ADVA Centaur Testosterone II (TSTII), ADVA Centaur Testosterone II (TSTII) Master Curve Material, ADVIA Centaur SHBG, ADVIA Centaur SHBG Calibrator, ADVIA Centaur SHBG Master Curve Material

Q: Who is the manufacturer of ADVA Centaur Testosterone II (TSTII), ADVA Centaur Testosterone II (TSTII) Master Curve Material, ADVIA Centaur SHBG, ADVIA Centaur SHBG Calibrator, ADVIA Centaur SHBG Master Curve Material?

Siemens Healthcare Diagnostics, Inc. filed the 510(k) submission for ADVA Centaur Testosterone II (TSTII), ADVA Centaur Testosterone II (TSTII) Master Curve Material, ADVIA Centaur SHBG, ADVIA Centaur SHBG Calibrator, ADVIA Centaur SHBG Master Curve Material (K151986).

Q: What is the FDA product code for ADVA Centaur Testosterone II (TSTII), ADVA Centaur Testosterone II (TSTII) Master Curve Material, ADVIA Centaur SHBG, ADVIA Centaur SHBG Calibrator, ADVIA Centaur SHBG Master Curve Material?

CDZ. It is classified under 21 CFR 862.1680 as a Class 1 device in the Clinical Chemistry panel.

Q: What is the regulatory pathway for ADVA Centaur Testosterone II (TSTII), ADVA Centaur Testosterone II (TSTII) Master Curve Material, ADVIA Centaur SHBG, ADVIA Centaur SHBG Calibrator, ADVIA Centaur SHBG Master Curve Material?

510(k) clearance (submission type: Traditional).

Q: What are the predicate devices for ADVA Centaur Testosterone II (TSTII), ADVA Centaur Testosterone II (TSTII) Master Curve Material, ADVIA Centaur SHBG, ADVIA Centaur SHBG Calibrator, ADVIA Centaur SHBG Master Curve Material?

Roche Diagnostics Elecsys Testosterone II (k093421); Siemens Healthcare Diagnostics ADVIA Centaur Testosterone (TSTO) Master Curve Material (k140505); Siemens Healthcare Diagnostics ADVIA Centaur SHBG Assay (k091867); Siemens Healthcare Diagnostics ADVIA Centaur SHBG Calibrator (k091867); Siemens Healthcare Diagnostics ADVIA Centaur SHBG Master Curve Material (k091867).

Q: Who can help prepare an FDA 510(k) submission like ADVA Centaur Testosterone II (TSTII), ADVA Centaur Testosterone II (TSTII) Master Curve Material, ADVIA Centaur SHBG, ADVIA Centaur SHBG Calibrator, ADVIA Centaur SHBG Master Curve Material?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA 510(k) submissions. See https://innolitics.com/services/510ks/ or contact https://innolitics.com/contact.

K151986 · Siemens Healthcare Diagnostics, Inc. · CDZ · Jun 29, 2016 · Clinical Chemistry

Device Facts

Record ID	K151986
Device Name	ADVA Centaur Testosterone II (TSTII), ADVA Centaur Testosterone II (TSTII) Master Curve Material, ADVIA Centaur SHBG, ADVIA Centaur SHBG Calibrator, ADVIA Centaur SHBG Master Curve Material
Applicant	Siemens Healthcare Diagnostics, Inc.
Product Code	CDZ · Clinical Chemistry
Decision Date	Jun 29, 2016
Decision	SESE
Submission Type	Traditional
Regulation	21 CFR 862.1680
Device Class	Class 1
Attributes	Pediatric

Intended Use

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 adrenogenital syndromes. 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. 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. The ADVIA Centaur SHBG Calibrator is for in vitro diagnostic use in calibrating the ADVIA Centaur SHBG assay on the ADVIA Centaur systems. 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.

Device Story

ADVIA Centaur TSTII and SHBG assays are quantitative immunoassays for use on the ADVIA Centaur XP system. TSTII is a competitive chemiluminescent immunoassay; SHBG is a sandwich chemiluminescent immunoassay. TSTII uses a releasing agent to dissociate testosterone from endogenous binding proteins. Both assays utilize magnetic latex particles and acridinium ester-labeled reagents. The system detects relative light units (RLUs) proportional (SHBG) or inversely proportional (TSTII) to analyte concentration. Results are calculated via master curves adjusted by high/low calibrators. Used in clinical laboratories by trained personnel. Output aids clinicians in diagnosing androgen-related disorders. Benefits include standardized, automated measurement of hormone levels to support clinical decision-making.

