(209 days)
The IDS-iSYS Free Testosterone assay is an in vitro diagnostic device intended for the quantitative determination of free testosterone in human serum or the IDS system. Measurement of free testosterone is used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, impotence in male and in females; hirsutism (excessive hair) and virilization) due to tumors, polycystic ovaries and androgenital syndromes.
The IDS-iSYS Free Testosterone assay consists of a reagent cartridge. The reagent cartridge contains multiple reagents:
- MP3: Magnetic particles coated with Streptavidin in a phosphate Pluronic buffer with sodium azide (NaN3) as preservative (< 0.1%). 1 bottle, 2.5 mL.
- CONJ: Testosterone labelled with an acridinium ester derivative, in phosphate buffer containing bovine protein with ProClin 300 as preservative (< 0.0015%). 1 bottle, 3.5 mL
- Ab-BIOT: Monoclonal anti-Testosterone labelled with Biotin in MES buffer with ProClin 300 as preservative (<0.0015%). 1 bottle, 7.5 mL
- Cal A: Human serum matrix containing human free testosterone with sodium azide and ProClin 300 as preservatives (<0.1% and 0.0024% respectively). 1.0 mL per bottle
- Cal B: Human serum matrix containing human free testosterone with sodium azide and ProClin 300 as preservatives (<0.1% and 0.0024% respectively). 1.0 mL per bottle
The provided document describes the analytical performance of the IDS-iSYS Free Testosterone assay but does not detail a device performance study with acceptance criteria in the typical format of a clinical trial for an AI/ML medical device. Instead, it focuses on the analytical characteristics of the in vitro diagnostic device, comparing it to a predicate device and demonstrating its performance through various laboratory tests.
Here's an attempt to structure the information based on your request, with the understanding that not all requested points are directly applicable to this type of IVD submission:
1. Table of Acceptance Criteria and Reported Device Performance
For an in vitro diagnostic device like the IDS-iSYS Free Testosterone, "acceptance criteria" and "reported device performance" are typically defined by analytical performance characteristics, such as sensitivity, precision, linearity, and interference. The document presents these values but does not explicitly state pre-defined acceptance criteria for each measurement that would be found in a clinical study protocol. However, we can infer performance targets based on the data presented and common medical device standards (e.g., CLSI guidelines).
| Acceptance Criteria (Inferred/Generic for IVD) | Reported Device Performance (IDS-iSYS Free Testosterone) |
|---|---|
| Analytical Sensitivity | |
| Limit of Blank (LoB) | 0.08 pg/mL |
| Limit of Detection (LoD) | 0.17 pg/mL |
| Limit of Quantitation (LoQ) | 0.40 pg/mL (with CV < 20%) |
| Precision (Repeatability) | |
| CV% for Low concentration (e.g., < 1 pg/mL) | 7.0% (S1: 0.7 pg/mL) |
| CV% for Mid concentration | 1.4% (S6: 10.8 pg/mL) |
| CV% for High concentration | 2.2% (S10: 56.0 pg/mL) |
| Precision (Within-Laboratory) | |
| CV% for Low concentration (e.g., < 1 pg/mL) | 9.9% (S1: 0.7 pg/mL) |
| CV% for Mid concentration | 3.7% (S6: 10.8 pg/mL) |
| CV% for High concentration | 3.4% (S10: 56.0 pg/mL) |
| Precision (Reproducibility) | |
| CV% (System to System, Low Conc.) | 11.1% (S2: 1.2 pg/mL) |
| CV% (System to System, High Conc.) | 3.9% (S10: 57.9 pg/mL) |
| CV% (Lot to Lot, Low Conc.) | 7.8% (S2: 1.2 pg/mL) |
| CV% (Lot to Lot, High Conc.) | 4.7% (S10: 58.9 pg/mL) |
| Linearity Range | |
| Linear measurement range | 0.12 pg/mL to 68.12 pg/mL |
| Interference/Cross-Reactivity | |
| Cross-reactivity % for various compounds | Mostly < 0.01% (e.g., 11-Deoxycortisol, Estradiol) |
| Bias for interfering agents (e.g., Bilirubin, Hemoglobin) | ≤ ±10% (observed at specified thresholds) |
| Method Comparison (vs. commercially available ELISA) | |
| Correlation Coefficient (r) | 0.98 |
| Slope | 1.02 (95% CI: 0.97 to 1.06) |
| Intercept | -0.02 pg/mL (95% CI: -0.26 to 0.07) |
| Matrix Comparison (vs. Serum) | |
| Correlation Coefficient (r) for SST, K2 EDTA, Li Heparin, Na Heparin | All 0.99 or 1.00 |
| Slope for SST, K2 EDTA, Li Heparin, Na Heparin | 0.96 - 0.97 |
2. Sample Size Used for the Test Set and Data Provenance
The "test set" in this context refers to the samples used for analytical validation studies.
