(248 days)
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No
The device description details a standard immunoenzymometric assay and the performance studies are based on traditional analytical methods. There is no mention of AI or ML in the intended use, device description, or performance studies.
No.
The document states that the device is "for In Vitro Diagnostic Use Only" and "intended for use as an aid in the diagnosis of androgen disorders," meaning it diagnoses a condition rather than treating or preventing it.
Yes.
The device is intended for the "quantitative measurement of sex hormone binding globulin (SHBG) in human serum or Na heparinized plasma" and is "intended for use as an aid in the diagnosis of androgen disorders." This explicitly states its purpose in aiding diagnosis.
No
The device is an in vitro diagnostic assay kit, which includes reagents and test cups, not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement in Intended Use: The document clearly states: "ST AIA-PACK SHBG is designed for In Vitro Diagnostic Use Only" and "The ST AIA-PACK SHBG Calibrator Set is intended for In Vitro Diagnostic Use Only".
- Measurement of Analytes in Biological Samples: The device measures sex hormone binding globulin (SHBG) in human serum or plasma, which are biological samples.
- Aid in Diagnosis: The intended use states it is "intended for use as an aid in the diagnosis of androgen disorders," which is a diagnostic purpose.
- Laboratory-Based Assay: The description of the device and the performance studies indicate it is a laboratory-based assay performed on an analyzer.
All of these points align with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
ST AIA-PACK SHBG is designed for In Vitro Diagnostic Use Only for the quantitative measurement of sex hormone binding globulin (SHBG) in human serum or Na heparinized plasma on Tosoh AIA System Analyzers. The ST AIA-PACK SHBG assay is intended for use as an aid in the diagnosis of androgen disorders.
The ST AIA-PACK SHBG Calibrator Set is intended for In Vitro Diagnostic Use Only for the calibration of the ST AIA-PACK SHBG assay.
Product codes (comma separated list FDA assigned to the subject device)
CDZ, JIT
Device Description
The ST AIA-PACK SHBG is a two-site immunoenzymometric assay which is performed entirely in the ST AIA-PACK SHBG test cups. SHBG present in the test sample is bound with monoclonal antibody immobilized on a maqnetic solid phase and enzyme-labeled monoclonal antibody in the test cups. The magnetic beads are washed to remove unbound enzyme-labeled antibody and are then incubated with a fluorogenic substrate, 4-methylumbelliferyl phosphate (4MUP). The amount of enzyme-labeled monoclonal antibody that binds to the beads is directly proportional to the SHBG concentration in the test sample. A standard curve is constructed, and unknown sample concentrations are calculated using this curve.
The following materials are required to perform SHBG analysis using the ST AIA-PACK SHBG (Cat. No. 025238) on the Tosoh AIA System Analyzer.
ST AIA-PACK SHBG Calibrator Set 025338
ST AIA-PACK SHBG Sample Diluting Solution 025538
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision Study:
Study Type: Precision study, developed with reference to the CLSI protocol entitled: Evaluation of Precision Performance of Quantitative Measurement Methods (EP5-A2).
Sample Size: Three levels of serum and heparinized plasma specimens.
Key Results:
Within-run precision: CV values ranging from 1.6% to 3.2%.
Total Precision: CV values ranging from 2.4% to 3.7%.
Between-run precision: CV values ranging from 1.5% to 3.1%.
Between-day precision: CV values ranging from 1.6% to 3.1%.
Representative Lot-to-Lot Precision: CV values ranging from 2.1% to 3.4% (Within-Run), 1.5% to 2.5% (Between-Run), and 2.3% to 3.3% (Total).
Combined Summary Table details CVs across various samples and conditions, showing overall total CVs from 4.6% to 6.8%.
Linearity Study:
Study Type: Linearity, based on guidance from CLSI Protocol EP6-A entitled: Evaluation of the Linearity of Quantitative Measurement Procedures: a Statistical Approach: Approved Guideline.
Key Results: Demonstrated to be linear from 0.2 to 250 nmol/L.
Method Comparison (Correlation) Study:
Study Type: Methods comparison, based on guidance from EP9-A2.
