The CA 125 II CalSet II is a lyophilized product consisting of human CA 125 in an equine (Cal 1) and a human (Cal 2) serum matrix. During manufacture, the analyte is spiked into the matrix at the desired concentration levels.

AI/ML Overview

The provided text describes a 510(k) Summary for the CA 125 II CalSet II device, which is a calibrator for immunoassay analyzers. The purpose of the submission is to change the calibrator from a liquid to a lyophilized material and to decrease the concentration of Cal 1. The document focuses on establishing substantial equivalence to a predicate device rather than providing a detailed study demonstrating device performance against specific acceptance criteria.

However, based on the information provided, we can infer some aspects related to "acceptance criteria" through the comparative nature of the 510(k) submission.

1. Table of Acceptance Criteria and Reported Device Performance

The submission does not explicitly state acceptance criteria in a quantitative table format as might be seen for diagnostic accuracy studies. Instead, it demonstrates equivalence through a comparison of characteristics and states that performance was evaluated. The implicit acceptance criterion is that the new device's performance (value assignment, stability, and reconstitution) is substantially equivalent to that of the predicate device.

Characteristic Evaluated	Acceptance Criteria (Implicit)	Reported Device Performance (Summary)
Value Assignment	Performance should be comparable to the predicate device, ensuring accurate calibration of the Elecsys CA 125 II assay.	The data demonstrate that the performance of the CA 125 II CalSet II (including value assignment) is substantially equivalent to that of the predicate device, Elecsys® CA 125 II CalSet.
Stability	The lyophilized and reconstituted stability of the new device should be suitable for its intended use and comparable to the predicate's stability (considering the format change).	Candidate Device (Lyophilized): - Lyophilized: Up until labeled expiration date - Reconstituted (-20°C): 20 weeks (freeze only once) - Reconstituted (2-8°C): 12 weeks - On analyzer (20-25°C): up to 5 hours (multiple uses) / use only once (single use)
Reconstitution	The device should reconstitute correctly and consistently to provide accurate calibration.	The data demonstrate that the performance of the CA 125 II CalSet II (including reconstitution) is substantially equivalent to that of the predicate device. The handling instructions detail the reconstitution process.

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

The document does not specify a "test set" in the context of diagnostic accuracy, nor does it provide a sample size for such a test. It describes the device as a calibrator, and its performance evaluation focused on its ability to calibrate the Elecsys CA 125 II assay. The data provenance (country of origin, retrospective/prospective) is not mentioned for these performance evaluations.

3. Number of Experts Used to Establish Ground Truth and Qualifications of Experts

This information is not applicable. The device is a calibrator, not a diagnostic device that requires expert interpretation for establishing ground truth data like pathology or imaging. The "ground truth" for a calibrator relates to the accuracy of its assigned values and its stability, which would be determined through laboratory analyses and comparisons to reference methods, not expert consensus on pathology/imaging.

4. Adjudication Method for the Test Set

This information is not applicable for a calibrator device.

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 patient cases, and the objective is to assess the impact of AI assistance on their performance. The CA 125 II CalSet II is a calibrator and does not involve human interpretation of cases.

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

The concept of "standalone performance" typically applies to AI algorithms for diagnostic interpretation. For a calibrator, the "performance" relates to its analytical characteristics (value assignment, stability, reconstitution) which are assessed in a laboratory setting through analytical methods, not an AI algorithm. The device itself (the calibrator) acts in a "standalone" analytical capacity by providing known concentration levels for instrument calibration.

7. The Type of Ground Truth Used

The "ground truth" for a calibrator concerns its traceability and the accuracy of its assigned target ranges.

Target Ranges: Cal 1: 0 U/mL, Cal 2: 500 U/mL.
Traceability: The Elecsys CA 125 II assay (which the calibrator supports) has been standardized against the Enzymun Test CA 125 II method. This in turn was standardized against the CA 125 II RIA from Fujirebio Diagnostics. This hierarchical standardization essentially establishes the "ground truth" for the CA 125 values being calibrated.

8. The Sample Size for the Training Set

This information is not applicable. The device is a calibrator, not an AI algorithm that undergoes training.

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

This information is not applicable.

Summary

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K14/0112

JUN 0 6 2014

510(k) Summary

Device Name

Proprietary name:	CA 125 II CalSet 11
Common name:	CA 125 II CalSet II
Classification name:	Calibrator, secondary

For the CA 125 II CalSet II, the establishment registration number (Roche Diagnostics GmbH Mannheim) is 9610126. The establishment registration

Diagnostics Only Internation United States is 1823260. Registration

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

Panel	ProductCode	Classification Name	RegulationCitation
Clinical Chemistry	JIT	Calibrator, Secondary	862.1150

PredicateDevice	The CA 125 II CalSet II is substantially equivalent to other products incommercial distribution intended for similar use. We claim equivalency tothe currently marketed CA 125 CalSet (K003969).
DeviceDescription	The CA 125 II CalSet II is a lyophilized product consisting of human CA 125in an equine (Cal 1) and a human (Cal 2) serum matrix. During manufacture,the analyte is spiked into the matrix at the desired concentration levels.
Intended Use	CA 125 II CalSet II is used for calibrating the quantitative Elecsys CA 125 IIassay on the Elecsys and cobas c immunoassay analyzers.
Reason forSubmission	The CA 125 II CalSet II is being changed from a liquid to lyophilizedmaterial. In addition, we are decreasing the concentration of Cal 1 to 0 U/mLby using equine serum.

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510(k) Summary

Table 1 below compares CA 125 II CalSet II with the predicate device, CA Comparison 125 II CalSct (K003969). Table

Changes in the new product include lowering Cal 1 to no CA 125 (by using equine serum), and going from liquid calibrators to lyophilized.

