(143 days)
No
The device description and performance studies focus on standard immunoassay technology and analytical performance metrics, with no mention of AI or ML algorithms for data processing or interpretation.
No.
This device is an in vitro diagnostic device used to aid in the diagnosis of androgen disorders by quantifying SHBG levels, not to directly treat or prevent a disease.
Yes
The "Intended Use / Indications for Use" section explicitly states, "The IDS SHBG assay is an in vitro diagnostic device intended for the quantitative determination of SHBG in human serum or plasma... Results are to be used as an aid in the diagnosis of androgen disorders." This directly identifies it as a diagnostic device.
No
The device is an in vitro diagnostic assay that includes physical reagents (magnetic particles, antibodies, conjugate, calibrators) and is intended for use on a specific automated system (IDS-iSYS). It is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement: The "Intended Use / Indications for Use" and "Device Description" sections both explicitly state that the IDS SHBG assay is an "in vitro diagnostic device."
- Purpose: The device is intended for the quantitative determination of SHBG in human serum or plasma, which are biological samples taken in vitro (outside the body).
- Clinical Use: The results are used as an aid in the diagnosis of androgen disorders, indicating a clinical diagnostic purpose.
- Methodology: The assay uses a chemiluminescence technology to measure an analyte in a biological sample, which is a common characteristic of IVDs.
- Reagents: The device consists of ready-to-use reagents for performing the test on the biological sample.
- Performance Studies: The document details performance studies like precision, linearity, traceability, detection limit, analytical specificity, method comparison, and matrix comparison, which are standard for demonstrating the analytical performance of an IVD.
- Predicate Device: A predicate device (Siemens ADVIA Centaur SHBG) is listed, which is another IVD, further supporting the classification of this device as an IVD.
All these factors clearly indicate that the IDS SHBG assay is an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The IDS SHBG assay is an in vitro diagnostic device intended for the quantitative determination of SHBG in human serum or plasma on the IDS System. Results are to be used as an aid in the diagnosis of androgen disorders
Product codes (comma separated list FDA assigned to the subject device)
CDZ
Device Description
The IDS SHBG assay is an in vitro diagnostic device intended for the quantitative determination of sex hormone binding globulin (SHBG) in human serum and plasma on the IDS-iSYS Multi-Discipline Automated System. Results are to be used in conjunction with other clinical and laboratory data to assist the clinician in the diagnosis of androgen disorders.
The assay is based on chemiluminescence technology. 5 uL of patient sample or calibrators are incubated with biotinylated monoclonal anti-SHBG antibody, an acridinium labelled monoclonal anti-SHBG conjugate and streptavidin labelled magnetic particles. The magnetic particles are captured using a magnet and a wash step performed to remove any unbound analyte. Trigger reagents are added; the resulting light emitted by the acridinium label is directly proportional to the concentration of analyte in the original sample.
The IDS SHBG assay is an in vitro diagnostic device consisting of ready to use reagents provided in individual compartments within the reagent cartridge.
The reagent cartridge contains:
- Magnetic particles magnetic particles coated with streptavidin in a phosphate buffer containing preservatives
- -Biotin antibody - monoclonal anti-SHBG labelled with biotin in a buffer containing proteins and preservatives
- Conjugate monoclonal anti-SHBG labelled with an acridinium ester derivative in a buffer containing proteins and preservatives
The calibrators consist of: - Calibrators A and B are included in the assay kit. The calibrators consist of a human serum matrix with defined concentrations of SHBG and preservatives. Together with a lot specific master calibration curve, the calibrators will be used to perform adjustment of the master calibration curve.
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
The expected values were assessed by using 671 serum samples from the United States in which the subjects were apparently healthy adults and aged between 21 and 77 years old.
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
- Analytical performance:
a. Precision/Reproducibility:
Precision was determined in accordance with CLSI EP5-A3, "Evaluation of Precision Performance of Quantitative Measurement Methods". Assessment was made for the following variables: within run precision, total precision.
Fourteen serum-based samples were used, at different SHBG concentration levels ranging from 1.6 nmol/L to approximately 180.00 nmol/L. This was to ensure that the assay measuring range of the IDS SHBG was covered.
Final claims data reported is representative of one kit lot (MB2) where 21 days were available for analysis.
b. Linearity/assay reportable range:
For the measuring range, a linearity study was conducted based on guidance from the CLSI EP6-A. A high human serum sample and a low human serum sample (low serum sample diluted in zero matrix) were analysed in addition to 14 evenly spaced dilutions which were created by mixing the high and low sample.
The IDS SHBG assay is linear over the measuring range from 1.60 to 180.00 nmol/L. The IDS SHBG assay is also linear across the reportable range of the assay which is 0.30 to 720.00 nmol/L when any sample with SHBG concentrations above 180nmol/L is automatically diluted 1:4 by the iSYS System.
To support the extended measuring range up to 720 nmol/L through the automated dilution by the analyzer, the guideline CLSI EP34 1st ed. was followed.
Nine native samples with known SHBG concentration (obtained on the predicate device Siemens Advia Centaur SHBG assay) were tested on the iSYS using the automated postdilution. Samples were tested in a single replicate on one kit lot.
When testing on the predicate device, samples above 180nmol/L were automatically 1:2 by the automate. If samples were still above the measurement range, the samples were manually diluted 1:5.
The accuracy of the IDS-iSYS system to read samples above 180 nmol/L using the automatic dilution is evaluated by calculating the recovery between IDS and Siemens Advia Centaur assays.
Conclusion: A recovery of between 87% to 100% was achieved. IDS SHBG assay shows good accuracy when measuring samples in the range 180 - 720 nmol/L using the automatic dilution.
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
The standardization of the IDS SHBG assay against the WHO 2nd international standard 08/266 was carried out in two phases, value assignment and verification.
