(143 days)
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
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.
The provided document is a 510(k) summary for the IDS SHBG assay, an in vitro diagnostic device for the quantitative determination of Sex Hormone Binding Globulin (SHBG). The document details the device's performance characteristics and compares it to a predicate device to demonstrate substantial equivalence.
Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text:
Key Takeaway: This document describes the validation of an in vitro diagnostic (IVD) assay, not an AI/ML-based diagnostic device that typically involves human readers or image analysis. Therefore, many of the requested categories (e.g., number of experts, adjudication method, MRMC studies, human reader improvement with AI, standalone AI performance) are not applicable to this type of device and study. The ground truth in this context is established by reference methods or validated reference materials, typical for IVD assays.
1. Table of Acceptance Criteria and Reported Device Performance
The document describes several analytical performance characteristics that serve as "acceptance criteria" for the IDS SHBG assay. These are primarily related to the accuracy, precision, limits of detection, and specificity of the assay.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Precision (Reproducibility) | Within-run and total precision (CV%) to be within acceptable limits for a quantitative assay. | Within Run CV: 1.7% to 3.7% across various SHBG concentration levels (e.g., IQC 1: 1.7% at 5.57 nmol/L; CV 3: 3.7% at 201.67 nmol/L). Total CV: 3.2% to 5.0% across various SHBG concentration levels (e.g., IQC 3: 3.2% at 96.82 nmol/L; CTL3: 5.0% at 93.43 nmol/L). (Compared favorably to predicate which reported 2.5-3.8% within run and 3.1-6.5% total precision.) |
| Linearity/Reportable Range | Assay to be linear over its claimed measuring range; accuracy demonstrated for automated dilution. | Measuring Range: Linear from 1.60 to 180.00 nmol/L for serum and K2 EDTA plasma (R2 values of 0.999 and 0.998 respectively). Reportable Range: 0.30 to 720.00 nmol/L with automated 1:4 dilution for samples >180 nmol/L. Recovery (Automated Dilution): 87% to 100% when compared to predicate for samples in the 180-720 nmol/L range (Mean recovery: 93%). |
| Detection Limits (LoB, LoD, LoQ) | Limits should be sufficiently low to meet diagnostic needs. | LoB: 0.01 nmol/L LoD: 0.15 nmol/L LoQ: 0.30 nmol/L |
| Traceability of Calibrator | Calibrator values must fall within specified acceptable ranges and internal quality controls within their respective ranges with defined precision. | Calibrator A: 0.10 to 0.30 nmol/L, precision CV ≤ 11%. Verified through internal QC procedures. Calibrator B: 110.00 to 130.00 nmol/L, precision CV ≤ 8%. Verified through internal QC procedures. Internal QC controls: CV ≤ 11% for IQC1, ≤ 8% for IQC2 and IQC3. Results from Table 11 show these were met (e.g., IQC1 Total CV 4.1%, IQC2 Total CV 3.4%, IQC3 Total CV 3.2%). |
| Analytical Specificity (Interference) | No significant interference from common biological substances and exogenous compounds up to tested concentrations. | No significant interference found for: - Triglycerides: up to 3000 mg/dL - Haemoglobin: up to 500 mg/dL - Bilirubin (conjugated/unconjugated): up to 40 mg/dL - Total Protein: up to 12 g/dL - Biotin: up to 6000 ng/mL (and 1500 ng/mL) - Rheumatoid Factor: up to 7000 IU/mL - HAMA: up to 3000 ng/mL - Cholesterol: up to 456 mg/dL - Various common drugs (e.g., Acetaminophen, Ibuprofen, Ascorbic acid, Creatinine, Dopamine, Tetracycline, Tolbutamide, Tolazamide, Uric Acid). |
