(22 days)
The Tina-Quant Hemoglobin A1c Gen.2 test is an in vitro diagnostic reagent system intended for the quantitative determination of percent hemoglobin A 1c in whole blood. HbAlc results are useful for monitoring of long-term blood glucose control in individuals with diabetes mellitus.
With the Tina-Quant Hemoglobin A 1 c Gen.2 test system, the anticoagulated whole blood specimen is hemolyzed prior to determination of HbA 1c 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 % HbA lc from the HbA 1c/ Hb ratio according to a user selected protocol.
Here's an analysis of the acceptance criteria and study information for the Tina-Quant® Hemoglobin A1c Gen.2 device, based on the provided text, categorized by your requested points:
1. Table of acceptance criteria and the reported device performance
The provided text describes a 510(k) submission for a modified device, primarily comparing its performance to a predicate device. It doesn't explicitly state "acceptance criteria" as pass/fail thresholds against a formal standard. Instead, it presents the new device's performance characteristics, implying that these are deemed acceptable given their comparison to the predicate and industry standards for such assays. The precision values are the most quantitative performance metrics provided that could be considered against implied acceptance criteria (e.g., meeting or exceeding predicate performance, or meeting typical analytical variation for HbA1c assays).
| Performance Characteristic | Predicate Device: original Tina-Quant HbA1c (K934070) | Tina-Quant HbA1c Gen.2 (Modified Device) | Implicit Acceptance Criteria (based on predicate comparison) |
|---|---|---|---|
| Precision (Whole Blood Application) | |||
| Within run: | 3.8% @ 5.2% HbA1c | 0.8% @ 5.4% HbA1c | Equivalent to or better than predicate (Gen.2 is better) |
| 4.0% @ 11.3% HbA1c | 0.9% @ 10.2% HbA1c | Equivalent to or better than predicate (Gen.2 is better) | |
| Between day: | 5.8% @ 5.2% HbA1c | 1.3% @ 5.3% HbA1c | Equivalent to or better than predicate (Gen.2 is better) |
| 5.6% @ 11.3% HbA1c | 1.0% @ 10.3% HbA1c | Equivalent to or better than predicate (Gen.2 is better) | |
| Precision (Hemolysate Application) | |||
| Within run: | N/A (Only manual pretreatment for predicate) | 1.0% @ 55% HbA1c | N/A (new application method) |
| N/A | 0.6% @ 10.6% HbA1c | N/A | |
| Between day: | N/A | 1.0% @ 5.3% HbA1c | N/A |
| N/A | 0.8% @ 10.7% HbA1c | N/A | |
| Linearity (HbA1c) | 0.3 g/dL up to highest calibrator for HbA1c | 0.3-2.6 g/dL HbA1c (Based on highest calibrator value) | Maintain or improve upon predicate's linear range |
| Linearity (Hb) | 9-24 g/dL Hb (before dilution) | 4-35 g/dL Hb (before dilution) | Maintain or improve upon predicate's linear range |
| Lower detection limit (HbA1c) | 0.3 g/dL HbA1c | 0.02 g/dL HbA1c | Equivalent to or better than predicate (Gen.2 is better) |
| Lower detection limit (Hb) | N/A | 0.09 g/dL Hb | N/A (new information) |
| Interferences (Lipemia) | up to 17.5 mg/dL (general) | up to 800 mg/dL (general) | Equivalent to or better than predicate (Gen.2 is better) |
| up to 1230 mg/dL (intralipid) | (Intralipid mentioned, but specific value for Gen.2 not given) | Equivalent to or better than predicate | |
| Interferences (Rheumatoid factor) | No interference (or not specified for high levels) | up to 750 IU/mL | Equivalent to or better than predicate |
| Interferences (Glycemia) | Not specified | up to 1000 mg/dL glucose | New information / No significant interference |
| Expected values (Reference range) | 4.3% - 5.8% HbA1c (1993 study, in-house) | 2.9-4.2% HbA1c (IFCC standardization) | Needs to be aligned with new IFCC standardization |
2. Sample size used for the test set and the data provenance
The document does not explicitly state the sample sizes used for the precision, linearity, detection limit, or interference studies. It describes various performance characteristics derived from testing, but "sample size" in terms of number of patient specimens or analytical replicates is not provided.
- Data provenance: Not explicitly stated (e.g., country of origin). The studies appear to be internal analytical validation studies conducted by the manufacturer, Roche Diagnostics, based in Indianapolis, IN. The studies are prospective in nature, as they are part of the validation for a new or modified device.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This information is not applicable and not provided in the document. This device is an in vitro diagnostic (IVD) assay for quantitative measurement of HbA1c. The "ground truth" for analytical performance studies is typically established by reference methods or gravimetric/volumetric standards, highly controlled samples, or comparison to an established, highly accurate predicate device or method, rather than through expert consensus on qualitative interpretation.
4. Adjudication method for the test set
This information is not applicable and not provided. Adjudication methods (like 2+1, 3+1) are typically used in studies involving human interpretation of images or complex qualitative data (e.g., radiology reads) to resolve discrepancies and establish a consensus ground truth. For a quantitative IVD assay like HbA1c, the "ground truth" is determined analytically, not through human adjudication.