Value assignment of kit calibrators: Candidate secondary standards (IRs) are value assigned directly to the WHO NIBSC 2nd international standard for SHBG (IS 08/266) through an internal QC procedure: at least 24 runs are performed using three iSYS instruments, 2 kit lots, 3 replicates for each run. Serial dilutions of the IS 08/266 in SHBG-depleted human serum are used as the reference to assign IR values. The IDS SHBG kit calibrators A and B and master curve are value assigned off the secondary standards and the IS-08/266 through an internal OC procedure. At least 20 runs (14 runs using the previous IR lot - 6 runs using the international standard as the reference) are performed using one iSYS instrument, 2 replicates for each run.
Value assignment verification: The kit calibrator A and B values are then verified on three different iSYS instruments following an approved OC procedure by testing internal quality controls in five replicates in one run and on each instrument.
Traceability to the NIBSC 2nd IS 08/266: A correlation study is also performed between the results obtained when using the 2-point calibration and the results derived from the international standard IS 08/266 curve. 189 samples (139 serum - 50 K2 EDTA plasmas) were tested in two replicates using three lots (MB1, MB2 and MB3) on one iSYS instrument. Their concentrations were derived from the 2-point calibration and compared to the concentration calculated by using a serial dilution of the NIBSC 2nd international standard 08/266 (from 180 nmol/L to 0 nmol/L using SHBG depleted human serum). Results were analysed using Passing Bablok analysis on Analyse-it.
d. Detection limit:
The limit of blank (LoB), limit of detection (LoD) and limit of quantitation (LoQ) were determined based on guidance from CLSI EP17-A2 "Protocols for the determination of limits of detection and limits of quantitation". For the measurement of LoB, LoD and LoQ three manufacture batches (MB1, MB2B and MB3) were tested.
The LoB sample was run in 12 replicates for each of 5 runs over 3 days, by one operator and on one different instrument for each kit lot for a total of 60 replicates per lot.
Each of the 7 LoD samples was measured in duplicate. For each kit lot, a total of 5 assays were run over 3 days by one operator and on a different instrument, for a total of 70 replicates.
For calculation of The LoO panel of 9 samples were measured in singlicate two times per day. For each kit lot, a total of 10 assays were run over 5 days by one operator and on a different instrument, for a total of 90 replicates.
e. Analytical specificity:
Interference and cross-reactivity studies were performed in accordance with the CLSI guidance EP7-A2"Interference testing in clinical chemistry".
To determine potential interference in the specific detection of SHBG, two serum samples at two different concentrations of SHBG were spiked with the potential interferent. Control samples (blank) for each of the two SHBG samples were spiked with a volume of relevant diluent equal to that of the spiked interferent. The mean concentration of the 26 replicate assays, determined for both the spiked and control samples, were then compared. The differences observed between the mean spiked and control sample values were examined and assessed according to acceptance criteria.
For total cholesterol the interference was tested by dilution of a high cholesterol native serum sample in zero matrix (SHBG depleted normal human serum) and calculation of the observed vs expected SHBG concentration.
- Comparison studies:
Method comparison:
The IDS SHBG assay was compared against a commercially available quantitative automated assay, following CLSI EP-9A3, "Method Comparison and Bias Estimation Using Patient Samples". A total of 136 samples, selected to represent a wide range of SHBG concentrations [sample concentration range: 2.54 - 172.12 nmol/L (0.24 - 16.35 ug/mL)], was assayed by each method. Passing-Bablok regression analysis was performed on the comparative data.
Matrix comparison:
The IDS SHBG matrix comparison study was performed to evaluate the difference across tube types (serum (without additives), serum gel separator tubes (TG), and K2 EDTA plasma.) following the CLSI EP9-A3 guideline.
A total of 69 samples (68 native, 1 diluted) to cover the range of 0.51 to 238.45 mol/L. Passing-Bablok regression analysis was performed on the comparative data.
- Expected values/Reference range:
The expected values were calculated using Analyse-it. Results were analysed to generate a nonparametric 95 % reference interval using the 2.5th and 97.5th percentiles as reference limits.
The expected values were assessed by using 671 serum samples from the United States in which the subjects were apparently healthy adults and aged between 21 and 77 years old. The observed ranges were established, according to CLSI C28-A3c "Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory".
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Sensitivity:
LoB: 0.01 nmol/L
LoD: 0.15 nmol/L
LoQ: 0.30 nmol/L
Precision:
Within Run Precision n = 84: 1.7% to 3.7% in the concentration range 5.57 to 201.67 nmol/L
Total Precision n = 84: 3.2% to 5.0% in the concentration range 5.57 to 201.67 nmol/L
Method Comparison (with predicate Siemens ADVIA Centaur SHBG):
N = 136
Passing Bablok regression: IDS SHBG = 0.9112 (ADVIA Centaur SHBG) 0.1556 nmol/L
Correlation coefficient (r) = 0.989
Linearity Serum:
Observed = 1.00 x (expected) -0.54 nmol/L
Regression coefficient R2: 0.999
Linearity K2 EDTA plasma:
Observed = 0.97 x (expected) -0.46 nmol/L
Regression coefficient R2: 0.998
Matrix comparison:
Serum (against Serum gel tube): Slope = 1.019, Intercept = 0.4897, r = 0.999, Mean bias v Serum = 0.7%
Serum (against K2 EDTA): Slope = 0.9854, Intercept = 0.0308, r = 0.998, Mean bias v Serum = -1.3%
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.
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.
