The Elecsys CYFRA 21-1 CalCheck 5 is an assayed control for use in calibration verification and for use in the verification of the assay range established by the Elecsys CYFRA 21-1 reagent on the indicated Elecsys and cobas e immunoassay analyzers.

Device Description

The Elecsys CYFRA 21-1 CalCheck 5 is a lyophilized product consisting of cytokeratin in a human serum matrix. During manufacture, the analyte is spiked into the matrix at the desired concentration levels.

CYFRA 21-1 CalCheck 5 is a lyophilized human serum matrix with added cytokeratin in five concentration ranges. The CalCheck includes:

o CYFRA 21-1 CalCheck 1: approximately <1.0 ng/mL
CYFRA 21-1 CalCheck 2: approximately 3.0 ng/mL ●
CYFRA 21-1 CalCheck 3: approximately 50.0 ng/mL
CYFRA 21-1 CalCheck 4: approximately 80.0 ng/mL ●
CYFRA 21-1 CalCheck 5: approximately 100 ng/mL

AI/ML Overview

This document describes the premarket notification (510(k)) for the Elecsys CYFRA 21-1 CalCheck 5, a control device used for calibration verification and assay range verification for the Elecsys CYFRA 21-1 reagent on specific immunoassay analyzers.

Here's an analysis of the provided text in relation to your request:

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

Acceptance Criteria	Reported Device Performance
Value Assignment: Assigned value for each CalCheck level on cobas e 601/MODULAR ANALYTICS E170 analyzers defined as the mean value obtained over at least six determinations (duplicate runs on at least three analyzers).	Value assignment testing was conducted and passed pre-defined acceptance criteria. The assigned values are published.
Assigned Range: For levels 2-5, the assigned range is calculated as ±21% of the assigned value.	The label states that each laboratory should establish appropriate acceptance criteria when using this product for its intended use.
Cross-Platform Comparability (cobas e 411 vs. cobas e 601): Mean value obtained on the additional analyzer (cobas e 411) must be within 10% of the master platform (cobas e 601) assigned value.	This acceptance criterion was met, deeming assigned values from the master platform valid for Elecsys 2010, MODULAR ANALYTICS E170, cobas e 411, cobas e 601, and cobas e 602 immunoassay analyzers.
Accelerated Stability (3 weeks at 35°C): Recovery of the stressed material compared to freshly reconstituted material was calculated. (Specific numerical acceptance criteria for recovery are not provided in the document, only that the study was conducted and recovery was calculated).	The study was conducted. No specific numerical performance values for recovery are explicitly stated as "met" or "non-met" in this summary section, only that the study was performed.
On-board Stability (6 hours at 20-25°C): Test material compared as a % to freshly reconstituted reference. (Specific numerical acceptance criteria for % comparison are not provided).	The study was conducted. No specific numerical performance values for % comparison are explicitly stated.
Real-Time Stability (Transferred from CalSet material): Stored CalSet reagents tested at T=0 and specified intervals over shelf life + one month. (Implies performance within expected ranges, but specific criteria are not listed).	The study was conducted, and the results are transferable to the CalCheck material to support a 12-month shelf life claim.

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

Value Assignment: For each Elecsys CYFRA 21-1 CalCheck 5 lot, each CalCheck level is run in duplicate on at least three cobas e 601/MODULAR ANALYTICS E170 analyzers. This means at least 6 determinations per CalCheck level per lot. The document implies this data is generated internally by Roche Diagnostics, likely in laboratories in the USA (Indianapolis), Germany (Mannheim, Penzberg) based on the establishment registration. This is prospective data generation for product release and verification.
Accelerated Stability: "One CYFRA 21-1 CalCheck 5 lot was evaluated on one cobas e 411 analyzer." Tests were performed in duplicate. This is likely prospective data.
On-board Stability: "One CYFRA 21-1 CalCheck 5 lot was evaluated on one cobas e 411 analyzer." Samples tested in duplicate. This is likely prospective data.
Real-Time Stability: Conducted on the CYFRA 21-1 CalSet material. "Stored CalSet reagents were tested at time point T=0 and at specified intervals over the shelf life of the device up to the planned shelf life plus one month." No specific sample size (number of lots or tests) is provided for the CalSet study. The data provenance is internal to Roche Diagnostics, prospective for shelf-life determination.