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
This is not applicable. The Tina-Quant Hemoglobin A1c Gen.2 is an in vitro diagnostic assay, not an AI-powered diagnostic imaging tool or a system requiring human "readers" or human-in-the-loop performance. Therefore, an MRMC study or assessment of AI assistance on human reader improvement is irrelevant to this device.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, this is a standalone device performance described. The performance characteristics (precision, linearity, detection limits, interferences) are measurements of the analytical performance of the automated assay system (reagents and instrument) itself, without human intervention in the measurement process (beyond sample loading and initiation). The device calculates the % HbA1c from the HbA1c/Hb ratio automatically.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The document implies the use of the following types of "ground truth" for its performance studies:
- Reference methods/Standardization: The new device's "Expected values" are "Based on study done with IFCC standardization," indicating alignment with an internationally recognized reference method for HbA1c. The previous device used "in-house standardization." This indicates a shift towards a more universally accepted ground truth.
- Highly characterized control materials and calibrators: Calibrators and control materials (e.g., Precinorm HbA1c, Precipath HbA1c) are used to ensure accuracy and traceability. These materials themselves have established values, serving as a ground truth for calibration and quality control.
- Comparisons to the predicate device: The extensive comparison table indicates that the predicate device's established performance served as a benchmark, implying that its results were accepted as a form of "ground truth" for establishing substantial equivalence.
8. The sample size for the training set
This information is not provided and is generally not applicable in the same way it would be for machine learning or AI models. This device is a traditional immunoassay, not an algorithm that undergoes a "training" phase with a dataset. Its development involves chemical and assay optimization, followed by analytical validation.
9. How the ground truth for the training set was established
As noted in point 8, there is no "training set" in the context of a traditional immunoassay like this. The immunoassay itself is designed based on known biochemical principles and optimized through laboratory experiments. Its accuracy and performance are then validated using reference materials and comparative studies, not "trained" on a dataset.
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SEP 3 0 2005
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 Diagnostics9115 Hague RdIndianapolis IN 46250(317) 521-3723Contact person: Theresa M. AmbroseDate prepared: Sept 7, 2005 |
| Device Name | Proprietary name: Tina-Quant® Hemoglobin A1c Gen.2 test |
| Common name: Hemoglobin A1c test | |
| Classification name: Glycosylated hemoglobin assay | |
| Device Description | With the Tina-Quant Hemoglobin A 1 c Gen.2 test system, the anticoagulated whole blood specimen is hemolyzed prior to determination of HbA 1c 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 % HbA lc from the HbA 1c/ Hb ratio according to a user selected protocol. |
| Intended use | The Tina-Quant Hemoglobin A 1c Gen.2 test is an in vitro diagnostic reagent system intended for the quantitative determination of percent hemoglobin Alc in whole blood.HbA1c results are useful for monitoring of long-term blood glucose control in individuals with diabetes mellitus. |
| Predicate Device | We claim substantial equivalence to the Tina-Quant ® Hemoglobin cleared as K934070. |
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The table below indicates the similarities between the modified Tina-Quant ® Substantial equivalency -Hemoglobin A1c Gen.2 test and its predicate device (original Tina-Quant ® Similarities Hemoglobin, K934070).
| Feature | Predicate device: original Tina-Quant HbAlc(K934070) | Modified device: Tina-QuantHbAlc Gen.2 |
|---|---|---|
| General | ||
| Intended Use/Indications forUse | For the quantitative determination ofhemoglobin Alc in whole blood.From summary: Measurements areuseful to provide an indication ofglycemic control in patients withdiabetes mellitus. | The Tina-Quant Hemoglobin AlcGen.2 test is an in vitro diagnosticreagent system intended for thequantitative determination ofpercent hemoglobin Alc in wholeblood.HbA1c results are useful formonitoring of long-term bloodglucose control in individuals withdiabetes mellitus |
| Specimen type | Capillary blood;EDTA orheparinized whole blood. | Same |
| Test principle | ||
| Determination ofHbAlc | 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. | Same. |
| Calculation of %HbAlc | % HbAlc is calculatedautomatically by instrumentaccording to user-selected protocol | Same |
| Reagent information | ||
| Hemolyzingreagent: sampleratio | 1:100 | Same |
| Antibody | Polyclonal anti-HbAlc from sheepblood | Same antibody. |
| Calibrator | Hemolysate derived from humanblood and sheep blood; TTABdetergent; stabilizer. | Same |
| Quality control | Precinorm HbAlcPrecipath HbAlc | Same |
| Performance characteristics | ||
| Specificity | No cross-reactivity with HbAo, HbA1a, HbA1b, acetylated hemoglobin, carbamylated hemoglobin, glycated albumin, labile HbA1c and HbA1d and an acetaldehyde hemoglobin adduct. | Stability claims transferred from predicate device due to use of same antibody and similar reagent: sample ratio. |
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The table below indicates the differences between the modified Tina-Quant ® Substantial equivalency -Hemoglobin A 1 c Gen.2 test and its predicate device (original Tina-Quant ® Differences Hemoglobin, K934070).