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June 17, 2019
Immunodiagnostic Systems Ltd. Mick Henderson Regulatory Affairs Manager 10 Didcot Way Boldon Business Park Boldon NE35 9PD GB
Re: K190121
Trade/Device Name: IDS SHBG Regulation Number: 21 CFR 862.1680 Regulation Name: Testosterone test system Regulatory Class: Class I, reserved Product Code: CDZ Dated: May 15, 2019 Received: May 17, 2019
Dear Mick Henderson:
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 medical devices and radiation-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, Ph.D. Acting Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K190121
Device Name IDS SHBG
Indications for Use (Describe)
The IDS SHBG assay is an in vitro diagnostic device intended for the quantitative determination of SHBG in human serum or plasma on the IDS System. Results are to be used as an aid in the diagnosis of androgen disorders
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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510(k) SUMMARY
| 510k Number | K190121 | |
|---|---|---|
| Introduction | According to the requirements of 21CFR807.92, the following | |
| information provides sufficient detail to understand the basis for a | ||
| determination of substantial equivalence. | ||
| Submitter | Immunodiagnostic Systems Ltd | |
| 10 Didcot Way | ||
| Boldon Business Park | ||
| Boldon | ||
| Tyne and Wear | ||
| NE35 9PD | ||
| United Kingdom | ||
| Contact Person: Mick Henderson | ||
| Phone: +44 191 5190660 | ||
| Fax: +44 191 5190760 | ||
| Email: mick.henderson@idsplc.com | ||
| Secondary Contact: Jenny Manolopoulou | ||
| Phone: +44 191 5190660 | ||
| Fax: +44 191 5190760 | ||
| Email: jenny.manolopoulou @idsplc.com | ||
| Date prepared: 11 June 2019 | ||
| Device Name | ||
| Proprietary name: | IDS SHBG | |
| Common name: | As above | |
| Classification: | 21CFR862.1680 Testosterone test system | |
| Product Code: | CDZ |
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Image /page/4/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters "ids" in a stylized, rounded sans-serif font, with the "i" having a red circular dot above it. Below the letters, the words "immunodiagnosticsystems" are written in a smaller, red sans-serif font. The overall design is clean and modern, with a focus on the company's name and its area of expertise.
- Predicate Device The IDS SHBG is substantially equivalent to other products in commercial distribution intended for similar uses. We claim equivalency to the currently marketed Siemens ADVIA Centaur SHBG (K151986).
Device Description
Description for IDS-iSYS SHBG assay
The IDS SHBG assay is an in vitro diagnostic device intended for the quantitative determination of sex hormone binding globulin (SHBG) in human serum and plasma on the IDS-iSYS Multi-Discipline Automated System. Results are to be used in conjunction with other clinical and laboratory data to assist the clinician in the diagnosis of androgen disorders.
The assay is based on chemiluminescence technology. 5 uL of patient sample or calibrators are incubated with biotinylated monoclonal anti-SHBG antibody, an acridinium labelled monoclonal anti-SHBG conjugate and streptavidin labelled magnetic particles. The magnetic particles are captured using a magnet and a wash step performed to remove any unbound analyte. Trigger reagents are added; the resulting light emitted by the acridinium label is directly proportional to the concentration of analyte in the original sample.
The IDS SHBG assay is an in vitro diagnostic device consisting of ready to use reagents provided in individual compartments within the reagent cartridge.
The reagent cartridge contains:
- Magnetic particles magnetic particles coated with streptavidin in a phosphate buffer containing preservatives
- -Biotin antibody - monoclonal anti-SHBG labelled with biotin in a buffer containing proteins and preservatives
- Conjugate monoclonal anti-SHBG labelled with an acridinium ester derivative in a buffer containing proteins and preservatives The calibrators consist of:
- Calibrators A and B are included in the assay kit. The calibrators consist of a human serum matrix with defined concentrations of SHBG and preservatives. Together with a lot specific master
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calibration curve, the calibrators will be used to perform adjustment of the master calibration curve.
Indications for Use
IDS SHBG
The IDS SHBG assay is an in vitro diagnostic device intended for the quantitative determination of SHBG in human serum or plasma on the IDS System. Results are to be used as an aid in the diagnosis of androgen disorders
Rx Only
Conditions for use: For in vitro diagnostic use only. Rx Only
Special instrument Requirements:
IDS-iSYS Multi-Discipline Automated System (K091849)
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Comparison Tables
Similarities compared to the chosen (FDA cleared; marketed) predicate device (K151986)
| Performance | Predicate Device
ADVIA Centaur SHBG (K151986) | Candidate Device
IDS SHBG |
|---------------------------------------------------|----------------------------------------------------------------|-------------------------------------|
| Intended use | for use as an aid in the diagnosis of
androgen disorders | Same |
| Analyte | Sex hormone binding globulin
(SHBG) | Same |
| Reagent storage | 2-8 °C | Same |
| Range of assay | 1.6-180 nmol/L | 1.6 to 180 nmol/L |
| Sample preparation
(pre-treatment) | Performed on-board the analyzer | Same |
| Method of
detection (Test
methodology) | Chemiluminescent Magnetic Latex
Particle Immunoassay | Same |
| Automation | Fully automated assay | Same |
| Quality Control | Requires three controls to validate the
calibration | Same |
| Calibration
procedure | 2 point calibration | Same |
| Traceability/
Standardization | Standardised to WHO 2nd
International Standard (08/266) | Same |
| Specificity,
Interfering
substances & Cross | Interference
Haemoglobin
No Interference up to 500 mg/dL | Interference
Haemoglobin
Same |
| Reactivity | Cross Reactivity | Cross Reactivity |
| | Cortisol
Not detectable | Cortisol
Same |
| | 5α-dihydroxytestosterone
Not detectable | 5α-dihydroxytestosterone
Same |
| | Testosterone
Not detectable | Testosterone
Same |
| | Fibrinogen
Not detectable | Fibrinogen
Same |
| | Plasminogen
Not detectable | Plasminogen
Same |
| | Human IgA
Not detectable | Human IgA
Same |
| Human IgG
Not detectable | Human IgG
Same | |
| Corticosteroid binding globulin
Not detectable | Corticosteroid binding
globulin
Same | |
| Thyrotropin (TSH)
Not detectable | Thyrotropin (TSH)
Same | |
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Image /page/7/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters "ids" in a stylized, lowercase font, with a red circle above the "i". Below the letters, the words "immunodiagnostic systems" are written in a smaller, red font. The logo is simple and modern, with a focus on the company's name and its area of expertise.
