(248 days)
Not Found
No
The device description and performance studies focus on a homogeneous, competitive chemiluminescent immunoassay based on LOCI technology, which is a standard laboratory technique. There is no mention of AI, ML, or any computational algorithms beyond standard data analysis for calculating results and performance metrics.
No.
The device is an in vitro diagnostic test used for the quantitative measurement of total testosterone, which aids in the diagnosis and treatment of disorders. It does not provide therapy or treatment itself.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is "an in vitro diagnostic test for the quantitative measurement of total testosterone... Measurements of testosterone are used in the diagnosis and treatment of disorders..." This clearly indicates its purpose is to aid in the diagnosis of medical conditions.
No
The device is an in vitro diagnostic test that involves physical reagents (Flex® reagent cartridge, calibrator) and is used on a physical system (Dimension Vista® System). It is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "The Dimension Vista® LOCI Total Testosterone Flex® reagent cartridge is an in vitro diagnostic test for the quantitative measurement of total testosterone in human serum and plasma on the Dimension Vista® System."
It also states: "The Dimension Vista® Testosterone Calibrator is an in vitro diagnostic product for the calibration of the Total Testosterone (TTST) assay on the Dimension Vista® System."
These statements clearly identify the device and its components as intended for use in vitro (outside of the living body) for diagnostic purposes.
N/A
Intended Use / Indications for Use
The Dimension Vista® LOCI Total Testosterone Flex® reagent cartridge is an in vitro diagnostic test for the quantitative measurement of total testosterone in human serum and plasma on the Vista@ System. Measurements of testosterone are used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in males, hirsutism (excessive hair), and virilization) due to tumors, polycystic ovaries, and adrenogenital syndromes.
The Dimension Vista® Testosterone Calibrator is an in vitro diagnostic product for the calibration of the Total Testosterone (TTST) assay on the Dimension Vista® System.
Product codes
CDZ, JIT
Device Description
Dimension Vista® LOCI Total Testosterone Flex® Reagent Cartridge: The Dimension Vista® LOCI Total Testosterone Flex® Reagent Cartridge (TTST) method is a homogeneous, competitive chemiluminescent immunoassay based on LOCI® technology. LOCI reagents include two synthetic bead reagents and labeled testosterone antibody. The first bead reagent (Chemibeads) is coated with a testosterone analog and contains a chemiluminescent dye. The second bead reagent (Sensibeads) is coated with streptavidin and contains photosensitive dye. Chemibeads and labeled testosterone antibody are added sequentially to the reaction vessel. Testosterone from the patient sample competes with the testosterone-analog-chemibead for a limited amount of labeled testosterone antibody. Sensibeads are then added and bind to the biotinylated portion of the labeled testosterone antibody to form bead pair immunocomplexes. Illumination of the complex by light at 680 nm generates singlet oxygen from the Sensibeads which diffuses to the Chemibeads triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is an inverse function of the concentration of total testosterone in the sample. Dimension Vista® LOCI Total Testosterone reagents are liquid and contained in reagent wells of a Flex® reagent cartridge. There are twelve (12) wells in each Flex® reagent cartridge. A barcode label on the Flex® reagent cartridge identifies the test method, lot number, expiration date, and fixed number of tests for which the Flex® reagent cartridge can supply reagent. There are eighty (80) tests per Flex® reagent cartridge and four (4) Flex® reagent cartridges per carton.
Calibrator: The Dimension Vista® Testosterone Calibrator (TTST CAL) is a lyophilized human serum based calibrator set containing testosterone and preservatives. Within each set of twelve (12) vials there are two (2) 1.0 mL amber glass vials for each calibrator level. There are six (6) calibrator levels labeled A, B, C, D, E, and F, which span the assay range. Each glass vial is closed with a plug and a color coded plastic cap. Vials are stored at 2-8°C. Lyophilized calibrators are reconstituted with reagent grade water using the steps listed in the instructions for use (IFU).
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
Adult Males 50 years old, Pre-menopausal females, Post-menopausal females.
Pediatric ranges: females ages 2-10 years, 11-15 years, and 16-21 years and males 2-10 years, 16-21 years, and individual ages 11,12,13, 14, and 15.
