CHOLESTRON PRO II CHOLESTEROL TEST

K981345 · Lifestream Diagnostics, Inc. · CHH · Oct 1, 1998 · Clinical Chemistry

Device Facts

• Record ID: K981345
• Device Name: CHOLESTRON PRO II CHOLESTEROL TEST
• Applicant: Lifestream Diagnostics, Inc.
• Product Code: CHH · Clinical Chemistry
• Decision Date: Oct 1, 1998
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1175
• Device Class: Class 1

Intended Use

The Cholestron™ Pro II Cholesterol Test (Cholestron) is a professional-use, point-of-care in vitro diagnostic device for the measurement of total cholesterol in fingerstick whole blood samples.

Device Story

The Cholestron Pro II is a point-of-care diagnostic system for professional use. It utilizes a photometer and single-use reagent strips. The user applies a fingerstick whole blood sample to the strip. The device employs an enzymatic Trinder reaction: cholesterol esterase splits cholesterol esters into cholesterol and fatty acids; cholesterol oxidase then oxidizes the cholesterol to produce hydrogen peroxide, which reacts with a reducing agent to create a blue color. The photometer measures this color intensity to quantify total cholesterol. Results are available in approximately three minutes. The device includes an external keypad for entering reagent lot information to ensure accuracy. Healthcare providers use the output to assess coronary heart disease risk and monitor lipid-lowering drug therapy. The device provides a rapid, quantitative measurement to assist clinical decision-making in a point-of-care setting.

Clinical Evidence

Accuracy was evaluated in two studies (n=62 each) comparing fingerstick whole blood results to the reference Abell-Kendall (A-K) method. Correlation coefficients (r) ranged from 0.93 to 0.95. Biases at 200 mg/dL and 240 mg/dL were within 3%. Precision was assessed using serum controls (n=30 replicates) and whole blood (n=30 replicates). Serum precision showed %CVs of 1.07-1.75% (Low) and 1.47-3.73% (High). Whole blood precision showed %CVs of 1.39% (Low) and 2.38% (High). All results met National Cholesterol Education Program (NCEP) guidelines for accuracy and precision.

Technological Characteristics

Photometric system using enzymatic Trinder reaction (cholesterol esterase/oxidase). Measures blue color intensity proportional to cholesterol concentration. Features 16-key user interface, 9-volt battery power, and external keypad for reagent lot code entry. Reportable range 150-300 mg/dL. Point-of-care, standalone device.

Indications for Use

Indicated for the measurement of total cholesterol in fingerstick whole blood to aid in the detection of individuals at risk for coronary heart disease and the management of patients undergoing lipid-lowering therapy.

Regulatory Classification

Identification

A cholesterol (total) test system is a device intended to measure cholesterol in plasma and serum. Cholesterol measurements are used in the diagnosis and treatment of disorders involving excess cholesterol in the blood and lipid and lipoprotein metabolism disorders.

Predicate Devices

• Accu-Chek® InstantPlus™ Cholesterol Test (Boehringer-Mannheim Diagnostics, also known as Accutrend GC Test)

Reference Devices

• Accutrend (K944458)

Submission Summary (Full Text)

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K9813415

Lifestream Technologies, Inc. Cholesteron™ Pro II Cholesterol Test

OCT 1 1998

# SECTION 10

# 510(K) SUMMARY (REVISED)

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Image /page/1/Picture/0 description: The image shows the logo for Lifestream Diagnostics Inc. The word "Lifestream" is written in a stylized, cursive font. Below the word "Lifestream" is the word "Diagnostics" written in a sans-serif font. The letters are spaced out.

### 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: K981345.

Submitter Information (21 CFR 807.92(a)(1))

Lifestream Technologies, Inc. 510 Clearwater Loop, Suite 101 Post Falls, ID 83854 phone: [phone] [phone] fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax: fax:

Contact:

Submitter:

Jackson B. Connolly Director, Product Development Lifestream Diagnostics, Inc. phone: [phone]

Summary Date: April 13, 1998

Name of Device and Classification (21 CFR 807.92(a)(2)) Name (trade): Cholestron™ Pro II Cholesterol Test

Name (usual): total cholesterol test system

Classification: 21 CFR 862.1175, Class I, CHH

Identification of Legally Marketed Predicate Device(s) (21 CFR 807.92 (a)(3))

Cholesteron TM Pro II Cholesterol Test (Cholestron) is substantially equivalent to the Accu-Chek® InstantPlus™ Cholesterol Test (Boehringer-Mannheim Diagnostics, Indianapolis, IN; also known as Accutrend GC Test). Cholestron and Accu-Chek share the same intended use, methodology and technology, testing matrix, reportable range, and risk to the patient.

age 2 515 Pine Street · Suite 200 · P.O. Box 2130 · Sandpoint, ID 83864 · Phone [phone] · Fax [phone]

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#### 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: K981345.

