(348 days)
No
The summary describes standard in vitro diagnostic immunoassay technology and does not mention any AI or ML components.
No
Explanation: This device is an in vitro diagnostic assay used for the quantitative determination of total testosterone and sex hormone-binding globulin in human serum and plasma, which aids in diagnosis. It does not directly treat or prevent a disease or condition.
Yes
This device, the ADVIA Centaur Testosterone II (TSTII) assay and the ADVIA Centaur SHBG assay, is explicitly stated to be "for in vitro diagnostic use" and its measurements are used "in the diagnosis and treatment of disorders." Specifically, the SHBG assay is intended for "use as an aid in the diagnosis of androgen disorders."
No
The device description explicitly lists physical components such as reagents, calibrators, and master curve materials, which are not software. The assays are also intended for use on the ADVIA Centaur XP system, which is a hardware platform.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states:
- "The ADVIA Centaur Testosterone II (TSTII) assay is for in vitro diagnostic use..."
- "The ADVIA Centaur Testosterone II (TSTI) Master Curve Material is for in vitro diagnostic use..."
- "The ADVIA Centaur SHBG assay is an in vitro diagnostic immunoassay..."
- "For in vitro diagnostic use in calibrating the ADVIA Centaur SHBG assay..."
- "The ADVIA Centaur SHBG Master Curve Material is for in vitro diagnostic use..."
These statements clearly indicate that the described devices are intended for use outside of the body to examine specimens from the human body for the purpose of providing information for the diagnosis, treatment, or prevention of disease.
N/A
Intended Use / Indications for Use
ADVIA Centaur® Testosterone II (TSTII)
The ADVIA Centaur Testosterone II (TSTII) assay is for in vitro diagnostic use in the quantitative determination of total testosterone (bound and unbound) in human serum and plasma using the ADVIA Centaur XP 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) due to tumors, polycystic ovaries, and adrenogenital syndromes.
ADVIA Centaur® Testosterone II (TSTII) Master Curve Material
The ADVIA Centaur Testosterone II (TSTI) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur Testosterone II (TSTII) assay.
ADVIA Centaur® SHBG
The ADVIA Centaur SHBG assay is an in vitro diagnostic immunoassay for the quantitative determination of sex hormone-binding globulin (SHBG) in human serum and plasma using the ADVIA Centaur XP system.
The ADVIA Centaur SHBG assay is intended for use as an aid in the diagnosis of androgen disorders.
ADVIA Centaur® SHBG Calibrator
For in vitro diagnostic use in calibrating the ADVIA Centaur SHBG assay on the ADVIA Centaur systems.
ADVIA Centaur® SHBG Master Curve Material
The ADVIA Centaur SHBG Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur SHBG assay.
Product codes (comma separated list FDA assigned to the subject device)
CDZ, JIT, JJX
Device Description
ADVIA Centaur TSTII Assay Components:
- ADVIA Centaur TSTII Primary Reagent ReadyPack:
- ADVIA Centaur TSTII Lite Reagent (10.0 mL/pack): Acridinium ester-labeled hapten (36 μg/mL) in buffered saline with preservatives.
- ADVIA Centaur TSTII Solid Phase Reagent (17.0 mL/pack): Streptavidin-coated latex particles (0.33 g/L) in buffered saline with preservatives.
- ADVIA Centaur TSTII Ancillary Reagent ReadyPack:
- ADVIA Centaur TSTII Releasing Agent (10.0 mL/pack): Steroid releasing agent (0.4 μg/mL) and biotinylated sheep monoclonal anti-testosterone antibody (27 μg/L) in buffered saline and preservatives.
- ADVIA Centaur TSTII Calibrator:
- ADVIA Centaur TSTII Low and High Calibrators (2.0 mL/vial): After reconstitution, low or high levels of USP-grade estradiol, testosterone, cortisol, and progesterone spiked in charcoal-stripped, defibrinated human plasma with sodium azide (0.1%) and preservatives.
- ADVIA Centaur TSTII Master Curve Material (sold separately):
- ADVIA Centaur TSTII MCM1 (1.0 mL/vial): Lyophilized human plasma with sodium azide (0.1% after reconstitution) and preservatives.
