(175 days)
No
The device description details a fluorescence immunoassay with microfluidic technology and a reader system that calculates results based on a ratio of fluorescent intensities and a pre-established calibration curve. There is no mention of AI or ML algorithms being used for data analysis, interpretation, or decision-making. The software controls hardware and data management but does not appear to incorporate learning or adaptive capabilities.
No
Explanation: This device is an in vitro diagnostic (IVD) test system used to quantify free thyroxine (FT4) in human serum and plasma for the diagnosis of thyroid disorders. It is not directly used to treat or prevent a disease, but rather to aid in diagnosis.
Yes
The "Intended Use / Indications for Use" section explicitly states, "Measurements of free thyroxine (FT4) are used in the diagnosis of thyroid disorders." This directly indicates the device's diagnostic purpose.
No
The device description clearly outlines a system that includes hardware components: a disposable test cartridge containing reagents and a sample port, and a benchtop fluorescence reader (the FREND™ System) with a touch screen, slot for the cartridge, motor, laser, and sensor. While the system includes software for control and data analysis, it is not a software-only medical device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The document explicitly states "For in vitro diagnostic use only." It also describes the device's use for "quantitation of free thyroxine (FT4) in human serum and lithium heparinized plasma specimens" and that these measurements are "used in the diagnosis of thyroid disorders." This clearly aligns with the definition of an IVD, which is used to examine specimens derived from the human body to provide information for the diagnosis, prevention, or treatment of a disease or condition.
- Device Description: The description details a "rapid fluorescence immunoassay" that measures an analyte (Free T4) in human samples (serum and plasma). It describes the reagents, the process of the assay, and how the results are obtained by analyzing the sample in vitro (outside the body).
- Intended User / Care Setting: The device is intended for use in "clinical laboratories," which is a typical setting for IVD testing.
The entire description points to a device designed to perform diagnostic tests on human samples in a laboratory setting, which is the core function of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The FREND™ Free T4 Test System is a rapid indirect competitive immunoassay for the quantitation of free thyroxine (FT4) in human serum and lithium heparinized plasma specimens using the FREND™ Free T4 system. Measurements of free thyroxine (FT4) are used in the diagnosis of thyroid disorders. The FREND™ Free T4 Test System is intended for use in clinical laboratories. For in vitro diagnostic use only. The test is not intended for point-of-care facilities.
Product codes (comma separated list FDA assigned to the subject device)
CEC
Device Description
The FREND™ Free T4 is a rapid fluorescence immunoassay that measures Free T4 in human serum and in lithium heparinized plasma using the FREND™ Free T4 Test System.
The FREND™ Free T4 is a single use fluorescence immunoassay designed to quantify the concentration of free thyroxine in serum and lithium heparinized plasma samples, The FREND™ Free T4 test is a two-step competitive immunoassay with gold nanoparticles labeled with T4-specific monoclonal anti-T4- antibody (mouse), T3-BSA labeled with fluorescent nanoparticles, and fluorescence detection by the FREND™ System.
The FREND™ Free T4 Test utilizes microfluidic technology and detects immunecomplexes bound to Free T4. A 70ul Sample is first incubated during Step 1 for five minutes at 37 degrees C in the Free T4 Gold AB Tube with monoclonal anti-T4 antibody conjugated with gold nanoparticles. In Step 2, 35 ul of the mixture from Step 1 is manually loaded into the inlet of the cartridge, where it hydrates a T3-BSA fluorescent bead conjugate and migrates along the test strip. During migration the bound Free T4 in the sample and the fluorescent bead conjugates of T3-BSA compete to form antigenantibody complex in the test zone. Unbound T3-BSA fluorescent conjugates flow through and bind to the anti-T4 antibody that is fixed on the surface in the reference zone. Step 2 takes approximately four minutes after which the fluorescent signals in the test and reference zones are measured.