| Analytical Specificity (Cross-Reactivity) | No significant cross-reactivity with structurally similar compounds or other biological substances up to tested concentrations. | Low/No significant cross-reactivity observed (<1% typically) for: - AFP (-0.3% to 0.5%) - Thyroxin binding globulin (0.0% to -0.1%) - Transferrin (0.0%) - Cortisol (0.0%) - 11-deoxycortisol (0.0% to -0.1%) - 5a-dihydroxytestosterone (0.0%) - Testosterone (0.0%) - Fibrinogen (0.0%) - Corticosteroid binding globulin (0.0%) - Thyrotropin (TSH) (0.0%) - Plasminogen (0.0%) - Human IgA (0.0%) - Human IgG (0.0%) Notable exceptions: Estradiol (-7.3% to -3.2%) and Thyroglobulin (5.1% to 90.2%), where the higher value indicates specific interference for Thyroglobulin. |
| Method Comparison | Good correlation and agreement with a predicate device. | Correlation Coefficient (r): 0.989 (n=136 samples, range 2.54 - 172.12 nmol/L). Passing-Bablok Regression: Slope 0.9112, Intercept 0.1556 nmol/L. |
| Matrix Comparison | Performance across different sample matrices (serum, serum gel, K2 EDTA plasma) should be comparable. | Good correlation: - Gel tube vs. Serum: r=0.999, Mean bias 0.7% - K2 EDTA vs. Serum: r=0.998, Mean bias -1.3% (n=69 samples, range 0.51 to 238.45 nmol/L) |
| Expected Values/Reference Range | Established typical ranges for different populations. | Males 21-49y: 11.47 – 58.07 nmol/L (n=165) Males >50y: 14.85 – 65.21 nmol/L (n=180) Premenopausal Females: 20.30 – 140.18 nmol/L (n=206) Postmenopausal Females: 11.30 – 127.31 nmol/L (n=120) (Based on 671 apparently healthy adults from the United States). |
2. Sample Size Used for the Test Set and Data Provenance
- Precision/Reproducibility: 14 serum-based samples at different SHBG concentration levels covering the assay range. Tested across 21 days for one kit lot. (Table 11 shows individual sample IDs, CTLs, CALBs, IQCs)
- Linearity/Assay Reportable Range:
- Linearity: A high human serum sample and a low human serum sample, plus 14 evenly spaced dilutions created by mixing high and low samples.
- Automated Post-dilution Accuracy: 9 native samples with known SHBG concentrations obtained from the predicate device.
- Traceability of Calibrator:
- Value assignment of Internal Reference Standards (IRs): At least 24 runs using three iSYS instruments, 2 kit lots, 3 replicates for each run. Serial dilutions of WHO 2nd international standard 08/266 used.
- Value assignment of kit calibrators: At least 20 runs (14 runs using previous IR lot, 6 runs using international standard) using one iSYS instrument, 2 replicates for each run.
- Value assignment verification: Internal quality controls at 3 SHBG levels tested in five replicates in one run and on each of three different iSYS instruments.
- Correlation study (2-point calibration vs. IS 08/266 curve): 189 samples (139 serum, 50 K2 EDTA plasmas). Tested in two replicates using three lots (MB1, MB2, MB3) on one iSYS instrument.
- Detection Limit (LoB, LoD, LoQ):
- LoB: LoB sample run in 12 replicates for each of 5 runs over 3 days, by one operator, on one different instrument for each of 3 manufacture batches (MB1, MB2B, MB3) = total 60 replicates per lot.
- LoD: 7 LoD samples measured in duplicate. For each of 3 kit lots, 5 assays over 3 days by one operator on a different instrument = total 70 replicates per lot.
- LoQ: Panel of 9 samples measured in singlicate two times per day. For each of 3 kit lots, 10 assays over 5 days by one operator on a different instrument = total 90 replicates per lot.
- Analytical Specificity (Interference): Two serum samples (low and high SHBG conc.) spiked with potential interferents. Control samples were also run. Number of replicates for each specific test not detailed but implied to be sufficient for statistical comparison.
