(151 days)
The Glucose Hexokinase II in vitro diagnostic procedure is intended to measure glucose in human serum, plasma and urine on the Bayer ADVIA® 1650 System. Such measurement is used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia and insulin overdose.
The Glucose Hexokinase II in vitro diagnostic procedure is intended to measure glucose in human serum, plasma and urine on the Bayer ADVIA® 1650 System. The assay buffer is in dual aliquots, allowing for blanking and subtraction of potential interference effects.
Acceptance Criteria and Device Performance for Glucose Hexokinase II method for Bayer ADVIA® 1650 System (K011963)
This submission (K011963) is a 510(k) for a new version of a Glucose Hexokinase assay, called Glucose Hexokinase II, for the Bayer ADVIA® 1650 System. The submission claims substantial equivalence to the predicate device, also a Glucose Hexokinase assay (K991576). The "acceptance criteria" can be inferred from the reported performance of the predicate device, with the new device demonstrating comparable or improved performance.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as numerical thresholds in this 510(k) summary. Instead, the sponsor demonstrates that the new device's performance characteristics (Imprecision, Correlation, Interfering Substances, Analytical Range) are comparable to, or improved relative to, those of the predicate device.
| Performance Characteristic | Acceptance Criteria (Predicate Device Performance) | Reported Device Performance (Glucose Hexokinase II) |
|---|---|---|
| Imprecision (Total CV%) | ||
| Serum (low) | 2.4% at 77 mg/dL | 2.2% at 75 mg/dL |
| Serum (high) | 3.3% at 279 mg/dL | 2.2% at 279 mg/dL |
| Urine (low) | 3.5% at 42 mg/dL | 4.1% at 46 mg/dL |
| Urine (high) | 3.6% at 285 mg/dL | 3.6% at 267 mg/dL |
| Correlation: Regression Equation (Y=new, X=predicate) | Close to Y=1.00x + 0.00 | |
| Serum | Y=1.02x-1.84 | Y=1.02x-1.84 |
| Urine | Y=0.97x-7.44 | Y=0.97x-7.44 |
| Plasma vs Serum* | Y=1.001x+0.088 | Y=1.001x+0.088 |
| Correlation: R-value | High (e.g., >0.99) | |
| Serum | 0.998 | 0.998 |
| Urine | 0.999 | 0.999 |
| Plasma vs Serum* | 0.9997 | 0.9997 |
| Correlation: Syx (mg/dL) | Low (e.g., <8 mg/dL) | |
| Serum | 7.49 | 7.49 |
| Urine | 5.68 | 5.68 |
| Plasma vs Serum* | 5.33 | 5.33 |
| Interfering Substances (Effect % change) | Minimized, ideally <10% | |
| Bilirubin (29.1 mg/dL) | 1.05% at 81.32 mg/dL glucose | 1.05% at 81.32 mg/dL glucose |
| Hemoglobin (522 mg/dL) | 0.78% at 80.6 mg/dL glucose | 0.78% at 80.6 mg/dL glucose |
| Lipids (Intralipid 630 mg/dL) | -4.7% at 80.2 mg/dL glucose | -4.7% at 80.2 mg/dL glucose |
| Analytical Range | 0 to 700 mg/dL (Serum/Plasma/Urine) | 0 to 700 mg/dL (Serum/Plasma/Urine) |
Note: The performance values for the "Reported Device Performance" are identical to the "Acceptance Criteria" because the submission presents the new device's performance directly and implicitly claims it meets the standard set by the predicate. The changes in the Glucose Hexokinase II assay are described as "improvements" due to the ability for blanking, which "eliminates interference effects," suggesting that the new device at least performs as well as, if not better than, the predicate in these areas.
2. Sample Size Used for the Test Set and Data Provenance
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Test Set Sample Sizes:
- Correlation (Serum): N = 194
- Correlation (Urine): N = 99
- Correlation (Plasma vs Serum): N = 35 (spiked samples used)
- Imprecision: Not explicitly stated as a single "test set" sample size but implied by the reported CVs for different levels in serum and urine. This typically involves running multiple replicates over several days.
- Interfering Substances: Not explicitly stated as individual sample sizes per substance, but implied to be sufficient for demonstrating the effect at the specified concentrations.
