Tina-quant Cystatin Gen.2 is an in vitro test for the quantitative determination of cystatin C in human serum and plasma on Roche/Hitachi cobas c systems. Cystatin C measurements are used as an aid in the diagnosis and treatment of renal diseases.

Device Description

The Roche Tina-quant Cystatin C Gen.2 assay provides quantitative measurement of the cystatin C that is present in human serum and plasma. The reagents are packaged in a cassette with two bottles labeled with their instrument positioning, R1 (Reagent 1) and R2 (Reagent 2).

R1 contains a solution of polymers in MOPS-buffered saline with preservative and stabilizers. R2 is latex particles coated with anti-cystatin C antibodies (rabbit) in glycine buffer with preservatives and stabilizers.

Human cystatin C agglutinates with the antibody coated latex particles. The aggregate is determined turbidimetrically.

AI/ML Overview

The provided text describes a 510(k) premarket notification for a modified in vitro diagnostic device, "Tina-quant Cystatin C Gen.2". The modifications primarily involve updated labeling information rather than changes to the device itself. Therefore, the study details are focused on validating these labeling changes.

Here's an analysis based on the provided document:

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

Feature/Metric	Acceptance Criteria (Predicate)	Reported Device Performance (Candidate)
Sample Stability	Not specified in provided text (new information added to labeling)	New room temperature and refrigerated serum and plasma sample stability information was added. Specific data not provided, but the process describes testing samples in triplicate at 15-25 °C and 2-8 °C, with results compared to time zero. The conclusion states "all of the acceptance criteria were met," implying satisfactory stability for the expanded claims.
High dose hook-effect	No false result occurs up to a cystatin C concentration of 20 mg/L.	No false result occurs up to a cystatin C concentration of 12 mg/L. (This is a more conservative and reduced claim compared to the predicate.)
HARA interference	Not specified in provided text (new warning added to labeling)	Warning added: "In very rare cases falsely elevated results for Cystatin C will be obtained from samples taken from patients who have been treated with rabbit antibodies or have developed anti-rabbit antibodies." This warning is supported by internal testing and cited literature, indicating the device exhibited interference in the presence of HARA, leading to the label change.
Intended use/Indications	Quantitative determination of cystatin C in human serum and plasma as an aid in diagnosis and treatment of renal diseases.	Same
Test principle	Particle enhanced immunoturbidimetric assay	Same
Instrument	Roche/Hitachi cobas c 501	Same
Sample type	Serum, Li-heparin, K2-, and K3- EDTA plasma	Same
Measuring Range	0.40 - 6.80 mg/L	Same
Precision	See predicate method sheet	Same
LoB	0.30 mg/L	Same
LoD	0.40 mg/L	Same
LoQ	0.40 mg/L	Same

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

Sample Stability: Human serum and plasma patient samples were adjusted with cystatin C. The exact number of samples is not explicitly stated, but it mentions "patient samples" and that "These samples are split into two sets". The text does not specify the country of origin or whether the data was retrospective or prospective, but it implies prospective testing for stability.
High dose hook-effect: A human serum pool was used, from which an 18-step dilution series was prepared. The exact volume or number of individual samples within the pool is not specified. Data provenance is not given.
HARA interference: "Internal testing was done at Roche to confirm the customer results." The number of samples tested internally and the provenance of customer data are not detailed.

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)

Not applicable. This device is an in vitro diagnostic (assay for a biomarker), not an imaging or diagnostic device requiring expert interpretation of results for ground truth. Ground truth for an assay is typically established through reference methods or spiked samples with known concentrations.

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

Not applicable. Adjudication methods like 2+1 or 3+1 are typically used in clinical trials or studies where subjective interpretations (e.g., image readings) are being evaluated. For an IVD, the results are quantitative measures.

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 study is for a laboratory assay, not an AI-assisted diagnostic tool for human readers.

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

This refers to the performance of the analytical device itself. The studies described for sample stability, hook effect, and HARA interference were standalone evaluations of the assay's performance characteristics.

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

Sample Stability: The ground truth for sample stability was the result of the fresh sample at time zero, which is considered the baseline and implicitly the "true" concentration at that point.
High dose hook-effect: The ground truth was the "known concentration" obtained from preparing a dilution series from a concentrated serum pool.
HARA interference: The ground truth was based on confirming "falsely elevated results" observed in patient samples and corroborated by peer-reviewed literature.

