(104 days)
The Cholestech L·D·X Alanine aminotransferase Test (ALT) is for the in vitro quantitative determination of alanine aminotransferase (ALT) in whole blood or serum on the Cholestech L.D.X Analyzer.
Alanine aminotransferase measurements are used in the diagnosis and treatment of certain liver diseases (e.g., viral hepatitis and cirrhosis) and heart diseases.
The Cholestech L·D·X Alanine Aminotransferase Test (ALT) combines an enzymatic methodology and a solid-phase technology to measure ALT in whole blood or serum. Blood from a fingerstick is collected into a lithium heparin coated capillary tube (venous whole blood serum is also acceptable) and dispensed into a L·D·X cassette. The cassette is then placed into the Cholestech L·D·X where a unique system separates the plasma from the blood cells. The plasma flows to both sides of the cassette and is transferred to the ALT reaction pad.
The Cholestech L•D•X Analyzer measures alanine aminotransferase by an enzymatic method based on the method formulation of Katsuyama et al. Alanine aminotransferase catalyzes the transfer of amino groups from L-Alanine and α-Ketoglutarate to pyruvate and glutamate. 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 ALT concentration of the sample. The resultant color in the reaction is measured by reflectance photometry.
L-Alanine + α -Ketoglutarate Alanine Aminotransferase → Pyruvate + Glutamate
Pyruvate + Phosphate + O2 + H2O Pyruvate Oxidase → Acetylphosphate + CO2 + H2O2
Indicator + H2O2 Peroxidase → Colored Blue Dye + H2O
A brown magnetic stripe on each cassette contains the calibration information required for the Cholestech L•D•X Analyzer to convert the reflectance reading to the ALT concentration in U/L at 37° C.
Here's an analysis of the provided text regarding the Cholestech L·D·X Alanine aminotransferase (ALT) Test, focusing on acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance
The submission primarily focuses on demonstrating substantial equivalence to a predicate device (Roche Diagnostics Reflotron GPT (ALT) test) rather than explicitly stating pre-defined acceptance criteria in the format of pass/fail thresholds. However, we can infer the performance characteristics the submitter aimed to demonstrate as being comparable or superior to the predicate.
| Performance Characteristic | Acceptance Criteria (Inferred from Predicate/Submission Goal) | Reported Device Performance (Cholestech L·D·X ALT) | Predicate Device Performance (Roche Diagnostics Reflotron GPT (ALT)) |
|---|---|---|---|
| Assay Range | Comparable or suitable for intended use | 10-400 U/L | 5 - 1200 U/L |
| Precision (Within run) | Comparable to predicate device | Level 1: Mean 30.6, SD 0.97, %CV 3.2Level 2: Mean 57.8, SD 1.80, %CV 3.1Serum Pool: Mean 168.9, SD 5.68, %CV 3.4 | Level I: Mean 51.0, SD 1.01, %CV 2.0Level II: Mean 110, SD 3.0, %CV 2.7Pool: Mean 166, SD 5.1, %CV 3.1 |
| Precision (Total/Day to Day) | Comparable to predicate device | Level 1: Mean 30.6, SD 1.67, %CV 5.4Level 2: Mean 57.8, SD 2.68, %CV 4.6Serum Pool: Mean 168.9, SD 11.02, %CV 6.5 | Level I: Mean 54.8, SD 1.7, %CV 3.1Level II: Mean 116.9, SD 4.2, %CV 3.6 |
| Method Comparison (vs. Reflotron GPT (ALT)) | Strong correlation ($r \ge 0.9$) and acceptable slope/intercept indicating agreement | Capillary Whole Blood: $y = 0.921x + 4.28$ ($r = 0.932$)Venous Whole Blood: $y = 0.916x + 0.269$ ($r = 0.975$)Serum: $y = 0.914x - 0.517$ ($r = 0.971$) | Not applicable (this is the reference for the comparison) |
| Interfering Substances | No significant interference at specified levels | Uric Acid: 15 mg/dl (No interference)Bilirubin: 5 mg/dL (No interference)Hematocrit: 50% (No interference)Lipemia: 450 mg/dL triglycerides (No interference) | Uric Acid: Not reportedBilirubin: Not reportedHematocrit: 55%Lipemia: 400 mg/dL (cholesterol), 1700 mg/dL (triglycerides) |
2. Sample Sizes Used for the Test Set and Data Provenance
- Precision Studies:
- Within-run:
- Cholestech L·D·X ALT: N=20 for each of 3 levels (Level 1, Level 2, Serum Pool).
