l. Test Principle:

In the ADVIA 1650 Chemistry Myoglobin assay, sample is diluted and then mixed with the R1 reagent (a buffer), followed by an addition of the R2 reagent (which contains latex particles coated with antibodies specific for myoglobin). The formation of the

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antibody-antigen complex during the reaction results in an increase in turbidity, which is measured at 571 nm. By constructing a standard curve from the absorbance of standards, myoglobin concentration of sample can be determined.

J. Substantial Equivalence Information:

Reagent

ReagentItem	New Device:ADVIA 1650 ChemistryMyoglobin	Predicate Device:ADVIA Centaur Myoglobin
Analyte	Myoglobin	Same
IntendedUse/Indications for Use	For in vitro diagnostic use inthe quantitative measurementof myoglobin. Measurement ofmyoglobin aids in the rapiddiagnosis of heart or renaldisease	Same - For in vitrodiagnostic use in thequantitative determinationof myoglobin in serum orplasma and as an aid in thediagnosis of acutemyocardial infarction
Measurement	quantitative	Same
Sample type	Serum , Heparinized Plasma	Same
Reference interval	< 110 ng/mL	Same
Format	Liquid	Liquid
Use of Calibrators	Yes	Yes
Analytical measuringinterval	22 - 680 ng/mL	3-1000 ng/mL
Method Principle	latex-particle-enhanced immuno-tubidimetric	chemiluminescence
Reagents	Two:R1 and R2	Two:Lite reagent and Solid Phase
Instrument to be used	ADVIA Chemistry	ADVIA Centaur

Calibrator

Item	New Device:ADVIA Chemistry Myoglobincalibrator	Predicate Device:Siemens Dimension ClinicalChemistry SystemMyoglobin calibrator
Intended Use	for in vitro diagnostic use in thecalibration of Myoglobin assay	Same
Instrument	ADVIA Chemistry Systems	Dimension Clinical ChemistrySystem
Measured Analytes(value assigned)	Myoglobin	Same
Form	Lyophilized	Liquid
Matrix	Human serum	Bovine serum

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Analyte source	Derived from human source	Same
Number of levels	Five (the lowest level is a zero-level, not included)	Same
Fill Volume	1.0 mL each vial	Same

K. Standard/Guidance Document Reference

Interference Testing in Clinical Chemistry; Approved Guideline Second Edition . (CLSI EP07-A2)
Protocols for Determination of Limits of Detection and Limits of Quantitation; . Approved Guideline (CLSI EP17-A)
Evaluation of Precision Performance of Quantitative Measurement Methods; . Approved Guideline-Second Edition (CLSI EP05-A2)

L. Performance Characteristics

Substantial equivalence was demonstrated by testing several performance characteristics including imprecision, method comparison, interfering substances and analytical range. All of the evaluation studies gave acceptable results when compared to the predicate device. These studies support that the ADVIA® 1650 Chemistry Myoqlobin Assay is substantially equivalent to the predicate device.

1. Precision

Within run and Total Precision were established by assaying serum sample pools and serum based controls. Each sample was assaved 2 replicates per run, 2 runs per day. for at least 20 days (Serum Pool 1 was assayed over a period of 5 days in a separate study). Precision estimates were computed according to CLSI document EP05-A2, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline.

Sample	#Day	#Run	#Rep	MEAN	SD	CV	SD	CV	SD	CV	SD	CV
Serum Pool 1	5	10	40	22.61	1.32	5.8	0.44	1.9	0.24	1.1	1.41	6.2
Control 1	20	40	80	60.3	1.22	2.0	1.09	1.8	1.13	1.9	1.99	3.3
Serum Pool 2	20	40	80	83.0	0.70	0.8	0.38	0.5	1.68	2.0	1.86	2.2
Control 2	20	40	80	155.0	1.08	0.7	1.32	0.9	3.31	2.1	3.73	2.4
Control 3	20	40	80	373.2	2.01	0.5	1.74	0.5	8.07	2.2	8.50	2.3
Serum Pool 3	20	40	80	395.2	2.36	0.6	1.66	0.4	7.20	1.8	7.76	2.0
Serum Pool 4	20	40	80	579.4	4.22	0.7	0.00	0.0	9.32	1.6	10.23	1.8

II. Linearity/assay reportable range

A linearity study across the entire measuring range was assessed using low and high serum pools. The low and high pools were mixed to make nine (9) intermediate levels

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and additional 2 levels at the low end of the assay. All samples were tested on the ADVIA 1650 Chemistry analyzer. The range of samples tested was from 13-817 ng/mL. The observed values were compared to the expected values. Linear/measuring range of the assay is 22 to 680 ng/mL. The low end of the assay range is calculated based on the Limit of Quantitation. The high end of the assay range is based on lowest possible value of the high calibrator and linearity calculations.

III. Limit of Blank, Limit of Detection, Limit of Quantitation

The estimations of the Limit of Blank (LoB), Limit of Detection (LoD) and Limit of Quantitation (LoQ) were performed according to CLSI guideline EP17-A, Protocols for Determination of Limits of Detection and Limits of Quantitation, by running 160 replicates of "zero" serum pool and several serum pools with myoglobin concentration up to 4 x LOD level. Data supports the following claims: LoB = 12 ng/mL, LoD = 21 ng/mL. LoQ = 22 ng/mL

Method and matrix comparison with predicate device IV.