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
Not Found
Summary of Performance Studies
a. Method Comparison: A method comparison study was performed to demonstrate the accuracy of the Dimension Vista® LOCI Total Testosterone Flex® reagent cartridge following CLSI EP09-A3. Dimension Vista® LOCI Total Testosterone Flex® reagent cartridge was tested versus the reference method, CDC Isotope dilution/liquid chromatographic-tandem mass spectrometry (CDC ID/LC-MS/MS). One hundred twenty (120) serum samples across the assay range were measured. Six (6) samples were removed because they measured below the Dimension Vista® TTST assay range and one (1) sample was removed for being above the assay range. A Passing & Bablok regression analysis was done on results within the reportable range of 8 ng/dL to 1000 ng/dL, for a total of 113 samples. Correlation coefficient is based on least squares regression statistics.
b. Precision: Reproducibility testing was conducted in accordance with CLSI EP05-A2. Serum pools, a plasma pool, and commercial controls were run in singlicate from two independent cups twice a day for twenty (20) days. The repeatability and within lab standard deviation and %CV were calculated by analysis of variance method.
c. Analytical Measuring Range/Linearity: Linearity was evaluated to determine the upper limit of the assay range according to CLSI EP6-A. For each sample type tested, a high pool (greater than the assay range) and low pool were combined in varying ratios to produce dilutions covering the measuring interval, 8 to 1,000 ng/dL. Each level was assayed N=5 replicates. Polynomial regression analysis was performed for the mean observed value vs. the expected value.
d. Limits of Detection and Quantitation: Limits of Blank (LoB) and Limit of Detection (LoD) were determined experimentally following CLSI EP 17-A2. The limit of blank was claimed as 4 ng/dL. The limit of detection was claimed as 5 ng/dL. Limit of Quantitation (LoQ) was determined experimentally following CLSI EP05-A2. The limit of quantitation, 8 ng/dL.
e. Interferences: Interference testing was evaluated according to CLSI EP07-A2. Hemolysate, Icterus, Bilirubin and Lipemia and several method specific interferents were tested using a paired-difference approach. Non-Interfering substances were tested according to CLSI EP07-A2.
f. Heterophilic Antibody Interference: Heterophilic antibody interference was evaluated and reagent was designed with blockers. Human anti-mouse antibodies (HAMA) interference was evaluated according to CLSI EP07-A2. Samples were individual human serum samples with low and high endogenous HAMA. Two levels of testosterone were tested, approximately 150 ng/dL testosterone and ~700-800 ng/dL.
g. Cross-reactivity: Cross-reactivity of multiple compounds was evaluated in two concentrations of testosterone, at a 0 ng/mL and 300 ng/mL. Spiked test samples were assayed and compared to control samples.
h. Serum and Plasma Equivalency: The recommended tube types for use with the Dimension Vista® LOCI Total Testosterone Flex® reagent cartridge are serum, lithium heparin plasma, sodium heparin plasma, and K2 EDTA. Sixty (60) matched sets were freshly drawn and tested. Samples included in the regression spanned the assay range. One sample was removed from analysis because it quantitated below the assay range. Regression analysis was performed on each sample type versus serum.
i. Expected Values (Reference Interval): The patient populations were tested to determine the reference interval for the Dimension Vista® Testosterone Assay following CLSI EP28-A3c. The reference intervals were calculated non-parametrically or using the "Robust" method of Horn & Pesce.
