The ALB test within the VITROS XT Chemistry Products ALB-TP Slides quantitatively measures albumin (ALB) concentration in serum and plasma using the VITROS XT 7600 Integrated System. Albumin measurements are used in the diagnosis and treatment of numerous diseases involving primarily the liver or kidneys.

Device Description

The new device, the VITROS XT Chemistry Products ALB-TP Slides is a single device that contains both an albumin test and a total protein test side by side separated by a plastic barrier sealed within a single slide frame. In this format, individual reactions occur and test results are generated for each analyte independently of the other analyte.

The ALB test is a multilayered, analytical element coated on a polyester support.

For the albumin measurement, a drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. When the fluid penetrates the reagent layer, the bromcresol green (BCG) dye diffuses to the spreading layer and binds to albumin in the sample. This binding results in a shift in wavelength of the reflectance maximum of the free dye. The color complex that forms is measured by reflectance spectrophotometry. The amount of albumin-bound dye is proportional to the concentration of albumin in the sample.

AI/ML Overview

The provided document describes the analytical performance of the VITROS XT Chemistry Products ALB-TP Slides for measuring albumin (ALB) concentration, and its substantial equivalence to a predicate device.

Here's an analysis of the acceptance criteria and study data:

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

The document does not explicitly state formal "acceptance criteria" for each performance metric in a dedicated table. Instead, performance is demonstrated through studies and compared against established clinical laboratory guidelines (CLSI protocols) or by showing strong correlation to the predicate device. For some metrics, an implied acceptance based on clinical relevance and comparison to the predicate can be inferred.

Here's a table summarizing the reported device performance, with inferred acceptance criteria based on the context of the studies:

Performance Metric	Inferred Acceptance Criteria (Contextual)	Reported Device Performance
Method Comparison	Strong correlation (e.g., correlation coefficient close to 1, slope close to 1, intercept close to 0) with the predicate device, following CLSI EP09-A3.	Correlation for ALB (g/dL):- N: 127- Slope: 1.00- Intercept: -0.03- Correlation Coeff.: 0.999- Test Range: 1.0 - 5.9- Measuring Range: 1.0 - 6.0
Matrix Comparison	Acceptable performance across different sample types (serum, plasma) compared to a reference serum type (red top plastic serum tube), with slopes near 1 and intercepts near 0, demonstrating equivalence.	Regression results vs. Serum Plastic:- Na Hep: Slope 0.96, Intercept 0.098- Li Hep: Slope 0.96, Intercept 0.088- PST: Slope 0.95, Intercept 0.107- SST: Slope 0.99, Intercept 0.033- Serum Glass: Slope 1.00, Intercept -0.007
Precision	Meets performance guidelines for precision (e.g., CLSI EP05-A3), demonstrating low variability (low SD and %CV) across different concentrations and over time (repeatability, within-day, within-lab). Specific criteria for SD/CV are not explicitly given but are generally expected to be within clinically acceptable limits.	Representative Lot Precision (g/dL Albumin):- Mean Conc. 1.6: Repeatability %CV 1.2, Within Lab %CV 1.4- Mean Conc. 2.7: Repeatability %CV 0.9, Within Lab %CV 1.2- Mean Conc. 3.4: Repeatability %CV 0.8, Within Lab %CV 1.1- Mean Conc. 4.1: Repeatability %CV 1.0, Within Lab %CV 1.3- Mean Conc. 4.4: Repeatability %CV 0.7, Within Lab %CV 0.9- Mean Conc. 5.2: Repeatability %CV 0.9, Within Lab %CV 1.2
Detection Limits (LoQ)	LoQ determined based on pre-defined Total Error (TE) goals, with a specific goal of ≤ 0.2 g/dL.	ALB (g/dL):- LOB: 0.24- LOD: 0.27- LOQ: 0.60- Claimed LOQ: 1.0 (This implies the device achieves a tighter LoQ than the claimed range allows)
Linearity	Supports the claimed measuring range (1.0 - 6.0 g/dL), demonstrated by a linear response across a wider range (e.g., 0.5 - 7.1 g/dL) with a high correlation (R close to 1) and appropriate slope/intercept. Follows CLSI EP06-A.	ALB:- Measuring Range: 1.0 - 6.0 g/dL- Linear Range: 0.5 - 7.1 g/dL- Least Squares Regression: y = 1.01x - 0.19 with R = 1.00
Specificity (Interference)	Bias < 0.24 g/dL at ~3.6 g/dL albumin and bias < 0.30 g/dL at ~4.5 g/dL albumin for non-interfering substances. Known interferents are identified and qualified. Follows CLSI EP07-A3 and EP37.	*Known Interferences (Bias):**- Dextran 40: 6 g/dL (3.8 g/dL ALB) -> -0.38; 4 g/dL (4.8 g/dL ALB) -> -0.58- Hemoglobin: 300 mg/dL (3.8 g/dL ALB) -> 0.32; 200 mg/dL (4.6 g/dL ALB) -> 0.3747 test substances found not to interfere (bias < 0.24 g/dL or < 0.30 g/dL).