8. The sample size for the training set

Not applicable. This device is an in vitro diagnostic reagent kit, not a machine learning or AI algorithm that requires a training set. The "training set" concept does not apply here.

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

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

Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized design featuring three human profiles facing to the right, resembling a bird-like shape.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

ROCHE DIAGNOSTICS OPERATIONS (RDO) PATRICK STIMART REGULATORY AFFAIRS CONSULTANT 9115 HAGUE ROAD INDIANAPOLIS IN 46250

July 27, 2016

Re: K161817

Trade/Device Name: Tina-quant Cystatin C Gen.2 Regulation Number: 21 CFR 862.1225 Regulation Name: Creatinine test system Regulatory Class: II Product Code: NDY Dated: June 27, 2016 Received: July 1, 2016

Dear Mr. Patrick Stimart:

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. 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 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 medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours.

Katherine Serrano -S

For : Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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

Indications for Use

510(k) Number (if known) K161817

Device Name Tina-quant Cystatin C Gen.2

Indications for Use (Describe)

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)

|X | Prescription Use (Part 21 CFR 801 Subpart D)

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

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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

Tina-quant Cystatin C Gen.2 510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.

In accordance with 21 CFR 807.87, Roche Diagnostics hereby submits official notification as required by Section 510(k) of the Federal Food, Drug and Cosmetics Act of our intention to market the device described in this Premarket Notification Special 510(k).

The purpose of this Special 510(k) Premarket Notification is to inform FDA of the proposed modifications to the Tina-quant Cystatin C Gen.2 labeling and provide sufficient detail to support a determination of substantial equivalence. The primary change is the addition and expansion of sample stability claims. Other changes that will also be addressed are a reduction in the hook effect interference level claim and the addition of a warning against testing of patient samples containing human anti-rabbit antibodies (HARA).

Note: There were no prior submissions for this device for which FDA provided feedback related to the data or information needed to support substantial equivalence.

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

Submitter Name	Roche Diagnostics
Address	9115 Hague RoadP.O. Box 50416Indianapolis, IN 46250-0415
Contact	Primary:Patrick StimartPhone (317) 521-3954FAX (317) 521-2324Email: patrick.stimart@roche.comSecondary:Miranda DeverallPhone (317) 521-2897FAX (317) 521-2324Email: miranda.deverall@roche.com
Date Prepared	June 24, 2016
Proprietary Name	Tina-quant Cystatin C Gen.2
Common Name	Cystatin C Gen.2
Classification Name	Cystatin C test system (21CFR862.1225, Class 2 device)
Product Codes	NDY
Predicate Devices	The candidate device is a modification of the predicate device. Thedevice name, Tina-quant Cystatin C Gen.2, is unchanged from how itwas cleared in 510(k) K141143
Establishment Registration	For the Tina-quant Cystatin C Gen.2, the establishment registrationnumber for Roche Diagnostics GmbH in Mannheim, Germany is9610126, and for Penzberg, Germany, 9610529. The establishmentregistration number for Roche Diagnostics in the United States is1823260.

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

1. DEVICE DESCRIPTION

Human cystatin C agglutinates with the antibody coated latex particles. The aggregate is determined turbidimetrically.

Note: Since Tina-quant Cystatin C Gen.2 is a reagent, drawings, schematics, illustrations, photos and figures are not pertinent to describe the device and therefore are not present in this submission.

2. INDICATIONS FOR USE

Tina-quant Cystatin C Gen.2 is an in vitro test for the quantitative determination of cystatin C in human serum and plasma on Roche/Hitachi cobas c systems. Cystatin C measurements are used as an aid in the diagnosis and treatment of renal diseases.

Note: The intended use of the modified device, as described in its labeling, has not changed as a result of the modification.

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

TECHNOLOGICAL CHARACTERISTICS 3.

The candidate device. Tina-quant Cystatin C Gen.2, has been modified from the predicated device with the addition of the following information to the assay method sheet.

Added new room temperature and refrigerated serum and plasma sample stability information to the Specimen collection and preparation section.
Added a warning to the Limitations and interference section regarding elevated cystatin . C results in patient samples containing human anti-rabbit antibodies (HARA)
In the Limitations and interference section, the Hook-effect limit was changed from 20 . mg/L to a more conservative 12 mg/L.

The following tables compare the Tina-quant Cystatin C Gen.2 with its predicate device, Tinaquant Cystatin C Gen.2 (K141143).

