For in vitro diagnostic use only. VITROS Chemistry Products TRFRN Reagent is used to quantitatively measure transferrin (TRFRN) concentration in human serum and plasma.

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.

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:

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).
2 The VITROS Chemistry Products MicroTip range of liquid reagent products (in this case VITROS Chemistry Products TRFRN Reagent, VITROS Chemistry Products Calibrator Kit 20 and VITROS Chemistry Products Protein Performance Verifiers I. II and III), which are combined by the VITROS 5,1 FS Chemistry System to perform the VITROS TRFRN assay.
3 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 5,1 FS Chemistry System premarket notification (K031924).
4 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 provided text describes the substantial equivalence of the VITROS Chemistry Products TRFRN Reagent, Calibrator Kit 20, and Protein Performance Verifiers to predicate devices. It does not contain information about acceptance criteria and a study design in the way one would typically describe a clinical validation for a medical imaging AI device. Instead, it focuses on demonstrating equivalence through comparison of assay characteristics and a correlation study.

Here's an attempt to extract relevant information and note the absence of others, aligning with your request:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in a quantitative, pre-defined manner for the performance of the new device relative to a gold standard. Instead, it demonstrates performance by showing correlation and similarity to a legally marketed predicate device.

Performance Metric	Acceptance Criteria (Implicit)	Reported Device Performance (VITROS TRFRN assay)
Correlation	Substantial equivalence to predicate device (IMMAGE® Immunochemistry System TRF Transferrin Reagent) as demonstrated by linear regression and a high correlation coefficient.	Correlation Coefficient: 0.986 (with IMMAGE Transferrin assay on Beckman IMMAGE Immunochemistry analyzer). Linear Regression: VITROS TRFRN assay = 0.96x X - 0.24 mg/dL (where X is the IMMAGE Transferrin assay).
Precision	(Not explicitly stated as an "acceptance criterion" in this summary; referenced as a study performed).	Studies were performed to determine precision, and results are summarized in the VITROS TRFRN Reagent Instructions For Use (Section 8). Specific values are not provided in this 510(k) summary.
Analytical Sensitivity	(Not explicitly stated as an "acceptance criterion" in this summary; referenced as a study performed).	Studies were performed to determine analytical sensitivity, and results are summarized in the VITROS TRFRN Reagent Instructions For Use (Section 8). Specific values are not provided in this 510(k) summary.
Specificity	(Not explicitly stated as an "acceptance criterion" in this summary; referenced as a study performed).	Studies were performed to determine specificity, and results are summarized in the VITROS TRFRN Reagent Instructions For Use (Section 8). Specific values are not provided in this 510(k) summary.
Expected Values	(Not explicitly stated as an "acceptance criterion" in this summary; referenced as a study performed).	Studies were performed to determine expected values, and results are summarized in the VITROS TRFRN Reagent Instructions For Use (Section 8). Specific values are not provided in this 510(k) summary.
Reportable Range	Similar to predicate device.	New Device (VITROS TRFRN assay): 80.00 - 750.00 mg/dL. Predicate Device (IMMAGE Transferrin assay): 75 - 750 mg/dL. (These are similar, with the new device having a slightly higher lower limit).

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

Sample Size: The document states that "patient samples" were used, but does not specify the exact sample size for the correlation study or other performance studies (precision, sensitivity, specificity, expected values).
Data Provenance: The document states that "commercially available reagents along with patient samples" were used. There is no information provided regarding the country of origin of the data or whether it was retrospective or prospective.

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

This type of information is not applicable to this submission. The "ground truth" for a quantitative diagnostic assay like transferrin measurement is typically the result obtained from a reference method or another validated diagnostic device (in this case, the predicate device). There is no mention of human experts establishing a ground truth for individual cases in this context, unlike a qualitative diagnostic device (e.g., an AI imaging algorithm).

4. Adjudication Method for the Test Set

This type of information is not applicable to this submission. Adjudication methods (like 2+1 or 3+1) are typically used for qualitative assessments where multiple human readers might disagree, and a consensus needs to be formed to establish ground truth or interpret results. For a quantitative assay, the comparison is directly between numerical results.

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 type of information is not applicable to this submission. An MRMC study is relevant for AI-assisted diagnostic tools that interpret images or other qualitative data, showing how AI impacts human reader performance. This submission is for a fully automated in vitro diagnostic assay with no human interpretation component in the direct measurement of transferrin.