- ADVIA Centaur TSTII MCM2-7 (1.0 mL/vial): Various levels of testosterone in lyophilized human plasma with sodium azide (0.1% after reconstitution) and preservatives.
ADVIA Centaur SHBG Assay Components:
- ADVIA Centaur SHBG Primary Reagent ReadyPack:
- ADVIA Centaur SHBG Lite Reagent (3.0 mL/pack): Mouse monoclonal anti-SHBG antibody (~130 ng/mL) labeled with acridinium ester in HEPES-buffered saline with bovine serum albumin, mouse serum, sodium azide (15 mg/dL for erroneous results, 20 mg/dL for -14.4% change), and unconjugated bilirubin (>20 mg/dL for erroneous results, 30 mg/dL for 20.1% change) were noted as interferents.
- ADVIA Centaur SHBG: Re-standardization did not influence interference.
Heterophile Interference:
- ADVIA Centaur TSTII: Tested by spiking 19 HAMA-positive serum samples with ~30 and ~300 ng/dL USP testosterone. Mean recovery for ~30 ng/dL spike was 98.69%, for ~300 ng/dL spike was 94.55%.
Cross-Reactivity:
- ADVIA Centaur TSTII: Cross-reactivity studies performed using two sample pools (~0 ng/dL and ~300 ng/dL testosterone) spiked with potential cross-reactants. Substances showing significant cross-reactivity included: 5-Androstene-3ß, 17ß-diol, Androstenedione, Cyproterone, Danazol, 5a-Dihydrotestosterone, 17β-Estradiol, Ethisterone, 11ß-Hydroxytestosterone, 11-Keto-testosterone, Norgestrel, Oxymetholone, Testosterone propionate.
- ADVIA Centaur SHBG: Re-standardization did not influence cross-reactivity.
Traceability and Value Assignment:
- ADVIA Centaur TSTII: Standardized using internal standards traceable to ID-LC-MS/MS, which is traceable to NMI M914. Calibrator values are assigned using standards traceable to ID-LC-MS/MS.
- ADVIA Centaur SHBG: Standardized to WHO 200 International Standard for SHBG, NIBSC code 08/266. Calibrator values are assigned using standards prepared from SHBG standardized against gravimetrically prepared dilutions of WHO 08/266.
Stability:
- ADVIA Centaur TSTII: Reagents, Calibrators and Master Curve Materials are stable until the date printed on the box label when stored at 2-8°C. Onboard stability of reagents is 18 days with a calibration interval of 28 days.
- ADVIA Centaur SHBG: Re-standardization did not influence stability.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
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
§ 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 shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, overlapping each other to create a sense of depth and connection.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
SIEMENS HEALTHCARE DIAGNOSTICS INC. MATTHEW GEE SENIOR MANAGER, REGULATORY AFFAIRS 511 BENEDICT AVENUE TARRYTOWN NY 10591-5097
June 29, 2016
Re: K151986 Trade/Device Name: ADVIA Centaur Testosterone II (TSTII), ADVIA Centaur Testosterone II (TSTII) Master Curve Material, ADVIA Centaur SHBG. ADVIA Centaur SHBG Calibrator, ADVIA Centaur SHBG Master Curve Material Regulation Number: 21 CFR 862.1680 Regulation Name: Testosterone test system Regulatory Class: I, reserved Product Code: CDZ, JIT, JJX Dated: June 3, 2016 Received: June 7, 2016
Dear Mr. Matthew Gee:
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
1
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.
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
Indications for Use
510(k) Number (if known) K151986
Device Name
ADVIA Centaur® Testosterone II (TSTII) ADVIA Centaur® Testosterone II (TSTII) Master Curve Material
Indications for Use (Describe) ADVIA Centaur® Testosterone II (TSTII)
The ADVIA Centaur Testosterone II (TSTII) assay is for in vitro diagnostic use in the quantitative determination of total testosterone (bound and unbound) in human serum and plasma using the ADVIA Centaur XP 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) due to tumors, polycystic ovaries, and adrenogenital syndromes.
