The Access Myoglobin assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of cardiac Myoglobin levels in human serum and plasma using the Access Immunoassay Systems.
Measurement of myoglobin aids in the rapid diagnosis of heart and renal disease.

Device Description

The Myoglobin reagents. Myoglobin calibrators, the Access Access Immunoassay Analyzer and the Access 2 Immunoassay Analyzer comprise the Access Immunoassay Systems for the quantitative determination of cardiac Myoglobin in human serum and plasma.

AI/ML Overview

The document provided describes the Access Myoglobin assay. Here's a breakdown of the acceptance criteria and study details:

1. Table of Acceptance Criteria and Reported Device Performance:

Parameter	Acceptance Criteria (Implied)	Reported Device Performance
Precision	Consistent and reproducible results (low %CV)	- Within-run imprecision: 1.58%CV to 2.20%CV- Between-run imprecision: 2.34%CV to 4.24%CV- Total imprecision: 3.03%CV to 4.54%CV
Analytical Sensitivity	Ability to detect low levels of Myoglobin (distinguishable from zero)	The lowest detectable level of Myoglobin distinguishable from zero (with 95% confidence) is <1.0 ng/mL.
Dilution Recovery (Linearity)	Average recovery above a certain threshold (e.g., ~90-110%)	- Average recovery: 93%- Individual sample average recoveries: 86% to 100%
Method Comparison	Good agreement with a predicate device (high correlation, low bias)	- Comparison of 148 samples (0.00 to 3.227.80 ng/mL): - Equation: Y = 1.113X + 15.903 - Correlation Coefficient (R): 0.997
Matched Sample Comparison	No clinically significant bias between different sample types	- Lithium heparin plasma vs. sodium heparin plasma or serum: No clinically significant bias noted.- EDTA plasma samples: A bias was noted (Y = 0.8925X + 5.0115, R = 0.9981). The document specifies "See Reference Interval section," indicating this bias was acknowledged and likely addressed with separate reference limits.
Analytical Specificity	No significant interference from common substances	- No significant interference from therapeutic drugs or biological substances.- None of the RF or HAMA samples tested above the Upper Reference Limit (URL).- Two heterophile samples tested above the URL and were not blocked by HBT, indicating a potential limitation for these specific samples.
Stability	Reagents and calibrators maintain performance over time	- Myoglobin reagents stable for 56 days after opening.- Calibrators stable for 60 days after opening.- Calibration curve stable for 56 days.
Reference Intervals	Established reference limits for different populations/sample types	- LHS (Lithium Heparin, Serum) URL (97.5th percentile): 66 ng/mL for Females, 106 ng/mL for Males.- EDTA URL (97.5th percentile): 58 ng/mL for Females, 91 ng/mL for Males.

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

Method Comparison: 148 samples were used.
Dilution Recovery (Linearity): An unspecified number of lithium heparin plasma samples were used.
Analytical Specificity: "None of the RF samples or the HAMA samples," and "Two heterophile samples."
Reference Intervals: No specific sample size is given for the population used to establish the reference intervals, but separate limits were computed for LHS and EDTA assays for males and females.
Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective.

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

This document describes an in vitro diagnostic (IVD) device for quantitative determination of Myoglobin levels. For such devices, "ground truth" is typically established through a reference measurement procedure or comparison to a legally marketed predicate device, rather than through expert human interpretation of images or clinical findings.
The predicate device used for comparison was the "Access® Myoglobin Beckman Coulter Inc." (510(k) Number: K000196). The performance of this predicate device serves as a benchmark for comparison.
No human experts were explicitly "establishing ground truth" in the sense of consensus reads for the analytical performance studies.

4. Adjudication Method for the Test Set:

Not applicable as this is an IVD device for quantitative measurement, not a system requiring human interpretation adjudication. Measurements are taken and compared to established analytical performance criteria and a 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 typically performed for diagnostic imaging or interpretation systems where human readers are involved. This document describes an automated immunoassay system.