- Analytical Specificity (Cross-Reactivity): Low and high SHBG samples spiked with various cross-reactants. Number of replicates for each specific test not detailed.
- Method Comparison: 136 samples, selected to represent a wide range of SHBG concentrations (2.54 - 172.12 nmol/L).
- Matrix Comparison: 69 samples (68 native, 1 diluted) covering a range of 0.51 to 238.45 nmol/L.
- Expected Values/Reference Range: 671 serum samples from apparently healthy adults (21-77 years old). Data Provenance: From the United States. Retrospective/Prospective: Not explicitly stated, but typically such studies for establishing reference ranges are retrospective collections of banked samples or a prospective study designed to collect samples from a healthy population.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
Not Applicable (N/A).
This is an in vitro diagnostic (IVD) assay quantifying a biomarker (SHBG). "Ground truth" for an IVD assay is established through:
- Reference Methods: Such as the WHO 2nd international standard 08/266 for SHBG, against which the calibrators are standardized.
- Known Concentrations: Use of accurately prepared standards, spiked samples, or samples extensively characterized by reference methods.
- Clinical Data: For expected values, SHBG concentrations are measured in samples from defined healthy populations.
Therefore, the concept of "experts establishing ground truth" in the way it applies to image interpretation or AI-assisted diagnostics (e.g., radiologists labeling images) is not relevant here. The ground truth is analytical and based on metrological traceability to international standards.
4. Adjudication Method for the Test Set
N/A.
Adjudication methods (like 2+1, 3+1) are relevant for subjective interpretations (e.g., radiology reads) where discrepancies between readers need to be resolved to establish a definitive ground truth. For a quantitative IVD assay like IDS SHBG, the "reading" is a numerical output from the instrument based on chemical reactions. Accuracy is determined by comparison to reference materials or established methods, not by human adjudication of interpretations.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
N/A.
This is an IVD assay, not an AI/ML diagnostic for human interpretation. No MRMC study or human reader improvement with AI assistance is applicable.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
N/A.
This is not an AI/ML algorithm. The "device" is a fully automated immunoassay system (IDS-iSYS Multi-Discipline Automated System) that performs the biochemical analysis and reports a quantitative result without human "interpretation" of a signal beyond reading the numerical output. Its performance is evaluated as a standalone analytical system.
7. The Type of Ground Truth Used
The ground truth for the analytical performance studies (precision, linearity, detection limits, specificity, method comparison) is based on:
- International Reference Standards: Specifically, the WHO 2nd international standard for SHBG (IS 08/266) for traceability and calibration. This is the primary reference.
- Known Concentrations/Spiked Samples: Samples with defined, known concentrations of SHBG or interferents, prepared in a laboratory setting.
- Comparison to a Legally Marketed Predicate Device: The Siemens ADVIA Centaur SHBG assay (K151986) was used as a comparative method to assess agreement and accuracy (e.g., for method comparison and automated dilution accuracy).
- Healthy Population Data: For expected values/reference ranges, a large cohort of apparently healthy individuals were tested to establish population-specific normal ranges.
8. The Sample Size for the Training Set
N/A (for AI/ML 'training set' in the traditional sense).
For an IVD assay, the equivalent of a "training set" would be the samples and calibrators used during the assay's development and optimization phases to set parameters, establish reagent formulations, and fine-tune the system. This information is typically proprietary development data and is not explicitly detailed as a 'training set' in 510(k) summaries, which focus on the final validation/test data.
The closest analogous "training" or "calibration" process mentioned is the traceability and value assignment of calibrators:
- Value assignment of secondary standards (IRs) involves at least 24 runs (using 3 instruments, 2 kit lots, 3 replicates) comparing to the WHO international standard.
- Value assignment of IDS SHBG kit calibrators A and B involves at least 20 runs (1 instrument, 2 replicates) using the secondary standards and IS-08/266.
