(58 days)
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No
The summary describes a standard immunoassay and analyzer system. There is no mention of AI, ML, or any computational methods beyond basic calibration and data processing for quantitative results.
No.
The device is an in vitro diagnostic test used to measure cancer antigen levels, which aids in monitoring the progression or regression of breast cancer. It does not provide treatment or therapy.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is "an in vitro diagnostic test."
No
The device is an in vitro diagnostic test that utilizes physical reagents and is intended for use on specific hardware analyzers (ADVIA Centaur family of analyzers). It is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The very first sentence explicitly states, "The ADVIA Centaur® BR assay is an in vitro diagnostic test..." This is the most direct confirmation.
- Nature of the Test: The test measures the concentration of a specific substance (cancer antigen CA 27.29) in human biological samples (serum and plasma). This is a hallmark of in vitro diagnostics, which are performed outside of the living body using samples taken from the body.
- Purpose of the Test: The test is used as an aid in monitoring patients and managing disease progression. This aligns with the purpose of IVDs, which provide information to aid in diagnosis, monitoring, or treatment decisions.
- Device Description: The description details a laboratory assay using reagents and a specific analyzer (ADVIA Centaur). This is consistent with the components and methods used in IVD testing.
N/A
Intended Use / Indications for Use
The ADVIA Centaur® BR assay is an in vitro diagnostic test for the quantitative serial determination of cancer antigen CA 27.29 in human serum and plasma (EDTA) using the ADVIA Centaur XP, and ADVIA Centaur XPT systems. The test is intended for use as an aid in monitoring patients previously treated for Stage III breast cancer. Serial testing for CA 27.29 in the serum and plasma of patients who are clinically free of disease should be used in conjunction with other clinical methods used for the early detection of cancer recurrence. The test is also intended for use as an aid in the management of breast cancer patients with metastatic disease by monitoring the progression or regression of disease in response to treatment.
Product codes (comma separated list FDA assigned to the subject device)
MOI
Device Description
The ADVIA Centaur BR assay is a fully automated, competitive immunoassay using direct, chemiluminescent technology. Results are determined using a calibration curve that is generated specifically on each instrument by a 2-point calibration and a master curve with the reagent bar code. The ADVIA Centaur BR assay is intended for use on the ADVIA Centaur family of analyzers. The ADVIA Centaur Calibrator G is a set of 2 level calibrators for the assay. Siemens recommends the use of commercially available quality control materials with at least two levels (low and high).
The ADVIA Centaur BR reagent kit contains the following:
- ADVIA Centaur BR ReadyPack primary reagent pack contains Lite Reagent and Solid Phase ● Reagent.
- Materials Required but Not provided:
- ADVIA Centaur Calibrator G: consists of 2 levels (low and high) of CA 27.29 calibrators in equine serum with sodium azide (0.1%) and preservatives; lyophilized.
- ADVIA Centaur BR Pretreatment Reagent: consists of sodium hydroxide (0.24 N) Optional Reagents:
- ADVIA Centaur Multi-Diluent 1: consists of equine serum with sodium azide (0.1%) and preservatives.
- . ADVIA Centaur BR Master Curve Material: consists of a set of 7 levels of CA 27.29 (MCM1-7) spiked in lyophilized equine serum with sodium azide (0.1% after reconstitution) and preservatives.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
The addition of the plasma (EDTA) sample and detection capability (LoB, LoD, LoQ) claims in the Instructions for Use (Package Inserts) for the ADVIA Centaur BR assay was demonstrated by testing the performance characteristics with the following studies:
- Detection Capability (LoB, LoD, LoQ)
- Specimen Equivalence by Method Comparison
- Interferences: EDTA
Detection Capability:
The Detection capability was determined in accordance with CLSI Document EP17-A2.
The LoB corresponds to the highest measurement likely to be observed for a blank sample with a probability of 95%.
The LoD corresponds to the lowest concentration of cancer antigen CA 27.29 that can be detected with a probability of 95%.
The LoQ corresponds to the lowest amount of cancer antigen CA 27.29 in a sample at which the within laboratory CV is ≤ 20%.
Specimen Equivalence by Method Comparison:
Specimen equivalency was determined with the Deming linear regression model in accordance with CLSI Document EP09-A3.
Comparison: Dipotassium EDTA Plasma vs. Serum
N: 101
Sample Interval: 10.80-444.42 U/mL
Slope (95%CI): 0.97 (0.955 – 0.993)
Intercept (95%CI): 2.21 U/mL (1.376 – 3.040)
Correlation Coefficient (r): 1.00
Interferences: EDTA:
Interference testing was performed in accordance with CLSI Document EP07-ed3.
