(206 days)
For the quantitative determination of percent hemoglobin A1c in whole blood (or hemolysate derived from whole blood) on Roche clinical chemistry analyzers. HbA1c determinations are useful for monitoring of long-term blood glucose control in individuals with diabetes mellitus.
With the Tina-Quant Hemoglobin A1c Gen.2 test system, the anticoagulated whole blood specimen is hemolyzed prior to determination of HbA1c by an turbidimetric inhibition immunoassay (TINIA). Liberated hemoglobin (Hb) in the hemolyzed sample is converted to a derivative having a characteristic absorption spectrum and measured bichromatically. The instrument calculates the % HbA1c from the HbA1c/ Hb ratio according to a user selected protocol.
Here's a summary of the acceptance criteria and study information for the Tina-Quant® Hemoglobin A1c Gen.2 Test System, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The submission primarily focuses on modifications to an already cleared device (K052464). The acceptance criteria for the new features or extended parameters are shown below, along with the reported performance where available.
| Feature | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Measuring Range (Integra 800/800 CTS) | 0.3 - 3.4 g/dL HbA1c (for HbA1c); 4-35 g/dL Hb (for Hb) | Modified Device (Integra 800/800 CTS): 0.3 - 3.4 g/dL HbA1c, 4-35 g/dL Hb (This is the expanded range, which is the acceptance criterion itself for this modification). Predicate Device (Integra 800): 0.3-2.6 g/dL HbA1c, 4-35 g/dL Hb |
| Endogenous Interferences (Whole blood application only) | No significant interference (bias within ± 10%) for: - Lipemia (up to 800 mg/dL Intralipid) - Bilirubin (up to 30 mg/dL Bilirubin/ditaurobilirubin) - Rheumatoid factor (up to 350 IU/mL RF) - Glycemia (up to 1000 mg/dL glucose) | Reported: No significant interference (bias within ± 10%) up to: - 800 mg/dL Intralipid - 30 mg/dL Bilirubin/ditaurobilirubin - 350 IU/mL RF - 1000 mg/dL Glucose |
| Anticoagulant (Potassium fluoride/Na2-EDTA) | Reagent-specific criteria: - Mean deviation of all samples: <= 0.2% HbA1c - Maximum deviation of single sample: <= 0.75% HbA1c General criteria for unlimited acceptance: - Median deviation of recovery against reference for all sample pairs <= 5% recovery - Maximum deviation of recovery of 80% of all sample pairs <= 10% recovery (up to 20% of samples can be within 10-15% recovery vs reference) | Reported: Supported via internally documented data. The submission states that acceptance criteria apply and are met, but specific data values for this study are not provided in the publicly available summary. It refers to "internally documented data." |
2. Sample Size Used for the Test Set and Data Provenance
- Measuring Range (Integra 800/800 CTS): Not explicitly stated, but the "Measuring Range" section indicates that the extended range for Integra 800/800 CTS is now 0.3 - 3.4 g/dL HbA1c. The previous range was 0.3-2.6 g/dL. No specific sample size for the range extension study is detailed in the provided text.
- Endogenous Interferences: The criteria implicitly suggest testing with relevant concentrations of interfering substances. No specific sample size per interferent is mentioned.
- Anticoagulant (Potassium fluoride/Na2-EDTA): "Testing of ≥ 50 paired samples (i.e. serum/plasma)". The provenance of this data is "internally documented data," suggesting it was generated by Roche Diagnostics, likely in-house. It is prospective data collection for this specific evaluation.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
This device measures a biochemical analyte (HbA1c). The "ground truth" or reference values are established through certified reference methods or calibrated devices. There are no "experts" in the human diagnostic image review sense to establish ground truth for a clinical chemistry assay like HbA1c. The assessment is based on comparison to an established reference method or predicate device performance. The text mentions "Based on study done with IFCC standardization" for expected values.
4. Adjudication Method
Not applicable. This is a quantitative chemical assay, not a subjective interpretation task requiring expert adjudication of results.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
Not applicable. This is not a diagnostic imaging or interpretive device that relies on human readers. Its performance is measured quantitatively against reference values.