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Data Provenance: The document does not explicitly state the country of origin or whether the data is retrospective or prospective. Given it's a 510(k) submission for a diagnostic device, the studies are typically prospective clinical laboratory evaluations conducted under controlled conditions, often in the country where the manufacturer is seeking approval (USA in this case, for FDA approval).
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
This submission describes a laboratory assay for glucose measurement. The "ground truth" for such assays is typically established by comparing the device's measurements against a reference method or a carefully calibrated, validated existing method (such as the predicate device itself in correlation studies). There are no "experts" in the sense of clinical reviewers required to establish the ground truth for individual samples in this context. The accuracy of the "ground truth" (e.g., the predicate device's readings or reference method readings) is based on the inherent precision and accuracy of that reference method.
4. Adjudication Method for the Test Set
Not applicable. As described in point 3, this is a quantitative laboratory assay. The assessment involves direct comparison of numerical results, not subjective interpretation requiring adjudication of expert opinions.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
Not applicable. MRMC studies are relevant for medical imaging or subjective diagnostic interpretations where multiple human readers assess cases. This submission is for an automated laboratory diagnostic assay, not an imaging device or a device requiring human interpretation of complex visual data.
6. Standalone Performance Study (Algorithm Only Without Human-in-the-Loop Performance)
Yes, this entire study is a standalone performance study. The Glucose Hexokinase II assay is an automated in vitro diagnostic procedure performed on the Bayer ADVIA® 1650 System. Its performance characteristics (imprecision, correlation, interference, analytical range) are evaluated inherently as an algorithm/system performance without human interpretation being a variable in the measurement process itself. Human involvement is limited to sample loading, system maintenance, and result review.
7. Type of Ground Truth Used
The ground truth for the performance studies is:
- For Imprecision: The mean glucose concentration of the control material or patient samples. The variability around this mean (CV%) indicates imprecision.
- For Correlation: The measurements obtained from the predicate device (ADVIA 1650 Glucose Hexokinase) are used as the comparative "ground truth" for the new device (ADVIA 1650 Glucose Hexokinase II). For plasma vs. serum correlation, the serum measurements from the ADVIA 1650 system are the reference.
- For Interfering Substances: The glucose concentration measured in the absence of the interfering substance, or the known spiking concentration, forms the basis for determining the "effect" of the interferent.
- For Analytical Range: The certified values of calibrators or spiked samples at the lower and upper limits of detection/linearity.
8. Sample Size for the Training Set
The document does not provide information about a "training set." This type of 510(k) submission for an in vitro diagnostic assay typically involves development and validation internally by the manufacturer, but the data presented here represents the validation studies to demonstrate substantial equivalence to an existing predicate. There isn't an "AI model" in the modern sense that needs a separate training set as it's a biochemical assay.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as a distinct "training set" for an AI model is not mentioned or relevant for this type of device. The development of the assay itself (e.g., optimizing reagent concentrations, reaction conditions) would have involved extensive R&D and internal testing using characterized samples and reference methods, which implicitly establishes "ground truth" during the development phase. However, these specific development details are not part of the 510(k) summary, which focuses on validation data against the predicate.
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510(k) SUMMARY OF SAFETY AND EFFECTIVENESS Glucose Hexokinase II method for Bayer ADVIA® 1650 System
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.
The assigned 510(k) number is: K011963
1. Intended Use
The Glucose Hexokinase II in vitro diagnostic procedure is intended to measure glucose in human serum, plasma and urine on the Bayer ADVIA® 1650 System. Such measurement is used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia and insulin overdose.
