(30 days)
In vitro test for the quantitative determination of glucose in serum, plasma, urine and cerebrospinal fluid (CSF) on COBAS INTEGRA systems.
Glucose measurements are used in diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and pancreatic islet cell tumors.
The cassette COBAS INTEGRA Glucose HK Gen. 3 contains an in vitro diagnostic reagent system intended for use on COBAS INTEGRA SYSTEMS for the quantitative determination of glucose in serum, plasma, urine, and cerebrospinal fluid (CSF). The test principle is an enzymatic reference method with hexokinase.
The provided text is a 510(k) Summary for the COBAS INTEGRA Glucose HK Gen. 3 device, which describes an in vitro diagnostic reagent system for the quantitative determination of glucose. This type of submission focuses on demonstrating substantial equivalence to a legally marketed predicate device rather than fulfilling specific acceptance criteria in the way a new, novel device might. Therefore, the information provided focuses on comparative performance rather than predefined acceptance thresholds.
Based on the provided document, here's a breakdown of the requested information:
1. A table of acceptance criteria and the reported device performance
For a 510(k) submission seeking substantial equivalence, the "acceptance criteria" are generally that the modified device performs as well as, or better than, the predicate device. The performance characteristics of the COBAS INTEGRA Glucose HK Gen. 3 (modified device) are compared with its predicate device (COBAS INTEGRA Glucose HK Liquid, K972250).
| Feature | Acceptance Criteria (Implied by Predicate Performance) | Reported Device Performance (COBAS INTEGRA Glucose HK Gen. 3) |
|---|---|---|
| Measuring Range | 0-40 mmol/L (0-720 mg/dL) | 0.12-40 mmol/L (0.12-720 mg/dL) |
| Extended Measuring Range | 0-400 mmol/L (0-7200 mg/dL) | 0.12-400 mmol/L (2.16-7200 mg/dL) |
| Precision (Within run CV%) | Serum & Plasma: 1.7% @ 5.3 mmol/L; 0.72% @ 33.2 mmol/L | Serum & Plasma: 0.41% @ 4.48 mmol/L; 0.47% @ 12.48 mmol/L |
| Urine: 1.7% @ 1.7 mmol/L; 1.8% @ 37.1 mmol/L | Urine: 1.35% @ 0.83 mmol/L; 0.64% @ 2.42 mmol/L | |
| CSF: 1.6% @ 1.7 mmol/L; 1.8% @ 3.3 mmol/L | CSF: 1.13% @ 3.20 mmol/L; 1.49% @ 9.31 mmol/L | |
| Precision (Between run/day CV%) | Serum & Plasma: 2.6% @ 5.3 mmol/L; 1.5% @ 33.2 mmol/L | Serum & Plasma: 1.09% @ 4.44 mmol/L; 0.90% @ 12.46 mmol/L |
| Urine: 4.3% @ 1.7 mmol/L; 2.9% @ 37.1 mmol/L | Urine: 0.75% @ 0.84 mmol/L; 0.83% @ 2.43 mmol/L | |
| CSF: 2.3% @ 1.7 mmol/L; 1.9% @ 3.3 mmol/L | (Not explicitly stated for between day in CSF, only within run) | |
| Linearity | 0-40 mmol/L (before dilution) | 0.12-40 mmol/L (before dilution) |
| Lower Detection Limit | Serum & Plasma: 0.033 mmol/L | Serum, Plasma, Urine & CSF: 0.12 mmol/L |
| Urine: 0.22 mmol/L | ||
| CSF: 0.023 mmol/L | ||
| Endogenous Interferences | Hemolysis, Icterus, Lipemia - no significant interferences for predicate | Hemolysis: up to 1200 H Index; Icterus: up to 60 I Index; Lipemia: up to 1900 L Index (quantitative limits provided) |
| Exogenous Interferences | Falsely low results by elevated pyruvates; Gammopathy may cause unreliable results | Tetracyclin can cause falsely low results in urine; Gammopathy may cause unreliable results |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
The document primarily describes comparative performance data. Specific sample sizes for "test sets" or the provenance of the data (country of origin, retrospective/prospective) are not explicitly stated. The data presented such as precision data, linearity, and interference studies imply internal validation studies were performed, but details on the samples used (e.g., number of patient samples, type of samples beyond serum/plasma/urine/CSF) are absent in this summary.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
This is an analytical performance study for an in vitro diagnostic device, not an imaging device or a device requiring human interpretation for "ground truth". Therefore, there are no "experts" in the sense of clinical specialists establishing ground truth for the test set. Ground truth for glucose measurements is typically established through a reference method or validated calibrators and controls.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
Not applicable for this type of analytical performance study. Adjudication methods are relevant for human interpretation tasks, such as reading medical images.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
Not applicable. This is an in vitro diagnostic device measuring glucose, not an AI-assisted diagnostic tool that aids human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This is an automated in vitro diagnostic test system. The reported performance characteristics (precision, linearity, lower detection limit, interferences) are inherent to the device and reagent system itself, operating without human intervention for the measurement process once the sample is loaded. Thus, the performance data provided can be considered standalone performance.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth for glucose measurements is established by:
- Reference method: The test principle is an "enzymatic reference method with hexokinase."