Free T4 quantification is based upon the ratio of the intensity of the test and reference zones. A lower ratio of fluorescence is indicative of a higher Free T4 concentration, in other words, the maqnitude of the fluorescence ratio is inversely proportional to the amount of Free T4 in the sample.
The free T4 detection range of the FREND™ Free T4 Test System is 0.4 to 6.0 ng/dL. Results are determined via a lot-specific calibration curve which is generated by the manufacturer using a six-point calibration determined from values averaged from five replicates at each level. The established curve is uploaded to the FREND™ System via the Free T4 Code-chip and is valid until the lot expiration date. The established curve is saved in the code-chip and valid until the expiration date of the test cartridge lot.
The FREND™ Free T4 Test cartridge is a disposable plastic device that houses the reagents and contains a port or opening (inlet) where the sample is applied. Once the sample is applied, it will mix with the reagents and travel towards the detection area via capillary action.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Clinical laboratories, For in vitro diagnostic use only.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision/Reproducibility: A single lot imprecision study was performed at the NanoEnTek laboratory as described in the CLS/ protocol EP5-A3. Three serum pools with low, intermediate and high Free T4 levels were assayed in duplicate twice per day for 20 days (80 total measurements).
Sample Pool 1 (Mean Free T4 Conc. 0.917 ng/dL): Repeatability SD 0.067, CV% 7.3; Between-run SD 0.000, CV% 0.0; Between-day SD 0.032, CV% 3.5; Within-laboratory SD 0.074, CV% 8.1.
Sample Pool 2 (Mean Free T4 Conc. 1.850 ng/dL): Repeatability SD 0.103, CV% 5.6; Between-run SD 0.000, CV% 0.0; Between-day SD 0.069, CV% 3.7; Within-laboratory SD 0.124, CV% 6.7.
Sample Pool 3 (Mean Free T4 Conc. 3.979 ng/dL): Repeatability SD 0.186, CV% 4.7; Between-run SD 0.152, CV% 3.8; Between-day SD 0.093, CV% 2.3; Within-laboratory SD 0.258, CV% 6.5.
Linearity/assay reportable range: A serum base pool with an elevated free thyroxine (7.5 ng/dL) was diluted to a total of 11 levels and measured in duplicate. The FREND™ Free T4 Test System was determined to have acceptable linearity across a free T4 range of 0.11 ~ 7.5 ng/dL, (Slope = 0.978, Intercept = -0.0881, R2 = 0.9938). The measuring range of the FREND™ Free T4 is 0.4 ~ 6 ng/dL, which is within the linearity range.
Stability: Real-time stability testing for the Free T4 reagent kit was performed according to CLSI EP25-A. Cartridges are good for at least one year from the date of manufacturer if stored refrigerated appropriately.
Detection Limit: The Limit of Detection (LoD) and Limit of Quantitation (LoQ) for the FREND™ Free T4 were established according to the CLSI EP17-A2 protocol and found to be 0.32 ng/dL, and 0.36 ng/dL, respectively.
Analytical specificity (Interference Studies): Recovery between 90% to 110% of the expected Free T4, in the presence of interferents, is considered acceptable performance. The interference studies were performed with two levels of free T4 using the recommendations in the CLSI EP07-A2 protocol.
Results showed all endogenous substances (Hemoglobin, Bilirubin conjugated, Bilirubin unconjugated, Triglyceride, Total protein, Biotin, IgG, IgA, IgM) and most pharmaceuticals tested were within the acceptable recovery range for both Free T4 Low and Free T4 High samples. Some pharmaceuticals (Iodide, Hydrocortisone, Propranolol, Propylthiouracil, Rifampicin, Theophylline, Thiamazole/Methimazole, Avidin) and Heterophilic Antibodies (RF, HAMA) had recoveries slightly outside the 90-110% range for one of the two Free T4 levels but generally close.
