This CalCheck set is an assayed control for use in calibration and for use in the verification of the assay range established by the Elecsys ß-CrossLaps/serum reagent on the cobas e immunoassay analyzers.

Device Description

The ß-CrossLaps CalCheck 5 is used for the calibration verification and the assessment of the measuring range as needed by the laboratory certification agencies such as College of American Pathologists or CLIA certification. The CalChecks are a customer convenience product and not required to assess the performance.

AI/ML Overview

The provided document describes the ß-CrossLaps CalCheck 5, a quality control material intended for calibration verification and assay range verification on cobas e immunoassay analyzers.

Here's an analysis of the acceptance criteria and the studies performed:

1. Table of Acceptance Criteria and Reported Device Performance:

Study/Parameter	Acceptance Criteria	Reported Device Performance (as per studies presented)
Value Assignment	Assigned range for Levels 2-5: ±27% of the assigned value. Target Value for Check 1: ≤0.05 ng/mL	The CalChecks are run in duplicate on at least two (2) modules (each with two measuring cells) of the cobas e 801 with at least two runs. The assigned value is the median of at least six (6) determinations. The acceptance criterion for the assigned range is applied.
Open Vial Stability	CalCheck Level 1: < 0.05 ng/mL CalCheck Levels 2-5: 90-110% recovery of reference material value	Data supports the method sheet claim that reconstituted B-CrossLaps CalCheck 5 is stable for 4 hours at 20-25°C.
Accelerated Stability	CalCheck Level 1: ≤ 0.05 ng/mL CalCheck Levels 2-5: 90-110% recovery of reference material value	Supports an initial shelf life claim of 18 months when stored at 2-8°C.
Real-time (Shelf-life) Stability	CalCheck Level 1: ≤ 0.05 ng/mL CalCheck Levels 2-5: 90-110% recovery of reference material value	Currently, the shelf-life claim is 18 months, supported by data from time-points at 0, 7, 13, and 19 months (on-going study).

2. Sample Size for Test Set and Data Provenance:

Value Assignment: For each lot, CalChecks are run in duplicate on at least two modules (with two measuring cells each) of the cobas e 801, with at least two runs. This results in at least six (6) determinations (runs) for the median assigned value.
Stability Studies:
- Open Vial Stability: On-test and reference materials were tested in duplicate.
- Accelerated Stability: Test and reference materials were tested in duplicate.
- Real-time Stability: Data for time-points at 0, 7, 13 and 19 months tested in duplicate for an on-going study.
Data Provenance: The studies were conducted by Roche Diagnostics, presumably in their facilities (Mannheim, Germany; Penzberg, Germany; or the United States, as per establishment registrations). The data is prospective for the stability studies, as specific studies were performed to verify claims.

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

Not applicable. This device is a quality control material whose "ground truth" is its own assigned value and specified stability characteristics, as determined by internal validation procedures using the stated analytical instruments. It does not rely on expert interpretation for its function or evaluation.

4. Adjudication Method for the Test Set:

Not applicable. As noted above, this is a quality control material, not an AI or diagnostic device requiring human adjudication of results. The "adjudication" is based on meeting the pre-defined quantitative acceptance criteria.

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

No. This is a quality control material for an immunoassay analyzer and does not involve human readers interpreting cases.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done:

Yes, in essence. The performance evaluations described (Value Assignment, Stability Studies) are intrinsic tests of the quality control material itself and its behavior on the immunoassay analyzer. There is no "human-in-the-loop" aspect to the performance of the control material, beyond the laboratory technician performing routine quality control tasks. The device's performance is standalone in the context of its intended use to verify the performance of an immunoassay analyzer.

7. The Type of Ground Truth Used:

The ground truth for the ß-CrossLaps CalCheck 5 is its assigned value, which is determined by a rigorous internal value assignment process (median of multiple determinations as described previously). For stability studies, the "ground truth" or reference is either a freshly reconstituted set of CalChecks or unstressed reference material, against which the test material's recovery is compared. This is a form of analytical reference standard determination.

