(66 days)
The Cholestech LDX aspartate aminotransferase (AST) test is for the in vitro quantitative determination of AST in whole blood or serum on the Cholestech LDX Analyzer. AST measurements are used in the diagnosis and treatment of certain liver diseases (e.g., viral hepatitis and cirrhosis), and heart diseases.
The Cholestech LDX System combines enzymatic methodology and solid-phase technology to measure AST. Samples used for testing can be whole blood from a fingerstick (collected in a lithium heparin coated capillary tube), venous whole blood or serum. The sample is applied to a Cholestech LDX AST cassette. The cassette is then placed into the Cholestech LDX Analyzer where a unique system on the cassette separates the plasma from the blood cells. The plasma flows to both sides of the cassette and is transferred to the AST reaction pad. The Cholestech LDX Analyzer measures Aspartate aminotransferase by an enzymatic method based on the method formulation of Katsuyama et al. 12- Aspartic acid aminotransferase catalyzes the transfer of amino groups from L-Aspartic acid to alpha-Ketoglutarate producing oxaloacetate and glutamate. Oxaloacetate Decarboxylase converts the Oxaloacetate to Pyruvate by the removal of CO2. Pyruvate oxidase, in the presence of oxygen, oxidizes the pyruvate to acetylphosphate and hydrogen peroxide. In a reaction catalyzed by horseradish peroxidase, the peroxide reacts with an indicator dye to form a blue color at a rate proportional to the AST concentration of the sample. The resultant color in the reaction is measured by reflectance photometry. A brown magnetic stripe on each cassette contains the calibration required for the Cholestech LDX Analyzer to convert the reflectance reading to the AST concentration in U/L. 37°C.
The Cholestech LDX aspartate aminotransferase (AST) Test, a colorimetric assay for the determination of AST, has been found substantially equivalent to the Synchron CX® AST system. The device uses enzymatic methodology and solid-phase technology to measure AST in whole blood or serum.
1. Table of Acceptance Criteria and Reported Device Performance
The submission does not explicitly state pre-defined acceptance criteria with pass/fail thresholds for each performance metric. Instead, it presents performance data for accuracy, precision, and linearity, which are implicitly compared against the performance characteristics of the predicate device (Synchron CX® AST) and laboratory standards.
| Performance Metric | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Assay Range | Comparable to predicate device (5-400 U/L) and suitable for clinical use. | 10 – 400 U/L |
| Accuracy | Strong correlation and agreement with the predicate device for serum samples. Close agreement between different sample types (venous whole blood, fingerstick whole blood) and serum samples within the device itself. | LDX AST vs Synchron CX AST (Serum): n=109, slope=0.97, y-intercept=1.6, r=0.983 (Range 12–396 U/L) |
| LDX AST (Venous Whole Blood vs Serum): n=46, slope=1.08, y-intercept=0.3, r=0.998 (Range 13-343 U/L) | ||
| LDX AST (Fingerstick Whole Blood vs Serum): n=21, slope=0.86, y-intercept=4.4, r=0.934 (Range 13-65 U/L) | ||
| Precision | Acceptable variability (coefficient of variation, %CV) for clinical diagnostic purposes across different AST levels and sample types. | Low Control (~31 U/L): %CV = 8.8% |
| High Control (~106 U/L): %CV = 4.4% | ||
| Whole Blood Sample (58 U/L): %CV = 4.8% | ||
| Interference | Less than 10% interference from evaluated endogenous and exogenous substances. | Less than 10% interference when challenged by evaluated levels of substances |
| Hematocrit | Tolerance up to 50% hematocrit. | Up to 50% Hematocrit tolerance |
2. Sample Sizes Used for the Test Set and Data Provenance
- Accuracy (LDX AST vs. Synchron CX AST): 109 matched serum samples.
- Accuracy (LDX AST: Venous Whole Blood vs. Serum): 46 matched samples.
- Accuracy (LDX AST: Fingerstick Whole Blood vs. Serum): 21 matched samples.
- Precision: 2 levels of controls tested in duplicate, twice a day, over 20 days (80 replicates per level). One whole blood sample tested with the same protocol (80 replicates).
