For use in the verification of the callbration established by the Elecsys Estradiol III reagent on the indicated Electys and cobas e immunoassay analyzers.

Device Description

The Elecsys Estradiol III CalCheck is a lyophilized product consisting of synthetic Estradiol in a human serum matrix. It has been standardized against CRM6004a via ID-GC/MS (isotope dilution gas chromatography mass spectrometry).

AI/ML Overview

The provided document describes the Elecsys Estradiol III CalCheck device, an in vitro diagnostic quality control material. It details its intended use, comparison to a predicate device, and studies conducted to support its stability claims.

Here's an analysis of the provided information according to your criteria:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria and performance are reported for two stability studies: Open-Vial Stability and Accelerated Stability.

Study	Characteristic	Acceptance Criterion	Reported Performance
Value Assignment	Assigned Range	±27% of the assigned value for all levels (1, 2, and 3).	"Value assignment testing was conducted and passed pre-defined acceptance criteria."
Analyser Consistency	Mean value on additional analyzer	Within 10% of the master platform assigned value.	"The assigned values from the master platform are deemed valid for the MODULAR ANALYTICS E170, Elecsys 2010, cobas e 411, cobas e 601, and cobas e 602 immunoassay analyzers."
Open-Vial Stability	Recovery (Level 1)	85-115% recovery of the reference material vlaue	"The data support the package insert claim that reconstituted Estradiol III CalCheck is stable up to 4 hours at 20-25°C." (Implies criteria met)
Open-Vial Stability	Recovery (Levels 2-3)	90-110% recovery of the reference material value	"The data support the package insert claim that reconstituted Estradiol III CalCheck is stable up to 4 hours at 20-25°C." (Implies criteria met)
Accelerated Stability	Recovery (Level 1)	85-115% recovery of the reference material value	"The accelerated stability model employed supports an initial shelf-life claim of 18 months when the Estradiol III CalCheck are stored under normal storage conditions of 2-8°C." (Implies criteria met)
Accelerated Stability	Recovery (Levels 2-3)	90-110% recovery of the reference material value	"The accelerated stability model employed supports an initial shelf-life claim of 18 months when the Estradiol III CalCheck are stored under normal storage conditions of 2-8°C." (Implies criteria met)

2. Sample Size Used for the Test Set and the Data Provenance

Open-Vial Stability Study:
- Sample Size: "One Estradiol III CalCheck lot was evaluated in duplicate" for on-test and reference materials. This means a single lot of the control material was used, with duplicate measurements taken.
- Data Provenance: The study was conducted internally by Roche Diagnostics on a cobas e 411 analyzer. It's a prospective internal validation study. The country of origin of the data is not explicitly stated but can be inferred as the location of Roche Diagnostics' testing facility (likely USA or Europe, given the submission location).
Accelerated Stability Study:
- Sample Size: "One Estradiol III CalCheck lot was evaluated in duplicate" for on-test and reference materials. Similar to the open-vial study, a single lot was used with duplicate measurements.
- Data Provenance: Conducted internally by Roche Diagnostics on a cobas e 411 analyzer. Prospective internal validation.
Value Assignment Test:
- Sample Size: For each lot, CalChecks are run in duplicate on at least three cobas e 601/MODULAR ANALYTICS E170 analyzers and the cobas e 411/Elecsys 2010. This implies at least 6 determinations for the assigned value and additional comparisons for other analyzers.
- Data Provenance: Internal testing by Roche Diagnostics.

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

This information is not applicable as the device is a quality control material for an in vitro diagnostic, not an AI or imaging device that requires expert interpretation for ground truth. The "ground truth" here refers to the reference values or stability characteristics, which are determined by established analytical methods and reference materials (CRM6004a via ID-GC/MS).

4. Adjudication Method for the Test Set

This is not applicable. Adjudication typically applies to studies where multiple human readers interpret data, and their interpretations need to be reconciled. For analytical performance of a quality control material, results are quantitative and compared against pre-defined analytical acceptance criteria.

