ADVIA Centaur Testosterone II (TSTII), ADVIA Centaur SHBG
Device Facts
| Record ID | K191533 |
|---|---|
| Device Name | ADVIA Centaur Testosterone II (TSTII), ADVIA Centaur SHBG |
| Applicant | Siemens Healthcare Diagnostics, Inc. |
| Product Code | CDZ · Clinical Chemistry |
| Decision Date | Aug 28, 2019 |
| 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® 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.
Device Story
ADVIA Centaur Testosterone II (TSTII) and SHBG are in vitro diagnostic immunoassays for use on the ADVIA Centaur XP system. TSTII is a competitive chemiluminescent immunoassay; SHBG is a sandwich chemiluminescent immunoassay. Both assays utilize automated processing of human serum or plasma samples. The TSTII assay uses an acridinium ester-labeled hapten and biotinylated anti-testosterone antibody; the SHBG assay uses acridinium ester-labeled anti-SHBG antibody and biotinylated anti-SHBG antibody with streptavidin-coated paramagnetic particles. The system performs quantitative measurements, which are interpreted by clinicians to diagnose and monitor androgen-related disorders. The device provides objective laboratory data to support clinical decision-making regarding hormonal health. Benefits include standardized, automated, and accurate hormone quantification for patient management.
Clinical Evidence
No clinical trials were performed. Evidence is based on analytical bench testing, including LoB/LoD/LoQ determination (CLSI EP17-A2), precision (CLSI EP5-A3), linearity (CLSI EP06-A), and method comparison (CLSI EP9-A3) against ID-LC-MS/MS and predicate devices. Method comparison showed high correlation (r=0.98-1.00). Reference intervals were established using healthy adult and pediatric populations (n≥120 for primary groups) per CLSI EP28-A3c. Biotin interference testing confirmed no significant bias at 30 ng/mL for TSTII and 300 ng/mL for SHBG.
Technological Characteristics
Chemiluminescent immunoassay; competitive (TSTII) or sandwich (SHBG) format. Reagents include acridinium ester-labeled haptens/antibodies and streptavidin-coated magnetic latex particles. Automated processing on ADVIA Centaur XP system. Traceable to ID-LC-MS/MS (TSTII) and WHO 2nd International Standard 08/226 (SHBG). Measuring ranges: 7-1,500 ng/dL (TSTII); 1.6-180 nmol/L (SHBG).
Indications for Use
Indicated for quantitative determination of total testosterone and SHBG in human serum and plasma to aid in the diagnosis and treatment of androgen disorders, including hypogonadism, delayed/precocious puberty, impotence, hirsutism, and virilization in males and females.
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
- ADVIA Centaur® Testosterone II (TSTII) (K151986)
- ADVIA Centaur® SHBG (K151986)
Reference Devices
- Dimension Vista LOCI Total Testosterone (K151529)
Related Devices
- K151986 — 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. · Jun 29, 2016
- K091867 — ADVIA CENTAUR SHBG READYPACK, LOW AND HIGH CALIBRATORS AND MASTER CURVE MATERIAL, MODELS 06520781, 04819274 AND 06520773 · Siemens Healthcare Diagnostics · Jan 14, 2010
- K120009 — TESTOSTERONE TEST SYSTEM; CALIBRATOR; AND QUALITY CONTROL MATERIAL (ASSAYED AND UNASSAYED) · Abbott Laboratories · Sep 11, 2012
Submission Summary (Full Text)
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Image /page/0/Picture/0 description: The image contains two logos. The logo on the left is the Department of Health & Human Services - USA logo. The logo on the right is the FDA U.S. Food & Drug Administration logo. The FDA logo is in blue.
September 20, 2019
Siemens Healthcare Diagnostics Inc. Paul DaSilva Regulatory Affairs Specialist 511 Benedict Avenue Tarrytown, NY 10591
Re: K191533
Trade/Device Name: ADVIA Centaur® Testosterone II (TSTII), ADVIA Centaur® SHBG Regulation Number: 21 CFR 862.1680 Regulation Name: Testosterone test system Regulatory Class: Class I, reserved Product Code: CDZ Dated: June 7, 2019 Received: June 10, 2019
Dear Paul DaSilva:
This letter corrects our substantially equivalent letter of August 28, 2019.