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

Yes, this describes a standalone performance study. The VITROS Chemistry Products TRFRN Reagent is designed to quantitatively measure transferrin concentration on the VITROS 5,1 FS Chemistry System. The correlation study compares the results generated by this new automated system (algorithm/device only) directly with the results from the predicate automated system. There is no human intervention in the result generation itself that would constitute a "human-in-the-loop" component.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

The "ground truth" in this context is the quantitative measurement of transferrin by the predicate device, the IMMAGE® Immunochemistry System TRF Transferrin Reagent on the Beckman IMMAGE® Immunochemistry System (K963427). This is a common approach for demonstrating substantial equivalence for new in vitro diagnostic devices, where the predicate device's established performance serves as the benchmark.

8. The Sample Size for the Training Set

The document does not provide information on a "training set" in the context of an AI/machine learning model. This submission is for a conventional chemical reagent and assay system, not an AI algorithm that undergoes a distinct training phase with a dedicated dataset. The correlation study mentioned uses "patient samples" which would typically be a test set for assessing performance.

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

As there is no mention of a "training set" in the context of AI/machine learning, this question is not applicable. For the performance evaluation, the predicate device results served as the reference for comparison.

Summary

{0}------------------------------------------------

NOV 1 9 2004

3.0 510(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.

K04 2471 The assigned 510(k) number is: _

3.1 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

3.2 Date of Preparation:

September 10, 2004

3.3 Device Proprietary Names:

Trade Names VITROS Chemistry Products TRFRN Reagent VITROS Chemistry Products Calibrator Kit 20 VITROS Chemistry Products Protein Performance Verifiers I, II and III

Common Name Transferrin assay

3.4 Classification Names

Classification Name: Transferrin test system (866.5880): 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.

Continued on next page

{1}------------------------------------------------

3.5 Predicate device

The VITROS Chemistry Products TRFRN Reagent and VITROS Chemistry 3.5.1 Products Calibrator Kit 20 are substantially equivalent to the IMMAGE® Immunochemistry System TRF Transferrin Reagent on the Beckman IMMAGE® Immunochemistry System.
3.5.2 The VITROS Chemistry Products Protein Performance Verifiers I, II and III are substantially equivalent to the VITROS Chemistry Products Performance Verifiers I and II.

3.6 Device description

The system is comprised of four main elements:

The VITROS 5,1 FS Chemistry System instrumentation, which provides automated 1 use of the chemistry reagents. The VITROS 5,1 FS Chemistry System was cleared for market by a separate 510(k) premarket notification (K031924).
2 The VITROS Chemistry Products MicroTip range of liquid reagent products (in this case VITROS Chemistry Products TRFRN Reagent, VITROS Chemistry Products Calibrator Kit 20 and VITROS Chemistry Products Protein Performance Verifiers I. II and III), which are combined by the VITROS 5,1 FS Chemistry System to perform the VITROS TRFRN assay.
3 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 5,1 FS Chemistry System premarket notification (K031924).
Common reagents used by multiple assays on the VITROS System (in this case, 4 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. Continued on next page

{2}------------------------------------------------

Device intended use 3.7

VITROS Chemistry Products TRFRN Reagent 3.7.1

For in vitro diagnostic use only. VITROS Chemistry Products TRFRN Reagent is used to quantitatively measure transferrin (TRFRN) concentration in human serum and plasma.

VITROS Chemistry Products Calibrator Kit 20 3.7.2

For in vitro diagnostic use only. 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.

VITROS Chemistry Products Protein Performance Verifiers I, II and III 3.7.3

3.8 Comparison to predicate device

3.8.1 The VITROS Chemistry Products TRFRN Reagent and VITROS Chemistry Products Calibrator Kit 20 are substantially equivalent to the IMMAGE® Immunochemistry System TRF Transferrin Reagent on the Beckman IMMAGE® Immunochemistry System (predicate device) which was cleared by the FDA (K963427) for IVD use.
The relationship between the VITROS TRFRN assay and the predicate device, determined by the least squares linear regression is:

VITROS TRFRN assay = 0.96x X - 0.24 mg/dL,

with a correlation coefficient of 0.986,

where X is the IMMAGE Transferrin assay on the Beckman IMMAGE Immunochemistry analyzer.

In addition to the above mentioned correlation study, studies were performed to determine the precision, analytical sensitivity, specificity and expected values of the VITROS TRFRN assay, (refer to VITROS TRFRN Reagent Instructions For Use in Section 8 for summaries of the results of these studies).