The performance of the ADVIA 1650 Chemistry Myoglobin assay (y) for serum samples was compared with the performance of ADVIA Centaur Myoglobin assay (x). Seventyone serum samples were tested. One sample was removed from calculations for being out of assay range. The sample results ranged from 19.9 - 684.0 ng/mL myoglobin (x), and gave a correlation coefficient of 0.99. The results calculated using least squares linear regression (1st replicate) are as follows:

ADVIA 1650 Chemistry Mvoalobin = 0.96 (predicate device) + 12.5 ng/mL Slope 95%CI: 0.95 - 0.98

Intercept 95% Cl: 8.3 – 16.7

V. Matrix comparison with predicate device

The performance of the ADVIA 1650 Chemistry assay (v) for plasma samples on ADVIA 1650 was compared with the performance of ADVIA Centaur Myoglobin assay (x). Sixty four plasma samples were tested; the sample results ranged from 18.9 - 624.1 ng/mL myoglobin (x), and gave a correlation coefficient of 0.99. The results calculated using linear regression (1st replicate) are as follows:

ADVIA 1650 Chemistry Myoglobin = 0.98 (predicate device) + 14.1 ng/mL Slope 95%CI: 0.96 - 1.00 İntercept 95% Cl: 8.1 - 20.1

VI. Analytical specificity

Interferences from icterus, lipemia, hemolysis, total protein and rheumatoid factor were evaluated in the Myoglobin assay using a significance criterion of > 10% variance from the control. No significant interference was found at unconjugated bilirubin levels from 0-60 mg/dL in 50. 100. and 400 ng/mL myoglobin samples. No significant interference

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was found at coniugated bilirubin levels from 0-60 mg/dL in 50. 100. and 400 ng/mL mvoglobin samples. No significant lipemia interference was found at Intralipid levels from 0-1000 mg/dL in a 100 and 400 ng/mL myoglobin samples, and at Intralipid levels from 0-750 mg/dL in a 50 ng/mL myoglobin sample. No significant hemoglobin interference was found at hemoglobin levels from 0-1000 mg/dL in a 400 ng/mL myoglobin sample, at hemoglobin levels from 0-500 mg/dL in a 100 ng/mL myoqlobin sample, and at hemoglobin levels from 0-250 mg/dL in a 50 ng/mL myoglobin sample. Hemolysed samples should not be used. No significant interference was found at total protein levels from 0-13 g/dL in a 50, 100, and 400 ng/mL myoglobin samples. No significant interference was found at RF levels from 0-800 U/L in a 50, 100, and 400 na/mL myoglobin samples.

VII. Reference Range

The reference range for the assay is < 110.0 ng/mL (< 110.0 µg/L). Results above 110 ng/mL (110.0 µg/ml) are highly suggestive of an early onset of myocardial necrosis. The reference range was established previously for the predicate device. ADVIA Chemistry Myoqlobin reference range is based on substantial equivalence to the predicate device (method comparison studies and the normal range verification study). Siemens provides this information for reference. As with all in vitro diagnostic assays, each laboratory should determine its own reference ranges for the diagnostic evaluation of patient results.

VIII. Clinical Studies

Not applicable.

IX. Clinical cut-off

Not applicable

L. Conclusion

The ADVIA 1650 Chemistry Myoglobin assay is substantially equivalent in principle and performance to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed Siemens Healthcare Diagnostics ADVIA Centaur Myoglobin Assay (K041133)

The ADVIA 1650 Chemistry Myoglobin calibrator is substantially equivalent n principle and performance to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed Siemens Healthcare Diagnostics Dimension Myoglobin Calibrator (K984193).

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Image /page/6/Picture/0 description: The image shows the seal of the Department of Health & Human Services (HHS). The seal features the department's name in a circular arrangement around the perimeter. In the center is a stylized depiction of a caduceus, a symbol often associated with healthcare, featuring a staff with a serpent entwined around it.

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, NY 10591

K122599 Re:

Trade Name: ADVIA® Chemistry Myoglobin Assay ADVIA® Chemistry Myoglobin Calibrator Regulation Number: 21 CFR §866.5680 Regulation Name: Myoglobin immunological test system Regulatory Class: Class II Product Codes: DDR, JIT Dated: August 24, 2012 Received: August 27, 2012

Dear Dr. 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).

OCT

3 2012

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Page 2

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please 11 you dosn't spocently as vitro Diagnostic Devices and Radiological Health at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" Also, prease note the regarding postmarket surveillance, please contact CDRY'S (21 Of R Pat 001197). 1 0 Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-576-. 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 Tou thay 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,

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

Enclosure

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Indication for Use

510(k) Number (if known): K122599

Device Name:

ADVIA® Chemistry Myoglobin Assay

ADVIA® Chemistry Myoglobin Calibrator

Indication For Use:

The ADVIA® Chemistry Myoglobin assay is intended for in vitro diagnostic use in the quantitative measurement of myoglobin in human serum or plasma on the ADVIA® Chemistry systems. Measurement of myoglobin aids in the rapid diagnosis of heart or renal disease.

The ADVIA Chemistry Myoglobin calibrator is intended for in vitro diagnostic use in the calibration of ADVIA® Chemistry system for Myoglobin assay

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)

Ruta Chester

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

5 9 1 ನ 10(k)

Regulation Number and Section

§ 866.5680 Myoglobin immunological test system.

(a)
Identification. A myoglobin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the myoglobin (an oxygen storage protein found in muscle) in serum and other body fluids. Measurement of myoglobin aids in the rapid diagnosis of heart or renal disease.(b)
Classification. Class II (performance standards).