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
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Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
# Kellie B. Kelm -S
Kellie B. Kelm, Ph.D. Acting Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Ouality Center for Devices and Radiological Health
Enclosure
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### Indications for Use
510(k) Number (if known) k191533
Device Name ADVIA Centaur® Testosterone II (TSTII) ADVIA Centaur® SHBG
Indications for Use (Describe)
ADVIA Centaur® Testosterone II (TSTII)
The ADVIA Centaur® Testosterone II (TSTI) assav is for 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® 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.
| Type of Use (Select one or both, as applicable) | |
|-------------------------------------------------------------------|------------------------------------------------------------------|
| <div> \[X] Prescription Use (Part 21 CFR 801 Subpart D) </div> | <div> \[ ] Over-The-Counter Use (21 CFR 801 Subpart C) </div> |
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This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of 21 CFR 807.92 and the Safe Medical Device Act of 1990.
The assigned 510(k) Number is: K191533
#### Date Prepared 1.
June 7, 2019
#### Applicant Information 2.
| Contact: | Paul DaSilva<br>Regulatory Affairs Specialist |
|----------|-----------------------------------------------------------------------------------------|
| Address: | Siemens Healthcare Diagnostics Inc.<br>511 Benedict Avenue<br>Tarrytown, NY 10591-5097 |
| Phone: | 914-524-3141 |
| Fax: | 914-524-2101 |
| Email: | paul.dasilva@siemens-healthineers.com |
#### Regulatory Information 3.
### Table 1. Regulatory Information for ADVIA Centaur® Testosterone II (TSTII)
| Trade Name | ADVIA Centaur® Testosterone II (TSTII) |
|---------------------|---------------------------------------------------------|
| Common Name | Radioimmunoassay, testosterones and dihydrotestosterone |
| Classification Name | Testosterone test system |
| FDA Classification | Class I (Reserved) |
| Review Panel | Clinical Chemistry |
| Product Code | CDZ |
| Regulation Number | 862.1680 |
### Table 2. Regulatory Information for ADVIA Centaur® SHBG
| Trade Name | ADVIA Centaur® SHBG |
|---------------------|---------------------------------------------------------|
| 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 |
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#### Predicate Device Information 4.
### ADVIA Centaur® Testosterone II (TSTII)
Predicate Device Name: ADVIA Centaur® Testosterone II (TSTII)
510(k) Number: K151986
The re-standardized ADVIA Centaur® Testosterone II (TSTII) is substantially equivalent to the ADVIA Centaur® Testosterone II (TSTII) that was cleared under 510(k) (K151986), as shown below in the Substantial Equivalence Information section.
### ADVIA Centaur® SHBG
Predicate Device Name: ADVIA Centaur® SHBG
510(k) Number: K151986
The ADVIA Centaur® SHBG with new reference intervals in the Instructions for Use (Package Insert) does not require any other device modifications (i.e. no change to design or manufacturing process). Therefore, as shown below in the Substantial Equivalence Information section, the predicate and subject devices are the same.
#### 5. 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 (masculinization) due to tumors, polycystic ovaries. and adrenogenital syndromes.
### 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.
#### Device Description 6.
### Table 3. Summary of Ingredients of the Re-standardized ADVIA Centaur® Testosterone II (TSTII) Components
| Component | Volume | Ingredients |
|--------------------------------------------------------------------------------------------------|--------------|-------------------------------------------------------------------------------------|
| <i>ADVIA Centaur</i> ® Testosterone II (TSTII) Primary Reagent ReadyPack (included in assay kit) | | |
| <i>ADVIA Centaur</i> ®<br>Testosterone II (TSTII)<br>Lite Reagent | 10.0 mL/pack | Acridinium ester-labeled hapten (36 µg/mL) in<br>buffered saline with preservatives |
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| Table 3. Summary of Ingredients of the Re-standardized ADVIA Centaur® Testosterone | |
|------------------------------------------------------------------------------------|--|
| II (TSTII) Components | |
| Component | Volume | Ingredients |
|-----------------------------------------------------------------------------------------------|--------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| ADVIA Centaur®<br>Testosterone II (TSTII)<br>Solid Phase Reagent | 17.0 mL/pack | Streptavidin-coated latex particles (0.33 g/L) in<br>buffered saline with preservatives |
