The cassette COBAS Integra Tina-quant Transferrin ver.2 contains an in vitro diagnostic reagent system intended for use on COBAS Integra systems for the quantitative immunological determination of human transferrin in serum and plasma. 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 and plasma. Measurement of transferrin levels aids in the diagnosis of malnutrition, acute inflammation, infection, and red blood cell disorders, such as iron deficiency anemia.

Device Description

The Tina-quant Transferrin ver.2 Assay is based on the principle of immunological agglutination. Human transferrin forms a precipitate with a specific antiserum which is determined turbidimetrically at 340 nm.

AI/ML Overview

Here's an analysis of the provided information regarding the Tina-quant Transferrin ver.2 device, structured to address your specific points:

1. Table of Acceptance Criteria and Reported Device Performance

The FDA 510(k) summary for Tina-quant Transferrin ver.2 establishes substantial equivalence to a predicate device (COBAS Integra Tina-quant Transferrin). The "acceptance criteria" can be inferred from the performance characteristics of the predicate device, against which the new device is compared. The reported performance of the new device demonstrates it meets or surpasses the predicate's performance.

Feature	Acceptance Criteria (Predicate Device Performance)	Reported Device Performance (Tina-quant Transferrin ver.2)
Intended Use	Quantitative immunological determination of human transferrin in serum (and other body fluids, for predicate)	Quantitative immunological determination of human transferrin in serum and plasma
Indication for Use	Aids in diagnosis of malnutrition, acute inflammation, infection, and red blood cell disorders (e.g., iron deficiency anemia)	Aids in diagnosis of malnutrition, acute inflammation, infection, and red blood cell disorders (e.g., iron deficiency anemia)
Assay Protocol	Immunoturbidimetric assay	Immunoturbidimetric assay
Instrument	COBAS Integra Clinical Chemistry Analyzers	COBAS Integra Clinical Chemistry Analyzers
Traceability/Standardization	Standardized against CRM 470 (RPPHS)	Standardized against CRM 470 (RPPHS)
Sample Type	Human serum (and plasma, other body fluids for predicate)	Human serum and plasma
Measuring Range	80 – 1280 mg/dL (or 0.8 - 12.8 g/L)	1.3 - 520 mg/dL (or 0.013 - 5.2 g/L)
Intra-assay Precision (% CV)	1.5% at 1.10 g/L, 0.83% at 3.32 g/L	0.86% at 1.35 g/L, 0.77% at 3.36 g/L
Between Day Precision (% CV)	1.6% at 1.10 g/L, 0.97% at 3.32 g/L	1.8% at 1.32 g/L, 1.9% at 3.70 g/L
Analytical Sensitivity (LDL)	0.58 g/L	0.013 g/L
Method Comparison (Correlation)	y = 1.06x + 0.01 g/L, r = 0.958 (vs. nephelometric determination)	y = 1.06x + 0.03, r = 0.996 (vs. predicate device)
Limitations (Interference)	Icterus: No significant interference; Hemolysis: No significant interference; Lipemia: No significant interference; Rheumatoid factors: No significant interference	Icterus: No significant interference; Hemolysis: No significant interference; Lipemia: No significant interference up to 500 mg/dL; Rheumatoid factors: No significant interference; Gammopathy (IgM): Flagged "High Act", correctable by post-dilution.
Calibration Frequency	After reagent lot change	After reagent lot change
Expected Values	2.0 – 3.6 g/L (200 – 360 mg/dL)	2.0 – 3.6 g/L (200 – 360 mg/dL)

Summary of how the device meets acceptance criteria:

The Tina-quant Transferrin ver.2 demonstrates substantial equivalence to the predicate device. It maintains the same intended use, indications for use, assay protocol, and instrument compatibility. Its precision (intra-assay and between-day) is comparable to, and in some cases better than, the predicate. A notable improvement is the significantly lower analytical sensitivity (LDL), indicating better detection of low transferrin levels. The method comparison shows a strong correlation with the predicate device, further supporting its equivalence. The limitations regarding common interferences are similar or explicitly managed (e.g., Gammopathy for the new device).

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

The provided document refers to the data as "performance characteristics" and "method comparison."

Method Comparison: The equation y = 1.06x + 0.03 with r = 0.996 implies a regression analysis was performed, comparing the new device (Y) to the predicate device (X). However, the specific sample size (number of patient samples) used for this comparison is not explicitly stated.
Precision (Intra-assay and Between-day): These studies typically involve multiple replicates of control or patient samples. The exact number of samples or replicates is not specified.
Limitations (Interference): These studies typically involve spiking known interferents into samples. The number of samples used for these interference studies is not specified.
Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective. It is generally assumed that studies for FDA submissions are conducted under controlled conditions, often in a prospective manner, but details are absent here.

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

This type of information (number and qualifications of experts for ground truth) is typically relevant for diagnostic imaging or subjective biomarker interpretation. For an immunological quantitative assay like transferrin, the "ground truth" is established by a reference method or a validated predicate device.

