For in vitro diagnostic use only. VITROS Chemistry Products d%A1c Reagent Kit is used to determine the percent glycated hemoglobin (%A1c) in human whole blood by quantitative measurement of hemoglobin (Hb) and hemoglobin A1c (HbA1c). Measurements of percentage A1c are effective in monitoring long-term glycemic 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 FS Calibrator 1 is used in conjunction with VITROS Chemistry Products Calibrator Kits 16, 17, 18, 19 and 28 to calibrate VITROS 5,1 FS Chemistry Systems.

Device Description

VITROS Chemistry Products d%A1c Reagent Kit, VITROS Chemistry Products Calibrator Kit 18, and VITROS Chemistry Products FS Calibrator 1 are combined with the VITROS 5,1 FS Chemistry System to perform the VITROS d%A1c assay.

VITROS d%A1c Reagent Kit contains two unique dual chambered reagent packs containing ready to use liquid reagents that are used to measure both hemoglobin A1c (HbA1c) and hemoglobin (Hb).

Hemoglobin A1c Reagent Pack (HbA1c)
The R1 chamber (HbA1c Reagent 1) consists of:
HbA1c antibody (ovine serum)
Buffers
Stabilizers
Preservatives
The R2 chamber (HbA1c Reagent 2) consists of:
HbAlc Polyhapten
Buffers
Stabilizers
Preservatives

Hemoglobin Reagent Pack (Hb)
The R1 chamber (Hb Reagent 1) consists of:
Buffer
Stabilizers
Preservatives
The R2 chamber (Hb Reagent 2) contains Hemolyzing Reagent, which consists of:
Tetradecyltrimethylammonium bromide (TTAB) <1% (w/v)
Water

VITROS Chemistry Products Calibrator Kit 18 is composed of a hemolysate derived from human and ovine blood to which surfactants, stabilizer, and preservative have been added. This lyophilized calibrator is reconstituted with VITROS Chemistry Products FS Reconstitution Diluent, which is composed of processed water.

VITROS Chemistry Products FS Calibrator 1 is composed of processed water and 0.9% w/v sodium chloride (saline).

The VITROS d%A1c assay is designed to use whole blood to determine %A1c on-board the VITROS 5,1 FS System without the need for sample pretreatment.

The determination of percent glycated hemoglobin (%A1c) is performed using the VITROS d%A1c Reagent Kit in conjunction with VITROS Calibrator Kit 18 and VITROS FS Calibrator 1 on the VITROS 5,1 FS Chemistry System. The VITROS d%A1c Reagents consists of two unique dual chambered packs containing complete ready-to-use liquid reagents. Whole blood samples are hemolyzed on the VITROS 5,1 FS Chemistry System during the sample analysis. Since this is a direct reacting assay, no sample pretreatment by the operator is required to perform this assay.
The VITROS 5,1 FS Chemistry System is designed specifically for use with the VITROS Chemistry Products range of products.

AI/ML Overview

Acceptance Criteria and Study Details for VITROS Chemistry Products d%A1c Reagent Kit (K060650)

This submission (K060650) describes a modification to an existing device, the VITROS Chemistry Products d%A1c Reagent Kit. The primary change is the automation of the hemolysis step, previously a manual pretreatment. Therefore, the study focuses on demonstrating substantial equivalence to the predicate device, not establishing entirely new performance criteria.

1. Table of Acceptance Criteria and Reported Device Performance

The provided document doesn't explicitly state quantitative acceptance criteria in terms of specific performance metrics (e.g., precision, accuracy thresholds). Instead, the acceptance criterion for this 510(k) is substantial equivalence to the predicate device, particularly regarding the performance of the modified reagent kit.

Acceptance Criterion (Implicit)	Reported Device Performance
Substantial Equivalence to the predicate device (VITROS Chemistry Products %A1c Reagent Kit) in terms of:	"Equivalence was demonstrated using manufactured reagents along with patient and quality control samples with measured %A1c values spanning the reportable range."
- Measurement of %A1c	The modified device performs the quantitative measurement of Hb and HbA1c to determine %A1c.
- Clinical Utility	Measurements of percentage A1c are effective in monitoring long-term glycemic control in individuals with diabetes mellitus (same as predicate).
- Reportable Range	No change; 4-14 %A1c NGSP (same as predicate).
- Basic Principle	No change; Turbidimetric inhibition immunoassay (same as predicate).
- Reagent Characteristics	Liquid ready to use (no change).
- Instrumentation	VITROS 5,1 FS Chemistry System (no change).

