The CardioMPO Reagent Kit is an enzyme immunoassay intended for the quantitative determination of myeloperoxidase in human plasma, to be used in conjunction with clinical history, ECG and cardiac biomarkers to evaluate patients presenting with chest pain that are at risk for major adverse cardiac events, including myocardial infarction, need for revascularization, or death.

The PrognostiX CardioMPO Calibrator Kit is intended for use with the CardioMPO Reagent Kit to establish a calibration curve that is used to determine MPO concentration.

The PrognostiX CardioMPO Control Kit is intended for use with the CardioMPO Reagent Kit as an assayed quality control sample to monitor and evaluate the precision and accuracy of the CardioMPO Test.

Device Description

The CardioMPO Test is a sandwich enzyme immunoassay that uses two highly specific antibodies, one monoclonal and one polyclonal, and an enzyme labeled anti-rabbit IgG antibody for the measurement of MPO concentration in human plasma. The CardioMPO Test is comprised of the CardioMPO Reagent Kit, the CardioMPO Calibrator Kit, and the CardioMPO Control Kit.

The CardioMPO Reagent Kit contains the following: a microtiter plate coated with a monoclonal anti-MPO antibody; a solution of primary polyclonal rabbit anti-MPO antibody; a solution of secondary goat anti-rabbit IgG antibody labeled with horseradish peroxidase solution; TMB substrate solution; Stop Solution; Wash Buffer Concentrate; Assay Buffer; and plate sealers.

The CardioMPO Calibrator Kit contains six Calibrators comprised of human MPO in a phosphatebuffered matrix containing proteins, detergents, and stabilizers. Calibrators are intended to establish a calibration curve that is used to determine MPO concentration. Calibrator values are provided on individual Calibrator labels. Calibrators are provided ready-to-use.

The CardioMPO Control Kit contains three Controls comprised of human MPO in a human plasma matrix. Controls are intended to monitor and evaluate the precision and accuracy of the CardioMPO Test. Ranges are provided on individual Control labels. Controls are freated in the same manner as patient samples.

Calibrators are added directly to the appropriate wells of the Microtiter Plate. Assay Buffer is added to all wells that are intended for Control or sample analysis. Aliquots of Controls or samples are added to the appropriate wells and the plate is incubated for 60 minutes at 20-26°C. The wells are then washed with Wash Buffer to remove antigens not specifically bound to the immobilized antibody.

A yellow primary polyclonal rabbit anti-MPO antibody is added to each well and incubated for 60 minutes at 20-26°C. This antibody binds to the MPO captured on the plate. The plate is again washed with Wash Buffer to remove unbound primary antibody.

A blue secondary goat anti-rabbit IgG antibody, labeled with the enzyme horseradish peroxidase (HRP), is then added to each well and incubated for 30 minutes at 20-26°C. This antibody binds to the primary antibody, and the MPO in the sample is "sandwiched" between the monoclonal antibody on the solid phase and a complex of the rabbit anti-MPO and the HRP-goat anti-rabbit IgG antibody. The wells are washed with Wash Buffer to remove unbound HRP-labeled antibody.

The substrate, tetramethylbenzidine (TMB), is then added to each well and incubated for 10 minutes at 20-26°C resulting in the development of a blue color. Color development is stopped with the addition of Stop Solution, changing the color to yellow.

The enzymatic turnover of the substrate is determined spectrophotometrically at 450 nm, preferably with correction at 630 nm, and is directly proportional to the concentration of MPO. The absorbances of the Calibrators are used to plot a standard curve of absorbance versus MPO concentration from which the MPO concentration in the Controls or samples can be determined.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and study for the PrognostiX CardioMPO™ Test:

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

The document does not explicitly state "acceptance criteria" for all performance characteristics in a separate section with numerical targets. Instead, it presents performance characteristic results and implies their acceptability by stating "The PrognostiX CardioMPO Test is acceptably precise, linear, accurate, and is not subject to appreciable cross-reactivity or interference." and "The detection limit of 13 pM is acceptable for the intended use of this test."