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

This section describes a quality control material, not a diagnostic device that relies on interpretation of data by experts. The "ground truth" here is the assigned value of the analyte concentration in the control material. This is established through a quantitative measurement process on pre-defined analyzers rather than expert consensus on, for example, medical images or patient diagnoses. Therefore, the concept of "experts establishing ground truth" as typically applied to image-based AI or clinical decision support AI is not directly applicable. The "experts" in this context would be the skilled laboratory personnel who perform the assays according to established protocols and the statisticians/scientists who determine the assigned values based on the collected analytical data. No specific number or qualifications are mentioned for such roles.

4. Adjudication method for the test set

Not applicable for a quality control material where quantitative analytical results are compared against pre-defined ranges and values. Adjudication methods like 2+1 or 3+1 are typically used for subjective assessments where multiple readers provide independent interpretations.

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 device is a quality control material used to verify the performance of an immunoassay analyzer and its reagents, not an AI-powered diagnostic tool for human readers.

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

This is a standalone device in the sense that it is a physical control material. The performance of the device itself (its stability and assigned values) is evaluated, not an algorithm's classification capabilities. It is used with an immunoassay analyzer, but its own performance doesn't involve an "algorithm only" classification.

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

The ground truth for this device is the analytically determined assigned value of the cytokeratin concentration within the control material. This is established through rigorous laboratory testing using calibrated instruments and methods, rather than expert consensus, pathology, or outcomes data.

8. The sample size for the training set

Not applicable. This device is a physical control material, not a machine learning model that requires a training set. The reference to "master platform assigned value" and "additional analyzer" implies a validation step, but not a training process in the AI sense.

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

January 12, 2017

Roche Diagnostics Mr. Adam Clark Regulatory Affairs Consultant 9115 Hague Road Indianapolis, IN 46250

Re: K162173

Trade/Device Name: Elecsys CYFRA 21-1 CalCheck 5 Regulation Number: 21 CFR 862.1660 Regulation Name: Quality Control Material (Assayed and Unassayed) Regulatory Class: I. Reserved Product Code: JJX Dated: December 15, 2016 Received: December 16, 2016

Dear Mr. Clark:

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 (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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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,

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FOR

Leonthena R. Carrington, MS, MBA, MT(ASCP) Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K162173

Device Name Elecsys CYFRA 21-1 CalCheck 5

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)

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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 21 CFR 807.92.

Submitter Name	Roche Diagnostics
Address	9115 Hague RoadIndianapolis, IN 46250
Contact	Adam ClarkPhone: (317) 521-4371FAX: (317) 521-2324Email: adam.clark@roche.com
Date Prepared	June 30, 2016
Proprietary Name	1) Elecsys CYFRA 21-1 CalCheck 5
Common Name	1) CYFRA 21-1 CalCheck 5
Classification Name	1) Single (specified) analyte Controls (assayed and unassayed)
Product Codes	1) JJX; 862.1660
Predicate Devices	1) Elecsys Progesterone III CalCheck 5
Establishment Registration	Roche Diagnostics GmbH in Mannheim, Germany: 9610126Roche Diagnostics GmbH in Penzberg, Germany: 9610529Roche Diagnostics in the United States: 1823260

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DEVICE DESCRIPTION 1.

1.1. CalCheck

CYFRA 21-1 CalCheck 5 is a lyophilized human serum matrix with added cytokeratin in five concentration ranges. The CalCheck includes:

o CYFRA 21-1 CalCheck 1: approximately <1.0 ng/mL
CYFRA 21-1 CalCheck 2: approximately 3.0 ng/mL ●
CYFRA 21-1 CalCheck 3: approximately 50.0 ng/mL
CYFRA 21-1 CalCheck 4: approximately 80.0 ng/mL ●
CYFRA 21-1 CalCheck 5: approximately 100 ng/mL

INDICATIONS FOR USE 2.

