The LOCI CA 125 II™ method is an in vitro diagnostic test for the quantitative measurement of CA 125 antigen in human serum and lithium heparin and EDTA plasma on the Dimension Vista® System. Measurements of CA 125 are used as an aid in monitoring disease progress or response to therapy or for the recurrent or residual disease for patients with epithelial ovarian cancer. Serial testing for patient CA 125 assay values should be used in conjunction with other clinical methods used for monitoring ovarian cancer. It is recommended that the LOCI CA 125 Il method be used in conjunction with signs and symptoms of a clinical evaluation by a physician trained and experienced in the management of gynecological cancers. This assay is not intended for screening or diagnosis of ovarian cancer or for use on any other system.

The LOCI 6 CAL is an in vitro diagnostic product for the calibration of Alpha-Fetoprotein (AFP), Carcinocmbryonic Antigen (CEA), and CA 125 (CA125) methods on the Dimension Vista® System.

Device Description

The LOCI CA 125Il™ method is a homogeneous, sandwich chemiluminescent immunoassay based on LOCI® technology. The LOCI® reagents include two synthetic bead reagents and a biotinylated anti-CA 125 monoclonal antibody (M11) fragment. The first bead reagent (Chemibeads) is coated with an anti-CA125 monoclonal antibody (OC 125) and contains a chemiluminescent dye. The use of the M11 antibody in combination with OC 125 defines this method as a second generation CA 125 assay. The second bead reagent (Sensibeads) is coated with streptavidin and contains a photosensitizer dye. Sample is incubated with biotinylated antibody and Chemibeads to form bead-CA 125-biotinylated antibody sandwiches. Sensibeads are added and bind to the biotin to form bead-pair immunocomplexes. Illumination of the complex at 680 nm generates singlet oxygen from Sensibeads which diffuses into the Chemibeads, triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is a direct function of the CA 125 concentration in the sample.

The LOCI 6 calibrator is a multi-analyte liquid, frozen bovine serum albumin based product containing Alpha-Fetoprotein from human cord blood, Carcinoembryonic Antigen from human cell culture and CA 125 from human cell culture. The kit consists of ten vials per level (A-E), 2.0 mL per vial. Description of the manufacturing, value assignment and stability testing process are provided in this submission report.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and study for the Dimension Vista® LOCI CA 125 (CA125) Flex® Reagent Cartridge, structured according to your request:

Based on the provided 510(k) Summary of Safety and Effectiveness, this document describes an in vitro diagnostic (IVD) device meant to quantify a biomarker (CA 125) rather than a device for image analysis or other AI-based diagnostics. Therefore, many of the requested fields (like "Number of experts used to establish the ground truth for the test set," "Adjudication method," "MRMC comparative effectiveness study," and details about AI performance) are not applicable to this type of device and submission.

The "acceptance criteria" for an IVD like this are typically demonstrated through various performance characteristics, often compared to a predicate device. The "study that proves the device meets the acceptance criteria" refers to a battery of analytical performance studies (e.g., precision, accuracy/method comparison, linearity, interference, limit of detection) rather than a clinical reader study typical for imaging AI.

1. Table of acceptance criteria and the reported device performance

The document does not explicitly state "acceptance criteria" in a table form with numerical targets, which is common for full submission documents but often summarized for the 510(k) summary. Instead, it states that "Comparative testing described in the submission report demonstrates substantial equivalent performance." This implies that the performance of the new device (LOCI CA 125II™ Flex® Reagent) was found to be statistically comparable to the predicate device (ADVIA Centaur CA125II assay) across various analytical parameters. The key comparison points highlighted in the document focus on feature similarities for substantial equivalence, not performance metrics.

