For in vitro diagnostic use only. VITROS Chemistry Products %A1c Reagent Kit is used to calculate percent glycated hemoglobin (%A1c) in pretreated human whole blood by quantitative measurement of hemoglobin (Hb) and hemoglobin A1c (HbA1c). Measurements of percentage Alc are effective in monitoring long-term glucose control in individuals with diabetes mellitus.

For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 18 is used in conjunction with VITROS Chemistry Products FS Calibrator 1 to calibrate VITROS 5,1 FS Chemistry Systems for the calculation of percent glycated hemoglobin (%A1c).

For in vitro diagnostic use only. VITROS Chemistry Products %A1c Performance Verifiers are assayed controls used to monitor performance of %A1c Reagent Kit on VITROS 5,1 FS Chemistry Systems.

Device Description

The VITROS 5,1 FS Chemistry System is a fully automated clinical chemistry analyzer intended for use in the in vitro determination of various analytes in human specimens (serum, plasma, urine, and cerebrospinal fluid). The VITROS 5,1 FS Chemistry System is designed for use with VITROS Chemistry Products MicroTip and Thin Film assays.

The system is comprised of four main elements:

The VITROS 5,1 FS Chemistry System instrumentation, which provides automated use of the chemistry reagents.
The VITROS Chemistry Products range of MicroTip assays, in this case the VITROS Chemistry Products %A1c Reagent Kit, VITROS Chemistry Products Hemolyzing Reagent, VITROS Chemistry Products Calibrator Kit 18, VITROS Chemistry Products FS Calibrator 1, and the VITROS Chemistry Products %A1c Performance Verifiers, which are combined by the VITROS 5,1 FS Chemistry System to perform the VITROS %A1c assay.
The VITROS Chemistry Products Thin Film range of products, which are dry, multilayered, analytical elements, coated on polyester supports.
Common reagents used by multiple assays on the VITROS System (in this case, VITROS Chemistry Products FS Diluent Pack 2 and VITROS Chemistry Products FS Reconstitution Diluent).

The VITROS System and reagents are designed specifically for use with the VITROS Chemistry Products range of products.

AI/ML Overview

The provided text describes the submission for 510(k) clearance of the VITROS Chemistry Products %A1c Assay and related components. It details the device, its intended use, and its comparison to predicate devices, but it does not contain a detailed study proving the device meets specific acceptance criteria in the format requested.

The document states that "studies were performed to determine the precision, expected values, linearity, and specificity of the VITROS %A1c assay," and these results are summarized in the "VITROS Chemistry Products %A1c Reagent Kit Instructions for Use." However, these specific study details, acceptance criteria, and reported performance are not included in the provided text.

Therefore, I cannot provide a complete answer to your request in the specified format from the given text. I can only infer what the general acceptance criteria might be based on the type of study mentioned (correlation, precision, linearity, specificity) for a device like this, but I cannot give the actual criteria and reported performance values.

Here's what I can extract and what is missing, based on your request:

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

Missing. The document states that studies were performed (precision, expected values, linearity, specificity) but does not provide the acceptance criteria for these studies or the reported performance values.

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 mentions a "correlation study" that used "patient samples."

Sample Size for Test Set: Not specified.
Data Provenance: "patient samples." No country of origin is mentioned. It is implied to be retrospective as existing patient samples would be used for correlation, but not explicitly stated as prospective or retrospective.

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/Not specified. This is an in-vitro diagnostic (IVD) chemistry assay, not an imaging device requiring expert interpretation for ground truth. The ground truth for such devices is typically established through direct comparison to a reference method or predicate device performance using quantitative measurements.

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

Not applicable/None. Adjudication methods like 2+1 or 3+1 are used in studies involving human interpretation (e.g., radiology reads) where discrepancies between readers need resolution. For a quantitative IVD assay, ground truth is typically established by laboratory measurements against a reference method or by comparing to a cleared predicate device, rather than 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

Not applicable. This device is an in-vitro diagnostic chemistry assay, not an AI-powered imaging or diagnostic tool designed to assist human readers. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance would not be relevant or performed for this type of product.