| ADVIA Centaur® Testosterone II (TSTII) Ancillary Reagent ReadyPack (included in assay<br>kit) | | |
| ADVIA Centaur®<br>Testosterone II (TSTII)<br>Releasing Agent | 10.0 mL/pack | Steroid releasing agent (0.4 $ \mu $ g/mL) and biotinylated<br>sheep monoclonal anti-testosterone antibody (27 $ \mu $ g/L) in buffered saline and preservatives |
| | | | | | | | Table 4. Summary of Ingredients of the ADVIA Centaur® SHBG Components |
|--|--|--|--|--|--|--|-----------------------------------------------------------------------|
|--|--|--|--|--|--|--|-----------------------------------------------------------------------|
| Component | Volume | Ingredients |
|-----------------------------------------------------------------------|--------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| ADVIA Centaur® SHBG Primary Reagent ReadyPack (included in assay kit) | | |
| ADVIA Centaur® SHBG<br>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, protein stabilizers and preservatives |
| ADVIA Centaur® SHBG<br>Solid Phase Reagent | 11.0 mL/pack | Streptavidin coupled to latex paramagnetic particles (~150 µg/mL) in HEPES buffered saline with bovine serum albumin, mouse serum, sodium azide (< 0.1%), surfactant, protein stabilizers and preservatives |
| ADVIA Centaur® SHBG<br>Ancillary Well Reagent | 3.0 mL/pack | Biotinylated monoclonal mouse anti-SHBG antibody (~6 µg/mL) in HEPES buffered saline with bovine serum albumin, mouse serum, sodium azide (< 0.1%), surfactant, protein stabilizers and preservatives |
#### Purpose of the Submission 7.
The purpose of this submission is to submit a re-standardized ADVIA Centaur® Testosterone II (TSTII) and to submit the new reference intervals data for the ADVIA Centaur® SHBG that was cleared under K151986. For the ADVIA Centaur® SHBG the only change is the new reference intervals.
#### Substantial Equivalence Information - Comparison of 8. Predicate Device and Modified Device
Both the re-standardized ADVIA Centaur® Testosterone II (TSTII) (Modified Device) and the current ADVIA Centaur® Testosterone II (TSTII) (Predicate Device cleared under K151986) employ the same prepackaged reagents for use on automated test systems. The Intended Use / Indications for Use, assay principle, and reagent formulations are the same. The major differences between the Modified and Predicate devices are the re-standardization and change in reference interval data. However, despite these differences, the performance and accuracy of the Modified Device are substantially equivalent to that of the Predicate
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Device. The method comparison study between the Modified Device and the Predicate Device demonstrate acceptable correlation between these assays. A comparison of these assays is shown in the following table:
| ltem | Re-standardized ADVIA Centaur®<br>Testosterone II (TSTII) (Candidate<br>Device) | ADVIA Centaur® Testosterone II<br>(TSTII) (Predicate Device -<br>K151986) |
|-----------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------|
| Intended Use | For in vitro diagnostic use in the<br>quantitative determination of total<br>testosterone (bound and unbound)<br>in serum using the ADVIA Centaur<br>and ADVIA Centaur XP Systems. | Same |
| Indications for Use | Measurements of testosterone are<br>used in the diagnosis and treatment<br>of disorders involving the male sex<br>hormones (androgens), including<br>primary and secondary<br>hypogonadism, delayed or<br>precocious puberty, impotence in<br>males and, in females hirsutism<br>(excessive hair) and virilization<br>(masculinization) due to tumors,<br>polycystic ovaries, and<br>adrenogenital syndromes. | Same |
| Methodology | Chemiluminescence | Same |
| Assay Protocol | Competitive immunoassay | Same |
| Traceability/<br>Standardization | ID-LC-MS/MS | Same |
| Specimen Type | Human serum and plasma | Same |
| Lower Limit of<br>Measuring Range | LoQ | Same |
| Sample Volume | 20 µL | Same |
| Measuring Range | 7.0-1500 ng/dL | Same |
| Calibration | 2-point calibration | Same |
| Table 5. Comparison of ADVIA Centaur® Testosterone II (TSTII) to Predicate | |
|----------------------------------------------------------------------------|--|
|----------------------------------------------------------------------------|--|
The following table demonstrates substantial equivalence between the ADVIA Centaur® SHBG (Candidate Device) with new reference intervals in the Instructions for Use (Package Insert) and the currently marketed ADVIA Centaur® SHBG (Predicate Device) that was cleared under 510(k) K151986.