Differences compared to the chosen predicate device (K151986)
| Performance | Predicate Device
ADVIA Centaur SHBG
(K151986) | Candidate Device
IDS SHBG |
|-----------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Indications for Use | 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 IDS SHBG assay is an in vitro diagnostic device intended
for the quantitative
determination of SHBG in
human serum or plasma on the
IDS System. Results are to be
used as an aid in the diagnosis
of androgen disorders. |
| Calibrator matrix | Equine serum | Human serum |
| Sample matrix
(primary tube type) | Human Serum, plasma (lithium
heparin) | Human serum, Plasma (K2
EDTA) |
| Sample volume | 10µL | 5µL |
| Kit reagent
components | Each SHBG Ready Pack
contains: 1) Solid Phase (11.0
mL) streptavidin coupled
magnetic
latex particles (~150 µg/mL), 2)
Lite Reagent (3.0 mL)
containing mouse monoclonal
anti-
SHBG antibody (~130 µg/mL)
labeled with acridinium ester,
and 3) Ancillary Well Reagent
(3.0 mL) containing a
biotinylated monoclonal mouse
anti-SHBG antibody (~6
µg/mL) | Reagent cartridge (1 vial each of
MPT1, CONJ, Ab-BIOT &
DIL), two concentration levels
of calibrators (A&B) (1 vial of
each) & a mini CD |
| | Each Ready Pack contains
reagents for 50 tests. | |
| Kit reagent
component
volumes | Reagent cartridge (1 vial each):
MPV1 (2.0mL), CONJ
(10.1mL), NaOH (13mL) &
BUF (26.0mL) | Reagent cartridge (1 vial each):
MPT1 (2.5mL), CONJ (7.5mL),
Ab- BIOT (7.55mL) & DIL
(18.0mL)
Calibrators(1.0mL) |
| Calibration interval | 35 days | 10 days |
| On board the
analyzer reagent
stability | 60 days | 14 days |
| Sensitivity | LoB: 1.2 nmol/L
LoD: 1.6 nmol/L
LoQ: 1.8 nmol/L | LoB: 0.01 nmol/L
LoD: 0.15 nmol/L
LoQ: 0.30 nmol/L |
| Expected values | Males 21 to 49 years
14.55 to 94.64 nmol/L
Males > 50 years
21.63 to 113.13 nmol/L
Premenopausal Females
10.84 to >180.00 nmol/L
Postmenopausal Females
23.15 to 159.07 nmol/L | Males 21 to 49 years
11.47 to 58.07 nmol/L
Males > 50 years
14.85 to 65.21 nmol/L
Premenopausal Females
20.30 to 140.18 nmol/L
Postmenopausal Females
11.30 to 127.31 nmol/L |
| Precision | Within Run Precision n = 40
2.5% to 3.8% in the
concentration range 9.04 to
142.87 nmol/L
Total Precision n = 40
3.1% to 6.5% in the
concentration range 9.04 to
142.87 nmol/L | Within Run Precision n = 84
1.7% to 3.7% in the
concentration range 5.57 to
201.67 nmol/L
Total Precision n = 84
3.2% to 5.0% in the
concentration range 5.57 to
201.67 nmol/L |
| Specificity,
Interfering
substances & Cross
Reactivity | Interference
Bilirubin, conjugated
No Interference up to 20 mg/dL
Bilirubin, unconjugated
No Interference up to 20 mg/dL
Biotin
No Interference up to 100 ng/mL
Cholesterol, total
No Claim
Human Anti Mouse Antibody
(HAMA)
No Claim | Interference
Bilirubin, conjugated
No Interference up to 40 mg/dL
Bilirubin, unconjugated
No Interference up to 40 mg/dL
Biotin
No Interference up to 1200
ng/mL
Cholesterol, total
No Interference up to 456 mg/dL
Human Anti Mouse Antibody
(HAMA)
No Interference up to 3000
ng/mL |
| | immunodiagnostiosystems | |
| Rheumatoid Factor
No Claim | Rheumatoid Factor
No Interference up to 7000
IU/mL | |
| Total Protein
No Claim | Total Protein
No Interference up to 12 g/dL | |
| Triglyceride
No Interference up to 1000
mg/dL | Triglyceride
No Interference up to 3000
mg/dL | |
| Acetaminophen
No Claim | Acetaminophen
No Interference up to 1324
µmol/L | |
| Ibuprofen
No Claim | Ibuprofen
No Interference up to 2425
µmol/L | |
| Ascorbic acid
No Claim | Ascorbic acid
No Interference up to 1700
µmol/L | |
| Acetylsalicylic acid
No Claim | Acetylsalicylic acid
No Interference up to 3.62
nmol/L | |
| Salicylic acid
No Claim | Salicylic acid
No Interference up to 4.34
mmol/L | |
| Creatinine
No Claim | Creatinine
No Interference up to 2.65
mmol/L | |
| Dopamine
No Claim | Dopamine
No Interference up to 850
µmol/L | |
| Tetracycline
No Claim | Tetracycline
No Interference up to 90 µmol/L | |
| Tolbutamine
No Claim | Tolbutamine
No Interference up to 3.7
mmol/L | |
| Tolazamide
No Claim | Tolazamide
No Interference up to 3.21
mmol/L | |
| Uric acid
No Claim | Uric acid
No Interference up to 1.4
mmol/L | |
| | | |
| | | |
| Specificity,
Interfering
substances & Cross
Reactivity | Cross Reactivity
AFP
Not detectable | Cross Reactivity
AFP
0.5 % |
| | Thyroglobulin
Not detectable | Thyroglobulin
90.2 % |
| | Thyroxin binding globulin
Not detectable | Thyroxin binding globulin
-0.1 % |
| | Transferrin
0.04 % | Transferrin
0.0 % |
| | 11-deoxycortisol
0.24 % | 11-deoxycortisol
-0.1 % |
| | Estradiol
Not detectable | Estradiol
-7.3 % |
| Method comparison | Against the Elecsys SHBG
assay
n = 194
Linear Regression
ADVIA Centaur SHBG =
$0.99(Elecsys) – 0.11$ nmol/L
Correlation coefficient (r) =
0.99 | Against the ADVIA Centaur
SHBG assay.