Note: The primary difference and therefore the focus of demonstrating equivalence is the automated hemolysis step. The submission implicitly asserts that the performance of the assay with the automated hemolysis is comparable to the predicate's performance with manual hemolysis, thus meeting the substantial equivalence criterion.

2. Sample Size Used for the Test Set and Data Provenance

Sample Size: The document states "patient and quality control samples with measured %A1c values spanning the reportable range." However, a specific number of samples (patients or QC samples) used in the test set is NOT provided.
Data Provenance: The document does not specify the country of origin for the data. The data is retrospective, as it compares the performance of the modified device to a previously cleared predicate device using existing methodologies. It used "manufactured reagents" (presumably, from the submitter) and "patient and quality control samples."

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications

This type of in vitro diagnostic device (reagent kit) typically does not involve human experts establishing "ground truth" for individual patient samples in the same way, for example, a radiology AI device would. Instead, the ground truth for an HbA1c assay is established through reference methods and calibration standards.

Number of Experts: Not applicable in the context of clinical expert review for individual cases.
Qualifications of Experts: Not applicable. The "ground truth" for the predicate device and implicitly for the modified device is linked to established standardization programs. The predicate device is "Traceable to the Diabetes Control and Complications Trial (DCCT) and IFCC reference methods. Certified by the National Glycohemoglobin Standardization Program (NGSP)." The modified device states "No change expected, NGSP certification testing is currently in progress." This indicates that compliance with these established external standards serves as the definition of "ground truth" for accuracy.

4. Adjudication Method for the Test Set

Adjudication methods (like 2+1, 3+1) are typically used in studies where there is disagreement among human readers or expert reviewers to derive a consensus ground truth. This is not applicable here as the "ground truth" is derived from standardized reference methods and the focus is on analytical performance comparison.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

Was an MRMC study done? No. This type of study is not relevant for a reagent kit used in an automated chemistry system. MRMC studies are designed to assess the impact of a device on human reader performance, particularly in image interpretation or diagnostic decision-making scenarios. The VITROS d%A1c Reagent Kit is for automated quantitative measurement.
Effect size of human readers improvement: Not applicable.

6. Standalone Performance Study

Was a standalone study done? Yes, in the sense that the performance of the VITROS Chemistry Products d%A1c Reagent Kit (modified) on the VITROS 5,1 FS Chemistry System was evaluated as a complete system (algorithm/device only). The study's objective was to demonstrate its performance and establish substantial equivalence to the predicate device. The results are implied by the statement: "Equivalence was demonstrated using manufactured reagents along with patient and quality control samples."

7. Type of Ground Truth Used

The ground truth for this device is based on reference methods and standardization programs for HbA1c measurement.

The predicate device is "Traceable to the Diabetes Control and Complications Trial (DCCT) and IFCC reference methods. Certified by the National Glycohemoglobin Standardization Program (NGSP)."
The modified device stated "NGSP certification testing is currently in progress," indicating adherence to these recognized standards as the ultimate ground truth.
The comparison study likely used samples with values established by these reference methods or by the predicate device (which is itself traceable).

8. Sample Size for the Training Set

Not Applicable. This is a reagent kit and chemistry system that performs a quantitative assay, rather than a machine learning algorithm that requires a "training set" in the conventional sense. The "training" of such a system involves chemical and engineering optimization, not data-driven machine learning model training.

9. How the Ground Truth for the Training Set Was Established

Not Applicable. As there is no machine learning model training set in the typical sense, there is no "ground truth" for a training set to be established. The system's accuracy and performance are inherently linked to its chemical reactions, instrumentation, and calibration using standardized calibrators.

Summary

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Summary Information

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: K060650

1. Submitter Ortho-Clinical Diagnostics, Inc. name. 100 Indigo Creek Drive address, Rochester, New York 14626-5101 contact (585) 453-3143
  Contact Person: Michael M. Byrne
1. Preparation Date Special 510(k) prepared: March 10, 2006 date
1. Device Trade or Proprietary Name: name VITROS Chemistry Products d%A1c Reagent Kit VITROS Chemistry Products Calibrator Kit 18 VITROS Chemistry Products FS Calibrator 1 Common Name : Glycohemoglobin assay Classification Name: Glycosylated hemoglobin assay (21 CFR 864.7470).
1. Predicate The VITROS Chemistry Products d%A1c Reagent Kit (modified), VITROS device Chemistry Products Calibrator Kit 18 and VITROS Chemistry Products FS Calibrator 1 are substantially equivalent to VITROS Chemistry Products %A1c Reagent Kit (current), VITROS Chemistry Products Calibrator Kit 18, and VITROS FS Calibrator 1 which were cleared by the FDA for in vitro diagnostic use.