Cross Reactivity: The following substances were evaluated for potential cross-reactivity with the FREND™ Free T4 at two concentrations: Levothyroxine, T4; Diiodothyronine, T2; Tetraiodothyroacetic Acid; Triiodothyroacetic Acid; Triiodothyropropionic Acid; Diiodotyrosine, DIT; L-Triiodothyronine, T3; Monoiodotyrosine; Reverse T3. No significant cross-reactivity was found except for the L-Thyroxine (Levothyroxine) itself. Levothyroxine showed 99.44% and 99.57% cross-reactivity for Free T4 Low and Free T4 High respectively.
Method comparison with predicate device: Comparison studies were performed with 358 samples against the Abbott ARCHITECT Free T4 Assay (K123379). Ordinary least square fit method: Slope: 1.010 (95% CI: 0.992 to 1.028), y-Intercept: 0.057 (95% CI: 0.021 to 0.094), r: 0.986, Range Tested: 0.43 ~ 5.99 ng/dL. The difference between the concentrations measured by the test device and the predicate device is less than the allowable difference.
Matrix comparison: The matrix comparison study was performed at the NanoEnTek laboratory according to CLSI EP14-A3. Free T4 concentrations in 48 paired serum and lithium heparin samples were measured. Passing-Bablok regression analysis of serum results (x) compared to lithium heparin plasma results (y) yielded: Slope: 1.017 (95% CI: 0.991 to 1.044), y-Intercept: -0.008 (95% CI: -0.055 to 0.0451), Number of Samples: 48, Range Tested: 0.44 ~ 5.63 ng/dL. This indicates that FREND™ Free T4 can be measured equally well in serum and lithium heparin plasma.
Expected values/Reference range: Serum samples from a total of 196 normal, apparently healthy adult individuals were assayed on 3 lots of the FREND™ Free T4 assay. The reference interval for the FREND™ Free T4 Test System, determined according to CLSI C28-A3 guidelines, was found to be 0.83-1.60 ng/dL.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 862.1695 Free thyroxine test system.
(a)
Identification. A free thyroxine test system is a device intended to measure free (not protein bound) thyroxine (thyroid hormone) in serum or plasma. Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may therefore determine the clinical metabolic status of thyroxine. Measurements obtained by this device are used in the diagnosis and treatment of thyroid diseases.(b)
Classification. Class II.
0
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
February 18,2016
NANOENTEK USA INC % MAUREEN GARNER NEW WORLD REGULATORY SOLUTIONS, INC. 1983 HAZELWOOD ROAD TOMS RIVER, NJ 08753
Re: K152422
Trade/Device Name: FREND™ Free T4 Test System Regulation Number: 21 CFR 862.1695 Regulation Name: Free thyroxine test system Regulatory Class: II Product Code: CEC Dated: December 31, 2015 Received: January 04, 2016
Dear Maureen Garner:
This letter corrects our substantially equivalent letter of February 17, 2016.
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the
1
electronic product radiation control provisions (Sections 531-542 of the Act): 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Katherine Serrano -S
For : Courtney H.Lias, Ph.D.
Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known)
Device Name FREND™ Free T4 Test System
Indications for Use (Describe)
The FREND™ Free T4 Test System is a rapid indirect competitive immunoassay for the quantitation of free thyroxine (FT4) in human serum and lithium heparinized plasma specimens using the FREND™ Free T4 system. Measurements of free thyroxine (FT4) are used in the diagnosis of thyroid disorders. The FREND™ Free T4 Test System is intended for use in clinical laboratories. For in vitro diagnostic use only. The test is not intended for point-of-care facilities.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| Prescription Use (Part 21 CFR 801 Subpart D) Over-The-Counter Use (21 CFR 801 Subpart C) |
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3
510(k) Summary
As required by the Safe Medical Devices Act (SMDA) of 1990 and in accordance with 21 CFR §807.92, a 510(k) summary is provided.