Sample Size: 126 serum specimens.
Key Results:
Deming Regression: Slope = 0.949 (0.926 to 0.972), Intercept = -0.64 (-2.61 to 1.34).
Regular Regression: Slope = 0.940 (0.917 to 0.964), Intercept = -0.09 (-2.06 to 1.89).
Correlation Coefficient (R): 0.991.
Result Ranges: Tosoh ST AIA-PACK SHBG (0.6 to 241.0 nmol/L), Predicate SHBG (0.5 to 221.6 nmol/L).
Matrix Comparison Study:
Study Type: Correlation between serum and Na heparinized plasma.
Sample Size: 116 patient specimens.
Key Results:
Deming Regression: Slope = 0.977 (0.964 to 0.991), Intercept = 0.269 (-0.629 to 1.168).
Regular Regression: Slope = 0.975 (0.961 to 0.988), Intercept = 0.415 (-0.483 to 1.313).
Correlation Coefficient (R): 0.997.
Result Ranges: Serum (0.2 to 219.1 nmol/L), Na heparinized plasma (0.2 to 219.9 nmol/L).
Specificity Study:
Study Type: Cross-reactivity testing of various substances.
Key Results: Most substances showed N.D. (not detectable) or very low cross-reactivity (e.g., Cortisol 0.003%, 11-Deoxycortisol 0.114%, Testosterone 0.019%, Human IgA 0.072%, Human IgG 0.218%). Thyroglobulin showed 2.544% cross-reactivity.
Reference Ranges Study:
Study Type: Reference range, conducted with reference to CLSI protocol C28-A3.
Sample Size: 488 apparently healthy American and European individuals (244 male, 244 female).
Key Results: Established reference ranges for different age and gender groups.
Interference Study:
Study Type: Tested for interference from specific substances.
Key Results: No interference from Hemoglobin (up to 446 mg/dL), free bilirubin (up to 17.6 mg/dL), conjugated bilirubin (up to 18.5 mg/dL), Lipemia (triglyceride concentration up to 1,667 mg/dL), Ascorbic acid (up to 20 mg/dL), Protein (human albumin concentration up to 5,00 g/dL), Na Heparin (up to 100.0 U/mL), Rheumatoid factor (up to 550 IU/mL), and HAMA (up to 24,269 ng/mL).
Limit of Detection (LoD) and Limit of Quantitation (LoQ) Study:
Study Type: Determined according to CLSI guideline EP17-A.
Key Results:
LoB: 0.017 nmol/L.
LoD: 0.063 nmol/L.
LoQ: 0.2 nmol/L (based on a % total error of 12%).
Calibrator Stability Study:
Study Type: Real Time Testing and Open Vial Stability.
Key Results:
Real Time Testing: Supports a 12-month shelf life at refrigerated temperatures.
Open Vial Stability: Supports an in-use claim of 1 day when refrigerated.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Specificity (Cross-reactivity) is provided:
Alpha-Fetoprotein (AFP): N.D.
Cortisol: 0.003%
11-Deoxycortisol: 0.114%
5alpha-Dihydroxytestosterone: 0.007%
Estradiol: N.D.
Testosterone: 0.019%
Thyroglobulin: 2.544%
Thyroxin-Binding Globulin: N.D.
Transferrin: N.D.
Fibrinogen: 0.120%
Plasminogen: N.D.
Human IgA: 0.072%
Human IgG: 0.218%
CBG: 0.012%
TSH: N.D.
Interference:
Absence of interference from Hemoglobin, Free bilirubin, Conjugated bilirubin, Lipemia, Ascorbic acid, Protein, Na Heparin, Rheumatoid factor, HAMA.
Limit of Detection (LoD): 0.063 nmol/L
Limit of Quantitation (LoQ): 0.2 nmol/L
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 862.1680 Testosterone test system.
(a)
Identification. A testosterone test system is a device intended to measure testosterone (a male sex hormone) in serum, plasma, and urine. Measurement of testosterone are used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in males and, in females hirsutism (excessive hair) and virilization (masculinization) due to tumors, polycystic ovaries, and adrenogenital syndromes.(b)
Classification. Class I.
