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

AI/ML Overview

Here's an analysis of the acceptance criteria and study information provided for the Elecsys Estradiol III CalSet, extracted from the given 510(k) summary:

Elecsys Estradiol III CalSet: Acceptance Criteria and Study Details

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Criteria	Reported Device Performance
CalSet Value Assignment	Pre-defined acceptance criteria for PreciControl Universal (Level 1 & 2) must be met.	"Value assignment testing was conducted and passed pre-defined acceptance criteria."
Stability (Study 1):
- 2-8°C, -20°C (reconstituted)	95 to 105 % signal recovery of the reference material value.	Not explicitly stated as passed/failed, but implied by "The on-test materials were reconstituted and stored...prior to testing." and "The on-test and reference materials were tested..." which generally indicates positive results if no failures are mentioned.
- Open vial (20-25°C)	95 to 105 % signal recovery of the reference material value.	Not explicitly stated as passed/failed, but implied.
- Freeze/thaw cycles	95 to 105 % signal recovery of the reference material value.	Not explicitly stated as passed/failed, but implied.
Accelerated Stability (Study 2):	95 to 105 % recovery of the reference material value.	Not explicitly stated as passed/failed, but implied by the description of the study and the overall conclusion of substantial equivalence.
Real-Time Stability (Study 3):	95-105 % recovery of the reference value for Estradiol III Calibrator 1 and 2 (stressed vs. unstressed).	"The testing will continue with this stability protocol until data to support a claim of 18 months are achieved." The study is ongoing.

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

Sample Size for Test Set:
- CalSet Value Assignment: Not explicitly stated as a "test set" in terms of number of calibrator vials. However, for each lot, calibrators are run in duplicate on at least three (3) Elecsys 2010/cobas e 411 analyzers and at least three (3) cobas e 601/MODULAR ANALYTICS E170 analyzers. The assigned value is the mean over at least six (6) runs on at least three (3) analyzers. This implies a significant number of measurements for value assignment.
- Stability Studies (Study 1 & 2): "On-test and reference materials were tested in duplicate."
- Real-Time Stability (Study 3): "CalSets are tested in duplicate at specified intervals." One Estradiol III CalSet lot was evaluated in duplicate for accelerated stability.
Data Provenance: Not explicitly stated (e.g., country of origin). The manufacturing establishments are Roche Diagnostics GmbH in Mannheim, Germany, and Penzberg, Germany. The US registration is for Roche Diagnostics United States. The testing locations are not specified, but typically studies for these types of devices are conducted in-house or by contract labs associated with the manufacturer. The studies are prospective in nature as they describe planned (real-time stability) or recently completed (value assignment, other stability) tests of the new device.

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

This section is not applicable as the device is a calibrator for an in vitro diagnostic assay. "Ground truth" in this context refers to metrologically traceable reference values rather than expert interpretation of clinical data.

Ground Truth Establishment: The Elecsys Estradiol III CalSet was standardized against ID-GC/MS (isotope dilution gas chromatography mass spectrometry). This is a highly accurate reference method.

4. Adjudication Method for the Test Set

This section is not applicable as it refers to a clinical data adjudication process. For this calibrator, "adjudication" is inherent in the analytical methods and statistical analysis of duplicates and runs on multiple systems. The acceptance criteria for recovery within a specific range serve as the "adjudication" of performance.

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

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic devices where human readers interpret medical images or data. The Elecsys Estradiol III CalSet is a laboratory calibrator, and its performance is assessed through analytical studies demonstrating its accuracy and stability against reference methods.

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

This question is not directly applicable in the traditional sense for an AI/algorithm. However, the performance studies described (CalSet Value Assignment, Stability Studies) are intrinsically "standalone" in that they evaluate the analytical performance of the calibrator itself, independent of operator interpretation in a clinical diagnostic sense. The device's "performance" is its ability to consistently produce accurate reference signals within defined parameters.

7. The Type of Ground Truth Used

The ground truth used for the Elecsys Estradiol III CalSet is analytical traceability to ID-GC/MS (isotope dilution gas chromatography mass spectrometry). This is a highly accurate and precise analytical method considered a "gold standard" for quantifying specific analytes.

8. The Sample Size for the Training Set

This question is not applicable as this device is not an AI/ML algorithm that requires a "training set." It is a physical calibrator for an immunoassay.

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

This question is not applicable as this device is not an AI/ML algorithm that requires a "training set."