A. Applicant
| Company Name: | NanoEnTek, Inc. |
|---|---|
| Address: | 12F 5 Digital-ro, 26-gil, Guro-gu |
| Seoul 152-740, KOREA | |
| Contact Person: | Sunmi Han |
| Phone Number: | +82-2-6220-7940 |
| Facsimile Number: | +82-2-6220-7721 |
B. 510(k) Preparer Information (Contact Person)
| Company Name: | New World Regulatory Solutions, Inc. |
|---|---|
| Address: | P.O. Box 5374 |
| Toms River, New Jersey 08754, USA | |
| Contact Person: | Maureen Garner |
| Phone Number: | (732) 779-7422 |
| Facsimile Number: | (732) 270-4829 |
| Email: | NWRSinc@gmail.com |
C. Purpose for Submission:
New Analyte on FREND™ System
D. Measurand:
Free thyroxine
E. Type of Test:
Quantitative, Fluorescence Immunoassay
F. Proprietary and Established Device Name:
FREND™ Free T4 Test System
Regulatory Information: G.
| Common Name: | FREND™ Free T4 (reagent cartridge) |
|---|---|
| Generic Name: | Competitive Immunoassay, Free T4 |
| Regulation Number: | 21 CFR §862.1695 |
| Product Code: | CEC |
| Classification: | Class II |
| Classification Name: | Free thyroxine test system |
| Panel: | Chemistry (75) |
H. Intended Use:
-
- Intended use: See indications for use below:
4
-
- Indication(s) for use:
The FREND™ Free T4 Test System, is a rapid indirect fluorescence immunoassay for the quantitative determination of free thyroxine (Free T4) in human serum and lithium heparinized plasma specimens using the FREND™ System. Measurements of free thyroxine (Free T4) are used in the diagnosis of thyroid disorders. The FREND™ Free T4 Test System is intended for use in clinical laboratories. For in vitro diagnostic use only. This test is not intended for point-of-care facilities.
- Indication(s) for use:
-
- Special conditions for use statement(s): For prescription use only.
-
- Special instrument requirements: NanoEnTek FREND™ System
l. Device Description
The FREND™ Free T4 is a rapid fluorescence immunoassay that measures Free T4 in human serum and in lithium heparinized plasma using the FREND™ Free T4 Test System.
The FREND™ Free T4 is a single use fluorescence immunoassay designed to quantify the concentration of free thyroxine in serum and lithium heparinized plasma samples, The FREND™ Free T4 test is a two-step competitive immunoassay with gold nanoparticles labeled with T4-specific monoclonal anti-T4- antibody (mouse), T3-BSA labeled with fluorescent nanoparticles, and fluorescence detection by the FREND™ System.
The FREND™ Free T4 Test utilizes microfluidic technology and detects immunecomplexes bound to Free T4. A 70ul Sample is first incubated during Step 1 for five minutes at 37 degrees C in the Free T4 Gold AB Tube with monoclonal anti-T4 antibody conjugated with gold nanoparticles. In Step 2, 35 ul of the mixture from Step 1 is manually loaded into the inlet of the cartridge, where it hydrates a T3-BSA fluorescent bead conjugate and migrates along the test strip. During migration the bound Free T4 in the sample and the fluorescent bead conjugates of T3-BSA compete to form antigenantibody complex in the test zone. Unbound T3-BSA fluorescent conjugates flow through and bind to the anti-T4 antibody that is fixed on the surface in the reference zone. Step 2 takes approximately four minutes after which the fluorescent signals in the test and reference zones are measured.
Free T4 quantification is based upon the ratio of the intensity of the test and reference zones. A lower ratio of fluorescence is indicative of a higher Free T4 concentration, in other words, the maqnitude of the fluorescence ratio is inversely proportional to the amount of Free T4 in the sample.
The free T4 detection range of the FREND™ Free T4 Test System is 0.4 to 6.0 ng/dL. Results are determined via a lot-specific calibration curve which is generated by the manufacturer using a six-point calibration determined from values averaged from five replicates at each level. The established curve is uploaded to the FREND™ System via the Free T4 Code-chip and is valid until the lot expiration date. The established curve is saved in the code-chip and valid until the expiration date of the test cartridge lot.