Interferent: Dipotassium EDTA
Interferent Concentration: 5.4 mg/mL
Analyte Concentration: 20.46 U/mL, Bias: 1.8%
Analyte Concentration: 318.39 U/mL, Bias: 3.7%
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
LoB: 3.5 U/mL
LoD: 7.0 U/mL
LoQ: 9.0 U/mL
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: a symbol on the left and the FDA name and title on the right. The symbol on the left is a stylized representation of a human figure, while the text on the right reads "FDA U.S. FOOD & DRUG ADMINISTRATION" in blue letters.
February 13, 2020
Siemens Healthcare Diagnostics Inc. Ian Thompson Regulatory Clinical Affairs Specialist 511 Benedict Avenue Tarrytown, New York 10591
Re: K193489
Trade/Device Name: ADVIA Centaur BR Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-Associated Antigen Immunological Test System Regulatory Class: Class II Product Code: MOI Dated: December 16, 2019 Received: December 17, 2019
Dear Ian Thompson:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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
1
requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Carolina Kagan Acting Chief Immunology and Flow Cytometry Branch Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K193489
Device Name ADVIA Centaur® BR
Indications for Use (Describe)
The ADVIA Centaur® BR assay is an in vitro diagnostic test for the quantitative serial determination of cancer antigen CA 27.29 in human serum and plasma (EDTA) using the ADVIA Centaur XP, and ADVIA Centaur XPT systems. The test is intended for use as an aid in monitoring patients previously treated for Stage III breast cancer. Serial testing for CA 27.29 in the serum and plasma of patients who are clinically free of disease should be used in conjunction with other clinical methods used for the early detection of cancer recurrence. The test is also intended for use as an aid in the management of breast cancer patients with metastatic disease by monitoring the progression or regression of disease in response to treatment.
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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This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of 21 CFR 807.92 and the Safe Medical Device Act of 1990.
The assigned 510(k) Number is: K193489
Date Prepared 1.
December 13, 2019
Applicant Information 2.
- Contact: lan Thompson Regulatory Clinical Affairs Specialist
- Address: Siemens Healthcare Diagnostics Inc. 511 Benedict Avenue Tarrytown, NY 10591 914-524-2296 Phone:
Fax: 914-524-2101
Email ian thompson@siemens-healthineers.com
Regulatory Information 3.
Table 1. Regulatory Information for ADVIA Centaur® BR
| Trade Name | ADVIA Centaur® BR |
|---|---|
| Device | System, Test, Immunological, Antigen, Tumor |
| Regulation Description | Tumor-associated antigen immunological test system |
| FDA Classification | Class II |
| Review Panel | Immunology |
| Product Code | MOI |
| Regulation Number | 21 CFR 866.6010 |
4. Predicate Device Information
Predicate Device Name: ADVIA Centaur® BR
510(k) Number: K982680
The ADVIA Centaur BR assay with the addition of the plasma (EDTA) sample and detection capability [Limit of Blank (LoB), Limit of Detection (LoD), and Limit of Quantitation (LoQ)] claims in the Instructions for Use (Package Inserts) is substantially equivalent to the ADVIA Centaur BR assay that was cleared under 510(k) K982680, as shown below in the Substantial Equivalence Information section.
5. Intended Use / Indications for Use
The ADVIA Centaur® BR assay is an in vitro diagnostic test for the quantitative serial determination of cancer antigen CA 27.29 in human serum and plasma (EDTA) using the ADVIA Centaur®, ADVIA Centaur XP, and ADVIA Centaur XPT systems. The test is intended for use as an aid in monitoring patients previously treated for Stage II or Stage III breast
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510(k) Summary of Safety and Effectiveness
cancer. Serial testing for CA 27.29 in the serum and plasma of patients who are clinically free of disease should be used in conjunction with other clinical methods used for the early detection of cancer recurrence. The test is also intended for use as an aid in the management of breast cancer patients with metastatic disease by monitoring the progression or regression of disease in response to treatment.
Special Conditions for Use Statement(s): For prescription use only
6. Device Description
The ADVIA Centaur BR assay is a fully automated, competitive immunoassay using direct, chemiluminescent technology. Results are determined using a calibration curve that is generated specifically on each instrument by a 2-point calibration and a master curve with the reagent bar code. The ADVIA Centaur BR assay is intended for use on the ADVIA Centaur family of analyzers. The ADVIA Centaur Calibrator G is a set of 2 level calibrators for the assay. Siemens recommends the use of commercially available quality control materials with at least two levels (low and high).