Continued on next page

{3}------------------------------------------------

Table 1 lists the characteristics of the VITROS TRFRN assay (new device) and the Table 1 IMMAGE Transferrin assay (predicate device).

DeviceCharacteristic	VITROS TRFRN assay(New Device)	IMMAGE Transferrin assay(Predicate Device)
Intended Use	For in vitro diagnostic use only.VITROS Chemistry ProductsTRFRN Reagent is used toquantitatively measure transferrin(TRFRN) concentration in humanserum.	TRF Reagent, when used inconjunction with IMMAGE®Immunochemistry Systems andCalibrator 1, is intended for thequantitative determination ofTransferrin (TRF) in human serumby rate nephelometry.
Method	Immunoturbidimetry	Rate nephelometry
Reportable Range	80.00 - 750.00 mg/dL	75 - 750 mg/dL
Instrumentation	VITROS 5,1 FS Chemistry Systems	Beckman IMMAGEImmunochemistry Systems
Sample types	Serum and plasma	Serum
Reactive Ingredient	Goat anti-sera to human transferrin	Processed goat sera

3.8.2 The VITROS Chemistry Products Protein Performance Verifiers I, II and III are substantially equivalent to the VITROS Chemistry Products Performance Verifiers (predicate device) which were cleared by the FDA (K041720) for IVD use.
Table 2 Table 2 lists the similarities and differences of the device characteristics between the 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 Verifier isan assayed control used tomonitor performance on VITROSChemistry Systems.
Matrix of PerformanceVerifiers	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.
Performance Verifier Levels	Low, Medium and High	Low and High

{4}------------------------------------------------

3.9 Conclusions

The data presented in the premarket notification provide a reasonable assurance that the VITROS TRFRN assay 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.

{5}------------------------------------------------

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 consists of a stylized eagle or bird-like figure with three curved lines representing its wings or body. The bird is positioned to the right of a circular arrangement of text that reads "DEPARTMENT OF HEALTH & HUMAN SERVICES USA".

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

NOV 1 9 2004

Ms. Darlene J. Phillips, RAC Regulatory Affairs Associate Ortho-Clinical Diagnostics 100 Indigo Creek Drive Rochester, NY 14626-5101

Re: K042477

Trade/Device Name: VITROS Chemistry Products TRFRN Reagent VITROS Chemistry Products Calibrator Kit 20 VITROS Chemistry Products Protein Performance Verifiers I, II and III Regulation Number: 21 CFR 866.5880 Regulation Name: Transferrin immunological test system Regulatory Class: Class II Product Code: DDG, JIT, JJX Dated: September 10, 2004 Received: September 13, 2004

Dear Ms Phillips:

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 application (PMA). You may, therefore, market these 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.

If your devices are classified (see above) into either class II (Special Controls) or class III (PMA), they may be subject to such 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

{6}------------------------------------------------

Page 2 – Ms. Darlene J. Phillips

forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic forth in the quality systems (Sections 531-542 of the Act); 21 CFR 1000-1050. product radiation control pro risions (seeting your devices as described in your Section 510(k) I ms letter will anow you to begin makemage yoursence of your devices to legally premarket nothroamon. - The PDFs 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), If you desire specific at ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 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,

Zohaff. Bestoof

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

{7}------------------------------------------------

1.0 Indications for Use

510(k) Number(if known):	K042477
Device Name:	VITROS Chemistry Products TRFRN 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 TRFRNReagent is used to quantitatively measure transferrin (TRFRN) concentrationin human serum and plasma.For in vitro diagnostic use. VITROS Chemistry Products Calibrator Kit 20 isused to calibrate VITROS 5,1 FS Chemistry Systems for the quantitativemeasurement of transferrin, C3, C4, IgA, IgG and IgM.For in vitro diagnostic use only. VITROS Chemistry Products ProteinPerformance Verifiers are assayed controls used to monitor the performanceof TRFRN, C3, C4, IgA, IgG and IgM Reagents on VITROS 5,1 FSChemistry 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 IF
NEEDED)Concurrence of CDRH, Office of Device Evaluation (ODE)

1 ma ﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼﺼ

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K042477

Page 1 of 1

Regulation Number and Section

§ 866.5880 Transferrin immunological test system.

(a)
Identification. A transferrin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the transferrin (an iron-binding and transporting serum protein) in serum, plasma, and other body fluids. Measurement of transferrin levels aids in the diagnosis of malnutrition, acute inflammation, infection, and red blood cell disorders, such as iron deficiency anemia.(b)
Classification. Class II (performance standards).