- Analytical Limits (LoB, LoD, LoQ): 60 replicates of 4 blank samples and 6 low-concentration samples for LoB/LoD; 105 replicates of 7 low-concentration samples for LoQ.
- Repeatability: 10 serum samples, 80 replicates per sample.
- Reproducibility (System/Operator): 9 serum samples, 75 replicates per sample.
- Reproducibility (Lot-to-Lot): 9 serum samples, 75 replicates per sample.
- Linearity: The number of unique samples is not specified, but the study evaluated the measurement procedure's linearity from 0.12 pg/mL to 68.12 pg/mL.
- Cross-Reactivity: 2 samples (1.0 and 15 pg/mL free testosterone) spiked with various cross-reactants.
- Interference: 2 samples (1.0 and 45.0 pg/mL free testosterone) spiked with various interfering agents.
- Method Comparison: 241 samples. The document does not specify the country of origin or if these were retrospective or prospective samples, but they are patient samples covering a wide range of concentrations.
- Matrix Comparison: 40 samples for each matrix (SST, K2 EDTA, Li Heparin, Na Heparin) compared against serum.
- Expected Values:
- Females: 130 (21-39 yrs), 57 (40-59 yrs), 67 (>=60 yrs)
- Males: 129 (21-39 yrs), 138 (40-59 yrs), 42 (>=60 yrs)
The provenance of these subjects is not stated, but they are described as "apparently healthy adults and children."
3. Number of Experts Used to Establish Ground Truth and Qualifications
This information is not applicable to this document. The "ground truth" for an IVD device like this is typically established by reference methods or gravimetric preparation of calibrators/controls, not by human expert opinion as would be the case for image-based AI/ML diagnostics. The values are quantitative measurements of a biochemical marker.
4. Adjudication Method for the Test Set
This information is not applicable. Adjudication methods (e.g., 2+1, 3+1) are common in studies where human readers interpret data (like medical images) and their agreement, or lack thereof, needs to be resolved. For an IVD, the "ground truth" is a measured concentration, and the accuracy is assessed against reference standards or established methods.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
This information is not applicable. An MRMC study assesses how human readers' performance changes with and without AI assistance. This device is an in vitro diagnostic assay, directly measuring a biomarker without human interpretation in the workflow described.
6. Standalone (Algorithm Only) Performance
The performance data presented throughout the document (LoB, LoD, LoQ, precision, linearity, cross-reactivity, interference, method comparison, matrix comparison) is the standalone performance of the IDS-iSYS Free Testosterone assay. This device is a fully automated assay system, and its performance is evaluated independent of human interpretive steps.
7. Type of Ground Truth Used
The ground truth for the analytical studies is generally based on:
- Known concentrations: For LoB, LoD, LoQ, linearity, cross-reactivity, and interference, samples are prepared with known or target concentrations of free testosterone and potential interfering substances.
- Comparative methods: For method comparison, a "commercially available quantitative free testosterone ELISA" serves as the comparative method against which the IDS-iSYS Free Testosterone is measured.
- Reference Intervals: For expected values, "95% reference interval for apparently healthy adults and children" was calculated using a non-parametric method, likely referring to the distribution of measurements in that population.