The ADVIA Centaur BR reagent kit contains the following:
- ADVIA Centaur BR ReadyPack primary reagent pack contains Lite Reagent and Solid Phase ● Reagent.
- Materials Required but Not provided:
- ADVIA Centaur Calibrator G: consists of 2 levels (low and high) of CA 27.29 calibrators in equine serum with sodium azide (0.1%) and preservatives; lyophilized.
- ADVIA Centaur BR Pretreatment Reagent: consists of sodium hydroxide (0.24 N) Optional Reagents:
- ADVIA Centaur Multi-Diluent 1: consists of equine serum with sodium azide (0.1%) and preservatives.
- . ADVIA Centaur BR Master Curve Material: consists of a set of 7 levels of CA 27.29 (MCM1-7) spiked in lyophilized equine serum with sodium azide (0.1% after reconstitution) and preservatives.
7. Purpose of the Submission
The purpose of this submission is for the addition of plasma (EDTA) sample claim and updating the detection capability claim for the ADVIA Centaur BR assay.
8. Substantial Equivalence Information - Comparison of Candidate Device and Predicate Device
The following table demonstrates substantial equivalence between the ADVIA Centaur BR assay (Candidate Device) that has modified Instructions for Use (Package Inserts) with the addition of plasma (EDTA) sample and detection capability (LoB, LoD, and LoQ) claims and the currently marketed ADVIA Centaur BR assay (Predicate Device) that was cleared under 510(k) K982680.
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| Trade Name | Candidate Device | Predicate Device |
|---|---|---|
| ADVIA Centaur BR | ADVIA Centaur BR | |
| (Modified Labeling) | (Unmodified Labeling) | |
| Intended Use | The ADVIA Centaur® BR assay is an in | |
| vitro diagnostic test for the quantitative | ||
| serial determination of cancer antigen | ||
| CA 27.29 in human serum and plasma | ||
| (EDTA) using the ADVIA Centaur®, | ||
| ADVIA Centaur XP, and ADVIA Centaur | ||
| XPT systems. | The ADVIA Centaur® BR assay is an in | |
| vitro diagnostic test for the quantitative | ||
| serial determination of cancer antigen | ||
| CA 27.29 in human serum using the | ||
| ADVIA Centaur, ADVIA Centaur XP, | ||
| and ADVIA Centaur XPT systems. | ||
| Indications for Use | The test is intended for use as an aid in | |
| monitoring patients previously treated for | ||
| Stage II or Stage III breast cancer. Serial | ||
| testing for CA 27.29 in the serum and | ||
| plasma of patients who are clinically free | ||
| of disease should be used in conjunction | ||
| with other clinical methods used for the | ||
| early detection of cancer recurrence. The | ||
| test is also intended for use as an aid in | ||
| the management of breast cancer | ||
| patients with metastatic disease by | ||
| monitoring the progression or regression | ||
| of disease in response to treatment. | The test is intended for use as an aid | |
| in monitoring patients previously | ||
| treated for Stage II or Stage III breast | ||
| cancer. Serial testing for CA 27.2G in | ||
| the serum of patients who are clinically | ||
| free of disease should be used in | ||
| conjunction with other clinical | ||
| methods used for the early detection of | ||
| cancer recurrence. The test is also | ||
| intended for use as an aid in the | ||
| management of breast cancer patients | ||
| with metastatic disease by monitoring | ||
| the progression or regression of | ||
| disease in response to treatment. | ||
| Measurement | Quantitative | Same |
| Detection Capability | LoB: 3.5 U/mL | |
| LoD: 7.0 U/mL | ||
| LoQ: 9.0 U/mL | Analytical Sensitivity: 3.5 U/mL | |
| NA | ||
| NA | ||
| Assay Range | Serum and Plasma: 9.0-450 U/mL | Serum: 3.5—450 U/mL |
| Operating Principle | Competitive immunoassay | Same |
| Technology | Direct chemiluminescent | Same |
| Sample Type | Serum, Plasma (EDTA) | Serum |
| Sample Volume | 20 µL (serum and plasma) | 20 µL (serum) |
| Traceability/ | ||
| Standardization | Traceable to an internal standard | |
| manufactured using highly purified CA | ||
| 27.29 | Same | |
| Calibration | 2-point | Same |
| Calibrator/Levels | Calibrator G/2 levels | Same |
| Controls/Levels | Commercial Controls/2 levels | Same |
| Master Curve | ||
| Materials | Seven levels (MCM1-7) | Same |
| Detection Antibody | Monoclonal mouse anti-CA 27.29 | |
| antibody (~1.2 µg/mL) labeled with | ||
| acridinium ester | Same | |
| Capture Antibody | Human CA 27.29 (~0.72 U/mL) | |
| covalently coupled to paramagnetic | Same | |
| particles | ||
| Limit of Blank (LoB) | 3.5 U/mL | |
| Limit of Detection (LoD) | 7.0 U/mL | |
| Limit of Quantitation (LoQ) | 9.0 U/mL |
Standard/Guidance Document References 9.