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

Yes, implicitly. This is a standalone diagnostic assay running on an automated chemistry system. The performance characteristics (precision, linearity, specificity, correlation with predicate) would be evaluated for the assay and instrument system without human-in-the-loop performance influencing the assay's direct analytical output. The "algorithm" here is the chemical reaction and measurement process within the device.

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

The ground truth or reference for comparison appears to be the predicate device's performance (A1c 2.2 Plus Glycohemoglobin Assay, Tosoh Medics, Inc.) as stated in the correlation study:

"The relationship between the VITROS %A1c assay and the predicate device in NGSP units, determined by least squares linear regression, is: VITROS %A1c assay = 1.0374 X = 0.3426 %A1c with a correlation coefficient of 0.9872, where X is the Tosoh A1c 2.2 Plus Glycohemoglobin Assay on the TOSOH Automated Glycohemoglobin Analyzer."

Additionally, the device's standardization is "Traceable to both the Diabetes Control and Complications Trial (DCCT) and IFCC reference methods and Certified by the National Glycohemoglobin Standardization Program (NGSP)," which implies these reference methods also form the basis of the "ground truth" for accurate HbA1c measurement.

8. The sample size for the training set

Not applicable/Not specified. This is a chemical assay, not a machine learning or AI model that requires a "training set" in the conventional sense. The "training" of the device involves calibration using calibrator kits. The document refers to "Calibrator Kit 18" and "FS Calibrator 1" for calibration but does not specify a sample size for this training/calibration process in terms of patient samples.

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

Not applicable (for a training set in the AI sense). For the calibration process (analogous to "training" for IVDs), the ground truth is established by using calibrator kits (VITROS Chemistry Products Calibrator Kit 18 and VITROS Chemistry Products FS Calibrator 1). These calibrators have known, assigned values traceable to reference methods (DCCT and IFCC, and NGSP certified). The instrument uses these known values to establish its measurement curve.

Summary

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1.0 510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is: KO417V4

1.1 Submitter name, address, contact

Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, New York 14626-5101 Phone: (585) 453-3482 Fax: (585) 453-3368

Contact Person: Carey A. Mayo, M.S., RAC

1.2 Date of Preparation: June 29, 2004

1.3 Device Proprietary Name(s)

VITROS Chemistry Products %A1c Reagent Kit Trade Name(s) VITROS Chemistry Products Hemolyzing Reagent VITROS Chemistry Products Calibrator Kit 18 VITROS Chemistry Products FS Calibrator 1 VITROS Chemistry Products %A1c Performance Verifiers I and II
Glycohemoglobin assay and controls Common Name

1.4 Classification Name(s)

Glycosylated hemoglobin assay: Class II (21 CFR 864.7470) Assaved Controls: Class I, reserved (21 CFR 862.1660)

1.5 Predicate device

The VITROS Chemistry Products %A1c Assay is substantially equivalent to the A1c 2.2 Plus Glycohemoglobin Assay (Tosoh Medics, Inc.).

The VITROS Chemistry Products %A1c Performance Verifiers are substantially equivalent to the VITROS Chemistry Products Performance Verifiers.

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Device description 1.6

The system is comprised of four main elements:

1. The VITROS 5,1 FS Chemistry System instrumentation, which provides automated use of the chemistry reagents. The VITROS 5,1 FS Chemistry System was cleared for market by a separate 510(k) premarket notification (K031924).
1. The VITROS Chemistry Products range of MicroTip assays, in this case the VITROS Chemistry Products %A1c Reagent Kit, VITROS Chemistry Products Hemolyzing Reagent, VITROS Chemistry Products Calibrator Kit 18, VITROS Chemistry Products FS Calibrator 1, and the VITROS Chemistry Products %A1c Performance Verifiers, which are combined by the VITROS 5,1 FS Chemistry System to perform the VITROS %A1c assay.
- 1. The VITROS Chemistry Products Thin Film range of products, which are dry, multilayered, analytical elements, coated on polyester supports. The thin film products each have there own 510(k) clearance numbers and were cleared for market for use on the VITROS 5.1 FS Chemistry System through submission of information required by the ODE Guidance Document: "Data For Commercialization Of Original Equipment Manufacturer, Secondary and Generic Reagents For Automated Analyzers". The required information was provided in the VITROS 5,1 FS Chemistry System premarket notification (K031924).
- 1. Common reagents used by multiple assays on the VITROS System (in this case, VITROS Chemistry Products FS Diluent Pack 2 and VITROS Chemistry Products FS Reconstitution Diluent).