However, we can infer acceptance criteria based on the comparison to the predicate device and from general good practices for in vitro diagnostic devices, and report the observed performance:

Acceptance Criteria (Inferred/Stated)	Reported Device Performance (CardioMPO™ Test)	Notes
Analytical Performance
Minimum Detection Limit	13 pM MPO	Calculated by interpolation of the mean + 2 SD of 24 replicates of 0 pM MPO Calibrator (F). Stated as "acceptable for the intended use."
Total Precision in Plasma	8.2%	Compares favorably with the predicate device's <8% total precision. The main summary table lists "<9%", so 8.2% meets this. NCCLS guidelines EP5-A followed.
Within-run Precision	5.5%	Compares favorably with the predicate device's <6% within-run precision. The main summary table lists "<6%", so 5.5% meets this. NCCLS guidelines EP5-A followed.
Linearity Range	13 pM to 5223 pM MPO	Within 60 pM or 9% in this interval. NCCLS guidelines EP6-A followed.
Interfering Substances Bias	≤10% for listed substances	No interference observed at tested concentrations (or <1500 mg/L hemoglobin). NCCLS guidelines EP7-A followed. Hemoglobin levels >1500 mg/L caused >10% bias.
Interfering Antibodies Recovery	89% to 118% (mean 108%)	No significant interference observed due to heterophilic antibodies.
Cross-reactivity	No significant cross-reaction	For a list of tested substances (e.g., α-1 antrypsin, C-reactive protein, etc.) up to indicated concentrations. NCCLS guidelines EP7-A followed.
Spiking Recovery	89% to 105% (mean 97%)	Fourteen lithium heparin plasma samples spiked with various MPO levels. Acceptable range for recovery in assays is typically 80-120%.
Dilution Recovery	1:2 dilution: 102% to 131% (mean 116%)	Recoveries at dilutions 1:4 through 1:16 rose to 132%-145% due to decreased plasma matrix effects. PrognostiX does not recommend further dilution for samples exceeding the highest calibrator.
Hook Effect	No hook effect up to 800,000 pM MPO	Roughly 150x greater than the upper end of the reportable range and 500x greater than the median clinical level.
Clinical Performance
Odds Ratio for MACE (All Patients)	Increases from 1.0 to 3.3 across 4 quartiles	Statistically significant (p < 0.001 for highest quartile). Demonstrates association with risk of MACE.
Odds Ratio for MACE (TnT negative)	Increases from 1.0 to 6.9 across 4 quartiles	Statistically significant (p < 0.001 for highest quartile). Stronger association in this subgroup, highlighting potential utility for early risk stratification.
Association with MACE	Demonstrated association	"The clinical evaluation... demonstrate[s] that plasma levels of MPO are associated with risk of myocardial infarction, revascularization, and death."

2. Sample size used for the test set and the data provenance

Test Set (Clinical Study):
- Sample Size: 560 banked plasma samples.
- Data Provenance: Retrospective study of patients presenting to the Emergency Department within 24 hours of the onset of chest pain. These samples were obtained from a prior study (Brennan, et al, N Engl J Med 2003; 349:1595-1604).
- Country of Origin: Not explicitly stated, but the cited paper by Brennan et al. is from the New England Journal of Medicine, suggesting a US or Western origin for the prior study.
Analytical Performance Studies (e.g., Precision, Linearity, Interference, etc.):
- Sample Size:
  - Sensitivity: 24 replicates of 0 pM MPO Calibrator.
  - Precision: 9 samples (4 Matrix Controls, 5 Plasma Controls) assayed in duplicate, for 20 days.
  - Linearity: 9 MPO concentrations created by intermixing spiked and neat plasma samples.
  - Interfering Substances: Plasma containing 3000 pM and 1000 pM MPO.
  - Interfering Antibodies: Twenty-one plasma samples.
  - Cross-reactivity: Plasma pools containing MPO and Assay Buffer.
  - Spiking Recovery: Fourteen lithium heparin plasma samples.
  - Dilution Recovery: Thirteen lithium heparin plasma samples.
  - Reference Interval: "a population of apparently healthy blood donors" with 145 males and 149 females after outlier adjustment (initial sample size not explicitly given but >294).
- Data Provenance: These are laboratory-based analytical studies, likely conducted internally by PrognostiX, Inc. and are prospective in nature for the purpose of this submission (i.e., substances were specifically "tested" and samples "analyzed" for the submission).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