The FREND™ Free T4 Test cartridge is a disposable plastic device that houses the reagents and contains a port or opening (inlet) where the sample is applied. Once the sample is applied, it will mix with the reagents and travel towards the detection area via capillary action.
5
The FREND™ System is a portable, automated FREND™ cartridge reader. The FREND™ System is based on quantitative immunoassay technology capable of quantifying single or multiple analytes by measuring laser-induced fluorescence in a single-use disposable reagent cartridge. The FREND™ cartridge utilizes micro-fluidics lateral flow technology where the analyte of interest in the sample forms immune complexes while moving through the fluidics pathway in the cartridge. The concentration of the analyte of interest in an unknown sample is calculated using the ratio of the fluorescent intensity of the test zone and the reference zone.
The FREND™ System is a bench top fluorescence reader containing a touch screen user interface. The System has a slot that accepts the FREND™ Free T4 Test Cartridge (which contains the reagents and sample), and is programmed to analyze the Test when the sample has fully reacted with the on-board in-cartridge reagents. Results of the test are displayed on the screen and can be printed on an optional printer.
The FREND™ System software controls the graphical user interface, communication with hardware, database manaqement and data analysis. The software also controls the functions of the mechanical components including the motor, laser, printer control and acquisition of data from the sensor. The user can set the time and date and enter patient ID through the graphic user interface. The user cannot make any changes to the software.
The FREND™ Free T4 Test System includes the following in the kit:
- 20 FREND™ Free T4 cartridges .
- . 20 Gold-T4 antibody tubes
- Disposable pipette tips .
- 1 FREND™ Free T4 Code Chip
- 1 FREND™ Free T4 Package Insert ●
The FREND™ System (previously cleared in K124056 (FREND™ PSA) and K131928 (FREND™ PSA)) is not provided with the kit but is required for the use of the FREND™ Free T4 test cartridge.
J. Substantial Equivalence Information:
A general comparison of the similarities and differences of the assays is presented in the table below:
6
| Similarities | |||
|---|---|---|---|
| ltem | FREND™ Free T4 Test System | Abbott ARCHITECT Free T4 | |
| (K123379) | |||
| Intended Use | The FREND™ Free T4 Test System | ||
| is a rapid indirect competitive | |||
| fluorescence immunoassay for the | |||
| quantitative determination of free | |||
| thyroxine (FT4) in human serum and | |||
| lithium heparinized plasma | |||
| specimens using the FREND™ | |||
| system. Measurements of free | |||
| thyroxine (FT4) are used in the | |||
| diagnosis of thyroid disorders. The | |||
| FREND™ Free T4 Test System is | The ARCHITECT Free T4 (FT4) is a | ||
| Chemiluminescent Microparticle | |||
| Immunoassay (CMIA) for the | |||
| quantitative determination of free | |||
| thyroxine (Free T4) in human serum | |||
| and plasma. The ARCHITECT Free | |||
| T4 assay is to be used as an aid in | |||
| the assessment of thyroid status. | |||
| The ARCHITECT Free T4 | |||
| Calibrators are for the calibration of | |||
| intended for use in clinical | |||
| laboratories. For in vitro diagnostic | |||
| use only. The test is not intended for | |||
| use in point-of-care facilities. | the ARCHITECT i System when | ||
| used for the quantitative | |||
| determination of free thyroxine | |||
| (FreeT4) in human serum and | |||
| plasma when using the ARCHITECT | |||
| Free T4 Reagent Kit. | |||
| The ARCHITECT Free T4 Controls | |||
| are for the verification of the | |||
| accuracy and precision of the | |||
| ARCHITECT i System when used | |||
| for the quantitative determination of | |||
| free thyroxine (Free T4) in human | |||
| serum and plasma when using the | |||
| ARCHITECT Free T4 Reagent Kit. | |||
| For in vitro diagnostic use only. | |||
| Sample Type | Human serum and lithium | Same | |
