For in vitro diagnostic use only. VITROS Chemistry Products C3 Reagent is used to quantitatively measure complement C3 (C3) concentration in human serum and plasma. Measurements of these proteins aids in the diagnosis of immunologic disorders, especially those associated with deficiencies of complement components.

For in vitro diagnostic use. VITROS Chemistry Products Calibrator Kit 20 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of transferrin, C3, C4, IgA, IgG and IgM.

For in vitro diagnostic use only. VITROS Chemistry Products Protein Performance Verifiers are assayed controls used to monitor the performance of TRFRN, C3, C4, IgA, IgG and IgM Reagents on VITROS 5,1 FS Chemistry Systems.

For in vitro diagnostic use only. VITROS Chemistry Products C4 Reagent is used to quantitatively measure complement C4 (C4) concentration in human serum and plasma. Measurements of these proteins aids in the diagnosis of immunologic disorders, especially those associated with deficiencies of complement components.

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 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 MicroTip range of liquid reagent products (in this case VITROS Chemistry Products C3 Reagent, VITROS Chemistry Products C4 Reagent, VITROS Chemistry Products Calibrator Kit 20 and VITROS Chemistry Products Protein Performance Verifiers I, II and III), which are combined on the VITROS 5,1 FS Chemistry System to perform the VITROS C3 and C4 assays.
The VITROS Chemistry Products Thin Film range of dry 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).

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

AI/ML Overview

The document describes the submission of a 510(k) premarket notification for several in vitro diagnostic devices, including VITROS Chemistry Products C3 Reagent, VITROS Chemistry Products C4 Reagent, VITROS Chemistry Products Calibrator Kit 20, and VITROS Chemistry Products Protein Performance Verifiers I, II and III. The purpose of the submission is to demonstrate substantial equivalence to legally marketed predicate devices.

1. Table of Acceptance Criteria and Reported Device Performance:

The document focuses on demonstrating substantial equivalence to predicate devices rather than defining specific acceptance criteria for a new clinical performance study. Instead, the "acceptance criteria" are implied by the statistical correlation to the predicate devices.

Device Characteristic	VITROS C3 assay (New Device #1)	Beckman C3 assay (Predicate Device #1)	VITROS C4 assay (New Device #2)	Dade Behring C4 assay (Predicate Device #2)
Correlation to Predicate	Y = 0.95X + 11 mg/dL	N/A	Y = 0.93X + 3.0 mg/dL	N/A
Correlation Coefficient (r)	0.98	N/A	0.976	N/A
Reportable Range	40 - 380 mg/dL	35 - 350 mg/dL	8.0 - 60.0 mg/dL	6 - 190 mg/dL
Method	Immunoturbidimetry	Rate nephelometry	Immunoturbidimetry	Rate nephelometry
Instrumentation	VITROS 5,1 FS Chemistry Systems	IMMAGE Immunochemistry Systems	VITROS 5,1 FS Chemistry Systems	Dade Behring BN® ProSpec Nephelometer
Sample type	Serum and plasma	Serum	Serum and plasma	Serum

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

The document does not explicitly state the specific sample size used for the correlation studies for C3 and C4 assays, nor does it specify the country of origin of the data. It generally refers to "patient samples" and "commercially available reagents." The studies appear to be retrospective analyses comparing the new device's performance to existing predicate devices.

3. Number of Experts Used to Establish Ground Truth and Qualifications:

Not applicable. The ground truth for the test set is established by the results obtained from the predicate devices, which are already legally marketed and established diagnostic systems. There is no mention of expert consensus for establishing ground truth in this submission.

4. Adjudication Method for the Test Set:

Not applicable. The study design involves direct comparison and correlation between the new device's measurements and those of the predicate devices. There is no mention of an adjudication process.

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

Not applicable. This document describes the performance of an in vitro diagnostic device (reagents and calibrators) used in a laboratory setting for quantitative measurement. It is not an imaging device or a system that involves human readers interpreting cases in a multi-reader, multi-case study.

6. Standalone Performance Study:

Yes, a standalone performance study in the form of correlation studies, precision, analytical sensitivity, specificity, and expected values was performed for the VITROS C3 and C4 assays, comparing them to the predicate devices. This demonstrates the algorithm-only performance in relation to established methods.

7. Type of Ground Truth Used:

The ground truth used for these studies is the measurement values obtained from the legally marketed predicate devices. The new devices' performance is assessed by how well their results correlate with those produced by the predicate devices.

8. Sample Size for the Training Set:

The document does not explicitly state a "training set" sample size in the context of machine learning or AI models. The development and validation of these in vitro diagnostic reagents would have involved extensive R&D and internal testing, which would serve a similar function to a training set, but no specific numbers are publicly disclosed in this 510(k) summary.

