Immunological in vitro immunoturbidometric test for the quantitative determination of ferritin in human serum and plasma using Roche/Hitachi clinical chemistry analyzers. Measurements obtained by this device are used in the aid of diagnosis of diseases affecting iron metabolism in conjunction with other clinical and laboratory findings.

Device Description

The Tina-quant Ferritin Gen. 4 assay employs an immunoturbidimetric test in which human ferritin agglutinates with latex particles coated with anti-ferritin antibodies. The precipitate is determined turbidimetrically at 570/800 nm.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Tina-quant Ferritin Gen. 4 Assay, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Feature	Acceptance Criteria (Implied)	Reported Device Performance (Tina-quant Ferritin Gen. 4 Assay)
Precision (Repeatability - Within Run %CV)	(Generally, < 10% for low concentrations, < 5% for higher concentrations)	PNP: 0.9% CV (Mean 128 ng/mL)
		PPP: 1.2% CV (Mean 332 ng/mL)
		HS1: 7.2% CV (Mean 8.48 ng/mL)
		HS2: 4.7% CV (Mean 25.5 ng/mL)
		HS3: 0.9% CV (Mean 235 ng/mL)
		HS4: 1.2% CV (Mean 619 ng/mL)
		HS5: 1.1% CV (Mean 820 ng/mL)
Precision (Intermediate Precision - Between Day %CV)	(Generally, < 15% for low concentrations, < 10% for higher concentrations)	PNP: 1.5% CV (Mean 128 ng/mL)
		PPP: 2.0% CV (Mean 332 ng/mL)
		HS1: 9.9% CV (Mean 8.48 ng/mL)
		HS2: 5.2% CV (Mean 25.5 ng/mL)
		HS3: 1.8% CV (Mean 235 ng/mL)
		HS4: 2.1% CV (Mean 619 ng/mL)
		HS5: 2.1% CV (Mean 820 ng/mL)
Analytical Sensitivity (Limit of Blank)	(Lower than any clinically relevant value)	3 ng/mL
Analytical Sensitivity (Limit of Detection)	(Lower than any clinically relevant value)	5 ng/mL
Functional Sensitivity (Limit of Quantitation)	(Lower than any clinically relevant value, usually above LoD)	7 ng/mL
Interference (Icterus)	No significant interference up to I index of 60 mg/dL	No significant interference up to an I index of 60 (approx. 60 mg/dL bilirubin)
Interference (Hemolysis)	No significant interference up to H index of 500 mg/dL	No significant interference up to an H index of 500 (approx. 500 mg/dL hemoglobin)
Interference (Lipemia)	No significant interference up to Intralipid concentration of 1000 mg/dL (on 912/917/MODULAR P) and 800 mg/dL (on 902)	No significant interference up to an Intralipid concentration of 1000 mg/dL on Roche/Hitachi 912, 917 and MODULAR P analyzers and up to an Intralipid concentration of 800 mg/dL on Roche/Hitachi 902 analyzers.
Interference (Rheumatoid factors)	No interference for RF < 1200 IU/ml	Rheumatoid factors < 1200 IU/ml do not interfere.
High-dose Hook Effect	No high-dose hook effect within a relevant assay range	No high-dose hook effect is seen up to a ferritin concentration of 80000 ng/mL on Roche/Hitachi 902/912/917/MODULAR P analyzers.
Method Comparison (Correlation with Predicate Device)	Strong correlation (e.g., r > 0.95 or similar Passing-Bablok parameters demonstrating equivalence)	Passing Bablok: y = 0.987x + 0.040, tau = 0.983; Linear regression: y = 0.987x + 0.591, r = 0.999
Measuring Range	Roche/Hitachi 902: 5 - 800 ng/mL; Roche/Hitachi 912/917/Modular P: 5 - 1000 ng/mL	Roche/Hitachi 902: 5 - 800 ng/mL; Roche/Hitachi 912/917/Modular P: 5 - 1000 ng/mL

Note on Acceptance Criteria: The provided text explicitly states the "reported device performance" and sometimes compares it to the predicate device's performance, but it does not explicitly define quantitative acceptance criteria for each metric. The "Acceptance Criteria (Implied)" column above reflects the common expectations for these types of assays and the comparison points given in the document. The fact that the device received 510(k) clearance implies that the reported performance met the FDA's requirements for substantial equivalence to the predicate.