These processes are used to establish the calibration curve for the assay.
9. How the Ground Truth for the Training Set Was Established
N/A (for AI/ML 'training set').
As explained in point 8, the concept of a "training set" for an IVD assay is different from that for AI/ML. The "ground truth" for establishing the calibration and parameters of the assay is based on:
- Metrological traceability to the WHO 2nd international standard for SHBG (IS 08/266). This involved serial dilutions of the international standard in SHBG-depleted human serum to create reference points.
- Use of internal reference calibrators (IRs) that were themselves value-assigned against the WHO standard.
The goal is that the assay's measurements accurately reflect the true concentration of SHBG as defined by an international reference.
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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 followinginformation provides sufficient detail to understand the basis for adetermination of substantial equivalence. | |
| Submitter | Immunodiagnostic Systems Ltd10 Didcot WayBoldon Business ParkBoldonTyne and WearNE35 9PDUnited KingdomContact Person: Mick HendersonPhone: +44 191 5190660Fax: +44 191 5190760Email: mick.henderson@idsplc.comSecondary Contact: Jenny ManolopoulouPhone: +44 191 5190660Fax: +44 191 5190760Email: jenny.manolopoulou @idsplc.comDate 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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- 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 DeviceADVIA Centaur SHBG (K151986) | Candidate DeviceIDS SHBG |
|---|---|---|
| Intended use | for use as an aid in the diagnosis ofandrogen 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 ofdetection (Testmethodology) | Chemiluminescent Magnetic LatexParticle Immunoassay | Same |
| Automation | Fully automated assay | Same |
| Quality Control | Requires three controls to validate thecalibration | Same |
| Calibrationprocedure | 2 point calibration | Same |
| Traceability/Standardization | Standardised to WHO 2ndInternational Standard (08/266) | Same |
| Specificity,Interferingsubstances & Cross | InterferenceHaemoglobinNo Interference up to 500 mg/dL | InterferenceHaemoglobinSame |
| Reactivity | Cross Reactivity | Cross Reactivity |
| CortisolNot detectable | CortisolSame | |
| 5α-dihydroxytestosteroneNot detectable | 5α-dihydroxytestosteroneSame | |
| TestosteroneNot detectable | TestosteroneSame | |
| FibrinogenNot detectable | FibrinogenSame | |
| PlasminogenNot detectable | PlasminogenSame | |
| Human IgANot detectable | Human IgASame | |
| Human IgGNot detectable | Human IgGSame | |
| Corticosteroid binding globulinNot detectable | Corticosteroid bindingglobulinSame | |
| Thyrotropin (TSH)Not detectable | Thyrotropin (TSH)Same |
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Differences compared to the chosen predicate device (K151986)
| Performance | Predicate DeviceADVIA Centaur SHBG(K151986) | Candidate DeviceIDS SHBG |
|---|---|---|
| Indications for Use | The ADVIA Centaur SHBGassay is an in vitro diagnosticimmunoassay for thequantitative determination ofsex hormone-binding globulin(SHBG) in human serum andplasma using the ADVIACentaur XP system. | The IDS SHBG assay is an in vitro diagnostic device intendedfor the quantitativedetermination of SHBG inhuman serum or plasma on theIDS System. Results are to beused as an aid in the diagnosisof androgen disorders. |