Feature	Acceptance Criteria (Implied: Substantial Equivalence to Predicate)	Reported Device Performance (Implied: Demonstrated Substantial Equivalence)
Intended Use	Similar to predicate for monitoring ovarian cancer progress/response	"Substantially equivalent" in aid of monitoring disease progress, response to therapy, or recurrent/residual disease for epithelial ovarian cancer. Not for screening or diagnosis.
Sample Type	Compatibility with serum (like predicate) and additional matrices	Serum, lithium heparin, and EDTA plasma (Broader than predicate's serum-only).
Measuring Range	Comparable to predicate (2-600 U/mL)	1.5 - 1000 U/mL (Broader than predicate's 2-600 U/mL).
Sample Size	Efficacy with appropriate sample volume	5 µL (Smaller than predicate's 50 µL).
Measurement Type	Chemiluminescent, sandwich immunoassay	Chemiluminescent: Homogeneous sandwich immunoassay based on LOCI® technology.

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

The document does not detail specific sample sizes for "test sets" in the way an AI study would. For IVD devices, "test set" data usually refers to samples used in analytical performance studies (e.g., precision, linearity, method comparison).

Sample Size: Not explicitly stated in the summary for individual analytical studies. Such details would typically be found in the full submission report's study protocols and results sections.
Data Provenance: Not specified in the summary. For IVD analytical studies, samples often come from clinical laboratories or biobanks, and the country of origin is not always highlighted unless there's a specific regulatory or demographic reason. The studies are prospective in the sense that they are conducted specifically to validate the device's performance, but the samples themselves might be retrospective collections.

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

Not Applicable (N/A): This is an in vitro diagnostic assay for measuring a biomarker concentration, not an imaging or AI diagnostic device requiring expert interpretation for ground truth. The "ground truth" for an IVD refers to the true concentration of the analyte, often established by reference methods or gravimetric preparation of controls/calibrators.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set

Not Applicable (N/A): Adjudication methods are relevant for human interpretation of data, typically in clinical trials or expert consensus for image labeling. This is an automated analytical device.

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 (N/A): This is an in vitro diagnostic assay, not an AI-assisted diagnostic tool. No human readers are involved in the direct output of this device.

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

Yes, in essence. The performance described for the LOCI CA 125II™ method is inherently "standalone" in that it's the direct analytical output of the instrument and reagents, quantifying CA 125 in a sample without human intervention in the measurement process itself. The "algorithm" here is the chemical reaction and light detection process. The summary implies the performance was evaluated on this basis.

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

For an IVD assay measuring a biomarker concentration (CA 125), the "ground truth" for analytical studies would typically be:

Reference Methods: For accuracy and method comparison, samples might be run on established, validated reference methods, or the predicate device itself serves as the comparator.
Known Concentrations: For linearity, limit of detection, and calibration, samples are often prepared with known, certified concentrations of the analyte (e.g., using purified CA 125 antigen).
Definitive Quantitation: In some cases, highly accurate quantitative techniques (e.g., mass spectrometry, although less common for routine biomarkers) might be considered a gold standard.

(The document does not explicitly state which ground truth method was used but it would be one of the above for an IVD.)

8. The sample size for the training set

Not Applicable (N/A): This is an in vitro diagnostic assay that is not based on machine learning or AI models requiring "training sets" in the traditional sense. The development of such assays involves reagent formulation, instrument design, and extensive analytical validation, but not machine learning training.

9. How the ground truth for the training set was established

Not Applicable (N/A): As there is no "training set" in the context of machine learning for this IVD, no ground truth was established in that manner. The "ground truth" established during the development and validation phase would be related to the chemical and physical properties of the reagents and the detection system, as described in point 7.

Summary

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510(k) Summary of Safety and Effectiveness for the

Dimension Vista® LOCI CA 125 (CA125) Flex® Reagent Cartridge

Dimension Vista® LOCI® 6 Calibrator

APR 1 2 2011

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

A. 510(k) Number: K100321

B. Date of Preparation: February 2, 2010

C. Proprietary and Established Names:

LOCI CA 125 Flex® Reagent Cartridge

Dimension Vista® LOCI 6 Calibrator

D. Applicant:

Siemens Healthcare Diagnostics Inc.