- Predicate: N=20 for each of 3 levels (Level I, Level II, Pool).
- Total/Day to Day:
- Cholestech L·D·X ALT: N=20 for each of 3 levels (Level 1, Level 2, Serum Pool).
- Predicate: N=15 for each of 2 levels (Level I, Level II).
- Within-run:
- Method Comparison Studies (Cholestech L·D·X ALT vs. predicate Reflotron GPT (ALT)):
- Capillary Whole Blood (x) vs. Capillary Whole Blood (y): n = 24
- Venous Whole Blood (x) vs. Venous Whole Blood (y): n = 53
- Serum (x) vs. Serum (y): n = 52
- Method Comparison Studies (Predicate Reflotron GPT (ALT) vs. GPT (ALT) IFCC Method): (Note: This data is for the predicate device's performance against a reference method, not the current device.)
- Venous Heparin Blood (x) vs. Heparin Plasma (y): n = 69
- Serum (x) vs. Serum (y): n = 36
- Venous Heparin Plasma (x) vs. Venous Heparin Plasma (y): n = 69
- Capillary Heparin Blood (x) vs. Capillary Heparin Plasma (y): n = 26
Data Provenance: The document does not specify the country of origin for the data or whether the studies were retrospective or prospective. Given the nature of laboratory testing submissions, it is generally assumed these are prospective controlled studies conducted in a lab environment.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of information is not applicable to this submission. This device is an in vitro diagnostic (IVD) device for quantitative biochemical measurement (Alanine aminotransferase, ALT). The "ground truth" for such a device is typically established against a recognized reference method (like the IFCC method for ALT) or by comparison to a legally marketed predicate device with established clinical utility and accuracy. It does not involve human expert interpretation of images or clinical cases that would require adjudication.
4. Adjudication Method for the Test Set
This is not applicable. As explained above, the assessment of an IVD involves quantitative measurements and comparisons to reference methods or predicate devices, not human interpretation that requires adjudication.
5. Was a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Done? If so, what was the effect size of how much human readers improve with AI vs without AI assistance?
This is not applicable. This submission concerns an in vitro diagnostic assay (a lab test), not an AI-assisted diagnostic imaging device that would involve human readers interpreting cases. Therefore, no MRMC study or AI assistance effect size is mentioned or relevant.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
This is not applicable. The Cholestech L·D·X ALT Test is a standalone IVD device (a test kit used with an analyzer), but it's not an AI algorithm. Its performance is inherent to the chemical reactions and reflectance photometry. The performance values reported (precision, method comparison) are the standalone performance of the device without human interpretation.
7. The Type of Ground Truth Used
The ground truth used for method comparison was primarily the predicate device, Roche Diagnostics Reflotron GPT (ALT) test, which itself was likely compared against a reference method such as the GPT (ALT) IFCC Method (as referenced in the predicate's method comparison section). For precision studies, the ground truth is the statistical properties of the measurements of known samples.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning or AI. For an IVD device like this, the "training" (calibration and optimization) of the assay methodology and the L·D·X Analyzer itself would have been done during the product development phase (R&D). The reported data represents performance characteristics verified subsequently. The sample sizes for these internal development and validation studies are not provided in this 510(k) summary.
9. How the Ground Truth for the Training Set Was Established
As there is no explicit mention of a "training set" in the AI/ML sense, this question is not fully applicable. However, for the development and optimization of the assay and instrument (analogous to "training" for an IVD):
- The ground truth would have been established through known concentrations of ALT in control materials, reference methods (like the IFCC method), and potentially split-sample comparisons against established laboratory instruments.
- This process would involve extensive experimentation to optimize reagent concentrations, reaction times, measurement parameters, and calibration curves to ensure accuracy and precision across the intended assay range. The details of these internal R&D processes are typically proprietary and not provided in a 510(k) summary.