Key Metrics
Method Comparison:
N=113
Range: 7.3 -1033 ng/dL CDC ID-LC-MS/MS; 8-949 ng/dL Vista TTST
Slope: 0.93
y-intercept: 4.0
Correlation coefficient (r): 0.994
95% confidence interval (Slope): 0.92 to 0.95
95% confidence interval (Intercept): 0.4 to 5.7
Precision:
Serum Pool 1: Mean=13 ng/dL, Repeatability SD=0.7, %CV=5.2; Within-Lab SD=1.0, %CV=7.3
Serum Pool 2: Mean=75 ng/dL, Repeatability SD=1.4, %CV=1.9; Within-Lab SD=1.6, %CV=2.1
Serum Pool 3: Mean=767 ng/dL, Repeatability SD=13.8, %CV=1.8; Within-Lab SD=18.2, %CV=2.4
Li Heparin Plasma Pool: Mean=384 ng/dL, Repeatability SD=14.3, %CV=3.7; Within-Lab SD=15.8, %CV=4.1
Bio-Rad Liquichek Level 1: Mean=71 ng/dL, Repeatability SD=1.2, %CV=1.7; Within-Lab SD=1.8, %CV=2.6
Bio-Rad Liquichek Level 2: Mean=441 ng/dL, Repeatability SD=4.1, %CV=0.9; Within-Lab SD=5.6, %CV=1.3
Bio-Rad Liquichek Level 3: Mean=855 ng/dL, Repeatability SD=13.2, %CV=1.6; Within-Lab SD=16.9, %CV=2.0
Analytical Measuring Range/Linearity (8 to 1,000 ng/dL):
Serum: Deming Regression=0.97x + 0.1, Correlation Coefficient=0.999, R2=0.998
Sodium Heparin: Deming Regression=0.98x + 0.1, Correlation Coefficient=0.998, R2=0.996
Lithium Heparin: Deming Regression=0.98x + 0.0, Correlation Coefficient=0.999, R2=0.999
EDTA: Deming Regression=0.96x + 0.1, Correlation Coefficient=0.999, R2=0.999
Limits of Detection and Quantitation:
Limit of Blank (LoB): 4 ng/dL
Limit of Detection (LoD): 5 ng/dL
Limit of Quantitation (LoQ): 8 ng/dL (with total precision of 50 years old: 2.5%=95 ng/dL; 97.5%=948 ng/dL (Sample Range: 24-1053 ng/dL, N=Not specified)
Pre-menopausal females: 2.5%=9 ng/dL; 97.5%=53 ng/dL (Sample Range: 3-64 ng/dL, N=Not specified)
Post-menopausal females: 2.5%=
§ 862.1680 Testosterone test system.
(a)
Identification. A testosterone test system is a device intended to measure testosterone (a male sex hormone) in serum, plasma, and urine. Measurement of testosterone are used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in males and, in females hirsutism (excessive hair) and virilization (masculinization) due to tumors, polycystic ovaries, and adrenogenital syndromes.(b)
Classification. Class I.
0
Image /page/0/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized design of three human profiles facing to the right. The profiles are stacked on top of each other, creating a sense of depth and unity. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the central design.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
SIEMENS HEALTHCARE DIAGNOSTICS, INC. JULIE WARREN REGULATORY TECHNICAL SPECIALIST 500 GBC DR. P.O. BOX 6101 M/S 514 NEWARK DE 19714
February 11, 2016
Re: K151529
Trade/Device Name: Dimension Vista® LOCI Total Testosterone Flex® Reagent Cartridge Dimension Vista® Testosterone Calibrator Regulation Number: 21 CFR 862.1680 Regulation Name: Testosterone test system Regulatory Class: I. Reserved Product Code: CDZ, JIT Dated: February 08, 2016 Received: February 09, 2016
Dear Julie Warren:
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 medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
1
If you desire specific advice for your device on our labeling regulations (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" (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 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
2
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)
Device Name
Dimension Vista® LOCI Total Testosterone Flex® reagent cartridge
Indications for Use (Describe)
The Dimension Vista® LOCI Total Testosterone Flex® reagent cartridge is an in vitro diagnostic test for the quantitative measurement of total testosterone in human serum and plasma on Vista@ System. Measurements of testosterone are used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in males, hirsutism (excessive hair), and virilization) due to tumors, polycystic ovaries, and adrenogenital syndromes.
| 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)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
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 time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, 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."
3
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)
Device Name Dimension Vista® Testosterone Calibrator
Indications for Use (Describe)
The Dimension Vista® Testosterone Calibrator is an in vitro diagnostic product for the calibration of the Total Testosterone (TTST) assay on the Dimension Vista® System.
Type of Use (Select one or both, as applicable)
2 Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
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 time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, 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."
4
510(k) Summary
This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.
