(358 days)
The AFP method is an in vitro diagnostic test for the quantitative measurement of alpha-fetoprotein in human serum on the Dimension Vista® system. Measurements of alpha-fetoprotein are used as an aid in managing non-seminomatous testicular cancer when used in conjunction with physical examination, histology/pathology, and other clinical evaluation procedures.
For the calibration of the Alpha-Fetoprotein (AFP) method on the Dimension Vista® System.
Method: The AFP method is a homogeneous, sandwich chemiluminescent immunoassay based on LOCI™ technology. The LOCT™ reagents include two synthetic bead reagents and a biotinylated anti-AFP monoclonal antibody fragment. The first bead reagent (Chemibeads) is coated with an anti-AFP monoclonal antibody and contains chemiluminescent dye. The second bead reagent (Sensibeads) is coated with streptavidin and contains a photosensitizer dve. Sample is incubated with biotinylated antibody and Chemibeads to form bead-AFP-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 AFP concentration in the sample.
Calibrator: The LOCI 5 Calibrator is a liquid multi-analyte product containing AFP from human cord serum. An additional analyte (CEA from human tissue culture) is contained in the product and will be included in the submission to FDA with its respective method. The kit consists of ten vials, two each of five levels containing 2 mL per vial. Description of the manufacturing, value assignment and stability testing processes are provided.
For the Siemens Healthcare Diagnostics Inc. Dimension Vista® AFP reagent cartridge and LOCI 5 calibrator (K071597):
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Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state acceptance criteria in a quantitative format (e.g., a specific threshold for correlation coefficient or slope). Instead, it presents performance data and concludes "good analytical and clinical agreement." The substantial equivalence claim is based on this agreement with the predicate device.
Performance Metric (Device: Dade Behring Dimension Vista® AFP Method) Reported Device Performance (vs. Predicate Abbott AxSYM® AFP Method) Slope (Passing-Bablok linear regression) 0.93 Intercept (ng/mL) 0.1 Correlation Coefficient 0.995 -
Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: 317 patient samples.
- Data Provenance: Not specifically mentioned, but the study is a "split sample method comparison," implying prospective collection of human serum samples for comparison against a predicate device. The country of origin is not specified.
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Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This study describes a method comparison for an in vitro diagnostic test measuring AFP levels in serum. The "ground truth" in this context is the quantitative result provided by the predicate device (Abbott AxSYM® AFP method). This is not a study requiring expert readers to establish ground truth from images or clinical assessments.
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Adjudication Method for the Test Set
Not applicable. This is a quantitative method comparison study against a predicate device, not a study involving expert adjudication of interpretations.
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Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No. This document describes a method comparison study for an in vitro diagnostic device, not a comparative effectiveness study involving human readers and AI assistance for interpretation.
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Standalone (i.e., algorithm only without human-in-the-loop performance) Study
Yes, in essence. The study evaluates the performance of the Dimension Vista® AFP method (the "algorithm/device") by directly comparing its quantitative results to those of a predicate device using patient samples. This is a standalone performance evaluation of the assay itself.
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Type of Ground Truth Used
The "ground truth" for this method comparison study is the quantitative Alpha-Fetoprotein (AFP) concentration obtained from the predicate device (Abbott AxSYM® AFP method) for each human serum sample.
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Sample Size for the Training Set
The document does not provide information about a separate "training set" for the Dimension Vista® AFP method itself. This is a performance validation of a finished assay and calibrator. The development and internal validation of the assay (e.g., defining reagent concentrations, detection parameters) likely involved numerous experiments and historical data, but these are not disclosed as a distinct "training set" in a machine learning sense. Clinical validation studies for IVDs typically focus on demonstrating performance against established methods or clinical outcomes.
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How the Ground Truth for the Training Set Was Established
As noted in point 8, a "training set" in the context of a machine learning algorithm is not explicitly described. For the development of the assay, the "ground truth" for calibrating and establishing the assay's performance characteristics would involve using certified reference materials (e.g., traceable to WHO Reference preparation for human AFP (72/225)) and well-characterized human samples. The document states that the device is "Traceable to the World Health Organization (WHO) Reference preparation for human AFP (72/225)," indicating the standard used for establishing accuracy and calibration.
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510(k) Summary
This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of SMDA 1990 and 21 CFR §807.92.
The assigned 510(k) number is: K071597
1. Manufacturer's Name, Address, Telephone, and Contact Person, Date of Preparation
| Manufacturer: | Siemens Healthcare Diagnostics Inc.P.O. Box 6101Newark, DE 19714 |
|---|---|
| Contact Information: | Siemens Healthcare Diagnostics Inc.P.O. Box 6101Newark, DE 19714Attn: Pamela A. JurgaTel: 302-631-8891 |
| Date of Preparation: | May 8, 2008 |
2. Device Name / Classification
- Dimension Vista® AFP reagent cartridge/ Class II .