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

Test Set Sample Sizes:
- Method Comparison: 127 patient samples.
- Matrix Comparison: Not explicitly stated as a number of unique patient samples, but various collection devices (serum: glass red top, plastic red top, SST; plasma: Na-heparin, Li-heparin, PST) were evaluated. The comparison used two replicates for the reference serum and two replicates for each feature tube.
- Precision: Patient pools and quality control materials. "80 observations (2 replicates per run, 2 runs per day over 20 days)" were used for the precision study, which implies that a smaller number of initial patient pools were tested multiple times.
- Linearity: A series of seventeen proportionally related admixtures of low and high test fluids were tested in quadruplicate.
- Specificity: Not explicitly stated as a number of unique patient samples; it likely used spiked samples or patient samples with known levels of interferents.
Data Provenance: The document does not specify the country of origin of the data or whether the data was retrospective or prospective. It refers to "patient samples" and "patient pools" but provides no further details on their source.

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

Not applicable. This is an in vitro diagnostic (IVD) device for quantitative measurement of albumin. "Ground truth" is established by the analytical method itself (measurement against a reference standard or validated method) rather than by expert consensus on qualitative interpretation of images or clinical findings. The predicate device (VITROS Chemistry Products ALB Slides) serves as the reference for method comparison.

4. Adjudication method for the test set

Not applicable. As this is an IVD device measuring a quantitative analyte, there is no subjective interpretation requiring an adjudication process for a "test set" in the way it would be applied to, for example, image-based diagnostic systems. The performance is assessed by comparing quantitative results against reference methods or established analytical performance criteria.

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 quantitative measurement of a biochemical analyte. It does not involve human readers interpreting images or data, nor does it involve AI assistance for such interpretation.

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

Yes, in essence, the performance studies described are for the standalone device (VITROS XT Chemistry Products ALB-TP Slides on the VITROS XT 7600 Integrated System) measuring albumin concentration. The device operates as a laboratory instrument without direct human-in-the-loop interpretation of the measurement itself. Human involvement is in operating the instrument and interpreting the quantitative result in a clinical context, but the device's analytical performance (accuracy, precision, linearity, etc.) is assessed independently.

7. The type of ground truth used

The "ground truth" for the performance studies is primarily established by:

Comparison to a legally marketed predicate device: The VITROS Chemistry Products ALB Slides (K023875) on the VITROS 5600 Integrated System served as the reference for the method comparison study.
Reference standards and established analytical methods: Precision, linearity, and detection limit studies rely on the inherent accuracy of the measurement procedure itself against known concentrations (e.g., patient pools, quality control materials, spiked samples, or reference materials).
Clinical Laboratory Standards Institute (CLSI) protocols: The studies specifically cite adherence to CLSI EP09-A3 (Method Comparison), EP05-A3 (Precision), EP17-A2 (Detection Limits), EP06-A (Linearity), EP07-A3, and EP37 (Interference), which are widely accepted guidelines for validating IVD performance.

