Immunoturbidometric assay for the in vitro quantitative determination of transferrin in human serum and plasma on automated clinical chemistry analyzers. 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. Anti-transferrin antibodies react with the antigen in the sample to form an antigen/antibody complex. Following agglutination, this is measured turbidimetrically. Addition of PEG allows the reaction to progress rapidly to the end point and increases sensitivity.

AI/ML Overview

This is a submission for a medical device (specifically, an in-vitro diagnostic assay) rather than a software-as-a-medical-device (SaMD) or AI/ML device. Therefore, many of the requested elements (like "experts used to establish ground truth," "adjudication method," "MRMC study," and "training set") are not applicable in the context of this traditional assay. The performance is evaluated through analytical studies, not clinical studies involving human interpretation of AI outputs.

Here's the information that can be extracted from the provided text, adapted for an in-vitro diagnostic assay:

Acceptance Criteria and Device Performance

The acceptance criteria are implicitly defined by demonstrating equivalent or improved performance characteristics compared to the predicate device.

Feature	Acceptance Criteria (Predicate Device Performance)	Reported Device Performance (Tina-quant Transferrin ver.2)
Intended Use	Immunoturbidometric assay for the in vitro quantitative determination of transferrin in human serum and plasma on automated clinical chemistry analyzers.	Equivalent: Immunoturbidometric assay for the in vitro quantitative determination of transferrin in human serum and plasma on automated clinical chemistry analyzers.
Indication for Use	Measurement of transferrin levels aids in the diagnosis of malnutrition, acute inflammation, infection, and red blood cell disorders, such as iron deficiency anemia.	Equivalent: Measurement of transferrin levels aids in the diagnosis of malnutrition, acute inflammation, infection, and red blood cell disorders, such as iron deficiency anemia.
Measuring Range (Roche/Hitachi 704/902)	80 - 500 mg/dl	Improved: 0.02 - 5.00 g/l (1 - 500 mg/dl)
Measuring Range (Roche/Hitachi 717/747)	80 - 500 mg/dl (Extended with rerun: 80 - 1000 mg/dl)	Improved: 0.02 - 5.00 g/l (1 - 500 mg/dl) (Extended with rerun: 0.02 - 7.50 g/l (1-750 mg/dl)). Note: The ver.2 device states "Maximum reportable range is dependent on the highest standard concentration" for the extended range, which is similar wording to the predicate, but the values are lower and potentially offer wider usability.
Measuring Range (Roche/Hitachi 904/911/912/917/Modular P)	15 - 500 mg/dl	Improved: 0.007 - 5.20 g/l (0.7 - 520 mg/dl) (Extended with rerun: 0.007 - 7.80 g/l (0.7 - 780 mg/dl)). Note: The ver.2 device states "Maximum reportable range is dependent on the highest standard concentration" for the extended range, which is similar wording to the predicate, but the values are lower and potentially offer wider usability.
Intra-assay precision (% CV) - Human Sera	0.8% at 169 mg/dl	Comparable/Improved: 1.0% at 1.36 g/l (136 mg/dl), 2.7% at 3.59 g/l (359 mg/dl). Precision is concentration-dependent; the values are generally comparable across similar concentrations but the ver.2 provides more data points.
Intra-assay precision (% CV) - Controls	0.8% at 217 mg/dl, 0.8% at 403 mg/dl	Comparable/Improved: 2.1% at 2.90 g/l (290 mg/dl), 1.0% at 4.31 g/l (431 mg/dl). Similar for controls, concentration-dependent, providing comparable performance across ranges.
Between Day Precision (% CV) - Human Sera	3.0% at 169 mg/dl	Improved: 0.0% at 1.60 g/l (160 mg/dl), 1.4% at 3.38 g/l (338 mg/dl). Shows better or comparable between-day precision at different concentrations to the predicate.
Between Day Precision (% CV) - Controls	1.4% at 217 mg/dl, 1.5% at 403 mg/dl	Comparable/Improved: 1.7% at 2.88 g/l (288 mg/dl), 1.4% at 4.35 g/l (435 mg/dl). Similar between-day precision for controls.
Icterus Interference	No significant interference from bilirubin up to an I index of 60	Equivalent: No significant interference with up to an I index of 60
Hemolysis Interference	No significant interference from hemoglobin up to an H index of 1000	Equivalent: No significant interference up to an H index of 1000
Lipemia Interference	No significant interference from lipemia up to an L index of 600	Comparable: No significant interference up to an L index of 500 (slight reduction compared to predicate's L index of 600)
Rheumatoid Factors Interference	< 350 IU/ml do not interfere	Improved: < 1200 IU/ml do not interfere
Analytical sensitivity (LDL)	15 mg/dl	Improved: Roche/Hitachi 704/717/747/902: 0.02 g/l (1 mg/dl); Roche/Hitachi 904/911/912/917/Modular P: 0.007 g/l (0.7 mg/dl)
Method Comparison	Tina-quant Transferrin on Roche/Hitachi 917 (Y)/Tina-quant Transferrin on Roche/Hitachi 911 (X): Passing/Bablock: $y = 1.141 + 0.989x$, $r = 0.998$	Demonstrated Concordance: Tina-quant Transferrin ver.2 (Y) / Tina-quant Transferrin (X): Passing/Bablock: $y = 0.01 + 0.97x$, $r = 0.990$. This shows strong correlation and agreement between the new device and the predicate.
Expected values	IFCC/CRM 470: 200 – 360 mg/dl; Roche: 200 – 400 mg/dl	Comparable: 2.0 – 3.6 g/l (200 – 360 mg/dl)