8. Sample Size for the Training Set
This information is not provided and is typically not applicable in the same way it would be for an AI/ML device. For an IVD assay, "training" involves the development and optimization of the assay reagents, protocols, and calibration, rather than training a machine learning model on a distinct dataset. The "training set" for an IVD refers to the samples used to develop and refine the assay's performance characteristics and establish its calibration curve, which is distinct from the analytical validation samples.
9. How the Ground Truth for the Training Set Was Established
This information is not explicitly provided in the document. For an IVD, the "ground truth" for developing a training set (i.e., for calibration) typically involves:
- Gravimetric preparation: Precisely weighing and dissolving a known amount of the analyte (free testosterone) in a suitable matrix to create primary calibrators with accurate, traceable concentrations.
- Reference methods: Using highly accurate and validated reference methods (e.g., LC-MS/MS, though not specified here) to assign values to calibrators or control materials.
- Standardization: Following established industry and regulatory standards (e.g., CLSI guidelines) for calibrator preparation and value assignment to ensure accuracy and traceability.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
October 23, 2024
Immunodiagnostic Systems Limited Mick Henderson Regulatory Affairs Manager 10 Didcot Way, Boldon Business Park Boldon Tyne and Wear NE35 9PD United Kingdom
Re: K240865
Trade/Device Name: IDS-iSYS Free Testosterone Regulation Number: 21 CFR 862.1680 Regulation Name: Testosterone Test System Regulatory Class: Class I, reserved Product Code: CDZ Dated: September 20, 2024 Received: September 20, 2024
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 (the 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 available 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.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device"
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(https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100. Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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.
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For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Paula V. Caposino -S
Paula Caposino, Ph.D. Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics 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) K240865
Device Name IDS-iSYS Free Testosterone
Indications for Use (Describe)
The IDS-iSYS Free Testosterone assay is an in vitro diagnostic device intended for the quantitative determination of free testosterone in human serum or the IDS system. Measurement of free testosterone is used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, impotence in male and in females; hirsutism (excessive hair) and virilization) due to tumors, polycystic ovaries and androgenital syndromes.
| 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 | K240865 |
|---|---|
| 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 Limited10 Didcot WayBoldon Business ParkBoldonTyne and WearNE35 9PDUnited KingdomContact Person: Mick HendersonPhone: +44 191 5190660Fax: +44 191 5190760Email: mick.henderson@idsplc.comSecondary Contact: Lee HarrisPhone: +44 191 5190660Fax: +44 191 5190760Email : lee.harris@idsplc.com |
| Date prepared: 20th September 2024 | |
| Device Name | Proprietary names: IDS-iSYS Free Testosterone |
| Common names: IDS Free Testosterone | |
| Classification: 21 CFR 862.1680 –Testosterone TestSystemClass 1 reserved | |
| Product Code: CDZ |
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Image /page/5/Picture/1 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters "ids" in a stylized, interconnected design, rendered in gray. A red circle is positioned above the "i", serving as a visual accent. Below the gray letters, the words "immunodiagnosticsystems" are written in red, completing the company's name.
| Predicate Device | Free Testosterone AccuBind® ELISA Test System (K181017) | |
|---|---|---|
| Device Description | The IDS-iSYS Free Testosterone assay consists of a reagent cartridge. The reagent cartridge contains multiple reagents:- MP3: Magnetic particles coated with Streptavidin in a phosphate Pluronic buffer with sodium azide (NaN3) as preservative (< 0.1%). 1 bottle, 2.5 mL.- CONJ: Testosterone labelled with an acridinium ester derivative, in phosphate buffer containing bovine protein with ProClin 300 as preservative (< 0.0015%). 1 bottle, 3.5 mL- Ab-BIOT: Monoclonal anti-Testosterone labelled with Biotin in MES buffer with ProClin 300 as preservative (<0.0015%). 1 bottle, 7.5 mL- Cal A: Human serum matrix containing human free testosterone with sodium azide and ProClin 300 as preservatives (<0.1% and 0.0024% respectively). 1.0 mL per bottle- Cal B: Human serum matrix containing human free testosterone with sodium azide and ProClin 300 as preservatives (<0.1% and 0.0024% respectively). 1.0 mL per bottle |
Indications for Use
The IDS-iSYS Free Testosterone assay is an in vitro diagnostic device intended for the quantitative determination of free testosterone in human serum or plasma on the IDS system. Measurement of free testosterone is used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, impotence in male and in females; hirsutism (excessive hair) and virilization (masculinization) due to tumors, polycystic ovaries and androgenital syndromes.