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| ltem | ADVIA Centaur® SHBG: WHO<br>08/226 2nd IS<br>(Candidate Device - New<br>Reference Intervals) | ADVIA Centaur® SHBG: WHO<br>08/226 2nd IS<br>(Predicate Device - Unmodified<br>Labeling) |
|----------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------|
| Intended Use | The ADVIA Centaur® SHBG assay<br>is an in vitro diagnostic<br>immunoassay for the quantitative<br>determination of sex hormone-<br>binding globulin (SHBG) in human<br>serum and plasma using the ADVIA<br>Centaur® XP system. | Same |
| Indications for Use | Measurement of SHBG are used in<br>the diagnosis and treatment of<br>disorders involving the male sex<br>hormones (androgens), including<br>primary and secondary<br>hypogonadism, delayed or<br>precocious puberty, impotence in<br>males and, in females, hirsutism<br>(excessive hair) and virilization<br>(masculinization) due to tumors,<br>polycystic ovaries, and<br>adrenogenital syndromes. | Same |
| Methodology | Chemiluminescence | Same |
| Assay Protocol | Sandwich immunoassay | Same |
| Traceability/<br>Standardization | WHO 2nd International Standard<br>(08/226) | Same |
| Specimen Type | Human serum and plasma | Same |
| Sample Volume | 20 µL | Same |
| Measuring Range | 1.60-180 nmol/L | Same |
| Calibration | 2-point calibration | Same |
### Table 6. Comparison of ADVIA Centaur® SHBG to Predicate
#### 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 Procedures; ■ Approved Guideline - Third Edition (CLSI EP05-A3, 2004; Recognition Number 7-251)
- . Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline - 1st Edition (CLSI EP06-A, 2003; Recognition Number 7-193)
- . 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: ■ Approved Guideline -- Second Edition (CLSI EP17-A2, 2013; Recognition Number 7-233)
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- I Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline - Third Edition (CLSI EP28-A3c - formerly C28-A3c, 2010; Recognition Number 7-224)
#### 10. Performance Characteristics: Re-standardized ADVIA Centaur® Testosterone II (TSTII)
Substantial equivalence of the re-standardized ADVIA Centaur® Testosterone II (TSTII) demonstrated by testing several performance characteristics with the following studies:
- . Detection Capability (LoB. LoD. and LoQ)
- . Linearity
- Precision
- Method Comparison
- Reference Interval ●
In addition, the following study was performed:
- Biotin Interference ●
The performance studies listed below were determined not to be impacted by the restandardization of the ADVIA Centaur® Testosterone II (TSTII). These studies are from the original 510(k) K151986 and are used in the labeling for the re-standardized ADVIA Centaur® Testosterone II (TSTII).
- Dilution Recovery
- . Cross reactivity
- . Interfering substances
- . Matrix Comparison
- Reagent shelf life stability ●
- Reagent On-Board Stability and Calibration Interval
- . Open Vial Stability
#### Detection Limit 10.1
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 Re-standardized ADVIA Centaur® Testosterone II (TSTII) 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%.
#### 10.2 Precision
A 20-day precision study was performed according to CLSI EP5-A3. Samples included three levels of controls, 5 medical decision pools and 1 female patient serum pool. Samples were assayed twice a day in replicates of 2, for 20 days (n = 80 replicates per sample). The following results were obtained:
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| | | | Repeatability<br>(Within-Run) | | Within-Lab<br>(Total Precision) | | |
|------------------------------|----|-----------------|-------------------------------|------|---------------------------------|------|--|
| Sample | n | Mean<br>(ng/dL) | SD | CV | SD | CV | |
| Control 1 | 80 | 257.38 | 9.06 | 3.5 | 14.38 | 5.6 | |
| Control 2 | 80 | 636.57 | 45.14 | 7.1 | 53.12 | 8.3 | |
| Control 3 | 80 | 1021.93 | 62.28 | 6.1 | 81.02 | 7.9 | |
| MDP1 | 80 | 20.92 | 1.3 | 6.2 | 1.86 | 8.9 | |
| MDP2 | 80 | 73.57 | 3.54 | 4.8 | 5.24 | 7.1 | |