0
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles a stylized caduceus, with three figures or lines intertwined.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
July 2, 2015
TOSOH BIOSCIENCE, INC. ROBERT WICK REGULATORY SPECIALIST 6000 SHORELINE COURT SUITE 101 SOUTH SAN FRANCISCO CA 94080
Re: K143075
Trade/Device Name: ST AIA-PACK SHBG, ST AIA-PACK SHBG Calibrator Set Regulation Number: 21 CFR 862.1680 Regulation Name: Testosterone Test System Regulatory Class: I. Reserved Product Code: CDZ, JIT Dated: June 22, 2015 Received: June 23, 2015
Dear Robert Wick:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
1
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Katherine Serrano -S
For: Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K143075
Device Name ST AIA-PACK SHBG, ST AIA-PACK SHBG Calibrator Set
Indications for Use (Describe)
ST AIA-PACK SHBG is designed for In Vitro Diagnostic Use Only for the quantitative measurement of sex hormone binding globulin (SHBG) in human serum or Na heparinized plasma on Tosoh AIA System Analyzers. The ST AIA-PACK SHBG assay is intended for use as an aid in the diagnosis of androgen disorders.
The ST AIA-PACK SHBG Calibrator Set is intended for In Vitro Diagnostic Use Only for the calibration of the ST AIA-PACK SHBG assay.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
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3
510(k) Summary
4
510(k) Summary
K143075
ST AIA-PACK SHBG
| Date: | June 30, 2015 |
|---|---|
| Submitter: | Tosoh Bioscience, Inc |
| 3600 Gantz Road | |
| Grove City, OH 43123 | |
| Contact Person: | Robert L. Wick |
| Regulatory Specialist | |
| 6000 Shoreline Ct., Ste. 101 | |
| South San Francisco, CA 94080 | |
| Phone: 650-636-8117 | |
| Fax: 650-636-8121 | |
| Email: Robert.Wick@tosoh.com | |
| Device Name: | ST AIA-PACK SHBG |
| Classification: | Class I, reserved |
| CDZ | |
| Clinical Chemistry | |
| 21 CFR 862.1680 | |
| Device Name: | ST AIA-PACK SHBG Calibrator Set |
| Classification | Class II |
| JIT | |
| Clinical Chemistry | |
| 21 CFR 862.1150 | |
| Predicate Device: | K060818 |
| Abbott/ BIOKIT S.A. | |
| ARCHITECT SHBG REAGENT KIT, ARCHITECT | |
| SHBG CALIBRATOR KIT |
5
510(k) Summary
ST AIA-PACK SHBG
According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.
Device Description:
The ST AIA-PACK SHBG is a two-site immunoenzymometric assay which is performed entirely in the ST AIA-PACK SHBG test cups. SHBG present in the test sample is bound with monoclonal antibody immobilized on a maqnetic solid phase and enzyme-labeled monoclonal antibody in the test cups. The magnetic beads are washed to remove unbound enzyme-labeled antibody and are then incubated with a fluorogenic substrate, 4-methylumbelliferyl phosphate (4MUP). The amount of enzyme-labeled monoclonal antibody that binds to the beads is directly proportional to the SHBG concentration in the test sample. A standard curve is constructed, and unknown sample concentrations are calculated using this curve.
The following materials are required to perform SHBG analysis using the ST AIA-PACK SHBG (Cat. No. 025238) on the Tosoh AIA System Analyzer.
| ST AIA-PACK SHBG Calibrator Set | 025338 |
|---|---|
| ST AIA-PACK SHBG Sample Diluting Solution | 025538 |
Device Intended Use:
ST AIA-PACK SHBG is designed for In Vitro Diagnostic Use Only for the quantitative measurement of sex hormone binding globulin (SHBG) in human serum or Na heparinized plasma on Tosoh AIA System Analyzers. The ST AIA-PACK SHBG assay is intended for use as an aid in the diagnosis of androgen disorders.
Calibrators:
The ST AIA-PACK SHBG Calibrator Set is intended for In Vitro Diagnostic Use Only for the calibration of the ST AIA-PACK SHBG assay.