The assigned 510(k) number is: K151529
1. Submitter
Siemens Healthcare Diagnostics, Inc. 500 GBC Dr. Newark, DE 19714
Contact Person: Julie Warren Tel: 302-631-8722 Fax: 302-631-6299 Email: julie.warren@siemens.com
Date of Preparation: February 5, 2016
2. Device Information
Name of Device: Dimension Vista® LOCI Total Testosterone Flex® reagent cartridge Common Name: Testosterone test system Regulatory Class: I (21 CFR §862.1680, Testosterone test system) Product Code: CDZ Panel: Clinical Chemistry
Name of Device: Dimension Vista® Testosterone Calibrator Common Name: Testosterone Calibrator Regulatory Class: II (21 CFR §862.1150, Calibrator) Product Code: JIT Panel: Clinical Chemistry
5
3. Predicate Device
Assay: Roche Diagnostics Corp. Device Name: Elecsys® Testosterone II Immunoassay 510(k) Number: K093421 Regulatory Class: I (21 CFR §862.1680, Testosterone test system) Classification Product Code: CDZ Panel: Clinical Chemistry
Calibrator: Roche Diagnostics Corp. Device Name: Elecsys® Testosterone Calset II 510(k) Number: K003411 Regulatory Class: II (21 CFR §862.1150, Calibrator) Classification Product Code: JIT Panel: Clinical Chemistry
4. Device Description
Dimension Vista® LOCI Total Testosterone Flex® Reagent Cartridge
The Dimension Vista® LOCI Total Testosterone Flex® Reagent Cartridge (TTST) method is a homogeneous, competitive chemiluminescent immunoassay based on LOCI® technology. LOCI reagents include two synthetic bead reagents and labeled testosterone antibody. The first bead reagent (Chemibeads) is coated with a testosterone analog and contains a chemiluminescent dye. The second bead reagent (Sensibeads) is coated with streptavidin and contains photosensitive dye. Chemibeads and labeled testosterone antibody are added sequentially to the reaction vessel. Testosterone from the patient sample competes with the testosterone-analog-chemibead for a limited amount of labeled testosterone antibody. Sensibeads are then added and bind to the biotinylated portion of the labeled testosterone antibody to form bead pair immunocomplexes. Illumination of the complex by light at 680 nm generates singlet oxygen from the Sensibeads which diffuses to the Chemibeads triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is an inverse function of the concentration of total testosterone in the sample.
Dimension Vista® LOCI Total Testosterone reagents are liquid and contained in reagent wells of a Flex® reagent cartridge. There are twelve (12) wells in each Flex® reagent cartridge. A barcode label on the Flex® reagent cartridge identifies the test method, lot number, expiration date, and fixed number of tests for which the Flex® reagent cartridge can supply reagent. There are eighty (80) tests per Flex® reagent cartridge and four (4) Flex® reagent cartridges per carton. The reagents for this assay are assigned to wells as per the table below.
6
Example Flex® Reagent Cartridge Well Configuration
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| --- | --- | --- | --- | --- | --- | --- | --- | --- | ---- | ---- | ---- |
| Wells | Form | Name | Concentration |
|---|---|---|---|
| 1-4 | Liquid | Testosterone Biotinylated | |
| Antibody Reagentc, d (Sheep | |||
| monoclonal); | |||
| Displacer | 31.3 ng/mL; | ||
| 1200 ng/mL | |||
| 5-8 | Liquid | Testosterone Chemibead Reagentd | 100 µg/mL |
| 9-12 | Liquid | Testosterone Sensibead Reagentd | 400 µg/mL |
Wells are numbered consecutively from the wide end of the cartridge. a.
- b. Nominal value per well in a cartridge.
- Antibody titer and conjugate activity may vary from lot to lot. C.
- Contain buffers, stabilizers and preservatives. d.
Calibrator
The Dimension Vista® Testosterone Calibrator (TTST CAL) is a lyophilized human serum based calibrator set containing testosterone and preservatives. Within each set of twelve (12) vials there are two (2) 1.0 mL amber glass vials for each calibrator level. There are six (6) calibrator levels labeled A, B, C, D, E, and F, which span the assay range. Each glass vial is closed with a plug and a color coded plastic cap. Vials are stored at 2-8°C. Lyophilized calibrators are reconstituted with reagent grade water using the steps listed in the instructions for use (IFU).
5. Intended Use/Indications for Use
Assay
The Dimension Vista® LOCI Total Testosterone Flex® reagent cartridge is an in vitro diagnostic test for the quantitative measurement of total testosterone in human serum and plasma on the Dimension Vista® System. Measurements of testosterone are used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in males, and in females, hirsutism (excessive hair), and virilization (masculinization) due to tumors, polycystic ovaries, and adrenogenital syndromes.
7
Calibrator
The Dimension Vista® Testosterone Calibrator is an in vitro diagnostic product for the calibration of the Total Testosterone (TTST) assay on the Dimension Vista® System.
7a. Standards Referenced
-
- CLSI EP25-A Evaluation of Stability of In Vitro Diagnostic Reagents, Approved Guideline; September 23, 2009
-
- CLSI EP05-A2 Evaluation of Precision Performance of Clinical Chemistry Devices, Approved Guideline, Second Edition; August 2004
-
- CLSI EP6-A: Evaluation of the Linearity of Quantitative Analytical Measurement Procedure: A Statistical Approach, Approved Guideline; April 2003.