2. Predicate Device
| Product Name | Reagent Part # | Calibrator Part # | Predicate Device # |
|---|---|---|---|
| ADVIA 1650 Glucose Hexokinase | B01-4129-01 | T03-1291-62 | K991576 |
3. Device / Method
| Product Name | REF | Calibrator Part # |
|---|---|---|
| ADVIA 1650 Glucose Hexokinase II | 04903429 | T03-1291-62 |
Imprecision
| ADVIA 1650 Glu Hex II | ADVIA 1650 Glucose Hexokinase | ||||
|---|---|---|---|---|---|
| Specimen type | Level(mg/dL) | Total CV(%) | Specimen type | Level(mg/dL) | Total CV(%) |
| Serum | 75 | 2.2 | Serum | 77 | 2.4 |
| Serum | 279 | 2.2 | Serum | 279 | 3.3 |
| Urine | 46 | 4.1 | Urine | 42 | 3.5 |
| Urine | 267 | 3.6 | Urine | 285 | 3.6 |
Correlation (Y=ADVIA 1650 Glucose Hexokinase II, X=ADVIA 1650 Glucose Hexokinase)
| Specimen type | ComparisonSystem (X) | N | Regression Equation | Syx(mg/dL) | R | Sample Range(mg/dL) |
|---|---|---|---|---|---|---|
| Serum | ADVIA 1650 | 194 | Y=1.02x-1.84 | 7.49 | 0.998 | 49.3-589.8 |
| Urine | ADVIA 1650 | 99 | Y=0.97x-7.44 | 5.68 | 0.999 | 0.0-690.8 |
| Plasma(y) vs Serum(x)* | ADVIA 1650 2 | 35 | Y=1.001x+0.088 | 5.33 | 0.9997 | 73.2-623.05 |
*spiked samples used
Interfering Substances
| InterferingSubstance | Interfering Sub.Conc. (mg/dL) | Glucose(mg/dL) | Effect(% change) |
|---|---|---|---|
| Bilirubin | 29.1 | 81.32 | 1.05 |
| Hemoglobin | 522 | 80.6 | 0.78 |
| Lipids (Intralipid) | 630 | 80.2 | -4.7 |
Analytical Range
Serum/Plasma/Urine: 0 to 700 mg/dL
Nonclinical testing demonstrates that this device is as safe and effective as the predicate device.
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| Package Insert Sections | Glucose Hexokinase assay(predicate device) | Glucose Hexokinase II assay |
|---|---|---|
| Intended Use | similar | similar |
| Summary | similar | similar |
| Principle | similar | similar |
| Reagents | Assay buffer in single aliquot forreaction | Assay buffer in dual aliquots.Formulation identical; new formatallows for blanking. |
| Storage | similar | similar |
| Stability | 25 days | Similar, actual dating TBD |
| Precautions | similar | similar |
| Indications ofDeterioration | similar | similar |
| PerformanceCharacteristics | similar | similar |
| Limitations | Blanking was impossible. Assaypotentially susceptible to interferences. | Blanking now possible;interference effects eliminated |
| Parameters | similar | similar |
Table of Similarities and Differences between Glucose Hexokinase and Glucose Hexokinase II assay:
The changes in the assay represent improvements and allow for blanking, with an aliquot of buffer, and hence subtraction of any potential interference effects.
Kenneth Cole
9/25/01
Date
Kenneth T. Edds Manager Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, New York 10591-5097
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Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized caduceus symbol, which is a staff with two snakes coiled around it, often associated with medicine and healthcare. The symbol is encircled by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA". The logo is black and white.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
NOV 2 0 2001
Kenneth T. Edds, Ph.D. Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, NY 10591-5097
Re: K011963
Trade/Device Name: Glucose Hexokinase II Assay for the Advia 1650 Regulation Number: 21 CFR 862.1345 Regulation Name: Glucose test system Regulatory Class: Class II Product Code: CFR Dated: September 25, 2001 Received: September 26, 2001
Dear Dr. Edds:
We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your becared is (a) the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for use sured in the encreate) to togens and ment 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). and Cosmetic . Its (. 10) and the device, subject to the general controls provisions of the Act. The r ou may, diereleve, mains 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 (PMA), it If your device to such additional controls. Existing major regulations affecting your device can may be subject to back as a substions, Title 21, Parts 800 to 898. 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 or any 1 with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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This letter will allow you to begin marketing your device as described in your 510(k) premarket I his lotter will and my of substantial equivalence of your device to a legally marketed nouticate 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 1 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, (Jease contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained 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/odrh/dsma/dsmamain.html".
Sincerely yours,
Steven Autman
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: K011963
NOV 2 0 2001
Device Name: Glucose Hexokinase II Assay for the Advia 1650
Indications for Use:
The Glucose Hexokinase II in vitto diagnostic procedure is intended to measure glucose in human serum, The Chaose Irences. In the Bayer Advia 1650 system. Such measurement is used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia and insulin overdose.
Thomas C. O'Brien
Division Sion-Off Division of Clinical Laboratory Devices K 011963 510(k) Number.
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use
(Per 21 CFR 801.109)
OR
Over-The-CounterUse
(Optional Format 1-2-96)
§ 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.