ADVIA Centaur® Testosterone II (TSTII) Master Curve Material
The ADVIA Centaur Testosterone II (TSTI) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur Testosterone II (TSTII) assay.
| 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
Indications for Use
510(k) Number (if known) K151986
Device Name ADVIA Centaur® SHBG ADVIA Centaur® SHBG Calibrator ADVIA Centaur® SHBG Master Curve Material
Indications for Use (Describe) ADVIA Centaur® SHBG
The ADVIA Centaur SHBG assay is an in vitro diagnostic immunoassay for the quantitative determination of sex hormone-binding globulin (SHBG) in human serum and plasma using the ADVIA Centaur XP system.
The ADVIA Centaur SHBG assay is intended for use as an aid in the diagnosis of androgen disorders.
ADVIA Centaur® SHBG Calibrator
For in vitro diagnostic use in calibrating the ADVIA Centaur SHBG assay on the ADVIA Centaur systems.
ADVIA Centaur® SHBG Master Curve Material
The ADVIA Centaur SHBG Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur SHBG assay.
| 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."
4
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: K151986
Date Prepared 1.
June 27, 2016
Applicant Information 2.
| Contact: | Matthew Gee, M.Sc.
Senior Manager, Regulatory Affairs |
|----------|----------------------------------------------------------------------------------------|
| Address: | Siemens Healthcare Diagnostics Inc.
511 Benedict Avenue
Tarrytown, NY 10591-5097 |
| Phone: | 914-524-2099 |
| Fax: | 914-524-3579 |
Email: matthew.gee@siemens.com
3. Regulatory Information
Table 1. Regulatory Information for ADVIA Centaur TSTII Assay
| Trade Name | ADVIA Centaur® Testosterone II (TSTII) |
|---|---|
| Model Numbers | 10696862 (1-pack); 10696863 (5-pack) |
| Common Name | Radioimmunoassay, testosterones and dihydrotestosterone |
| Classification Name | Testosterone test system |
| FDA Classification | Class I (Reserved) |
| Review Panel | Clinical Chemistry (75) |
| Product Code | CDZ |
| Regulation Number | 862.1680 |
Table 2. Regulatory Information for ADVIA Centaur TSTII Master Curve Material
| Trade Name | ADVIA Centaur® Testosterone II (TSTII) Master Curve Material |
|---|---|
| Model Numbers | 10492623 |
| Common Name | Single (specified) analyte controls (assayed and unassayed) |
| Classification Name | Quality control material (assayed and unassayed) |
| FDA Classification | Class I |
| Review Panel | Clinical Chemistry (75) |
| Product Code | JJX |
| Regulation Number | 862.1660 |
5
Table 3. Regulatory Information for ADVIA Centaur SHBG Assay
| Trade Name | ADVIA Centaur® SHBG |
|---|---|
| Model Numbers | 10997191 (1-pack) |
| Common Name | Radioimmunoassay, testosterones and dihydrotestosterone |
| Classification Name | Testosterone test system |
| FDA Classification | Class I (Reserved) |
| Review Panel | Clinical Chemistry (75) |
| Product Code | CDZ |
| Regulation Number | 862.1680 |
Table 4. Regulatory Information for ADVIA Centaur SHBG Calibrator
| Trade Name | ADVIA Centaur® SHBG Calibrator |
|---|---|
| Model Numbers | 10997192 |
| Common Name | Calibrator, Secondary |
| Classification Name | Calibrator |
| FDA Classification | Class II |
| Review Panel | Clinical Chemistry (75) |
| Product Code | JIT |
| Regulation Number | 862.1150 |
Table 5. Regulatory Information for ADVIA Centaur SHBG Master Curve Material
| Trade Name | ADVIA Centaur® SHBG Master Curve Material |
|---|---|
| Model Numbers | 10997193 |
| Common Name | Single (specified) analyte controls (assayed and unassayed) |
| Classification Name | Quality control material (assayed and unassayed) |
| FDA Classification | Class I |
| Review Panel | Clinical Chemistry (75) |
| Product Code | JJX |
| Regulation Number | 862.1660 |
Predicate Device Information 4.