Submitter Information (21 CFR 807.92(a)(1))

Submitter: Lifestream Technologies, Inc. 510 Clearwater Loop, Suite 101 Post Falls, ID 83854 phone: [phone] fax: [phone]

Contact:

Jackson B. Connolly Director, Product Development Lifestream Diagnostics, Inc. phone: [phone]

Summary Date: April 13, 1998

Name of Device and Classification (21 CFR 807.92(a)(2)) Name (trade): Cholestron™ Pro II Cholesterol Test

Name (usual): total cholesterol test system

Classification: 21 CFR 862.1175, Class I, CHH

Identification of Legally Marketed Predicate Device(s) (21 CFR 807.92 (a)(3))

Cholesteron TM Pro II Cholesterol Test (Cholestron) is substantially equivalent to the Accu-Chek® InstantPlus™ Cholesterol Test (Boehringer-Mannheim Diagnostics, Indianapolis, IN; also known as Accutrend GC Test). Cholestron and Accu-Chek share the same intended use, methodology and technology, testing matrix, reportable range, and risk to the patient.

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## Description of Device (21 CFR 807.92 (a)(4))

The Cholestron system consists of a photometer with a display assembly keypad, and single-use, disposable reagent strips. Fingerstick whole blood is applied directly to the device, and cholesterol results are available in approximately three minutes.

### Intended Use (21 CFR 807.92 (a)(5))

The Cholestron™ Pro II Cholesterol Test is a professional-use, point-of-care in vitro diagnostic device for the measurement of total cholesterol in fingerstick whole blood samples. Total cholesterol measurements aid in the detection of persons who may be at risk for coronary heart disease, and aid in the management of patients undergoing therapy with lipid lowering drugs.

## Similarities to the Predicate(s) (21 CFR 807.92 (a)(6))

A summary table of the similarities and differences between Cholestron and the predicate device (Accu-Chek) follows.

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| CHARACTERISTIC | CHOLESTRON | Accu-Chek |
|---------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | total cholesterol<br>measurement to aid in the<br>diagnosis and management of<br>coronary heart disease | total cholesterol<br>measurement to aid in the<br>diagnosis and management of<br>coronary heart disease |
| Analyte Measured | total cholesterol | total cholesterol |
| Methodology/Technology | Enzymatic: cholesterol<br>esterase and cholesterol<br>oxidase (Trinder Reaction)<br>Cholesterol esterase reacts<br>with lipoproteins in the<br>sample to split the<br>cholesterol ester into<br>cholesterol and fatty acid.<br>Cholesterol is oxidized to 4-<br>cholesten-3-one and H2O2 in<br>the presence of cholesterol<br>oxidase. Hydrogen peroxidase<br>reacts with a reducing agent<br>to produce a blue color that is<br>measured photometrically. | Enzymatic: cholesterol<br>esterase and cholesterol<br>oxidase (Trinder Reaction)<br>Cholesterol esterase reacts<br>with lipoproteins in the<br>sample to split the<br>cholesterol ester into<br>cholesterol and fatty acid.<br>Cholesterol is oxidized to 4-<br>cholesten-3-one and H2O2 in<br>the presence of cholesterol<br>oxidase. Hydrogen peroxidase<br>reacts with a reducing agent<br>to produce a blue color that is<br>measured photometrically. |
| Testing Matrix | fingerstick whole blood | fingerstick whole blood |
| Reportable Range | 150-300 mg/dL | 150-300 mg/dL |
| Risk to Patient | minimal, not a sole<br>discriminate; total<br>cholesterol results are<br>interpreted along with<br>medical histories and other<br>biochemical markers | minimal, not a sole<br>discriminate; total<br>cholesterol results are<br>interpreted along with<br>medical histories and other<br>biochemical markers |
| CHARACTERISTIC | CHOLESTRON | ACCUTREND<br>K944458<br>(cholesterol portion) |
| Safety Feature for Correct<br>Reagent Strip Usage | includes external keypad that<br>requires correct entry of<br>reagent strip lot information | no such feature |
| User Interface | 16-key | 4-key |
| Battery Power | 1 9-volt | 3 AAA |
| Electronics | Diagnostic + Memory +<br>Display Conversion + Code #<br>Correlation to Lot # (safety)<br>+ Cardiac Risk Assessment | Diagnostic + Memory |