Table 1. Comparison of Candidate and Predicate Devices

Characteristic	CA 125 II CalSet II(Candidate Device)	Elecsys ® CA 125 II CalSet(K003969)
IntendedUse	CA 125 II CalSet II is used forcalibrating the quantitative ElecsysCA 125 II assay on the Elecsys andcobas e immunoassay analyzers.	Same
Format	Lyophilized	Liquid
Analyte	Human CA 125	Same
Matrix	Equine serum (Call) and Humanserum (Cal 2)	Same
Levels	Two	Same
TargetRanges	Cal 1: 0 U/mLCal 2: 500 U/mL	Cal 1: 35 U/mLCal 2: 500 U/mL
Stability	Lyophilized:• Up until labeled expiration dateReconstituted:• -20°C: 20 weeks (freeze only once)• 2-8248C: 12 weeks• on the Elecsys 2010 and cobas e411(20-25°C): up to 5 hours• on the MODULAR ANALYTICSE170, cobas e601 and cobas e602analyzers: use only once	Unopened:• Store at 2-8°C until expiration dateOpened:• at 2-8°C: 12 weeks• on the Elecsys 2010 and cobas e411(20-25°C): up to 5 hours• on the MODULAR ANALYTICSE170, cobas e601 and cobas e602analyzers: use only once
Characteristic	CA 125 II CalSet II(Candidate Device)	Elecsys® CA 125 II CalSet(K003969)
Handling	Carefully dissolve the contents ofone bottle by adding exactly 1.0 mLof distilled or deionized water andallow to stand closed for 15 minutesto reconstitute. Mix carefully,avoiding foam formation.Transfer the reconstituted calibratorsinto the supplied empty labeled snap-cap bottles.Elecsys 2010 and cobas e 411analyzers: The reconstitutedcalibrators should only be left on theanalyzers during calibration at 20-25°C. After use, close the bottles assoon as possible and store upright at2-8°C. Due to possible evaporationeffects, not more than 5 calibrationprocedures per bottle set should beperformed.If necessary, freeze in aliquots.MODULAR ANALYTICS, cobas e601 and cobas e 602 analyzers:Unless the entire volume is necessaryfor calibration on the analyzers,transfer aliquots of the reconstitutedcalibrators into empty snap-capbottles (CalSet Vials). Attach thesupplied labels to these additionalbottles. Aliquots intended forstorage at -20°C should be frozenimmediately.Perform only one calibrationprocedure per aliquot.	The calibrators are supplied ready-for-use in bottles compatible with thesystem.Elecsys 2010 and cobas e 411analyzers: The calibrators shouldonly be left on the analyzers duringcalibration at 20-25°C. After use,close the bottles as soon as possibleand store at 2-8°C.Due to possible evaporation effects,not more than 5 calibrationprocedures per bottle set should beperformed.MODULAR ANALYTICS E170,cobas e 601 and cobas e 602analyzers: Unless the entire volumeis necessary for calibration on theanalyzers, transfer aliquots of theready-for-use calibrators to emptysnap-cap bottles (CalSet Vials).Attach the supplied labels to theseadditional bottles. Store the aliquotsat 2-8°C for later use.Perform only one calibrationprocedure per aliquot.
Characteristic	CA 125 II CalSet II(Candidate Device)	Elecsys CA 125 II CalSet(K003969)
Traceability	The Elecsys CA 125 II assay hasbeen standardized against theEnzymun Test CA 125 II method.This in turn was standardized againstthe CA 125 II RIA from FujirebioDiagnostics.	Same

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510(k) Summary, Continued

Table 1. Comparison of Candidate and Predicate Devices, continued

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PerformanceCharacteristics	The CA 125 II CalSet II was evaluated for value assignment, stability, andreconstitution.
Conclusion	The data demonstrate that the performance of the CA 125 II CalSet II issubstantially equivalent to that of the predicate device, Elecsys® CA 125 IICalSet.

. . . . . . .

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 109113 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

June 6, 2014

ROCHE DIAGNOSTICS C/O DR. JANE ELLEN PHILLIPS REGULATORY PROGRAM MANAGER 9115 HAGUE ROAD INDIANAPOLIS, IN 46250

Re: K140112

Trade/Device Name: CA 125 II CalSet II Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: II Product Code: JIT Dated: May 16, 2014 Received: May 19, 2014

Dear Dr. Phillips:

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 commerce provide to may no may and 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 it may be subject to numbers, Title 21, Parts 800 to 898. In addition, FDA may round in the announcements concerning your device in the Federal Register.

Please be advised that FDA is 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 mat I DA has made a sold regulations administered by other Federal agencies. You must of any I cochi statutes and regenments. including, but not limited to: registration and listing (21 Comply with an the Act 3 requirements 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements medical device-related adverse events) (2) carren (21 CFR Part 820); and if application (201 as set form in the qualify by actions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2-Dr. Jane Ellen Phillips

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance 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.fdagov/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 Small Manufacturers, International and Consumer Assistance 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.

Sincerely yours,

Maria M. Chan -S

Maria M. Chan, Ph.D. 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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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Indications for Use

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

510(k) Number (if known) K140112

Device Name Elecsys CA 125 II CalSet II

Indications for Use (Describe) CA 125 II CalSet II is used for calibrating the quantitative Elecsys CA 125 II assay on the Elecsys and 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)

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)

Elizabeth A. Stafford -S

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 semble I he burden instructions, search existing data sources, gather and maintain the data needed and completer lifite to review instructions, search existing asia common, generaling this burden estimate or any other aspect and teller the occasion, 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."

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.