N = 136
Passing Bablok regression
IDS SHBG = $0.9112$ (ADVIA
Centaur SHBG) $0.1556$ nmol/L
Correlation coefficient (r) =
0.989 |
| Linearity | Weighted Linear regression of
the observed concentrations
versus the expected
concentrations: Observed =
$0.984$ x (Expected) +
$0.245$ ng/dL | Linear regression of the
observed concentrations versus
the expected concentrations:
Serum
Observed = $1.00$ x (Expected) -
$0.54$ nmol/L
Regression of coefficient (R2) =
$0.999$
K2 EDTA
Observed = $0.97$ x (Expected) -
$0.46$ nmol/L
Regression of coefficient (R2) =
$0.998$ |
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Image /page/8/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters "ids" in a stylized, interconnected font, with a red circle above the "i". Below the letters, the words "immunodiagnosticsystems" are written in a smaller, sans-serif font. The overall design is clean and modern.
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Image /page/9/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters 'ids' in a stylized, lowercase font, with the 'i' having a red circular dot above it. Below the 'ids' is the full name 'immunodiagnosticsystems' in a smaller, sans-serif font. The overall design is clean and modern, with a focus on the company's initials.
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Image /page/10/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters 'ids' in a stylized, lowercase font, with a red circle above the 'i'. Below the letters, the words 'immunodiagnosticsystems' are written in a smaller, sans-serif font. The overall design is clean and modern.
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Image /page/11/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters "ids" in a stylized, sans-serif font, with the "i" having a red circular dot above it. Below the letters "ids", the words "immunodiagnosticsystems" are written in a smaller, sans-serif font, with the same red color as the dot above the "i". The background is plain white.
Performance Characteristics (if/when applicable):
-
- Analytical performance:
a. Precision/Reproducibility:
Precision was determined in accordance with CLSI EP5-A3, "Evaluation of Precision Performance of Quantitative Measurement Methods". Assessment was made for the following variables: within run precision, total precision.
Fourteen serum-based samples were used, at different SHBG concentration levels ranging from 1.6 nmol/L to approximately 180.00 nmol/L. This was to ensure that the assay measuring range of the IDS SHBG was covered.
Final claims data reported is representative of one kit lot (MB2) where 21 days were available for analysis.
| ID | Mean | Within
Run SD | Within
Run CV | Between
Run SD | Between
Run CV | Within
Day SD | Within
Day CV | Between
Day SD | Between
Day CV | Total
SD | Total
CV |
|-------------|--------|------------------|------------------|-------------------|-------------------|------------------|------------------|-------------------|-------------------|-------------|-------------|
| CALB
MB2 | 124.95 | 3.93 | 3.1% | 1.64 | 1.3% | 4.26 | 3.4% | 2.02 | 1.6% | 4.71 | 3.8% |
| CTL1
MB2 | 9.08 | 0.20 | 2.2% | 0.12 | 1.3% | 0.23 | 2.5% | 0.33 | 3.6% | 0.40 | 4.4% |
| CTL2
MB2 | 36.54 | 1.03 | 2.8% | 0.00 | 0.0% | 1.03 | 2.8% | 1.32 | 3.6% | 1.67 | 4.6% |
| CTL3
MB2 | 93.43 | 2.93 | 3.1% | 3.61 | 3.9% | 4.65 | 5.0% | 0.00 | 0.0% | 4.65 | 5.0% |
| CV 1
MB2 | 8.96 | 0.20 | 2.2% | 0.12 | 1.4% | 0.23 | 2.6% | 0.29 | 3.3% | 0.37 | 4.2% |
| CV 2
MB2 | 90.58 | 2.68 | 3.0% | 2.86 | 3.2% | 3.92 | 4.3% | 0.37 | 0.4% | 3.94 | 4.3% |
| CV 3
MB2 | 201.67 | 7.49 | 3.7% | 4.90 | 2.4% | 8.95 | 4.4% | 2.56 | 1.3% | 9.31 | 4.6% |
| IQC 1 | 5.57 | 0.09 | 1.7% | 0.06 | 1.1% | 0.11 | 2.0% | 0.20 | 3.5% | 0.23 | 4.1% |
| IQC 2 | 52.45 | 1.24 | 2.4% | 0.92 | 1.8% | 1.55 | 2.9% | 0.87 | 1.7% | 1.77 | 3.4% |
| IQC 3 | 96.82 | 2.76 | 2.8% | 0.43 | 0.4% | 2.79 | 2.9% | 1.26 | 1.3% | 3.06 | 3.2% |
| Sample
1 | 16.56 | 0.28 | 1.7% | 0.14 | 0.9% | 0.32 | 1.9% | 0.51 | 3.1% | 0.60 | 3.6% |
| Sample
2 | 85.46 | 2.15 | 2.5% | 0.00 | 0.0% | 2.15 | 2.5% | 1.63 | 1.9% | 2.70 | 3.2% |
| Sample
3 | 38.81 | 0.69 | 1.8% | 0.40 | 1.0% | 0.80 | 2.1% | 0.93 | 2.4% | 1.22 | 3.2% |
Results from one representative lot:
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Image /page/12/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters "ids" in a stylized, lowercase font, with a red circle above the "i". Below the letters "ids" is the word "immunodiagnosticsystems" in a smaller, lowercase font, with the "immuno" portion in red and the rest in gray. The overall design is clean and modern.