The VITROS System and reagents are designed specifically for use with the VITROS Chemistry Products range of products.

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Device intended use 1.7

VITROS Chemistry Products %A1c Reagent Kit: For in vitro diagnostic use only. VITROS Chemistry Products %A1c Reagent Kit is used to calculate percent glycated hemoglobin (%A1c) in pretreated human whole blood by quantitative measurement of hemoglobin (Hb) and hemoglobin A1c (HbA1c). Measurements of percentage A1c are effective in monitoring long-term glucose control in individuals with diabetes mellitus.

VITROS Chemistry Products Calibrator Kit 18: For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 18 is used in conjunction with VITROS Chemistry Products FS Calibrator 1 to calibrate VITROS 5,1 FS Chemistry Systems for the calculation of percent glycated hemoglobin (%A1c).

VITROS Chemistry Products %A1c Performance Verifier I and II: For in vitro diagnostic use only. VITROS Chemistry Products %A1c Performance Verifiers are assayed controls used to monitor performance of %A1c Reagent Kit on VFTROS 5,1 FS Chemistry Systems.

Comparison to predicate device: Reagent Kit and Calibrators 1.8

The VITROS Chemistry Products %A1c Reagent Kit, VITROS Chemistry Products Calibrator Kit 18 and VITROS Chemistry Products FS Calibrator 1 are substantially equivalent to the A1c 2.2 Plus Glycohemoglobin Assay (Tosoh Medics, Inc.), which was cleared by FDA (K972265) for IVD use.

The relationship between the VITROS %A1c assay and the predicate device in NGSP units, determined by least squares linear regression, is:

VITROS %A1c assay = 1.0374 X = 0.3426 %A1c with a correlation coefficient of 0.9872, where X is the Tosoh A1c 2.2 Plus Glycohemoglobin Assay on the TOSOH Automated Glycohemoglobin Analyzer.

In addition to the above mentioned correlation study, studies were performed to determine the precision, expected values, linearity, and specificity of the VITROS %A1c assay, (refer to the VITROS Chemistry Products %A1c Reagent Kit Instructions for Use for summaries of the results of these studies).

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The table below lists the characteristics of the VITROS %A1c Assay and the A1c 2.2 Plus Glycohemoglobin Assay (Tosoh Medics, Inc.).

DeviceCharacteristic	VITROS %A1c Assay(New device)	A1c 2.2 PlusGlycohemoglobin Assay(Predicate device)
Intended Use	To determine %A1c inwhole blood	To determine %A1c inwhole blood
Standardization	Traceable to both theDiabetes Control andComplications Trial(DCCT) and IFCCreference methods.Certified by the NationalGlycohemoglobinStandardization Program(NGSP).	Traceable to both theDiabetes Control andComplications Trial(DCCT) and IFCCreference methods.Certified by the NationalGlycohemoglobinStandardization Program(NGSP).
Basic principle	Turbidimetric inhibitionimmunoassay	High performance liquidchromatography (HPLC)
Reportable Range	4 – 14 %A1c NGSP	4 – 19 %A1c NGSP
Reagents	Liquid ready to use	Non-porous cationexchange column
Instrumentation	VITROS 5,1 FS ChemistrySystem	A1c 2.2 Plus AutomatedGlycohemoglobinAnalyzer (Tosoh Medics,Inc.)
Sample type	Whole blood (EDTA,heparin, sodiumfluoride/potassium oxalate)	Whole blood (undiluted ordiluted)

Comparison to predicate device: Performance Verifiers 1.9

VITROS Chemistry Products %A1c Performance Verifiers are substantially equivalent to VITROS Chemistry Products Performance Verifiers (predicate device) which were cleared by the FDA (K904768) for IVD use.

