The Alpha Dx Cardiac Panel Test Kit is intended for use with the Alpha Dx Analyzer to provide rapid, quantitative and simultaneous measurement of myoglobin, creatine kinase (CK), creatine kinase MB isoenzyme (CK-MB) and cardiac troponin I (TnI) in whole blood or serum to aid in the diagnosis of acute myocardial infarction (AMI). The Analyzer and Cardiac Panel Test Kit combine ease of use and rapid turnaround time with laboratory-quality performance and reliability. With factory calibration, built-in bilevel quality controls and closed tube sampling, the system can be used in the central laboratory, STAT lab, emergency department, coronary care unit, chest pain center and other point of care locations.

Device Description

The Alpha Dx Cardiac Panel Test Kits, when used with the Alpha Dx Analyzer, are fluorescence immunoassays for the rapid measurement of myoglobin, CK, CK-MB and TnI in human whole blood or serum. The Alpha Dx Cardiac Panel Test Kits are two-site fluorescence immunoassays. Monoclonal and polyclonal antibodies are used in the Alpha Dx Cardiac Panel Test Kits.

AI/ML Overview

Acceptance Criteria and Device Performance for Alpha Dx System

The Alpha Dx System is intended for rapid, quantitative, and simultaneous measurement of myoglobin, creatine kinase (CK), creatine kinase MB isoenzyme (CK-MB), and cardiac troponin I (TnI) in whole blood or serum to aid in the diagnosis of acute myocardial infarction (AMI). The acceptance criteria and device performance are primarily demonstrated through correlation studies with predicate devices and an assessment of clinical sensitivity and specificity for cardiac troponin I (TnI) and CK-MB.

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Analyte	Acceptance Criteria (Implicit from Predicate Equivalence)	Reported Device Performance (Alpha Dx System)	Predicate Device Performance (where applicable)
Correlation with Predicate Methods	Myoglobin	Slope ~1.0, r ~1.0	Slope = 0.81, r = 0.98	N/A (Predicate: Dade Stratus Myoglobin)
	CK	Slope ~1.0, r ~1.0	Slope = 0.77, r = 0.97	N/A (Predicate: Johnson & Johnson Vitros CK)
	CK-MB	Slope ~1.0, r ~1.0	Slope = 1.07, r = 0.97	N/A (Predicate: Dade Stratus CK-MB)
	TnI (Stratus)	Slope ~1.0, r ~1.0	Slope = 0.18, r = 0.93	N/A (Predicate: Dade Stratus Cardiac Troponin I)
	TnI (Access)	Slope ~1.0, r ~1.0	Slope = 1.44, r = 0.88	N/A (Predicate: Beckman Access Troponin I)
Clinical Sensitivity (95% CI)	TnI	Comparable to predicate (e.g., within 95% CI)	93 ± 6	Stratus TnI: 93 ± 6, Access TnI: 92 ± 6
Clinical Specificity (95% CI)	TnI	Comparable to predicate (e.g., within 95% CI)	94 ± 3	Stratus TnI: 93 ± 3, Access TnI: 88 ± 4
Clinical Sensitivity (95% CI)	CK-MB	Comparable to predicate (e.g., within 95% CI)	N/A (Compared to Stratus CK-MB, not directly stated to be "Alpha Dx CK-MB")	Stratus CK-MB: 89 ± 7
Clinical Specificity (95% CI)	CK-MB	Comparable to predicate (e.g., within 95% CI)	N/A (Compared to Stratus CK-MB, not directly stated to be "Alpha Dx CK-MB")	Stratus CK-MB: 90 ± 4
Concordance (TnI vs CK-MB)	TnI vs CK-MB	Not explicitly stated, but "no statistically significant difference"	92% concordant	N/A
Analytical Sensitivity	Myoglobin	N/A	1.1 ng/mL	N/A
	CK	N/A	1.8 ng/mL	N/A
	CK-MB	N/A	0.04 ng/mL	N/A
	TnI	N/A	0.017 ng/mL	N/A
Precision (Median %CV) Whole Blood	Myoglobin	N/A	3.9	N/A
	CK	N/A	5.3	N/A
	CK-MB	N/A	3.9	N/A
	TnI	N/A	7.3	N/A
Precision (Median %CV) Serum	Myoglobin	N/A	4.0	N/A
	CK	N/A	7.0	N/A
	CK-MB	N/A	2.7	N/A
	TnI	N/A	2.4	N/A

