The device is an immunoturbidimetric test for the quantitative determination of per cent Hemoglobin A1c in anticoagulated venous or capillary whole blood for use on the INTEGRA family of analyzers.

AI/ML Overview

The provided text describes a 510(k) premarket notification for a medical device, the INTEGRA Reagent Cassette for Hemoglobin A1c. This document focuses on demonstrating substantial equivalence to a predicate device rather than presenting a detailed study proving the device meets acceptance criteria in the way this term is typically used for AI/ML devices (e.g., performance thresholds of sensitivity/specificity).

Therefore, the following response will interpret "acceptance criteria" as the performance characteristics reported for the device, and the "study" as the information provided to support the claim of substantial equivalence, which includes comparisons of performance characteristics.

Here is the information based on the provided text:

1. A table of acceptance criteria and the reported device performance

For a traditional IVD device like this, the "acceptance criteria" are generally implied to be that the device's performance characteristics are equivalent to a legally marketed predicate device. The document presents performance characteristics for the modified device and compares them to those of the predicate (implicitly arguing for equivalence).

Feature	Acceptance Criteria (Implied: Equivalent to Predicate Device)	Reported Device Performance (Modified Device)
Precision	Within-run CV comparable to predicate device.	Whole Blood Application:Within-run CV: 2.3% at 4.7%, 2.2% at 10.3%Total CV: 2.4% at 4.7%, 2.4% at 10.3%
	Total CV comparable to predicate device.	Hemolysate Application:Within-run CV: 1.5% at 4.8%, 1.8% at 12.1%Total CV: 2.8% at 4.8%, 2.4% at 12.1%
AnalyticalSensitivity	Hb sensitivity comparable to predicate device.	Hb: 1.5 mg/dL
	HbA1c sensitivity comparable to predicate device.	HbA1c: 0.4 mg/dL
InterferingSubstances	No significant interference from common substances.	No significant interference from unconjugated bilirubin (60 mg/dL), lipemia (2000 mg/dL), or glycemia (1000 mg/dL), acetylated Hb, carbamylated Hb, and labile HbA1c. (For both applications)
CalibrationStability	Calibration stability comparable to predicate device.	Whole Blood Application: Each lot and every 57 days
		Hemolysate Application: Each lot and every 43 days

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 does not explicitly state the sample size for any test set or the data provenance (country of origin, retrospective/prospective). The presented data are performance characteristics like precision, analytical sensitivity, and interference, which are typically derived from laboratory studies.

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)

Not applicable. For an in vitro diagnostic (IVD) device measuring Hemoglobin A1c, the ground truth is established by the analytical method itself and its accuracy against a reference method or standard, not by expert consensus on interpretations of images or clinical cases.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable. Adjudication methods like 2+1 or 3+1 are typically used in studies involving subjective interpretation (e.g., imaging); this is an objective quantitative assay.

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, not an AI/ML device that assists human readers.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, the device (INTEGRA Reagent Cassette for Hemoglobin A1c on an INTEGRA analyzer) performs as a standalone diagnostic assay to quantitatively determine Hemoglobin A1c. Its performance characteristics are reported directly.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The ground truth for an IVD such as this would typically be established by established reference methods for Hemoglobin A1c or validated laboratory standards. The document does not explicitly state the specific reference method used for comparison, but it is implied that the stated performance characteristics (precision, sensitivity) are validated against such methods.

8. The sample size for the training set

Not applicable. This is a traditional IVD device, not an AI/ML algorithm that requires a "training set."

9. How the ground truth for the training set was established

Not applicable. This is a traditional IVD device, not an AI/ML algorithm that requires a "training set."

Summary

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SEP 3 0 1999

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K990992

510(k) Summary

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.
Submittername, address,contact	Roche Diagnostics Corporation9115 Hague RdIndianapolis, IN 46250(317) 576-3723
	Contact person: Priscilla A. Hamill
	Date prepared: September 28, 1999
Device name	Proprietary name: INTEGRA Reagent Cassette for Hemoglobin A1c
	Common name: Hemoglobin A1c
	Classification name: Glycosylated Hemoglobin Assay
Predicatedevice	The INTEGRA Reagent Cassette for Hemoglobin A1c is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed Roche INTEGRA Reagent Cassette for Hemoglobin A1c (K961824)
Devicedescription	The device is an immunoturbidimetric test for the quantitative determination of per cent Hemoglobin A1c in anticoagulated venous or capillary whole blood for use on the INTEGRA family of analyzers.
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Intended use	For in vitro quantitative determination Hemoglobin A1c in anticoagulatedwhole blood.
Substantialequivalence --similarities	The INTEGRA Reagent Cassette for Hemoglobin A1c is substantiallyequivalent to other products in commercial distribution intended for similaruse. Most notably, it is substantially equivalent to the currently marketedRoche INTEGRA Reagent Cassette for Hemoglobin A1c (K961824).
	The following table illustrates the similarities between the modifiedINTEGRA Reagent Cassette for Hemoglobin A1c and the predicate device.Draft labeling is included in Section V of this submission. Labeling for thepredicate device is provided in Section VI.
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Feature	Modified Device (RocheINTEGRA Cassette forHemoglobin A1c WholeBlood Application)	Modified Device (RocheINTEGRA Cassette forHemoglobin A1c HemolysateApplication)
Intended use	For the quantitativedetermination of HemoglobinA1c.	For the quantitativedetermination of HemoglobinA1c.
Indicationsfor use	For monitoring of long termblood glucose control inindividuals with diabetesmellitus.	For monitoring of long termblood glucose control inindividuals with diabetesmellitus.
Methodology	Immunoturbidimetric testfor HbA1c Colorimetric test for TotalHb	Immunoturbidimetric testfor HbA1c Colorimetric test for TotalHb
Measure-mentapproach	Spectrophotometric	Spectrophotometric
Instrumentrequired	INTEGRA family of analyzers	INTEGRA family of analyzers
Measuringrange	Hb: 81-644 mg/dL HbA1c: range depends onvalue of HbA1c calibrator;a typical range is 1.3-41.9mg/dL For a typical value of Hbof 13.2 g/dL, the test rangefor the final HbA1c(%)results is 3-31%	Hb: 81-644 mg/dL HbA1c: range depends onvalue of HbA1c calibrator;a typical range is 1.3-41.9mg/dL For a typical value of Hb of13.2 g/dL, the test range forthe final HbA1c(%) resultsis 3-31%
Sample type	Anticoagulated venous orcapillary blood	Anticoagulated venous orcapillary blood

