(40 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 the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus and idiopathic hypoglycemia.
The cassette COBAS INTEGRA Glucose HK New Formulation 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.
Here's a breakdown of the acceptance criteria and the study details for the COBAS INTEGRA Glucose HK Gen. 3 device, based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
The 510(k) summary primarily focuses on demonstrating substantial equivalence to a predicate device by comparing performance characteristics. Explicit "acceptance criteria" against numerical targets are not clearly defined in the provided text as separate from the performance data. Instead, the "acceptance" is implied by demonstrating that the new formulation's performance is similar to or improved compared to the predicate device's performance.
However, based on the comparative tables provided, we can infer the desired performance characteristics for the new device. The predicate device's performance effectively serves as the benchmark.
| Acceptance Criteria (Implied from Predicate) | Reported Device Performance (COBAS INTEGRA Glucose HK New Formulation) |
|---|---|
| Precision (Serum and Plasma): | |
| Within run CV%: 1.7% @ 5.3 mmol/L | Within run CV%: 1.8% @ 4.54 mmol/L |
| Within run CV%: 0.72% @ 33.2 mmol/L | Within run CV%: 1.6% @ 13.5 mmol/L |
| Between run CV%: 2.6% @ 5.3 mmol/L | Between run CV%: 2.1% @ 4.54 mmol/L |
| Between run CV%: 1.5% @ 33.2 mmol/L | Between run CV%: 2.0% @ 13.5 mmol/L |
| Precision (Urine Application): | |
| Within run CV%: 1.7% @ 1.7 mmol/L | Within run CV%: 1.2% @ 1.63 mmol/L |
| Within run CV%: 1.8% @ 37.1 mmol/L | Within run CV%: 1.1% @ 16.3 mmol/L |
| Between run CV%: 4.3% @ 1.7 mmol/L | Between day CV%: 1.2% @ 1.63 mmol/L |
| Between run CV%: 2.9% @ 37.1 mmol/L | Between day CV%: 1.1% @ 16.3 mmol/L |
| Precision (CSF Application): | |
| Within run CV%: 1.6% @ 1.7 mmol/L | Within run CV%: 0.87% @ 3.43 mmol/L |
| Within run CV%: 1.8% @ 3.3 mmol/L | Within run CV%: 1.3% @ 1.72 mmol/L |
| Between run CV%: 2.3% @ 1.7 mmol/L | Between run CV%: 0.91% @ 3.43 mmol/L |
| Between run CV%: 1.9% @ 3.3 mmol/L | Between run CV%: 1.4% @ 1.72 mmol/L |
| Lower Detection Limit: | |
| Serum and plasma: 0.033 mmol/L | Serum, plasma, urine and CSF: 0.03 mmol/L |
| Urine application: 0.22 mmol/L | (Covered by combined 0.03 mmol/L) |
| CSF application: 0.023 mmol/L | (Covered by combined 0.03 mmol/L) |
| Interferences (Endogenous): | |
| Hemolysis: No significant interferences | Same |
| Icterus: No significant interferences | Same |
| Lipemia: No significant interferences | Same |
| Gammopathy (IgM): May cause unreliable results in rare cases | In rare cases gammopathy, in particular type IgM (Waldenstrom's macroglobulinemia) may cause unreliable results. |
| Interferences (Exogenous): | |
| Pyruvates: Falsely low results may be caused by elevated levels | (Not specifically mentioned for new formulation, but assumed comparable unless stated otherwise due to "same" comparisons) |
| Measuring Range: 0-40 mmol/L (0-720 mg/dL) | 0-40 mmol/L (0-720 mg/dL) |
| Extended Measuring Range: 0-400 mmol/L (0-7200 mg/dL) with 10x dilution | 0-400 mmol/L (0-7200 mg/dL) with 10x dilution |
| Stability: Same as predicate | Same as predicate |
2. Sample Size for the Test Set and Data Provenance
The provided document does not specify the exact sample sizes used for the precision and lower detection limit studies. It presents the results of these studies but doesn't detail the number of replicates or individual samples.
- Test Set Sample Size: Not explicitly stated.
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, given it's a 510(k) submission for a diagnostic kit, the studies would typically be prospective and conducted in a controlled laboratory environment to generate the performance data.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not applicable to this type of device (in vitro diagnostic reagent system). The "ground truth" for a glucose test is established by comparison to recognized reference methods (e.g., enzymatic reference method with hexokinase, which is the principle of both the predicate and new device, and traceability to isotope standards). It does not involve expert consensus on pathological images or clinical outcomes.