8. The sample size for the training set

Not applicable. This is not an AI/Machine Learning device that requires a "training set" in the conventional sense. It is a traditional in vitro diagnostic chemical assay. Its development involves chemical and engineering principles, not statistical learning from a data 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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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

June 7, 2019

Ortho-Clinical Diagnostics, Inc. Darlene Phillips Manager, Regulatory Affairs 100 Indigo Creek Drive Rochester, NY 14626

Re: K191316

Trade/Device Name: VITROS XT Chemistry Products ALB-TP Slides Regulation Number: 21 CFR 862.1035 Regulation Name: Albumin test system Regulatory Class: Class II Product Code: CIX Dated: May 14, 2019 Received: May 15, 2019

Dear Darlene 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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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

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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Kellie B. Kelm, Ph.D. Acting Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K191316

Device Name VITROS XT Chemistry Products ALB-TP Slides

Indications for Use (Describe) Rx Only

For in vitro diagnostic use only

Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)

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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: K191316

Submitter's Information

Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, New York 14626-5101 Phone: (585) 453-4253 Fax: (585) 453-3113

Contact Person:

Darlene J Phillips, RAC Manager, Regulatory Affairs

Date of Preparation: May 14, 2019 Revised:

Device Proprietary Name(s):

VITROS XT Chemistry Products ALB-TP Slides

Common Names:

Albumin assay

Classification Names

Test	ProductCode	Class	Regulation Section	Panel
ALB	CIX	Class II	21 CFR 862.1035 Albumin test system	ClinicalChemistry(75)

Predicate Device(s)

Predicate Devices	FDA 510(k) Number
VITROS Chemistry Products ALB Slides	K023875

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Intended Use Statement(s) VITROS XT Chemistry Products ALB-TP Slides

Rx Only For in vitro diagnostic use only

Device Description

The ALB test is a multilayered, analytical element coated on a polyester support.

Comparison to Predicate Devices

The following tables show similarities and differences between the new and predicate devices.

Summary of the technological characteristics of the device compared to the predicatedevice
DeviceCharacteristic	New DeviceVITROS XT ALB-TP Slide[K191316](New)	Predícate DeviceVITROS ALB Slide [K023875](Current)

Intended Use	No changeFor in vitro diagnostic use only.The ALB test within the VITROSXT ALB-TP Chemistry ProductsSlides measures albumin (ALB)concentration in serum andplasma.	For in vitro diagnostic use only.VITROS Chemistry Products ALBSlides quantitatively measurealbumin (ALB) concentration inserum and plasma.
DeviceDescription	No Change	Multilayered, analytical elementcoated on a polyester support
Basic Principle	No Change	Colorimetric

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Summary of the technological characteristics of the device compared to the predicatedevice
DeviceCharacteristic	New DeviceVITROS XT ALB-TP Slide[K191316](New)	Predicate DeviceVITROS ALB Slide [K023875](Current)
Incubation timeand temperature	No Change	Approximately 2.5 minutes37°C (98.6° F)
Sample type	No Change	Serum and plasma
Amount of SlideReactiveIngredients percm² (test)	The composition of the analyticalelement of each test within theVITROS XT Slide will remainthe same as that used in eachpredicate device	Bromcresol green dye 104 µg.
Assay Range	No Change	1.0 - 6.0 g/dL
Calibrators	No Change	VITROS Chemistry ProductsCalibrator Kit 4
Controls	No Change	VITROS Chemistry ProductsPerformance Verifier I and II
Differences
Instrumentation	VITROS XT 7600 IntegratedSystem	VITROS 250/350, 5,1 FS and 4600Chemistry SystemsVITROS 5600 and XT 7600Integrated Systems
Sample volume	4.2 µL	5.5 µL