Summary

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510(k) Summary, Elecsys Estradiol III CalSet

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.

Device Name	Proprietary name:	Elecsys Estradiol III CalSet
	Common name:	Estradiol III CalSet
	Classification:	21 CFR 862.1150, Calibrator, Secondary
	Product Code:	JIT

For the Estradiol III CalSet, the establishment registration number for Establishment Roche Diagnostics GmbH in Mannheim, Germany, is 9610126 and for Registration Penzberg, Germany, is 9610529. The establishment registration number for Roche Diagnostics United States is 1823260.

Classification FDA has classified the product as a Class II device.

Product Name	Panel	Product Code	Classification Name	Regulation Citation
Estradiol IIICalSet	ClinicalChemistry	JIT	Calibrator,Secondary	21 CFR 862.1150

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DeviceDescription	Elecsys Estradiol III CalSet:• The Elecsys Estradiol III CalSet is a lyophilized product consisting ofsynthetic Estradiol in a human serum matrix. It has been standardizedagainst ID-GC/MS (isotope dilution gas chromatography massspectrometry).
Intended use	Elecsys Estradiol III CalSet:• Estradiol III CalSet is used for calibrating the quantitative ElecsysEstradiol III assay on the Elecsys and cobas e immunoassay analyzers.
Predicatedevice	The Elecsys Estradiol III CalSet is substantially equivalent to the predicatedevice, Elecsys Estradiol II CalSet II (K992981).
SubstantialEquivalenceComparison	The following tables compare the Elecsys Estradiol III CalSet with thepredicate device.

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Comparison The table below compares Elecsys Estradiol III CalSet with the predicate device, Table Elecsys Estradiol II CalSet II (K992981).

The change in the new product was a shift in the Cal 2 target value.

Table

Characteristic	Elecsys Estradiol III CalSet(Candidate)	Elecsys Estradiol II CalSet II(K992981)
Intended Use	Estradiol III CalSet is used forcalibrating the quantitativeElecsys Estradiol III assay onthe Elecsys and cobas eimmunoassay analyzers.	Estradiol II CalSet II is used forcalibrating the quantitativeElecsys Estradiol II assay on theElecsys and cobas eimmunoassay analyzers.
Analyte	Estradiol (synthetic)	Same
Matrix	Human serum matrix	Same
Levels	Two	Same
Target Ranges	Cal 1: 20 pg/mLCal 2: 2000 pg/mL	Cal 1: 20 pg/mLCal 2: 3000 pg/mL
Format	Lyophilized	Same
Handling	Carefully dissolve the contentsof one bottle by adding exactly1.0 mL of distilled or deionizedwater and allow to stand closedfor 15 minutes to reconstitute.Mix carefully, avoiding thefoam formation.Transfer aliquots of thereconstituted calibrators intoempty labeled snap-cap bottles(CalSet Vials). Attach thesupplied labels to the additionalbottles. Store the aliquotsimmediately at -20°C.Perform only one calibrationprocedure per aliquot.	Same.
Table continued
Characteristic	Elecsys Estradiol III CalSet(Candidate)	Elecsys Estradiol II CalSet II(K992981)
Stability	Unopened:• Store at 2-8°C until expirationdateOpened:• 2-8°C: 24 hours• 20-25°C: 5 hours on Elecsys2010/cobas e 411; use onlyonce on MODULARANALYTICS E170, cobas e601 and cobas e 602analyzers• -20°C: 31 days (freeze onlyonce)	Unopened:• Store at 2-8°C until expirationdateOpened:• 2-8°C: 24 hours• 20-25°C: use only once• -20°C: 3 month
Traceability	The Elecsys Estradiol III CalSet was standardized against ID-GC/MS(isotope dilution gas chromatography mass spectrometry).
EvaluationsSummary	The Elecsys Estradiol III CalSet was evaluated for value assignment,reconstitution and stability.
CalSet ValueAssignment	Value assignment testing was conducted and passed pre-defined acceptancecriteria. The target values for the two levels of the Estradiol III CalSet kit arechosen to obtain the best fit with the Master Calibration Curve, together withthe Rodbard curve parameters encoded in the reagent barcode. For eachElecsys Estradiol III CalSet lot manufactured, the calibrators are run induplicate on at least three (3) Elecsys 2010/cobas e 411 analyzers and at leastthree (3) cobas e 601/MODULAR ANALYTICS E170 analyzers with allEstradiol III reagent lots available. The assigned value of each calibrator isdefined as the mean value obtained over at least six (6) runs on at least three (3)analyzers) of the respective calibrator.Measurement values for PreciControl Universal (Level 1 & 2), a multi-analytecontrol recommended for use to monitor accuracy and precision of specifiedanalytes, are read from the calibration curves generated. The pre-definedacceptance criteria for PreciControl Universal have to be met to release theAssigned Values for Estradiol III CalSet.