VITROS %A1c Reagent Kit: (K041764, Cleared September 9, 2004) VITROS Calibrator Kit 18: (K041764, Cleared September 9, 2004) VITROS FS Calibrator 1: (K052645, Cleared December 14, 2005).

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1. VITROS Chemistry Products d%A1c Reagent Kit, VITROS Chemistry 5. Device description Products Calibrator Kit 18, and VITROS Chemistry Products FS Calibrator 1 are combined with the VITROS 5,1 FS Chemistry System to perform the VITROS d%A1c assay.
- a. VITROS d%A1c Reagent Kit contains two unique dual chambered reagent packs containing ready to use liquid reagents that are used to measure both hemoglobin A1c (HbA1c) and hemoglobin (Hb).

i. Hemoglobin A1c Reagent Pack (HbA1c)

1. The R1 chamber (HbA1c Reagent 1) consists of:
- a. HbA1c antibody (ovine serum)
- b. Buffers
- c. Stabilizers
- d. Preservatives
1. The R2 chamber (HbA1c Reagent 2) consists of:
- a. HbAlc Polyhapten
- b. Buffers
- c. Stabilizers
- d. Preservatives

ii. Hemoglobin Reagent Pack (Hb)

1. The R1 chamber (Hb Reagent 1) consists of:
- a. Buffer
- b. Stabilizers
- c. Preservatives
1. The R2 chamber (Hb Reagent 2) contains Hemolyzing Reagent, which consists of:
- a. Tetradecyltrimethylammonium bromide (TTAB) <1% (w/v)
- b. Water
b. VITROS Chemistry Products Calibrator Kit 18 is composed of a hemolysate derived from human and ovine blood to which surfactants, stabilizer, and preservative have been added. This lyophilized calibrator is reconstituted with VITROS Chemistry Products FS Reconstitution Diluent, which is composed of processed water.
VITROS Chemistry Products FS Calibrator 1 is composed C. of processed water and 0.9% w/v sodium chloride (saline).

Continued on next page

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5. Device description (con't)

The VITROS d%A1c assay is designed to use whole blood to determine %A1c on-board the VITROS 5,1 FS System without the need for sample pretreatment.

1. The determination of percent glycated hemoglobin (%A1c) is performed using the VITROS d%A1c Reagent Kit in conjunction with VITROS Calibrator Kit 18 and VITROS FS Calibrator 1 on the VITROS 5,1 FS Chemistry System. The VITROS d%A1c Reagents consists of two unique dual chambered packs containing complete ready-to-use liquid reagents. Whole blood samples are hemolyzed on the VITROS 5,1 FS Chemistry System during the sample analysis. Since this is a direct reacting assay, no sample pretreatment by the operator is required to perform this assay.
  The VITROS 5,1 FS Chemistry System is designed specifically for use with the VITROS Chemistry Products range of products.
VITROS Chemistry Products d % A1c Reagent Kit: For in vitro diagnostic 6. Device intended use only. VITROS Chemistry Products d%A1c Reagent is used to determine use the percent glycated hemoglobin (%A1c) in human whole blood by quantitative measurement of hemoglobin (Hb) and hemoglobin A1c (HbA1c). Measurements of percentage A1c are effective in monitoring long-term glycemic 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 FS Calibrator 1: For in vitro diagnostic use only. VITROS Chemistry Products FS Calibrator 1 is used in conjunction with VITROS Chemistry Products Calibrator Kits 16, 17, 18, 19 and 28 to calibrate VITROS 5,1 FS Chemistry Systems.

Continued on next page

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510(k) Summary, Continued

The VITROS Chemistry Products d%A1c Reagent Kit (modified), VITROS 7. Comparison to predicate Chemistry Products Calibrator Kit 18 and VITROS Chemistry Products FS device Calibrator 1 are substantially equivalent to VITROS Chemistry Products %A1c Reagent Kit (current), VITROS Chemistry Products Calibrator Kit 18. and VITROS FS Calibrator 1 which were cleared by the FDA for in vitro diagnostic use. VITROS %A1c Reagent Kit: (K041764, Cleared September 9, 2004) VITROS Calibrator Kit 18: (K041764, Cleared September 9, 2004) VITROS FS Calibrator 1: (K052645, Cleared December 14, 2005).
Table 1 lists the characteristics of the tests performed using the VITROS d%A1c Reagent Kit (modified) and the VITROS %A1c Reagent Kit (current).