8. The Sample Size for the Training Set:

Not applicable. This device is a quality control material; it is not an algorithm that requires a "training set" in the context of machine learning.

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

Not applicable, as there is no training set.

Summary

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

April 4, 2017

ROCHE DIAGNOSTICS EDIE BRUNT PRINCIPAL, REGULATORY AFFAIRS 9115 HAGUE ROAD INDIANAPOLIS IN 46250

Re: K170678

Trade/Device Name: ß-CrossLaps CalCheck 5 Regulation Number: 21 CFR 862.1660 Regulation Name: Quality control material (assayed and unassayed) Regulatory Class: I. Reserved Product Code: JJX Dated: March 3, 2017 Received: March 6, 2017

Dear Edie Brunt:

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.

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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,

Kellie B. Kelm -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

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

510(k) Number (if known) K170678

Device Name B-CrossLaps CalCheck 5

Indications for Use (Describe)

This CalCheck set is an assayed control for use in calibration and for use in the verification of the assay range established by the Elecsys B-CrossLaps/serum reagent on the cobas e immunoassay analyzers.

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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ß-CrossLaps CalCheck 5 510(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 510(k).

The purpose of this Traditional 510(k) Premarket Notification is to obtain FDA review and clearance for the ß-CrossLaps CalCheck 5.

Submitter Name	Roche Diagnostics
Address	9115 Hague RoadP.O. Box 50416Indianapolis, IN 46250-0457
Contact	Edie BruntPhone: (317) 521-4668FAX: (317) 521-2324Email: edie.brunt@roche.com
Date Prepared	March 3, 2017
Proprietary Name	ß-CrossLaps CalCheck 5
Common Name	Beta-CrossLaps CalCheck 5
Classification Name	Single (Specified) Analyte Controls (Assayed and Unassayed))
Product Codes,Regulation Numbers	JJX, 862.1660
Predicate Devices	CalCheck Vitamin D Total II
Establishment Registration	For the B-CrossLaps CalCheck 5, the establishment registration number forRoche Diagnostics GmbH in Mannheim, Germany is 9610126, and forPenzberg, Germany, 9610529. The establishment registration number for RocheDiagnostics in the United States is 1823260.

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1. DEVICE DESCRIPTION

INDICATIONS FOR USE 2.

This CalCheck set is an assayed control for use in calibration verification and for use in the verification of the assay range established by the Elecsys ß-CrossLaps/serum reagent on the cobas e immunoassay analyzers.

TECHNOLOGICAL CHARACTERISTICS 3.

The following table compares the ß-CrossLaps CalCheck 5 with its predicate device, CalCheck Vitamin D Total II (K162840).

CalCheck Comparison Table 1:

Feature	CalCheck Vitamin D Total II	β-CrossLaps CalCheck 5
Intended Use/Indications for Use	This CalCheck set is an assayedcontrol for use in calibrationverification and for use in theverification of the assay rangeestablished by the ElecsysVitamin D total II reagent on thecobas e 411 immunoassayanalyzer.	This CalCheck set is an assayedcontrol for use in calibrationverification and for use in theverification of the assay rangeestablished by the Elecsys β-CrossLaps/serum reagent on thecobas e immunoassay analyzers.
Analyte	25-hydroxyvitamin D3	Synthetic β-CTx peptide in aCrossLaps free human serummatrix
Matrix	Human serum	Same
Levels	Five	Same