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Precision: The sample size for precision studies is not explicitly stated as a single number but lists 7 different samples (PNP, PPP, HS1-HS5) tested. For the predicate device's imprecision study, n=21. While "human samples and controls" are mentioned for the new device, specific numbers for each sample type are not provided beyond the samples tested.
Method Comparison: 94 human serum and plasma samples.
Interferences: No specific sample sizes for interference studies are provided; the results are reported as thresholds (e.g., "up to an I index of 60").
Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective. It only mentions "human samples and controls."

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This is an in vitro diagnostic (IVD) quantitative assay, not a device requiring expert interpretation of images or clinical data for ground truth. The "ground truth" for method comparison and precision in IVDs is typically established by measurements from a reference method (in this case, the predicate device) or by spiking known concentrations of the analyte. Therefore, the concept of "experts" establishing ground truth in the way described is not applicable here.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable. This is not a study involving human readers or interpretation requiring adjudication.

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 assay, not an imaging or clinical decision support AI device that would involve human readers or MRMC studies.

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

Yes, the studies described (Precision, Analytical Sensitivity, Functional Sensitivity, Analytical Specificity, Interferences, Method Comparison) are all standalone performance evaluations of the assay itself, without human-in-the-loop performance being a variable. The "algorithm" here is the biochemical reaction and the instrument's measurement system.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

Precision: Internal analysis using human samples and controls. The "ground truth" here is the mean concentration determined by repeated measurements of the same sample.
Analytical Sensitivity: Established internally through method validation, typically by analyzing blank samples and low-concentration samples.
Functional Sensitivity: Established internally, usually based on the lowest concentration at which acceptable precision (e.g., <20% CV) is achieved.
Method Comparison: The predicate device (Tina-Quant Ferritin assay cleared in K964282) on the same analyzer was used as the reference method. So, the "ground truth" for comparison was the results generated by the predicate device.

8. The sample size for the training set

This is an IVD assay, not a machine learning model. Therefore, the concept of a "training set" in that context does not apply. The development process for such an assay involves various R&D experiments and optimization over time, but not a distinct "training set" in the AI sense.

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

Not applicable, as there is no training set in the context of a machine learning model.

Summary

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

K100538

Tina-quant Ferritin Gen. 4 Assay

JUN 2 2 2010

510(k) Summary

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 Diagnostics9115 Hague RoadIndianapolis, IN 46250Phone: (317) 521 - 3831Fax: (317) 521 - 2324
	Contact Person: Kathie Goodwin, Regulatory Principal
	Roche Diagnostics, Indianapolis
	Phone: 317-521-3831
	Fax: 317-521-2324
	Date Prepared: February 22nd, 2010
Device Name	Proprietary names: Tina-Quant Ferritin Gen. 4 Assay
	Common names: Ferritin Gen. 4 assay
	Regulation: 21 CFR 866.5340
	Classification names: Ferritin Immunological Test System
	Product codes: DBF
Device Description	The Tina-quant Ferritin Gen. 4 assay employs an immunoturbidimetric test in which human ferritin agglutinates with latex particles coated with anti-ferritin antibodies. The precipitate is determined turbidimetrically at 570/800 nm.
Intended use	In vitro test for the quantitative determination of ferritin in human serum and plasma on Roche automated clinical chemistry analyzers.
	Continued on next page

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

Immunological in vitro immunoturbidometric test for the quantitative Indications for Use determination of ferritin in human serum and plasma using Roche/Hitachi clinical chemistry analyzers. Measurements obtained by this device are used in the aid of diagnosis of diseases affecting iron metabolism in conjunction with other clinical and laboratory findings.

