IDS-iSYS Free Testosterone

K240865 · Immunodiagnostic Systems Limited · CDZ · Oct 23, 2024 · Clinical Chemistry

Device Facts

• Record ID: K240865
• Device Name: IDS-iSYS Free Testosterone
• Applicant: Immunodiagnostic Systems Limited
• Product Code: CDZ · Clinical Chemistry
• Decision Date: Oct 23, 2024
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1680
• Device Class: Class 1

Intended 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.

Device Story

IDS-iSYS Free Testosterone is an in vitro diagnostic assay for quantitative measurement of free testosterone in human serum or plasma. The device utilizes a competitive immunoassay principle on the IDS-iSYS Multi-Discipline Automated System. The reagent cartridge contains magnetic particles coated with streptavidin, biotinylated monoclonal anti-testosterone antibody, and testosterone labeled with an acridinium ester derivative. The system performs automated chemiluminescent detection. Used in clinical laboratories by trained personnel; results assist physicians in diagnosing and managing androgen-related conditions like hypogonadism, hirsutism, and virilization. The device provides quantitative values that inform clinical decision-making regarding hormone therapy or further diagnostic investigation.

Clinical Evidence

Bench testing only. Performance validated per CLSI guidelines. Precision (repeatability/reproducibility) evaluated with CVs generally <10%. Linearity established from 0.12 to 68.12 pg/mL. Analytical specificity (cross-reactivity) and interference (including biotin up to 500 ng/mL) showed no significant bias (≤±10%). Method comparison against a commercial ELISA (N=241) yielded a slope of 1.02 and correlation coefficient (r) of 0.98. Matrix equivalence confirmed for serum, SST, and various plasma types (K2 EDTA, Li/Na Heparin).

Technological Characteristics

Competitive immunoassay using chemiluminescence detection. Reagents: magnetic particles (streptavidin-coated), biotinylated monoclonal anti-testosterone antibody, acridinium ester-labeled testosterone. Form factor: reagent cartridge for automated IDS-iSYS system. Connectivity: integrated with IDS-iSYS platform. Software: automated system control. Sterilization: not applicable (reagent kit).

Indications for Use

Indicated for quantitative determination of free testosterone in human serum or plasma to aid in diagnosis and treatment of androgen-related disorders, including primary/secondary hypogonadism, impotence, hirsutism, and virilization in males and females.

Regulatory Classification

Identification

A testosterone test system is a device intended to measure testosterone (a male sex hormone) in serum, plasma, and urine. Measurement of testosterone are used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in males and, in females hirsutism (excessive hair) and virilization (masculinization) due to tumors, polycystic ovaries, and adrenogenital syndromes.

Predicate Devices

• Free Testosterone AccuBind® ELISA Test System (k181017)

Submission Summary (Full Text)

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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 ([e-mail]) or phone [phone] 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) | |
|-------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------|
| <span style="font-size: 10pt;"> <input checked="true" type="checkbox"/> Prescription Use (Part 21 CFR 801 Subpart D) </span> | <span style="font-size: 10pt;"> <input type="checkbox"/> Over-The-Counter Use (21 CFR 801 Subpart C) </span> |

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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 Limited<br>10 Didcot Way<br>Boldon Business Park<br>Boldon<br>Tyne and Wear<br>NE35 9PD<br>United Kingdom<br><br>Contact Person: Mick Henderson<br>Phone: [phone]<br>Fax: [phone]<br>Email: [e-mail]<br><br>Secondary Contact: Lee Harris<br>Phone: [phone]<br>Fax: [phone]<br>Email : [e-mail] |
| | Date prepared: 20th September 2024 |
| Device Name | Proprietary names: IDS-iSYS Free Testosterone |
| | Common names: IDS Free Testosterone |
| | Classification: 21 CFR 862.1680 –Testosterone Test<br>System<br>Class 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:<br>- MP3: Magnetic particles coated with Streptavidin in a phosphate Pluronic buffer with sodium azide (NaN3) as preservative (< 0.1%). 1 bottle, 2.5 mL.<br>- 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<br>- Ab-BIOT: Monoclonal anti-Testosterone labelled with Biotin in MES buffer with ProClin 300 as preservative (<0.0015%). 1 bottle, 7.5 mL<br>- 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<br>- 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)

| Assay<br>Performance | Predicate Device<br>Free Testosterone<br>AccuBind® ELISA Test<br>System (k181017) | Candidate Device<br>IDS-iSYS Free Testosterone |
|----------------------|-----------------------------------------------------------------------------------|------------------------------------------------|
| Intended Use | The direct quantitative<br>determination of Free<br>Testosterone | Same |
| Test Principle | Competitive immunoassay | Same |

# Differences compared to the chosen (FDA cleared; marketed) predicate device (k181017)

| Assay Performance | Predicate Device<br>Free Testosterone<br>AccuBind® ELISA Test<br>System (k181017) | Candidate Device<br>IDS-iSYS Free Testosterone |
|--------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Antibody | Utilizes a highly specific rabbit<br>polyclonal antibody at a low<br>binding capacity | Monoclonal anti-testosterone<br>labelled with biotin |
| Detection<br>Method | Microplate colorimetric reader | Chemiluminescence |
| Sample Type | Human serum | Human serum or plasma |
| Measuring<br>range | 0.11 - 60 pg/ml | 0.40 - 60 pg/mL |
| Expected Range of Values | Males 20-39: 9.2-34.6<br>Males 40-59: 6.1-30.3<br>Males ≥60: 6.1-27.9<br>Females 20-39:0.2-6.1<br>Females 40-59: 0.3-4.4<br>Females >60: 0.5-3.4 | Males 21 - 39: 4.91 - 21.64<br>Males 40 - 59: 3.73 - 14.96<br>Males ≥60: 2.25 - 11.37<br>Females 21 - 39: 0.46 - 2.20<br>Females 40 - 59: 0.40 - 1.74<br>Females >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.

| Sample<br>ID | N | Mean Conc.<br>(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.

| Sample<br>ID | N | Mean Conc.<br>(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 | Concentration<br>Tested | % 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% |

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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% |

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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 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<br>(RLUs) | Percent B/Bo (%) |
|--------------------|-------------------------------------|------------------|
| 0 | 281560 | 100% |
| 6.25 | 284970 | 101% |
| 12.5 | 282335 | 100% |
| 50 | 278307 | 99% |
| 200 | 262790 | 93% |

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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<br>(pg/mL) | 95% CI | Correlation<br>coefficient (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<br>(pg/mL) | 95% CI | Corr.<br>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 |

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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, 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)<br>(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)<br>(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.