-
- CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures, Approved Guideline, Second Edition; June 18, 2012
-
- CLSI EP07-A2 Interference Testing in Clinical Chemistry, Approved Guideline, Second Edition; November 23, 2005
-
- CLSI EP09-A3 Measurement Procedure Comparison and Bias Estimation Using Patient Samples, Approved Guideline, Third Edition; August 30, 2013
-
- CLSI EP28-A3c Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory, Approved Guideline, Third Edition; October 19, 2010
-
- CLSI EP32-R Metrological Traceability and Its Implementation, A Report, February 17, 2006
7b. Guidance Documents Referenced
- . Guidance for Industry and FDA Staff: Bundling Multiple Devices or Multiple Indications in a Single Submission - June 22, 2007
- . In Vitro Diagnostic Devices: Guidance for the Preparation of 510(k) Submissions - Jan. 1997
- . Format for Traditional and Abbreviated 510(k)'s – Guidance for Industry and Staff - Nov. 17, 2005
- Administrative Procedures for CLIA Categorization Guidance for Industry . and Food and Drug Administration Staff - March 12, 2014
- Guidance for Industry and Food and Drug Administration Staff eCopy . Program for Medical Device Submissions - October 10, 2013
- Refuse to Accept Policy for 510(k)s Guidance for Industry and Food and . Drug Administration Staff - December 31, 2012
8. Medical Device to Which Equivalence is Claimed
The Siemens Healthcare Diagnostics Inc. Dimension Vista® LOCI Total Testosterone Flex® reagent cartridge and the Roche Diagnostics Elecsys Testosterone II Assay (K093421) are in vitro diagnostic devices intended to be used for the quantitation of testosterone in human serum and plasma. The Siemens Healthcare Diagnostics Inc.
8
Dimension Vista® Testosterone Calibrator and the Roche Diagnostics Cal II Set (K003411) are in vitro diagnostic devices intended to be used for calibrating quantitative testosterone assays on automated clinical chemistry analyzers. The proposed and predicate devices support the use in quantitating testosterone in human serum and plasma. The proposed devices were compared side by side via the following tables to examine their similarities and differences. The predicate labeling is enclosed in Attachment 12.
The intended usage and observed performance characteristics between the proposed devices and their predicates are substantially equivalent. Any differences in performance based on experimental data do not raise any questions of safety and effectiveness of the assay and calibrator. Siemens Healthcare Diagnostics Inc. claims substantial equivalence to the currently marketed Roche Diagnostics Elecsys® Testosterone II Assay (K093421) and Roche Diagnostics Testosterone CalSet II (K003411).
| Attribute | Predicate Device
Roche Elecsys®
Testosterone II Assay
(K093421) | Proposed Device
Dimension Vista® LOCI
Total Testosterone Flex®
reagent cartridge |
|---------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------|
| Similarities | | |
| Intended Use | Immunoassay for the in vitro
quantitative determination of
testosterone in human serum
and plasma. | The TTST assay is an in vitro diagnostic test for the
quantitative measurement
of total testosterone in
human serum and plasma. |
| Indications for Use | Measurements of testosterone
are used in the diagnosis and
treatment of disorders
involving the male sex
hormones (androgens),
including primary and
secondary hypogonadism,
delayed or precocious
puberty, impotence in males
and, in females hirsutism
(excessive hair) and
virilization (masculinization)
due to tumors, polycystic
ovaries, and adrenogenital
syndromes. | Same |
| Measurand | Testosterone | Same |
Substantial Equivalence Comparison of Technological Characteristics with the Predicate Device
9
| Attribute | Predicate Device
Roche Elecsys®
Testosterone II Assay
(K093421) | Proposed Device
Dimension Vista® LOCI
Total Testosterone Flex®
reagent cartridge |
|-----------------------|--------------------------------------------------------------------------|-------------------------------------------------------------------------------------------|
| Similarities | | |
| Measurement Method | Immunoassay | Same |
| Test Principle | Competitive assay with sheep
monoclonal antibody | Same |
| Reagent Form | Ready to use, in a unit that
cannot be separated | Same |
| Differences | | |
| Technology | electrochemiluminescence