| heparinized plasma | |||
| Analyte | |||
| Type of Test | Free thyroxine | ||
| Fluorescent immunoassay | Same | ||
| Chemiluminescent immunoassay | |||
| determination of FT4 | determination of FT4 | ||
| Quality Control | Internal procedural/instrument quality | ||
| controls; External positive and | |||
| negative assay controls | Same | ||
| Interpretation of | |||
| Results | Interpolation from a lot-specific | ||
| calibration curve | Same | ||
| Measuring Range | 0.40- 6.00 ng/dL | Same | |
| Differences | |||
| Item | FREND™ Free T4 Test System | Abbott ARCHITECT Free T4 | |
| (K123379) | |||
| Sample Size | 70µL for the incubation step and | ||
| 35 µL for the running of the test | 95 µL for the first Free T4 test plus | ||
| 45 µL for each additional Free T4 | |||
| from the same test cup | |||
| Test Cartridge | Disposable single-use cartridge | No single-use cartridge | |
| Random | |||
| Access/Degree of | |||
| Automation | No random access, manual | ||
| manipulation | Random access, semi-automated |
7
K. Performance Characteristics (if/when applicable)
1. Analytical performance:
a. Precision/Reproducibility:
A single lot imprecision study was performed at the NanoEnTek laboratory as described in the CLS/ protocol EP5-A3. Three serum pools with low, intermediate and high Free T4 levels were assayed in duplicate twice per day for 20 days (80 total measurements). The results are summarized below:
| Sample
Pool | Mean Free T4 Conc.
(ng/dL) | Repeatabilit
y | | Between-
run | | Between-
day | | Within-
laboratory | |
|----------------|-------------------------------|-------------------|-----|-----------------|-----|-----------------|-----|-----------------------|-----|
| | | SD | CV% | SD | CV% | SD | CV% | SD | CV% |
| 1 | 0.917 | 0.067 | 7.3 | 0.000 | 0.0 | 0.032 | 3.5 | 0.074 | 8.1 |
| 2 | 1.850 | 0.103 | 5.6 | 0.000 | 0.0 | 0.069 | 3.7 | 0.124 | 6.7 |
| 3 | 3.979 | 0.186 | 4.7 | 0.152 | 3.8 | 0.093 | 2.3 | 0.258 | 6.5 |
| FREND™ Free T4 Single Site Single Lot Precision | ||
|---|---|---|
| ------------------------------------------------- | -- | -- |
b. Linearity/assay reportable range:
To demonstrate the linearity of the assay, a serum base pool with an elevated free thyroxine (7.5 ng/dL) was diluted to a total of 11 levels according to the dilution protocol outlined in CLSI EP6-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach. At each dilution level, the samples were measured in duplicate to determine the experimental value of free thyroxine. The FREND™ Free T4 Test System was determined to have acceptable linearity across a free T4 range of 0.11 ~ 7.5 ng/dL, (Slope = 0.978, Intercept = -0.0881, R2 = 0.9938). The measuring range of the FREND™ Free T4 is 0.4 ~ 6 ng/dL, which is within the linearity range.
c. Traceability, Stability, Expected values (controls, calibrators or methods):
The standards/calibrators are internally prepared according to the guideline of CLSI (Clinical Laboratory and Standards Institute), C45-A Measurement of Free Thyroid Hormones; Approved Guideline - first Edition. This internal standard is manufactured by gravimetric methods based on the L-Thyroxine (Sigma T1775, Cell culture grade). At each concentration level, the free T4 levels of calibrators are confirmed by measurement on ARCHITECT i free T4 assay (K123379). There is no need for calibration by the operator as the calibration information is coded in the individual cartridge.
d. Stability
Real-time stability testing for the Free T4 reagent kit was performed according to CLSI EP25-A, Evaluation of Stability of In Vitro Diagnostic Reagent stability studies based on procedures and criteria in the NanoEnTek quality system showed that the cartridges for FREND™ Free T4 are good for at least one year from the date of manufacturer if stored refrigerated appropriately as directed.
e. Detection Limit:
The Limit of Detection (LoD) and Limit of Quantitation (LoQ) for the FREND™ Free T4 were established according to the CLSI EP17-A2 protocol and found to be 0.32 ng/dL, and 0.36 ng/dL, respectively.