Implicit Acceptance Criteria: The primary acceptance criterion for the Alpha Dx system is substantial equivalence to legally marketed predicate devices. This is demonstrated by showing comparable analytical and clinical performance. For correlation studies, slopes near 1 and high correlation coefficients (r values near 1) indicate good agreement. For clinical sensitivity and specificity, the acceptance is that the Alpha Dx performance is within the confidence intervals of the predicate devices, indicating no statistically significant difference in diagnostic performance.

2. Sample Sizes and Data Provenance for Test Set

Correlation between Whole Blood and Serum Samples (Table 45):
- Sample Size: Paired whole blood and serum samples from 72 chest pain patients and 24 healthy individuals.
- Data Provenance: Not explicitly stated, but implied to be from patient populations where AMI diagnosis is relevant. Retrospective or prospective is not specified, but the "serial draws" suggest a prospective collection with follow-up.
Correlation between Alpha Dx System and Predicate Methods (Table 46):
- Sample Size: Serial samples from 410 chest pain patients and 134 healthy individuals.
- Data Provenance: Not explicitly stated, but implied to be from patient populations where AMI diagnosis is relevant. Retrospective or prospective is not specified, but "serial samples" hint at a prospective component.
Clinical Sensitivity and Specificity (Table 47) and Concordance:
- Sample Size: 362 subjects were tested for concordance between Alpha Dx TnI and Stratus CK-MB. The specific number of patients used to calculate the sensitivity and specificity values for each method (Alpha Dx TnI, Stratus TnI, Access TnI, Stratus CK-MB) is not explicitly stated but is derived from the overall clinical study population involving chest pain patients and healthy individuals.
- Data Provenance: Not explicitly stated, but implied to be from patient populations relevant to AMI diagnosis.

3. Number of Experts and Qualifications for Ground Truth for the Test Set

The document does not mention the use of experts to establish ground truth in the traditional sense (e.g., radiologists interpreting images). The "ground truth" for this in-vitro diagnostic device appears to be the clinical diagnosis of AMI, established through standard clinical practice for chest pain patients. This likely involves a combination of clinical assessment, EKG findings, and results from other diagnostic tests, as would be performed by medical professionals (e.g., emergency physicians, cardiologists). The specific number or qualifications of these clinical experts are not detailed in the provided text.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method for the test set in the context of expert consensus or disagreement. The "ground truth" (clinical diagnosis of AMI) would have been established through a standard clinical diagnostic process, which inherently involves medical professionals making a diagnosis. There is no mention of a separate adjudication panel for discordant cases beyond the typical clinical decision-making process.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed. This study pertains to an in-vitro diagnostic device (a blood test kit and analyzer), not an imaging device or AI-assisted diagnostic tool that would typically involve human readers interpreting output. Therefore, the concept of human readers improving with or without AI assistance does not apply here.

6. Standalone (Algorithm Only) Performance Study

Yes, the studies presented are essentially standalone performance studies for the Alpha Dx System (the "algorithm/device only" in this context). The correlation studies (comparing Alpha Dx to predicate devices) and the clinical sensitivity/specificity calculations demonstrate the performance of the Alpha Dx System itself in measuring biomarkers and its diagnostic utility relative to established methods. There is no human element interacting with the "algorithm" output that would require a human-in-the-loop study in the way it's typically understood for AI systems.