ADVIA Centaur Testosterone II (TSTII)
Predicate Device Name: Elecys Testosterone II
510(k) Number: K093421
ADVIA Centaur Testosterone II (TSTII) Master Curve Material
Predicate Device Name: ADVIA Centaur Testosterone (TSTO) Master Curve Material
510(k) Number: K140505
6
ADVIA Centaur SHBG
Predicate Device Name: ADVIA Centaur SHBG
510(k) Number: K091867
ADVIA Centaur SHBG Calibrator
Predicate Device Name: ADVIA Centaur SHBG Calibrator
510(k) Number: K091867
ADVIA Centaur SHBG Master Curve Material
Predicate Device Name: ADVIA Centaur SHBG Master Curve Material
510(k) Number: K091867
Intended Use / Indications for Use 5.
ADVIA Centaur Testosterone II (TSTII)
The ADVIA Centaur Testosterone II (TSTII) assay is for in vitro diagnostic use in the quantitative determination of total testosterone (bound and unbound) in human serum and plasma using the ADVIA Centaur XP 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 adrenoqenital syndromes.
ADVIA Centaur TSTII Master Curve Material
The ADVIA Centaur Testosterone II (TSTII) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur Testosterone II (TSTII) assay.
ADVIA Centaur SHBG
The ADVIA Centaur SHBG assay is an in vitro diagnostic immunoassay for the quantitative determination of sex hormone-binding globulin (SHBG) in human serum and plasma using the ADVIA Centaur XP system.
The ADVIA Centaur SHBG assay is intended for use as an aid in the diagnosis of androgen disorders.
ADVIA Centaur SHBG Calibrator
For in vitro diagnostic use in calibrating the ADVIA Centaur SHBG assay on the ADVIA Centaur systems.
ADVIA Centaur SHBG Master Curve Material
The ADVIA Centaur SHBG Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur SHBG assay.
7
6. Device Description
Table 6. Summary of Ingredients of the ADVIA Centaur TSTII Assay Components
| Component | Volume | Ingredients |
|---|---|---|
| ADVIA Centaur TSTII Primary Reagent ReadyPack (included in assay kit) | ||
| ADVIA Centaur TSTII Lite | ||
| Reagent | 10.0 mL/pack | Acridinium ester-labeled hapten (36 $μ$ g/mL) in |
| buffered saline with preservatives | ||
| ADVIA Centaur TSTII | ||
| Solid Phase Reagent | 17.0 mL/pack | Streptavidin-coated latex particles (0.33 g/L) in |
| buffered saline with preservatives | ||
| ADVIA Centaur TSTII Ancillary Reagent ReadyPack (included in assay kit) | ||
| ADVIA Centaur TSTII | ||
| Releasing Agent | 10.0 mL/pack | Steroid releasing agent (0.4 $μ$ g/mL) and biotinylated |
| sheep monoclonal anti-testosterone antibody (27 $μ$ g/L) in buffered saline and preservatives | ||
| ADVIA Centaur TSTII Calibrator (included in assay kit) | ||
| ADVIA Centaur TSTII | ||
| Low and High Calibrators | 2.0 mL/vial | After reconstitution, low or high levels of USP-grade |
| estradiol, testosterone, cortisol, and progesterone | ||
| spiked in charcoal-stripped, defibrinated human | ||
| plasma with sodium azide (0.1%) and preservatives | ||
| ADVIA Centaur TSTII Master Curve Material (sold separately) | ||
| ADVIA Centaur TSTII | ||
| MCM1 | 1.0 mL/vial | Lyophilized human plasma with sodium azide (0.1% |
| after reconstitution) and preservatives | ||
| ADVIA Centaur TSTII | ||
| MCM2-7 | 1.0 mL/vial | Various levels of testosterone in lyophilized human |
| plasma with sodium azide (0.1% after reconstitution) | ||
| and preservatives |
Table 7. Summary of Ingredients of the ADVIA Centaur SHBG Assay Components
| Component | Volume | Ingredients |
|---|---|---|
| ADVIA Centaur SHBG Primary Reagent ReadyPack (included in assay kit) | ||
| ADVIA Centaur SHBG | ||
| Lite Reagent | 3.0 mL/pack | Mouse monoclonal anti-SHBG antibody (~130 ng/mL) |
| labeled with acridinium ester in HEPES-buffered | ||
| saline with bovine serum albumin, mouse serum, | ||
| sodium azide (180.00 | ||
| Females Post-Menopause (Age 45-89) | 134 | 61.44 |
FAI
| Group | n | Median | Reference
Values |
|------------------------------------|-----|--------|---------------------|
| Males Age 10% interference, serial measurements were taken and analyzed by linear regression. Results are presented below.