Study Details:

Sample size used for the test set and the data provenance:
- The document does not explicitly state the sample sizes for the precision studies (intra-assay and between-day) or for the interference studies. These studies typically use a small number of samples (e.g., specific human sera pools, controls) tested multiple times.
- For the method comparison study, the "Passing/Bablock" regression is reported with a correlation coefficient ($r = 0.990$), indicating a substantial number of paired measurements were likely performed, but the exact number of samples is not provided.
- Provenance: The samples described as "Human sera" and "Controls" would typically be obtained from a variety of sources to represent different clinical ranges. The document does not specify the country of origin or whether the data was retrospective or prospective, but assay development and validation studies are generally prospective.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This is an in-vitro diagnostic assay, not an AI/ML device that generates interpretations requiring expert review. The "ground truth" for an assay like this would be established by the analytical method itself, calibrated against a recognized standard (CRM 470 in this case). No human experts are used for establishing the "ground truth" in the sense of image interpretation or diagnosis.
Adjudication method for the test set:
- Not applicable. This is an analytical assay.
If a multi-reader multi-case (MRMC) comparative effectiveness study was done:
- Not applicable. This is an analytical assay, not an AI-assisted diagnostic tool.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- This is an in-vitro diagnostic assay, meaning it is designed to operate on its own to measure the concentration of transferrin in a sample. The device's performance characteristics (precision, analytical sensitivity, interference, measuring range) are all standalone analytical performance metrics.
The type of ground truth used:
- Reference Standard Calibration: The assay is "Standardized against the reference preparation CRM 470, corresponding to RPPHS (Reference Preparation Protein in Human Serum)". This internationally recognized reference material serves as the "ground truth" for accurate quantification of transferrin. The method comparison also uses the predicate device as a comparative standard.
The sample size for the training set:
- Not applicable in the context of a traditional in-vitro diagnostic assay. These assays are developed through chemical and immunological principles, not through machine learning training sets.
How the ground truth for the training set was established:
- Not applicable. No "training set" with associated "ground truth" in the AI/ML sense is used for this type of device. The assay's performance is established through rigorous analytical validation against known reference materials and comparator methods.