P.O. Box 6101, Newark, DE 19714-6101

Pamela A. Jurga, Regulatory & Clinical Affairs Specialist

Office Number: (302) 631-8891 fax Number: (302) 631-6299

E. Regulatory Information:

LOCI CA125 Flex® Reagent Cartridge:

Regulation section: 21 CFR § 866.6010 Tumor-Associated antigen immunological test system
Classification: Class II
Product Code: LTK - Test, Epithelial Ovarian Tumor-Associated Antigen (Ca125)
Panel: Immunology

LOCI 6 Calibrator:

Regulation section: 21 CFR § 862.1150 Calibrator
Classification: Class II
Product Code: JIX - Calibrator, Multi-Analyte Mixture
Panel: Immunology

F. Predicate Device:

The predicate device used to demonstrate substantial equivalence to the LOCI CA125|I™ Flex® Reagent Cartridge is the CA 125II Assay for the ADVIA Centaur System previously cleared under K020828.

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The predicate device used to demonstrate substantial equivalence to the Dimension Vista® LOCI 6 Calibrator is the Dimension Vista® LOCI 5 Calibrator previously cleared under K071597 and K071603.

G. Device Description:

H. Intended Use:

The LOCI CA 125 II™ method is an in vitro diagnostic test for the quantitative measurement of CA 125 antigen in human serum and lithium heparin and EDTA plasma on the Dimension Vista® System. Measurements of CA 125 are used as an aid in monitoring disease progress or response to therapy or for the recurrent or residual disease for patients with epithelial ovarian cancer. Serial testing for patient CA 125 assay values should be used in coniunction with other clinical methods used for monitoring ovarian cancer. It is recommended that the LOCI CA 125 Il method be used in conjunction with signs and symptoms of a clinical evaluation by a physician trained and experienced in the management of gynecological cancers. This assay is not intended for screening or diagnosis of ovarian cancer or for use on any other system.

The LOCI 6 CAL is an in vitro diagnostic product for the calibration of Alpha-Fetoprotein (AFP), Carcinoembryonic Antigen (CEA) and Cancer Antigen125II™ (CA125) methods on the Dimension Vista® system.

l. Substantial Equivalence Information:

The LOCI CA 125||™ method is substantially equivalent to other CA125 test systems such as the ADVA Centaur CA125Il assay (K020828). The LOCI 6 calibrator is substantially equivalent to other calibrators such as the LOCI 5 calibrator (K071597 and K071603). The following table provides a comparison of the important similarities and differences:

Feature	LOCI CA 125II™ Flex® Reagentcartridge	CA 125II Assay for the ADVIA CentaurSystem (K020828)
Intended Use	The LOCI CA 125 II™ method is an in vitrodiagnostic test for the quantitativemeasurement of CA 125 antigen in humanserum and lithium heparin and EDTAplasma on the Dimension Vista® System.Measurements of CA 125 are used as anaid in monitoring disease progress orresponse to therapy or for the recurrentor residual disease for patients withepithelial ovarian cancer. Serial testing forpatient CA 125 assay values should beused in conjunction with other clinicalmethods used for monitoring ovarian	For in vitro diagnostic use in thequantitative, serial determination in humanserum and to aid in the management ofpatients with ovarian carcinoma using theADVIA Centaur and ADVIA Centaur XPsystems. The test is intended for use as anaid in monitoring patients who are clinicallyfree of disease and should be used inconjunction with other clinical methods usedfor monitoring ovarian cancer. Serialtesting for CA 125 in the serum of patientswho are clinically free of disease should beused in conjunction with other clinicalmethods used for early detection of cancerrecurrence. The test is also intended for

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	cancer. It is recommended that the LOCICA 125 II method be used in conjunctionwith signs and symptoms of a clinicalevaluation by a physician trained andexperienced in the management ofgynecological cancers. This assay is notintended for screening or diagnosis ofovarian cancer or for use on any othersystem.	use as an aid in the management of ovariancancer patients with metastatic disease bymonitoring the progression or regression ofdisease in response to treatment. It isrecommended that the ADVIA Centaur CA125 II assay be used under the order of aphysician trained and experienced in themanagement of gynecological cancers.This assay is not intended for screening ordiagnosis of ovarian cancer or for use onany other system.
Sample Type	Serum and lithium heparin and EDTAplasma	Serum
MeasuringRange	1.5 -1000 U/mL	2-600 U/mL
Sample Size	5 µL	50 µL
Measurement	Chemiluminescent:	Chemiluminescent:
	Homogenous sandwich immunoassaybased on LOCI® technology	Two site sandwich immunoassay usingdirect chemiluminometric technology