Non-Clinical Testing Analytical Performance

Method Comparison

Method Comparison testing followed CLSI Protocol EP09-A3, Measurement Procedure Comparison and Bias Estimation Using Patient Samples. Serum samples were evaluated on the VITROS XT Chemistry Products ALB-TP Slides using the VITROS XT 7600 Integrated System and on VITROS Chemistry Products ALB Slides using the VITROS 5600 Integrated System. The correlation between the predicate and the ALB test within the VITROS XT ALB-TP Slides on the VITROS XT 7600 Integrated System is summarized below.

Ordinary Deming regression was performed to determine the correlation for the ALB test within the VITROS XT ALB-TP Slides.

Summary of Method Comparison Regression Analysis Data
Test	N	Slope	Intercept	Corr. Coeff.	Test Range	Measuring range
ALB (g/dL)	127	1.00	-0.03	0.999	1.0 - 5.9	1.0 - 6.0

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Matrix comparison:

To demonstrate equivalence between serum and plasma samples, serum (glass red top, plastic red top and SST) and plasma (Na-heparin, Li-heparin, and PST) specimen collection tubes were evaluated to verify acceptable performance.

All collection devices were compared to the red top plastic serum tube using Weighted Deming regression. The regression assessments use the mean of the red top plastic serum tube (two replicates) versus the replicates of the feature tube (two replicates).

Sample Type	Slope	Intercept
Na Hep vs. Serum Plastic	0.96	0.098
Li Hep vs. Serum Plastic	0.96	0.088
PST vs. Serum Plastic	0.95	0.107
SST vs. Serum Plastic	0.99	0.033
Serum Glass vs. Serum Plastic	1.00	- 0.007

Precision

Precision was evaluated with patient pools and quality control materials following CLSI Protocol EP05-A3, Evaluation of Precision Performance of Quantitative Methods; Approved Guideline-Third Edition, using the VITROS XT Chemistry Products ALB-TP Slides on the VITROS XT 7600 Integrated System. The test included 80 observations (2 replicates per run, 2 runs per day over 20 days) using three lots of VITROS XT ALB-TP Slides. The ALB test long term precision analysis for a representative lot is summarized below.

The data presented are a representation of test performance and are provided as a guideline. Variables such as sample handling and storage, reagent handling and storage, laboratory environment, and system maintenance can affect reproducibility of test results.

Conventional Units (g/dL Albumin)
MeanConcentration	RepeatabilitySD*	%CV	Within DaySD**	%CV	Within LabSD***	%CV	No. ofObs.	No. ofDays
1.6	0.02	1.2	0.02	1.2	0.02	1.4	80	20
2.7	0.02	0.9	0.02	0.9	0.03	1.2	80	20
3.4	0.03	0.8	0.03	0.9	0.04	1.1	80	20
4.1	0.04	1.0	0.04	1.0	0.05	1.3	80	20
4.4	0.03	0.7	0.03	0.8	0.04	0.9	80	20
5.2	0.05	0.9	0.05	1.1	0.06	1.2	80	20

*Repeatability (formerly called within-run precision) was determined using two replicates per run.

** Within Day precision was determined using two runs per day with two replicates per run

***Within Lab precision was determined using a single lot of slides and a single calibration

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Detection Limits

Detection capability studies for the ALB test within the VITROS XT ALB-TP Slides were evaluated according to CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures.

LoQ determination was set on pre-defined Total Error (TE) goals based on the Westgard model. The Total Error goal used to accept the LoQ was ≤ 0.2 g/dL.

The results of this analysis are summarized below:

	ALB (g/dL)
LOB	0.24
LOD	0.27
LOQ	0.60
Claimed LOQ	1.0

Linearity

Linearity studies were performed according to CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approved Guideline (2003). VITROS XT ALB-TP Slides were tested on the VITROS XT 7600 Integrated System. A series of seventeen proportionally related admixtures of low and high test fluids were tested to verify linearity of the ALB test; each sample was tested in quadruplicate. The linearity study supports the claimed measuring range for the ALB test within the VITROS XT ALB-TP Slides.

