(72 days)
This reagent is intended for the quantitative enzymatic determination of glucose in serum or plasma. For in vitro diagnostic use only. This glucose test system is a device intended to measure glucose quantitatively in serum or plasma. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell tumors.
Glucose test system
This is a 510(k) premarket notification for a Glucose Test System. The provided document does not contain a detailed study report with acceptance criteria and device performance as typically expected for a full medical device evaluation. Instead, it is a letter from the FDA confirming substantial equivalence to a predicate device, based on information provided in the original 510(k) submission (K041052), which is not fully included here.
However, based on the Indications for Use (Page 2), we can infer the primary function of the device and thus, conceptualize what typical acceptance criteria and study designs would entail for such a device.
Here's an interpretation and hypothetical construction of the requested information, given the limitations of the provided document.
Understanding the Device: The device is a "Glucose Test System" intended for the "quantitative enzymatic determination of glucose in serum or plasma." It's for "in vitro diagnostic use only" and its measurements are used in the "diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, gestational diabetes, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell tumors." The intended patient population is "adult, pediatric, and neonatal."
1. Table of Acceptance Criteria and Reported Device Performance
Since specific acceptance criteria and detailed performance data are not explicitly stated in this FDA letter, the following table represents typical performance characteristics and acceptance criteria for a glucose test system, along with hypothetical "reported device performance" values that would generally be expected for a device receiving FDA clearance. These are inferred based on standard practices for such devices.
| Performance Characteristic | Acceptance Criteria (Typical for Glucose Meters) | Reported Device Performance (Hypothetical) |
|---|---|---|
| Accuracy (Bias) | Within ±10% vs. reference for >95% of samples; within ±15% for >99% of samples (ISO 15197 for point-of-care). For lab systems, tighter standards may apply, often within ±5% or fixed mg/dL difference. | Achieved >98% of results within ±10% vs. reference, and >99.5% within ±15%. Mean bias: -2.0 mg/dL. |
| Precision (Repeatability/Reproducibility) | Coefficient of Variation (CV) ≤ 5% at clinically relevant levels (e.g., low, normal, high glucose). | CV < 3% at 50 mg/dL, < 2% at 150 mg/dL, < 2.5% at 300 mg/dL. |
| Linearity/Reportable Range | Demonstrates linear response across the claimed detection range (e.g., 20-600 mg/dL). | Linear from 20 mg/dL to 600 mg/dL with R² > 0.999. |
| Interferences | No significant interference from common endogenous (e.g., bilirubin, triglycerides, hemoglobin) or exogenous substances (e.g., acetaminophen, ascorbic acid) at specified concentrations. | No significant interference observed at clinically relevant concentrations for tested interferents. |
| Sample Matrix Equivalence | No significant difference in results between serum and plasma samples where both are indicated. | Demonstrated equivalent performance between serum and plasma samples. |
| Stability | Reagents and calibrators maintain claimed performance over their stated shelf life under specified storage conditions. | Reagents and calibrators stable for X months/years under specified conditions. |
Note: The FDA letter indicates this is a "Glucose Test System" for serum or plasma, suggesting it's likely a lab-based or professional-use system, which typically has stricter accuracy and precision requirements than home-use blood glucose meters. The "enzymatic determination" further points to a robust analytical method.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: The document does not specify the sample size for any test set. For a glucose test system evaluating accuracy, typical studies involve hundreds to thousands of patient samples (e.g., 100-200 samples per comparison, if comparing to a reference method across the clinical range, with additional samples for interference, precision, and other studies). For FDA submission, it would likely involve a sufficient number of samples to cover the entire clinically reportable range from low to high glucose concentrations, usually with adequate representation across different patient populations (e.g., diabetic, non-diabetic, pediatric, neonatal, as indicated).
- Data Provenance: The document does not specify the country of origin of the data or whether it was retrospective or prospective. Typically, clinical studies for FDA submissions are prospective and conducted in the United States, though multi-center international studies are also common.
3. Number of Experts Used to Establish Ground Truth and Qualifications
For a glucose test system, "ground truth" is typically established by a highly accurate and precise reference method, not by human expert interpretation in the same way as imaging studies.
- Ground Truth Establishment: Ground truth for glucose measurements is typically established using a primary measurement procedure such as isotope dilution-mass spectrometry (ID-MS) or a well-validated secondary reference method like a hexokinase reference method performed on a highly calibrated and quality-controlled laboratory analyzer.
- "Experts": The "experts" in this context would be highly trained clinical chemists or laboratory personnel with extensive experience in operating and maintaining these reference methods, ensuring their accuracy, calibration, and quality control. There isn't a "number of experts" in the sense of inter-rater agreement for diagnosis; rather, it's about the rigor of the reference laboratory and method.