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9 1999 SEP
510(k) Summary
| Introduction | According to the requirements of 21 CFR 807.92, the following informationprovides sufficient detail to understand the basis for a determination ofsubstantial equivalence. | |||
|---|---|---|---|---|
| 1.Submittername, address,contact | Cholestech Corporation3347 Investment Blvd.Hayward, CA 94545-3808(510) 293-8002Fax: (510) 732-7227 | |||
| Contact Person: Thomas WorthyDate Prepared: 26 May 1999 | ||||
| 2.Device name | Proprietary name: Cholestech L·D·X Alanine aminotransferase (ALT) TestCommon name: Colorimetric assay for the determination of alanineaminotransferase.Classification name: Alanine aminotransferase (ALT/SGPT) test system | |||
| 3.PredicateDevice | The Cholestech L·D·X Alanine aminotransferase Test is substantiallyequivalent to other products in commercial distribution intended for similaruse. Most notably it is substantially equivalent to the currently marketedRoche Diagnostics Reflotron GPT (ALT) test. | |||
| 4.DeviceDescription | The Cholestech L·D·X Alanine Aminotransferase Test (ALT) combines anenzymatic methodology and a solid-phase technology to measure ALT inwhole blood or serum. Blood from a fingerstick is collected into a lithiumheparin coated capillary tube (venous whole blood serum is also acceptable)and dispensed into a L·D·X cassette. The cassette is then placed into theCholestech L·D·X where a unique system separates the plasma from the bloodcells. The plasma flows to both sides of the cassette and is transferred to theALT reaction pad. | |||
| 4.DeviceDescription,cont. | The Cholestech L•D•X Analyzer measures alanine aminotransferase by anenzymatic method based on the method formulation of Katsuyama et al.Alanine aminotransferase catalyzes the transfer of amino groups from L-Alanine and α-Ketoglutarate to pyruvate and glutamate. Pyruvate oxidase, inthe presence of oxygen, oxidizes the pyruvate to acetylphosphate andhydrogen peroxide. In a reaction catalyzed by horseradish peroxidase, theperoxide reacts with an indicator dye to form a blue color at a rateproportional to the ALT concentration of the sample. The resultant color inthe reaction is measured by reflectance photometry. | |||
| L-Alanine + α -Ketoglutarate | Alanine Aminotransferase→ | Pyruvate + Glutamate | ||
| Pyruvate + Phosphate + O2 + H2O | Pyruvate Oxidase→ | Acetylphosphate + CO2 + H2O2 | ||
| Indicator + H2O2 | Peroxidase→ | Colored Blue Dye + H2O | ||
| A brown magnetic stripe on each cassette contains the calibration informationrequired for the Cholestech L•D•X Analyzer to convert the reflectancereading to the ALT concentration in U/L at 37° C. | ||||
| 5.Intended use | The Cholestech L•D•X Alanine aminotransferase (ALT) Test is for the in vitroquantitative determination of alanine aminotransferase (ALT) in whole bloodor serum on the Cholestech L•D•X Analyzer | |||
| 6.Comparison topredicatedevice | The Cholestech L•D•X Alanine aminotransferase Test is substantiallyequivalent to other products in commercial distribution intended for similaruse. Most notably it is substantially equivalent to the currently marketedRoche Diagnostics Reflotron GPT (ALT) test (K864082). |
continued on next page
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- Comparison to predicate device, cont.
The following table compares the Cholestech L·D·X Alanine aminotransferase Test with the predicate device, Roche Diagnostics Reflotron GPT (ALT) test. Specific data on the performance of the test have been incorporated into the draft labeling in Section 5. Labeling for the predicate device is provided in Section 6.
Similarities:
·Intended Use: Colorimetric assay for the in vitro quantitative determination of alanine aminotransferase (glutamate pyruvate transaminase).