4. Adjudication Method for the Test Set
This information is not applicable as there is no human interpretation or subjective assessment involved that would require an adjudication method. The device provides quantitative measurements.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a MRMC comparative effectiveness study was not done. This type of study is typically performed for imaging devices or AI-assisted diagnostic tools where human readers are interpreting results, and the AI's impact on their performance is being evaluated. This device is an in vitro diagnostic reagent system for quantitative measurement.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
The performance data presented (precision, lower detection limit) are standalone performance characteristics of the assay itself, independent of human interpretation or intervention in the measurement process beyond standard laboratory procedures for running the test. The "algorithm" here refers to the chemical and enzymatic reactions and the instrument's measurement capabilities.
7. The Type of Ground Truth Used
The ground truth for evaluating the performance of this glucose test is based on:
- Reference Methods: The device itself uses an "enzymatic reference method with hexokinase," which is a highly standardized and accepted method for glucose determination.
- Traceability: The device is "Standardized against Isotope." This indicates traceability to a fundamental, highly accurate measurement standard, which forms the ultimate "ground truth" for chemical concentration.
- Comparison to Predicate: A significant part of the submission relies on demonstrating substantial equivalence through direct comparison of performance characteristics (precision, detection limits, interferences) against a legally marketed predicate device, whose "ground truth" establishment would have followed similar principles.
8. The Sample Size for the Training Set
The concept of a "training set" is typically associated with machine learning or artificial intelligence models. This device is an in vitro diagnostic reagent system based on established chemical and enzymatic reactions. Therefore, there is no "training set" in the AI sense.
However, the development and optimization of such a diagnostic reagent would involve extensive R&D, including testing with numerous samples during formulation and assay development to fine-tune reagent concentrations, reaction conditions, and ensure stability and performance across different sample types and glucose concentrations. The document does not specify the number of samples used in this developmental or "training" phase.
9. How the Ground Truth for the Training Set Was Established
As there is no "training set" in the context of an AI/ML device, this question is not applicable. The "ground truth" for optimizing the chemical formulation and performance during development would rely on similar principles as described in point 7: comparisons to known glucose concentrations, reference methods, and established analytical performance metrics.
{0}------------------------------------------------
SEP ] 1 2006
510(k) Summary -- COBAS INTEGRA Glucose HK Gen. 3
| Introduction | According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence |
|---|---|
| Submitter name, address, contact | Roche Diagnostics9115 Hague RdIndianapolis IN 46250(317) 521-3723 |
| Contact person: Theresa (Tracy) Ambrose Bush | |
| Date prepared: | |
| Device Name | Proprietary name: COBAS INTEGRA Glucose HK New Formulation |
| Common name: Gluc2 | |
| Classification name: Glucose Test System | |
| Device Description | The cassette COBAS INTEGRA Glucose HK New Formulation 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. | |
| Intended use | In vitro test for the quantitative determination of glucose in serum, plasma, urine and cerebrospinal fluid (CSF) on COBAS INTEGRA systems. |
| Predicate Device | We claim substantial equivalence to the COBAS INTEGRA Glucose HK Liquid cleared as K972250. |
| Substantial equivalency - Similarities | The table below indicates the similarities between the modified COBAS INTEGRA Glucose HK New Formulation test and its predicate device (COBAS INTEGRA Glucose HK Liquid, K972250). |
{1}------------------------------------------------
| Feature | Predicate device: Glucose HKLiquid(K972250) | Modified device: Glucose HKNew formulation |
|---|---|---|
| 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). Glucose measurementsare used in the diagnosis andtreatment of carbohydratemetabolism disorders includingdiabetes mellitus and idiopathichypoglycemia. | In vitro test for the quantitativedetermination of glucose in serum,plasma, urine and cerebrospinalfluid (CSF) on COBAS INTEGRAsystems. Glucose measurements areused in the diagnosis and treatmentof carbohydrate metabolismdisorders including diabetesmellitus and idiopathichypoglycemia. |
| 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 8ºC | Same |
| Calibrator | Calibrator f.a.s. | Same |
| Quality control | Interval: each lotSerum and plasma :Precinorm U and Precinorm U PlusPrecipath U and Precipath U PlusUrine:Quantitative urine controlsCSF:Quantitative CSF controlsInterval: 24 hrs recommended | Same |