4. Adjudication Method for the Test Set
This concept is not applicable to the type of device described. Adjudication methods (like 2+1, 3+1) are used for resolving discrepancies in human expert interpretations, particularly in qualitative or semi-quantitative assessments (e.g., reading medical images, clinical event classification). For a quantitative diagnostic device like a glucose meter, "ground truth" is an objective numerical value obtained from a reference method, not a subjective interpretation requiring adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- Not applicable. MRMC studies are typically performed for devices that involve human interpretation, such as diagnostic imaging AI tools, to assess how an AI system might improve human reader performance. A glucose test system provides a quantitative numerical output that doesn't inherently involve human "reading" or "interpretation" in the same way. The device's output is directly used by healthcare professionals.
6. Standalone (Algorithm Only) Performance Study
- Yes, a standalone study is fundamental. For a glucose test system, the primary performance evaluation is a standalone study of the algorithm/device itself. This involves:
- Comparing the device's quantitative glucose measurements against those obtained from a recognized reference method.
- Evaluating precision (repeatability and reproducibility).
- Testing for linearity, limits of detection/quantitation, and interferences.
- These studies assess the device's inherent analytical performance without human intervention in the result generation process.
7. Type of Ground Truth Used
- As described in Section 3, the ground truth is established by a highly accurate and precise reference method, typically a hexokinase reference method or isotope dilution-mass spectrometry (ID-MS), recognized as the gold standard for glucose measurement. This is essentially an objective laboratory measurement from a certified reference laboratory.
8. Sample Size for the Training Set
The document does not provide information on a training set size.
- For enzymatic glucose test systems, specifically for the reagent itself, there isn't a "training set" in the machine learning sense. The device's underlying chemical and enzymatic reactions are based on known spectrophotometric or electrochemical principles. Manufacturers would perform extensive development and validation using a large number of samples, analytical studies, and calibration sets to optimize the reagent formulation, instrument parameters, and ensure robust performance across various conditions. This development might involve hundreds to thousands of samples, but it's not typically categorized as a "training set" for an algorithm in the way AI/ML devices do. If there were any sophisticated signal processing or calibration algorithms, those would be developed on proprietary datasets.
9. How the Ground Truth for the Training Set Was Established
- As mentioned above, for a traditional enzymatic glucose test system, the concept of a "training set" with ground truth (as in AI/ML) is not directly applicable.
- Instead, during the development phase, manufacturers would use well-characterized glucose solutions of known concentrations (often traceable to NIST standards) and patient samples whose glucose levels have been verified by a reference method to:
- Calibrate the device.
- Optimize reagent formulations and reaction conditions.
- Verify basic analytical performance (e.g., linearity, sensitivity).
- This "ground truth" for development and calibration would similarly be derived from highly accurate reference methods or certified reference materials.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Image /page/0/Picture/2 description: The image shows the seal of the Department of Health & Human Services USA. The seal features an abstract eagle design with three stylized wing strokes. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the eagle.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
JUN 3 0 2004
Mr. James J. Miller Official Correspondent General Manager Hemagen Diagnostics, Inc. Raichem Division 9033 Red Branch Road Columbia, MD 21045
K041052 Re:
Trade/Device Name: Glucose test System Regulation Number: 21 CFR 862.1345 Regulation Name: Glucose test system Regulatory Class: Class II Product Code: CFR Dated: March 5, 2004 Received: April 19, 2004
Dear Mr. Miller:
We have reviewed your Section 510(k) premarket notification of intent to market the device we nave roviewed your be determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for use stated in the enactment date of the Medical Device Amendments, or to conner of the 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). and Cosmetic For (10) that the device, subject to the general controls provisions of the Act. The I ou may, morelor, mains of the Act include requirements for annual registration, listing of general vontrols proficiouring 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 your device to such additional controls. Existing major regulations affecting your device it may be subject to bach additions (CFR), Parts 800 to 895. In additions (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 I least of advised that I Dr brissantly wour device complies with other requirements of the Act that I DA has made a acterimalations administered by other Federal agencies. You must or any 1 cataled and the Act's requirements, including, but not limited to: registration and listing (21 Comply with and the tree (21 CFR Parts 801 and 809); and good manufacturing practice Of It I art 807), as set forth in the quality systems (QS) 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,
Jean M. Cooper, MS, DVM.
MS, DVM
Jean M. Cooper, MS, D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known): K041052
Device Name: Glucose test system
Indications For Use:
This reagent is intended for the quantitative enzymatic determination of glucose in serum or plasma. For in vitro diagnostic use only.
This glucose test system is a device intended to measure glucose quantitatively in I his glucose tool oyotom to a casurements are used in the diagnosis and treatment of Scrum or plasma. Glass and idiopathic hypoglycemia, and of pancreatic islet cell tumors.
The intended patient population may be adult, pediatric, and neonatal.
Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use (21 CFR 807 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Carol C Benson
Division Sign-Off
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510/k)
Page 1 of __ 1 ___
§ 862.1345 Glucose test system.
(a)
Identification. A glucose test system is a device intended to measure glucose quantitatively in blood and other body fluids. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.(b)
Classification. Class II (special controls). The device, when it is solely intended for use as a drink to test glucose tolerance, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.