7. Type of Ground Truth Used

The primary type of ground truth used for assessing clinical performance (sensitivity and specificity) is the clinical diagnosis of Acute Myocardial Infarction (AMI). This diagnosis in clinical practice is typically based on a combination of:

Patient symptoms (chest pain)
Electrocardiogram (ECG) changes
Biomarker levels (including those measured by predicate devices, and presumably, overall clinical assessment and follow-up from medical professionals).

For the analytical performance (correlation studies, precision, analytical sensitivity), the "ground truth" is established by the measurements from the predicate devices (e.g., Dade Stratus, Johnson & Johnson Vitros, Beckman Access systems) and by the known concentrations in samples used for analytical sensitivity and precision testing.

8. Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning or AI algorithm development. For an in-vitro diagnostic device like the Alpha Dx System, the "training" (calibration and optimization of the assays) would be performed during the development phase using various controlled samples with known concentrations and patient samples. The information provided focuses on the validation studies, which serve as the "test set." Therefore, a specific sample size for a "training set" as understood in AI is not applicable or provided.

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

Given that this is an in-vitro diagnostic device and not an AI algorithm in the common sense, the concept of "ground truth for a training set" as it applies to AI is not directly relevant. For the development and calibration of the Alpha Dx assays, the "ground truth" would have been established through:

Known concentrations of purified analytes: Used to create calibration curves and set analytical sensitivity.
Reference materials and spiked samples: Used to optimize assay performance and ensure linearity and recovery.
Carefully characterized patient samples: Used during assay development to ensure performance across a range of physiological concentrations and patient conditions, likely confirmed by predicate methods and clinical diagnosis.

The process involves standard laboratory practices for assay development and validation, rather than the "ground truth establishment" methods used for AI training data.

Summary

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MEDICAL, INC. FIRST

X 510(k) SUMMARY OF SAFETY AND EFFECTIVENESS

Alpha Dx System
A. Name and Address of Submitter
- . Company Name and Address:
- Telephone: ●
- FAX: .

Contact Person: ●

. Date 510(k) summary was prepared:
Device Names B.
- 1. Trade Names

The Alpha Dx System consists of:

The Alpha Dx Analyzer, and .
The Alpha Dx Myo/CK/CK-MB/TnI Cardiac Panel Test Kit, or .
The Alpha Dx CK/CK-MB Panel Test Kit, or .
The Alpha Dx Myo/TnI Panel Test Kit .
Common Names 2.
- a. Alpha Dx Analyzer

Fully integrated benchtop analyzer capable of performing in vitro diagnostic measurement of a panel of tests.

b. Alpha Dx Panel Test Kits
Rapid, quantitative and simultaneous measurement of myoglobin (Myo), creatine kinase (CK), creatine kinase MB isoenzyme (CK-MB) and cardiac troponin I (TnI) in whole blood or serum to aid in the diagnosis of acute myocardial infarction (AMI).
1. Classification Names
- a. Alpha Dx Analyzer

Fluorescence Immunoassay Analyzer for use with the Alpha Dx Panel Test Kits for the rapid measurement of a panel of tests (Clinical Chemistry Panel Classification Device List).

First Medical, Inc. 530 Logue Avenue Mountain View, CA 94043 (650) 903-5974 (650) 903-9040 Van N. Johnson December 23, 1997

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b. Alpha Dx Panel Test Kits
Fluorescence Immunoassays for myoglobin, CK, CK-MB and TnI (Clinical Chemistry Panel and Immunology Classification Device List).
C. Legally Marketed Devices
- 1. Panel Test Kits
  - Dade Stratus Myoglobin Fluorometric Enzyme Immunoassay .
  - Johnson & Johnson Vitros CK Slide .
  - Dade Stratus CK-MB Fluorometric Enzyme Immunoassay ●
  - Dade Stratus Cardiac Troponin I Fluorometric Enzyme Immunoassay ●
  - . Beckman Access Troponin I Immunoassay System
- 1. Analyzer
  - Dade Stratus II Fluorometric Immunoassay System ●
D. Device Description

The Alpha Dx Cardiac Panel Test Kits, when used with the Alpha Dx Analyzer, are fluorescence immunoassays for the rapid measurement of myoglobin, CK, CK-MB and TnI in human whole blood or serum.