Comparison to predicate device: Reagent Kit
	New device (modified)	Predicate device (current)
DeviceCharacteristics	VITROS Chemistry Products d%A1cReagent Kit	VITROS Chemistry Products % A1cReagent Kit
SpecimenHemolysis	Specimen hemolysis to be performed as anautomated step by the VITROS 5,1 FSChemistry System using VITROSChemistry Products Hemolyzing Reagent,which has been placed in the R2 chamber ofthe VITROS Hb Reagent Pack.	Pretreatment step performed by manuallyadding 1 part sample to 100 parts VITROSChemistry Products Hemolyzing Reagentprior to analysis.
Intended Use	For in vitro diagnostic use only. VITROSChemistry Products d%A1c Reagent Kit isused to determine the percent glycatedhemoglobin (%A1c) in human whole bloodby quantitative measurement of hemoglobin(Hb) and hemoglobin A1c (HbA1c). Meas-urements of percentage A1c are effective inmonitoring long-term glycemic control inindividuals with diabetes mellitus.	For in vitro diagnostic use only. VITROSChemistry Products %A1c Reagent Kit isused to calculate percent glycatedhemoglobin (%Alc) in pretreated humanwhole blood by quantitative measurement ofhemoglobin (Hb) and hemoglobin Alc(HbAlc). Measurements of percentage Alcare effective in monitoring long-term glucosecontrol in individuals with diabetes mellitus..
Sample Type	Whole Blood (EDTA)	Whole Blood (EDTA, Heparin, sodiumfluoride, potassium oxalate)
Standardization	No change expected, NGSP certificationtesting is currently in progress.	Traceable to the Diabetes Control andComplications Trial (DCCT) and IFCCreference methods. Certified by the NationalGlycohemoglobin Standardization Program(NGSP)
Basic Principle	No Change	Turbidimetric inhibition immunoassay
Reportable Range	No Change	4-14 %Alc NGSP
Reagents	No Change	Liquid ready to use
Instrumentation	No Change	VITROS 5,1 FS Chemistry System

Table 1 List of Reagent Characteristics: Comparison to Predicate Device

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510(k) Summary, Continued

The information presented in this pre-market notification demonstrates that 8. Conclusions the performance of the VITROS Chemistry Products d%A1c Reagent for use with human whole blood is substantially equivalent to the cleared predicate device.

Equivalence was demonstrated using manufactured reagents along with patient and quality control samples with measured %A1c values spanning the reportable range.

The information presented in this premarket notification provides a reasonable assurance that the VITROS Chemistry Products d%A1c assay for use with human whole blood is safe and effective for the stated intended use.

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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 its wings forming a protective shape. The eagle is black and is positioned in the center of a circular border. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged around the border of the circle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

APR 6 2006

Mr. Michael M. Byrne Regulatory Affairs Associate Ortho-Clinical Diagnostics 100 Indigo Creek Drive Rochester, NY 14626-5101

Re: K060650

Trade/Device Name: VITROS Chemistry Products d%A1c Reagent Kit VITROS Chemistry Products Calibrator Kit 18 VITROS Chemistry Products FS Calibrator 1 Regulation Number: 21 CFR8864.7470 Regulation Name: Glycosylated hemoglobin assay

Regulatory Class: Class II

Product Code: LCP, JIT

Dated: March 10. 2006

Received: March 13, 2006

Dear Mr. Byrne:

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 ean 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 vours.

Alberto Gutierrez

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

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Indications for Use Statement

Page 1 of 1

510(k) Number (if known):

Device Name:

Image /page/7/Picture/4 description: The image shows a handwritten text "Kd60650" in black ink. The text appears to be a code or identifier, with a mix of uppercase letters and numbers. A horizontal line is present beneath the text, possibly indicating an underline or a separation mark.

VITROS Chemistry Products d%A1c Reagent Kit VITROS Chemistry Products Calibrator Kit 18 VITROS Chemistry Products FS Calibrator 1

For in vitro diagnostic use only. Indications for Use: VITROS Chemistry Products d%A1c Reagent Kit is used to determine the percent glycated hemoglobin (%A1c) in human whole blood by quantitative measurement of hemoglobin (Hb) and hemoglobin A1c (HbA1c). Measurements of percentage Alc are effective in monitoring long-term glycemic 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).

Prescription Use X (Per 21 CFR 801.109)

Over-The-Counter Use

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Carol C Benson

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K060650

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).