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

This information is not applicable. An MRMC study is relevant for AI or imaging devices that assist human readers in diagnosis or interpretation. The Elecsys Estradiol III CalCheck is a quality control material used for calibration verification of an immunoassay analyzer, not a diagnostic tool for human interpretation.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

This information is not applicable. The device is an in vitro diagnostic reagent, not an algorithm or AI. Its performance is evaluated through analytical studies, not through AI standalone performance metrics.

7. The Type of Ground Truth Used

The "ground truth" for the Elecsys Estradiol III CalCheck's performance is established by:

Reference Material Traceability: Standardization against CRM6004a via ID-GC/MS (isotope dilution gas chromatography mass spectrometry). This is a highly accurate and precise analytical method that establishes the true value of Estradiol.
Reference Measurements: For stability studies, "freshly reconstituted set of CalChecks" stored under optimal conditions (2-8°C) served as the reference material for comparison against stressed samples.

8. The Sample Size for the Training Set

This information is not applicable. The Elecsys Estradiol III CalCheck is not an AI or machine learning model that requires a training set. It is a manufactured reagent whose characteristics are determined by its chemical composition and analytical methods.

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

This information is not applicable for the same reason as point 8.

Summary

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

ROCHE DIAGNOSTICS KELLI TURNER REGULATORY AFFAIRS PRINCIPAL 9115 HAGUE ROAD INDIANAPOLIS IN 46250

December 16, 2014

Re: K143284

Trade/Device Name: Elecsys Estradiol III CalCheck Regulation Number: 21 CFR 862.1660 Regulation Name: Quality control material (assayed and unassayed) Regulatory Class: I. Reserved Product Code: JJX Dated: November 14, 2014 Received: November 17, 2014

Dear Kelli Turner:

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,

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

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Indications for Use

510(k) Number (if known) K143284

Device Name Elecsys Estradiol III CalCheck

Indications for Use (Describe)

For use in the verification of the callbration established by the Elecsys Estradiol III reagent on the indicated Electys and cobas e immunoassay analyzers.

Type of Use (Select one or both, as applicable)
-------------------------------------------------

X Prescription Use (Part 21 CFR 801 Subpart D)

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

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510(k) Summary, Elecsys Estradiol III CalCheck

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.
Submittername, address, contact	Roche Diagnostics9115 Hague Road, P.O. Box 50416Indianapolis, IN 46250-0416Contact Person: Kelli TurnerPhone: 317-521-4515Fax: 317-521-2324Email: kelli.turner@roche.comSecondary Contact: Michael LeutherPhone: 317-521-3930Fax: 317-521-2324Email: michael.leuther@roche.comDate Prepared: December 12, 2014
Device Name	Proprietary name:Common name:	Elecsys Estradiol III CalCheckEstradiol III CalCheck
	Classification:	Class 1, reserved21 CFR 862.1660, Single (specified) analyte controls (assayed and unassayed)
	Product Code:	JJX

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Device Description	Elecsys Estradiol III CalCheck: The Elecsys Estradiol III CalCheck is a lyophilized product consisting of synthetic Estradiol in a human serum matrix. It has been standardized against CRM6004a via ID-GC/MS (isotope dilution gas chromatography mass spectrometry).
Intended use	Elecsys Estradiol III CalCheck: For use in the verification of the calibration established by the Elecsys Estradiol III reagent on the indicated Elecsys and cobas e immunoassay analyzers.
Predicate device	The Elecsys Estradiol III CalCheck is substantially equivalent to other products in commercial distribution intended for similar use. We claim equivalency to the currently marketed Elecsys CalCheck Estradiol (K970148).

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	Comparison The table below compares Elecsys Estradiol III CalCheck with the predicate
Table	device, Elecsys CalCheck Estradiol (K970148).