| Interferent | ~30 ng/dL Testosterone | ~300 ng/dL Testosterone | ||||
|---|---|---|---|---|---|---|
| Dose | ||||||
| Without | ||||||
| Interferent | ||||||
| (ng/dL) | Dose | |||||
| With | ||||||
| Interferent | ||||||
| (ng/dL) | % | |||||
| Interference | Dose | |||||
| Without | ||||||
| Interferent | ||||||
| (ng/dL) | Dose | |||||
| With | ||||||
| Interferent | ||||||
| (ng/dL) | % | |||||
| Interference | ||||||
| Hemoglobin | ||||||
| (500 mg/dL) | 32.16 | 34.02 | 5.8 | 240.66 | 239.81 | -0.4 |
| Triglycerides | ||||||
| (1000 mg/dL) | 31.23 | 31.61 | 1.2 | 233.78 | 213.84 | -8.5 |
| Conjugated Bilirubin | ||||||
| (15 mg/dL) | 20.21 | 21.05 | 4.2 | 269.61 | 258.61 | -4.1 |
| Unconjugated Bilirubin | ||||||
| (20 mg/dL) | 20.81 | 22.81 | 9.6 | 258.77 | 261.97 | 3.2 |
| Cholesterol | ||||||
| (500 mg/dL) | 21.91 | 23.32 | 6.4 | 263.43 | 238.58 | -9.4 |
| Rheumatoid Factor | ||||||
| (200 IU/mL) | 24.46 | 25.59 | 4.6 | 271.95 | 273.98 | 0.7 |
The concentration of biotin that causes 10% interference, as determined by linear regression, is 30 ng/mL. Specimens that contain 40 ng/mL of biotin demonstrate a 14.6% change in results.
Samples with conjugated bilirubin concentrations > 15 mg/dL will cause erroneous results. Specimens that contain 20 mg/dL of conjugated billirubin demonstrate a -14.4% change in results.
Samples with unconjugated bilirubin concentrations > 20 mg/dL will cause erroneous results. Specimens that contain 30 mg/dL of unconjugated bilirubin demonstrate a 20.1% change in results.
10.9 Heterophile Interference
Heterophile interference testing was performed by spiking 19 HAMA-positive serum samples with ~30 and ~300 ng/dL USP testosterone. The Expected Dose was calculated by adding the "spiked" testosterone concentration to the endogenous (neat) testosterone concentration of the sample. The percent recoveries were determined by dividing the Observed Dose by the Expected Dose. The mean recovery for all samples spiked with ~30 ng/dL USP testosterone was 98.69%. The mean recovery for all samples spiked with ~300 ng/dL USP testosterone was 94.55%.
10.10 Cross-Reactivity
Cross-reactivity studies were performed using two sample pools of approximately 0 ng/dL and 300 ng/dL testosterone. These sample pools were spiked with potential cross-reactants.
16
Control samples were prepared by spiking sample pools with the appropriate diluent at the same volume as the interfering substance stock. Results are presented below.