The ground truth for the clinical study was the occurrence of "major adverse cardiac events (MACE), including myocardial infarction, need for revascularization, or death" over a 30-day and 6-month interval. This outcome was assessed by follow-up phone calls. The document does not specify:

The number of experts used to establish this ground truth.
The qualifications of those experts (e.g., cardiologists, emergency physicians).
The methods used to adjudicate MACE events (e.g., review of medical records, independent committee).
Given it was "assessed by follow up phone calls," it's highly likely that trained personnel (possibly nurses or research coordinators) collected this information, potentially with physician review for confirmation, but the details are absent.

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

The document does not specify any formal adjudication method (like 2+1, 3+1) for the clinical outcomes (MACE) in the test set. The assessment relied on "follow up phone calls."

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done.
The CardioMPO™ Test is an in vitro diagnostic (IVD) assay for measuring a biomarker (myeloperoxidase) in plasma. It is not an imaging AI device that would involve human "readers" interpreting images with or without AI assistance. The test provides a quantitative result which is then used by clinicians in conjunction with other clinical information.

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

Yes, the analytical performance and clinical utility data presented are for the device operating in a standalone manner. The device measures MPO concentration; there is no human-in-the-loop performance component for the measurement itself. The interpretation of the MPO result (in conjunction with clinical history, ECG, and cardiac biomarkers) is where human expertise is applied. The clinical study demonstrated the MPO test's predictive power as a standalone biomarker.

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

The ground truth for the clinical study was outcomes data, specifically the occurrence of "major adverse cardiac events (MACE), including myocardial infarction, need for revascularization, or death" within 30 days and 6 months after presentation with chest pain.

8. The sample size for the training set

The document does not explicitly describe a separate "training set" for the clinical study. The 560 banked plasma samples were used to evaluate the device's performance in predicting MACE. The study used multivariate logistic regression models for analysis, which are typically applied to a dataset to assess relationships, but there's no mention of a separate training phase to develop the MPO test itself or a decision rule based on MPO levels from this dataset, beyond assessing its association with outcomes. It's more of a validation of the biomarker's utility.

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

As there's no explicitly defined separate "training set" for the clinical study from the perspective of developing an AI algorithm, this question isn't directly applicable in the conventional sense of AI/ML model development. However, if we interpret "training set" as the data used to understand the reference ranges or analytical characteristics, the ground truth was established as follows:

Reference Interval: Plasma samples from "a population of apparently healthy blood donors" were screened, and outliers were removed using a two-stage method (Box-Cox transformation followed by robust outlier detection). The "ground truth" for normality was based on this statistical analysis of healthy individuals.
Analytical Studies (Precision, Linearity, etc.): Ground truth for these was established by standard laboratory practices (e.g., using known concentrations of MPO, spiked samples, or reference materials) according to NCCLS guidelines. These studies aim to characterize the assay's performance against expected analytical values.

Summary

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K050029

510(k) Summary

PrognostiX CardioMPO™ Test

This 510(k) summary is being submitted in accordance with the Safe Medical Devices Act of 1990 and 21 CFR 807.92.