6. Standalone Performance Study (Algorithm Only Without Human-in-the-Loop Performance)
Yes, the studies described are standalone performance evaluations of the assay system itself. For example, the precision, lower detection limit, endogenous interferences, and anticoagulant validation are all tests of the device's inherent analytical performance, independent of human interpretation.
7. Type of Ground Truth Used
- Measuring Range: Established by the ability of the assay to accurately quantify HbA1c within that range, likely by measuring samples with known HbA1c concentrations (e.g., control materials, spiked samples) traceable to a reference method (like IFCC).
- Endogenous Interferences: Established by comparing measurements of samples containing known concentrations of HbA1c with and without the interfering substance, using a reference method if necessary, or comparing to the predicate's performance.
- Anticoagulant: Ground truth for this would be the HbA1c values obtained from samples collected with the originally accepted anticoagulants or a reference method, against which samples collected with the new anticoagulant (potassium fluoride/Na2-EDTA) are compared. The reference values are NGSP values (National Glycohemoglobin Standardization Program), indicating traceability to a globally accepted standardization system for HbA1c.
8. Sample Size for the Training Set
Not applicable. This is a laboratory diagnostic assay, not a machine learning algorithm that requires a "training set" in the conventional sense. The "training" of such a system involves the development of reagents and optimization of the assay protocol by Roche Diagnostics.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" in the context of machine learning. The assay's analytical performance (linearity, accuracy, precision) is established through validation studies using reference materials and patient samples with known values. The expected values for HbA1c are based on "IFCC standardization," which provides a robust, internationally recognized reference system.
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APR 1 8 2008
510(k) Summary – Tina-Quant® Hemoglobin A1c Gen.2
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 Diagnostics 9115 Hague Rd Indianapolis IN 46250 (317) 521-3723
Contact person: Tracy Bush
Oct 15, 2007 Date prepared:
Submission Purpose and History
The Tina-Quant Hemoglobin A 1c Gen.2 assay was originally cleared for use as K052464. The purpose of this submission is to modify the device by extending the labeled measuring range for the HbA Ic portion of the %HbAlc measurement in the application for Integra 800 analyzers.
Since the clearance of K052464, a number of changes have taken place to the device, for which an additional filing was not deemed necessary. We hereby provide notification of these changes:
- . Inclusion of additional anticoagulant type (potassium fluoride/ Na2-EDTA) in the Specimen Collection and Preparation section of the labeling (supported via internally documented data)
Device Name
Proprictary name: Tina-Quant® Hemoglobin A1c Gen.2 test
Common name: Hemoglobin A1c test
Classification name: Glycosylated hemoglobin assay
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| DeviceDescription | With the Tina-Quant Hemoglobin A1c Gen.2 test system, the anticoagulatedwhole blood specimen is hemolyzed prior to determination of HbA1c by anturbidimetric inhibition immunoassay (TINIA). Liberated hemoglobin (Hb)in the hemolyzed sample is converted to a derivative having a characteristicabsorption spectrum and measured bichromatically. The instrumentcalculates the % HbA1c from the HbA1c/ Hb ratio according to a userselected protocol. |
|---|---|
| Intended use | The Tina-Quant Hemoglobin A1c Gen.2 test is in vitro diagnostic reagentsystem intended for use on the COBAS INTEGRA 800 analyzers for thequantitative determination of percent hemoglobin A1c in hemolysate orwhole blood. HbA1c determinations are useful for monitoring of long-termblood glucose control in individuals with diabetes mellitus. |
| PredicateDevice | We claim substantial equivalence to the Tina-Quant ® Hemoglobin A1cGen.2 cleared as K052464. |