- Traceability: It is "Standardized against Isotope Dilution Mass Spectrometry," which is a highly accurate and precise reference method for measuring glucose.
8. The sample size for the training set
This document does not specify a "training set" in the context of machine learning or AI models. It refers to the development and validation of an analytical measurement system. Data used for method development (e.g., reagent formulation optimization) would be part of standard product development but is not explicitly defined as a "training set" in this summary.
9. How the ground truth for the training set was established
Not applicable as there is no mention of a "training set" for an AI/ML algorithm. For the analytical method development, ground truth would be established through highly accurate reference methods and calibrators, similar to how the device's performance is validated.
{0}------------------------------------------------
510(k) Summary – COBAS INTEGRA Glucose HK Gen. 3
です。 で
| Introduction | According to the requirements of 21 CFR 807.92, the following informationprovides sufficient detail to understand the basis for a determination ofsubstantial equivalence | |
|---|---|---|
| Submittername, address,contact | Roche Diagnostics9115 Hague RdIndianapolis IN 46250(317) 521-3723 | |
| Contact person: Corina Harper | ||
| Date prepared: April 11, 2006 | ||
| Device Name | Proprietary name: COBAS INTEGRA Glucose HK Gen. 3 test | |
| Common name: Glucose HK Gen. 3 | ||
| Classification name: Glucose Test System | ||
| DeviceDescription | The cassette COBAS INTEGRA Glucose HK Gen. 3 contains an in vitrodiagnostic reagent system intended for use on COBAS INTEGRA SYSTEMSfor the quantitative determination of glucose in serum, plasma, urine, andcerebrospinal fluid (CSF). | |
| The test principle is an enzymatic reference method with hexokinase. | ||
| Intended use | In vitro test for the quantitative determination of glucose in serum, plasma,urine and cerebrospinal fluid (CSF) on COBAS INTEGRA systems. | |
| PredicateDevice | We claim substantial equivalence to the COBAS INTEGRA Glucose HKLiquid cleared as K972250. | |
| Substantialequivalency -Similarities | The table below indicates the similarities between the modified COBASINTEGRA Glucose HK Gen. 3 test and its predicate device (COBASINTEGRA Glucose HK Liquid, K972250). | |
| Feature | Predicate device: Glucose HKLiquid(K972250) | Modified device: Glucose HKGen. 3 |
| General | ||
| Intended Use/Indications forUse | The cassette COBAS INTEGRAGlucose HK Liquid contains an invitro diagnostic reagent systemintended for use on COBASINTEGRA systems for thequantitative determination ofglucose concentration in serum,plasma, urine and cerebrospinalfluid (CSF). | In vitro test for the quantitativedetermination of glucose in serum,plasma, urine and cerebrospinalfluid (CSF) on COBAS INTEGRAsystems |
| Specimen type | Serum, plasma, urine, CSF | Same |
| Test principle | ||
| Referencemethod | Enzymatic reference method withhexokinase. | Same |
| Reagent information | ||
| Stability - shelflife and on-board | 2-8 °C until expiration dateCOBAS INTEGRA 4008 weeks at 10 to 15° CCOBAS INTEGRA 700/8008 weeks at 8°C | Same |
| Calibrator | Calibrator f.a.s.Interval: each lot | Same |
| Quality control | Serum and plasma:Precinom U and Precinorm U PlusPrecipath and Precipath U PlusUrine:Quantitative urine controlsCSF:Quantitative CSF controlsInterval: 24 hrs recommended | Same |
| Traceability | Standardized against IsotopeDilution Mass Spectrometry | Same |
| Performance characteristics | ||
| Measuring range | 0-40 mmol/L (0-720 mg/dL)Extended measuring range withrecommended post dilution factor of10: 0-400 mmol/L (0-7200 mg/dL) | 0.12-40 mmol/L (0.12-720 mg/dL)Extended measuring range withrecommended post dilution factorof 10: 0.12-400 mmol/L (2.16-7200mg/dL) |
| Expected values(literaturereference)Additional valuesare referenced inthe method sheet | Plasma (fasting): 3.88-6.38 mmol/LUrine:1st morning urine 0.3-1.1 mmol/L24 h urine 0.11-0.50 mmol/24hSerum/plasma:Adults 4.11-5.89 mmol/L | Plasma (fasting): 3.88-6.38 mmol/LUrine:1st morning urine 0.3-1.1 mmol/L24 h urine 0.3-0.96 mmol/LSame |
: : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : :
{1}------------------------------------------------
.