6
Substantial Equivalence:
Comparison between the Tosoh ST AIA-PACK SHBG and the Abbott Architect SHBG Immunoassay (K060818)
Similarities
| Parameter | ST AIA-PACK SHBG | Abbott Architect SHBG Kit
(K060818) |
|------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended use | For the quantitative
measurement of SHBG in
human serum and plasma. | For the quantitative
measurement of SHBG in
human serum and plasma. |
| Indications for Use | ST AIA-PACK SHBG is
designed for In Vitro
Diagnostic Use Only for the
quantitative measurement of
sex hormone binding globulin
(SHBG) in human serum or
Na heparinized plasma on
Tosoh AIA System Analyzers.
The ST AIA-PACK SHBG
assay is intended for use as
an aid in the diagnosis of
androgen disorders. | The ARCHITECTTM SHBG
assay is a chemiluminescent
microparticle immunoassay
(CMIA) for the quantitative
determination of sex hormone
binding globulin (SHBG) in
human serum and plasma on
the ARCHITECT iSystem.
The ARCHITECT SHBG
assay is intended for use as
an aid in the diagnosis of
androgen disorders. |
| Specimen type | Serum or sodium heparinized
plasma | Human serum or plasma
(Lithium Heparin, Sodium
Heparin, Ammonium Heparin,
Potassium EDTA) |
| Interference | No interference from:
Hemoglobin
Free bilirubin
Conjugated bilirubin
Lipemia, as indicated by
triglyceride concentration
Protein, as indicated by
human albumin concentration
HAMA | Non-significant interferences
with:
Hemoglobin
Bilirubin
Triglycerides
Protein |
| Limit of detection | 0.02 nmol/L | 0.02 nmol/L |
| Specificity/Cross Reactivity | Non-cross reactive:
Alpha-Fetoprotein (AFP)
Estradiol
Thyroxin-Binding Globulin
Transferrin
11-Deoxycortisol
5alpha-Dihydroxytestosterone
Cortisol
Testosterone
Thyroglobulin | Non-cross reactive:
AFP
Estradiol
Thyroxin-Binding Globulin
Transferrin
11-Deoxycortisol
5alpha-Dihydroxytestosterone
Cortisol
Testosterone
Thyroglobulin |
| Precision | Within-run:
10,000 nmol/L. | The "hook effect"
phenomenon may occur only
at SHBG concentrations >
10,000 nmol/L. |
7
Differences
| Parameter | ST AIA-PACK SHBG | Abbott Architect SHBG Kit
(K060818) |
|------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Test Methodology | Fluorescence Immunosassay | Chemiluminescent
Microparticle
Immunoassay (CMIA) |
| Components | Unit dose test cups
containing twelve lyophilized
magnetic beads coated with
anti-SHBG mouse
monoclonal antibody and 100
µL of anti-SHBG mouse
monoclonal antibody
conjugated to bovine alkaline
phosphatase with sodium
azide as a preservative. | Microparticles
1 or 4 Bottle(s) (6.6 ml each)
Anti-SHBG(mouse
monoclonal) coated
microparticles in TRIS buffer.