Characteristic	Elecsys Estradiol III CalCheck(Candidate)	Elecsys CalCheck Estradiol(K970148)
Intended Use	For use in the verification of thecalibration established by theElecsys Estradiol III reagent onthe indicated Elecsys and cobase immunoassay analyzers.	The Elecsys CalCheck Estradiolis for use in the verification ofthe calibration established by theElecsys Estradiol reagent on theindicated Elecsys and cobas eimmunoassay analyzers.
Analyte	Estradiol (synthetic)	Same
Matrix	Human serum matrix	Same
Levels	Three	Same
AssayMeasuringRange	5 - 3000 pg/mL	5 - 4300 pg/mL
Check TargetValues	Check 1: 100 pg/mLCheck 2: 1500 pg/mLCheck 3: 2400 pg/mL	Check 1: 200 pg/mLCheck 2: 2000 pg/mLCheck 3: 4000 pg/mL
Format	Lyophilized	Same
Handling	Reconstitute Check 1, Check 2,and Check 3with exactly 1.0 mLdistilled or deionized water.Allow to stand closed for 15minutes, then mix gently byinversion to ensurehomogeneity.	Reconstitute the contents ofCheck 1, Check 2 and Check 3with exactly 1.5 mL distilled ordeionized water. Allow thebottle to stand closed for 15minutes. Mix gently byinversion to ensurehomogeneity.
Stability	Unopened:• Store at 2-8°C until expirationdateOpened:• 20-25°C: 4 hours	Unopened:• Store at 2-8°C until expirationdateOpened:• 15-25°C: 4 hours

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Traceability	The Elecsys Estradiol III CalCheck was standardized against CRM6004a via ID-GC/MS (isotope dilution gas chromatography mass spectrometry).
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Value Assignment	Value assignment testing was conducted and passed pre-defined acceptance criteria. For each Elecsys Estradiol III CalCheck lot manufactured, the CalChecks are run in duplicate on at least three cobas e 601/MODULAR ANALYTICS E170 analyzers. The assigned value of each CalCheck is defined as the mean value obtained over at least 6 determinations (duplicate runs on at least 3 analyzers) of the respective CalCheck. The CalCheck assigned range is calculated as ±27% of the assigned value for all levels (1, 2 and 3). 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/Elecsys 2010. The assigned values obtained are compared to those obtained on the cobas e 601. 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 MODULAR ANALYTICS E170, Elecsys 2010, cobas e 411, cobas e 601, and cobas e 602 immunoassay analyzers.
Target Values	The CalCheck target values for the Elecsys Estradiol III are as follows: Check Target Values Check 1: 100 pg/mL Check 3: 1500 pg/mL Check 3: 2400 pg/mL	Check Target Values	Check 1: 100 pg/mLCheck 3: 1500 pg/mLCheck 3: 2400 pg/mL
Check Target Values	Check 1: 100 pg/mLCheck 3: 1500 pg/mLCheck 3: 2400 pg/mL

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Two studies were performed in order to verify the stability claims for the Stability Estradiol III CalCheck. Additionally, a real-time stability study is ongoing to Studies support the shelf-life stability claim.

Opened-vial and accelerated stability studies were completed on the cobas e 411. Because these studies are not analyzer-dependent, these results, in addition to real-time stability study results, can be applied to the Elecsys 2010, MODULAR ANALYTICS E170, cobas e 601 and cobas e 602.

Study 1. Open-Vial Stability:

The on-test and reference materials were tested in duplicate. The on-test material was reconstituted and stored for 6 hours at 25℃ (in an open vial). The reference material was a freshly reconstituted set of CalChecks. The ontest recovery was calculated as a percent of the reference value.

One Estradiol III CalCheck lot was evaluated in duplicate on the cobas e 411. The acceptance criterion for CalCheck Level 1 is 85-115% recovery; and for CalCheck Levels 2-3, the acceptance criterion is recovery of 90-110% recovery of the reference material value.

The data support the package insert claim that reconstituted Estradiol III CalCheck is stable up to 4 hours at 20-25°C.

The CalCheck products are not stored on-board the analyzers, therefore no on-board stability claims are made.

Study 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℃). 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 accelerated stability model employed supports an initial shelf-life claim of 18 months when the Estradiol III CalCheck are stored under normal storage conditions of 2-8°C.

Real-time stability studies are ongoing.

Conclusion We trust that the data and information provided in this Premarket Notification 510(k) submission will support a determination of substantial equivalence for the Elecsys Estradiol III CalCheck.

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.