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Stability Three studies were performed in order to verify the stability claims for the Studies Estradiol III CalSet. Stability studies after reconstitution and an accelerated stability study were completed on the cobas e 411. Additionally, a real-time stability study is planned.

Study 1. Stability at 2-8ºC, -20ºC, in open vial and freeze/thaw cycles (after reconstitution):

The on-test materials were reconstituted and stored closed for 73 hours at 2 to 8°C, and for 32 days at -20°C and for 7 hours at 20 to 25°C in open vial prior to testing. In addition, the stability of the Estradiol III CalSet for two (2) freeze/thaw cycles was evaluated.

The on-test and reference materials were tested in duplicate and the recovery was calculated as percent of the reference value.

The acceptance criterion was 95 to 105 % signal recovery of the reference material value. The reference material was a freshly reconstituted set of Estradiol III CalSet.

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 Estradiol III CalSet (stored at 2 to 8℃). After 3 weeks, the on-test and reference materials were tested in duplicate. The on-test recovery was calculated as a percent of the reference value. One Estradiol III CalSet lot was evaluated in duplicate.

The acceptance criterion was 95 to 105 % recovery of the reference material value.

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Stability Studies, continued	Study 3. Real-Time Stability: In addition, real-time stability is being evaluated as follows: In the on-going real-time stability study, the Estradiol III CalSet test material is stored at 2-8°C. The CalSets are tested in duplicate at specified intervals over the shelf life of the device up to the planned shelf life plus one month (19 months). Real-time stability is calculated based on the recovery of signal of stressed calibrator (stored at 2-8°C) vs. unstressed calibrator (stored at -20°C). At the specified intervals over the shelf life, the mean value of the stressed calibrator was calculated as percent recovery of the unstressed value (each tested in duplicates at the same time point). The acceptance criterion for Estradiol III Calibrator 1 and 2 is recovery of 95-105 % of the reference value. The testing will continue with this stability protocol until data to support a claim of 18 months are achieved.
Conclusion	We trust that the information provided in this Premarket Notification (510(k)) will support a determination of substantial equivalence for the Elecsys Estradiol III CalSet.

Stability Studies, continued

Study 3. Real-Time Stability: In addition, real-time stability is being evaluated as follows: In the on-going real-time stability study, the Estradiol III CalSet test material is stored at 2-8°C. The CalSets are tested in duplicate at specified intervals over the shelf life of the device up to the planned shelf life plus one month (19 months). Real-time stability is calculated based on the recovery of signal of stressed calibrator (stored at 2-8°C) vs. unstressed calibrator (stored at -20°C). At the specified intervals over the shelf life, the mean value of the stressed calibrator was calculated as percent recovery of the unstressed value (each tested in duplicates at the same time point). The acceptance criterion for Estradiol III Calibrator 1 and 2 is recovery of 95-105 % of the reference value. The testing will continue with this stability protocol until data to support a claim of 18 months are achieved.

Conclusion

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

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Public Health Service

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

August 29, 2014

ROCHE DIAGNOSTICS KELLI TURNER REGULATORY AFFAIRS PRINCIPAL 9115 HAGUE ROAD INDIANAPOLIS IN 46250-0416

Re: K142021

Trade/Device Name: Elecsys Estradiol III CalSet Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: II Product Code: JIT Dated: July 24, 2014 Received: July 25, 2014

Dear Ms. Kelli Turner:

This letter corrects our substantially equivalent letter of August 12, 2014. 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

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Page 2 - Ms. Kelli Turner

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.

If you desire specific advice for your device on our labeling regulation (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/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

510(k) Number (if known) k 142021

Device Name Elecsys Estradiol III CalSet

Indications for Use (Describe)

Estradiol III CalSet is used for calibrating the quantitative Elecsys Estradiol III assay on the Elecsys and cobas e immunoassay analyzers.

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

2 Prescription Use (Part 21 CFR 801 Subpart D)

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

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

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Regulation Number and Section

§ 862.1150 Calibrator.

(a)
Identification. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. (See also § 862.2 in this part.)(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.