(170 days)
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. 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.
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.
Here's an analysis of the acceptance criteria and study findings for the Lifestream Technologies, Inc. Cholesteron™ Pro II Cholesterol Test, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (NCEP Guidelines) | Reported Device Performance |
|---|---|---|
| Accuracy | Bias within 3% of reference method | All comparative biases were within 3% (e.g., Operator #1: 1.50% bias at 200 mg/dL, -1.25% at 240 mg/dL; Operator #2: 2.50% bias at 200 mg/dL, -0.42% at 240 mg/dL) |
| Precision (CV) | %CVs within 3% | Serum Precision: |
| - Low Control (184.4 mg/dL): Weekly %CV = 1.72% | ||
| - High Control (230.9 mg/dL): Weekly %CV = 2.91% | ||
| Whole Blood Precision: | ||
| - Low (179.4 mg/dL): %CV = 1.39% | ||
| - High (228.1 mg/dL): %CV = 2.38% |
2. Sample Size Used for the Test Set and Data Provenance
- Accuracy Studies: Two studies, each involving 62 subjects.
- Precision Studies (Serum): A two-level commercial control set was assayed 30 times for each level (6 times a day over 5 days).
- Precision Studies (Whole Blood): Two levels of venous heparinized whole blood were tested 30 times each.
- Data Provenance: The document does not explicitly state the country of origin or if the data was retrospective or prospective. Given the nature of a 510(k) submission for a new device, it is highly likely these were prospective studies conducted specifically for regulatory submission. The location of Lifestream Technologies Inc. (Post Falls, ID) suggests the studies were likely conducted in the United States.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- Accuracy Studies (Ground Truth): The reference method used was the Abell-Kendall (A-K) method for venous serum samples. This is a recognized laboratory reference method and does not rely on expert consensus for ground truth establishment.
- Precision Studies (Ground Truth): For serum, commercially prepared control samples with label-assigned mean values were used. For whole blood, "venous heparinized whole blood" samples were targeted at specific cholesterol concentrations. Again, these are analytical ground truths, not dependent on expert consensus.
4. Adjudication Method for the Test Set
- Adjudication methods (like 2+1, 3+1) are typically used when human interpretation of results is involved, often in imaging or diagnostic pathology.
- For the Cholesteron™ Pro II Cholesterol Test, which is an in vitro diagnostic device providing quantitative results, the "ground truth" for accuracy was established using a reference laboratory method (Abell-Kendall). Therefore, no adjudication method as typically understood in qualitative diagnostic studies was required or described. The device's results were compared directly to the quantitative output of the reference method.
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 MRMC comparative effectiveness study was done. This type of study is relevant for devices involving human interpretation (e.g., AI in radiology). The Cholesteron™ Pro II Cholesterol Test is an automated quantitative diagnostic device for measuring total cholesterol; therefore, MRMC studies are not applicable.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
- The accuracy and precision studies evaluate the standalone performance of the Cholesteron™ Pro II Cholesterol Test device itself. While the device is "professional-use," meaning operated by trained personnel, the performance metrics (accuracy, precision compared to a reference method) are for the device's analytical capability, not for improved human interpretation with or without the device. The data provided in the "CHOLESTRON ACCURACY STATISTICS" table shows "Operator #1 vs A-K," "Operator #2 vs A-K," etc., indicating multiple operators used the device, but this is to demonstrate consistency across operators, not to measure human improvement with device assistance.
7. The Type of Ground Truth Used
- For accuracy: The ground truth was established by comparing the Cholestron device's results to a reference laboratory method: the Abell-Kendall (A-K) method using venous serum samples.
- For precision: The ground truth was established using commercial control samples with label-assigned values (for serum) and venous heparinized whole blood samples targeted at specific concentrations. These represent analytical ground truths.
8. The Sample Size for the Training Set
- The document does not provide information on a training set sample size. This is because the Cholesteron™ Pro II Cholesterol Test is not described as an AI/machine learning device that requires a distinct training and test set in the modern sense. It is a traditional in vitro diagnostic device based on enzymatic reactions and photometric measurement. Its development would involve calibration and optimization, but typically not a "training set" in the context of recent AI regulatory submissions.
9. How the Ground Truth for the Training Set Was Established
- As noted above, the concept of a "training set" and its associated ground truth as relevant for AI/ML devices is not applicable to this traditional in vitro diagnostic device. The device's calibration and optimization would have been based on established chemical and photometric principles, likely using reference materials and laboratory standards, rather than a "ground truth" derived from a separate training dataset.
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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: (208) 457-9409 (208) 457-9509 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: (208) 457-9409
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 (208) 263-5433 · Fax (208) 263-6
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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: (208) 457-9409 fax: (208) 457-9509
Contact:
Jackson B. Connolly Director, Product Development Lifestream Diagnostics, Inc. phone: (208) 457-9409
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 cholesterolmeasurement to aid in thediagnosis and management ofcoronary heart disease | total cholesterolmeasurement to aid in thediagnosis and management ofcoronary heart disease |
| Analyte Measured | total cholesterol | total cholesterol |
| Methodology/Technology | Enzymatic: cholesterolesterase and cholesteroloxidase (Trinder Reaction)Cholesterol esterase reactswith lipoproteins in thesample to split thecholesterol ester intocholesterol and fatty acid.Cholesterol is oxidized to 4-cholesten-3-one and H2O2 inthe presence of cholesteroloxidase. Hydrogen peroxidasereacts with a reducing agentto produce a blue color that ismeasured photometrically. | Enzymatic: cholesterolesterase and cholesteroloxidase (Trinder Reaction)Cholesterol esterase reactswith lipoproteins in thesample to split thecholesterol ester intocholesterol and fatty acid.Cholesterol is oxidized to 4-cholesten-3-one and H2O2 inthe presence of cholesteroloxidase. Hydrogen peroxidasereacts with a reducing agentto produce a blue color that ismeasured 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 solediscriminate; totalcholesterol results areinterpreted along withmedical histories and otherbiochemical markers | minimal, not a solediscriminate; totalcholesterol results areinterpreted along withmedical histories and otherbiochemical markers |
| CHARACTERISTIC | CHOLESTRON | ACCUTRENDK944458(cholesterol portion) |
| Safety Feature for CorrectReagent Strip Usage | includes external keypad thatrequires correct entry ofreagent strip lot information | no such feature |
| User Interface | 16-key | 4-key |
| Battery Power | 1 9-volt | 3 AAA |
| Electronics | Diagnostic + Memory +Display Conversion + Code #Correlation to Lot # (safety)+ 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 at200 mg/dL(% bias) | Bias at240 mg/dL(% bias) |
|---|---|---|---|---|---|---|
| Operator #1 vs A-K | 57* | 0.95 | 0.855 | 32 | 203(1.50%) | 237(-1.25%) |
| Operator #2 vs A-K | 62** | 0.94 | 0.840 | 37 | 205(2.50%) | 239(-0.42%) |
| Operator #3 vs A-K | 62 | 0.94 | 0.858 | 32 | 204(2.00%) | 238(-0.83%) |
| Operator #4 vs A-K | 62 | 0.93 | 0.882 | 28 | 204(2.00%) | 240(-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 | STANDARDDEVIATION | PERCENTCOEFFICIENTOF 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 | STANDARDDEVIATION | PERCENTCOEFFICIENTOF 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 | STANDARDDEVIATION | PERCENTCOEFFICIENTOF 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 (770) 488-7655.
This letter will allow you to begin marketing your device as described in your 510 (k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (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 (800) 638-2041 or (301) 443-6597 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
§ 862.1175 Cholesterol (total) test system.
(a)
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.(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.