3. DISCUSSION OF ANALYZER PLATFORMS

The following summary of the Elecsys platforms is provided.

The cobas e 411 analyzer is an updated version of the Elecsys 2010 analyzer. Roche Diagnostics pursued a conservative course and submitted a 510(k) for the analyzer under K062279. The submission was closed out under 'exempt' since the submission was only for the analyzer and the 'Joint Risk Assessment' performed internally identified no potential impact on reagent performance. However, to be on the conservative side, Roche Diagnostics conducted recovery and reproducibility testing with representative Elecsys assays, and those data are documented internally. The modifications did not alter the measurement components of the analyzer or the means by which results are calculated. The systems are analytically identical. The majority of the hardware changes, outside of the obvious name change, were cosmetic (e.g., change to color

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scheme, an external PC versus an internal PC) or related to safety (e.g., protective shields added over moving parts), or were made to improve customer satisfaction (e.g., a larger external waste container, flash drive replacement of floppy drive). The user-interface changes were made for aesthetics, customer satisfaction, or to bring the 'old' 2010 analyzer up to parity with those features already designed into the cobas 6000 series system.

The cobas e 601 analyzer is an updated version of the MODULAR ANALYTICS E170 analyzer. The MODULAR ANALYTICS E170 analyzer was acknowledged by FDA under Add-to-File K961481/A003 on May 23, 2001. The cobas e 601 analyzer was reviewed and cleared as a component of the cobas 6000 series system submission K060373. The submission was required to introduce the other component of the cobas 6000 series system: the cobas c 501 analyzer, a new clinical-chemistry analyzer.

The cobas e 602 analyzer, part of the cobas 8000 analyzer series, was cleared via Internal Documentation, in keeping with the Reagent Replacement and Instrument Family Policy, as a new member of the Roche/Elecsys family of analyzers. The cobas e 602 is analytically identical to the cobas e 601 analyzer, part of the cobas 6000 analyzer series cleared in K060373.

4. TECHNOLOGICAL CHARACTERISTICS

Characteristic	Candidate Device: Elecsys CYFRA21-1 CalCheck 5	Predicate Device: Elecsys ProgesteroneIII CalCheck 5 (K150955)
Intended Use	The Elecsys CYFRA 21-1 CalCheck 5is an assayed control for use incalibration verification and for use inthe verification of the assay rangeestablished by the Elecsys CYFRA 21-1 reagent on the indicated Elecsys andcobas e immunoassay analyzers.	The Elecsys Progesterone III CalCheck 5is an assayed control for use incalibration verification and for use in theverification of the assay range establishedby the Elecsys Progesterone III reagenton the indicated Elecsys and cobas eimmunoassay analyzers.
Analyte	Cytokeratin, human	Progesterone (plant material)
Matrix	Human serum matrix	Human serum matrix
Levels	Five	Five
Assay measuring range	0.5 - 100 ng/mL	0.05 - 60 ng/mL
Target Ranges	Check 1: ≤ 1.0 ng/mLCheck 2: 3.0 ng/mLCheck 3: 50.0 ng/mLCheck 4: 80.0 ng/mLCheck 5: 100 ng/mL	Check 1: ≤ 0.15 ng/mLCheck 2: 2.0 ng/mLCheck 3: 30.0 ng/mLCheck 4: 45.0 ng/mLCheck 5: 60.0 ng/mL
Format	Lyophilized	Lyophilized
Handling	Reconstitute the contents of Check 1,Check 2, Check 3, Check 4 and Check5 with exactly 1.0 mL distilled ordeionized water.Allow thebottles to stand closed for 15 minutes.	Reconstitute Check 1, Check 2, Check 3,Check 4, and Check 5 with exactly1.0mL distilled or deionized water.Allow to stand closed for 15 minutes,then mix gently by inversion to ensure

Table 4.1.1: CalCheck Comparison
----------------------------------	--	--

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	Mix gently by inversion to ensure homogeneity.	homogeneity.
Stability	Unopened:· Store at 2-8°C until expiration dateOpened:· 20-25°C: 5 hours	Unopened:· Store at 2-8°C until expiration dateOpened:· 20-25°C: 4 hours

5. NON-CLINICAL PERFORMANCE EVALUATION

5.1. CYFRA 21-1 CalCheck 5 Stability

CYFRA 21-1 CalCheck 5 was evaluated for value assignment and stability; three studies were executed.