Feature	Predicate Device Tina-quant Cystatin CGen.2 (K141143)	Candidate Device Tina-quantCystatin C Gen.2
Intended use / Indications for use	In vitro test for the quantitativedetermination of cystatin C in human serumand plasma on Roche/Hitachi cobas csystems. Cystatin C measurements are usedas an aid in the diagnosis and treatment ofrenal diseases.	same
Test principle	Particle enhanced immunoturbidimetricassay	same
Instrument	Roche/Hitachi cobas c 501	same
Sample type	Serum, Li-heparin, K2-, and K3- EDTAplasma	same
Calibrator	C.f.a.s. Cystatin C	same
Calibration frequency	After reagent lot change and after 90 days	same
Controls	Cystatin C Control Set Gen.2	same
Traceability/Standardization	This method has been standardized againstERM-DA471/IFCC	same
Reagent stability	Shelf life at 2-8°C: See expiration date oncobas c pack labelOn-board in use and refrigerated on theanalyzer: 8 weeks	same

Table 1 Assay Comparison, General Assay Features

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

Feature	Predicate Device Tina-quant Cystatin CGen.2 (K141143)	Candidate Device Tina-quant CystatinC Gen.2
Measuring Range	0.40 - 6.80 mg/L	Same
Precision	See predicate method sheet	Same
LoB	0.30 mg/L	Same
LoD	0.40 mg/L	Same
LoQ	0.40 mg/L	Same
Hook effect	No false result occurs up to a cystatin Cconcentration of 20 mg/L.	No false result occurs up to a cystatin Cconcentration of 12 mg/L.
Method Comparison	See predicate method sheet	Same
Limitations -interference	See predicate method sheet	Same as predicate except for thefollowing change and addition:"High dose hook-effect: No false resultoccurs up to a cystatin C concentrationof 20 mg/L " was changed to"High dose hook-effect: No false resultoccurs up to a cystatin C concentrationof 12 mg/L"The warning statement "In very rarecases falsely elevated results for CystatinC will be obtained from samples takenfrom patients who have been treated withrabbit antibodies or have developed anti-rabbit antibodies." was added along withthe supporting reference number 33Kricka LH. Human Anti-AnimalAntibody Interferences inImmunological Assays. Clin Chem1999;45(7):942-956.

Table 2: Assay Comparison, Labeled Performance Characteristics

NON-CLINICAL PERFORMANCE EVALUATION 4.

Based on the risk analysis, the modifications to the Tina-quant Cystatin C Gen.2 method sheet did not introduce any new risks to the performance of the assay.

To address the modifications, verification and validation activities, which are summarized below, demonstrated that all of the acceptance criteria were met.

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

4.1. Sample stability

Human serum and plasma (Li-heparin, K2-EDTA, K3-EDTA) patient samples are adjusted with cystatin C to cover the Tina-quant Cystatin C Gen.2 assay reportable measuring range. These samples are split into two sets, one set stored at 15-25 °C and the other at 2-8 °C. The samples are tested in triplicate on a cobas c 501 analyzer, and the median value is used to calculate the % difference from the result of the fresh sample at time zero.

4.2. High dose hook-effect

A human serum pool is adjusted to obtain a cystatin C concentration of > 24 mg/L. A 18 step dilution series is prepared by diluting with 0.9 % saline. These samples are tested on the cobas c 501 analyzer and the known concentration is compared to the result reported by the analyzer.

4.3. HARA interference

A customer inquiry made Roche aware of the potential for interference with Tina-quant Cystatin C Gen.2 assay test results in patient samples containing human anti rabbit antibodies (HARA). Internal testing was done at Roche to confirm the customer results.

This testing, customer information, and the information presented in the peer reviewed and published literature reference cited in the method sheet, support the addition of a warning statement, regarding the use of patient samples containing HARA, to the Limitations and interference section of the method sheet.

ADDITIONAL INFORMATION 5.

The Tina-quant Cystatin C Gen.2 assay will continue to use the current C.f.a.s. Cystatin C (K080811) for calibration, and the Cystatin C Control Set Gen.2 (K141143) for quality control. There have been no changes to the C.f.a.s. Cystatin C and the Cystatin C Control Set Gen.2.

CONCLUSIONS 6.

The submitted information in this premarket notification supports a substantial equivalence decision. The differences between predicated and candidate do not impact the indications for use or technological characteristics.

Regulation Number and Section

§ 862.1225 Creatinine test system.

(a)
Identification. A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.(b)
Classification. Class II.