- Conditions for use For in vitro diagnostic use. Rx Only
Special instrument Requirements:
IDS-iSYS Multi-Discipline Automated System (K091849)
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Image /page/6/Picture/0 description: The image is a logo for Immunodiagnostic Systems (IDS). The logo features the letters "ids" in a stylized, sans-serif font, with a red circle above the "i". Below the letters, the words "immunodiagnosticsystems" are written in a smaller, red, sans-serif font. A circled "R" trademark symbol is located in the upper right corner of the logo.
Comparison Tables
Similarities compared to the chosen (FDA cleared; marketed) predicate device (K181017)
| AssayPerformance | Predicate DeviceFree TestosteroneAccuBind® ELISA TestSystem (K181017) | Candidate DeviceIDS-iSYS Free Testosterone |
|---|---|---|
| Intended Use | The direct quantitativedetermination of FreeTestosterone | Same |
| Test Principle | Competitive immunoassay | Same |
Differences compared to the chosen (FDA cleared; marketed) predicate device (K181017)
| Assay Performance | Predicate DeviceFree TestosteroneAccuBind® ELISA TestSystem (K181017) | Candidate DeviceIDS-iSYS Free Testosterone |
|---|---|---|
| Antibody | Utilizes a highly specific rabbitpolyclonal antibody at a lowbinding capacity | Monoclonal anti-testosteronelabelled with biotin |
| DetectionMethod | Microplate colorimetric reader | Chemiluminescence |
| Sample Type | Human serum | Human serum or plasma |
| Measuringrange | 0.11 - 60 pg/ml | 0.40 - 60 pg/mL |
| Expected Range of Values | Males 20-39: 9.2-34.6Males 40-59: 6.1-30.3Males ≥60: 6.1-27.9Females 20-39:0.2-6.1Females 40-59: 0.3-4.4Females >60: 0.5-3.4 | Males 21 - 39: 4.91 - 21.64Males 40 - 59: 3.73 - 14.96Males ≥60: 2.25 - 11.37Females 21 - 39: 0.46 - 2.20Females 40 - 59: 0.40 - 1.74Females >60: 0.42-2.20 |
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Image /page/7/Picture/0 description: The image contains a logo for Immunodiagnostic Systems (IDS). The logo features the letters 'ids' in a stylized, interconnected design, with the 'i' having a red circular dot above it. Below the main logo, the words 'immunodiagnosticsystems' are written in a smaller font size, with 'immuno' in red and the rest of the word in gray.
Performance Characteristics
Analytical Limits at Low levels
The limit of blank (LoB), limit of detection (LoD) and limit of quantitation (LoO) were determined with guidance from CLSI EP17-A2, "Protocols for Determination of Limits of Detection and Limits of Quantitation" with three (3) IDS Free testosterone kit lots. I LoB and LoD were determined with 60 replicates of 4 blank samples and 6 low concentration samples per reagent lot. LoQ was determined with 105 replicates of 7 low concentration samples per reagent lot. The LoQ was determined as the lowest concentration with a within-laboratory precision CV < 20%.
| Sensitivity | Concentration (pg/mL) |
|---|---|
| Limit of Blank (LoB) | 0.08 |
| Limit of Detection (LoD) | 0.17 |
| Limit of Quantitation (LoQ) | 0.40 |
Precision (Repeatability/Reproducibility)
Precision studies were performed with guidance from CLSI EP05 A3 "Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline".