"ECLIA" | chemiluminescent "LOCI®" |
| Instrument | Elecsys® 2010 and Cobas e
Immunoassay analyzers | Dimension Vista® System |
| Sample Size | 20 µL | 10 µL |
| Sample Type | Human Serum and Li-heparin,
K2- and K3-EDTA plasma. | Human Serum, Li and Na
Heparin, K2 EDTA |
| Detection | Electrochemiluminescence
(ECLIA) | Chemiluminescence
LOCI® technology |
| Measuring Range | 2.5 -1500 ng/dL
(0.087 – 52.0 nmol/L) | 8-1000 ng/dL
(0.278 – 34.7 nmol/L) |
| High Samples | Generally not necessary due
to the broad measuring range. | Samples outside the assay
range are diluted with
MULTI 2 SDIL 1:2 dilution |
| Limits of Detection | Limit of Blank: 1.2 ng/dL
Limit of Detection: 2.5 ng/dL | Limit of Blank: 4 ng/dL
Limit of Detection: 5 ng/dL |
| Limit of Quantitation | 12.0 ng/dL | 8 ng/dL |
| Attribute | Roche Elecsys
Testosterone Calset II
(K003411) | Dimension Vista®
Testosterone Calibrator |
|-------------------|------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------|
| Similarities | | |
| Intended Use | Elecsys Testosterone
CalSet II is used for
calibrating the quantitative
Testosterone assay. | The TTST CAL is an in vitro diagnostic product
for the calibration of the
Total Testosterone
(TTST) assay. |
| Measurand | Testosterone | Same |
| Calibrator Form | Lyophilized | Same |
| Calibrator Matrix | Human Serum | Same |
10
| Attribute | Roche Elecsys
Testosterone Calset II
(K003411) | Dimension Vista®
Testosterone Calibrator |
|------------------------------|---------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Differences | | |
| Instrument | Elecsys and Cobas e
immunoassay analyzers | Dimension Vista®
System |
| Traceability/Standardization | ID-GC/MS (Isotope Dilution
Gas
Chromatography/Mass
Spectrometry) | ID-LC/MS/MS
(Isotope dilution liquid
chromatography/tandem
mass spectrometry) |
| Calibrator | Two levels
Cal 1: 0.05.
| Sample Type | Deming
Regression | Correlation
Coefficient | R2 |
|-----------------|----------------------|----------------------------|-------|
| Serum | $0.97x + 0.1$ | 0.999 | 0.998 |
| Sodium Heparin | $0.98x + 0.1$ | 0.998 | 0.996 |
| Lithium Heparin | $0.98x + 0.0$ | 0.999 | 0.999 |
| EDTA | $0.96x + 0.1$ | 0.999 | 0.999 |
- d. Limits of Detection and Quantitation
Limits of Blank (LoB) and Limit of Detection (LoD) were determined experimentally following CLSI EP 17-A2 Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline; Second Edition. The limit of blank was claimed as 4 ng/dL based on data using testosterone free serum samples. The limit of detection was claimed as 5 ng/dL based on data obtained from low testosterone serum samples.
Limit of Quantitation (LoQ) was determined experimentally following CLSI EP05-A2 Evaluation of Precision Performance of Clinical Chemistry Devices; Approved Guideline; Second Edition. The limit of quantitation, 8 ng/dL, is based on the lowest analyte concentration that can be reproducibly measured with a total precision of ≤20%.
- e. Interferences
Interference testing was evaluated according to CLSI EP07-A2 Interference Testing in Clinical Chemistry, Approved Guideline, Second Edition. Hemolysate, Icterus, Bilirubin and Lipemia and several method specific interferents were tested using a paired-difference approach. Results are summarized below.
13
| | Substance | Substance
Concentration | TTST
Bias (%)
@ 50 ng/dL | TTST
Bias (%)
@ 300 ng/dL |
|--|-----------------------------|----------------------------|--------------------------------|---------------------------------|
| | Hemoglobin | 1000 mg/dL | 2% | -7% |
| | Bilirubin
(unconjugated) | 60 mg/dL | 2% | -8% |
| | Bilirubin
(conjugated) | 60 mg/dL | -2% | 6% |
| | Lipemia
(Intralipid) | 1000 mg/dL | 2% | 0% |
Non-Interfering substances were tested according to CLSI EP07-A2 Interference Testing in Clinical Chemistry, Approved Guideline, Second Edition. Results are as follows. Albumin at 6 g/dL increases TTST results by 19% at a testosterone concentration of 50 ng/dL. Immunoglobulin G at 5 g/dL decreases TTST results 27% at a testosterone concentration of 300 ng/dL. Nandrolone decanoate (19-nortestosterone) shows significant cross-reactivity with the TTST assay at 1,000 ng/mL. Do not use samples from patients under Nandrolone treatment. The following compounds at the specified concentrations tested did not show significant interference.