Clinical Evidence

Bench testing only. Precision study (20 days, 80 replicates) showed total %CV 5.3-12.6% for TSTII. Linearity confirmed 7.0-1500 ng/dL (TSTII) and 1.6-180 nmol/L (SHBG). Method comparison against CDC ID-LC-MS/MS (n=128) yielded slope 0.971, r=0.982. Pediatric samples (n=61) showed r=0.99. Interference testing evaluated hemoglobin, bilirubin, triglycerides, and biotin; limitations noted for high-dose biotin and specific bilirubin levels. HAMA interference testing showed mean recovery 94.55-98.69%.

Technological Characteristics

Competitive (TSTII) and sandwich (SHBG) chemiluminescent immunoassays. Components: acridinium ester-labeled haptens/antibodies, streptavidin-coated magnetic latex particles. Energy source: ADVIA Centaur XP system. Connectivity: Standalone analyzer. Calibration: 2-point. Traceability: TSTII to CDC ID-LC-MS/MS; SHBG to WHO 2nd IS (08/226). Software: Embedded firmware for system control and data processing.

Indications for Use

Indicated for quantitative determination of total testosterone and SHBG in human serum/plasma to aid in diagnosis/treatment of androgen disorders (e.g., hypogonadism, delayed/precocious puberty, impotence, hirsutism, virilization) in male and female patients.

Regulatory Classification

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.

Predicate Devices

Roche Diagnostics Elecsys Testosterone II (k093421)
Siemens Healthcare Diagnostics ADVIA Centaur Testosterone (TSTO) Master Curve Material (k140505)
Siemens Healthcare Diagnostics ADVIA Centaur SHBG Assay (k091867)
Siemens Healthcare Diagnostics ADVIA Centaur SHBG Calibrator (k091867)
Siemens Healthcare Diagnostics ADVIA Centaur SHBG Master Curve Material (k091867)

Related Devices

K191533 — ADVIA Centaur Testosterone II (TSTII), ADVIA Centaur SHBG · Siemens Healthcare Diagnostics, Inc. · Aug 28, 2019
K233480 — Access SHBG · Beckman Coulter, Inc. · Feb 8, 2024
K223405 — Access Testosterone · Beckman Coulter, Inc. · Jan 13, 2023

Submission Summary (Full Text)