Repeatability
A total of 10 serum samples were measured using 1 reagent lot, in duplicate, twice a day for 20 days on 1 IDS system for a total of 80 replicates per sample to assess the repeatability.
| SampleID | N | Mean Conc.(pg/mL) | Repeatability | Within Laboratory | ||
|---|---|---|---|---|---|---|
| SD | CV% | SD | CV% | |||
| S1 | 80 | 0.7 | 0.05 | 7.0% | 0.07 | 9.9% |
| S2 | 80 | 1.1 | 0.05 | 4.3% | 0.06 | 5.2% |
| S3 | 80 | 1.2 | 0.04 | 3.0% | 0.06 | 5.0% |
| S4 | 80 | 3.8 | 0.06 | 1.7% | 0.12 | 3.3% |
| S5 | 80 | 9.2 | 0.20 | 2.2% | 0.27 | 2.9% |
| S6 | 80 | 10.8 | 0.15 | 1.4% | 0.39 | 3.7% |
| S7 | 80 | 19.7 | 0.28 | 1.4% | 0.44 | 2.3% |
| S8 | 80 | 32.2 | 0.77 | 2.4% | 1.03 | 3.2% |
| S9 | 80 | 43.4 | 0.76 | 1.8% | 1.45 | 3.3% |
| S10 | 80 | 56.0 | 1.24 | 2.2% | 1.90 | 3.4% |
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Image /page/8/Picture/0 description: The image contains a logo for Immunodiagnostic Systems (IDS). The logo features the letters "ids" in a stylized, gray font, with a red circle above the "i". Below the gray letters, the words "immunodiagnosticsystems" are written in a smaller, red font. The "®" symbol is located to the right of the "s" in "ids".
Reproducibility
A total of 9 serum samples were measured using one reagent lot in 5 replicates, once a day for 5 days on 3 IDS systems by three operators (one operator per system) for a total of 75 replicates per sample to determine the reproducibility.
| Sample ID | N | Mean Conc. (pg/mL) | Repeatability | Reproducibility | ||
|---|---|---|---|---|---|---|
| SD | CV% | SD | CV% | |||
| S2 | 75 | 1.2 | 0.09 | 7.1% | 0.13 | 11.1% |
| S3 | 75 | 1.3 | 0.08 | 5.9% | 0.08 | 6.5% |
| S4 | 75 | 3.8 | 0.16 | 4.2% | 0.17 | 4.5% |
| S5 | 75 | 9.2 | 0.35 | 3.8% | 0.35 | 3.8% |
| S6 | 75 | 10.8 | 0.38 | 3.5% | 0.44 | 4.1% |
| S7 | 75 | 19.8 | 0.69 | 3.5% | 0.83 | 4.2% |
| S8 | 75 | 32.6 | 1.66 | 5.1% | 1.82 | 5.6% |
| S9 | 75 | 44.4 | 1.77 | 4.0% | 1.94 | 4.4% |
| S10 | 75 | 57.9 | 1.97 | 3.4% | 2.24 | 3.9% |
A total of 9 serum samples were tested using three (3) reagents lot in 5 replicates, once a day for 5 days on 1 IDS system by 1 operator per system for a total of 75 replicates per sample to determine the reproducibility.
| SampleID | N | Mean Conc.(pg/mL) | Repeatability | Reproducibility | ||
|---|---|---|---|---|---|---|
| SD | CV% | SD | CV% | |||
| S2 | 75 | 1.2 | 0.09 | 7.8% | 0.09 | 7.8% |
| S3 | 75 | 1.3 | 0.07 | 5.5% | 0.07 | 5.8% |
| S4 | 75 | 3.7 | 0.13 | 3.4% | 0.15 | 4.1% |
| S5 | 75 | 9.3 | 0.44 | 4.7% | 0.44 | 4.7% |
| S6 | 75 | 10.9 | 0.44 | 4.0% | 0.46 | 4.2% |
| S7 | 75 | 20.1 | 0.87 | 4.3% | 0.89 | 4.4% |
| S8 | 75 | 33.1 | 2.33 | 7.0% | 2.85 | 8.6% |
| S9 | 75 | 45.4 | 2.32 | 5.1% | 2.36 | 5.2% |
| S10 | 75 | 58.9 | 2.80 | 4.7% | 2.80 | 4.7% |
Linearitv
Linearity was evaluated based on CLSI EP06 Ed2, "Evaluation of Linearity of Quantitative Measurement Procedures". For concentration by IDS Free testosterone assay, the measurement procedure shows the linearity between 0.12 pg/mL and 68.12 pg/mL, was within the allowable deviation of linearity (ADL) of ≤ ±13.6 %, or ≤+/- 0.40 pg/mL for concentrations below 1 pg/mL.