For Method Comparison: The predicate device itself (COBAS Integra Transferrin) serves as the reference for comparison. The predicate device's performance was, in turn, previously established against a "nephelometric determination" (another analytical method) for its own method comparison, with an r = 0.958.
For Standardization: Both devices are standardized against the CRM 470 reference preparation, which corresponds to RPPHS (Reference Preparation Protein in Human Serum). This is a primary standard, not derived from expert consensus.

Therefore, the concept of "experts establishing ground truth" as you might see in imaging (e.g., radiologists) is not applicable in the same way for this type of quantitative biochemical assay. The ground truth is the analytically measured concentration against recognized standards.

4. Adjudication Method for the Test Set

Again, for a quantitative biochemical assay, an "adjudication method" (like 2+1 or 3+1 for clinical diagnoses) is not typically employed. The results are numerical values output by the instrument. Any discrepancies between the new device and the predicate are analyzed statistically (e.g., correlation, bias), not through clinical adjudication in the human sense.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

No, an MRMC comparative effectiveness study was not done for this device. This type of study investigates how human readers (e.g., clinicians, radiologists) perform with and without AI assistance on various cases. The Tina-quant Transferrin ver.2 is a fully automated in-vitro diagnostic reagent system that provides a quantitative measurement; it does not involve human interpretation in a diagnostic workflow that could be "assisted" by AI in the MRMC sense.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

The device is essentially a standalone system in that it provides a direct quantitative measurement. The "performance characteristics" (precision, analytical sensitivity, measuring range, interference) represent the performance of the algorithm/reagent system without human intervention influencing the measurement itself. The results are then read and interpreted by a human user, but the measurement is algorithmic. So, in essence, its core performance evaluation is "standalone."

7. The Type of Ground Truth Used

The ground truth for evaluating the Tina-quant Transferrin ver.2 is primarily established through:

Reference Standards: Standardization against the CRM 470 (RPPHS) reference preparation.
Comparison to a Validated Predicate Device: The performance of the new device is directly compared to an already legally marketed and accepted device (COBAS Integra Tina-quant Transferrin). This predicate device itself had its performance validated against other established analytical methods (e.g., nephelometric determination).
Analytical Measurement: The inherent analytical capabilities of the immunoturbidimetric assay technology to accurately quantify transferrin concentration.

8. The Sample Size for the Training Set

This document describes a premarket submission for a medical device that is a reagent system for a laboratory assay. It is not an AI/ML-based device in the common sense that would involve a "training set" for model development. The parameters and performance of such a device are determined through chemical and mechanical engineering, and extensive analytical validation. Therefore, the concept of a "training set sample size" as used for AI/ML algorithms does not apply to this specific device.

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

As explained in point 8, the concept of a "training set" and associated "ground truth" (in the context of AI/ML) is not applicable to this device. For traditional in-vitro diagnostic assays, the "ground truth" for calibrating the system and establishing its performance involves using precisely characterized reference materials (like CRM 470) and known concentrations of analytes, which are then used to set the instrument's calibration curve and validate its analytical accuracy across its measuring range.

Summary

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510(k) Summary	K012393
Introduction	According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.
Submitter name, address, contact	Roche Diagnostics Corporation9115 Hague RoadIndianapolis, IN 46250(317) 521 - 3831Contact Person: Sherri L. CoenenDate Prepared: July 25, 2001
Device Name	Proprietary name: Tina-quant Transferrin ver.2Common name: TransferrinClassification name: Transferrin immunological test system
Device Description	The Tina-quant Transferrin ver.2 Assay is based on the principle of immunological agglutination. Human transferrin forms a precipitate with a specific antiserum which is determined turbidimetrically at 340 nm.
Intended use	The cassette COBAS Integra Tina-quant Transferrin ver.2 contains an in vitro diagnostic reagent system intended for use on COBAS Integra systems for the quantitative immunological determination of human transferrin in serum.
Indications for Use	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 and plasma. Measurement of transferrin levels aids in the diagnosis of malnutrition, acute inflammation, infection, and red blood cell disorders, such as iron deficiency anemia.

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510(k) Summary, Continued

Substantial Equivalence The Tina-quant Transferrin ver.2 is substantially equivalent to other devices legally marketed in the United States. We claim equivalence to the COBAS Integra Tina-quant Transferrin (K951595).

Substantial equivalence similarities

The following table compares the Tina-quant Transferrin ver.2 Assay with the predicate device.