b. Linearity/assay reportable range:
For the measuring range, a linearity study was conducted based on guidance from the CLSI EP6-A. A high human serum sample and a low human serum sample (low serum sample diluted in zero matrix) were analysed in addition to 14 evenly spaced dilutions which were created by mixing the high and low sample as indicated below:
| Sample | Dilution | Dilution Factor (%) |
|---|---|---|
| 1: | Low (L) | 0 |
| 2: | 0.995L + 0.005H | 0.5 |
| 3: | 0.99L + 0.01H | 1 |
| 4: | 0.9875L + 0.0125H | 1.25 |
| 5: | 0.975L + 0.025H | 2.5 |
| 6: | 0.95L + 0.05H | 5 |
| 7: | 0.90L + 0.10H | 10 |
| 8: | 0.80L + 0.20H | 20 |
| 9: | 0.70L + 0.30H | 30 |
| 10: | 0.60L + 0.40H | 40 |
| 11: | 0.50L + 0.50H | 50 |
| 12: | 0.40L + 0.60H | 60 |
| 13: | 0.30L + 0.70H | 70 |
| 14: | 0.20L + 0.80H | 80 |
| 15: | 0.10L + 0.90H | 90 |
| 16: | High (H) | 100 |
Serum:
Observed = 1.00 x (expected) -0.54 nmol/L Regression coefficient R2: 0.999
K2 EDTA plasma:
Observed = 0.97 x (expected) -0.46 nmol/L Regression coefficient R2: 0.998
The measuring range is defined as the range of values the instrument can report directly without sample dilution. The reportable range is the range of values the instrument can report as a quantitative result with sample dilution.
The IDS SHBG assay is linear over the measuring range from 1.60 to 180.00 nmol/L. The IDS SHBG assay is also linear across the reportable range of the assay which is 0.30 to 720.00 nmol/L when any sample with SHBG concentrations above 180nmol/L is automatically diluted 1:4 by the iSYS System
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Image /page/13/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters 'ids' in a stylized, interconnected design, with a red circle above the 'i'. Below the letters, the words 'immunodiagnosticsystems' are written in red, completing the company's name. The overall design is modern and clean, emphasizing the company's focus on immunodiagnostics.
To support the extended measuring range up to 720 nmol/L through the automated dilution by the analyzer, the guideline CLSI EP34 1st ed. was followed.
Nine native samples with known SHBG concentration (obtained on the predicate device Siemens Advia Centaur SHBG assay) were tested on the iSYS using the automated postdilution. Samples were tested in a single replicate on one kit lot.
When testing on the predicate device, samples above 180nmol/L were automatically 1:2 by the automate. If samples were still above the measurement range, the samples were manually diluted 1:5.
The accuracy of the IDS-iSYS system to read samples above 180 nmol/L using the automatic dilution is evaluated by calculating the recovery between IDS and Siemens Advia Centaur assays as below:
% Recovery = (SHBG estimate on iSYS / SHBG concentration on predicate) x 100
| sample ID | IDS run 1 | Predicate | %
recovery |
|-----------|---------------|-----------|---------------|
| sample 1 | 288.19 | 310.24 | 93% |
| sample 2 | 327.17 | 352.32 | 93% |
| sample 3 | 274.71 | 291.04 | 94% |
| sample 4 | 294.01 | 294.34 | 100% |
| sample 5 | 507.35 | 573.23 | 89% |
| sample 6 | 484.94 | 555.05 | 87% |
| sample 7 | 569.31 | 610.95 | 93% |
| sample 8 | 287.53 | 317.10 | 91% |
| sample 9 | 686.73 | 726.84 | 94% |
| | Mean recovery | | 93% |
between IDS and Siemens Advia centaur (predicate) assays
Table 1: Comparison of SHBG concentration of diluted samples
Conclusion
A recovery of between 87% to 100% was achieved.
IDS SHBG assay shows good accuracy when measuring samples in the range 180 - 720 nmol/L using the automatic dilution.
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Image /page/14/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters 'ids' in a stylized, connected font, with a red circle above the 'i'. Below the letters, the words 'immunodiagnosticsystems' are written in a smaller, red font. The overall design is clean and modern, suggesting a company focused on diagnostics.
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
Traceability of calibrator to a reference material
The standardization of the IDS SHBG assay against the WHO 2nd international standard 08/266 was carried out in two phases, value assignment and verification, as described below:
Value assignment of kit calibrators
This phase includes the value assignment of the secondary standards (Internal reference calibrators, IRs). The candidate secondary standards (IRs) are value assigned directly to the WHO NIBSC 2nd international standard for SHBG (IS 08/266) through an internal QC procedure: at least 24 runs are performed using three iSYS instruments, 2 kit lots, 3 replicates for each run. Serial dilutions of the IS 08/266 in SHBG-depleted human serum are used as the reference to assign IR values.
The IDS SHBG kit calibrators A and B and master curve are value assigned off the secondary standards and the IS-08/266 through an internal OC procedure. At least 20 runs (14 runs using the previous IR lot - 6 runs using the international standard as the reference) are performed using one iSYS instrument, 2 replicates for each run.
Value assignment verification
The kit calibrator A and B values are then verified on three different iSYS instruments following an approved OC procedure by testing internal quality controls in five replicates in one run and on each instrument.
Internal quality controls are at 3 SHBG levels:
- IQC 1 between 5.00 and 8.00 nmol/L
- IQC 2 between 45.00 and 65.00 nmol/L ●
- IQC 3 between 80.00 and 120.00 nmol/L ●
Acceptance Criteria
The values of the calibrators must fall within specified acceptable ranges:
- Calibrator A between 0.10 to 0.30 nmol/L precision CV ≤ 11% ●
- Calibrator B between 110.00 to 130.00 nmol/L precision CV ≤ 8% ●
Internal quality controls must be within their respective ranges with a precision CV ≤ 11% for IQC1 and ≤ 8% for IQC2 and IQC3.
