The Envoy® 500 HDL Cholesterol Reagent and Envoy® 500 HDL Calibrator are intended for use with the Envoy® 500 Chemistry System as a system for the quantitative determination of high density lipoprotein (HDL) cholesterol in serum and plasma. HDL cholesterol measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases, and for the assessment of the risk of developing cardiovascular disease.

Device Description

The Envoy® 500 HDL Cholesterol Reagent is a two-part reagent that is calibrated with the Envoy® 500 HDL Calibrator for use with the Envoy® 500 Chemistry System. This reagent determines high density lipoprotein cholesterol through the accelerator selective detergent methodology. This procedure measures HDL-cholesterol in a two step reaction sequence. In the first step, non-HDL cholesterol is rendered non-reactive. In the second step, HDL cholesterol is solubilized using a selective detergent and reacts to produce a red chromogen.

AI/ML Overview

Here's an analysis of the acceptance criteria and study detailed in the provided text for the Envoy® 500 HDL Cholesterol Reagent and Envoy® 500 HDL Calibrator:

1. Table of Acceptance Criteria and Reported Device Performance

The provided text focuses on demonstrating the performance of the device without explicitly stating pre-defined "acceptance criteria" in a structured table. However, we can infer the acceptance criteria based on the reported performance for each study.

Performance Characteristic	Stated Acceptance Criteria (Inferred)	Reported Device Performance
Usable Range (Linearity)	- Recovery of linearity related solutions across the expected range (5 to at least 150 mg/dL).	- Linear range from 5 to at least 150 mg/dL. - Linear regression: (Envoy Recoveries) = - 0.6 mg/dL + 19.284 x (Dilution Factor), r = 0.9998, syx = 1.11 mg/dL, n = 44, range = 0.1 to 173.5 mg/dL.
Limit of Detection (LoD)	- LoD with proportions of false positives (a) less than 5% and false negatives (B) less than 5%.	- Limit of Blank (LoB): 0.29 mg/dL. - Reported LoD: 0.46 mg/dL. - Proportions of false positives (a) less than 5% and false negatives (B) less than 5%.
Precision	- Precision to be demonstrated by replicate assay of control sera.	Level 1 (mean 36.8 mg/dL): - Within Run: 1 SD = 0.52, %CV = 1.4% - Total: 1 SD = 0.72, %CV = 2.0% Level 2 (mean 71.1 mg/dL): - Within Run: 1 SD = 0.68, %CV = 1.0% - Total: 1 SD = 1.25, %CV = 1.8%
Correlation	- Comparison to a commercially available method using least squares linear regression and Passing-Bablok regression.	Least Squares Linear Regression: - Envoy 500 = 0.7 mg/dL + 1.021 × Competitive Method - r = 0.995 - S = 2.42 mg/dL - 95% CI y-intercept: 0.07 to 1.38 mg/dL - 95% CI slope: 1.010 to 1.032 Passing-Bablok Regression: - Envoy 500 = 0.7 mg/dL + 1.015 × Competitive Method - 95% CI y-intercept: 0.2 to 2.0 mg/dL - 95% CI slope: 1.000 to 1.029
Stability	- Statistical estimates of total imprecision to be less than 1.5 mg/dL over claimed stability periods (14-day onboard reagent, 7-day calibration).	- Total imprecision less than 1.5 mg/dL for 14-day onboard reagent stability and 7-day calibration stability.

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

Usable Range:
- Sample Size: n = 44 (reference pools prepared by diluting human HDL cholesterol concentrate with stripped human serum pool).
- Data Provenance: Not explicitly stated (e.g., country of origin). The samples are referred to as "human HDL cholesterol concentrate" and "stripped human serum pool," suggesting they are derived from human biological materials.
- Retrospective/Prospective: Not specified.
Limit of Detection:
- Sample Size: 40 blank samples and 40 low-level samples.
- Data Provenance: Not explicitly stated.
- Retrospective/Prospective: Not specified.
Precision:
- Sample Size: Level 1: n = 45; Level 2: n = 48 (replicate assays of commercially available control sera).
- Data Provenance: "Commercially available control sera." Not explicitly stated (e.g., country of origin).
- Retrospective/Prospective: Not specified, but generally implies a prospective experimental setup for precision studies.
Correlation:
- Sample Size: n = 312 (mixed serum and plasma specimens).
- Data Provenance: "Collected from adult patients." Not explicitly stated (e.g., country of origin).
- Retrospective/Prospective: Not specified, but "collected from adult patients" often implies a retrospective collection or a prospective collection for this specific study.