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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, rounded font, with the "i" having a red circle above it. Below the letters, the words "immunodiagnosticsystems" are written in a smaller, red font. The logo has a registered trademark symbol in the upper right corner.
K240865 Analytical Specificity
Cross Reactivity
Cross-reactivity studies were performed in accordance with the CLSI guidance EP07-A3 "Interference testing in clinical chemistry". The study was conducted by spiking the crossreacting compounds into 2 samples containing approximately 1.0 and 15 pg/mL concentrations of free testosterone. Results are shown in the table below:
| Cross Reactant | ConcentrationTested | % Cross Reactivity |
|---|---|---|
| 11-Deoxycortisol | 100000 ng/ml | < 0.01% |
| 11-Ketotestosterone | 100 ng/ml | 0.02% |
| 11-β-Hydroxytestosterone | 1000 ng/ml | < 0.01% |
| 17-Hydroxypregnenolone | 1000 ng/ml | < 0.01% |
| 17OH-Progesterone | 500 ng/ml | < 0.01% |
| 17a-Estradiol | 1000 ng/ml | < 0.01% |
| 17α-Ethinilestradiol | 500 ng/ml | < 0.01% |
| 3-EstriolGluc | 1000 ng/ml | < 0.01% |
| 3-EstriolSul | 1000 ng/ml | < 0.01% |
| 5a-Androstane-3β,17β-diol | 1000 ng/ml | < 0.01% |
| Aldosterone | 3000 ng/ml | < 0.01% |
| Amitriptyl HCI | 1000 ng/ml | < 0.01% |
| Androstenedione | 100 ng/ml | 0.02% |
| Androsterone | 500 ng/ml | < 0.01% |
| Clomiphene Citrate | 1000 ng/ml | < 0.01% |
| Corticosterone | 1000 ng/ml | < 0.01% |
| Cortisol | 1000 ng/ml | < 0.01% |
| Cortisone | 2000 ng/ml | < 0.01% |
| Cyproterone | 2000 ng/ml | < 0.01% |
| Cyproterone acetate | 1000 ng/ml | < 0.01% |
| D-5-Androstene-3β,17β-diol | 1000 ng/ml | < 0.01% |
| Danazol | 1000 ng/ml | < 0.01% |
| Desogestrel | 100 ng/ml | < 0.01% |
| Dexamethasone | 2000 ng/ml | < 0.01% |
| DHEA | 50000 ng/ml | < 0.01% |
| DHEA-S | 100000 ng/ml | < 0.01% |
| Dihydrotestosterone | 500 ng/ml | < 0.01% |
| Epitestosterone | 500 ng/ml | < 0.01% |
| Estradiol | 1000 ng/ml | < 0.01% |
| Estriol | 100 ng/ml | < 0.01% |
| Estrone | 1000 ng/ml | < 0.01% |
| Ethisterone | 1000 ng/ml | < 0.01% |
| Ethynodiol | 1000 ng/ml | < 0.01% |
| Ethynodiol diacetate | 50 ng/ml | <0.01% |
| K240865 | immunodiagnostiosystems | |
| Flunisolide | 1000 ng/ml | < 0.01% |
| Fluoxymesterone | 1000 ng/ml | < 0.01% |
| Lynestrol | 1000 ng/ml | < 0.01% |
| Medoxyprogesterone acetate | 1000 ng/ml | < 0.01% |
| Mestranol | 1000 ng/ml | < 0.01% |
| Methyltestosterone | 100 ng/ml | 0.04% |
| Norethindrone | 50 ng/ml | < 0.01% |
| Norethinodrone acetate | 50 ng/ml | < 0.01% |
| Norethynodrel | 50 ng/ml | < 0.01% |
| Norgestimate | 1000 ng/ml | < 0.01% |
| Norgestrel | 1000 ng/ml | < 0.01% |
| Oxymetholone | 10000 ng/ml | < 0.01% |
| Prednisolone | 1000 ng/ml | < 0.01% |
| Prednisone | 1000 ng/ml | < 0.01% |
| Pregnenolone | 5000 ng/ml | < 0.01% |
| Progesterone | 1000 ng/ml | < 0.01% |
| Salbutamol | 1000 ng/ml | < 0.01% |
| Spironolactone | 1000 ng/ml | < 0.01% |
| Stanozolol | 1000 ng/ml | < 0.01% |
| Testosterone Cypionate | 12 ng/ml | < 0.01% |
| Testosterone enanthate | 100 ng/ml | < 0.01% |