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The table below lists the characteristics of the VITROS Chemistry Products %A1c Performance Verifiers and the VITROS Chemistry Products Performance Verifiers.

DeviceCharacteristic	VITROS %A1cPerformance Verifiers(New device)	VITROS PerformanceVerifiers(Predicate device)
Intended Use	VITROS %A1cPerformance Verifier is anassayed control used tomonitor performance of%A1c Reagent Kit onVITROS 5,1 FS ChemistrySystems.	VITROS PerformanceVerifier is an assayed controlused to monitor performanceon VITROS ChemistrySystems.
Matrix	A base matrix of freeze-dried hemolysate derivedfrom human and ovineblood to which surfactants,stabilizer, and preservativeshave been added.	A base matrix of freeze-driedhuman serum to whichenzymes, electrolytes,stabilizers, preservatives andother organic analytes havebeen added.
Levels	Low and High	Low and High

1.10 Conclusions

The data presented in the premarket notification provide a reasonable assurance that the VITROS Chemistry Products %A1c assay and the VITROS %A1c Performance Verifiers are safe and effective for the stated intended uses and are substantially equivalent to the cleared predicate devices. Equivalence to the predicates was demonstrated using a commercially available assay along with patient samples.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image is a black and white logo for the Department of Health & Human Services. The logo features a stylized eagle with three lines forming its body and wings. The eagle is facing to the right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the eagle.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Carey A. Mayo, M.S., RAC Regulatory Affairs Associate Ortho-Clinical Diagnostics 100 Indigo Creek Drive Rochester, NY 14626

K041764 Re:

Trade/Device Name: VITROS Chemistry Products %A1c Reagent Kit VITROS Chemistry Products Calibrator Kit 18 VITROS Chemistry Products FS Calibrator 1 VITROS Chemistry Products %A1c Performance Verifiers I and II Regulation Number: 21 CFR 864.7470 Regulation Name: Glycosylated Hemoglobin assay

SEP = 9 2004

Regulatory Class: Class II Product Code: LCP, JIT, JJX Dated: June 29, 2004 Received: June 30, 2004

Dear Ms. Mayo:

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 (301) 594-3084. 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/dsma/dsmamain.html.

Sincerely yours,

Jean M. Cooper MS, DVM.

Tean M. Cooper, MS. 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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2.0 Indications for Use Statement

6041764

510(k) Number (if known):

Device Name:

1. VITROS Chemistry Products %A1c Reagent Kit
1. VITROS Chemistry Products Calibrator Kit 18
1. VITROS Chemistry Products FS Calibrator 1
1. VITROS Chemistry Products %A1c Performance Verifiers I and II

Indications for Use:

For in vitro diagnostic use only. VITROS Chemistry 1. Products %A1c Reagent Kit is used to calculate percent glycated hemoglobin (%A1c) in pretreated human whole blood by quantitative measurement of hemoglobin (Hb) and hemoglobin A1c (HbA1c). Measurements of percentage Alc are effective in monitoring long-term glucose control in individuals with diabetes mellitus.
1. & 3. For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 18 is used in conjunction with VITROS Chemistry Products FS Calibrator 1 to calibrate VITROS 5,1 FS Chemistry Systems for the calculation of percent glycated hemoglobin (%A1c).
For in vitro diagnostic use only. VITROS Chemistry 4. Products %A1c Performance Verifiers are assayed controls used to monitor performance of %A1c Reagent Kit on VITROS 5,1 FS Chemistry Systems.

Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use AND/OR (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Carol Benson

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K041764

Ortho-Clinical Diagnostics, Inc.

Page 6 of 38 VITROS Chemistry Products %A1c Assay and Controls

Page 1 of 1

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).