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f. Analytical specificity:
Interference Studies
Recovery between 90% to 110% of the expected Free T4, in the presence of interferents, is considered acceptable performance. The interference studies were performed with two levels of free T4 using the recommendations in the CLSI EP07-A2 protocol. Results are summarized in the table below.
| | Interferent (Concentration tested) | %Recovery
Free T4 Low | %Recovery
Free T4 High |
|-----------------------------------|------------------------------------|--------------------------|---------------------------|
| Endogenous
substances | Hemoglobin (500 mg/dL) | 109.5 | 106.3 |
| | Bilirubin conjugated (20 mg/dL) | 90.5 | 101.5 |
| | Bilirubin unconjugated (20 mg/dL) | 103.0 | 101.0 |
| | Triglyceride (3 g/dL) | 108.1 | 105.5 |
| | Total protein (12 g/dL) | 107.7 | 103.6 |
| | Biotin (2.5 µ/mL) | 101.5 | 94.0 |
| | IgG (2.5 mg/mL) | 102.9 | 101.7 |
| | IgA (60 µg/mL) | 100.7 | 95.8 |
| | IgM (45 µ/mL) | 106.2 | 94.7 |
| Pharmaceuticals | Acetaminophen (200 µ/mL) | 104.4 | 100.3 |
| | Erythromycin (60 µ/mL) | 102.7 | 100.2 |
| | Diltiazem (6.24 µ/mL) | 109.5 | 91.1 |
| | Verapamil (2 µ/mL) | 108.2 | 90.5 |
| | Acetylcysteine (415 µ/mL) | 102.7 | 109.4 |
| | Acetylsalicylic acid (250 µ/mL) | 96.5 | 98.3 |
| | Amiodarone (6 µ/mL) | 105.0 | 99.1 |
| | Ampicillin-Na (50.3 µ/mL) | 99.7 | 91.8 |
| | Ascorbic acid (60 µ/mL) | 100.0 | 91.9 |
| | Carbimazole (500 ng/mL) | 90.5 | 91.2 |
| | Cefoxitin (66 µ/mL) | 93.5 | 92.7 |
| | Cyclosporine (3 µ/mL) | 103.8 | 96.2 |
| | Doxycycline (30 µ/mL) | 104.8 | 95.1 |
| | Fluocortolone (400 µ/mL) | 90.1 | 99.5 |
| | Furosemide (12.5 µ/mL) | 100.3 | 101.4 |
| | Heparin (3,000 U/L) | 102.2 | 91.2 |
| | Hydrocortisone (1.8 µ/mL) | 96.9 | 90.1 |
| | Ibuprofen (250 µ/mL) | 98.6 | 109.0 |
| | lodide (380 µ/mL) | 98.0 | 86.8 |
| | Levodopa (4 mg/mL) | 99.2 | 103.9 |
| | Methyldopa (15 µ/mL) | 100.0 | 90.0 |
| | Metronidazole (120 µ/mL) | 99.0 | 92.9 |
| | Octreotide (2 ng/mL) | 101.7 | 90.8 |
| | Perchlorate (16 ng/mL) | 99.0 | 91.6 |
| | Prednisolone (3 µ/mL) | 98.6 | 91.6 |
| | Propranolol (2 µ/mL) | 96.9 | 90.0 |
| | Propylthiouracil (10 µ/mL) | 90.5 | 90.8 |
| Rifampicin (640 µ/mL) | 91.5 | 93.9 | |
| Theophylline (400 µ/mL) | 107.1 | 94.5 | |
| Thiamazole/Methimazole (500 µ/mL) | 102.0 | 90.7 | |
| Avidin (5 µg/mL) | 107.7 | 90.4 | |
| Au-nanoparticles (5 µg/mL) | 103.4 | 97.4 | |
| Heterophilic
Antibodies | RF (1075 IU/mL) | 109.2 | 93.5 |
| | HAMA (70 ng/mL) | 104.4 | 96.5 |
9
Cross Reactivity
The following substances were evaluated for potential cross-reactivity with the FREND™ Free T4 at two concentrations. Testing was done according to the CLSI protocol EP07-A2. No significant cross-reactivity was found except for the L-Thyroxine (Levothyroxine) itself.