General Information

Name and Address of Applicant:	PrognostiX, Inc.10265 Carnegie AvenueCleveland, OH 44106216-445-7469Thomas M. Jackson, Ph.D.
Date Prepared:	January 5, 2005
Device Trade Name:	CardioMPO™ Test
Common Name:	Myeloperoxidase Test

Identification of Legally Marketed Device

diaDexus PLAC™ Test 510(k) number K030477 diaDexus, Inc. 343 Oyster Point Blvd. South San Francisco, CA 94080

Intended Use

The CardioMPO Test is an enzyme immunoassay intended for the quantitative determination of myeloperoxidase in human plasma, to be used in conjunction with clinical history, ECG and cardiac biomarkers to evaluate patients presenting with chest pain that are at risk for major adverse cardiac events, including myocardial infarction, need for revascularization, or death.

Device Description

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Comparison of New Device to Predicate Device

The chart below identifies the similarities and differences between the PrognostiX CardioMPO Test and the predicate device, the diaDexus PLAC™ Test.

Characteristic	PrognostiX CardioMPO Test(Proposed)	diaDexus PLAC™ Test(K030477)
Intended Use	Quantitative in vitro diagnostic test to detect myeloperoxidase in human plasma, to be used in conjunction with clinical history, ECG and cardiac biomarkers to evaluate patients presenting with chest pain that are at risk for major adverse cardiac events, including myocardial infarction, need for revascularization, or death.	Quantitative in vitro diagnostic test for the determination of Lp-PLA2 in human plasma, to be used in conjunction with clinical evaluation and patient risk assessment as an aid in predicting risk for coronary heart disease.
Analyte	Myeloperoxidase	Lipoprotein-associatedphospholipase A2
Sample	Lithium Heparin Plasma	EDTA Plasma
Methodology	ELISA	ELISA
Detection Method	Optical Density at 450 nm	Optical Density at 450 nm
Risk to Patients	Minimal Risk	Minimal Risk
LaboratoryEnvironment	Professional Laboratory	Professional Laboratory
Precision in plasma,Total	<9%	<8%
Within-run	<6%	<6%
Interferences	No interference observed at the suggested NCCLS test concentrations of triglycerides, cholesterol, bilirubin, and albumin.No interference up to 1500 mg/L hemoglobin.	No interference observed at the suggested NCCLS test concentrations of hemoglobin, triglycerides, cholesterol, bilirubin, and albumin.
Clinical study results	Odds ratio increases from 1.0 to a max. of 5.2 across 4 quartiles	Risk ratio increases from 1.0 to a max. of 2.5 across 3 tertiles

Performance Characteristics

Sensitivity

The minimum detection limit, as calculated by interpolation of the mean plus two standard deviations of 24 replicates of the 0 pM MPO Calibrator (F), is 13 pM MPO.

Assay Precision

Total and within-run precision were determined by testing four Matrix Controls, containing human MPO in Calibrator matrix, and five Plasma Controls, containing human MPO in human lithium heparin plasma, with MPO concentrations distributed throughout the calibration range of the assay, according to NCCLS guidelines EP5-A. The nine samples were assayed in duplicate, using a single lot of reagents and Calibrators, on two separate plates per day, for twenty days. A new calibration curve was run in duplicate on each plate. Total precision in plasma samples was 8.2% and within-run precision was 5.5%.

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Linearity

Lithium heparin plasma samples spiked to high MPO levels were intermixed with neat plasma samples with low MPO levels to create nine MPO concentrations across and exceeding the anticipated linear range. Linearity of the MPO levels measured in the mixtures was assessed using the polynomial evaluation of linearity as recommended in NCCLS guidelines EP6-A. The CardioMPO Test was linear from 13 pM to 5223 pM MPO, within 60 pM or 9% in this interval.

Interfering Substances

The following substances, when tested in plasma containing 3000 pM and 1000 pM MPO, according to NCCLS guidelines EP7-A, were found not to interfere up to the concentrations indicated. Bias of 10% or less was not considered interference.

