(97 days)
The ActiMed ENA C.T™ Total Cholesterol Test is a non-instrumented, enzymatic assay intended for the in vitro quantitative determination of total cholesterol in fingerstick whole blood. It is indicated for professional use in settings such as clinical laboratories and physician office laboratories (POLs) to screen for elevated cholesterol as a risk factor in coronary heart disease (CHD).
The ENA-C-T™ Total Cholesterol Test is based on stable, dry chemistry reagents embedded in a flow device with a factory calibrated scale. The device provides a direct visual read-out of test results. It has built-in controls to indicate that a sufficient volume of whole blood has been added as sample, to verify that the reagents are functioning, and to confirm when the test has been completed. The test device is self-actuating, requiring neither timing nor handling between addition of the sample and reading the result.
The ENA.C.T™ Total Cholesterol Test starts when a sufficient amount of whole blood has been introduced into the sample well. A self-actuating siphon, in turn, transfers the blood to an absorbent pad located immediately below the "START" window. The blood saturated pad shows through the clear window as a red indicator, signaling that enough sample has been added and that the analytical process has been initiated. The absorbent pad and a second filter separate red cells from plasma. The plasma subsequently flows into an enzyme pad containing cholesterol esterase and cholesterol oxidase which completely convert cholesterol and cholesterol esters into cholestenone and hydrogen peroxide. A flow delay pad restricts passage of the plasma to permit completion of the enzymatic reactions. Subsequently, the plasma flows into the measurement zone which acts as a capillary. In this zone, colorless dyes and the enzyme peroxidase are immobilized on a thin fabric layer. The hydrogen peroxide converted from cholesterol in the plasma converts the colorless dye layer into a blue color bar, the length of which is proportional to the amount of hydrogen peroxide, and in turn, cholesterol in the sample. The bar extends until a precise amount of plasma has completely filled the measurement zone and "END/QA" draw zone. This draw zone turns green at the end of the procedure when the cholesterol converting enzymes dissolved in the plasma react with control cholesterol contained in the draw zone. The appearance of a green color signals that the test is complete and that reagents were active. The total cholesterol concentration is directly read from the factory calibrated scale on the device. The entire process typically requires 12 to 15 minutes. The color bar formed is stable and may be read at any time within 48 hours.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
ENA·C·T™ Total Cholesterol Test: Acceptance Criteria and Study Details
The provided text details the 510(k) summary for the ENA·C·T™ Total Cholesterol Test, comparing it to the predicate device, the ChemTrak, Inc. AccuMeter® Cholesterol Test (K905405). The primary goal is to demonstrate substantial equivalence to the predicate device.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated in a dedicated section with specific numerical thresholds. Instead, the document discusses performance in relation to the predicate device and national recommendations (NRS/CHOL, LSP). I've inferred the "acceptance criteria" based on these comparisons and stated recommendations.
| Performance Characteristic | Acceptance Criteria (Inferred from comparisons & recommendations) | Reported ENA·C·T™ Performance |
|---|---|---|
| Linear Range | Comparable to predicate device (125-400 mg/dL) | 120 mg/dL to 360 mg/dL |
| Interfering Substances | No interference comparable to predicate device | No interference: up to 8 mg/dL ascorbic acid, 1 mg/dL acetaminophen, 14 mg/dL bilirubin, 200 mg/dL hemoglobin, 800 mg/dL triglycerides. (Comparable to AccuMeter's reported limits) |
| Precision (CV) | Generally less than 5% for controls at medical decision points (Comparable to predicate device) | Within-run CVs < 5% (Level 1 control), < 4% (Level 2 control). Total CVs ≤ 5% (Level 1), < 4% (Level 2). |
| Bias (vs. Abell-Kendall) | Not to exceed 3% (LSP recommendation) | 1.6% at 200 mg/dL, 0.9% at 240 mg/dL |
| Correlation (ENA·C·T™ vs. Abell-Kendall) | Within 10% (Compared to predicate device, though exact R-value for predicate is not given for this comparison) | r = 0.932 |
| Correlation (ENA·C·T™ vs. AccuMeter®) | Within 10% | r = 0.901 |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: 198 paired fingerstick whole blood and venous samples.