CYFRA 21-1 CalCheck 5 Value Assignment 5.1.1.

Value assignment testing was conducted and passed pre-defined acceptance criteria. For each Elecsys CYFRA 21-1 CalCheck 5 lot manufactured, each CalCheck is run in duplicate on at least three cobas e 601/MODULAR ANALYTICS E170 analyzers. The assigned valued of each CalCheck level is defined as the mean value obtained over at least six determinations (duplicate runs on at least three analyzers) of the respective CalCheck level.

The assigned range is calculated as ±21% of the assigned value for levels two through five. The label states that each laboratory should establish appropriate acceptance criteria when using this product for its intended use.

The same value assignment procedure is performed on the cobas e 411 analyzer. The assigned values obtained are compared to those obtained on the cobas e 601 analyzer. The mean value obtained on the additional analyzer must be within 10% of the master platform assigned value. After this acceptance criterion is met, the assigned values from the master platform are deemed valid for the Elecsys 2010, MODULAR ANALYTICS E170, cobas e 411, cobas e 601, and cobas e 602 immunoassay analyzers.

5.1.2. Study 1. CYFRA 21-1 CalCheck 5 Accelerated Stability

One CYFRA 21-1 CalCheck 5 lot was evaluated on one cobas e 411 analyzer. A set of CYFRA 21-1 CalCheck 5 was stored for 3 weeks at 35°C. After the three week period the test material and reference materials were tested in duplicate.

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The reference material used was a freshly reconstituted set of CYFRA 21-1 CalCheck 5. Recovery of the stressed CYFRA 21-1 CalCheck 5 compared to the freshly reconstituted CYFRA 21-1 CalCheck 5 was calculated.

Study 2. CYFRA 21-1 CalCheck 5 Stability (On-board) 5.1.3.

One CYFRA 21-1 CalCheck 5 lot was evaluated on one cobas e 411 analyzer. A set of CYFRA 21-1 CalCheck 5 was reconstituted and stored on-board for 6 hours at 20-25°C. Test CYFRA 21-1 CalCheck 5 was compared as a % to the freshly reconstituted CYFRA 21-1 CalCheck 5 reference.

Samples tested in duplicate include five CalCheck levels.

Study 3. CYFRA 21-1 CalCheck 5 Stability (Real-Time Stability) 5.1.4.

Accelerated Stability testing was done to support the current shelf life claim of 12 months.

Additional testing was done to support the shelf-life of the CalCheck material. CalChecks and CalSets contain the same analyte, are identical in composition and are handled the same for testing. Real time stability was done on the CYFRA 21-1 CalSet material and is transferable to the CalCheck material. In the real-time stability study, the CYFRA 21-1 CalSet material was stored at 2 to 8°C. The stored CalSet reagents were tested at time point T=0 and at specified intervals over the shelf life of the device up to the planned shelf life plus one month. Testing was performed using PreciControl Tumor Marker 1 and 2 (stored at -20°C).

6. CONCLUSIONS

The information provided in this 510(k) Premarket Notification will support a determination of substantial equivalence for the CYFRA 21-1 CalCheck 5. The data supports a safe, effective device which performs as well as or better than the predicate device.

Regulation Number and Section

§ 862.1660 Quality control material (assayed and unassayed).

(a)
Identification. A quality control material (assayed and unassayed) for clinical chemistry is a device intended for medical purposes for use in a test system to estimate test precision and to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. A quality control material (assayed and unassayed) may be used for proficiency testing in interlaboratory surveys. This generic type of device includes controls (assayed and unassayed) for blood gases, electrolytes, enzymes, multianalytes (all kinds), single (specified) analytes, or urinalysis controls.(b)
Classification. Class I (general controls). Except when intended for use in donor screening tests, quality control materials (assayed and unassayed) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.