Feature	LOCI 6 calibrator	LOCI 5 CalibratorK071597 and K071603
Intended Use	The LOCI 6 CAL is an in vitrodiagnostic product for the calibration ofAlpha-Fetoprotein (AFP),Carcinoembryonic Antigen (CEA) andCancer Antigen12511™ (CA125)methods on the Dimension Vista®system.	an in vitro diagnostic product for thecalibration of Alpha-Fetoprotein (AFP),Carcinoembryonic Antigen (CEA)methods on the Dimension Vista®system.
Matrix	BSA-based matrix	BSA-based matrix
Preparation	Liquid:Provided ready to use.	Liquid:Provided ready to use.
TargetConcentrationsCA 125	Level 1 (CAL A): 0U/mLLevel 2 (CAL B): 8U/mLLevel 3 (CAL C): 60U/mLLevel 4 (CAL D): 250 U/mLLevel 5 (CAL E): 1050 U/mL	None
Storage	Store at -15 to - 25 °C.	Store at 2 to 10°C.

J. Conclusion:

The LOCI CA 125II™ method Flex® reagent cartridge is substantially equivalent to the ADVIA Centaur CA125II assay (K020828). Comparative testing described in the submission report demonstrates substantial equivalent performance.

The Dimension Vista® LOCI 6 CAL is substantially equivalent to the Dimension Vista® LOCI 5 CAL (K071597 and K071603).

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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with its wings spread, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES-USA" arranged in a circular pattern around the eagle. The eagle is depicted in a simple, abstract style, with flowing lines suggesting movement. The text is in all caps and is evenly spaced around the circle.

Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993

Siemens Healthcare Diagnostics c/o Ms. Pamela A. Jurga Regulatory and Clinical Affairs Specialist PO Box 6101 Mailstop 514 Newark, DE 19714-6101

APR 1 2 201

Re: K100321

Trade/Device Name: Dimension Vista® LOCI CA125 Flex® reagent cartridge Dimension Vista® LOCI 6 Calibrator Regulation Number: 21 CFR §866.6010 Regulation Name: Tumor-Associated antigen immunological test system Regulatory Class: Class II Product Code: LTK. JIT Dated: March 31, 2011 Received: April 1, 2011

Dear Ms. Jurga:

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.

If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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

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Page 2 – Ms. Pamela A. Jurga

CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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 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/cdrh/industry/support/index.html.

Sincerely yours,

Marie M Chan

Maria M. Chan. Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known):

K100321

Device Name: Dimension Vista® CA 125 Flex® Reagent

Indications For Use:

X Prescription Use (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Reena Philip

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety Page 1 of

K100321 510K

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Indications For Use Statement

510(k) Number (if known):

Device Name:

Dimension Vista® LOCI 6 Calibrator

Indications for Use:

The LOCI 6 CAL is an in vitro diagnostic product for the calibration of Alpha-Fetoprotein (AFP), Carcinocmbryonic Antigen (CEA), and CA 125 (CA125) methods on the Dimension Vista® System.

Prescription Use X (Per 21 CFR 801 Subpart D) AND/OR

Over-the-counter Use (21 CFR 801 Subpart C)

(PI.EASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

-------------------------------------==============================================================================================================================================================================

Concurrence of CDRH, Office of -In Vitro Diagnostic Devices (OIVD)

Reene Philip

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and 9 afety

510K k/0032)

Regulation Number and Section

§ 866.6010 Tumor-associated antigen immunological test system.

(a)
Identification. A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.(b)
Classification. Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.