{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) | | |----------------------------------------------------------------------------------|--------------------------------------------------------------------------------| | <div> Prescription Use (Part 21 CFR 801 Subpart D) </div> | <div> Over-The-Counter Use (21 CFR 801 Subpart C) </div> | ### 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 (< 0.1%), surfactant, and preservatives | | ADVIA Centaur SHBG Solid Phase Reagent | 11.0 mL/pack | Streptavidin coupled to latex paramagnetic particles (~150 $\mu$ g/mL) in HEPES buffered saline with bovine serum albumin, mouse serum, sodium azide (< 0.1%), surfactant, and preservatives | | ADVIA Centaur SHBG Ancillary Well Reagent | 3.0 mL/pack | Biotinylated monoclonal mouse anti-SHBG antibody (~6 $\mu$ g/mL) in HEPES buffered saline with bovine serum albumin, mouse serum, sodium azide (< 0.1%), surfactant, and preservatives | | ADVIA Centaur SHBG Calibrator (sold separately) | | | | ADVIA Centaur SHBG Low and High Calibrators | 2.0 mL/vial | After reconstitution, low or high levels of SHBG in equine serum, detergents and preservatives | {8}------------------------------------------------ | Component | Volume | Ingredients | |------------------------------------------------------------|-------------|-----------------------------------------------------------------------------| | ADVIA Centaur SHBG Master Curve Material (sold separately) | | | | ADVIA Centaur SHBG MCM1-5 | 1.0 mL/vial | Various levels of SHBG in equine serum with detergents and preservatives | #### Purpose of the Submission 7. The purpose of this submission is to submit a new device (ADVIA Centaur TSTII assay) and to submit a modification to the ADVIA Centaur SHBG assay due to the re-standardization to the WHO 2nd International Standard for SHBG (08/266). #### Comparison of Predicate Device and Modified Device 8. | Item | ADVIA Centaur Testosterone II (TSTII) Assay (Candidate Device) | Elecsys Testosterone II Assay (Predicate Device) | |-----------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Intended Use | For in vitro diagnostic use in the quantitative determination of total testosterone (bound and unbound) in serum using the ADVIA Centaur and ADVIA Centaur XP Systems. | Immunoassay for the in vitro quantitative determination of testosterone in human serum and plasma. The electrochemiluminescence immunoassay "ECLIA" is intended for use on Elecsys and cobas e immunoassay analyzers. | | 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 | | Methodology | Chemiluminescence | Electrochemiluminescence | | Assay Protocol | Competitive immunoassay | Same | | Traceability/ Standardization | ID-LC-MS/MS (CDC HoSt Testosterone Reference Measurement Procedure) | ID-GC/MS | | Specimen Type | Human serum and plasma | Same | | Sample Volume | 20 µL | Same | | Lower Limit of Measuring Range | LoQ | LoD | | Measuring Range | 7.0-1500 ng/dL | 2.5-1500 ng/dL | | Calibration | 2-point calibration | Same | ### Table 8. Comparison of ADVIA Centaur TSTII Assay to Predicate {9}------------------------------------------------ | Item | ADVIA Centaur Testosterone II (TSTII) MCM (Candidate Device) | ADVIA Centaur Testosterone (TSTO) MCM (Predicate Device) | |------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Intended Use | 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. | The ADVIA Centaur Testosterone (TSTO) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur Testosterone assay. | | Approximate Target Values (Actual Number Varies by Lot) | Level 1: 0.00 ng/dL Level 2: 50.0 ng/dL Level 3: 100.0 ng/dL Level 4: 500.0 ng/dL Level 5: 750.0 ng/dL Level 6: 1000.0 ng/dL Level 7: 1600.0 ng/dL | Same | | Matrix | Lyophilized human plasma | Same | | Value Assignment Process | Full curve testing | Two point nested testing | ### Table 9. Comparison of ADVIA Centaur TSTII Master Curve Material to Predicate ### Table 10. Comparison of ADVIA Centaur SHBG Assay to Predicate | ltem | ADVIA Centaur SHBG Assay: WHO 08/266 200 IS (Candidate Device) | ADVIA Centaur SHBG Assay: WHO 95/560 1st IS (Predicate Device) | |----------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------| | Intended Use | The ADVIA Centaur SHBG assay is an in vitro diagnostic immunoassay for the quantitative determination of sex hormone-binding qlobulin (SHBG) in human serum and plasma using the ADVIA Centaur XP system. | Same | | Indications