| Potential | ~0 nq/dL Testosterone | ~300 ng/dL Testosterone | ||||
|---|---|---|---|---|---|---|
| Cross-Reacting | ||||||
| Substance | Dose | |||||
| Without | ||||||
| Substance | ||||||
| (ng/dL) | Dose | |||||
| With | ||||||
| Substance | ||||||
| (ng/dL) | % | |||||
| Cross- | ||||||
| Reactivity | Dose | |||||
| Without | ||||||
| Substance | ||||||
| (ng/dL) | Dose | |||||
| With | ||||||
| Substance | ||||||
| (ng/dL) | % | |||||
| Cross- | ||||||
| Reactivity | ||||||
| 5-Androstene-3ß, 17ß-diol | ||||||
| (10,0000) | 0.00 | 124.12 | 0.124 | 315.34 | 147.87 | -0.167 |
| Androstenedione | ||||||
| (10,000) | 1.98 | 141.69 | 1.397 | 329.36 | 240.73 | -0.886 |
| Androsterone | ||||||
| (100,000) | 2.18 | 4.99 | 0.003 | 320.65 | 294.93 | -0.026 |
| Canrenone | ||||||
| (18,000) | 2.18 | 2.25 | 0.000 | 320.65 | 332.50 | 0.066 |
| Canrenone | ||||||
| (50,000) | 2.18 | 2.82 | 0.001 | 320.65 | 323.09 | 0.005 |
| Canrenone | ||||||
| (100,000) | 2.18 | 2.70 | 0.001 | 320.65 | 329.04 | 0.008 |
| Corticosterone | ||||||
| (100,000) | 2.18 | 1.72 | 0.000 | 320.65 | 334.39 | 0.014 |
| Cortisol | ||||||
| (100,000) | 2.18 | 2.68 | 0.000 | 320.65 | 342.27 | 0.022 |
| Cyproterone | ||||||
| (10,000) | 2.18 | 15.01 | 0.128 | 320.65 | 326.09 | 0.054 |
| Danazol | ||||||
| (100,000) | 2.18 | 122.24 | 0.120 | 320.65 | 199.51 | -0.121 |
| 11-Deoxycortisol | ||||||
| (100,000) | 2.18 | 4.11 | 0.002 | 320.65 | 322.85 | 0.002 |
| Dexamethasone | ||||||
| (100,000) | 2.18 | 2.00 | 0.000 | 320.65 | 326.69 | 0.006 |
| DHEA | ||||||
| (100,000) | 2.18 | 7.86 | 0.006 | 320.65 | 278.20 | -0.042 |
| DHEAs | ||||||
| (5,000,000) | 2.18 | 73.88 | 0.001 | 320.65 | 278.70 | -0.001 |
| 5a-Dihydrotestosterone | ||||||
| (10,000) | 2.18 | 77.56 | 0.754 | 320.65 | 179.68 | -1.410 |
| 17β-Estradiol | ||||||
| (100,000) | 0.09 | 21.12 | 0.021 | 355.52 | 88.27 | -0.267 |
| Estrone | ||||||
| (10,000) | 2.18 | 2.41 | 0.002 | 320.65 | 319.76 | -0.009 |
| Ethisterone | ||||||
| (100,000) | 0.00 | 445.99 | 0.446 | 271.00 | 678.95 | 0.408 |
| 113-Hydroxytestosterone | ||||||
| (10,000) | 0.00 | 1546.85 | 15.469 | 271.00 | 1612.34 | 13.413 |
| 11-Keto-testosterone | ||||||
| (100,000) | 0.00 | 1765.93 | 1.766 | 271.00 | 1854.41 | 1.583 |
| Nandrolone decanoate | ||||||
| (100,000) | N/A* | N/A* | N/A* | N/A* | N/A* | N/A* |
| Norgestrel | ||||||
| (100,000) | 0.00 | 145.01 | 0.145 | 271.00 | 197.62 | -0.073 |
17
| Potential | ~0 ng/dL Testosterone | ~300 ng/dL Testosterone | ||||
|---|---|---|---|---|---|---|
| Cross-Reacting | ||||||
| Substance | Dose | |||||
| Without | ||||||
| Substance | ||||||
| (ng/dL) | Dose | |||||
| With | ||||||
| Substance | ||||||
| (ng/dL) | % | |||||
| Cross- | ||||||
| Reactivity | Dose | |||||
| Without | ||||||
| Substance | ||||||
| (ng/dL) | Dose | |||||
| With | ||||||
| Substance | ||||||
| (ng/dL) | % | |||||
| Cross- | ||||||
| Reactivity | ||||||
| Oxymetholone | ||||||
| (10,000) | 2.18 | 2.94 | 0.008 | 320.65 | 263.08 | -0.576 |
| Prednisolone | ||||||
| (100,000) | 0.00 | 0.00 | 0.000 | 271.00 | 364.17 | 0.093 |
| Prednisone | ||||||
| (100,000) | 0.00 | 0.00 | 0.000 | 271.00 | 282.17 | 0.011 |
| Progesterone | ||||||
| (100,000) | 2.18 | 2.45 | 0.000 | 320.65 | 335.04 | 0.014 |
| Spironolactone | ||||||
| (8,000) | 2.18 | 2.59 | 0.005 | 320.65 | 329.06 | 0.105 |
| Spironolactone | ||||||
| (100,000) | 2.18 | 2.09 | 0.000 | 320.65 | 331.68 | 0.011 |
| Testosterone propionate | ||||||
| (10,000) | 0.00 | 3.54 | 0.035 | 271.00 | 565.56 | 2.946 |
| 7α-Thiomethyl spironolactone | ||||||
| (40,000) | 2.18 | 2.45 | 0.001 | 320.65 | 320.96 | 0.001 |
| 7α-Thiomethyl spironolactone | ||||||
| (100,000) | 2.18 | 2.40 | 0.000 | 320.65 | 318.27 | -0.002 |
- Crossreactivity for this compound could not be calculated. This compound tested above the measuring interval.