| MDP3 | 80 | 312.81 | 13.4 | 4.3 | 23.99 | 7.7 | |
| MDP4 | 80 | 776.64 | 42.59 | 5.5 | 58.26 | 7.5 | |
| MDP5 | 80 | 1123.83 | 59.22 | 5.3 | 109.57 | 9.7 | |
| Female Patient<br>Serum Pool | 80 | 15.86 | 1.84 | 11.6 | 2.39 | 15.1 | |
#### 10.3 Linearity
A linearity study was performed using the modified device according to CLSI EP06-A using 9 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<br>Dose (ng/dL) | Mean<br>Observed<br>Dose (ng/dL) | Weighted<br>Linear Fit<br>Estimate | Deviation<br>from<br>Linear Fit<br>(Percentage) | Deviation<br>From<br>Linear Fit |
|--------|--------------------------|----------------------------------|------------------------------------|-------------------------------------------------|---------------------------------|
| 1 | 6.94 | 6.94 | 6.95 | -0.15 | -0.01 |
| 2 | 11.65 | 11.95 | 11.68 | 2.33 | 0.27 |
| 3 | 16.35 | 18.84 | 16.40 | 14.88 | 2.44 |
| 4 | 110.00 | 102.03 | 110.39 | -7.57 | -8.35 |
| 5 | 213.06 | 228.35 | 213.82 | 6.79 | 14.53 |
| 6 | 419.18 | 430.72 | 420.69 | 2.38 | 10.03 |
| 7 | 831.42 | 819.33 | 834.43 | -1.81 | -15.10 |
| 8 | 1243.66 | 1317.80 | 1248.16 | 5.58 | 69.64 |
| 9 | 1655.90 | 1655.90 | 1661.90 | -0.36 | -6.00 |
The weighted linear regression equation is presented below.
Observed = 1.004(Expected) - 0.015 ng/dL
#### 10.4 Method Comparison
A method comparison study was performed by comparing the Re-standardized ADVIA Centaur® Testosterone II (TSTII) to the ID-LC-MS/MS with 108 adult male and female serum samples distributed over the assay range (7.27-1394.00 ng/dL). The samples were assigned testosterone concentrations by the CDC HoSt RMP ID-LC/MS/MS. The study duration was 3 days using day 1 calibration and all samples run in singlicate. The analysis was performed
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using Weighted Deming regression. The regression equation from the analysis is presented below.
Re-standardized ADVIA Centaur® Testosterone II (TSTII) (y) = 0.97 (x) (ID-LC-MS/MS)-0.22 ng/dL (r = 0.98)
For the re-standardized ADVIA Centaur® Testosterone II (TSTII) and the current ADVIA Centaur® Testosterone II (TSTII) method comparison study, an analysis was performed on a total of 108 individual male and female adult serum samples spanning the assay range (10.93-14.39.77 ng/dL) The analysis was performed using Weighted Deming regression. The regression equation from the analysis is presented below.
Re-standardized ADVIA Centaur® Testosterone II (TSTII) (y) = 1.04 (x) (ADVIA Centaur TSTII) - 4.14 ng/dL (r = 1.00)
A further method comparison study was performed by comparing the Re-standardized ADVIA Centaur® Testosterone II (TSTII) to the Dimension Vista LOCI Total Testosterone with 124 serum samples (79 samples from adults and 45 samples from pediatric subjects) ranging from 9.00–984.00 ng/dL (0.31–34.12 nmol/L). An analysis was also performed with the 45 samples from pediatric subjects (31 females, ages 7 years to 18 years; and 14 males, ages 22 months to 18 years) ranging from 11.00–762.00 ng/dL. The analyses were performed using Weighted Deming regression. The regression equations from the analyses are:
### Adult and pediatric specimens
Re-standardized ADVIA Centaur® Testosterone II (TSTII) (y) = 1.01(x) (Dimension Vista TST) - 3.32 ng/dL (r = 0.99)
### Pediatric specimens
Re-standardized ADVIA Centaur® Testosterone II (TSTII) (y) = 1.01(x) (Dimension Vista TST) - 4.74 ng/dL (r = 1.00)
#### 10.5 Reference Intervals
Reference intervals for the ADVIA Centaur® Testosterone II (TSTII), ADVIA Centaur® SHBG and the Free Androgen Index (FAI) were obtained using samples from apparently healthy, normal adult females and males. The testosterone, SHBG, and FAI results provided in the tables below were obtained using results from the ADVIA Centaur® TSTII and ADVIA Centaur® SHBG. Central 90% reference intervals were established in accordance with the CLSI guideline EP28-A3c using a non-parametric approach for sample sizes of at least 120. For populations with a sample size of 40–119, the reference interval was calculated using an approach to accommodate the smaller sample size.