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Feature	CalCheck Vitamin D Total II	ß-CrossLaps CalCheck 5
Target Ranges	Approximate targetconcentrations:Check 1: ≤ 5 ng/mLCheck 2: 17.5 — 22.4 ng/mLCheck 3: 46.5 - 54.4 ng/mLCheck 4: 75.5 - 84.4 ng/mLCheck 5: 94.5 -> 100 ng/mL	Approximate targetconcentrations:Check 1: ≤ 0.05 ng/mLCheck 2: 0.4-0.6 ng/mLCheck 3: 2.7 - 3.3 ng/mLCheck 4: 4.0 - 5.0 ng/mLCheck 5: 5.4 ->6.0 ng/mL
Format	Lyophilized	Same
Handling	Reconstitute the contents of eachCalCheck vial with exactly 1.0mL distilled or deionized water.Allow the bottles to stand closedfor 15 minutes. Mix gently byinversion to ensure homogeneity.	Same
Storage and Stability	Reconstituted control serum:At 20-25°C - 4 hours	Same

NON-CLINICAL PERFORMANCE EVALUATION 4.

The ß-CrossLaps CalCheck 5 matrix, human serum, is identical to the Master Calibrators (human serum sample panel) used for the Elecsys ß-CrossLaps/serum assay.

ß-CrossLaps CalCheck 5 was evaluated for value assignment and stability.

Value Assignment 4.1.

For each ß-CrossLaps CalCheck 5 lot manufactured, the CalChecks are run in duplicate on at least two (2) modules (each with two measuring cells) of the cobas e 801 with at least two runs. The assigned value of each CalCheck is defined as the median value obtained over at least six (6) determinations (runs) of the respective CalCheck.

The CalCheck assigned range is calculated as ± 27% of the assigned value for levels 2 through 5. The label states that each laboratory should establish appropriate acceptance criteria when using this product for its intended use.

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Target Values

β-CrossLaps CalCheck 5 Level	Target Value [ng/mL]
Check 1	≤0.05
Check 2	0.5
Check 3	3.0
Check 4	4.5
Check 5	6.0

4.2. Stabilitv

The following studies were performed in order to verify the stability claims for the ß-CrossLaps CalCheck 5:

Study 1: Open vial stability

Study 2: Accelerated stability

Study 3: Real-time stability

4.2.1. Open Vial Stability

The on-test and reference materials were tested in duplicate. The on-test material was reconstituted and stored for 4 hours at 25℃ (in an open vial). The reference material was a freshly reconstituted set of CalChecks. The on-test recovery was calculated as a percent of the reference value. The acceptance criterion for CalCheck Level 1 was < 0.05 ng/mL and for CalCheck Levels 2 -5 was 90-110% recovery of the reference material value. The data supports the method sheet claim that reconstituted B-CrossLaps CalCheck 5 is stable for 4 hours at 20-25°C.

The CalCheck products are not stored on-board the analyzer, therefore no on-board stability claim is made.

4.2.2. Accelerated Stability

The on-test material was stored lyophilized (as supplied to the user) at 35°C for 3 weeks. The reference material was a freshly reconstituted set of CalChecks (stored at 2-8°C). After 3 weeks, the test and reference materials were tested in duplicate. The on-test recovery was calculated as a percent of the reference value. The acceptance criterion for CalCheck Level 1 was ≤ 0.05 ng/mL

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and for CalCheck Levels 2 -5 was 90-110% recovery of the reference material value. The accelerated stability model employed supports an initial shelf life claim of 18 months when the ß-CrossLaps CalCheck 5 are stored under normal storage conditions of 2-8°C.

Real-time (Shelf-life) Stability 4.2.3.

In the on-going real-time stability study, the ß-CrossLaps CalCheck 5 test material is stored at 2-8°C. The CalChecks are tested at T=0 and at specified intervals over the shelf life of the device up to the planned shelf life plus one month. For the lot on stability, data for the time-points at 0, 7, 13 and 19 months tested in duplicate will be available. The average on-test recovery value will be calculated as percent recovery compared to the unstressed reference value (stored at -20°C). The acceptance criterion for CalCheck Level 1 was ≤ 0.05 ng/mL and for CalCheck Levels 2 -5 was 90-110% recovery of the reference material value. Currently the shelf-life claim is 18 months.

Conclusions

The information provided in this 510(k) Premarket Notification will support a determination of substantial equivalence for the ß-CrossLaps 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.