| Substance | Concentration Tested |
|---|---|
| Acetaminophen | 20 mg/dL |
| Acetylcysteine | 150 mg/L |
| Amikacin | 8 mg/dL |
| Ampicillin | 5.3 mg/dL |
| Ascorbic Acid | 6 mg/dL |
| Biotin | 100 ng/mL |
| Calcium Dobesilate | 200 mg/L |
| Caffeine | 6 mg/dL |
| Carbamazepine | 3 mg/dL |
| Cefoxitin | 2500 mg/L |
| Chloramphenicol | 5 mg/dL |
| Chlordiazepoxide | 1 mg/dL |
| Chlorpromazine | 0.2 mg/dL |
| Cholesterol | 503 mg/dL |
| Cimetidine | 2 mg/dL |
| Creatinine | 30 mg/dL |
| Cyclosporine | 5 mg/L |
| Dextran 40 | 5000 mg/dL |
| Diazepam | 0.51 mg/dL |
| Digoxin | 6.1 ng/mL |
| Doxycycline | 50 mg/L |
| Enoxaparin Sodium | 60 mg/L |
| Erythromycin | 6 mg/dL |
| Ethanol | 400 mg/dL |
14
| Substance | Concentration
Tested |
|-------------------|-------------------------|
| Ethosuximide | 25 mg/dL |
| Furosemide | 6 mg/dL |
| Gentamicin | 1 mg/dL |
| Heparin | 3 U/mL |
| Ibuprofen | 50 mg/dL |
| Immunoglobulin G | 4 g/dL |
| Levodopa | 20 mg/L |
| Lidocaine | 1.2 mg/dL |
| Lithium | 2.2 mg/dL |
| Leuprolide | 200 ng/mL |
| Methyldopa | 20 mg/L |
| Metronidazole | 200 mg/L |
| Nicotine | 0.1 mg/dL |
| Penicillin G | 25 U/mL |
| Pentobarbital | 10 mg/dL |
| Phenobarbital | 15 mg/dL |
| Phenylbutazone | 400 mg/L |
| Phenytoin | 5 mg/dL |
| Primidone | 4 mg/dL |
| Propoxyphene | 0.16 mg/dL |
| Protein: Albumin | 5 g/dL |
| Protein: Total | 10.5 g/dL |
| Rheumatoid Factor | 1110 IU/mL |
| Rifampicin | 60 mg/L |
| Salicylic Acid | 60 mg/dL |
| Theophylline | 4 mg/dL |
| Triglycerides | 900 mg/dL |
| Urea | 500 mg/dL |
| Uric Acid | 20 mg/dL |
| Valproic Acid | 50 mg/dL |
| Vancomycin | 10 mg/dL |
- f. Heterophilic Antibody Interference
Heterophilic antibody interference was evaluated and reagent was designed with blockers based on the efficacy in minimizing the extent of potential interference. Human anti-mouse antibodies (HAMA) interference was evaluated according to CLSI EP07-A2 Interference Testing in Clinical Chemistry, Approved Guideline, Second Edition. Samples were individual human serum samples with low and high endogenous HAMA. Two levels of testosterone were tested, approximately 150 ng/dL testosterone and ~700-800 ng/dL. Less than 10% interference was observed for HAMA at 285ng/mL and 1248 ng/mL in the presence of ~150 ng/dL and ~700-800 ng/dL testosterone.