Central 90% reference intervals characterized by age and Tanner stage were established for the ADVIA Centaur® Testosterone II (TSTII) for a pediatric population (children and adolescents) in accordance with the CLSI guideline EP28-A3c using a non-parametric approach for sample sizes of at least 120. For populations with a sample size of < 120, the central 90% reference interval was calculated using an approach to accommodate the smaller sample size. Samples were collected prospectively from apparently healthy pediatric subjects (good
endocrinological health) using predefined inclusion criteria.
Samples were also clinically characterized according to Tanner Stage.
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### Testosterone
| | | | | ng/dL | | | nmol/L | | |
|------------------|----------------|-----|--------|---------------------------|--------|--------|---------------------------|-------|--|
| | | | | Central 90th Ref Interval | | | Central 90th Ref Interval | | |
| | TSTII | N | Median | 5th | 95th | Median | 5th | 95th | |
| Adult | Under 50 | 250 | 409.72 | 197.44 | 669.58 | 14.22 | 6.85 | 23.23 | |
| Male | 50 and Over | 135 | 377.46 | 187.72 | 684.19 | 13.10 | 6.51 | 23.74 | |
| Adult | Under 50 | 224 | 18.01 | 8.38 | 35.01 | 0.62 | 0.29 | 1.21 | |
| Female | 50 and Over | 151 | 14.18 | < 7.00 | 35.92 | 0.49 | < 0.24 | 1.25 | |
| Pediatric Male | Tanner Stage 1 | 101 | < 7.00 | < 7.00 | 13.06 | < 0.24 | < 0.24 | 0.45 | |
| | Tanner Stage 2 | 78 | < 7.00 | < 7.00 | 79.13 | < 0.24 | < 0.24 | 2.75 | |
| | Tanner Stage 3 | 64 | 59.67 | < 7.00 | 499.18 | 2.07 | < 0.24 | 17.32 | |
| | Tanner Stage 4 | 88 | 376.84 | 79.10 | 747.17 | 13.08 | 2.74 | 25.93 | |
| | Tanner Stage 5 | 129 | 451.17 | 224.83 | 669.65 | 15.66 | 7.80 | 23.24 | |
| | Age 2-10 | 147 | < 7.00 | < 7.00 | 10.50 | < 0.24 | < 0.24 | 0.36 | |
| | Age 11 | 34 | 10.73 | < 7.00 | 478.50 | 0.37 | < 0.24 | 16.60 | |
| | Age 12 | 35 | 132.47 | < 7.00 | 487.97 | 4.60 | < 0.24 | 16.93 | |
| | Age 13 | 34 | 199.02 | 8.28 | 549.79 | 6.91 | 0.29 | 19.08 | |
| | Age 14 | 34 | 228.39 | 8.91 | 535.34 | 7.93 | 0.31 | 18.58 | |
| | Age 15 | 27 | 327.89 | 65.96 | 756.50 | 11.38 | 2.29 | 26.25 | |
| | Age 16-21 | 149 | 453.86 | 228.16 | 710.74 | 15.75 | 7.92 | 24.66 | |
| Pediatric Female | Tanner Stage 1 | 138 | < 7.00 | < 7.00 | 10.06 | < 0.24 | < 0.24 | 0.35 | |
| | Tanner Stage 2 | 60 | 8.17 | < 7.00 | 30.11 | 0.28 | < 0.24 | 1.04 | |
| | Tanner Stage 3 | 49 | 12.98 | < 7.00 | 30.49 | 0.45 | < 0.24 | 1.06 | |
| | Tanner Stage 4 | 98 | 17.37 | < 7.00 | 35.19 | 0.60 | < 0.24 | 1.22 | |
| | Tanner Stage 5 | 133 | 19.76 | 11.80 | 39.30 | 0.69 | 0.41 | 1.36 | |
| | Age 2-10 | 159 | < 7.00 | < 7.00 | 11.86 | < 0.24 | < 0.24 | 0.41 | |
| | Age 11-15 | 174 | 12.95 | < 7.00 | 27.57 | 0.45 | < 0.24 | 0.96 | |
| | Age 16-21 | 145 | 19.81 | 11.78 | 43.34 | 0.69 | 0.41 | 1.50 | |
### SHBG
| | SHBG | N | | µg/mL | | | nmol/L | | |
|--------|-------------|-----|--------|---------------------------|-------|--------|---------------------------|--------|--|
| | | | | Central 90th Ref Interval | | | Central 90th Ref Interval | | |
| | | | Median | 5th | 95th | Median | 5th | 95th | |
| Adult | Under 50 | 250 | 2.26 | 1.10 | 5.18 | 23.80 | 11.54 | 54.49 | |
| Male | 50 and Over | 135 | 3.51 | 1.65 | 6.79 | 36.91 | 17.33 | 71.50 | |
| Adult | Under 50 | 224 | 4.44 | 1.68 | 13.13 | 46.72 | 17.69 | 138.26 | |
| Female | 50 and Over | 151 | 4.55 | 2.25 | 10.51 | 47.86 | 23.65 | 110.61 | |
### FAI
| | FAI | N | Percent (%) | | |