| Substantialequivalency –Similarities | The table below indicates the similarities between the modified Tina-Quant ®Hemoglobin A1c Gen.2 test and its predicate device (original Tina-Quant®Hemoglobin A1c Gen.2, K052464). |
:
| Feature | Predicate: Tina-Quant ®Hemoglobin A1c Gen.2 (K052464) | Modified device: Tina-QuantHbA1c Gen.2 |
|---|---|---|
| General | ||
| Intended Use/Indications forUse | For the quantitative determination ofpercent hemoglobin A1c in wholeblood (or hemolysate derived fromwhole blood) on COBAS Integra800 anlayzers. HbA1cdeterminations are useful formonitoring of long-term bloodglucose control in individuals withdiabetes mellitus. | For the quantitative determinationof percent hemoglobin A1c inwhole blood (or hemolysate derivedfrom whole blood) on Rocheclinical chemistry analyzers. |
| Indications forUse | HbA1c determinations are useful formonitoring of long-term bloodglucose control in individuals withdiabetes mellitus. | HbA1c determinations are usefulfor monitoring of long-term bloodglucose control in individuals withdiabetes mellitus. |
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| Specimen type | Anticoagulated venous or capillaryblood. Acceptable anticoagulants include Li-heparin, K2-EDTA, K3-EDTA | Anticoagulated venous or capillaryblood. Acceptable anticoagulants include Li-heparin, K2-EDTA, K3-EDTA and potassium fluoride/Na2-EDTA |
|---|---|---|
| Instrumentplatform | Integra 800 analyzer | Integra family including Integra400/400 plus, 800, 800 CTS(Closed Tube Sampling), cobasc111; also cobas c501 |
| Test principle | ||
| Determination ofHbA1c | Turbidimetric immunoinhibition(TINIA). Antigen-antibodycomplexes are formed and excessAb aggregate with polyhapten toform insoluble complexes. | Same |
| Determination ofHb | Bichromatic photometricdetermination after conversion to acolored derivative.Hb is measured in same channelduring preincubation phase ofHbA1c determination (sample +R1). | Same. |
| Calculation of %HbA1c | % HbA1c is calculatedautomatically by instrumentaccording to user-selected protocol | Same |
| Pretreatment | Two options for pretreatment:Hemolysate application:same (Manual pretreatment withhemolyzing reagent)Whole blood application:automated on-board samplepretreatment with hemolyzingreagent | Same |
| Reagent information | ||
| Antibody | Polyclonal anti-HbA1c from sheepblood | Same. |
| Calibrator | Hemolysate derived from humanblood and sheep blood; TTABdetergent; stabilizer. | Same |
| Quality control | Precinorm HbA1cPrecipath HbA1c | Same |
| R1 | Buffer: 25 mM MES/ 15 mM TRISpH 6.2Antibody; stabilizers | Same |
| R2 | Buffer: 25 mM MES/15mM Tris, ph 6.2;Polyhapten modified withaminodextran AD500; concentration> 8ug/mL; Stabilizers | Same |
| Hemolyzingreagent | Different concentrations used | Same |
| Hemolysate application:Uses separate hemolyzing reagentwith 20 mM EDTA | ||
| Whole blood application:Uses Hemolyzing reagent Gen.2 –fourfold increase in concentration | ||
| Reagent stability | 2-8 °C until expiration dateOn-board: 28 days | Same |
| Performance characteristics (Integra) | ||
| Precision | Whole blood application:Within run:0.8% @ 5.4% HbA1c0.9% @ 10.2% HbA1c | Same |
| Between day:1.3% @ 5.3% HbA1c1.0% @ 10.3% HbA1c | ||
| Hemolysate applicationWithin run:1.0% @ 5.5% HbA1c0.6% @ 10.6% HbA1c | ||
| Between day:1.0% @ 5.3% HbA1c0.8% @ 10.7% HbA1c | ||
| Lower detectionlimit | 0.02 g/dL HbA1c0.09 g/dL Hb | Same |
| Endogenousinterferences | Whole blood application:No significant interference from:Icterus | Same |
| Lipemia: up to 800 mg/dL Intralipid | ||
| Rheumatoid factor: up to 750 IU/mL | ||
| Glycemia: up to 1000 mg/dL glucose | ||
| Expected values | 2.9-4.2% HbA1cBased on study done with IFCCstandardization | Same |
| Specificity | No cross reaction with HbAo,HbAla, HbA1b, acetylatedhemoglobin, carbamylatedhemoglobin, glycated albumin andlabile HbA1c were found for theanti-HbA1c antibodies used in thiskit.Specimens containing high amountsof HbF (>10%) may yield lower thanexpected HbA1c results. | Same |
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Substantial The table below indicates the differences between the modified Tina-Quant ® equivalency --Hemoglobin A 1c Gen.2 test and its predicate device (original Tina-Quant ® Differences Hemoglobin A1c Gen.2, K052464).