Assay	Measuring Range	Linear Range
ALB	1.0 - 6.0 g/dL	0.5 - 7.1 g/dL

A least squares regression was performed on the data collected, y = 1.01x-0.19 with R = 1.00.

Serum and plasma samples with values greater than the ALB test measuring range may be diluted with 10 parts sample and 1 part diluent. Reagent-grade water and isotonic saline are acceptable diluents for the ALB test within the VITROS XT Chemistry Products ALB-TP Slides.

Expected Values

The expected values of the ALB test within the VITROS XT ALB-TP Slides are not changed from that of the predicate assay. Each laboratory should confirm the validity of these intervals for the population it serves.

ALB Reference Interval "

ALB Test Expected Values
3.5–5.0 g/dL

Each laboratory should confirm the validity of these intervals for the population it serves.

4 Peters T. All about Albumin San Diego: Academic Press; 256; 1996.

Specificity

The ALB test within the VITROS XT Chemistry Products ALB-TP Slide was screened for interfering substances following CLSI document EP07-A3, Interference Testing in Clinical

Ortho-Clinical Diagnostics, Inc.

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Chemistry. The supplemental tables in CLSI document EP37 were referenced for recommended testing concentrations for analytes and endogenous substances that may interfere in clinical chemistry measurement procedures.

Point estimates of the effects of potential interferents on the ALB test within the VITROS XT ALB-TP Slides were made using the paired difference method. Dose-response analysis was conducted to characterize the degree of interference for each substance that exceeded the acceptance criterion in the initial screening test, and expected bias was reported at the lowest test level which did not meet acceptance criteria for bias as shown in the product claims.

Two (2) substances were found to interfere with the ALB test in VITROS XT Chemistry Products ALB-TP Slides. The substances listed in the table, when tested at the concentrations indicated, caused the bias shown. The bias is an estimate of the maximum bias observed.

It is possible that other interfering substances may be encountered. These results are representative; however, your results may differ somewhat due to test-to-test variation. The degree of interference at concentrations other than those listed might not be predictable.

Known Interferences ALB test
Interferent	InterferentConcentration(Conv. Units)	AlbuminConcentration(g/dL)	Bias*(g/dL)
Dextran 40	6 g/dL	3.8	-0.38
Dextran 40	4 g/dL	4.8	-0.58
Hemoglobin	300 mg/dL	3.8	0.32
Hemoglobin	200 mg/dL	4.6	0.37

采 The bias is an estimate of the maximum bias observed

Forty-seven (47) test substances, when tested at the concentrations indicated, were found not to interfere with the ALB test within VITROS XT ALB-TP Slides, bias < 0.24 g/dL at approximately 3.6 g/dL albumin and bias < 0.30 g/dL at approximately 4.5 g/dL albumin.

Other Limitations

Certain drugs and clinical conditions are known to alter albumin concentrations in vivo. For additional information, refer to the published summaries.

Young DS. Effects of Drugs on Clinical Laboratory Tests. ed. 4. Washington D.C.: AACC Press; 1995.

Friedman RB. Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C .: AACC Press; 1990.

Conclusion

The conclusions drawn from the nonclinical tests (discussed above) demonstrate the ALB test within the VITROS XT Chemistry Products ALB-TP Slides for use on the VITROS XT 7600 Integrated System is as safe, effective, and performs as well as the predicate device. The information submitted in the premarket notification is complete and supports a substantial equivalence decision.

Regulation Number and Section

§ 862.1035 Albumin test system.

(a)
Identification. An albumin test system is a device intended to measure the albumin concentration in serum and plasma. Albumin measurements are used in the diagnosis and treatment of numerous diseases involving primarily the liver or kidneys.(b)
Classification. Class II.