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

Not explicitly stated. For in vitro diagnostic devices, the "training" (development and optimization) would typically involve using known reference materials, spiked samples, and characterized patient samples, with their true values established through highly accurate reference methods or clinical standards. This information is usually part of internal development and not fully detailed in a 510(k) summary focused on substantial equivalence.

Summary

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular emblem with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the top half of the circle. Inside the circle is a stylized image of an eagle with its wings outstretched. The eagle is depicted in a simple, abstract style, with only a few lines used to create its form.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

NOV 8 - 2004

Ms. Darlene Phillips Regulatory Affairs Associate Ortho-Clinical Diagnostics 100 Indigo Creek Drive Rochester, New York 14626-5101

Re: K042494

Trade/Device Name: VITROS Chemistry Products C3 Reagent VITROS Chemistry Products C4 Reagent VITROS Chemistry Products Calibrator Kit 20 VITROS Chemistry Products Protein Performance Verifiers I, II and III

Regulation Number: 21 CFR 866.5240 Regulation Name: Complement Components Immunological Test System Regulatory Class: Class II Product Code: CZW, DBI, JIT, JJY Dated: September 13, 2004 Received: September 14, 2004

Dear Ms Phillips:

This letter corrects our substantially equivalent letter of October 19, 2004 regarding the VITROS Chemistry Products C3 Reagent, VITROS Chemistry Products C4 Reagent, VITROS Chemistry Products Calibrator Kit 20 and VITROS Chemistry Products Protein Performance Verifiers I, II and III in which the VITROS Chemistry Products C4 Reagent was omitted from the listing of the trade name(s).

We have reviewed your Section 510(k) premarket notification of intent to market the devices referenced above and have determined the devices are 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 (PMA). You may, therefore, market the devices, 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.

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Page 2

If your devices are classified (see above) into either class II (Special Controls) or class III (PMA), they may be subject to additional controls. Existing major regulations affecting your devices can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your devices 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 devices comply 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (sections 531-542 of the Act); 21 CFR 1000-1050.

This letter will allow you to continue marketing your devices as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your devices to legally marketed predicate devices results in a classification for your devices and thus, permits your devices to proceed to the market.

If you desire specific advice for your devices on our labeling regulation (21 CFR Part 801), please contact the Office of Compliance 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 vours.

Robert Beckerh

Robert L. Becker, Jr., M.D., PhD DIRECTOR Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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1.0 Indications for Use for VITROS C3 assay

510(k) Number (if known):	K042494
Device Name:	VITROS Chemistry Products C3 ReagentVITROS Chemistry Products Calibrator Kit 20VITROS Chemistry Products Protein Performance Verifiers I, II and III
Indications for Use:	For in vitro diagnostic use only. VITROS Chemistry Products C3 Reagent is used to quantitatively measure complement C3 (C3) concentration in human serum and plasma. Measurements of these proteins aids in the diagnosis of immunologic disorders, especially those associated with deficiencies of complement components.For in vitro diagnostic use. VITROS Chemistry Products Calibrator Kit 20 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of transferrin, C3, C4, IgA, IgG and IgM.For in vitro diagnostic use only. VITROS Chemistry Products Protein Performance Verifiers are assayed controls used to monitor the performance of TRFRN, C3, C4, IgA, IgG and IgM Reagents on VITROS 5,1 FS Chemistry Systems.
Prescription Use	X
(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 Device Evaluation (ODE)

Mara In Chan

Division Sign-Off

Office of In Vitro Diagn

Office of In Vitro Diagnostic
Device Evaluation and Safety

510(k) K042494

Page 1 of 2

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Indications for Use for VITROS C4 assay 2.0

510(k) Number (if known):	KO42494
Device Name:	VITROS Chemistry Products C4 ReagentVITROS Chemistry Products Calibrator Kit 20VITROS Chemistry Products Protein Performance Verifiers I, II and III
Indications for Use:	For in vitro diagnostic use only. VITROS Chemistry Products C4 Reagent is used to quantitatively measure complement C4 (C4) concentration in human serum and plasma. Measurements of these proteins aids in the diagnosis of immunologic disorders, especially those associated with deficiencies of complement components.For in vitro diagnostic use. VITROS Chemistry Products Calibrator Kit 20 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of transferrin, C3, C4, IgA, IgG and IgM.For in vitro diagnostic use only. VITROS Chemistry Products Protein Performance Verifiers are assayed controls used to monitor the performance of TRFRN, C3, C4, IgA, IgG and IgM Reagents on VITROS 5,1 FS Chemistry Systems.
Prescription Use(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 IFNEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Mana M. Clan

Division Sign-Off

Office of in Vitro Diagnosilic Device Evaluation and Safety

510(k) K042494

Page 2 of 2

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OCT 1 9 2004

4.0 510(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: KOYA 494

4.1 Submitter name, address, contact

Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, New York 14626-5101 Phone: (585) 453-4253 Fax: (585) 453-3368