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

This device is an in-vitro diagnostic (IVD) reagent for determining a biochemical analyte (HDL cholesterol). The ground truth for such devices is established through reference methods or by the intrinsic properties of reference materials, not typically by human experts making diagnoses or interpretations like in imaging studies.

For Usable Range, ground truth is based on known dilution factors of a reference standard.
For Limit of Detection, ground truth is based on blank samples and low-level samples, with expected very low or zero concentrations.
For Precision, ground truth is the "true" concentration of the control sera, established by the manufacturer of the control sera or a reference lab, not individual experts.
For Correlation, the ground truth is the measurement obtained by a "commercially available method" (the predicate or another established method), not human experts.

Therefore, the concept of "number of experts" and "qualifications of those experts" as typically applied in AI/ML performance evaluation (e.g., radiologists interpreting images) is not directly applicable here.

4. Adjudication Method for the Test Set

As explained in point 3, the ground truth for chemical analyte measurements is typically established by reference methods or material properties, not through expert adjudication in the classic sense. Therefore, no adjudication method (like 2+1 or 3+1 consensus) is described or applicable for this type of device.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) reagent, not an imaging or diagnostic AI tool that assists human readers. Its performance is evaluated biochemically against reference methods and statistical parameters.

6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, the studies presented (Usable Range, Limit of Detection, Precision, Correlation, Stability) evaluate the performance of the Envoy® 500 HDL Cholesterol Reagent and Calibrator directly on serum/plasma samples using the Envoy® 500 Chemistry System. This represents a standalone performance evaluation of the assay system without human interpretation being a primary variable in the measurement outcome. The role of "human-in-the-loop" would be limited to operating the analyzer and interpreting the numerical results, not making subjective diagnoses from raw data.

7. The Type of Ground Truth Used

Usable Range: The ground truth is based on the known concentrations of HDL cholesterol in reference pools prepared by diluting a human HDL cholesterol concentrate with stripped human serum. The dilution factors provide the expected "true" values.
Limit of Detection: The ground truth is based on blank samples (expected zero concentration) and low-level samples with known, very low concentrations.
Precision: The ground truth is the assigned value of commercially available control sera, which are typically established through rigorous inter-laboratory comparisons or against reference methods by the control manufacturer.
Correlation: The ground truth is the measurement obtained by a "commercially available method" (the predicate device or another established method) used as a comparative standard.
Stability: The ground truth is again the assigned value of serum controls.

In summary, the ground truth is established through a combination of:

Reference materials with known concentrations.
Established analytical methods.
Commercially validated control materials.

8. The Sample Size for the Training Set

The provided summary describes performance evaluation studies. For an IVD reagent like this, the "training set" doesn't apply in the same way as it would for an AI/ML algorithm. Reagents and calibrators are developed through a formulation and optimization process that involves wet lab experimentation, but this experimental data is not typically referred to as a "training set" in the context of device submission. The studies detailed here are for validation of the finalized product.

Therefore, no specific sample size for a "training set" is mentioned because it's not a relevant concept for this type of device.

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

Given that the concept of a "training set" is not applicable here as for AI/ML algorithms, the establishment of ground truth for such a set is also not relevant or described. The performance data presented demonstrates the analytical characteristics of the final reagent and calibrator.

Summary

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DEC 2 0 2007

Summary of 510(k) Safety and Effectiveness Information

Envoy® 500 HDL Cholesterol Reagent and Envoy® 500 HDL Calibrator

This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

Submitted by:

	Vital Diagnostics, Inc.1075 West Lambert Road, Building DBrea, California 92861
Contact Person:	Wynn StockingRegulatory Affairs Manager
Date Submitted:	December 4, 2007
Device Names:
Proprietary names:	Envoy® 500 HDL Cholesterol Reagent Kit, andEnvoy® 500 HDL Calibrator Kit
Common names:	High density lipoprotein (HDL) cholesterol reagent andHigh density lipoprotein (HDL) cholesterol calibrator
Classification names:	LDL & VLDL precipitation, cholesterol via esterase-oxidase, HDL, andCalibrator, primary

Device Description:

Intended Use:

The Envoy® 500 HDL Cholesterol Reagent and Calibrator are for the quantitative determination of high density lipoprotein (HDL) cholesterol in serum and plasma using the Envoy® 500 Chemistry System. HDL Cholesterol measurements are used in the diagnosis and treatment of lipid disorders mellitus), atherosclerosis, and various liver and renal diseases, and for the assessment of the risk of developing cardiovascular disease.