Substance tested	Test concentration(mg/L)	Comments
Acetylsalicylic acid	600	Toxic dose
Albumin	50000	High*
Amoxicillin	75	3x therapeutic dose
Bilirubin, conjugated	50	High*
Bilirubin, unconjugated	150	High*
Captopril	5	Toxic dose
Ceruloplasmin	600	High
Cholesterol	1000	High*
DNA	16.7	High
Fenofibrate	45	3x therapeutic dose
Hemoglobin	1500	Hemolysis **
Heparin, lithium	3000 U/L	3x therapeutic dose
Hydrochlorothiazide	6	3x therapeutic dose
Hydrocortisone	0.69	Toxic dose
Ibuprofen	500	Toxic dose
Indomethacin	36	2x therapeutic dose
Isosorbide dinitrate	0.15	3x therapeutic dose
Lovastatin	53	2x therapeutic dose
Methotrexate	160	Therapeutic dose
Metoprolol	5	Toxic dose
Naproxen	500	4x therapeutic dose
Niacin	0.5	5x therapeutic dose
Nifedipine	0.4	2x therapeutic dose
Salicylic acid	600	Toxic dose
Sodium azide	0.50%	5x preservative dose
Triglycerides	5000	Lipemia

High level of interfering substance per NCCLS EP7-A

** Hemoglobin levels of 5000 mg/L produced a bias of >10%. A doseresponse series showed a bias of <10% at <1500 mg/L hemoglobin within a 95% prediction interval.

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Interfering Antibodies

Twenty-one plasma samples known to have elevated levels of heterophilic or other potentially interfering antibodies, such as HAMA, RF, anti-MPO p-ANCA, etc., were analyzed for interference in the CardioMPO Test. The mean recovery of MPO from samples containing heterophilic antibodies was 108% with individual recoveries ranging from 89 to 118%. Therefore, no evidence of significant interference was observed due to the heterophilic antibodies tested in the CardioMPO Test.

Cross-reactivity

The following potential cross-reactants, tested in both a plasma pool containing MPO and Assay Buffer according to NCCLS guidelines EP7-A, showed no significant cross-reaction in the assay up to the concentrations indicated.

Substance tested	Concentrationstested (nM)
α-1 antrypsin, human	1250, 125, 12.5
C-reactive protein, human	543, 54.3, 5.43
Lysozyme, human	4464, 446.4, 44.64
IgA, human	417, 41.7, 4.17
Elastase, human	2500, 250, 25
Lactoperoxidase, bovine	801, 80.1, 8.01
Lactoferrin, human	781, 78.1, 7.81
COX1, ovine	893, 89.3, 8.93
COX2, human	868, 86.8, 8.68
Thyroid peroxidase, human	595, 59.5, 5.95
Troponin I, human	2155, 215.5, 21.55

Spiking recovery

Fourteen lithium heparin plasma samples were spiked with 509.9, 1016, and 1500 pM MPO and analyzed for recovery. The percent recovery was calculated by dividing the mean measured MPO concentration of the spiked sample by the expected MPO concentration, where the expected MPO concentration was the sum of the measured MPO concentration in the neat plasma sample and the concentration of the MPO spike. The overall recovery of spiked MPO ranged from 89% to 105% with a mean of 97%.

Dilution recovery

Thirteen lithium heparin plasma samples were spiked with 1500 pM MPO and diluted 1:2, 1:4, 1:8, and 1:16 with Assay Buffer. The percent recovery was calculated by dividing the mean MPO concentration of the pre-diluted sample multiplied by the dilution factor by the mean MPO concentration of the sample with no pre-dilution. The mean recovery of a 1:2 dilution was 116%, with recoveries ranging from 102% to 131%. The mean recovery at dilutions of 1:4 through 1:16 rose from 132% to 145% due to decreased plasma matrix effects. The PrognostiX CardioMPO Test is formulated to account for matrix effects associated with a 5 µL human plasma sample. PrognostiX does not recommend further dilution of samples with MPO levels exceeding the value of the highest Calibrator should be reported as greater than that level, e.g. > 5000 pM.