- Data Provenance: The studies were conducted at four Physician Office Laboratories (POLs) in the US. This implies a prospective collection of samples as part of the clinical studies.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The text does not specify the number of experts for interpreting the ENA·C·T™ or AccuMeter® test results at the POL sites. However, the ground truth (Abell-Kendall serum reference method) was performed at a Cholesterol Reference Method Network Laboratory (CRMLN). While the number of experts isn't given, CRMLN laboratories are specialized and highly qualified for cholesterol measurement. The Abell-Kendall method itself is a complex, gold-standard chemical assay, not typically interpreted by a single "expert" in the way a diagnostic image would be. The interpretation of the visual read-out of the ENA·C·T™ and AccuMeter® devices was likely performed by the POL staff who are the intended users, but their qualifications are not detailed beyond "potential users in POL settings."
4. Adjudication Method for the Test Set
The text indicates that the ENA·C·T™ and AccuMeter® results were "read and recorded by one operator" in the precision studies. For the clinical studies, where 198 samples were tested, it doesn't explicitly state an adjudication method for the device readings. Given the nature of a visual color bar reading from a factory-calibrated scale, a formal adjudication process (like 2+1 or 3+1) is typically not applicable as it would be for subjective interpretations (e.g., radiology). The Abell-Kendall method (ground truth) is an objective laboratory assay, not subject to individual interpretation in the same way.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No, an MRMC comparative effectiveness study was not done in the context of comparing human readers with AI vs. without AI assistance. The ENA·C·T™ device is a standalone diagnostic test, not an AI-assisted tool for human readers. The clinical studies involved human operators reading the visual results of the ENA·C·T™ and AccuMeter® devices, but not in a comparative "with AI vs. without AI" effectiveness study.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done
Yes, the studies essentially assess the standalone performance of the device, as it is designed for a single operator to read the result visually. While a human is "in-the-loop" for reading the visual output, there is no separate "algorithm only" component that would perform the diagnosis without any human interaction (e.g., an AI system autonomously diagnosing from images). The device itself acts as the "algorithm" that produces a visual result for human interpretation.
7. The Type of Ground Truth Used
The primary ground truth used was the Abell-Kendall serum reference method, performed at a Cholesterol Reference Method Network Laboratory (CRMLN) on venous blood samples. This is considered a gold standard and a highly accurate reference method for total cholesterol measurement.
8. The Sample Size for the Training Set
The document does not explicitly state a separate "training set" for the ENA·C·T™ device in the context of machine learning. However, it mentions:
- "Each lot of devices is calibrated by using paired fingerstick blood and venous blood samples covering the dynamic range of the test." These samples are used to determine "calibration coefficients" and generate "measurement scales for each lot." This can be considered an internal calibration or "training" process for the physical device's scale. The sample size for this internal calibration is not specified.
- The clinical studies (198 samples) and analytical studies would be considered part of the validation or test set, not a training set.
9. How the Ground Truth for the Training Set Was Established
As noted above, if we consider the lot-specific calibration a form of "training," the ground truth for these samples was established using the Abell-Kendall serum reference method on venous blood samples. This ensures the device's fingerstick whole blood results are traceable to the National Reference System for Cholesterol (NRS/CHOL) and automatically converted to serum values.
{0}------------------------------------------------
510(k) SUMMARY
MAY - 2 1996
ACTIMED LABORATORIES, INC. ENA.C.T™ Total Cholesterol Test
Submitter's Name, Address, Telephone Number, Contact Person and Date Prepared
Susan McGeehan Manager, Quality Assurance ActiMed Laboratories, Inc. 5 Terri Lane Burlington, NJ 08016 (609) 387-7700, Ext. 119 Phone: Facsimile: (609) 387-2700
Contact Person: same as above
Date Prepared: January 25, 1996
Name of Device and Name/Address of Sponsor
ENA·C·T™ Total Cholesterol Test
ActiMed Laboratories, Inc. 5 Terri Lane Burlington, NJ 08016
Classification Name
Cholesterol (total) test system
Predicate Device
ChemTrak, Inc. AccuMeter® Cholesterol Test (K905405)
{1}------------------------------------------------
460377
Intended Use and Indications for Use
The ActiMed ENA C.T™ Total Cholesterol Test is a non-instrumented, enzymatic assay intended for the in vitr‹› quantitative determination of total cholesterol in fingerstick whole blood. It is indicated for professional use in settings such as clinical laboratories and physician office laboratories (POLs) to screen for elevated cholesterol as a risk factor in coronary heart disease (CHD).