The Tina-quant Ferritin Gen. 4 assay is substantially equivalent to the Tina-Substantial equivalence Quant Ferritin assay cleared in K964282.

Substantial equivalence comparison

Feature	Tina-quant Ferritin Gen. 4 Assay	Predicate Device: Tina-Quant Ferritin (K964283)
Intended Use	In vitro test for the quantitativedetermination of ferritin in humanserum and plasma on Rocheautomated clinical chemistryanalyzers.	Immunoturbidimetric assay for the invitro quantitative determination offerritin in human serum and plasmausing automated clinical chemistryanalyzers.
Assay Protocol	Same	ImmunoturbidimetricAnti-ferritin antibodies bound to latexreact with the antigen in the sample toform an antigen-antibody complex.Following agglutination, this ismeasured turbidimetrically.
Sample Type	Serum and Li-heparin, K2-EDTA orK3-EDTA plasma	Serum and heparinized, citrated or K2or K3-EDTA plasma

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

Feature	Tina-quant Ferritin Gen. 4 Assay	Predicate Device: Tina-QuantFerritin (K964283)
ReagentComposition	R1: TRIS Buffer, pH 7.5,stabilizing polyclonal antibodies,NaCl preservative	R1: TRIS Buffer, pH 8.2, stabilizingpolyclonal antibodies, NaClPreservative
	R3: Aqueous matrix containinglatex particles coated with anti-human ferritin antibodies (rabbit);preservative, stabilizers	R2: Aqueous matrix containing latexparticles coated with anti-humanferritin antibodies (rabbit);preservative, stabilizers
LabeledInstrumentPlatform	Roche/Hitachi	Roche/Hitachi
Calibrator	Same	C.f.a.s. Proteins
CalibrationFrequency	Same	After lot change and as requiredfollowing quality control procedures
Controls	Same	Precinorm and Precipath Protein
ReagentStability	Unopened: Up to stated expirationdate of 24 months	Unopened: Up to stated expirationdate of 15 months
	Opened:84 days, refrigerated on the analyzer	Opened:28 days, refrigerated on the analyzer
MeasuringRange	Roche/Hitachi 902:5 - 800 ng/mL	Roche/Hitachi 902:5 - 400 ng/mL
	Roche/Hitachi 912/917/Modular P:5 - 1000 ng/mL	Roche/Hitachi 912/917/Modular P:15 - 800 ng/mL

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

Feature	Tina-quant Ferritin Gen. 4 Assay		Predicate Device: Tina-Quant Ferritin (K964283)
Precision	Precision was determined using human samples and controls in accordance with the CLSI EP5 requirements.		Imprecision: Reproducibility was determined using human samples and controls in an internal protocol: n=21. The following results were obtained.
		RepeatabilityWithin run	Intermediate Precision -Between Day
	Sample	Meanng/mL	% CV	Meanng/mL	% CV	Sample	Meanng/mL	% CV	Meanng/mL	% CV
	PNP	128	0.9	128	1.5	HS	32	6.0	32	5.6
	PPP	332	1.2	332	2.0	PNP	77	2.5	76	2.7
	HS1	8.48	7.2	8.48	9.9	PPP	333	1.2	329	1.3
	HS2	25.5	4.7	25.5	5.2
	HS3	235	0.9	235	1.8
	HS4	619	1.2	619	2.1
	HS5	820	1.1	820	2.1
AnalyticalSensitivity	Limit of Blank = 3 ng/mLLimit of Detection = 5 ng/mL
FunctionalSensitivity	Limit of Quantitation = 7 ng/mL					NA
AnalyticalSpecificity	Same					The polyclonal antibodies used in the assay are specific for ferritin from human liver and also recognize ferritin from human spleen. The antibodies show no cross reactivity to the human ferritin H subunit; which is the major component of human heart ferritin.

