For in vitro diagnostic use only. VITROS Chemistry Products mALB Reagent is used to quantitatively measure albumin concentration in human urine (mALB). Measurement of urinary albumin aids in the diagnosis of diabetic nephropathy, hypertension and cardiovascular disease.

For in vitro diagnostic use. VITROS Chemistry Products Calibrator Kit 24 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of albumin in urine (mALB).

For in vitro diagnostic use only. VITROS Chemistry Products mALB Performance Verifiers are assayed controls used to monitor the performance of mALB Reagent 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:

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 mALB Reagent, VITROS Chemistry Products Calibrator Kit 24 and VITROS Chemistry Products mALB Performance Verifiers I and II), which are combined by the VITROS 5,1 FS Chemistry System to perform the VITROS mALB assay.
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 provided text describes the 510(k) submission for the VITROS Chemistry Products mALB Reagent, Calibrator Kit 24, and Performance Verifiers. The submission focuses on demonstrating substantial equivalence to a predicate device, rather than defining and proving acceptance criteria with a standalone study against a ground truth as would be typical for an AI/ML device.

Therefore, many of the requested categories (e.g., sample size for test set, number of experts, adjudication method, MRMC study, training set details) are not directly applicable or explicitly mentioned in the context of this 510(k) submission. This document describes a traditional in-vitro diagnostic device, not an AI/ML device.

However, I will extract the available information and indicate where data is not provided or applicable given the nature of the submission.

1. Table of Acceptance Criteria and Reported Device Performance

For the VITROS Chemistry Products mALB Reagent and Calibrator Kit 24, the primary method for demonstrating performance and equivalence was a correlation study against a predicate device. For the Performance Verifiers, it was a comparison of device characteristics.

Acceptance Criteria Category	Specific Acceptance Criteria (as implied or stated)	Reported Device Performance (VITROS mALB assay)
Correlation to Predicate	Good correlation to the predicate device.	Linear Regression: VITROS mALB assay = 0.93x + 0.03 (where X is the result for the predicate device)Correlation Coefficient: 0.977
Precision	Not explicitly stated as acceptance criteria.	Studies performed; results summarized in VITROS mALB Reagent Instructions For Use (not provided in this document).
Analytical Sensitivity	Not explicitly stated as acceptance criteria.	Studies performed; results summarized in VITROS mALB Reagent Instructions For Use (not provided in this document).
Specificity	Not explicitly stated as acceptance criteria.	Studies performed; results summarized in VITROS mALB Reagent Instructions For Use (not provided in this document).
Expected Values	Not explicitly stated as acceptance criteria.	Studies performed; results summarized in VITROS mALB Reagent Instructions For Use (not provided in this document).
Reportable Range	Not explicitly stated as acceptance criteria.	0.6 to 19.0 mg/dL (Predicate: 0.0 to 34.0 mg/dL)
Substantial Equivalence	Demonstrated equivalence to predicate devices.	"The data presented...provide a reasonable assurance that the VITROS mALB assay and the VITROS Chemistry Products mALB Performance Verifiers are safe and effective for the stated intended uses and are substantially equivalent to the cleared predicate devices."

2. Sample size used for the test set and the data provenance

Sample Size for Test Set: Not explicitly stated for the correlation study. The document mentions "commercially available reagents along with patient samples" were used to demonstrate equivalence, but the number of such samples is not disclosed in the provided text.
Data Provenance: Not explicitly stated. Given the context of a 510(k) for an in-vitro diagnostic device from a US-based company (Ortho-Clinical Diagnostics, Inc. Rochester, New York), it's likely the studies were conducted in the US, but this is not confirmed.
Retrospective or Prospective: Not explicitly stated. For a correlation study of this nature, samples could be collected either retrospectively or prospectively.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This concept is not applicable in the context of this 510(k) submission. The "ground truth" for the performance evaluation of the new device (VITROS mALB assay) was essentially the results obtained from the predicate device (N Antiserum to Human Albumin assay on the Dade Behring BN ProSpec System). The performance of the predicate device itself would have been established through its own validation studies, often involving clinical correlation and robust analytical performance, rather than expert consensus on individual cases.

4. Adjudication method for the test set

Not applicable. There was no expert "adjudication" in the sense of reviewing disagreements on a test set, as the performance was assessed analytically by comparing results to a predicate device.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. This is an In-Vitro Diagnostic device for measuring albumin levels in urine, not an AI/ML-driven imaging or diagnostic tool requiring human reader studies.

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

This refers to the independent analytical performance of the new device (VITROS mALB assay). Yes, standalone studies were performed as indicated by the mention of studies for:

Precision
Analytical sensitivity
Specificity
Expected values

The results of these studies are stated to be in the "VITROS mALB Reagent Instructions For Use," which is not part of the provided text. The correlation study against the predicate device also represents a standalone performance assessment of the new device against another established method.

7. The type of ground truth used

The primary "ground truth" for demonstrating substantial equivalence for the VITROS mALB assay was the results obtained from the legally marketed predicate device (N Antiserum to Human Albumin assay on the Dade Behring BN ProSpec System). This is a well-established method for demonstrating equivalence for IVD devices. The predicate device's own performance would have been validated against clinical outcomes or reference methods.

8. The sample size for the training set

Not applicable. This is not an AI/ML device, so there is no concept of a "training set" in the context of machine learning model development. The development and optimization of the reagent and assay method would have involved various experimental batches and iterative testing, but this is distinct from an AI training set.

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

Not applicable, as there is no training set for this type of device.

Summary

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NOV 1 8 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.