Data Provenance: The document does not specify the country of origin for the data or explicitly state whether the studies were retrospective or prospective. Given the nature of a 510(k) submission for a new device, it is highly likely that these were prospective studies conducted in a controlled environment as part of the device's validation. No specific patient demographics or disease states are detailed beyond the general "diagnosis and treatment of certain liver diseases (e.g., viral hepatitis and cirrhosis), and heart diseases."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
N/A. This is an in vitro diagnostic device for quantitative determination of a biomarker (AST). The "ground truth" for the test set is established by comparative measurements against a legally marketed predicate device (Synchron CX® AST system) or by internal comparison to reference methods/sample types within the new device's system. It does not involve human expert interpretation of images or clinical assessments to establish a ground truth in the way medical imaging AI devices do. Therefore, no experts for ground truth establishment are applicable in this context.
4. Adjudication Method for the Test Set
N/A. This is not applicable as the test set involves quantitative measurements against a comparator device and internal comparisons, not subjective assessments requiring expert adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
N/A. This is an in vitro diagnostic device, not a medical imaging AI device requiring human reader interpretation or multi-reader studies. The device provides a quantitative measurement, and its effectiveness is determined by its analytical performance metrics (accuracy, precision, linearity) compared to established methods.
6. Standalone Performance Study
Yes, a standalone performance study was done in the sense that the Cholestech LDX AST device's performance was evaluated independently through precision studies, interference testing, hematocrit tolerance, and then compared to a predicate device (Synchron CX AST) as well as within its own system for different sample types. The reported accuracy metrics directly compare the LDX AST to the predicate and also compare results from various sample types processed by the LDX AST itself (venous whole blood, fingerstick whole blood vs. serum). This represents the algorithm's (device's) performance in generating the quantitative AST value.
7. Type of Ground Truth Used
The primary ground truth used for performance evaluation is comparative measurement against a legally marketed predicate device (Synchron CX® AST system) for accuracy. Additionally, internal comparisons of different sample types (venous whole blood, fingerstick whole blood) against serum samples measured by the same device serve as a verification of consistency and accuracy across intended sample matrices. The precision studies use control materials with known or established AST levels.
8. Sample Size for the Training Set
The document does not specify a separate training set or its sample size. For in vitro diagnostic (IVD) devices like this, the development process might involve initial experimentation and optimization, but the "training set" concept common in machine learning for image analysis or risk prediction is typically not directly applicable in the same way. Performance data presented relates to validation studies, not necessarily a distinct "training set" as understood in AI/ML contexts.
9. How the Ground Truth for the Training Set Was Established
N/A. As mentioned above, the concept of a "training set" with established ground truth as it applies to AI/ML is not explicitly detailed or typically relevant for this type of quantitative IVD submission in the same manner. The device's methodology is based on established enzymatic reactions, and its parameters would likely have been optimized during development rather than "trained" on a dataset with a defined ground truth in a machine learning sense.
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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: K032021
Submitter Information (21 CFR 807.92(a)(1))
| Submitter: | Cholestech Corporation |
|---|---|
| 3347 Investment Boulevard | |
| Hayward, CA 94545 | |
| phone: (510) 732-7200 | |
| fax: (510) 732-7227 |
Thomas E. Worthy, PhD. Contact: Vice President, Research and Regulatory Affairs Cholestech Corporation.
Summary Date: June 30, 2003
Name of Device and Classification (21 CFR 807.92(a)(2))
Name (trade): Cholestech LDX aspartate aminotransferase (AST)
Name (usual): Colorimetric assay for the determination of aspartate amino transferase (SGOT/AST)
Classification: 21 CFR 862.1100, Class II, CIS (75)
Identification of Legally Marketed Predicate Device(s) (21 CFR 807.92 (a)(3))
LDX AST is substantially equivalent to the Synchron CX® AST system (Synchron CX, Beckman Coulter, Inc., Fullerton, CA). The LDX AST method is identical or similar to its predicate in terms of: intended use, measurement principle (enzymatic reactions), measurement (assay) range, specimen type, and the requirement for an analyzer.