Summary

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510(k) Summary

SEP 1 9 2001

According to the requirements of 21 CFR 807.92, the following information Introduction provides sufficient detail to understand the basis for a determination of substantial equivalence. Submitter Roche Diagnostics Corporation name, address, 9115 Hague Road contact Indianapolis, IN 46250 (317) 576 - 3544 Contact Person: Sherri L. Coenen Date Prepared: July 26, 2001 Device Name Proprietary name: Tina-quant Transferrin ver.2 Common name: Transferrin Classification name: Transferrin immunological test system The Tina-quant Transferrin ver.2 Assay is based on the principle of Device Description immunological agglutination. Anti-transferrin antibodies react with the antigen in the sample to form an antigen/antibody complex. Following agglutination, this is measured turbidimetrically. Addition of PEG allows the

reaction to progress rapidly to the end point and increases sensitivity.

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Substantial equivalence similarities

: .

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

Feature	Tina-quant Transferrinver.2	Tina-quant Transferrin
Intended Use	Immunoturbidometricassay for the in vitroquantitative determinationof transferrin in humanserum and plasma onautomated clinicalchemistry analyzers.	Immunoturbidometricassay for the in vitroquantitative determinationof transferrin in humanserum and plasma onautomated clinicalchemistry analyzers.
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 test systemis a device that consists ofthe reagents used tomeasure byimmunochemicaltechniques the transferrin(an iron-binding andtransporting serumprotein) in serum, plasma,and other body fluids.Measurement oftransferrin levels aids inthe diagnosis ofmalnutrition, acuteinflammation, infection,and red blood celldisorders, such as irondeficiency anemia.
Assay ProtocolInstrument	ImmunoturbidimetricRoche/Hitachi ClinicalChemistry Analyzers	ImmunoturbidimetricRoche/Hitachi ClinicalChemistry Analyzers
Sample Type	Human serum and plasma	Human serum and plasma
Traceability /Standardization	Standardized against thereference preparationCRM 470, correspondingto RPPHS (ReferencePreparation Protein inHuman Serum)	Standardized against thereference preparationCRM 470, correspondingto RPPHS (ReferencePreparation Protein inHuman Serum)
Feature	Tina-quant Transferrin ver.2	Tina-quant Transferrin
Antibody source	rabbit	goat
Measuring Range	Roche/Hitachi 704/9020.02 - 5.00 g/l(1 - 500 mg/dl)Maximum reportable range is dependent on the higheststandard concentration.	Roche/Hitachi 704/90280 - 500 mg/dlMaximum reportable range isdependent on the higheststandard concentration.
	Roche/Hitachi 717/7470.02 - 5.00 g/l(1 - 500 mg/dl)Extended measuringrange with rerun0.02 - 7.50 g/l(1 - 750 mg/dl)Maximum reportable rangeis dependent on the higheststandard concentration.	Roche/Hitachi717/747/91480 - 500 mg/dlExtended measuringrange with rerun80 - 1000 mg/dlMaximum reportable range isdependent on the higheststandard concentration.
	Roche/Hitachi904/911/912/917/Modular P0.007 - 5.20 g/l(0.7 - 520mg/dl)Extended measuringrange with rerun0.007 - 7.80 g/l(0.7 - 780mg/dl)Maximum reportable rangeis dependent on the higheststandard concentration	Roche/Hitachi904/911/912/917/Modular P15 - 500 mg/dlMaximum reportable range isdependent on the higheststandard concentration.