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Hook Effect

There is no evidence of hook effect in the CardioMPO Test up to 800,000 pM MPO, roughly 150 times greater than the upper end of the reportable range and 500 times greater than the median level of patients in the clinical study.

Reference Interval

Plasma samples from a population of apparently healthy blood donors, were evaluated with the CardioMPO Test. A two-stage outlier detection scheme, a Box-Cox transformation followed by a robust outlier detection method, was used to eliminate six outliers. Since there was no significant difference in MPO levels between males (n=145) and females (n=149) after adjustment for outliers, the reference range was estimated from the adjusted normal subject population.

The median MPO level for subjects in the adjusted normal subject population was 193 pM and the range of results was 48 to 924 pM. The non-parametric distribution of mveloperoxidase levels in this normal population vields a two-tailed central 95% reference interval, corrected for the influence of outlier rejection, of 78 - 708 pM. However, in this application the more appropriate single-tailed lower 95% reference interval, again corrected for the influence of the outlier rejection method, is < 539 pM.

Summary of Clinical Study

To determine the efficacy of the PrognostiX CardioMPO Test as a predictor of risk for major adverse cardiac events (MACE), MPO levels were measured in 560 banked plasma samples from a prior study of patients presenting to the Emergency Department within 24 hours of the onset of chest pain (Brennan, et al, N Engl J Med 2003; 349:1595-1604). Patients were followed for the development of myocardial infarction, need for revascularization, or death over the next 30-day and 6 month interval. Samples assayed with the PrognostiX CardioMPO Kits were from patients aged 23 to 96 years. Median age was 64. The incidence of MACE was assessed by follow up phone calls at 30 davs and 6 months.

Multivariate logistic-rearession models (SAS version 8.0, SAS Institute) were developed to calculate odds ratios and 95% confidence intervals. The adjusted covariates were age, gender, race, Troponin T (≤0.03 ng/mL vs. >0.03 ng/mL) (McErlean et al. Am J Cardiol 2000;85:421-426), C-reactive Protein (<1 mg/L. >3 mg/L. >3 mg/L) (Brennan et al. N Engl J Med 2003;349:17, 1595-1604), CK-MB (≤8.8 ng/mL vs. >8.8 ng/mL) (McErlean et al. Am J Cardiol 2000;85:421-426), history of smoking, history of diabetes, history of hypertension, and history of high cholesterol. Missing covariate information on some subjects reduced the study population. The risk of MACE in all patients in the ensuing 30-day period increased with increasing quartiles of myeloperoxidase levels. Adjusted odds ratios and the percentage of patients within an MPO quartile with and without MACE at 30 days are shown in the following graph and table.

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Risk of MACE in All Patients

Image /page/7/Figure/1 description: This image is a bar graph that shows the percentage of patients within a quartile. The x-axis shows the MPO by Quartile (pM) with the ranges <1082, 1082-1853, 1854-2990, and >2990. The y-axis shows the percentage of patients within a quartile, ranging from 0 to 100. The graph compares the percentage of patients with MACE and without MACE in each quartile.

MPO (pM)	MACE at 30 days, All Patients (n=523)
	<1082	1082-1853	1854-2990	>2990
Odds Ratio	1.0	2.5	2.8	3.3
95% CI	NA	1.3-4.8	1.5-5.6	1.7-6.4
p value		p = 0.007	p = 0.0021	p < 0.001

*In each analysis the first quartile served as the reference group

Similar analysis of patients that were persistently negative for Troponin T (≤0.03 ng/mL) also revealed a significantly higher risk of MACE for patients with plasma MPO levels in higher quartiles.