E. Intended Use
The Alpha Dx Cardiac Panel Test Kit is intended for use with the Alpha Dx Analyzer to provide rapid, quantitative and simultaneous measurement of myoglobin, creatine kinase (CK), creatine kinase MB isoenzyme (CK-MB) and cardiac troponin I (TnI) in whole blood or serum to aid in the diagnosis of acute myocardial infarction (AMI). The Analyzer and Cardiac Panel Test Kit combine ease of use and rapid turnaround time with laboratory-quality performance and reliability. With factory calibration, built-in bilevel quality controls and closed tube sampling, the system can be used in the central laboratory, STAT lab, emergency department, coronary care unit, chest pain center and other point of care locations.
F. Comparison of Methodology with Predicate Devices
The Alpha Dx Cardiac Panel Test Kit, when used with the Alpha Dx Analyzer, provides quantitative determinations of human myoglobin, CK, CK-MB and TnI in whole blood or serum. The current Stratus Myoglobin, CK-MB and Troponin I Fluorometric Enzyme Immunoassays when used with the Stratus II Fluorometric System Analyzer, the Vitros CK Slides when used with the Vitros 700 and the Access Troponin I Assay when used with the Access Immunoassay System are examples of other devices currently marketed for the same uses.

The Alpha Dx Cardiac Panel Test Kits are two-site fluorescence immunoassays. The current Stratus Myoglobin, CK-MB and Cardiac Troponin I Fluorometric Enzyme Immunoassays and the Stratus II Fluorometric Immunoassay Analyzer are examples of currently available products that employ the immunofluorometric procedure and fluorometric detection.

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Monoclonal and polyclonal antibodies are used in the Alpha Dx Cardiac Panel Test Kits. The use of monoclonal and polyclonal antibodies for immunoassay procedures has been clearly demonstrated in other currently commercially available assays and in numerous scientific reports.

G. Summary of Analytical Data
- 1. Dilution Recoveries

The mean recoveries by diluting serum samples with high myoglobin, CK, CK-MB or TnI are as follows:

Analyte	VIVO	AV	------------------------------------------------------------------------------------------------------------------------------------------------------------------------------AV 120JA-MD	1------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
CONTRACTORIAL COLLEGICAL COLLEGION CONSULTION OF. Mean % Recoveries------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	C	AND LIES GENER1A SECT ANNUAL------------------------------------------------------------------------------------------------------------------------------------------------	103Carmer Research and Concell a co	-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------A CONSULTION COLLEGION OF COLLEGION

Table 43 Dilution Recoveries

Analytical Sensitivity 2.
The analytical sensitivity for the Alpha Dx myoglobin, CK, CK-MB and TnI assays are 1.1 ng/mL, 1.8 ng/mL, 0.04 ng/mL, 0.017 ng/mL, respectively.
1. Precision
  Median %CV of the assays are as follows:

%CV	Myo	CK	CK-MB	Tnl
Whole Blood Samples	3.9	5.3	3.9	7.3
Serum Samples	4.0	7.0	2.7	2.4

Table 44 Precision

H. Summary of Clinical Data
- 1. Correlation Between Paired Whole Blood and Serum Samples Tested with the Alpha Dx System

Paired whole blood and serum samples from serial draws of 72 chest pain patients and 24 healthy individuals were tested. Linear regression analyses, after exclusion of samples with levels outside the reportable ranges of the test methods, are as follows:

Method	Myo	CK	CK-MB	Tnl
N	322	309	294	73
Slope	1.05	1.04	1.07	0.90
Intercept	-3	5	-0.1	0.08
r	0.99	0.99	1.00	0.99