Technological Characteristics and Substantial Equivalence
The ENA-C-T™ Total Cholesterol Test is based on stable, dry chemistry reagents embedded in a flow device with a factory calibrated scale. The device provides a direct visual read-out of test results. It has built-in controls to indicate that a sufficient volume of whole blood has been added as sample, to verify that the reagents are functioning, and to confirm when the test has been completed. The test device is self-actuating, requiring neither timing nor handling between addition of the sample and reading the result.
The ENA.C.T™ Total Cholesterol Test starts when a sufficient amount of whole blood has been introduced into the sample well. A self-actuating siphon, in turn, transfers the blood to an absorbent pad located immediately below the "START" window. The blood saturated pad shows through the clear window as a red indicator, signaling that enough sample has been added and that the analytical process has been initiated. The absorbent pad and a second filter separate red cells from plasma. The plasma subsequently flows into an enzyme pad containing cholesterol esterase and cholesterol oxidase which completely convert cholesterol and cholesterol esters into cholestenone and hydrogen peroxide. A flow delay pad restricts passage of the plasma to permit completion of the enzymatic reactions. Subsequently, the plasma flows into the measurement zone which acts as a capillary. In
{2}------------------------------------------------
this zone, colorless dyes and the enzyme peroxidase are immobilized on a thin fabric laver.
1460377
The hydrogen peroxide converted from cholesterol in the plasma converts the colorless dye layer into a blue color bar, the length of which is proportional to the amount of hydrogen peroxide, and in turn, cholesterol in the sample. The bar extends until a precise amount of plasma has completely filled the measurement zone and "END/QA" draw zone. This draw zone turns green at the end of the procedure when the cholesterol converting enzymes dissolved in the plasma react with control cholesterol contained in the draw zone. The appearance of a green color signals that the test is complete and that reagents were a tive. The total cholesterol concentration is directly read from the factory calibrated scale on the device. The entire process typically requires 12 to 15 minutes. The color bar formed is stable and may be read at any time within 48 hours.
Each lot of devices is calibrated by using paired fingerstick blood and venous blood samples covering the dynamic range of the test. Fingerstick blood samples are assayed by the ENA.C. TM device, while venous samples are assayed by the Abell-Kendall serum reference method. Calibration coefficients are determined by comparing the fingerstick results to the serum reference method results. These calibration coefficients are used to generate the measurement scales for each lot of devices. Thus, the standardization of the ENA.C.T™ Total Cholesterol Test is traceable to the National Reference System for Cholesterol (NRS/CHOL), and results using fingerstick whole blood samples are automatically converted to serum values.
The ENA C.T™ Total Cholesterol Test is substantially equivalent to the AccuMeter® Cholesteron Test in terms of intended use, design, materials, operational features, and performance. Both devices are based upon an enzymatic reaction that occurs when whole blood is added to dry chemistry reagents embedded in a flow device. Both devices are
3
{3}------------------------------------------------
standardized to the NRS/CHOL. Results from both devices are read visually within approximately 15 minutes of addition of sample to the device. ENA C TM Total Cholesterol Test results in mg/dL are read directly from a lot-specific, factory-calibrated scale printed on the device, while results for the AccuMeter® Cholesterol Test require conversion of the color peak height to total cholesterol in mg/dL using a lot-specific conversion chart that accompanies the kit. This difference does not raise new questions of safety and effectiveness.
Both the ENA C T™ Total Cholesterol Test and the AccuMeter® Cholesterol Test have built-in controls. The ENA.C.T™ Total Cholesterol has controls to indicate that a sufficient volume of whole blood has been added as sample, to verify that the reagents are functioning, and to confirm when the test has been completed, while the AccuMeter® Cholesterol Test has controls to indicate that the reagents are functioning and when the test is completed.
Performance characteristics generated during analytical and clinical studies on the ENA.C.T™ Total Cholesterol Test are comparable to those published for the AccuMeter® Cholesterol Test in its package insert. The linear range of the ENA.C.T™ Total Cholesterol Test is 120 mg/dL to 360 mg/dL, while the measurement range for the AccuMeter® Cholesterol Test is reported to be 125 to 400 mg/dL.