for Use | The ADVIA Centaur SHBG assay is intended for use as an aid in the diagnosis of androgen disorders. | Same | | Methodology | Chemiluminescence | Same | | Assay Protocol | Sandwich immunoassay | Same | | Traceability/ Standardization | Standardized to WHO 200 International Traceable to WHO 1* International Standard (08/266) | Standard (95/560) | | Specimen Type | Human serum and plasma | Same | | Sample Volume | 10 µL | Same | | Measuring Range | 1.60–180 nmol/L | Same | | Calibration | 2-point calibration | Same | {10}------------------------------------------------ | Item | ADVIA Centaur SHBG Calibrator: WHO 08/266 2nd IS (Candidate Device) | ADVIA Centaur SHBG Calibrator: WHO 95/560 1st IS (Predicate Device) | |-----------------------------|-------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------| | Intended Use | For in vitro diagnostic use in calibrating the ADVIA Centaur SHBG assay on the ADVIA Centaur systems. | Same | | Target Values | Low Calibrator: 10.0 nmol/L High Calibrator: 140.0 nmol/L | Same | | Matrix | Equine serum | Same | | Traceability | WHO 2nd International Standard | WHO 1st International Standard | | Value Assignment Process | Full curve testing | Two point nested testing | ### Table 11. Comparison of ADVIA Centaur SHBG Calibrator to Predicate | Table 12. Comparison of ADVIA Centaur SHBG Master Curve Material to Predicate | | | | | |-------------------------------------------------------------------------------|--|--|--|--| |-------------------------------------------------------------------------------|--|--|--|--| | Item | ADVIA Centaur SHBG MCM: WHO 08/266 2nd IS (Candidate Device) | ADVIA Centaur SHBG MCM: WHO 95/560 1st IS (Predicate Device) | |------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------| | Intended Use | 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. | Same | | Approximate Target Values (Actual Number Varies by Lot) | Level 1: 0.1 nmol/L Level 2: 10.0 nmol/L Level 3: 50.0 nmol/L Level 4: 100.0 nmol/L Level 5: 200.0 nmol/L | Same | | Matrix | Equine serum | Same | | Traceability | WHO 2nd International Standard | WHO 1st International Standard | | Value Assignment Process | Two point nested testing | Same | #### Standard/Guidance Document References 9. The following recognized standards from Clinical Laboratory Standards Institute (CLSI) were used as a basis of the study procedures described in this submission: - Evaluation of Precision Performance of Quantitative Measurement Methods; l Approved Guideline - Second Edition (CLSI EP05-A2, 2004; Recognition No. 7-110) - 트 Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline (CLSI EP06-A, 2003; Recognition No. 7-193) - Interference Testing in Clinical Chemistry; Approved Guideline - Second Edition (CLSI EP07-A2, 2005; Recognition No. 7-127) - Measurement Procedure Comparison And Bias Estimation Using Patient Samples --Third Edition (CLSI EP9-A3, 2013; Recognition Number 7-245) - Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; l Approved Guideline -- Second Edition (CLSI EP17-A2, 2013: Recognition No. 7-233) {11}------------------------------------------------ - Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline - Third Edition (CLSI EP28-A3c - formerly C28-A3c, 2010; Recognition No. 7-224) - Medical devices - Application of risk management to medical devices (ANSI/AAMI/ISO 14971:2007/(R)2010; Recognition No. 5-70) #### 10. Performance Characteristics: ADVIA Centaur TSTII #### 10.1 Precision A 20-day precision study was performed according to CLSI EP5-A2. Samples included 5 serum patient pools, three levels of controls and one female patient serum specimen. Samples were assayed twice a day in replicates of 2, for 20 days (n = 80 replicates per sample). The following results were obtained: | Sample | Mean (ng/mL) | Repeatability | | Within-Lab | | |-------------------------------|-----------------|---------------|-----|---------------|------| | | | SD (ng/mL) | %CV | SD (ng/mL) | %CV | | Female Patient Serum Specimen | 10.58 | 0.90 | 8.5 | 1.33 | 12.6 | | Serum Patient Pool 1 | 26.45 | 1.41 | 5.3 | 2.07 | 7.8 | | Serum Patient Pool 2 | 81.78 | 2.49 | 3.0 | 4.29 | 5.3 | | Serum Patient Pool 3 | 311.97 | 12.37 | 4.0 | 16.54 | 5.3 | | Serum Patient Pool 4 | 768.74 | 23.81 | 3.1 | 41.71 | 5.4 | | Serum Patient Pool 5 | 1127.07 | 54.15 | 4.9 | 77.67 | 6.9 | | Control 1 | 226.34 | 7.11 | 3.1 | 10.19 | 4.5 | | Control 2 | 578.19 | 19.28 | 3.3 | 34.53 | 6.0 | | Control 3 | 735.72 | 24.61 | 3.3 | 44.43 | 6.0 | #### 10.2 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 <10%. | Sample | Expected Dose (ng/dL) | Observed Dose (ng/dL) | Weighted Linear Fit Estimate | Deviation from Linear Fit (ng/dL) | Deviation from Linear Fit (%) | |--------|-----------------------------|-----------------------------|------------------------------------|--------------------------------------------|----------------------------------------| | A | 1653.77 | 1653.77 | 1521.25 | 132.52 | 8.71 | | B | 1242.01 | 1155.85 | 1142.43 | 13.43 | 1.18 | | C | 830.24 | 834.69 | 763.61 | 71.09 | 9.31 | | D | 418.48 | 402.81 | 384.78 | 18.03 | 4.68 | | E | 212.60 | 198.74 | 195.37 | 3.36 | 1.72 | | F | 109.66 | 103.94 | 100.67 | 3.27 | 3.25 | | G | 58.19 | 49.48 | 53.32 | -3.84 | -7.19 | | H | 32.46 | 27.04 | 29.64 | -2.59 | -8.75 | | I | 19.59 | 15.80 | 17.80 | -2.00 | -11.25 | | J | 13.15 | 10.53 | 11.88 | -1.35 | -11.35 | | K | 6.72 | 6.72 | 5.96 | 0.76 | 12.71 | {12}------------------------------------------------ The weighted linear regression equation is presented below. Observed = 0.92(Expected) - 0.22 na/dL #### 10.3 Dilution Recovery Five serum samples in the range of 1520.24–1715.58 ng/dL of testosterone were diluted 1:2 with ADVIA Centaur Multi-Diluent 3, and assayed for recovery. The recoveries ranged from 93.9 to 114.2% with a mean of 106.7%. | Sample | Dilution Factor | Observed Dose (ng/dL) | Expected Dose (ng/dL) | % Recovery | |--------|-----------------|--------------------------|--------------------------|------------| | 1 | Neat | 1581.78 | 1684.06 | 93.9% | | | 1:2 | 790.89 | 842.03 | | | 2 | Neat | 1757.54 | 1636.03 | 107.4% | | | 1:2 | 878.77 | 818.01 | | | 3 | Neat | 1730.52 | 1520.25 | 113.8% | | | 1:2 | 865.26 | 760.12 | | | 4 | Neat | 1825.77 | 1598.79 | 114.2% | | | 1:2 | 912.89 | 799.39 | | | 5 | Neat | 1782.64 | 1715.58 | 103.9% | | | 1:2 | 891.32 | 857.79 | | | Mean | | | | 106.7% | #### Method Comparison 10.4 A method comparison study was performed by comparing the ADVIA Centaur TSTII assay to the CDC HoSt Testosterone ID-LC-MS/MS method with 128 serum samples distributed over the assay range (8.61 to 1394.00 ng/dL). The analysis was performed using Passing-Bablok regression. The regression equation from the analysis is presented below. ADVIA Centaur TSTII = 0.97(ID-LC-MS/MS) + 1.94 ng/dL (r = 0.98) An additional method comparison study was performed against the Dimension Vista Total Testosterone assay (k151529) with 117 serum samples from adults and 61 samples from pediatrics) ranging from 8.00 ng/dL to 825.00 ng/dL. An analysis was also performed with the 61 samples from pediatric subjects (27 females age 7 to 18 and 34 males age 9 to 18) ranging from 8.00 to 732.00 ng/dL. The analyses were performed using Weighted Deming regression. The regression equations from the analyses are presented below. Adult and pediatric specimens: ADVIA Centaur TSTII = 1.01(Dimension Vista TST) + 0.99 ng/dL (r = 0.99) Pediatric specimens: ADVIA Centaur TSTII = 1.04/Dimension Vista TST) + 0.22 ng/dL (r = 0.99) #### 10.5 Matrix Comparison The ADVIA Centaur TSTII assay was evaluated using different specimen matrices and tube collection types. A specimen collection study was performed using a minimum of 50 matched specimens drawn in different tube types including serum red top, serum separator tube, plasma separator tube, dipotassium EDTA, lithium heparin, and sodium heparin. No significant difference between tube types was observed. The following results were obtained: {13}------------------------------------------------ | Tube Types | Slope | Intercept (ng/dL) | r | |---------------------------------|-------|-------------------|-------| | Serum vs. serum separator tube | 0.98 | 3.76 | 0.991 | | Serum vs. plasma separator tube | 0.94 | 3.56 | 0.993 | | Serum vs. dipotassium EDTA | 0.97 | -1.61 | 0.994 | | Serum vs. lithium heparin | 0.95 | 4.50 | 0.996 | | Serum vs. sodium heparin | 0.94 | 2.85 | 0.996 | #### 10.6 Reference Intervals Reference intervals for the ADVIA Centaur TSTII assay were established for pediatrics and adults according to CLSI EP28-A3c. Reference intervals for the ADVIA Centaur SHBG assay for adults according to CLSI EP28-АЗс. The adult population included samples from apparently healthy normal cycling women, postmenopausal women, and normal males. Based on a central 95% interval, the following reference intervals