Preservative: sodium azide |
| Specificity/Cross Reactivity | Non cross reactive:
Plasminogen
TSH
Fibrinogen
Human IgA
Human IgG
Corticosteroid Binding
Globulin | Not specified |
| Expected Values | 488 samples - 244 male and
244 female
Male (21 to 49 years old) 10 -
68 nmol/L
Male (≥50 years old)16-125
nmol/L
Females (pre-menopausal)
18 – 260 nmol/L
Females (post-menopausal)
15 - 185 nmol/L | 319 samples - 152 male and
167 female
Male 11.2 - 78.1 nmol/L
Female 11.7 - 137.2 nmol/L |
| Interference | No interference from:
Ascorbic acid
Heparin | Not specified or tested |
| Linearity (measuring range) | 0.2 to 250 nmol/L. | 0.1 to 250 nmol/L |
Similarities
Calibrator Set
| Parameter | ST AIA-PACK SHBG
Calibrator Set | Architect SHBG Calibrator
Kit (K060818) |
|--------------|------------------------------------|--------------------------------------------|
| Intended use | The ST AIA-PACK SHBG | The ARCHITECT "" SHBG |
8
| | Calibrator Set is intended for
In Vitro Diagnostic Use Only
for the calibration of the ST
AIA-PACK SHBG assay. | Calibrators are for the
calibration of the
ARCHITECT iSystem when
used for the quantitative
determination of SHBG in
human serum and plasma. |
|-----------------------|-------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Number of Calibrators | 6 | 6 |
Differences
Calibrator Set
| Parameter | AIA-PACK SHBG Calibrator
Set | Architect SHBG Calibrator
Kit (K060818) |
|------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------|
| Components | Bovine serum with assigned
levels of sex hormone binding
globulin (SHBG). | SHBG (human, purified) in
phosphate buffered saline
with protein (goat) stabilizer |
| Traceability/Standardization | Traceable to the 2nd
International Standard for
SHBG from the National
Institute for Biological
Standards and Control
(NIBSC) code 08/266. | Traceable to the WHO
Standard Material NIBSC
CODE: 95/560. |
PERFORMANCE CHARACTERISTICS
Precision
The precision study was developed with reference to the CLSI protocol entitled: Evaluation of Precision Performance of Quantitative Measurement Methods (EP5-A2).
The precision study for the ST AIA-PACK SHBG assay was evaluated utilizing three AIA-2000 analyzers and three different lots of reagents. Precision was assessed by assaying three levels of serum and heparinized plasma specimens. Estimates of total and within run precision were obtained from measurements of 2 replicates in a single run, 2 times a day for 20 non-consecutive days. The mean of each duplicate was used to obtain the pooled standard deviation (SD), which was then used to calculate the coefficient of variation (CV). In addition, all of the data were combined to assess the within run, between run, between lot and total precision.
Within run precision
| Mean | Pooled SD | CV | |
|---|---|---|---|
| Sample | (nmol/L) | (nmol/L) | (%) |
| Serum 1L | 17.3 | 0.454 | 2.6 |
| Serum 1M | 52.7 | 1.48 | 2.8 |
| Serum 1H | 154.9 | 4.96 | 3.2 |
| Serum 2L | 18.0 | 0.39 | 2.1 |
| Serum 2M | 54.8 | 1.29 | 2.3 |
| Serum 2H | 158.9 | 4.07 | 2.6 |
| Serum 3L | 18.8 | 0.56 | 2.9 |
9
| Serum 3M | 58.4 | 1.40 | 2.4 |
|---|---|---|---|
| Serum 3H | 175.6 | 5.26 | 3.0 |
| Heparinized Plasma 1L | 15.5 | 0.48 | 3.1 |
| Heparinized Plasma 1M | 62.9 | 1.70 | 2.7 |
| Heparinized Plasma 1H | 139.6 | 3.92 | 2.8 |
| Heparinized Plasma 2L | 16.1 | 0.39 | 2.4 |
| Heparinized Plasma 2M | 65.2 | 1.03 | 1.6 |
| Heparinized Plasma 2H | 142.2 | 3.70 | 2.6 |
| Heparinized Plasma 3L | 17.2 | 0.43 | 2.5 |
| Heparinized Plasma 3M | 70.7 | 1.59 | 2.3 |