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Description of Device (21 CFR 807.92 (a)(4))
The Cholestech LDX System combines enzymatic methodology and solid-phase technology to measure AST. Samples used for testing can be whole blood from a fingerstick (collected in a lithium heparin coated capillary tube), venous whole blood or serum. The sample is applied to a Cholestech LDX AST cassette. The cassette is then placed into the Cholestech LDX Analyzer where a unique system on the cassette separates the plasma from the blood cells. The plasma flows to both sides of the cassette and is transferred to the AST reaction pad.
The Cholestech LDX Analyzer measures Aspartate aminotransferase by an enzymatic method based on the method formulation of Katsuyama et al. 12- Aspartic acid aminotransferase catalyzes the transfer of amino groups from L-Aspartic acid to alpha-Ketoglutarate producing oxaloacetate and glutamate. Oxaloacetate Decarboxylase converts the Oxaloacetate to Pyruvate by the removal of CO2. Pyruvate oxidase, in the presence of oxygen, oxidizes the pyruvate to acetylphosphate and hydrogen peroxide. In a reaction catalyzed by horseradish peroxidase, the peroxide reacts with an indicator dye to form a blue color at a rate proportional to the AST concentration of the sample. The resultant color in the reaction is measured by reflectance photometry.
Image /page/1/Figure/5 description: This image shows a series of four chemical reactions. In the first reaction, L-Aspartic acid and alpha-Ketoglutarate react with Aspartate Aminotransferase to produce Oxaloacetate and Glutamate. In the second reaction, Oxaloacetate reacts with Oxaloacetate Decarboxylase to produce Pyruvate and CO2. In the third reaction, Pyruvate, Phosphate, O2, and H2O react with Pyruvate Oxidase to produce Acetylphosphate, CO2, and H2O2. In the fourth reaction, Indicator and H2O2 react with Peroxidase to produce Colored Blue Dye and H2O.
A brown magnetic stripe on each cassette contains the calibration required for the Cholestech LDX Analyzer to convert the reflectance reading to the AST concentration in U/L. 37°C.
Intended Use (21 CFR 807.92 (a)(5))
The Cholestech LDX aspartate aminotransferase (AST) test is for the in vitro quantitative determination of aspartate aminotransferase (AST) in whole blood or serum on the Cholestech LDX Analyzer. AST measurements are used in the diagnosis and treatment of certain liver diseases (e.g., viral hepatitis and cirrhosis), and heart diseases.
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Similarities to the Predicate(s) (21 CFR 807.92 (a)(6))
A summary table of the similarities and differences between the LDX AST and the predicate device follows.
| Device Name | LDX AST(new device) | Synchron CX® AST(K952427) |
|---|---|---|
| Indicationsfor use | The Cholestech LDX aspartateaminotransferase (AST) test is forthe in vitro quantitativedetermination of AST in wholeblood or serum on the CholestechLDX Analyzer. | The Synchron CX reagent, in conjunction withthe Synchron® Enzyme Validator Set, isintended for the quantitative determination ofAST activity in serum or plasma on SynchronCX Clinical Systems. |
| AST measurements are used in thediagnosis and treatment of certainliver diseases (e.g., viral hepatitisand cirrhosis), and heart diseases. | AST measurements are used in the diagnosisand treatment of certain types of liver andheart diseases. | |
| InstrumentRequired | LDX Analyzer | Synchron CX Clinical System |
| Technology | Enzymatic methodology and asolid-phase technology | Enzymatic rate method; appropriate sampleand reagent volumes are introduced to thesystem's cuvette. |
| Assay Range | 10 to 400 U/L | 5 to 400 U/L |
| Sample Type | Whole blood (capillary and venous)and serum | Serum or plasma |
| CalibrationRequirements | No calibration performed by theuser; test information is encoded onthe magnetic stripe of the cassette,and the stripe is read by the LDXAnalyzer each time a cassette isrun. | Calibration required via the use of theSynchron Enzyme Validator Set; under typicaloperating conditions, the AST reagentcartridge must be calibrated every 5 days, andalso with certain parts replacement ormaintenance procedures. |
| Testing | Professional-Use, point-of-care | Professional-Use, conventional laboratory |
Comparison Table: Cholestech LDX AST vs Beckman Coulter Synchron CX AST
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| Device Name | LDX AST(new device) | Synchron CX® AST(K952427) |
|---|---|---|
| Environment |
Brief Discussion of Nonclinical and Clinical Performance Data (21 CFR 807.92(b)(1,2, 3)}
- 10 -- 400 U/L Assay range: .