were established. ### Testosterone | Group | n | Median (ng/dL) | Reference Values (ng/dL) | |------------------------------------|-----|-------------------|--------------------------------| | Males Age <50 (21-49) | 119 | 388.24 | 123.06 – 813.86 | | Males Age ≥50 (50-89) | 137 | 374.72 | 86.98 – 780.10 | | Females Pre-Menopause (Age 21-60) | 167 | 22.26 | 9.01 - 47.94 | | Females Post-Menopause (Age 45-89) | 127 | 15.18 | < 7.00 - 45.62 | ### SHBG | Group | n | Median (nmol/L) | Reference Values (nmol/L) | |------------------------------------|-----|--------------------|---------------------------------| | Males Age <50 (21-49) | 122 | 34.97 | 14.55 - 94.64 | | Males Age ≥50 (50-89) | 137 | 52.49 | 21.63 - 113.13 | | Females Pre-Menopause (Age 21-60) | 167 | 58.21 | 10.84 - >180.00 | | Females Post-Menopause (Age 45-89) | 134 | 61.44 | 23.15 - 159.07 | ### FAI | Group | n | Median | Reference Values | |------------------------------------|-----|--------|---------------------| | Males Age <50 (21-49) | 119 | 39.14 | 11.14 - 81.01 | | Males Age ≥50 (50-89) | 137 | 27.17 | 8.99 - 46.51 | | Females Pre-Menopause (Age 21-60) | 167 | 1.28 | 0.27 - 7.64 | | Females Post-Menopause (Age 45-89) | 127 | 0.87 | 0.17 - 4.15 | Reference intervals characterized by age and Tanner stage were established for the ADVIA Centaur TSTII assay for a pediatric population in accordance with the CLSI guideline EP28-АЗс. {14}------------------------------------------------ For groups of 120 or more subjects, the lower and upper reference limits were estimated as the 2.5" and the 97.5" percentiles of the distribution of test results using a non-parametric approach in accordance with the recommendation in CLSI quideline EP28-A3. For groups of 40 to 119 subjects, the lower and upper reference limits were estimated as the 2.5" and the 97.5" percentiles of the distribution of test results using a robust measure of location and spread, as developed by Horn and Pesce. For groups of less than 40 subjects, the lower and upper reference limits were estimated as the 5th and the 95th percentiles of the distribution of test results. Samples were collected prospectively from apparently healthy pediatric subjects (good endocrinological health) using predefined inclusion criteria. | Group | n | Median (ng/dL) | Reference Values (ng/dL) | |------------------------|-----|-------------------|--------------------------------| | Males Age 2-10 | 40 | < 7.00 | < 7.00 - 29.44 | | Males Age 11 | 20 | 11.89 | < 7.00 - 353.00 | | Males Age 12 | 25 | 70.30 | < 7.00 - 562.42 | | Males Age 13 | 21 | 120.37 | 8.12 - 582.87 | | Males Age 14 | 31 | 284.90 | 20.35 - 777.38 | | Males Age 15 | 22 | 334.86 | 127.21 - 849.36 | | Males Age 16-21 | 44 | 456.26 | 113.19 - 882.10 | | Males Tanner Stage 1 | 36 | < 7.00 | < 7.00 - 47.43 | | Males Tanner Stage 2 | 38 | 11.79 | < 7.00 - 174.45 | | Males Tanner Stage 3 | 44 | 250.44 | 10.54 - 802.75 | | Males Tanner Stage 4 | 44 | 356.12 | 63.89 - 736.20 | | Males Tanner Stage 5 | 42 | 458.24 | 55.69 - 897.40 | | Females Age 2-10 | 40 | < 7.00 | < 7.00 - 117.76 | | Females Age 11-15 | 130 | 16.03 | < 7.00 - 38.92 | | Females Age 16-21 | 36 | 25.20 | 15.06 - 42.41 | | Females Tanner Stage 1 | 44 | < 7.00 | < 7.00 - 89.56 | | Females Tanner Stage 2 | 42 | 12.81 | < 7.00 - 38.29 | | Females Tanner Stage 3 | 42 | 16.71 | < 7.00 - 33.86 | | Females Tanner Stage 4 | 40 | 19.82 | < 7.00 - 38.72 | | Females Tanner Stage 5 | 42 | 22.79 | 10.83 - 50.08 | #### 10.7 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 TSTII assay has an LoB of 2.50 ng/dL, an LoD of 5.00 ng/dL, and an LoQ of 7.00 ng/dL. 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 testosterone that can be detected with 95% probability. The LoQ is defined as the lowest concentration of testosterone that can be detected at a total CV of 20%. {15}------------------------------------------------ #### 10.8 Interference Interference studies were performed according to CLSI EP07-A2. Two sample pools were tested. One sample pool had approximately 30 ng/dL testosterone. The second sample pool had approximately 300 ng/dL testosterone. These sample pools were spiked with potential interferents. Control samples were prepared by spiking sample pools with the appropriate diluent at the same volume as the interfering substance stock. For substances spiked at doses that caused >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-standardizati…