The following recognized standards from Clinical Laboratory Standards Institute (CLSI) were used as a basis of the study procedures described in this submission:
- Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved . Guideline-Third Edition (CLSI EP09-A3).
6
- . Interference Testing in Clinical Chemistry; Approved Guideline-Third Edition (CLSI EP07ed3).
- Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved . Guideline-Second Edition (EP17-A2).
Test Principle 10.
The ADVIA Centaur BR assay is a fully automated, competitive immunoassay using direct, chemiluminescent technology. The Lite Reagent is composed of a monoclonal mouse antibody specific for CA 27.29, labeled with acridinium ester. The antibody used in the assay, MAb B27.29, binds to a peptide epitope in the tandem repeat region of the MUC-1 gene product. The Solid Phase is composed of purified CA 27.29, which is covalently coupled to paramagnetic particles. After onboard pretreatment, the sample is incubated with both Lite Reagent and Solid Phase simultaneously for 7.5 minutes.
11. Performance Characteristics
The addition of the plasma (EDTA) sample and detection capability (LoB, LoD, LoQ) claims in the Instructions for Use (Package Inserts) for the ADVIA Centaur BR assay was demonstrated by testing the performance characteristics with the following studies:
- Detection Capability (LoB, LoD, LoQ) ●
- Specimen Equivalence by Method Comparison ●
- . Interferences: EDTA
The plasma (EDTA) sample and detection capability (LoB, LoQ) claims for the ADVIA Centaur BR assay do not require the collection of additional analytical performance data. Therefore, all analytical performance data previously reviewed for the ADVIA Centaur BR assay continues to apply to this assay, because the assay was not modified.
Detection Capability 11.1
The Detection capability was determined in accordance with CLSI Document EP17-A2.
The LoB corresponds to the highest measurement likely to be observed for a blank sample with a probability of 95%.
The LoD corresponds to the lowest concentration of cancer antigen CA 27.29 that can be detected with a probability of 95%.
The LoQ corresponds to the lowest amount of cancer antigen CA 27.29 in a sample at which the within laboratory CV is ≤ 20%. CV is ≤ 20%.
Specimen Equivalence by Method Comparison 11.2
Specimen equivalency was determined with the Deming linear regression model in accordance with CLSI Document EP09-A3. The following results were obtained:
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510(k) Summary of Safety and Effectiveness
| Comparison | N* | Sample Interval | Slope
(95%CI) | Intercept
(95%CI) | Correlation
Coefficient (r) |
|--------------------------------------|-----|-------------------|-------------------------|------------------------------|--------------------------------|
| Dipotassium EDTA Plasma
vs. Serum | 101 | 10.80-444.42 U/mL | 0.97
(0.955 – 0.993) | 2.21 U/mL
(1.376 – 3.040) | 1.00 |
- N = Number of samples tested.
Interferences: EDTA 11.3
Interference testing was performed in accordance with CLSI Document EP07-ed3. The following results were obtained:
| Interferent | Interferent
Concentration | Analyte Concentration
(U/mL) | Bias (%) |
|------------------|------------------------------|---------------------------------|----------|
| Dipotassium EDTA | 5.4 mg/mL | 20.46 | 1.8 |
| | | 318.39 | 3.7 |
11.4 Clinical Studies
Not applicable.
11.5 Clinical Cut-off
Not applicable.
Conclusion 12.
The ADVIA Centaur BR assay with the addition of the plasma (EDTA) sample and detection capability (LoB, LoQ) claims in the Instructions for Use (package insert) is substantially equivalent to the currently marketed ADVIA Centaur BR assay (K982680).