| Traceability | Standardized against Isotope | Same |
| Measuring range | 0-40 mmol/L (0-720 mg/dL) | 0-40 mmol/L (0-720 mg/dL) |
| Extended measuring range withrecommended post dilution factor of | Extended measuring range withrecommended post dilution factor of | |
| 10: 0-400 mmol/L (0-7200 mg/dL) | 10: 0 -400 mmol/L (0-7200mg/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 |
| Endogenousinterferences | Hemolysis no significantinterferences | Same |
| Icterus no significant interferences | ||
| Lipemia no significant interferences |
and the comments of the comments of
{2}------------------------------------------------
and the comments of the country
:
:
| Substantial | The table below indicates the similarities between the modified COBAS |
|---|---|
| equivalency -Differences | INTEGRA Glucose HK New Formulation test and its predicate device(COBAS INTEGRA Glucose HK Liquid, K972250). |
| Feature | Predicate device: Glucose HKLiquid(K972250) | Modified device: Glucose HKNew Formulation |
|---|---|---|
| Reagent information | ||
| R1 | Mono reagent in vial A and B(liquid) | R1:100 mmol/L TRIS, 1.7 mmol/LATP, 4 mmol/L Mg++, 1 mmol/LNADP, pH 7.8 |
| R2 | 100 mmol/L MOPS, 12 mmol/LATP, 6 mmol/L NAD+, 10 mmol/LMg++, =50 $\mu$ cat/L HK(yeast), =50$\mu$ cat/L G6PDH (microbial), 0.09%Sodium azide, pH 7.1 | R2:4.0 mmol/L Mg++, 30 mmol/LHEPES, =130 $\mu$ cat/L HK (yeast),=250 $\mu$ cat/L G6PDH (microbial),pH 7.0 |
{3}------------------------------------------------
| Precision | Serum and plasma: | Serum and plasma : |
|---|---|---|
| Within run: | Within run CV%: | |
| 1.7% @ 5.3 mmol/L | 1.8% @ 4.54 mmol/L | |
| 0.72% @ 33.2 mmol/L | 1.6% @ 13.5 mmol/L | |
| Between run: | Between run: | |
| 2.6% @ 5.3 mmol/L | 2.1% @ 4.54 mmol/L | |
| 1.5% @ 33.2 mmol/L | 2.0% @ 13.5 mmol/L | |
| Urine application | Urine application | |
| Within run: | Within run: | |
| 1.7% @ 1.7 mmol/L | 1.2% @ 1.63 mmol/L | |
| 1.8% @ 37.1 mmol/L | 1.1% @ 16.3 mmol/L | |
| Between run: | Between day: | |
| 4.3% @ 1.7 mmol/L | 1.2% @ 1.63 mmol/L | |
| 2.9% @ 37.1 mmol/L | 1.1% @ 16.3 mmol/L | |
| CSF application | CSF application | |
| Within run: | Within run: | |
| 1.6% @ 1.7 mmol/L | 0.87% @ 3.43 mmol/L | |
| 1.8% @ 3.3 mmol/L | 1.3% @ 1.72 mmol/L | |
| Between run: | Between run: | |
| 2.3% @ 1.7 mmol/L | 0.91% @ 3.43 mmol/L | |
| 1.9% @ 3.3 mmol/L | 1.4% @ 1.72 mmol/L | |
| Lower detectionlimit | Serum and plasma:0.033 mmol/L | Serum, plasma, urine and CSF:0.03 mmol/L |
| Urine application:0.22 mmol/L | ||
| CSF application:0.023 mmol/L | ||
| ExogenousInterferences | Falsely low results may be causedby elevated pyruvates levels | In rare cases gammopathy, inparticular type IgM(Waldenstrom'smacroglobulinemia) may causeunreliable results. |
| Gammopathy, in particular IgM,may cause unreliable results in rarecases | ||
and the state of the states of the states
:
:
.
.
:
{4}------------------------------------------------
| 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 assay, resulting in theGlucose HK New Formulation assay, did not affect the intended use orindications for use of the device as described in the labeling, nor did it alterthe fundamental scientific technology of the device. Therefore, we trust theinformation provided in this Special 510(k) will support a decision ofsubstantial equivalence of the COBAS INTEGRA Glucose HK Gen.3 to thepredicate.If you have any questions or require further information, please do nothesitate to contact this office.• Phone: (317) 521-3723• FAX: (317) 521-2324• email: tracy.bush@roche.com |
{5}------------------------------------------------
DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three wing-like shapes, symbolizing health and human services. The eagle is positioned to the right of a circular text element that reads "DEPARTMENT OF HEALTH & HUMAN SERVICES . USA".
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
SEP 1 1 2006
Ms. Theresa Abrose Bush Roche Diagnostics 9115 Hague Rd. Indianapolis, IN 46250
ﺮ ﺍﻟﻤﺴﺘﻘﻠﺔ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟ
Re: K062239 Trade/Device Name: Glucose HK New Formulation (Gluc2) Regulation Number: 21 CFR 862.1345 Regulation Name: Glucose test system Regulatory Class: Class II Product Code: CFR Dated: August 1, 2006 Received: August 2, 2006
Dear Ms. Abrose Bush:
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 Gutt
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}------------------------------------------------
510(k) Number (if known):
Device Name: Glucose HK New Formulation (Gluc2)
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 the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus and idiopathic hypoglycemia.
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)
Albuts Siz
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
KOL 2239 510(k)________________________________________________________________________________________________________________________________________________________________________
§ 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.