Contact Person: Darlene J. Phillips

4.2 Date of Preparation:

September 13, 2004

4.3 Device Proprietary Names:

VITROS Chemistry Products C3 Reagent Trade Names VITROS Chemistry Products C4 Reagent VITROS Chemistry Products Calibrator Kit 20 VITROS Chemistry Products Protein Performance Verifiers I. II and III

Common Name Complement C3 and C4 assays

4.4 Classification Names

Classification Name: Complement components immunological test systems (866.5240): Class: II (Performance standards)

Classification Name: Calibrator (862.1150): Class II The Clinical Chemistry and Toxicology Panel of the FDA has placed calibrators in Class II.

Classification Name: Quality Control material (assayed and unassayed) (862,1660): Class I: The Clinical Chemistry and Toxicology Panel of the FDA has placed Quality Control material (assayed and unassayed) for clinical chemistry in Class I. Since this device is an assayed control, it meets the reserved criteria under Section 510(1) of the Food, Drug, and Cosmetic Act.

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4.5 Predicate device

4.5.1 The VITROS Chemistry Products C3 Reagent and VITROS Chemistry Products Calibrator Kit 20 are substantially equivalent to the IMMAGE® Immunochemistry System Complement C3 Reagent assayed on the Beckman IMMAGE® Immunochemistry System.
The VITROS Chemistry Products C4 Reagent and VITROS Chemistry Products 4.5.2 Calibrator Kit 20 are substantially equivalent to the Dade Behring N Antisera to Human Complement C4 assayed on the Dade Behring BN® ProSpec Nephelometer.
4.5.3 The VITROS Chemistry Products Protein Performance Verifiers 1, II and III are substantially equivalent to the VITROS Chemistry Products Performance Verifiers I and II.

4.6 Device description

The system is comprised of four main elements:

l . 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 MicroTip range of liguid reagent products (in this case VITROS Chemistry Products C3 Reagent, VITROS Chemistry Products C4 Reagent, VITROS Chemistry Products Calibrator Kit 20 and VITROS Chemistry Products Protein Performance Verifiers I, II and III), which are combined on the VITROS 5,1 FS Chemistry System to perform the VITROS C3 and C4 assays.
1. The VITROS Chemistry Products Thin Film range of dry products, which are dry, multilayered, analytical elements, coated on polyester supports. The thin film products each have their 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, I FS Chemistry System premarket notification (K031924).

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1. Common reagents used by multiple assays on the VITROS System (in this case, VITROS Chemistry Products FS Diluent Pack 2).
  The VITROS System and reagents are designed specifically for use with the VITROS Chemistry Products range of products.

4.7 Device intended use

4.7.1 VITROS Chemistry Products C3 Reagent

4.7.2 VITROS Chemistry Products C4 Reagent

4.7.3 VITROS Chemistry Products Calibrator Kit 20

4.7.4 VITROS Chemistry Products Protein Performance Verifiers I, II and III

For in vitro diagnostic use only. VITROS Chemistry Products Protein Performance Verifiers are assayed controls used to monitor the performance of TRFRN. C3. C4. IgA, IgG and IgM Reagents on VITROS 5,1 FS Chemistry Systems.

4.8 Comparison to predicate device

4.8.1 The VITROS Chemistry Products C3 Reagent and VITROS Chemistry Products Calibrator Kit 20 are substantially equivalent to the IMMAGE® Immunochemistry System Complement C3 Reagent assayed on the Beckman IMMAGE® Immunochemistry System (predicate device #1) which was cleared by the FDA (K964842) for IVD use.
Continued on next page

The relationship between the VITROS C3 assay and the predicate device, determined by the least squares linear regression is:

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VITROS C3 assav = 0.95x X + 11 mg/dL.

with a correlation coefficient of 0.98.

where X is the IMMAGE® Immunochemistry System Complement C3 Reagent assayed on the Beckman IMMAGE® Immunochemistry System.

In addition to the above mentioned correlation studies were performed to determine the precision, analytical sensitivity, specificity and expected values of the VITROS C3 assay, (refer to VITROS C3 Reagent Instructions For Use for summaries of the results of these studies).

The VITROS Chemistry Products C4 Reagent and VITROS Chemistry Products 4.8.2 Calibrator Kit 20 are substantially equivalent to the Dade Behring N Antisera to Human Complement C4 assayed on the Dade Behring BN® ProSpec Nephelometer (predicate device #2) which was cleared by the FDA (K860894) for IVD use,
The relationship between the VITROS C4 assay and the predicate device. determined by the least squares linear regression is:

VITROS C4 assay = 0.93x X + 3.0 mg/dL.

with a correlation coefficient of 0.976,

where X is the Dade Behring N Antisera to Human Complement C4 assayed on the Dade Behring BN® ProSpec Nephelometer.