Traceability to the NIBSC 2nd IS 08/266
A correlation study is also performed between the results obtained when using the 2-point calibration and the results derived from the international standard IS 08/266 curve.
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Image /page/15/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters 'ids' in a stylized, connected font, with a red circle above the 'i'. Below the letters, the words 'immunodiagnosticsystems' are written in a smaller, red font. The overall design is clean and modern.
189 samples (139 serum - 50 K2 EDTA plasmas) were tested in two replicates using three lots (MB1, MB2 and MB3) on one iSYS instrument. Their concentrations were derived from the 2-point calibration and compared to the concentration calculated by using a serial dilution of the NIBSC 2nd international standard 08/266 (from 180 nmol/L to 0 nmol/L using SHBG depleted human serum). Results were analysed using Passing Bablok analysis on Analyse-it.
d. Detection limit:
The limit of blank (LoB), limit of detection (LoD) and limit of quantitation (LoQ) were determined based on guidance from CLSI EP17-A2 "Protocols for the determination of limits of detection and limits of quantitation".
The statistical approach used when calculating Detection limits are:-
The equations used in Analyse-It are:
- LoB Lc = z(1-a)σ is the same as MB + CpSDB —
- LoD LD = Lc + Z(1-b)o is the same as LoB + cpSDL -
EP17-A2 formula:
- Formula (2), page 25: LoB= MB + CpSDB ー
- Formula (5), page 27: LoD = LoB + CB SDt
For the measurement of LoB, LoD and LoQ three manufacture batches (MB1, MB2B and MB3) were tested.
The LoB sample was run in 12 replicates for each of 5 runs over 3 days, by one operator and on one different instrument for each kit lot for a total of 60 replicates per lot. Where two assays were performed in one day the set-up time between assays start time was at least 2 hours.
Each of the 7 LoD samples was measured in duplicate. For each kit lot, a total of 5 assays were run over 3 days by one operator and on a different instrument, for a total of 70 replicates. Where two assays were performed in one day the set- up time between assays start time was at least 2 hours.
For calculation of The LoO panel of 9 samples were measured in singlicate two times per day. For each kit lot, a total of 10 assays were run over 5 days by one operator and on a different instrument, for a total of 90 replicates. Where two assays were performed in one day the set- up time between assays start time was at least 2 hours.
| Sensitivity | Concentration |
|---|---|
| LoB | 0.01 nmol/L |
| LoD | 0.15 nmol/L |
| LoQ | 0.30 nmol/L |
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Image /page/16/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters "ids" in a stylized, rounded font, with a red circle above the "i". Below the letters, the words "immunodiagnosticsystems" are written in a smaller, sans-serif font. The overall design is clean and modern.
e. Analytical specificity:
Interference and cross-reactivity studies were performed in accordance with the CLSI guidance EP7-A2"Interference testing in clinical chemistry".
To determine potential interference in the specific detection of SHBG, two serum samples at two different concentrations of SHBG were spiked with the potential interferent. Control samples (blank) for each of the two SHBG samples were spiked with a volume of relevant diluent equal to that of the spiked interferent. The mean concentration of the 26 replicate assays, determined for both the spiked and control samples, were then compared. The differences observed between the mean spiked and control sample values were examined and assessed according to acceptance criteria.
For total cholesterol the interference was tested by dilution of a high cholesterol native serum sample in zero matrix (SHBG depleted normal human serum) and calculation of the observed vs expected SHBG concentration.
% Interference was calculated using the formula below:
% Interference = (mean spiked concentration - mean un-spiked concentration) x 100 mean un-spiked concentration
% Observed/Expected (%O/E) was calculated using the formula below:
| % O/E= (observed mean concentration - expected concentration) x 100 | |
|---|---|
| expected concentration | |
| The following table provides the levels of interferents tested. |
| Potential interferents | Highest concentration
tested that
demonstrated no
significant interference |
|-------------------------|-------------------------------------------------------------------------------------|
| Triglycerides | 3000 mg/dL |
| Haemoglobin | 500 mg/dL |
| Bilirubin, conjugated | 40 mg/dL |
| Bilirubin, unconjugated | 40 mg/dL |
| Total Protein | 12 g/dL |
| Biotin | 6000 ng/mL |
| Biotin | 1500 ng/mL |
| Rheumatoid Factor | 7000 IU/mL |
| HAMA | 3000 ng/mL |
| Cholesterol | 456 mg/dL |
| Acetaminophen | 1324 $ \mu $ mol/L |
| Acetylsalicylic acid | 3.62 nmol/L |
| Salicylic acid | 4.34 mmol/L |
| Ibuprofen | 2425 $ \mu $ mol/L |
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Image /page/17/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters 'ids' in a stylized, connected, sans-serif font, with a red circle above the 'i'. Below the 'ids' is the text 'immunodiagnosticsystems' in a smaller, sans-serif font, with the same red color as the circle above.
| Ascorbic acid (Vit C) | 1700 µmol/L |
|---|---|
| Creatinine | 2.65 mmol/L |
| Dopamine | 850 µmol/L |
| Tetracycline | 90 µmol/L |
| Tolbutamide | 3.7 mmol/L |
| Tolazamide | 3.21 mmol/L |
| Uric Acid | 1.4 mmol/L |
Cross-reactivity testing was performed for alpha fetoprotein, cortisol, 11-deoxycortisol, estradiol, testosterone, 5-dihydrotestosterone, thyroglobulin, thyroxin binding globulin, transferrin, TSH, Human IgA, human IgG, plasminogen, fibrinogen and corticosteroid binding globulin.