Traceability and Value Assignment 10.11
The ADVIA Centaur TSTII assay is standardized using internal standards made from USPgrade testosterone, which are traceable to isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS). The ID-LC-MS/MS is traceable to the primary testosterone standard National Measurement Institute (NMI) M914.
The calibrator values used for two-point calibration of the ADVIA Centaur TSTII assay are value assigned using standards traceable to the ID-LC-MS/MS method.
The ADVIA Centaur TSTII Master Curve Material assigned values are lot specific of target values.
10.12 Stability
The ADVIA Centaur TSTII Reagents, Calibrators and Master Curve Materials are stable until the date printed on the box label when stored at 2-8°C.
The onboard stability of the ADVIA Centaur TSTII Reagents is 18 days with a calibration interval of 28 days.
18
Performance Characteristics: ADVIA Centaur SHBG 11.
11.1 Precision
A 5-day precision study was performed using the modified device to verify existing claims. Samples included 3 patient serum specimens, 2 patient pools and three levels of controls. Samples were assayed once a day in replicates of 5, for 5 days (n = 25 replicates per sample). The following results were obtained:
| Sample | Mean
(nmol/L) | Repeatability | | Within-Lab | |
|--------------------|------------------|----------------|-----|----------------|-----|
| | | SD
(nmol/L) | %CV | SD
(nmol/L) | %CV |
| Patient specimen 1 | 70.71 | 1.58 | 2.2 | 1.89 | 2.7 |
| Patient specimen 2 | 115.95 | 3.05 | 2.6 | 3.84 | 3.3 |
| Patient specimen 3 | 145.59 | 4.39 | 3.0 | 6.44 | 4.4 |
| Patient pool 1 | 10.69 | 0.21 | 1.9 | 0.26 | 2.4 |
| Patient pool 2 | 39.89 | 0.72 | 1.8 | 0.82 | 2.1 |
| Control 1 | 22.49 | 0.40 | 1.8 | 0.43 | 1.9 |
| Control 2 | 44.95 | 0.96 | 2.1 | 0.99 | 2.2 |
| Control 3 | 39.54 | 0.93 | 2.3 | 1.00 | 2.5 |
11.2 Linearity
A linearity study was performed using the modified device according to CLSI EP06-A using 11 serially diluted samples spanning the assay range. The mean was taken from each sample tested in duplicate. As presented below, the bias from the linear fit estimate was ≤15%.
| Sample | Expected
Dose
(nmol/L) | Observed
Dose
(nmol/L) | Weighted
Linear Fit
Estimate | Deviation
from
Linear Fit
(nmol/L) | Deviation
from
Linear Fit
(%) |
|--------|------------------------------|------------------------------|------------------------------------|---------------------------------------------|----------------------------------------|
| A | 198.79 | 195.95 | 195.83 | 0.12 | 0.06 |
| B | 183.50 | 183.50 | 180.79 | 2.71 | 1.50 |
| C | 159.03 | 161.07 | 156.72 | 4.36 | 2.78 |
| D | 119.27 | 117.44 | 117.60 | -0.16 | -0.13 |
| E | 59.64 | 59.43 | 58.92 | 0.51 | 0.87 |
| F | 29.82 | 29.28 | 29.58 | -0.31 | -1.04 |
| G | 14.91 | 14.77 | 14.91 | -0.15 | -0.99 |
| H | 7.45 | 7.51 | 7.58 | -0.07 | -0.97 |
| I | 3.73 | 3.92 | 3.91 | 0.01 | 0.30 |
| J | 1.86 | 2.04 | 2.08 | -0.04 | -2.03 |
| K | 0.93 | 1.16 | 1.16 | 0.00 | -0.10 |
The weighted linear regression equation is presented below.