| Calibrator matrix | Equine serum | Human serum |
| Sample matrix(primary tube type) | Human Serum, plasma (lithiumheparin) | Human serum, Plasma (K2EDTA) |
| Sample volume | 10µL | 5µL |
| Kit reagentcomponents | Each SHBG Ready Packcontains: 1) Solid Phase (11.0mL) streptavidin coupledmagneticlatex particles (~150 µg/mL), 2)Lite Reagent (3.0 mL)containing mouse monoclonalanti-SHBG antibody (~130 µg/mL)labeled with acridinium ester,and 3) Ancillary Well Reagent(3.0 mL) containing abiotinylated monoclonal mouseanti-SHBG antibody (~6µg/mL) | Reagent cartridge (1 vial each ofMPT1, CONJ, Ab-BIOT &DIL), two concentration levelsof calibrators (A&B) (1 vial ofeach) & a mini CD |
| Each Ready Pack containsreagents for 50 tests. | ||
| Kit reagentcomponentvolumes | 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 theanalyzer reagentstability | 60 days | 14 days |
| Sensitivity | LoB: 1.2 nmol/LLoD: 1.6 nmol/LLoQ: 1.8 nmol/L | LoB: 0.01 nmol/LLoD: 0.15 nmol/LLoQ: 0.30 nmol/L |
| Expected values | Males 21 to 49 years14.55 to 94.64 nmol/LMales > 50 years21.63 to 113.13 nmol/LPremenopausal Females10.84 to >180.00 nmol/LPostmenopausal Females23.15 to 159.07 nmol/L | Males 21 to 49 years11.47 to 58.07 nmol/LMales > 50 years14.85 to 65.21 nmol/LPremenopausal Females20.30 to 140.18 nmol/LPostmenopausal Females11.30 to 127.31 nmol/L |
| Precision | Within Run Precision n = 402.5% to 3.8% in theconcentration range 9.04 to142.87 nmol/LTotal Precision n = 403.1% to 6.5% in theconcentration range 9.04 to142.87 nmol/L | Within Run Precision n = 841.7% to 3.7% in theconcentration range 5.57 to201.67 nmol/LTotal Precision n = 843.2% to 5.0% in theconcentration range 5.57 to201.67 nmol/L |
| Specificity,Interferingsubstances & CrossReactivity | InterferenceBilirubin, conjugatedNo Interference up to 20 mg/dLBilirubin, unconjugatedNo Interference up to 20 mg/dLBiotinNo Interference up to 100 ng/mLCholesterol, totalNo ClaimHuman Anti Mouse Antibody(HAMA)No Claim | InterferenceBilirubin, conjugatedNo Interference up to 40 mg/dLBilirubin, unconjugatedNo Interference up to 40 mg/dLBiotinNo Interference up to 1200ng/mLCholesterol, totalNo Interference up to 456 mg/dLHuman Anti Mouse Antibody(HAMA)No Interference up to 3000ng/mL |
| immunodiagnostiosystems | ||
| Rheumatoid FactorNo Claim | Rheumatoid FactorNo Interference up to 7000IU/mL | |
| Total ProteinNo Claim | Total ProteinNo Interference up to 12 g/dL | |
| TriglycerideNo Interference up to 1000mg/dL | TriglycerideNo Interference up to 3000mg/dL | |
| AcetaminophenNo Claim | AcetaminophenNo Interference up to 1324µmol/L | |
| IbuprofenNo Claim | IbuprofenNo Interference up to 2425µmol/L | |
| Ascorbic acidNo Claim | Ascorbic acidNo Interference up to 1700µmol/L | |
| Acetylsalicylic acidNo Claim | Acetylsalicylic acidNo Interference up to 3.62nmol/L | |
| Salicylic acidNo Claim | Salicylic acidNo Interference up to 4.34mmol/L | |
| CreatinineNo Claim | CreatinineNo Interference up to 2.65mmol/L | |
| DopamineNo Claim | DopamineNo Interference up to 850µmol/L | |
| TetracyclineNo Claim | TetracyclineNo Interference up to 90 µmol/L | |
| TolbutamineNo Claim | TolbutamineNo Interference up to 3.7mmol/L | |
| TolazamideNo Claim | TolazamideNo Interference up to 3.21mmol/L | |