| Heparinized Plasma 3H | 159.3 | 4.90 | 3.1 |
Total Precision
| Mean | Pooled SD | CV | |
|---|---|---|---|
| Sample | (nmol/L) | (nmol/L) | (%) |
| Serum 1L | 17.3 | 0.485 | 2.8 |
| Serum 1M | 52.7 | 1.62 | 3.1 |
| Serum 1H | 154.9 | 5.13 | 3.3 |
| Serum 2L | 18.0 | 0.54 | 3.0 |
| Serum 2M | 54.8 | 1.75 | 3.2 |
| Serum 2H | 158.9 | 4.80 | 3.0 |
| Serum 3L | 18.8 | 0.61 | 3.2 |
| Serum 3M | 58.4 | 1.51 | 2.6 |
| Serum 3H | 175.6 | 6.43 | 3.7 |
| Heparinized Plasma 1L | 15.5 | 0.54 | 3.5 |
| Heparinized Plasma 1M | 62.9 | 2.03 | 3.2 |
| Heparinized Plasma 1H | 139.6 | 5.13 | 3.7 |
| Heparinized Plasma 2L | 16.1 | 0.52 | 3.2 |
| Heparinized Plasma 2M | 65.2 | 1.55 | 2.4 |
| Heparinized Plasma 2H | 142.2 | 4.39 | 3.1 |
| Heparinized Plasma 3L | 17.2 | 0.52 | 3.0 |
| Heparinized Plasma 3M | 70.7 | 1.98 | 2.8 |
| Heparinized Plasma 3H | 159.3 | 5.42 | 3.4 |
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Between run precision
| Mean | Pooled SD | CV | |
|---|---|---|---|
| Sample | (nmol/L) | (nmol/L) | (%) |
| Serum 1L | 17.3 | 0.33 | 1.9 |
| Serum 1M | 52.7 | 1.17 | 2.2 |
| Serum 1H | 154.9 | 3.75 | 2.4 |
| Serum 2L | 18.0 | 0.37 | 2.0 |
| Serum 2M | 54.8 | 1.32 | 2.4 |
| Serum 2H | 158.9 | 3.39 | 2.1 |
| Serum 3L | 18.8 | 0.43 | 2.3 |
| Serum 3M | 58.4 | 1.14 | 2.0 |
| Serum 3H | 175.6 | 4.99 | 2.8 |
| Heparinized Plasma 1L | 15.5 | 0.42 | 2.7 |
| Heparinized Plasma 1M | 62.9 | 1.63 | 2.6 |
| Heparinized Plasma 1H | 139.6 | 4.29 | 3.1 |
| Heparinized Plasma 2L | 16.1 | 0.41 | 2.5 |
| Heparinized Plasma 2M | 65.2 | 0.95 | 1.5 |
| Heparinized Plasma 2H | 142.2 | 2.88 | 2.0 |
| Heparinized Plasma 3L | 17.2 | 0.42 | 2.4 |
| Heparinized Plasma 3M | 70.7 | 1.40 | 2.0 |
| Heparinized Plasma 3H | 159.3 | 4.16 | 2.6 |
Between day precision
| Mean | Pooled SD | CV | |
|---|---|---|---|
| Sample | (nmol/L) | (nmol/L) | (%) |
| Serum 1L | 17.3 | 0.28 | 1.6 |
| Serum 1M | 52.7 | 0.91 | 1.7 |
| Serum 1H | 154.9 | 2.59 | 1.7 |
| Serum 2L | 18 | 0.39 | 2.1 |
| Serum 2M | 54.8 | 1.29 | 2.3 |
| Serum 2H | 158.9 | 4.07 | 2.6 |
| Serum 3L | 18.8 | 0.56 | 2.9 |
| Serum 3M | 58.4 | 1.4 | 2.4 |
| Serum 3H | 175.6 | 5.26 | 3.0 |
| Heparinized Plasma 1L | 15.5 | 0.48 | 3.1 |
| Heparinized Plasma 1M | 62.9 | 1.7 | 2.7 |
| Heparinized Plasma 1H | 139.6 | 3.92 | 2.8 |
| Heparinized Plasma 2L | 16.1 | 0.39 | 2.4 |
| Heparinized Plasma 2M | 65.2 | 1.03 | 1.6 |
| Heparinized Plasma 2H | 142.2 | 3.7 | 2.6 |
| Heparinized Plasma 3L | 17.2 | 0.43 | 2.5 |
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| Heparinized Plasma 3M | 70.7 | 1.59 | 2.3 |
|---|---|---|---|
| Heparinized Plasma 3H | 159.3 | 4.9 | 3.1 |
Representative Lot-to-Lot Precision
| Sample | Mean
(n=80)
nmol/L | Within-Run | | Between-Run | | Total | |
|-------------------|--------------------------|------------|-----|-------------|-----|-------|-----|
| | | SD | %CV | SD | %CV | SD | %CV |
| Serum Low | 18.0 | 0.39 | 2.1 | 0.37 | 2.0 | 0.53 | 3.0 |
| Serum medium | 54.8 | 1.29 | 2.3 | 1.32 | 2.4 | 1.8 | 3.3 |
| Serum High | 158.9 | 4.07 | 2.6 | 3.39 | 2.1 | 4.93 | 3.1 |
| Hep Plasma Low | 16.1 | 0.4 | 2.4 | 0.4 | 2.5 | 0.6 | 3.4 |
| Hep Plasma Medium | 65.2 | 1.0 | 1.6 | 1.0 | 1.5 | 1.5 | 2.3 |
| Hep Plasma High | 142.2 | 3.7 | 2.6 | 2.9 | 2.0 | 4.4 | 3.1 |
Combined Summary Table
| Sample | | Serum-
1 | Serum-
2 | Serum-
3 | Hep
Plasma-
1 | Hep
Plasma-
2 | Hep
Plasma-
3 |
|------------------------|-----|-------------|-------------|-------------|---------------------|---------------------|---------------------|
| Mean Conc.