Feature	Tina-quant Transferrinver.2	Transferrin
Intended Use	The cassette COBASIntegra Tina-quantTrasferrin ver.2 (TRSF2)contains an in vitrodiagnostic reagent systemintended for use onCOBAS Integra systemsfor the quantitativeimmunologicaldetermination of humantransferrin in serum.	The cassette COBASIntegra Transferrin(TRSF) contains an invitro diagnostic reagentsystem intended for useon COBAS Integrasystems for thequantitativeimmunologicaldetermination of humantransferrin in serum.
Indication for Use	A transferrinimmunological test systemis a device that consists ofthe reagents used tomeasure byimmunologicaltechniques the transferrin(an iron-binding andtransporting serum protein)in serum and plasma.Measurement oftransferrin levels aids inthe diagnosis ofmalnutrition,acuteinflammation, infection,and red blood celldisorders,such as irondeficiency anemia.	A transferrinimmunological testsystem is a device thatconsists of the reagentsused to measure byimmunochemicaltechniques thetransferrin (an iron-binding andtransporting serumprotein) in serum,plasma, and other bodyfluids. Measurement oftransferrin levels aids inthe diagnosis ofmalnutrition, acuteinflammation, infection,and red blood celldisorders, such as irondeficiency anemia.

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510(k) Summary, Continued

Substantial equivalence similarities

The following table compares the Tina-quant Transferrin ver.2 Assay with the predicate device.

Feature	Tina-quant Transferrinver.2	Transferrin
Assay Protocol	Immunoturbidimetricassay	Immunoturbidimetricassay
Instrument	COBAS Integra ClinicalChemistry Analyzers	COBAS IntegraClinical ChemistryAnalyzers
Traceability /Standardization	Standardized against thereference preparationCRM 470, correspondingto RPPHS (ReferencePreparation Protein inHuman Serum)	Standardized againstthe referencepreparation CRM 470,corresponding toRPPHS (ReferencePreparation Protein inHuman Serum)

Substantial equivalence differences

The following table compares the Tina-quant Transferrin ver.2 Assay with the predicate device.

Feature	Tina-quantTransferrin ver.2	Transferrin
Sample Type	Human serum andplasma	Human serum
Measuring Range	1.3 - 520 mg/dL	80 – 1280 mg/dL

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Substantial equivalence – performance characteristics, cont.

The performance characteristics of the Tina-quant Transferrin ver.2 Assay and the predicate device are compared in the table below. .

Feature	Tina-quant Transferrinver.2	Transferrin
Intra-assayprecision (% CV)	0.86% at 1.35 g/L0.77% at 3.36 g/L	1.5% at 1.10 g/L0.83% at 3.32 g/L
Between DayPrecision (% CV)	1.8% at 1.32 g/L1.9% at 3.70 g/L	1.6% at 1.10 g/L0.97% at 3.32 g/L
Limitations	Icterus: No significant interference Hemolysis: No significant interference Lipemia: No significant interference up to an Intralipid level of 500 mg/dL Rheumatoid factors: No significant interference Interference of Gammopathy type IgM (Waldenstroem) sera is recognized by the “High Activity” check. In case samples are flagged “High Act”, correct results can be obtained after post-dilution.	Icterus: No significant interference Hemolysis: No significant Lipemia: No significant interference Rheumatoid factors: No significant interference
Analyticalsensitivity (LDL)	0.013 g/L	0.58 g/L
Methodcomparison	Tina-quant Transferrin ver.2 (Y) / COBAS Integra Transferrin (X)$y = 1.06x + 0.03$ $r = 0.996$	Transferrin (Y) / nephelometric determination (X)$y = 1.06x + 0.01 g/L$ $r = 0.958$

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100000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000

and the comments of the country of

Substantial equivalence performance characteristics, cont.

. ·

The performance characteristics of the Tina-quant Transferrin The porcennance the predicate device are compared in the table below.

11:11:1

Feature	Tina-quant Transferrinver.2	Transferrin
Calibrationfrequency	• after reagent lot change	• after reagent lot change
Expected values	2.0 – 3.6 g/l (200 – 360 mg/dl)	2.0 – 3.6 g/l (200 – 360 mg/dl)

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo consists of a circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, with flowing lines representing hair or clothing.

SEP 1 9 2001

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Sherri L. Coenen Regulatory Submissions, Centralized Diagnostics Roche Diagnostics Corporation 9115 Hague Road P.O. Box 50457 Indianapolis, Indiana 46250-0457

K012393 Re:

Trade Name: Roche Diagnostics Tina-quant® Transferrin ver.2 Regulatory Class: 21 CFR § 866.5880 Regulatory Class: II Product Code: DDG Dated: July 25, 2001 Received: July 27, 2001

Dear Ms. Coenen:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Page 2

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

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and If you desire specific darices), please contact the Office of Compliance at additionally 607.10 for in This angliestions on the promotion and advertising of your device, (201) 59 rttact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small mormation on your responsibility on sumer Assistance at its toll-free number (800) 638-2041 or 1101) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Putman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use Statement

Roche Diagnostics Corp.

510(k) Number (if known): K012393

Device Name: Tina-quant Transferrin ver.2

Indications For Use:

Prescription Use V (Per 21 CFR 801.109)

Over-The-Counter Use_

(Optional Format 1-2-96)

Soumen S. Altare

Ivision Sian-Off Division of Clinical Laboratory Devices

510(k) Number K012393

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).