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

Feature	Tina-quant Ferritin Gen. 4 Assay	Predicate Device: Tina-QuantFerritin (K964283)
Interferences	Icterus:No Significant interference up to an Iindex of 60 (approximate conjugatedand unconjugated bilirubinconcentration: 60 mg/dL)	Icterus:No Significant interference up to an Iindex of 60 (approximate conjugated andunconjugated bilirubin concentration: 60mg/dL)
	Hemolysis:No significant interference up to an Hindex of 500 (approximate hemoglobinconcentration: 500 mg/dL)	Hemolysis:No significant interference up to an Hindex of 500 (approximate hemoglobinconcentration: 500 mg/dL)
	Lipemia (Intralipid):No significant interference up to anIntralipid concentration of 1000 mg/dLon Roche/Hitachi 912, 917 andMODULAR P analyzers and up to anIntralipid concentration of 800 mg/dLon Roche/Hitachi 902 analyzers. Thereis poor correlation between theIntralipid concentration (corresponds toturbidity) and triglyceridesconcentration.	Lipemia (Intralipid):No significant interference up to an Lindex of 750 (approximate triglycerideconcentration: 1500 mg/dL). There ispoor correlation between turbidity andtriglyceride concentration.
	Rheumatoid factors <1200 IU/ml donot interfere.	Rheumatoid factors <100 IU/ml do notinterfere.
	No high-dose hook effect is seen up toa ferritin concentration of 80000 ng/mLon Roche/Hitachi902/912/917/MODULAR P analyzers.	A high-dose hook effect may occur atferritin concentrations above 20,000ng/mL (Roche/Hitachi911/912/917/MODULAR P).
	Drugs: No interference was found attherapeutic concentrations usingcommon drug panels.
Feature	Tina-quant Ferritin Gen. 4 Assay	Predicate Device: Tina-Quant Ferritin (K964283)
ExpectedValues	Men (20-60 yrs):30-400 ng/mLWomen (17-60 yrs):15-150 ng/mL	Men:30-400 ng/mLWomen:15-150 ng/mLChildren (3 months - 16 years):20-200 ng/mL2nd-3rd month:80-500 ng/mL1st month:150-450 ng/mLUmbilical cord blood:50-250 ng/mL
MethodComparison	A comparison of the Roche Tina-quant Ferritin Gen. 4 assay on theRoche/Hitachi 917 analyzer (y) with the Roche Tina-quant Ferritin assay onthe same analyzer (x) using human serum and plasma samples gave thefollowing correlation (ng/mL):Passing Bablok:y = 0.987x + 0.040tau = 0.983Number of samples measured: 94The sample concentrations were between 15.0 and 775 ng/mL (according themeasuring range of the predicate device).Linear regression:y = 0.987x + 0.591r = 0.999

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

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

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with its wings spread, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged in a circular fashion around the eagle. The text is in all capital letters and is relatively small compared to the eagle symbol.

Food & Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993

Roche Diagnostics c/o Ms. Kathie Goodwin, MBA, MT (ASCP)BB, RAC Regulatory Affairs Principal 9115 Hague Road, PO Box 50416 Indianapolis, IN 46250-0416

JUN 2 2 2010

Re: K100538

Trade/Device Name: Tina-Quant Ferritin Gen. 4 Regulation Number: 21 CFR § 866.5340 Regulation Name: Ferritin Immunological Test System Regulatory Class: Class II Product Code: DBF Dated: May 7, 2010 Received: May10, 2010

Dear Ms. Goodwin:

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 class II (Special Controls), 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); medical device reporting (reporting of

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

Page 2 - Ms. Kathie Goodwin

medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). 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 advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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 the CDRH's Office

of Surveillance and Biometrics/Division of Postmarket Surveillance.

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) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Marie M Chan

Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

{8}------------------------------------------------

Indications for Use Form

K100538 510(k) Number (if known):

Device Name: Tina-Quant Ferritin Gen. 4

Indications for Use:

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Reena Philip

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K100538

Page 1 of 1

Regulation Number and Section

§ 866.5340 Ferritin immunological test system.

(a)
Identification. A ferritin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the ferritin (an iron-storing protein) in serum and other body fluids. Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism, such as hemochromatosis (iron overload) and iron deficiency amemia.(b)
Classification. Class II (performance standards).