- up to 50% Hematocrit tolerance: .
- less than 10% interference when challenged by evaluated levels of . Interference testing: endogenous and exogenous (therapeutic) substances
- Precision: 2 levels of Controls (Low- ~31 U/L AST, and High- ~106 U/L AST) were tested . in duplicate, twice a day, over a 20 day period for a total of 80 replicates per level. The percent coefficient of variation (%CV) from the testing of the Low Control was 8.8%, and 4.4% from the testing of the High Control. When the same testing protocol was performed with a whole blood sample at 58 U/L, the %CV was 4.8%.
- Accuracy: The LDX AST test was compared to the Synchron CX AST test with 109 . matched serum samples. The comparative data appear below (Synchron CX on x-axis).
| LDX AST vs Synchron CX AST | ||||
|---|---|---|---|---|
| n | slope | y-intercept | “r” | Range of Values |
| 109 | 0.97 | 1.6 | 0.983 | 12 – 396 U/L |
A study was performed where results obtained from testing whole blood samples (both venous and fingerstick) on the LDX were compared to results obtained from testing matched serum samples on the LDX. The comparative data appear below (serum results on x-axis).
| LDX AST: venous whole blood samples vs serum samples | ||||
|---|---|---|---|---|
| n | slope | y-intercept | "r" | Range of Values |
|---|---|---|---|---|
| 46 | 1.08 | 0.3 | 0.998 | 13 - 343 U/L |
LDX AST: fingerstick whole blood samples vs serum samples
| n | slope | y-intercept | "r" | Range of Values |
|---|---|---|---|---|
| 21 | 0.86 | 4.4 | 0.934 | 13 - 65 U/L |
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Image /page/4/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized depiction of a human figure in profile, with three overlapping faces suggesting a sense of community or interconnectedness. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the figure.
SEP - 5 2003
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Thomas E. Worthy, Ph.D. Vice President, Research and Regulatory Affairs Cholestech Corporation 3347 Investment Boulevard Hayward, CA 94545
K032027 -Re:
Trade/Device Name: Cholestech LDX aspartate aminotransferase (AST) Test Regulation Number: 21 CFR § 862.1100 Regulation Name: Aspartate amino transferase (AST/SGOT) Test System Regulatory Class: II Product Code: CIS Dated: June 30, 2003 Received: July 1, 2003
Dear Dr. Worthy
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. Iisting 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 (OS) 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 (301) 594-3084. 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/dsma/dsmamain.html.
Sincerely yours,
Steven Sutman
Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use Statement
510(K) Number (if known):
Device Name: Cholestech LDX aspartate aminotransferase (AST) Test
Indications for Use:
The Cholestech LDX aspartate aminotransferase (AST) test is for the in vitro quantitative determination of AST in whole blood or serum on the Cholestech LDX Analyzer.
AST measurements are used in the diagnosis and treatment of certain liver diseases (e.g., viral hepatitis and cirrhosis), and heart diseases.
Carol C Benson for Jean Cooper, DVM
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K032027
(PLEASE DO NOT WRITE BELOW THIS LINE- CONTINUE ON ANOTHER PAGE AS NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use * (Per 21 CFR 801.109)
OR
Over -the-Counter Use ________________________________________________________________________________________________________________________________________________________
§ 862.1100 Aspartate amino transferase (AST/SGOT) test system.
(a)
Identification. An aspartate amino transferase (AST/SGOT) test system is a device intended to measure the activity of the enzyme aspartate amino transferase (AST) (also known as a serum glutamic oxaloacetic transferase or SGOT) in serum and plasma. Aspartate amino transferase measurements are used in the diagnosis and treatment of certain types of liver and heart disease.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.