(nmol/L) | | 18.1 | 55.3 | 163.1 | 16.3 | 66.3 | 147.0 |
| Within | SD | 0.47 | 1.39 | 4.79 | 0.43 | 1.47 | 4.21 |
| Run | %CV | 2.6 | 2.5 | 2.9 | 2.7 | 2.2 | 2.9 |
| Between | SD | 0.38 | 1.21 | 4.10 | 0.42 | 1.36 | 3.83 |
| Run | %CV | 2.1 | 2.2 | 2.5 | 2.6 | 2.0 | 2.6 |
| Between | SD | 0.72 | 2.57 | 9.59 | 0.74 | 3.47 | 9.19 |
| Day | %CV | 4.0 | 4.6 | 5.9 | 4.6 | 5.2 | 6.3 |
| Between | SD | 0.77 | 1.54 | 2.77 | 0.84 | 1.59 | 1.79 |
| Lot | %CV | 4.3 | 2.8 | 1.7 | 5.1 | 2.4 | 1.2 |
| | SD | 0.84 | 2.88 | 9.42 | 0.85 | 3.75 | 10.04 |
| Total | %CV | 4.6 | 5.2 | 5.8 | 5.3 | 5.7 | 6.8 |
Linearity:
Linearity: The linearity for ST AIA-PACK SHBG was determined, based on guidance from CLSI Protocol EP6-A entitled: Evaluation of the Linearity of Quantitative Measurement Procedures: a Statistical Approach: Approved Guideline. The linearity was measured on the AIA-2000 instrument and has been demonstrated to be linear from 0.2 to 250 nmol/L.
Correlation
The methods comparison study was based on guidance from EP9-A2.
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Method Comparison
A total of 126 serum specimens were assayed in singleton utilizing the ST AIA-PACK SHBG assay on the AIA-2000 analyzer and the predicate SHBG.
| Deming | Regular | |
|---|---|---|
| Slope: | 0.949 (0.926 to 0.972) | 0.940 (0.917 to 0.964) |
| Intercept: | -0.64 (-2.61 to 1.34) | -0.09 (-2.06 to 1.89) |
| Corr Coef (R): | 0.991 | |
| Result Ranges: | Tosoh ST AIA-PACK SHBG | |
| Predicate SHBG | 0.6 to 241.0 nmol/L | |
| 0.5 to 221.6 nmol/L |
*95% Confidence Intervals are shown in parentheses
Matrix Comparison
The correlation between serum (x) and Na heparinized plasma (y) on ST AIA-PACK SHBG was carried out using 116 patient specimens were diluted to obtain the low end of the measuring range.
| Deming | Regular | |
|---|---|---|
| Slope: | 0.977 (0.964 to 0.991) | 0.975 (0.961 to 0.988) |
| Intercept: | 0.269 (-0.629 to 1.168) | 0.415 (-0.483 to 1.313) |
| Corr Coef (R): | 0.997 | |
| Result Ranges | Serum: | |
| Na heparinized plasma: | 0.2 to 219.1 nmol/L | |
| 0.2 to 219.9 nmol/L |
95% Confidence Intervals are shown in parentheses
Specificity
The following substances were tested for cross-reactivity. Cross-reactivity is the percentage of the compound which will be identified as SHBG.