6. Standalone (Algorithm Only) Performance:

Yes, the entire submission describes the standalone performance of the Access Myoglobin assay, which is an algorithm-driven automated immunoassay system. The reported performance metrics (precision, sensitivity, linearity, method comparison, etc.) are all for the algorithm (assay) itself, without human-in-the-loop performance being a variable.

7. Type of Ground Truth Used:

For the analytical performance studies:
- Method Comparison: The "ground truth" for the new device was established by comparing its measurements against those obtained from the predicate device (Access® Myoglobin Beckman Coulter Inc., K000196). This is a common approach for demonstrating substantial equivalence for IVDs.
- Other analytical studies (e.g., precision, linearity, sensitivity): Ground truth is inherent in the experimental design, using known concentrations, samples with established values, or statistical methods to define performance characteristics. For instance, for sensitivity, the detection limit is determined against a zero calibrator.

8. Sample Size for the Training Set:

The document does not specify a training set size. For an immunoassay, the "training" analogous to machine learning models often refers to the development and optimization of the assay reagents and protocols. The studies described are typically considered verification and validation studies (test sets) for the finalized assay.

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

As above, explicit "training set ground truth establishment" in the context of machine learning is not directly applicable here. The development of an immunoassay involves extensive laboratory work to optimize reagent concentrations, reaction conditions, and calibration curves. This optimization process, drawing on many samples and experiments, is analogous to training. The performance of these optimized parameters is then validated through the analytical studies described.

Summary

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JUN 2 8 2002

510(k) SUMMARY

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.

The assigned 510(k) number is:

: K021229

Submitter's Name and Address

Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318 Telephone: (952)368-1611 Fax: (952)368-7610 Contact: Bruce Backlund

Date Prepared: April 17, 2002

Device Names

Myoglobin and Myoglobin Calibrators on the Access® Immunoassay Proprietary Name: Systems Common Name: Myoglobin Enzyme Immunoassay Classification Name: Myoglobin, Antigen, Antiserum, Control

Predicate Device

Access® Myoglobin Beckman Coulter Inc. Chaska, MN 55416

510(k) Number: K000196

Device Description

Intended Use

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Image /page/1/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a stylized oval shape on the left, with two curved lines running through it. To the right of the oval is the text "BECKMAN" in bold, uppercase letters, stacked above the word "COULTER", also in bold, uppercase letters. The logo is black and white.

Parameter	Access New Myoglobin	Access Current BCIMyoglobin
Intended Use	For the quantitativedetermination of Myoglobinlevels in human serum andplasma	For the quantitativedetermination of Myoglobin levelsin human serum and plasma
Assay Principles	A two-siteimmunoenzymatic("sandwich") assay. Asample is added to areaction vessel with mousemonoclonal anti-myoglobin-alkaline phosphataseconjugate, mousemonoclonal anti-myoglobin-biotin conjugate, andparamagnetic particlescoated with goat anti-biotin.	A two-siteimmunoenzymatic("sandwich") assay. Asample isadded to a reaction vesselwith mouse monoclonalanti-myoglobin-alkalinephosphataseconjugate, andparamagnetic particlescoated with mousemonoclonal anti-myoglobin.
Solid Support	Paramagnetic Particles	Paramagnetic Particles
Detection System	Utilizes dioxetane-basedchemiluminescentsubstrate;Measures light productionfrom a chemiluminescentreaction	Utilizes dioxetane-basedchemiluminescentsubstrate;Measures light productionfrom a chemiluminescentreaction
Calibrators	Liquid calibrators (frozen)prepared from bufferedbovine serum albuminmatrix with human cardiacMyoglobin at specifiedlevels	Liquid calibrators preparedfrom buffered bovineprotein matrix and humanskeletal Myoglobin atspecified levels

Comparison of Technological Characteristics

Summary of Analytical Studies

Precision: Within run imprecision ranged from 1.58%CV to 2.20%CV, betweenrun imprecision ranged from 2.34%CV to 4.24%CV and total imprecision ranged from 3.03%CV to 4.54%CV.