The recovery of cholesterol in the presence of potentially interfering substances was determined for the ENA ()T™ device and compared to the information provided in the AccuMeter® device package insert. For both devices, no interference was found in samples containing up to 1 mg/dL of acetaminophen or up to 200 mg/dL of henroglobin. No interference was seen with the AccuMeter® device in samples ontaining up to 1000 mg/dL of triglycerides, while no interference was seen with the ENA.C.T™ device in samples containing up to 800 mg/dL, the highest concentration tested. No interference was seen with the AccuMete:® device in samples containing up
4
{4}------------------------------------------------
to 15 mg/dL of bilirubin, while no interference was seen with the ENA.C.T™ device in samples containing up to 14 mg/dL. Both assays are affected by high concentrations of ascorbic acid.
Precision results for these two visually read tests are comparable, with percent coefficients of variation generally less than 5% for controls at the medical decision points.
In clinical studies at four POL sites, ENA C T™ Total Cholesterol Test, AccuMeter® Cholesterol Test, and Abell-Kendall results were generated on 198 paired fingerstick whole blood and venous samples. Correlations between the ENA C T™ Total Cholesterol Test and the Abell-Kendall method and between the ENA.C.T™ Total Cholesterol Test and the AccuMeter® Cholesterol Test were acceptable. Thus, the ENA-C-T™ Total Cholesterol Test is substantially equivalent to the Ac uMeter® Cholesterol Test in terms of performance characteristics, as well as intended use, design, materials, and operational features.
Analytical and Clinical Testing
Linear Range
Results from NCCLS Linearity Protocol testing and from testing 40 normal and 40 abnormal clinical samples demonstrated that the linear range of the ENA C T™ Total Cholesterol Test is 120 mg/dL to 360 mg/dL.
Interfering Substances
Studies of the recovery of cholesterol in the presence of potentially interfering substances were carried out. No interference was found in samples containing up to 8 mg/dL of ascorbic acid, 1 mg/dL of acetaminophen, 14 mg/dL of bilirubin, 200 mg/dL of hemoglobin, or 800 mg/dL of triglycerides.
5
{5}------------------------------------------------
Precision
Precision studies were carried out at the four POLs using two controls near the medical decision points, according to NCCLS EP5-T, User Evaluation of Precision Performance of Clinical Chemistry Devices. Two levels of the ENA C TM Assayed Total Cholesterol Controls were assayed in duplicate, twice a day for five days at each site. Results were read and recorded by one operator. Within-run CVs were less than 5% for the Level 1 control (range of mean = 178 to 183.75 mg dL) and less than 4% for the Level 2 control (range of mean = 254 to 261 mg/dL). Total CVs were 5% or less for the Level 1 control and less than 4% for the Level 2 control. These results demonstrate that the visually read ENA C T™ Total Cholesterol Test was reproducible in the hands of potential users in POL settings.
Clinical Studies
A total of 198 paired fingerstick whole blood and venous samples were tested during clinical studies at four POL sites. Fingerstick whole blood samples were assayed at the sites by the ENA-C.T™ Total Cholesterol Test and the AccuMeter® Cholesterol Test, and venous samples were assayed at a Cholesterol Reference Method Network Laboratory (CRMLN) by the Abell-Kendall serum reference method . For the comparison between the ENA C T™ Total Cholesterol Test and the Abell-Kendall method, the least squares regression equation for all sites was y = 0.976x + 7.93, with a correlation coefficient of r = 0.932. Bias calculations for the ENACT™ at 200 mg/dL and at 240 mg/dL were 1.6% and 0.9%, respectively. For the comparison between the ENA.C.T™ Total (Cholesterol Test and the AccuMeter® Cholesterol Test, the least squares regression equation for all sites was y = 0.917x + 21.3, with a correlation coefficient of r = 0.901.
Bias calculations for the ENA.C.T™ device, compared to the Abell-Kendall serum reference method were 1.6% at the 200 mg/dL level and 0.9%
G
{6}------------------------------------------------
Goi37
at the 240 mg/dL level. These figures were well within the recommendation of the Laboratory Standardization Panel (LSP) on Blood Cholesterol Measurement that bias not exceed 3%. Correlations between the ENA.C. TTM device and the Abell-Kendall Method and between the ENA.C. T™ device and the AccuMeter® device were within 10%. Thus, the ENA.C.T™ Total Cholesterol Test has demonstrated acceptable precision, bias and accuracy, and was shown to be substantially equivalent to the AccuMeter® Cholesterol Test.
§ 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.