| Substance | Concentration
added | Cross-reactivity
(%) |
|------------------------------|------------------------|-------------------------|
| Alpha-Fetoprotein (AFP) | 48.4 $\mu$ g/dL | N.D. |
| Cortisol | 100 $\mu$ g/mL | 0.003 |
| 11-Deoxycortisol | 4 $\mu$ g/mL | 0.114 |
| 5alpha-Dihydroxytestosterone | 20 $\mu$ g/mL | 0.007 |
| Estradiol | 3600 pg/mL | N.D. |
| Testosterone | 20 $\mu$ g/mL | 0.019 |
| Thyroglobulin | 300 $\mu$ g/mL | 2.544 |
| Thyroxin-Binding Globulin | 200 $\mu$ g/mL | N.D. |
| Transferrin | 4 mg/mL | N.D. |
| Fibrinogen | 4.5 g/L | 0.120 |
| Plasminogen | 250 mg/L | N.D. |
| Human IgA | 367 mg/dL | 0.072 |
| Human IgG | 335 mg/dL | 0.218 |
| CBG | 35 mg/dL | 0.012 |
| TSH | 180 mIU/L | N.D. |
(N.D.: not detectable)
13
Reference Ranges
The reference range study was conducted with reference to the CLSI protocol entitled: How to Define and Determine Reference Intervals in the Clinical Laboratory (C28-A3) entitled: Defining, Establishing, and verifying Reference Intervals in the Clinical Laboratory; Approved Guideline -Third Edition.
The interval given here was determined in serum samples from 488 apparently healthy American and European individuals.
| n | Range (nmol/L) | |
|---|---|---|
| Male (21 to 49 years old) | 121 | 10 - 68 |
| Male (≥50 years old) | 123 | 16 - 125 |
| Females (pre-menopausal ≥ 21 years if age) | 122 | 18 - 260 |
| Females (post-menopausal) | 122 | 15 - 185 |
Interference
Interference is defined, for the purposes of this study, with recovery outside of 10 % of the known concentration of the specimen after the following substances are added to human specimens.
- Hemoglobin (up to 446 mg/dL), free bilirubin (up to 17.6 mg/dL), and conjugated bilirubin ● (up to 18.5 mq/dL) do not interfere with the assay.
- Lipemia, as indicated by triglyceride concentration (up to 1,667 mg/dL), does not interfere with the assay.
- Ascorbic acid (up to 20 mg/dL) does not interfere with the assay. .
- Protein, as indicated by human albumin concentration (up to 5,00 g/dL added to samples ● from apparently healthy subjects), does not interfere with the assay.
- Na Heparin (up to 100.0 U/mL) does not interfere with the assay. ●
- . Rheumatoid factor (up to 550 IU/mL) does not interfere with the assay.
- . HAMA (up to 24,269 ng/mL) does not interfere with the assay.
Limit of Detection (LoD) and Limit of Quantitation (LoQ):
The LoD and LoQ for ST AIA-PACK SHBG was determined, according to CLSI quideline EP17-A entitled: Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline.
The LoB was determined by 60 measurements of 4 different blank specimens. The LoB was the value at the 95th percentile. In this case LoB was determined to be 0.017 nmol/L.
The LoD was determined by 12 measurements of 10 low level sample range was chosen to be between LoB and 5XLoB. The LoD was determined to be 0.063 nmol/L.
The Limit of Quantification (LoQ) 12 measurements of 5 samples for ST AIA-PACK SHBG. The test results from the LoD study were used to calculate the %TE at that level. The LoQ was determined to be 0.2 nmol/L based on a % total error of 12%.
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Calibrator Stability
Real Time Testing
ST AIA-PACK SHBG Calibrator Set were stored at refrigerated temperatures and assayed at 3, 6, 9, 12 and 13 months after the day of the first assay.
The acceptance criteria for recovery was within 100 +/- 10%.
The criterion for reproducibility (CV %) was