Predicate Device:

The Envoy 500 HDL Cholesterol Reagent and Calibrator are substantially equivalent to the Genzyme Ultra N-geneous HDL Cholesterol Reagent, product nos. 80-6283-00 and 80-6277-00 and the Genzyme Ultra N-geneous HDL Cholesterol Calibrator, product no. 80-6449-00, which are currently marketed by Genzyme Corporation of Cambridge, MA.

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Summary of Performance Data:

The effectiveness of Envoy® 500 HDL Cholesterol Reagent and the Envoy® 500 HDL Calibrator for the Envoy® 500 Chemistry System is shown by the following studies.

Usable Range

The linear range of the Envoy 500 HDL Cholesterol Reagent is from 5 to at least 150 mg/dL, as shown by the recovery of linearity related solutions that span the linear range. Least squares regression statistics compare recoveries to the dilution factors of a set of reference pools prepared by diluting a human HDL cholesterol concentrate with stripped human serum pool.

(Envoy Recoveries) = - 0.6 mg/dL + 19.284 x (Dilution Factor), r = 0.9998, syx = 1.11 mg/dL, n = 44, range = 0.1 to 173.5 mg/dL

Limit of Detection

The limit of detection (LoD) for HDL cholesterol was determined based on CLSI protocol EP17-A. Forty blank samples and 40 low level samples were assayed. The Limit of Blank (LoB) is 0.29 mg/dL. The reported LoD is 0.46 mg/dL with proportions of false positives (a) less than 5% and false negatives (B) less than 5%.

Precision

Precision is demonstrated by the replicate assay of commercially available control sera. Precision statistics, calculated analogous to the method described in NCCLS Guideline EP3-T, are shown below.

Sample	n	mean	Within Run		Total
			I SD	%CV	1 SD	%CV
Level 1	45	36.8	0.52	1.4%	0.72	2.0%
Level 2	48	71.1	0.68	1.0%	1.25	1.8%

Correlation

Mixed serum and plasma specimens, collected from adult patients, were assayed for HDL cholesterol using the Envoy 500 HDL cholesterol application and another commercially available method. Results were compared by least squares linear regression and Passing-Bablok regression and the following statistics were obtained.

Least Squares Linear Regression

Envoy 500 = 0.7 mg/dL + 1.021 × Competitive Method r = 0.995 S = 2.42 mg/dL = 2.42 mg/dL = n = 312 = range = 5 - 158 mg/dL 95% CI y-intercept: 0.07 to 1.38 mg/dL 95% CI slope: 1.010 to 1.032

Passing - Bablok Regression

Envoy 500 = 0.7 mg/dL + 1.015 × Competitive Method 95% CI y-intercept: 0.2 to 2.0 mg/dL 95% CI slope: 1.000 to 1.029

Stability

The 14 day onboard reagent stability and 7 day calibration stability claims are documented through the assay of serum controls over the claimed periods. In all cases, statistical estimates of total imprecision are less than 1.5 mg/dL.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo features a stylized depiction of an eagle or bird with three curved lines representing its wings or feathers. The bird is positioned to the right of the text, which is arranged in a circular pattern around the logo. The text reads "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA".

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC 2 0 2007

Clinical Data, Inc. c/o Mr. Wynn Stocking Manager, Regulatory Affairs 1075 West Lambert Road, Building D Brea. CA 92821

Re: K071706

Trade Name: Envoy® 500 HDL Cholesterol Reagent Kit and Envoy® 500 HDL Calibrator Regulation Number: 21 CFR 862.1475 Lipoprotein test system Regulation Name: Regulatory Class: Class I, subject to limitation to exemption in 21 CFR 862.9(c)(4) Product Code: LBS, JIT Dated: November 14, 2007 Received: November 15, 2007

Dear Mr. Stocking:

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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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 logally marketed predicate device results in a classification for your device and thus, perroits 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) 276-0490. 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 (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Jean M. Cooper, M.S., D.V.M.

Jean M. Cooper, M.S., 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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Indication for Use

510(k) Number (if known): K071706

Device Name: Envoy® 500 HDL Cholesterol Reagent and Envoy® 500 HDL Calibrator

Indication For Use:

This reagent is intended to be used by trained personnel in a professional setting and is not intended for home use.

Prescription Use X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OVD)

Signature of Officer

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

$\underset{510(k)}{V}$ K071706

Regulation Number and Section

§ 862.1475 Lipoprotein test system.

(a)
Identification. A lipoprotein test system is a device intended to measure lipoprotein in serum and plasma. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.