· Testing Sites: Clinical laboratories and point of care
· Test principle: Pyruvate oxidase and peroxidase catalyzed reactions
Differences:
| Feature | L.D.X ALT | Reflotron GPT (ALT) |
|---|---|---|
| Instrumentrequired | L·D·X Analyzer | Reflotron System |
| Assay Range | 10-400 U/L | 5 - 1200 U/L |
| Sample Type | Whole blood (capillary andvenous) and serum | Whole blood (capillary andvenous), serum and plasma |
| Feature | L-D-X ALT | Reflotron GPT (ALT) |
| Precision | NCCLS (modified): | (From Reflotron Package Insert) |
| Within run (U/L) | Within run (U/L) | |
| Level 1 Level 2 Serum Pool | Level I Level II Pool | |
| N | 20 20 20 | 20 20 20 |
| Mean | 30.6 57.8 168.9 | 51.0 110 166 |
| SD | 0.97 1.80 5.68 | 1.01 3.0 5.1 |
| %CV | 3.2 3.1 3.4 | 2.0 2.7 3.1 |
| Total (U/L): | Day to Day Precision (U/L): | |
| Level 1 Level 2 Serum Pool | Level I Level II | |
| N | 20 20 20 | 15 15 |
| Mean | 30.6 57.8 168.9 | 54.8 116.9 |
| SD | 1.67 2.68 11.02 | 1.7 4.2 |
| %CV | 5.4 4.6 6.5 | 3.1 3.6 |
| MethodComparison | Vs Reflotron GPT (ALT): | Vs GPT (ALT) IFCC Method: |
| x = Capillary Whole Bloody = Capillary Whole Bloodn = 24y = $0.921x + 4.28$ ; r = 0.932 | x = Venous Heparin Bloody = Heparin Plasman = 69y = $1.02x - 3.6$ ; r = 0.995 | |
| x = Venous Whole Bloody = Venous Whole Bloodn = 53y = $0.916x + 0.269$ ; r = 0.975 | x = Serumy = Serumn = 36y = $1.01x + 0.2$ ; r = 0.999 | |
| x = Serumy = Serumn = 52y = $0.914x - .517$ ; r = 0.971 | x = Venous Heparin Plasmay = Venous Heparin Plasman = 69y = $1.04x - 3.3$ ; r = 0.993 | |
| x = Capillary Heparin Bloody = Capillary Heparin Plasman = 26y = $0.969x + 4.7$ ; r = 0.994 |
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Performance Characteristics:
Comparison to predicate device cont.
Continued on next page
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Performance Characteristics, cont.:
Comparison to predicate device, (cont.)
| Feature | L-D-X ALT | Reflotron GPT (ALT) |
|---|---|---|
| Interferingsubstances | No interference at: | No interference at: |
| Uric Acid | 15 mg/dl | Not reported |
| Bilirubin | 5 mg/dL | Not reported |
| Hematocrit | 50% | 55% |
| Lipemia | 450 mg/dL triglycerides | 400 mg/dL (cholesterol),1700 mg/dL (triglycerides) |
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Image /page/5/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 resembling an eagle or bird in flight, composed of three stylized human profiles facing to the right.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
19 1999 SEP
Thomas E. Worthy, Ph.D. Director, Technical Affairs Cholestech Corporation 3347 Investment Blvd. Hayward, California 94545-3808
Re: K991834
Trade Name: Cholestech L·D·X Alanine Aminotransferase (ALT) Test Regulatory Class: I Product Code: CKD Dated: July 23, 1999 Received: July 26, 1999
Dear Dr. Worthy:
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 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). 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 Regulations, 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 action. In addition, FDA may publish further announcements 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 regulations.
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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/dsma/dsmamain.html".
Sincerely yours,
Steven Butman
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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510(k) Number (if known): N/A K991834
Device Name: Cholestech L·D·X Alanine aminotransferase Test (ALT)
Indications For Use:
The Cholestech L·D·X Alanine aminotransferase Test (ALT) is for the in vitro quantitative determination of alanine aminotransferase (ALT) in whole blood or serum on the Cholestech L.D.X Analyzer.
Alanine aminotransferase measurements are used in the diagnosis and treatment of certain liver diseases (e.g., viral hepatitis and cirrhosis) and heart diseases.
Jeans Cooper
(Division Sign-Off)
Division of Clinical Laboratory Devices 9910 11 510(k) Number_
| Concurrence of CDRH, Office of Device Evaluation (ODE) |
|---|
| -------------------------------------------------------- |
| Prescription Use(Per 21 CFR 801.109) | OR | Over-The-Counter Use |
|---|---|---|
| ------------------------------------------ | ---- | ---------------------- |
(Optional Format 1-2-96)
§ 862.1030 Alanine amino transferase (ALT/SGPT) test system.
(a)
Identification. An alanine amino transferase (ALT/SGPT) test system is a device intended to measure the activity of the enzyme alanine amino transferase (ALT) (also known as a serum glutamic pyruvic transaminase or SGPT) in serum and plasma. Alanine amino transferase measurements are used in the diagnosis and treatment of certain liver diseases (e.g., viral hepatitis and cirrhosis) and heart 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.