| Testosterone propionate | 100 ng/ml | < 0.01% |
| Testosterone SO4 | 1000 ng/ml | < 0.01% |
| Testosterone Undecanoate | 12 ng/ml | < 0.01% |
| Triamcinolone | 50 ng/ml | < 0.01% |
{10}------------------------------------------------
Image /page/10/Picture/0 description: The image shows the logo for IDS, which stands for ImmunoDiagnosticSystems. The logo features the letters 'ids' in a stylized, interconnected design, with a red circle above the 'i'. Below the 'ids' is the full name 'immunodiagnosticsystems' in a smaller, red font. The logo is simple and modern, with a focus on the company's initials and its area of expertise.
Interference
The interference testing of IDS Free Testosterone was evaluated following the CLSI EP07-ED3, "Interference Testing in Clinical Chemistry". The study was performed using 2 samples containing 1.0, and 45.0 pg/mL concentrations of free testosterone. No significant interference (≤±10% bias) was observed when the interfering substances were tested at the following threshold concentration:
| Potentially Interfering Agent | Threshold Concentration |
|---|---|
| Acetylsalicylic Acid | 1.67 mmol/L |
| Acetaminophen | 1030 umol/L |
| Bilirubin (Conjugated) | 40 mg/dL |
| Bilirubin (Unconjugated) | 40 mg/dL |
| Biotin* | 500 ng/mL |
| Human Anti Mouse Antibody (HAMA) | 1000 ng/dL |
| Haemoglobin | 300 mg/dL |
| Ibuprofen | 1060 umol/L |
| Total Protein | 10 g/dL |
| Red Blood Cells | 0.4% |
{11}------------------------------------------------
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 a red circle above the "i". Below the letters, the words "immunodiagnosticsystems" are written in a smaller, sans-serif font, with the first word in red and the second word in gray. A registered trademark symbol is located to the right of the letters "ids".
| K240865 | immunodiagnostic |
|---|---|
| Salicylic Acid | 2.07 mmol/L |
| Triglycerides | 1500 mg/dL |
| Rheumatoid Factor (RhF) | 1500 IU/mL |
- A study was conducted to evaluate biotin interference on the IDS Free Testosterone assay. Up to 750 ng/mL biotin was spiked into serum samples containing three concentrations of free testosterone, approximately 1.5 pg/mL, 20 pg/mL, and 45 pg/mL.
No significant interference (≤±10% bias) was observed at biotin concentrations ≤ 500 ng/mL for all three concentrations of free testosterone tested.
SHBG at concentration ranging from 6.25 – 200 µg/mL was added to a charcoal-stripped human serum sample and was measured with the IDS Free Testosterone assay. All concentrations exhibited less than 10% binding. Results are tabulated below:
| SHBG added (µg/mL) | Mean Relative Light Units(RLUs) | Percent B/Bo (%) |
|---|---|---|
| 0 | 281560 | 100% |
| 6.25 | 284970 | 101% |
| 12.5 | 282335 | 100% |
| 50 | 278307 | 99% |
| 200 | 262790 | 93% |
{12}------------------------------------------------
Image /page/12/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo consists of the letters "ids" in a stylized, connected font, with a red circle above the "i". The letters are gray. Below the gray letters, the words "immunodiagnosticsystems" are written in a smaller, red font.