| Uric acidNo Claim | Uric acidNo Interference up to 1.4mmol/L | |
| Specificity,Interferingsubstances & CrossReactivity | Cross ReactivityAFPNot detectable | Cross ReactivityAFP0.5 % |
| ThyroglobulinNot detectable | Thyroglobulin90.2 % | |
| Thyroxin binding globulinNot detectable | Thyroxin binding globulin-0.1 % | |
| Transferrin0.04 % | Transferrin0.0 % | |
| 11-deoxycortisol0.24 % | 11-deoxycortisol-0.1 % | |
| EstradiolNot detectable | Estradiol-7.3 % | |
| Method comparison | Against the Elecsys SHBGassayn = 194Linear RegressionADVIA Centaur SHBG =$0.99(Elecsys) – 0.11$ nmol/LCorrelation coefficient (r) =0.99 | Against the ADVIA CentaurSHBG assay.N = 136Passing Bablok regressionIDS SHBG = $0.9112$ (ADVIACentaur SHBG) $0.1556$ nmol/LCorrelation coefficient (r) =0.989 |
| Linearity | Weighted Linear regression ofthe observed concentrationsversus the expectedconcentrations: Observed =$0.984$ x (Expected) +$0.245$ ng/dL | Linear regression of theobserved concentrations versusthe expected concentrations:SerumObserved = $1.00$ x (Expected) -$0.54$ nmol/LRegression of coefficient (R2) =$0.999$K2 EDTAObserved = $0.97$ x (Expected) -$0.46$ nmol/LRegression 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 | WithinRun SD | WithinRun CV | BetweenRun SD | BetweenRun CV | WithinDay SD | WithinDay CV | BetweenDay SD | BetweenDay CV | TotalSD | TotalCV |
|---|---|---|---|---|---|---|---|---|---|---|---|
| CALBMB2 | 124.95 | 3.93 | 3.1% | 1.64 | 1.3% | 4.26 | 3.4% | 2.02 | 1.6% | 4.71 | 3.8% |
| CTL1MB2 | 9.08 | 0.20 | 2.2% | 0.12 | 1.3% | 0.23 | 2.5% | 0.33 | 3.6% | 0.40 | 4.4% |
| CTL2MB2 | 36.54 | 1.03 | 2.8% | 0.00 | 0.0% | 1.03 | 2.8% | 1.32 | 3.6% | 1.67 | 4.6% |
| CTL3MB2 | 93.43 | 2.93 | 3.1% | 3.61 | 3.9% | 4.65 | 5.0% | 0.00 | 0.0% | 4.65 | 5.0% |
| CV 1MB2 | 8.96 | 0.20 | 2.2% | 0.12 | 1.4% | 0.23 | 2.6% | 0.29 | 3.3% | 0.37 | 4.2% |
| CV 2MB2 | 90.58 | 2.68 | 3.0% | 2.86 | 3.2% | 3.92 | 4.3% | 0.37 | 0.4% | 3.94 | 4.3% |
| CV 3MB2 | 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% |
| Sample1 | 16.56 | 0.28 | 1.7% | 0.14 | 0.9% | 0.32 | 1.9% | 0.51 | 3.1% | 0.60 | 3.6% |
| Sample2 | 85.46 | 2.15 | 2.5% | 0.00 | 0.0% | 2.15 | 2.5% | 1.63 | 1.9% | 2.70 | 3.2% |
| Sample3 | 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 concentrationtested thatdemonstrated nosignificant 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 insamples less than 30 | % Cross Reactivityin samples between55 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.
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| 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 | CorrelationCoefficient(r) |
|---|---|---|---|---|---|
| 136 | 0.9112 | 0.88 to 0.94 | 0.1556nmol/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 vSerum | 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.
| Males21 – 49years | Males> 50 years | Femalespremenopausal | Femalespostmenopausal | |
|---|---|---|---|---|
| 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 97.5thpercentile 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:
| Males21 – 49 years | Males> 50 years | Femalespremenopausal | Femalespostmenopausal | |
|---|---|---|---|---|
| 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 97.5thpercentile 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.
§ 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.