In addition to the above mentioned correlation study, studies were performed to determine the precision, analytical sensitivity, specificity and expected values of the VITROS C4 assay, (refer to VITROS C4 Reagent Instructions For Use for summaries of the results of these studies).

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DeviceCharacteristic	VITROS C3 assay(New Device #1)	Beckman C3 assay(Predicate Device #1)
Intended Use	For in vitro diagnostic use only.VITROS Chemistry Products C3Reagent is used to quantitativelymeasure complement C3 (C3)concentration in human serum.Measurements of these proteins aids inthe diagnosis of immunologic disorders.especially those associated withdeficiencies of complement components.	C3 Reagent, when used inconjunction with IMMAGEImmunochemistry Systems andCalibrator 1, is intended for thequantitative determination ofComplement C3 (C3) in humanserum by rate nephelometry.
Method	Immunoturbidimetry	Rate nephelometry
Reportable Range	40 - 380 mg/dL	35- 350 mg/dL
Instrumentation	VITROS 5,1 FS Chemistry Systems	IMMAGE ImmunochemistrySystems
Sample type	Serum and plasma	Serum
Reactive Ingredient	Goat anti-sera to human C3	C3 Antibody (processed goat sera)

Table 1 lists the characteristics of the VITROS C3 assay (new device #1) and the Beckman Table 1 C3 assay (predicate device #1).

Table 2 Table 2 lists the characteristics of the VITROS C4 assay (new device #2) and the Dade Behring C4 assay (predicate device #2).

DeviceCharacteristic	VITROS C4 assay(New Device #2)	Dade Behring C4 assay(Predicate Device #2)
Intended Use	For in vitro diagnostic use only.VITROS Chemistry Products C4Reagent is used to quantitativelymeasure complement C4 (C4)concentration in human serum.Measurements of these proteins aidsin the diagnosis of immunologicdisorders, especially those associatedwith deficiencies of complementcomponents.	In vitro diagnostic reagents for thequantitative determination ofcomplement factor (C4) in humanserum using the BN Systems.
Method	Immunoturbidimetry	Rate nephelometry
Reportable Range	8.0 - 60.0 mg/dL	6 - 190 mg/dL
Instrumentation	VITROS 5,1 FS Chemistry Systems	Dade Behring Nephlometer
Sample type	Serum and plasma	Serum
Reactive Ingredient	Goat anti-sera to human C4	Antiserum to human C4

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The VITROS Chemistry Products Protein Performance Verifiers I, II and III are 4.8.3 substantially equivalent to the VITROS Chemistry Products Performance Verifiers (predicate device) which were cleared by the FDA (K041720) for IVD use.
Table 3 lists the similarities and differences of the device characteristics between the Table 3 VITROS Protein Performance Verifiers with the predicate device, VITROS Performance Verifiers I and II.

DeviceCharacteristic	New device	Predicate device
Intended Use	For in vitro diagnostic use only.VITROS Chemistry Products ProteinPerformance Verifiers are assayedcontrols used to monitor theperformance of TRFRN, C3, C4,IgA, IgG and IgM Reagents onVITROS 5,1 FS Chemistry Systems.	For in vitro diagnostic use only.VITROS Performance Verifiersare assayed controls used tomonitor performance on VITROSChemistry Systems.
Fluid Matrix	A base matrix of human serum towhich inorganic salts, buffers andpreservatives have been added.	A base matrix of freeze-driedhuman serum to which enzymes,electrolytes, stabilizers,preservatives and other organicanalytes have been added.
Analyte Levels	Low, Medium and High	Low and High
Analytes Monitored	TRFRN, C3, C4, IgA, IgG and IgM	Multiple analytes including ALBALT, AMYL, Bc, Bu, BUN, Ca,Cl-, DGXN, ECO2, Fe, GLU,K+, LDH, Li, Mg, Na+, PHOS,TBIL, TP, URIC

4.9 Conclusions

The data presented in the premarket notification provide a reasonable assurance that the VITROS C3 and C4 assays and the VITROS Chemistry Products Protein 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 commercially available reagents along with patient samples.

Regulation Number and Section

§ 866.5240 Complement components immunological test system.

(a)
Identification. A complement components immunological test system is a device that consists of the reagents used to measure by immunochemical techniques complement components C1q , C1r , C1s , C2 , C3 , C4 , C5 , C6 , C7 , C8 , and C9 , in serum, other body fluids, and tissues. Complement is a group of serum proteins which destroy infectious agents. Measurements of these proteins aids in the diagnosis of immunologic disorders, especially those associated with deficiencies of complement components.(b)
Classification. Class II (performance standards).