Observed = 0.984(Expected) + 0.245 ng/dL
19
11.3 Dilution Recovery
Five serum samples in the range of 161.14-175.13 nmol/L of SHBG were diluted 1:2 with ADVIA Centaur Multi-Diluent 1, and assayed for recovery. The recoveries ranged from 87 to 101% with a mean of 92%.
| Sample | Onboard Dilution Dose
(nmol/L) | Manual Dilution Dose
(nmol/L) | % Recovery |
|--------|-----------------------------------|----------------------------------|------------|
| 1 | 175.13 | 173.59 | 101% |
| 2 | 164.64 | 188.37 | 87% |
| 3 | 161.14 | 172.77 | 93% |
| 4 | 162.89 | 181.78 | 90% |
| 5 | 164.34 | 179.9 | 91% |
| Mean | | | 92% |
11.4 Method Comparison
A method comparison study was performed by comparing the ADVIA Centaur SHBG assay to the Elecsys SHBG assay with 174 serum samples distributed over the assay range. The analysis was performed using Weighted Deming regression equation from the analysis is presented below.
ADVIA Centaur SHBG = 0.99(Elecsys) - 0.11 nmol/L (r = 0.99)
11.5 Matrix Comparison
The re-standardization of the ADVIA Centaur SHBG assay did not influence sample matrices.
11.6 Reference Intervals
See Section 10.6 (Reference Intervals) for ADVIA Centaur TSTII assay.
11.7 Detection Limit
The limit of blank (LoB). limit of detection (LoD). and the limit of quantitation (LoQ) were determined as described in CLSI protocol EP17-A2. The ADVIA Centaur SHBG assay has an LoB of 1.2 nmol/L, an LoD of 1.6 nmol/L, and an LoQ of 1.8 nmol/L.
The LoB is defined as the highest measurement result that is likely to be observed for a blank sample. The LoD is defined as the lowest concentration of SHBG that can be detected with 95% probability. The LoQ is defined as the lowest concentration of SHBG that can be detected at a total CV of 20%.
11.8 Interference
The re-standardization of the ADVIA Centaur SHBG assay did not influence interference. This information is described in K091867.
11.9 Cross-Reactivity
The re-standardization of the ADVIA Centaur SHBG assay did not influence cross-reactivity. This information is described in K091867.
11.10 Traceability and Value Assignment
The ADVIA Centaur SHBG assay is standardized to World Health Organization (WHO) 200 International Standard for SHBG, NIBSC code 08/266.
20
The calibrator values used for two-point calibration of the ADVIA Centaur SHBG assay are value assigned using standards prepared from SHBG standardized against gravimetrically prepared dilutions of the 200 International Reference Preparation (WHO 08/266) from NIBSC.
The ADVIA Centaur SHBG Master Curve Material assigned values are lot specific of target values.
11.11 Stability
The re-standardization of the ADVIA Centaur SHBG assay did not influence stability. This information is described in K091867.
12. Conclusions
The new ADVIA Centaur Testosterone II (TSTII) assay (Reagents and Calibrators) is substantially equivalent in principle and performance to the currently-marketed predicate device, the Elecsys Testosterone II assay, cleared under 510(k) K093421.
The ADVIA Centaur TSTII Master Curve Material is substantially equivalent in principle and performance to the currently-marketed predicate device, the ADVIA Centaur Testosterone (TSTO) Master Curve Material, cleared under 510(k) K140505.
The modified ADVIA Centaur SHBG assay (Reagents, Calibrators, Master Curve Material) is substantially equivalent in principle and performance to the currently-marketed predicate device, the ADVIA Centaur SHBG assay, cleared under 510(k) K091867.