- . Dimension Vista® LOCI 5 calibrator/ Class II
3. Identification of the Predicate Device
- Abbott AxSYM® AFP Method (P820060/S019) .
- . Beckman Access AFP Calibrators on the Access® Immunoassay System (K981354).
FDA Guidance Document(s):
- "Bundling Multiple Devices or Multiple Indications in a Single Submission"-. 11/26/2003
- . "Guidance on Informed Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually Identifiable -Guidance for Sponsors, Institutional Review Boards, Clinical Investigators and FDA Staff "- 4/25/2006
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4. Device Description(s):
Method
The AFP method is a homogeneous, sandwich chemiluminescent immunoassay based on LOCI™ technology. The LOCT™ reagents include two synthetic bead reagents and a biotinylated anti-AFP monoclonal antibody fragment. The first bead reagent (Chemibeads) is coated with an anti-AFP monoclonal antibody and contains chemiluminescent dye. The second bead reagent (Sensibeads) is coated with streptavidin and contains a photosensitizer dve. Sample is incubated with biotinylated antibody and Chemibeads to form bead-AFP-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 AFP concentration in the sample.
Calibrator
The LOCI 5 Calibrator is a liquid multi-analyte product containing AFP from human cord serum. An additional analyte (CEA from human tissue culture) is contained in the product and will be included in the submission to FDA with its respective method. The kit consists of ten vials, two each of five levels containing 2 mL per vial. Description of the manufacturing, value assignment and stability testing processes are provided.
5. Device Intended Use:
Method
The AFP method is an in vitro diagnostic test for the quantitative measurement of alpha-fetoprotein in human on the Dimension Vista® System. Measurements of alpha-fetoprotein are used as an aid in managing non-seminomatous testicular cancer when used in conjunction with physical examination, histology/pathology, and other clinical evaluation procedures.
Calibrator
For the calibration of Alpha-Fetoprotein (AFP) method on the Dimension Vista® System.
6. Medical device to which equivalence is claimed:
Substantial Equivalence:
These products are substantially equivalent to other AFP test systems, such as the Abbott AxSYM® AFP Method (P820060/S019) and calibrators; Beckman Access AFP Calibrators on the Access® Immunoassay System (K981354).
Comparison to Predicate Device:
The proposed Dade Behring Dimension Vista® AFP method and the predicate Abbott AxSYM® AFP method are both in vitro diagnostic immunoassays intended for the measurement of alphafetoprotein (AFP) as an aid in managing non-seminomatous testicular cancer when used in conjunction with physical examination, histology/pathology, and other clinical evaluation procedures.
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The Dade Behring Dimension Vista® LOCI 5 calibrator and the predicate Beckman Access AFP Calibrators are both calibrators intended to calibrate their associated AFP methods.
A comparison summary of the features of the products is included in the following table.
Method:
| Similarities | ||
|---|---|---|
| Item | Device | Predicate |
| Intended Use | The AFP method is an in vitrodiagnostic test for thequantitative measurement ofalpha-fetoprotein in humanserum on the Dimension Vista®System. Measurements of alpha-fetoprotein are used as an aid inmanaging non-seminomatoustesticular cancer when used inconjunction with physicalexamination,histology/pathology, and otherclinical evaluation procedures. | AxSYM AFP is a MicroparticleEnzyme Immunoassay (MEIA)for the quantitativedetermination of alpha-fetoprotein (AFP) in:1. Human serum or plasma toaid in the management ofpatients with non-seminomatous testicularcancer. |
| Standardization | Traceable to the World HealthOrganization (WHO) Referencepreparation for human AFP(72/225). | Traceable to the World HealthOrganization (WHO)Reference preparation forhuman AFP (72/225). |
| Measurementmethod | Chemiluminescent:Homogenous sandwichimmunoassay based on LOCITMtechnology | Microparticle EnzymeImmunoassay (MEIA)technology |
| Differences | ||
| Item | Device | Predicate |
| Intended Use | Same as above | for the quantitativedetermination of alpha-fetoprotein (AFP) in:Human serum, plasma andamniotic fluid at 15 to 21weeks gestation to aid in thedetection of fetal open neuraltube defects (NTD). Testresults when used inconjunction withultrasonography or |
| amniography are a safe andeffective aid in the detection offetal open NTD. | ||
| Measuring Range | 0.5-1000.0 ng/mL | 0.4-350.0 ng/mL |
| Sample Types | Serum | Serum, plasmaAmniotic fluid |
| Sample Size | 2 uL | 58 uL |
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Calibrator:
| Similarities | ||
|---|---|---|
| Item | Device | Predicate |
| Intended Use | For the calibration of Alpha-Fetoprotein (AFP) method on theDimension Vista® system. | The Access AFP Calibrators areintended to calibrate the AccessAFP assay for the quantitativedetermination of AFP levels inhuman serum, using the AccessImmunoassay System. |
| Traceability | AFP- World HealthOrganization (WHO) ReferencePreparation 72/225 | AFP- World HealthOrganization (WHO) ReferencePreparation 72/225 |
| Matrix | BSA-based matrix | BSA-based matrix |
| Preparation | Liquid:Provided ready to use. | Liquid:Provided ready to use. |
| Differences | ||
| Item | Device | Predicate |
| TargetConcentrationsAFP | Level 1 (CAL A): 0 ng/mLLevel 2 (CAL B): 8 ng/mLLevel 3 (CAL C): 100 ng/mLLevel 4 (CAL D): 500 ng/mLLevel 5 (CAL E): 1050 ng/mL | Level 1 : 0 ng/mLLevel 2: 2.5 ng/mLLevel 3 5 ng/mLLevel 4 25 ng/mLLevel 5: 100 ng/mLLevel 6: 500 ng/mLLevel 7: 3000 ng/mL |
| Storage | Store at 2 to 8°C. | Store at 2 to 10°C. |
Comments on Substantial Equivalence:
Method
The Dade Behring Dimension Vista® AFP method and the predicate Abbott AxSYM® AFP method are both in vitro diagnostic immunoassays intended for the measurement of alpha-fetoprotein (AFP)
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as an aid in managing non-seminomatous testicular cancer when used in conjunction with physical examination, histology/pathology, and other clinical evaluation procedures.