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Image /page/2/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a stylized, abstract symbol on the left, resembling an oval shape with two curved lines running through it. To the right of the symbol is the company name, "BECKMAN COULTER," written in a bold, sans-serif font, with "BECKMAN" stacked above "COULTER."

Analytical Sensitivity: The lowest detectable level of Myoglobin distinguishable from zero (Access Myoglobin calibrator S0) with 95% confidence is <1.0 ng/mL.

Dilution Recovery (Linearity): Linearity studies performed by diluting lithium heparin plasma samples with Access Sample Diluent A provided an average recovery of the samples of 93%, with individual sample average recoveries ranging from 86% to 100%.

Method Comparison: A comparison of cardiac Myoglobin values from 148 samples, ranging from 0.00 to 3.227.80 ng/mL, run with both the Access New Myoglobin assay and the Current BCI Myoglobin assay demonstrated good agreement with the following statistical data: Y =1.113X + 15.903 R=0.997

Matched Sample Comparison: No clinically significant bias was noted between lithium heparin plasma and sodium heparin plasma or serum samples. A bias was noted when using EDTA plasma samples. (Y= 0.8925X + 5.0115 R=0.9981)*.

Analytical Specificity: There was no significant interference from therapeutic drugs or biological substances. None of the RF samples or the HAMA samples tested above the Upper Reference Limit (URL). Two heterophile samples tested above the URL. Of this group, both heterophile samples tested did not prove to be blocked by treatment with HBT (heterophile blocking tubes).

Stability: Myoglobin reagents are stable for 56 days after opening and calibrators are stable for 60 days after opening. The calibration curve is stable for 56 days.

Reference Intervals: Separate reference limits were computed for LHS (Lithium Heparin, Serum) and EDTA assays for males and females.

The Lithium Heparin and Serum (LHS) upper reference limit (97.5th percentile) was determined to be 66 ng/mL for Females and the 106 ng/mL for Males. The EDTA upper reference limit (97.5" percentile) was determined to be 58 ng/mL for females and 91 ng/mL for males

Conclusion

Access Myoglobin and Myoglobin calibrators on the Access Immunoassay Systems are substantially equivalent to another test currently in commercial distribution for the measurement of Myoglobin.

See Reference Interval section Beckman Coulter, Inc.

1000 Lake Hazeltine Drive Chaska, MN 55318-1084

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUN 2 8 2002

Re: K021229

Mr. Bruce Backlund

Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318-1084

Senior Regulatory Specialist

Trade/Device Name: Myoglobin 100 and Myoglobin Calibrators on the Access® Immunoassay System Regulation Number: 21 CFR 866.5680; 21 CFR 862.1150 Regulation Name: Myoglobin immunological test system; Calibrator Regulatory Class: Class II Product Code: DDR; JIS Dated: April 17, 2002 Received: April 18, 2002

Dear Mr. Backlund:

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. Iisting 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 the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA mav 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 Part 801); 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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Page 2 -

This letter will allow you to begin marketing your device as described in your 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.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and ' additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrb/dsmaldsmamain.html".

Sincerely yours,

Steven Putman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory-Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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INDICATIONS FOR USE STATEMENT

Page

510(k) Number (if known): KO21229

Device Name: Myoglobin™ and Myoglobin Calibrators on the Access® Immunoassay System

Indications For Use:

Measurement of myoglobin aids in the rapid diagnosis of heart and renal disease.

Gran Coops

(Division Sign-Off)
Division of Clinical Laboratory Devices

Division of Clinical Laboratory Devices
510(k) Number K021229

(Please do not write Below This Line-continue on another PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use Counter Use (Per 21 CFR 801.109)

Over-The

(Optional Format 1-2-96)

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).