Table 45 Correlation Between Whole Blood and Serum

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Correlations Between Whole Blood Samples Assayed with the Alpha Dx System and 2. Paired Serum Samples Assayed with the Predicate Methods
The relation between myoglobin, CK, CK-MB and TnI measurements with the Alpha Dx System and the predicate devices was determined in serial samples from 410 chest pain patients and 134 healthy individuals, after exclusion of samples with levels outside the reportable range of the test methods. Results of the regression analyses are as follows:

	Myo	CK	CK-MB	TnI	TnI
Predicate	Stratus	Vitros	Stratus	Stratus	Access
N	955	923	676	226	244
Slope	0.81	0.77	1.07	0.18	1.44
Intercept (ng/mL)	-2	-1	1.1	0.56	0.96
r	0.98	0.97	0.97	0.93	0.88

Table 46 Correlation Between Alpha Dx System and Predicate Methods

1. Clinical Sensitivity and Specificity of the Alpha Dx TnI, Stratus TnI, Access TnI and Stratus CK-MB Assays
  The clinical cutoffs, sensitivity and specificity for the Alpha Dx TnI, Stratus TnI, Access TnI and the Stratus CK-MB are as follows:

Method	Cutoff Value(ng/mL)	Sensitivity(95% Cl)	Specificity(95% Cl)
Alpha Dx Tnl	0.40	93 ± 6	94 ± 3
Stratus Tnl	1.50	93 ± 6	93 ± 3
Access Tnl	0.15	92± 6	88 ± 4
Stratus CK-MB	7.0	89± 7	90 ± 4

Table 47 Tnl and CK-MB Sensitivity and Specificity Comparison

Sensitivity and specificity for the Alpha Dx TnI and Stratus CK-MB are comparable within the 95% confidence intervals of the two methods. The Alpha Dx TnI assay results were 92% concordant versus the Stratus CK-MB results in 362 subjects tested with both devices. McNemar's test indicates no statistically significant difference between the two assays in diagnostic performance.

Conclusion I.
The Alpha Dx Cardiac Test Discs are used with the Alpha Dx Analyzer for the rapid, quantitative and simultaneous measurement of myoglobin, creatine kinase (CK), creatine kinase MB isoenzyme (CK-MB) and cardiac troponin I (TnI) in whole blood or serum to aid in the diagnosis of acute myocardial infarction (AMI). The data shows that the Alpha Dx Cardiac Test Discs are substantially equivalent to other tests currently in commercial distribution for the purpose of analyzing unknown concentrations of myoglobin, CK, CK-MB and TnI.

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

1 1338 FR

Van N. Johnson . Vice President, Clinical and Regulatory Affairs First Medical, Inc. 530 Logue Avenue Mountain View, California 94043

Re : K974839 Alpha DX System Requlatory Class: I, II Product Code: MMI,JHX, DDR, CGX, KHO December 23, 1997 Dated: Received: December 24, I997

Dear Ms. Johnson:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set """" forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note:

this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

This letter will allow you to begin marketing your device as The FDA described in your 510 (k) premarket notification. 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 Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".

Sincerely yours,
Steven Litman

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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Page _ / of _ /

K97483 510(k) Number (if known):_

Device Name:

Indications For Use:

Statement of Indication for Use

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Qyruic
(Division Sign-Off)

Division of Clinical Laboratory Devices
510(k) Number. 4974839
Over-The-Counter Use

Prescription Use_ 2 (Per 21 CFR 801.109) OR

(Optional Format 1-2-96)

Regulation Number and Section

§ 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system.

(a)
Identification. A creatine phosphokinase/creatine kinase or isoenzymes test system is a device intended to measure the activity of the enzyme creatine phosphokinase or its isoenzymes (a group of enzymes with similar biological activity) in plasma and serum. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.(b)
Classification. Class II.