## Similarities Between Cholestron and Accu-Chek

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## Differences Between Cholestron and Accutrend

## Brief Discussion of Nonclinical Data (21 CFR 807.92(b)(1))

Laboratory tests were conducted to assess the effects of potential interferents on the cholesterol results; both biological and therapeutic were evaluated. The results appear below.

| Potential Interferent | Level of Interference |
|--------------------------------------|----------------------------------------------|
| Bilirubin | no interference in samples containing up to |
| | 10 mg/dL |
| Hemoglobin | hemolyzed samples (as would be seen in |
| | cases of excessive squeezing at the puncture |
| | site) should be avoided |
| High Hematocrit | cholesterol values were not affected when |
| | hematocrit levels ranged from 30% to 55% |
| Triglycerides | no interference in samples containing up to |
| | 400 mg/dL |
| Uric Acid | no interference in samples containing up to |
| | 9 mg/dL |
| Excessive Squeezing of Puncture Site | excessive squeezing and milking of the |
| | puncture site may produce erroneous |
| | results |

INTERFERENCE TESTING WITH BIOLOGICAL COMPOUNDS

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## Therapeutic Compounds

Specificity testing was performed with common therapeutic compounds. The following compounds, when present in pathological concentrations, were found to possibly alter cholesterol results.

> Acetaminophen Ascorbic Acid Dopamine Gentisic Acid Methyldopa

## Brief Discussion of Clinical Data (21 CFR 807.92 (b)(2)

Studies were performed to evaluate accuracy and precision. Accuracy was evaluated by two studies of 62 subjects each, where results from testing with the Cholestron on fingerstick whole blood samples by each of two operators were compared to venous serum samples assayed by the reference Abell-Kendall (A-K) method. Precision was evaluated in both serum and whole matrices with two levels of cholesterol samples. Serum samples (commercial controls) were assayed in multiple "runs" over several days, and whole blood samples were assayed in single runs on a single day.

| Comparison | n = | r = | Slope | y-intercept | Bias at<br>200 mg/dL<br>(% bias) | Bias at<br>240 mg/dL<br>(% bias) |
|--------------------|------|------|-------|-------------|----------------------------------|----------------------------------|
| Operator #1 vs A-K | 57* | 0.95 | 0.855 | 32 | 203<br>(1.50%) | 237<br>(-1.25%) |
| Operator #2 vs A-K | 62** | 0.94 | 0.840 | 37 | 205<br>(2.50%) | 239<br>(-0.42%) |
| Operator #3 vs A-K | 62 | 0.94 | 0.858 | 32 | 204<br>(2.00%) | 238<br>(-0.83%) |
| Operator #4 vs A-K | 62 | 0.93 | 0.882 | 28 | 204<br>(2.00%) | 240<br>(-zero) |

#### CHOLESTRON ACCURACY STATISTICS

* 5 Cholestron values out of range ** 1 Cholestron value out of range

The data demonstrate all comparative biases were within 3%, as specified by National Cholesterol Education Program (NCEP) guidelines. Each operator obtained Cholestron results that compared closely with the A-K results, and the Cholestron meets NCEP's guidelines for accuracy.