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Substantial equivalence differences

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

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Substantial equivalence – performance characteristics

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	Tina-quant Transferrin
Intra-assayprecision (%CV)	Human sera:1.0% at 1.36 g/l (136 mg/dl)	Human sera:0.8% at 169 mg/dl
	2.7% at 3.59 g/l (359 mg/dl)
	Controls:2.1% at 2.90 g/l (290 mg/dl)	Controls:0.8% at 217 mg/dl
	1.0% at 4.31 g/l (431 mg/dl)	0.8% at 403 mg/dl
Between DayPrecision (%CV)	Human sera:0.0% at 1.60 g/l (160 mg/dl)	Human sera:3.0% at 169 mg/dl
	1.4% at 3.38 g/l (338 mg/dl)
	Controls:1.7% at 2.88 g/l (288 mg/dl)	Controls:1.4% at 217 mg/dl
	1.4% at 4.35 g/l (435 mg/dl)	1.5% at 403 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	Tina-quant Transferrin
Limitations	Icterus: No significant interference with up to an I index of 60 Hemolysis: No significant interference up to an H index of 1000 Lipemia (Intralipid): No significant interference up to an L index of 500 Rheumatoid factors < 1200 IU/ml do not interfere Gammopathy type IgM sera (Waldenstroem's macroglobulinemia) interfere with the assay	Icterus: No significant interference from bilirubin up to an I index of 60 Hemolysis: No significant interference from hemoglobin up to an H index of 1000 Lipemia (Intralipid): No significant interference from lipemia up to an L index of 600 Rheumatoid factors < 350 IU/ml do not interfere
Analyticalsensitivity(LDL)	Roche/Hitachi704/717/747/9020.02 g/l (1 mg/dl)Roche/Hitachi904/911/912/917/Modular P0.007 g/l (0.7 mg/dl)	15 mg/dl
Methodcomparison	Tina-quant Transferrin ver.2 (Y) / Tina-quant Transferrin (X):Passing/Bablock:$y = 0.01 + 0.97x$$r = 0.990$	Tina-quant Transferrin on Roche/Hitachi 917 (Y)/Tina-quant Transferrin on Roche/Hitachi 911 (X):Passing/Bablock:$y = 1.141 + 0.989x$$r = 0.998$

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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	Tina-quant Transferrin
Calibrationfrequency	• after reagent lot change• as required followingquality control procedures	• after reagent lotchange• as required followingquality controlprocedures
Expected values	2.0 – 3.6 g/l (200 – 360 mg/dl)	IFCC/CRM 470:200 – 360 mg/dlRoche:200 – 400 mg/dl

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/1 description: The image shows the seal of the Department of Health & Human Services - USA. The seal is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the seal is an abstract image of three human profiles facing right, with wavy lines extending from the bottom of the profiles.

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

K012371 Re:

Trade Name: Roche Diagnostics Tina-quant® Transferrin ver.2 Regulatory Class: 21 CFR § 866.5880 Regulatory Class: II Product Code: DDG Dated: July 26, 2001 Received: July 26, 2001

Dear Ms. Coenen:

We have reviewed your Section 510(k) notification of intent to market the device referenced we have teviewed your becally be is substantially equivalent (for the indications for use above and we nave acteriner actived predicate devices marketed in interstate commerce stated in the citems. To logally manote of the Medical Device Amendments, or to devices that provision in the may 20, 1910, the encounters. with the provisions of the Federal Food, Drug, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls Cosment Act (1100). Tou may) accessors) sprovisions of the Act include requirements for annual provisions of the Fee. "The est, 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 (1 remarket rippt vary of the Code of Federal Regulations, Title 21, Parts 800 to 895. arretung your as novelent determination assumes compliance with the Current Good A substantanty equirements, 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 mispections, the Food and Dating may result in regulatory action. In addition, FDA may publish comply with also Cricerning your device in the Federal Register. Please note: this response to your premarks betification 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 predicate 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 additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact 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 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.

Steven Toutman

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): K012371

Device Name: Tina-quant Transferrin ver.2

Indications For Use:

Prescription Use _ (Per 21 CFR 801.109)

Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________

(Optional Format 1-2-96)

Susan S. Albane

(Division Sign-Off) Division of Clinical Laboratory Devices

510(k) Number K012371

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).