Comparative data for human serum samples demonstrate good analytical and clinical agreement between the methods including the split sample method comparison described below:
A split sample method comparison demonstrated good agreement between the Dade Behring Dimension Vista® AFP method and the predicate Abbott AxSYM® AFP method following CLSI Approved Guideline for Method Comparison and Bias Estimation Using Patient Samples; EP9-A2.
| Comparative Method | Slope | Interceptng/mL | CorrelationCoefficient | n |
|---|---|---|---|---|
| AxSYM® AFP | 0.93 | 0.1 | 0.995 | 317 |
AxSYM® is a registered trademark of Abbott Laboratories, Abbott Park, III 60064 USA
The method used to fit the lincar regression line was Passing-Bablok. The range of 317 values in the correlation study was 0.97 - 881.24 ng/mL.
Calibrator
The Dade Bchring Dimension Vista® LOCI 5 calibrator and the predicate Beckman Access AFP Calibrators are both calibrators intended to calibrate their associated AFP methods.
Conclusion:
The Dade Behring Dimension Vista® AFP method and the predicate Abbott AxSYM® AFP method (P820060/S019) are substantially equivalent based on their intended use and performance characteristics as described above. The calibrator products, the Dade Behring Dimension Vista® LOCI 5 calibrator and the predicate Beckman Access AFP calibrators are also substantially equivalent in its design and intended use with their respective assay systems (K981354).
Pamela A. Ivez
Pamela A area Regulatory Affairs and Compliance Manager May 8, 2008
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Image /page/5/Picture/0 description: The image shows the logo for the Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES" around the perimeter. Inside the circle is a stylized symbol that resembles a caduceus, a traditional symbol of medicine, but with three parallel lines instead of a single staff.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Siemens Healthcare Diagnostics Inc. c/o Ms. Pamela A Jurga Regulatory Affairs and Compliance Manager P.O. Box 6101, M/S 514 Newark, DE 19714-6101
Re: K071597
Trade/Device Name: Dimension Vista® AFP reagent cartridge Dimension Vista® LOCI 5 calibrator Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-associated antigen immunological test system Regulatory Class: Class II Product Code: LOJ, JIX Dated: May 28, 2008 Received: May 29, 2008
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.
JUN - 4 2008
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such 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 Part 801); 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
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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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0450. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21 CFR Part 807.97), For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. 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 (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Robert Becker
Robert L. Becker, Jr., M.D., 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): K071597
Indications For Use:
The AFP method is an in vitro diagnostic test for the quantitative measurement of alpha-fetoprotein in human serum on the Dimension Vista® system. Measurements of alpha-fetoprotein are used as an aid in managing non-seminomatous testicular cancer when used in conjunction with physical examination, histology/pathology, and other clinical evaluation procedures.
Prescription Use _____________________________________________________________________________________________________________________________________________________________ (Per 21 CFR 801 Subpart D) AND/OR
Over-the-counter Use (21 CFR 801 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)
Page 1 of 1
Mana M. Chan
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K071597
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Dade Behring Inc. Dimension Vista® AFP Method and LOCI 5 Calibrator Updated 510(k) Premarket Notification - K071597
Indications for Use
Device Name:
Dimension Vista® LOCI 5 Calibrator
Indications for Use:
For the calibration of the Alpha-Fetoprotein (AFP) method on the Dimension Vista® System.
Prescription Use J (Per 21 CFR 801 Subpart D)
r w m m m m w m m w w w w w w w w m w m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m
AND/OR
Over-the-counter Use (21 CFR 801 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)
Page 1 of 1
Mana M. Chan
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
10/1) Ko 71597
§ 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.