| Feature | Predicate device: original Tina-Quant HbA1c(K934070) | Modified device: Tina-QuantHbA1c Gen.2 |
|---|---|---|
| Pretreatment | Manual pretreatment withhemolyzing reagent | Two options for pretreatment:Hemolysate application:same (Manual pretreatment withhemolyzing reagent)Whole blood application:automated on-board samplepretreatment with hemolyzingreagent |
| Instruments | Automated analyzers includingHitachi family | Integra 800 |
| Determination ofHb | Occurs in separate channel withseparate reagent. | Hb is measured in same channelduring preincubation phase ofHbA1c determination (sample +R1). No separate reagent or channelneeded. |
| R1 | Buffer: 50 mM MES, pH6.2Antibody; stabilizers | Buffer: 25 mM MES/ 15 mM TRISpH 6.2Antibody; stabilizers |
| R2 | Buffer: 50 mM MES, pH 6.2;Polyhapten modified withaminodextran AD50; concentration> 20 ug/mLStabilizers | Buffer: 25 mM MES/15mM Tris,ph 6.2;Polyhapten modified withaminodextran AD500;concentration > 8ug/mL; Stabilizers |
| Hemolyzingreagent | Contains 10 mM EDTA and TTABdetergent | Different concentrations used |
| Hemolysate application:Uses separate hemolyzing reagentwith 20 mM EDTA | ||
| Whole blood application:Uses Hemolyzing reagent Gen.2 –fourfold increase in concentrationNo separate reagent needed. | ||
| Hb reagent | Phosphate buffer 20 mM, pH 7.4;stabilizers | |
| Calibrator | Provided with kit as lyophilisate infour levels. | Provided separately as single level;diluted on-board the analyzer. |
| Traceability | In-house reference materials | Standardized against approvedIFCC reference method |
| Reagent stability | 2-8 °C until expiration dateopened: 4 weeks at 2-12 °C | 2-8 °C until expiration dateOn-board: 28 days |
| Precision | Within run:3.8% @ 5.2% HbA1c4.0% @ 11.3% HbA1cTotal:5.8% @ 5.2% HbA1c5.6% @ 11.3% HbA1c | Whole blood application:Within run:0.8% @ 5.4% HbA1c0.9% @ 10.2% HbA1cBetween day:1.3% @ 5.3% HbA1c1.0% @ 10.3% HbA1cHemolysate applicationWithin run:1.0% @ 55% HbA1c0.6% @ 10.6% HbA1cBetween day:1.0% @ 5.3% HbA1c0.8% @ 10.7% HbA1c |
| Linearity | 0.3 g/dL up to highest calibrator forHbA1c.9-24 g/dL Hb(before dilution) | 0.3-2.6 g/dL HbA1c4-35 g/dL Hb(before dilution)(Based on highest calibrator value) |
| Lower detectionlimit | 0.3 g/dL HbA1c | 0.02 g/dL HbA1c0.09 g/dL Hb |
| Endogenousinterferences | No interference from Acetylsalicylicacid; Gamma globulin; Rheumatoidfactor or ascorbic acid | Whole blood application:No significant interference from:Icterus |
| Lipemia up to 17.5 mg/dL | Lipemia: up to 800 mg/dL | |
| Lipemia (intralipid) up to 1230 mg/dL | Intralipid | |
| Rheumatoid factor: up to 750IU/mL | ||
| Glycemia: up to 1000 mg/dLglucose | ||
| Expected values | 4.3% - 5.8% HbA1cBased on 1993 study with in-housestandardization | 2.9-4.2% HbA1cBased on study done with IFCCstandardization |
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DEPARTMENT OF HEALTH & HUMAN SERVICES
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Public Health Service
Food and Drug Administratio 2098 Gaither Road Rockville MD 20850
SEP 3 0 2005
Ms. Theresa Ambrose Regulatory Affairs Principal Roche Diagnostics 9115 Hague Road PO Box 50457 Indianapolis, IN 46250
Re: K052464
Trade/Device Name: Tina-Quant® Hemoglobin A1c Gen.2 Test Regulation Number: 21 CFR 864.7470 Regulation Name: Glycosylated hemoglobin assay Regulatory Class: Class II Product Code: LCP Dated: September 07, 2005 Received: September 08, 2005
Dear Ms. Ambrose:
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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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,
Carol C. Benam
Carol C. Benson, M.A. Acting 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): K052464
Device Name: Tina-Quant® Hemoglobin A1c Gen.II
Indications For Use:
The Tina-Quant Hemoglobin A1c Gen.2 test is an in vitro diagnostic reagent system intended for the quantitative determination of percent hemoglobin A 1c in whole blood. HbAlc results are useful for monitoring of long-term blood glucose control in individuals with diabetes mellitus.
Prescription Use XXX (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)
Division Sign-Off
Page 1 of
Office In Vitro Diagnostic Device Evaluation and Safety
510(k) K052464
§ 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).