K240865 Method Comparison
The IDS Free Testosterone was compared against a commercially available quantitative free testosterone ELISA, following CLSI EP09c, "Method Comparison and Bias Estimation Using Patient Samples". A total of 241 samples, selected to represent a wide range of free testosterone concentrations, 0.41 to 55.98 pg/mL, was tested by each method. Passing-Bablok regression analysis was performed on the comparative data:
| N | Slope | 95% CI | Intercept(pg/mL) | 95% CI | Correlationcoefficient (r) |
|---|---|---|---|---|---|
| 241 | 1.02 | 0.97 to 1.06 | -0.02 | -0.26 to 0.07 | 0.98 |
Matrix comparison
The assay should be performed using serum (standard sampling tubes or tubes containing serum separating gel) or plasma (lithium heparin, sodium heparin or potassium (K2) EDTA) samples. Samples should be separated as soon as possible after collection.
The matrix comparison studies, based on guidance from CLSI EP35 Ed.1 "Assessment of Equivalence for Suitability of Specimen Types for Medical Laboratory Measurement Procedures", were performed to assess the equivalence between serum (serum without additives, serum gel separator tubes (SST)) and plasma (K2 EDTA, Sodium Heparin and Lithium Heparin) sample matrices in the IDS Free Testosterone assay. Passing-Bablok regression analysis was performed on the comparative data:
| Sample Type | N | Slope | 95% CI | Intercept(pg/mL) | 95% CI | Corr.Coeff. (r) |
|---|---|---|---|---|---|---|
| SST | 40 | 0.96 | 0.92 to 0.98 | 0.08 | -0.04 to 0.22 | 1.00 |
| K2 EDTA | 40 | 0.97 | 0.94 to 1.01 | 0.08 | -0.08 to 0.26 | 0.99 |
| Li Heparin | 40 | 0.97 | 0.92 to 1.00 | 0.03 | -0.04 to 0.14 | 0.99 |
| Na Heparin | 40 | 0.97 | 0.93 to 1.00 | 0.00 | -0.06 to 0.17 | 0.99 |
{13}------------------------------------------------
Image /page/13/Picture/0 description: The image shows the logo for Immunodiagnostic Systems (IDS). The logo features the letters "ids" in a stylized, gray font, with a red circle above the "i". Below the gray letters, the words "immunodiagnostic systems" are written in a smaller, red font. The "®" symbol is located to the right of the "s" in "ids".
Expected Values
The following ranges were determined using the IDS Free Testosterone and are provided for information only. The 95 % reference interval for apparently healthy adults and children were calculated by a non-parametric method following guidance from CLSI C28-A3 "Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory".
| Females | 21 to 39 years | 40 to 59 years | ≥ 60 years |
|---|---|---|---|
| N of subjects | 130 | 57 | 67 |
| Mean (pg/mL) | 1.16 | 0.82 | 0.97 |
| SD (pg/mL) | 0.44 | 0.35 | 0.43 |
| Median (pg/mL) | 1.13 | 0.71 | 0.89 |
| Observed Range (pg/mL)(2.5th to 97.5th percentile) | 0.46 to 2.20 | 0.40 to 1.74 | 0.42 to 2.20 |
| Males | 21 to 39 years | 40 to 59 years | ≥ 60 years |
|---|---|---|---|
| N of subjects | 129 | 138 | 42 |
| Mean (pg/mL) | 12.50 | 8.80 | 7.76 |
| SD (pg/mL) | 4.03 | 2.71 | 2.17 |
| Median (pg/mL) | 12.36 | 8.70 | 7.78 |
| Observed Range (pg/mL)(2.5th to 97.5th percentile) | 4.91 to 21.64 | 3.73 to 14.96 | 2.25 to 11.37 |
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.
Conclusion
The IDS-iSYS Free Testosterone 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.