{2}------------------------------------------------
| Substantial | The table below indicates the similarities between the modified COBAS |
|---|---|
| equivalency - | INTEGRA Glucose HK Gen. 3 test and its predicate device (COBAS |
| Differences | INTEGRA Glucose HK Liquid, K972250). |
·
:
| Feature | Predicate device: Glucose HKLiquid(K972250) | Modified device: Glucose HKGen.3 |
|---|---|---|
| Reagent information | ||
| R1 | Mono reagent in vial A and B(liquid) | R1:5.0 mmol/L MES, ≥4.5 mmol/LATP, 24 mmol/L Mg++, ≥7.0mmol/L NADP, pH 6.0 |
| R2 | 100 mmol/L MOPS, 12 mmol/LATP, 6 mmol/L NAD+, 10 mmol/L Mg++, ≥50 µcat/L HK(yeast), ≥50µcat/L G6PDH (microbial), 0.09%Sodium azide, pH 7.1 | R2:4.0 mmol/L Mg++, 200 mmol/LHEPES, ≥300 µcat/L HK (yeast),≥300 µcat/L G6PDH (microbial),pH 8.0 |
| Performance characteristics | ||
| Precision | Serum and plasma:Within run:1.7% @ 5.3 mmol/L0.72% @ 33.2 mmol/LBetween run:2.6% @ 5.3 mmol/L1.5% @ 33.2 mmol/L | Serum and plasma:Within run CV%:0.41% @ 4.48 mmol/L0.47% @ 12.48 mmol/LBetween day:1.09% @ 4.44 mmol/L0.90% @ 12.46 mmol/L |
| Urine applicationWithin run:1.7% @ 1.7 mmol/L1.8% @ 37.1 mmol/LBetween run:4.3% @ 1.7 mmol/L2.9% @ 37.1 mmol/L | Urine applicationWithin run:1.35% @ 0.83 mmol/L0.64% @ 2.42 mmol/LBetween day:0.75% @ 0.84 mmol/L0.83% @ 2.43 mmol/L | |
| CSF applicationWithin run:1.6% @ 1.7 mmol/L1.8% @ 3.3 mmol/LBetween run:2.3% @ 1.7 mmol/L1.9% @ 3.3 mmol/L | CSF applicationWithin run:1.13% @ 3.20 mmol/L1.49% @ 9.31 mmol/L | |
| Linearity | 0-40 mmol/L(before dilution) | 0.12-40 mmol/L(before dilution) |
| Lower detectionlimit | Serum and plasma:0.033 mmol/LUrine application:0.22 mmol/LCSF application:0.023 mmol/L | Serum, plasma, urine and CSF:0.12 mmol/L |
| Endogenousinterferences | Hemolysis no significantinterferencesIcterus no significant interferences | Hemolysis: up to 1200 H IndexIcterus: up to 60 I Index |
| Lipemia no significant interferences | Lipemia: up to 1900 L Index | |
| ExogenousInterferences | Falsely low results may be causedby elevated pyruvates levels | Tetracyclin at therapeuticconcentration gives falsely lowresults in urine samples |
| Gammopathy, in particular IgM,may cause unreliable results in rarecases | Same | |
| ProposedLabeling | Proposed labeling sufficient to describe the device, its intended use, and thedirections for use can be found in Section V. We believe the proposed versionof the device labeling presented contains all of the technical informationrequired per 21 CFR 809.10. | |
| Validation andDesign Control | Development activities were conducted under appropriate design controlprocedures and the overall product specifications were met. The Declarationof Conformity with Design Controls and Results of Risk Analysis areprovided in Section 5.1. Analytical Performance. | |
| Confidentiality | Roche Diagnostics Corporation requests that the FDA not disclose the natureor existence of this submission until the substantial equivalence decision hasbeen reached. | |
| Closing | Modification of the COBAS INTEGRA Glucose HK Gen.3 does not affectthe intended use or indications for use of the device as described in thelabeling, nor does it alter the fundamental scientific technology of the device.Therefore, we trust the information provided in this Special 510(k) willsupport a decision of substantial equivalence of the COBAS INTEGRAGlucose HK Gen.3 to the predicate.If you have any questions or require further information, please do nothesitate to contact this office.• Phone: (317) 521-3831• FAX: (317) 521-2324• email: corina.harper@roche.com |
{3}------------------------------------------------
{4}------------------------------------------------
:
{5}------------------------------------------------
DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/5/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized emblem featuring an abstract design that resembles an eagle or a bird in flight.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
MAY 17 2006
Ms. Corina Harper Regulatory Affairs Consultant Roche Diagnostics 9115 Hague Road PO Box 50416 Indianapolis, IN 46250-0416
K061048 Re: Trade/Device Name: COBAS INTEGRA Glucose HK Gen 3 Regulation Number: 21 CFR$ 862.1345 Regulation Name: Glucose test system Regulatory Class: Class II Product Code: CFR Dated: April 14, 2006 Received: April 17, 2006
Dear Ms. Harper:
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, 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 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 (QS) regulation (21 CFR Part 820).
{6}------------------------------------------------
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 (240) 276-0484. 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/industry/support/index.html.
Sincerely yours,
Alberto Setti, Ph.D.
Alberto Gutierrez, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
{7}------------------------------------------------
Indications for Use
510(k) Number (if known):
61048
Device Name: COBAS INTEGRA Glucose HK Gen 3
Indications For Use:
In vitro test for the quantitative determination of glucose in serum, plasma, urine and cerebrospinal fluid (CSF) on COBAS INTEGRA systems.
Glucose measurements are used in diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and pancreatic islet cell tumors.
Prescription Use XXXX (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR 801 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)
CLL
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safe
s106(k) K661048
§ 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.