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## SERUM PRECISION

A two-level commercial control set was assayed six times a day (three replicates in the morning, and three replicates in the afternoon) over five days for a total of 30 replicates for each level. The controls were label-assigned at mean values of 180 mg/dL ("Low", range 154-207 mg/dL) and 256 mg/dL ("High", range 221-292 mg/dL), and testing was performed via the pipetting of 25μL of sample onto each of two Cholestron devices.

| DAY | N = | MEAN | STANDARD<br>DEVIATION | PERCENT<br>COEFFICIENT<br>OF VARIATION |
|--------|-----|-------|-----------------------|----------------------------------------|
| 1 | 6 | 184.7 | 2.58 | 1.40 |
| 2 | 6 | 186.3 | 3.27 | 1.75 |
| 3 | 6 | 183.7 | 2.94 | 1.60 |
| 4 | 6 | 186.3 | 2.50 | 1.34 |
| 5 | 6 | 181.2 | 1.94 | 1.07 |
| Weekly | 30 | 184.4 | 3.17 | 1.72 |

#### SUMMARIZED SERUM PRECISION DATA-LOW CONTROI

## SUMMARIZED SERUM PRECISION DATA-HIGH CONTROL

| DAY | N = | MEAN | STANDARD<br>DEVIATION | PERCENT<br>COEFFICIENT<br>OF VARIATION |
|--------|-----|-------|-----------------------|----------------------------------------|
| 1 | 6 | 228.5 | 6.38 | 2.79 |
| 2 | 6 | 233.2 | 4.26 | 1.83 |
| 3 | 6 | 233.0 | 7.38 | 3.17 |
| 4 | 6 | 234.2 | 8.73 | 3.73 |
| 5 | 6 | 225.8 | 3.31 | 1.47 |
| Weekly | 30 | 230.9 | 6.73 | 2.91 |

Cholestron's within-day imprecision ranged from 1.07 %CV to 1.75 %CV with the Low control, and from 1.47 %CV to 273. %CV with the High Control. The between-day (or total) imprecision was 1.72 %CV for the Low Control, and 2.91% CV for the High Control. Testing of the serum controls demonstrated Cholestron meets the NCEP guidelines for precision with %CVs within 3%.

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#### WHOLE BLOOD PRECISION

Whole blood precision was evaluated by repeat testing of two levels of venous heparinized whole blood; the whole blood samples were targeted at 200 mg/dL and 240 mg/dL. Whole blood precision was included in the clinical trial as this is the relevant matrix for the Cholestron. Testing was performed via the pipetting of 25uL of sample onto the devices.

| LEVEL ID | N = | MEAN | STANDARD<br>DEVIATION | PERCENT<br>COEFFICIENT<br>OF VARIATION |
|----------|-----|-------|-----------------------|----------------------------------------|
| LOW | 30 | 179.4 | 2.50 | 1.39 |
| HIGH | 30 | 228.1 | 5.43 | 2.38 |

#### SUMMARIZED WHOLE BLOOD PRECISION DATA

The data demonstrated %CVs of 1.39% ("Low"), and 2.38% ("High"). The whole blood precision testing corroborated the serum precision testing, and confirms Cholestron meets the NCEP guidelines for precision with %CVs within 3%.

#### Performance Data - Conclusions (21 CFR 807.92 (b)(3))

Studies were conducted to evaluate Cholestron's accuracy and precision. Accuracy was assessed by paired testing of 62 whole blood/serum samples in two separate evaluations, and precision was assessed by repeated analyses of serum controls and whole blood samples.

The data demonstrated Cholestron meets the NCEP guidelines for accuracy and precision, with estimated biases within 3% of the reference method, and with percent coefficients of variation within 3%.

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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" around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or a bird in flight, composed of three stylized human profiles facing to the right.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

1 1998 OCT

Lifestream Technologies, Inc. · C/O Erika B. Ammirati, R.A.C. MT(ASCP) Ammirati Requlatory Consulting 575 Shirlynn Court Los Altos, California 94022

Re : K981345 Cholestron™ Pro II Cholesterol Test Requlatory Class: I Product Code: СНН Dated: August 26, 1998 Received: Auqust 28, 1998

Dear Ms. Ammirati:

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 In addition, FDA may publish further announcements action. 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 requlations.

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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 [phone].

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 [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number [phone] or [phone] or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".

Sincerely yours,
Steven Bitman

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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## SECTION 3 INTENDED USE/INDICATIONS FOR USE

#### INTENDED USE

The Cholestron™ Pro II Cholesterol Test (Cholestron) is a professional-use, point-ofcare in vitro diagnostic device for the measurement of total cholesterol in fingerstick whole blood samples.

#### INDICATIONS FOR USE

Total cholesterol measurements aid in the detection of persons who may be at risk for coronary heart disease, and aid in the management of patients undergoing therapy with lipid lowering drugs.

The measurement range for the Cholestron is 150 - 300 mg/dL.

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K981345