The assigned 510(k) number is: _ KO 2 2 4 3

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 24, 2004

3.3 Device Proprietary Names:

VITROS Chemistry Products mALB Reagent Trade Names VITROS Chemistry Products Calibrator Kit 24 VITROS Chemistry Products mALB Performance Verifiers I and II Common Name Microalbumin assay

3.4 Classification Names

Classification Name: Albumin immunological test system (866.5040): Class: II (Special controls)

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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3.5 Predicate device

3.5.1 The VITROS Chemistry Products mALB Reagent and VITROS Chemistry Products Calibrator Kit 24 are substantially equivalent to the N Antiserum to Human Albumin assayed on the Dade Behring BN System.
3.5.2 The VITROS Chemistry Products mALB Performance Verifiers I and II 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 fiquid reagent products (in this case VITROS Chemistry Products mALB Reagent, VITROS Chemistry Products Calibrator Kit 24 and VITROS Chemistry Products mALB Performance Verifiers I and II), which are combined by the VITROS 5,1 FS Chemistry System to perform the VITROS mALB assay.
The VITROS Chemistry Products Thin Film range of dry products, which are dry, 3 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).
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.

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3.7 Device intended use

3.7.1 VITROS Chemistry Products mALB Reagent

For in vitro diagnostic use only. VITROS Chemistry Products mALB Reagent is used to quantitatively measure albumin concentration in human urine (mALB).

3.7.2 VITROS Chemistry Products Calibrator Kit 24

For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 24 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of albumin.

3.7.3 VITROS Chemistry Products mALB Performance Verifiers I and II

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

3.8 Comparison to predicate device

3.8.1 The VITROS Chemistry Products mALB Reagent and VITROS Chemistry Products Calibrator Kit 24 are substantially equivalent to the N Antiserum to Human Albumin assay on the Dade Behring BN ProSpec System (predicate device) which was cleared by the FDA (K972929) for IVD use.
The relationship between the VITROS mALB assay and the predicate device, determined by the Passing & Bablock linear regression is:

VITROS mALB assay = 0.93x + 0.03

with a correlation coefficient of 0.977,

where X is the result for the N Antiserum to Human Albumin assay on the Dade Behring BN ProSpec System.

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

Continued on next page

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Table 1	Table 1 lists the characteristics of the VITROS mALB assay (new device) and the Dade N
	Antiserum to Human Albumin assay (predicate device).

DeviceCharacteristic	VITROS mALB assay(New Device)	Dade Albumin assay(Predicate Device)
Intended Use	For in vitro diagnostic use only.VITROS Chemistry Products mALBReagent is used to quantitativelymeasure albumin concentration inhuman urine (mALB).	In vitro diagnostic reagents for thequantitative determination of albuminin human urine using the BNSystems.
Method	Immunoturbidimetry	Rate nephelometry
Reportable Range	0.6 to 19.0 mg/dL	0.0 to 34.0 mg/dL
Instrumentation	VITROS 5,1 FS Chemistry Systems	Dade Behring BN ProSpec Systems
Sample type	Urine	Urine
Reactive Ingredient	Goat anti-sera to human albumin	Rabbit antiserum to human albumin

3.8.2 The VITROS Chemistry Products mALB Performance Verifiers I and II are substantially equivalent to the VITROS Chemistry Products Performance Verifiers (predicate device) which were cleared by the FDA (K041720) for IVD use.

Table 2 lists the similarities and differences of the device characteristics between the VITROS Table 2 mALB 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 mALBPerformance Verifiers are assayedcontrols used to monitor theperformance of mALB 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.
Fluid Matrix	A base matrix of processed humanserum to which inorganic salt,buffers, protein, surfactant andpreservative 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 and High	Low and High

3.9 Conclusions

The data presented in the premarket notification provide a reasonable assurance that the VITROS mALB assay and the VITROS Chemistry Products mALB 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.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/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 symbol on the right side. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES U.S.A." is arranged in a circular fashion around the left side of the emblem.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

NOV 18 2004

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

Re: K042643

Trade/Device Name: VITROS Chemistry Products mALB Reagent VITROS Chemistry Products Calibrator Kit 24 VITROS Chemistry Products mALB Performance Verifiers I and II Regulation Number: 21 CFR 866.5040 Regulation Name: Albumin immunological test system Regulatory Class: Class II Product Code: DCF, JJX, JIT Dated: September 24, 2004 Received: September 27, 2004

Dear Ms. Phillips:

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 US. Div.

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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1.0 Indications for Use

510(k) Number (if known):	K042643
Device Name:	VITROS Chemistry Products mALB ReagentVITROS Chemistry Products Calibrator Kit 24VITROS Chemistry Products mALB Performance Verifiers I and II
Indications for Use:	For in vitro diagnostic use only.VITROS Chemistry Products mALB Reagent is used to quantitatively measure albumin concentration in human urine (mALB). Measurement of urinary albumin aids in the diagnosis of diabetic nephropathy, hypertension and cardiovascular disease.For in vitro diagnostic use.VITROS Chemistry Products Calibrator Kit 24 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of albumin in urine (mALB).For in vitro diagnostic use only.VITROS Chemistry Products mALB Performance Verifiers are assayed controls used to monitor the performance of mALB Reagent 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 IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

and the comments of the comments of the country of the country of the country of the country of the country of the country of the country of the country of the country of the

Carol Benam

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

210(K) Koy2663

Page 1 of 1

Regulation Number and Section

§ 866.5040 Albumin immunological test system.

(a)
Identification. An albumin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the albumin (a plasma protein) in serum and other body fluids. Measurement of albumin aids in the diagnosis of kidney and intestinal diseases.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.