|--------|-------------|-----|---------------------------|--------|---------|
| | | | Central 90th Ref Interval | | |
| | | | Median | 5th | 95th |
| Adult | Under 50 | 250 | 55.86% | 26.18% | 107.07% |
| Male | 50 and Over | 135 | 36.01% | 17.38% | 60.86% |
| Adult | Under 50 | 224 | 1.37% | 0.33% | 4.37% |
| Female | 50 and Over | 151 | 1.05% | 0.31% | 2.53% |
Siemens Healthcare Diagnostics Inc., Tarrytown, NY Re-standardized ADVIA Centaur TSTII and new Reference Intervals for ADVIA Centaur SHBG Traditional 510(k) K191533
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#### 10.6 Biotin Interference
Specimens that contain biotin at a concentration of 30 ng/mL demonstrate no significant effect on the assay. A summary of the results is presented below.
| Analyte<br>Concentration<br>(ng/dL) | Biotin Test Level (ng/mL) | | | | | | |
|-------------------------------------|---------------------------|----|-----|-----|-----|------|------|
| | 30 | 50 | 100 | 250 | 500 | 1200 | 1500 |
| % Bias | | | | | | | |
| 83.27 | 4 | 6 | 23 | 84 | 370 | 3981 | 6837 |
| 289.24 | 2 | 7 | 19 | 107 | 441 | >AR* | >AR* |
* AR = Assay Range
#### Performance Characteristics: ADVIA Centaur® SHBG 11.
The change in reference intervals in the Instructions for Use (Package Inserts) for the ADVIA Centaur® SHBG that was cleared in 2016 under 510(k) K151986 does not require the collection of additional analytical performance data. Therefore, all analytical performance data previously reviewed for the ADVIA Centaur® SHBG continues to apply to this assay. because the assay was not modified. These performance data are cross-referenced to the 510(k) submission for the ADVIA Centaur® SHBG (K151986 and K091867).
Specifically, the following studies are not needed for the purpose of this submission:
- Detection Capability (LoB, LoD, LoQ)
- Linearity ●
- Precision
- . Dilution Recovery
- Method Comparison
- Calibrator/Assay Traceability ●
- Reagent On-Board Stability and Calibration Interval
- Cross reactivity ●
- Interfering substances
- Matrix Comparison
- Shelf Life Stabilitv ●
- Onboard Stability ●
- Open Vial Stability ●
#### Clinical Studies 11.1
Not applicable.
#### 11.2 Clinical Cut-off
Not applicable.
#### 11.3 Biotin Interference
Specimens that contain biotin at a concentration of 300 ng/mL demonstrate a less than or equal to 10% change in results. A summary of the results is presented below.
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| Analyte<br>Concentration<br>(nmol/L) | Biotin Test Level (ng/mL) | | | | | |
|--------------------------------------|---------------------------|----|-----|-----|-----|------|
| | 38 | 75 | 150 | 300 | 600 | 1200 |
| % Bias | | | | | | |
| 19.6 | -3 | -3 | -9 | -7 | -7 | -25 |
| 44.1 | -2 | 1 | -3 | -7 | -9 | -26 |
#### Conclusions 12.
Based on the results of comparative testing, the re-standardized ADVIA Centaur® Testosterone II (TSTII) is substantially equivalent in principle and performance to the currently-marketed predicate device, the ADVIA Centaur® Testosterone II (TSTII) cleared under 510(k) K151986.
The ADVIA Centaur® SHBG with the new reference intervals in the Instructions for Use (package insert) is substantially equivalent to the currently marketed ADVIA Centaur® SHBG (K151986). The new reference intervals that will replace the current reference intervals in the Instructions for Use (Package Inserts) for the currently marketed assay do not require collection of additional analytical performance data.