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Substantial equivalence -differences

The primary difference between the modified device and the predicate device is that the preparation of hemolysate is automated on the INTEGRA analyzer. Minor modifications in formulation and application parameters have also been made.

The following table illustrates the differences between the INTEGRA Reagent Cassette for Hemoglobin A1c and the predicate device.

Feature	Modified Device (RocheINTEGRA Cassette forHemoglobin A1c Whole BloodApplication)	Modified Device (RocheINTEGRA Cassette forHemoglobin A1cHemolysate Application)
Samplepreparation	Automated preparation ofhemolysate from anticoagulatedvenous or capillary blood	Manual preparation ofhemolysate fromanticoagulated venous orcapillary blood
ReagentFormulation	Modification in componentconcentrations.	Latex coated with mouseMAB for HbA1c Buffer, pH 11.5 BSA Formate Agglutinator
Hemolyzingreagent	80 mmol/L citric acid pepsin >1500 kU/L	20 mmol/L citric acid pepsin >100kU/L
Wavelength	Hb - 552/659 HbA1c - 552 nm	Hb - 552/659 HbA1c - 552 nm

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Substantial equivalence -performance characteristics Performance characteristics of the two devices are equivalent.

Feature	Modified Device (RocheINTEGRA Cassette forHemoglobin A1c Whole BloodApplication)	Modified Device (RocheINTEGRA Cassette forHemoglobin A1c HemolysateApplication)
Precision	Within-run CV2.3% at 4.7%2.2% at 10.3%Total CV2.4% at 4.7%2.4% at 10.3%	Within-run CV1.5% at 4.8%1.8% at 12.1%Total CV2.8% at 4.8%2.4% at 12.1%
Analyticalsensitivity	Hb: 1.5 mg/dLHbA1c: 0.4 mg/dL	Hb: 1.5 mg/dLHbA1c: 0.4 mg/dL
Interferingsubstances	No significant interference fromunconjugated bilirubin (60 mg/dL),lipemia (2000 mg/dL), or glycemia(1000 mg/dL), acetylated Hb,carbamylated Hb, and labileHbA1c.	No significant interferencefrom icterus (25 mg/dL),lipemia (2000 mg/dL), orglycemia (1000 mg/dL),acetylated Hb, carbamylatedHb, and labile HbA1c.
Calibrationstability	Each lot and every 57 days	Each lot and every 43 days

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Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three lines representing its body and wings. The eagle is enclosed in a circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" surrounding it.

SEP 3 0 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Priscilla Hamill Laboratory Systems Roche Diagnostics Corporation 9115 Hague Road P.O. Box 50457 Indianapolis, Indiana 46250-0457

K990992 Re: Trade Name: INTEGRA Reagent Cassette for Hemoglobin A1c Regulatory Class: II Product Code: LCP Dated: July 30, 1999 Received: August 2, 1999

Dear Ms. Hamill:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and 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, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597, or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Sutman

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 (if known):

Device Name: INTEGRA Reagent Cassette for Hemoglobin Alc

Indications for Use:

For the quantitative determination of Hemoglobin A 1c in anticoagulated whole blood.

Hemoglobin A I c is indicated for the monitoring of long term blood glucose control in individuals with diabetes mellitus.

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IS NEEDED) (PLEASE DO NOT WINTE BEBO # THIS LANS-----------------------------------------------------------------------------------------------------------------------------------------Concurrence of CDRH, Office of Device Evaluation (ODE)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use (Per 21 CFR 801.109)

Over-the-Counter Use _

(Optional format 1-2-96)

Peter E. Martini

(Division Sign-Off)
Division of Clinical Laboratory Devices K990992
510(k) Number

Regulation Number and Section

§ 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).