Cross-reactants were prepared by manufacturing a 'top dose' of the relevant analyte which was then diluted down to a range of stock concentrations in undetectable SHBG matrix (serum based zero matrix). The stock cross reactant or zero matrix was spiked directly into a low sample and a high SHBG sample. The cross reactivity was then determined using the below equation
% cross reactivity = (Mean conc. of spiked sample – mean conc. of un-spiked sample) x100% Spike concentration
| Cross Reactant | Spike Concentration | % Cross Reactivity in
samples less than 30 | % Cross Reactivity
in samples between
55 and 130 |
|---------------------------------|---------------------|-----------------------------------------------|--------------------------------------------------------|
| AFP | 5000 ng/mL | -0.3% | 0.5% |
| Thyroglobulin | 3000 ng/mL | 5.1% | 90.2% |
| Thyroxin binding globulin | 200 µg/mL | 0.0% | -0.1% |
| Transferrin | 4 mg/mL | 0.0% | 0.0% |
| Cortisol | 100000 ng/mL | 0.0% | 0.0% |
| 11-deoxycortisol | 4000 ng/mL | 0.0% | -0.1% |
| 5a-dihydroxytestosterone | 20000 ng/mL | 0.0% | 0.0% |
| Estradiol | 3600 pg/mL | -7.3% | -3.2% |
| Testosterone | 20000 ng/mL | 0.0% | 0.0% |
| Fibrinogen | 4.5 g/L | 0.0% | 0.0% |
| Corticosteroid binding globulin | 35 mg/dL | 0.0% | 0.0% |
| Thyrotropin (TSH) | 180 mIU/mL | 0.0% | 0.0% |
| Plasminogen | 250 mg/L | 0.0% | 0.0% |
| Human IgA | 367 mg/dL | 0.0% | 0.0% |
The following table provides the levels of cross-reactants tested.
18
| Immunodiagnosticsystem | |||
|---|---|---|---|
| Human IgG | 335 mg/dL | 0.0% | 0.0% |
f. Assay cut-off:
Not applicable
2. Comparison studies:
Method comparison:
The IDS SHBG assay was compared against a commercially available quantitative automated assay, following CLSI EP-9A3, "Method Comparison and Bias Estimation Using Patient Samples". A total of 136 samples, selected to represent a wide range of SHBG concentrations [sample concentration range: 2.54 - 172.12 nmol/L (0.24 - 16.35 ug/mL)], was assayed by each method. Passing-Bablok regression analysis was performed on the comparative data:
| N | Slope | 95% CI | Intercept | 95% CI | Correlation
Coefficient
(r) |
|-----|--------|--------------|-------------------------------------|----------------------------------------------|-----------------------------------|
| 136 | 0.9112 | 0.88 to 0.94 | 0.1556
nmol/L
(-0.0148 µg/mL) | -0.35 to 0.9 nmol/L
(-0.03 to 0.85 µg/mL) | 0.989 |
Matrix comparison:
The IDS SHBG matrix comparison study was performed to evaluate the difference across tube types (serum (without additives), serum gel separator tubes (TG), and K2 EDTA plasma.) following the CLSI EP9-A3 guideline.
A total of 69 samples (68 native, 1 diluted) to cover the range of 0.51 to 238.45 mol/L. Passing-Bablok regression analysis was performed on the comparative data:
| Sample matrix | Gel tube | K2 EDTA |
|---|---|---|
| n | 69 | 69 |
| Slope | 1.019 | 0.9854 |
| Intercept | 0.4897 | 0.0308 |
| r | 0.999 | 0.998 |
| Mean bias v | ||
| Serum | 0.7% | -1.3% |
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Image /page/19/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters 'ids' in a stylized, lowercase font, with a red circle above the 'i'. Below the 'ids' is the text 'immunodiagnosticsystems' in a smaller, red font. The 'ids' letters are in gray.
3. Expected values/Reference range:
The expected values were calculated using Analyse-it. Results were analysed to generate a nonparametric 95 % reference interval using the 2.5th and 97.5th percentiles as reference limits.
The package insert recommends considering "the above ranges as guidelines only; it is recommended that each laboratory establish its own expected range based upon its own patient population.
The expected values were assessed by using 671 serum samples from the United States in which the subjects were apparently healthy adults and aged between 21 and 77 years old.
| | Males
21 – 49
years | Males
50 years | Females
premenopausal | Females
postmenopausal |
|-----------------------------------------------|---------------------------|---------------------|--------------------------|---------------------------|
| Number of subjects | 165 | 180 | 206 | 120 |
| Mean nmol/L | 29.74 | 35.32 | 54.37 | 52.11 |
| Median nmol/L | 28.39 | 33.92 | 46.35 | 48.48 |
| Observed 2.5th to 97.5th
percentile nmol/L | 11.47 –
58.07 | 14.85 –
65.21 | 20.30 –
140.18 | 11.30 – 127.31 |
The observed ranges were established, according to CLSI C28-A3c "Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory" is summarised in the table below:
| | Males
21 – 49 years | Males
50 years | Females
premenopausal | Females
postmenopausal |
|----------------------------------------------|------------------------|---------------------|--------------------------|---------------------------|
| Number of subjects | 165 | 180 | 206 | 120 |
| Mean µg/mL | 2.83 | 3.36 | 5.17 | 4.95 |
| Median µg/mL | 2.70 | 3.22 | 4.40 | 4.61 |
| Observed 2.5th to 97.5th
percentile µg/mL | 1.09 –
5.52 | 1.41 –
6.19 | 1.93 – 13.32 | 1.07 – 12.09 |
The above ranges should be considered as guidelines only; it is recommended that each laboratory establish its own expected range based upon its own patient population.
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Image /page/20/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters 'ids' in a stylized, connected font, with a red circle above the 'i'. Below the letters, the words 'immunodiagnosticsystems' are written in a smaller, red font.
Conclusion:
The IDS SHBG data presented and provided is complete and supports the basis for substantial equivalence to the predicate device.