15
| HAMA Concentration | Testosterone
Level | % Interference |
|--------------------|-----------------------|----------------|
| 1248 ng/mL | 149 ng/dL | -4% |
| 285 ng/mL | 156 ng/dL | -2% |
| 1248 ng/mL | 887 ng/dL | -6% |
| 285 ng/mL | 746 ng/dL | -5% |
- g. Cross-reactivity
Cross-reactivity of multiple compounds was evaluated in two concentrations of testosterone, at a 0 ng/mL and 300 ng/mL. Spiked test samples were assayed and compared to control samples. Percent cross-reactivity was calculated between the means, where ND denotes not detected. Observed results are shown below.
| Cross Reactant | Conc. Tested | Testosterone 0 ng/dL | Testosterone 300 ng/dL |
|---|---|---|---|
| 5α-dihydrotestosterone | 500 ng/mL | 0.3% | -0.1% |
| 5α-androstane-3- | |||
| beta,17-beta-diol | 1000 ng/mL | 0.02% | -0.03% |
| 5-androstene-3b,17b- | |||
| diol | 1000 ng/mL | 0.2% | 0.1% |
| 5β-androstane-3b,17b- | |||
| diol | 100 ng/mL | ND | -0.2% |
| 11b-hydroxytestosterone | 100 ng/mL | 1.9% | 1.0% |
| 11-deoxycortisol | 1000 ng/mL | ND | 0.01% |
| 11-ketotestosterone | 1000 ng/mL | 0.2% | 1.6% |
| 17α-methyltestosterone | 100 ng/mL | 4.2% | 1.7% |
| 17β-Estradiol | 1000 ng/mL | 0.01% | -0.02% |
| Androstenedione | 100 ng/mL | 0.2% | -0.1% |
| Androsterone | 1000 ng/mL | ND | 0.004% |
| Corticosterone | 1000 ng/mL | ND | 0.001% |
| Cortisol | 1000 ng/mL | ND | 0.01% |
| Danazol | 1000 ng/mL | 0.1% | 0.04% |
| Dehydroepiandrosterone | |||
| (DHEA) | 1000 ng/mL | ND | -0.01% |
| Dehydroepiandrosterone | |||
| sulfate (DHEA-S) | 50,000 ng/mL | 0.02% | 0.03% |
| Dexamethasone | 2000 ng/mL | ND | 0% |
| Estrone | 1000 ng/mL | ND | -0.01% |
| Ethisterone | 1000 ng/mL | 0.1% | -0.003% |
| Norethindrone | 50 ng/mL | 0.4% | 0.5% |
| Norgestrel | 1000 ng/mL | 0.1% | -0.02% |
| Oxymetholone | 100 ng/mL | ND | 0.02% |
| Progesterone | 1000 ng/mL | ND | 0% |
| Testosterone Propionate | 100 ng/mL | ND | 0% |
| Prednisone | 1000 ng/mL | ND | 0.01% |
| Prednisolone | 1000 ng/mL | ND | -0.002% |
| Cortisone | 2000 ng/mL | ND | 0.003% |
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h. Serum and Plasma Equivalency
The recommended tube types for use with the Dimension Vista® LOCI Total Testosterone Flex® reagent cartridge are serum, lithium heparin plasma, sodium heparin plasma, and K2 EDTA. Sixty (60) matched sets were freshly drawn and tested. Samples included in the regression spanned the assay range. One sample was removed from analysis because it quantitated below the assay range. Regression analysis was performed on each sample type versus serum.
| Comparative | Correlation | Number of | ||
|---|---|---|---|---|
| Specimen | Slope | Intercept | Coefficient | Samples |
| Li Hep Plasma | 0.98 | -1.6 ng/dL | 0.998 | 59 |
| Na Hep Plasma | 0.99 | -1.4 ng/dL | 0.996 | 59 |
| K2 EDTA Plasma | 1.00 | -1.1 ng/dL | 0.995 | 59 |
- i. Expected Values (Reference Interval)
The following patient populations were tested to determine the reference interval for the Dimension Vista® Testosterone Assay following CLSI EP28-A3c Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory, Approved Guideline, Third Edition.
The reference intervals were calculated non-parametrically and represent the central 95% of results determined from healthy males ≤50 years old, males >50 years of, normal cycling females and postmenopausal females.
| Reference Range
Category | Observed TTST Value
(ng/dL) | Sample Range
TTST (ng/dL) | Number
of
Samples |
|------------------------------|-----------------------------------------|---------------------------------------|-------------------------|
| Adult Males ≤50
years old | 2.5% = 113 ng/dL;
97.5% = 1065 ng/dL | 41-1465 ng/dL | 174 |
| | Adult Males >50
years old | 2.5% = 95 ng/dL;
97.5% = 948 ng/dL | 24-1053 ng/dL |
| Pre-menopausal
females | | 2.5% = 9 ng/dL;
97.5% = 53 ng/dL | 3-64 ng/dL |
| | Post-menopausal
females | 2.5% =