| Feature | Predicate: Tina-Quant ®Hemoglobin A1c Gen.2 (K052464) | Modified device: Tina-QuantHbA1c Gen.2 |
|---|---|---|
| General | ||
| Specimen type | Anticoagulated venous or capillaryblood. Acceptable anticoagulants include Li-heparin, K2-EDTA, K3-EDTA | Anticoagulated venous or capillaryblood. Acceptable anticoagulants include Li-heparin, K2-EDTA, K3-EDTA and potassium fluoride/Na2-EDTA |
| Instrumentplatform | Integra 800 analyzer | Integra family including Integra400/400 plus, 800, 800 CTS(Closed Tube Sampling), cobasc111; also cobas c501 |
| Performance Characteristics (Integra) | ||
| MeasuringRange | 0.3-2.6 g/dL HbAlc*4-35 g/dL Hb*Based on concentration of thehighest standard | Integra 400/400 plus:sameIntegra 800/ 800 CTS:0.3 - 3.4 g/dL HbA1c4-35 g/dL Hb |
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| Endogenous interferences(whole blood applicationonly) | Analyte recovery in presenceof interfering agent. Testedfor:Lipemia (Intralipid) Bilirubin (conjugatedand unconjugated) Rheumatoid Factor Glucose | No significant interference(bias within ± 10%) up to:800 mg/dL Intralipid 30 mg/dL Bilirubin/ditaurobilirubin 350 IU/mL RF 1000 mg/dL Glucose |
|---|---|---|
| Anticoagulant | Testing of ≥ 50 paired samples(i.e. serum/plasma) | Both reagent-specific andgeneral criteria apply(based on NGSP values)Reagent-specific criteria Mean deviation of allsamples: <= 0.2% HbA1c Maximum deviation ofsingle sample: <= 0.75%HbA1c General criteria for unlimitedacceptance of anticoagulanttype: Median deviation ofrecovery against referencefor all sample pairs <= 5%recovery Maximum deviation ofrecovery of 80% of allsample pairs <= 10%recovery ( up to 20% ofsamples can be within 10-15% recovery vs reference) |
| Specificity | Testing not required providedantibody does not change andreagent/sample ratio remainssimilar | Specificity claims transferredfrom predicate Tina-QuantHbA1c device |
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Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Roche Diagnostics Corp. c/o Theresa A. Bush, Ph.D. Regulatory Affairs Principal 9115 Hague Road Indianapolis, IN 46250
APR 1 8 2008
Re: K072714
Trade/Device Name: Tina-Quant® Hemoglobin A1c Gen.2 Test System Regulation Number: 21 CFR 864.7470 Regulation Name: Glycosylated hemoglobin assay. Regulatory Class: Class II Product Code: LCP Dated: March 19, 2008 Received: March 20, 2008
Dear Dr. 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).
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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) 276-0490. 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 (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Jean M. Cooper, M.S., D.V.M.
Sean M. Cooper, M.S., 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):
Device Name: Tina-Quant® Hemoglobin A1c Gen.2 Test System
Indication For Use:
For the quantitative determination of percent hemoglobin Alc in whole blood (or hemolysate derived from whole blood) on Roche clinical chemistry analyzers.
HbAlc determinations are useful for monitoring of long-term blood glucose control in individuals with diabetes mellitus.
Prescription Use XXX (21 CFR Part 801 Subpart D) And/Or
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
Carol Benson
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K072714
§ 864.7470 Glycosylated hemoglobin assay.
(a)
Identification. A glycosylated hemoglobin assay is a device used to measure the glycosylated hemoglobins (A1a , A1b , and A1c ) in a patient's blood by a column chromatographic procedure. Measurement of glycosylated hemoglobin is used to assess the level of control of a patient's diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient.(b)
Classification. Class II (performance standards).