Image /page/7/Figure/5 description: This bar graph shows the percentage of patients within a quartile. The x-axis shows the MPO by Quartile (pM) with values of <1082, 1082-1853, 1854-2990, and >2990. The y-axis shows the percentage of patients within a quartile from 0 to 100. The graph compares the percentage of patients with MACE and No MACE for each quartile.

Risk of MACE in Patients Persistently Negative for Troponin T

	MACE at 30 days, TnT negative Patients (n=304)
MPO (pM)	<1082	1082-1853	1854-2990	>2990
Odds Ratio	1.0	3.4	4.1	6.9
95% CI	NA	1.2-9.4	1.5-11.4	2.5-19.2
p value		p = 0.0194	p = 0.007	p < 0.001

*In each analysis the first quartile served as the reference group

It should be noted that different cut-off points may be appropriate for different clinical populations.

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Conclusions

The PrognostiX CardioMPO Test is acceptably precise, linear, accurate, and is not subject to appreciable cross-reactivity or interference. The detection limit of 13 pM is acceptable for the intended use of this test. The test is reproducible across several reagent lots, several instruments and multiple operators and should provide reliable and reproducible results when used by professional clinical laboratories.

The clinical evaluation of the CardioMPO Test involved re-analysis of 560 banked lithium heparin plasma samples from an earlier study of patients with chest pain. The results of this study demonstrate that plasma levels of MPO are associated with risk of myocardial infarction, revascularization, and death. The performance testing and clinical data support the safety and effectiveness of the CardioMPO Test as an aid in evaluating patients presenting with chest pain that are at risk for major adverse cardiac events, including myocardial infarction, need for revascularization, or death.

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Image /page/9/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle or other bird-like figure, represented by three curved lines that suggest wings or feathers.

Food and Druq Administration 2098 Gaither Road Rockville MD 20850

MAY 1 0 2005

Thomas M Jackson, Ph.D. Director of Product Development Prognostix, Inc. 10265 Carnegie Avenue Cleveland, OH 44106

K050029 Re:

Trade/Device Name: CardioMPO™M Test Regulation Number: 21 CFR 866.5600 Regulation Name: Low- density lipoprotein immunological test system Regulatory Class: Class II Product Code: NTV, JJX, JIS Dated: April 19, 2005 Received: April 20, 2005

Dear Dr. Jackson:

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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240)276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html

Sincerely yours,

Jean M. Cooper, MS, DUM

Jean M. Cooper, MS, D.V.M. 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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PrognostiX, Inc. 510(k) Notification for CardioMPO

Indications for Use

510(k) Number (if known): K050029

Device Name:__CardioMPO™ Test

Indications for Use:

The CardioMPO™ Test is comprised of the CardioMPO Reagent Kit, the CardioMPO Calibrator Kit, and the CardioMPO Control Kit.

The PrognostiX CardioMPO Calibrator Kit is intended for use with the CardioMPO Reagent Kit to establish a calibration curve that is used to determine MPO concentration.

The PrognostiX CardioMPO Control Kit is intended for use with the CardioMPO Reagent Kit as an assayed quality control sample to monitor and evaluate the precision and accuracy of the CardioMPO Test.

Prescription Use _ X (Part 21 CFR 801 Subpart D) AND/OR

Over-the-Counter Use (21 CFR 807 Subpart C)

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

nce of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Division Sign-Off

Office of In Vitro Diagnostic
Device Evaluation and Safety

51000 K050029

Submitted on: 05 January 2005

Page vii

Regulation Number and Section

§ 866.5600 Low-density lipoprotein immunological test system.

(a)
Identification. A low-density lipoprotein immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the low-density lipoprotein in serum and other body fluids. Measurement of low-density lipoprotein in serum may aid in the diagnosis of disorders of lipid (fat) metabolism and help to identify young persons at risk from cardiovascular diseases.(b)
Classification. Class II (performance standards).