| Cross-reactant | % Cross-reactivity | |||
|---|---|---|---|---|
| Cross-reactant | Concentration (ng/dL) | Free T4 Low | Free T4 High | |
| Levothyroxine, T4 (1 ug/dL) | 1.000 | 99.44 | 99.57 | |
| Diiodothyronine, T2 (5 ug/dL) | 5.000 | 0.0001 | 0.0006 | |
| Tetraiodothyroacetic Acid (10 ug/dL) | 10,000 | 0.00005 | 0.00005 | |
| Triiodothyroacetic Acid (1 ug/dL) | 1.000 | 0.004 | 0.0157 | |
| Triiodothyropropionic Acid (5 ug/dL) | 5.000 | 0.0019 | 0.0055 | |
| Diiodotyrosine. DIT (1 ug/dL) | 1,000,000 | 1E-06 | 2E-06 | |
| L-Triiodothyronine, T3 (1 ug/dL) | 1.000 | 0.0037 | 0.026 | |
| Monoiodotyrosine (1 ug/dL) | 1,000,000 | 1E-06 | 0.000019 | |
| Reverse T3 (10 ug/dL) | 10.000 | 0.0009 | 0.0022 |
% Cross-reactivity = 100x((Measured value) / interferent concentration), as absolute value
g. Assay cut-off:
Not applicable
2. Comparison studies
a. Method comparison with predicate device:
Comparison studies were performed in a CLIA-certified laboratory testing facility at the time the clinical samples were evaluated. If the predicate device and the FREND™ system could be run at the same time, samples were validated simultaneously using the same aliquot of sample. If that was not practical, two separate aliquots of each sample, freshly defrosted prior to analysis, were used - one for each method. The instrument reagent system used as the predicate device was the Abbott ARCHITECT Free T4 Assay (K123379) run on the Abbott ARCHITECT i System. All samples (358) used in the clinical testing were analyzed by both the predicate and the subject device.
Results generated using the FREND™ Free T4 on the FREND™ System (v) were compared to those obtained using a previously FDA cleared ARCHITECT free T4 assay (x) by Ordinary least square fit method. Results of this study are shown in the table below:
| Slope: 1.010 (95% CI: 0.992 to 1.028) | y-Intercept: 0.057 (95% CI: 0.021 to 0.094) |
|---|---|
| Number of Samples: 358 | |
| r: 0.986 | Range Tested: 0.43 ~ 5.99 ng/dL |
Comparability using CLSI guideline EP09-A3, shows that the difference between the concentrations measured by the test device and the predicate device is less than the allowable difference and the two methods compare favorably.
b. Matrix comparison:
The matrix comparison study was performed at the NanoEnTek laboratory according to CLSI EP14-A3. Free T4 concentrations in 48 paired serum and lithium heparin samples were measured using the FREND™ Free T4. Passing-Bablok regression analysis of serum results (x) compared to lithium heparin plasma results (y) yielded the following regression, indicating that FREND™ Free T4 can be measured equally well in serum and lithium heparin plasma.
10
| Slope: 1.017 (95% CI: 0.991 to 1.044) | y-Intercept: -0.008 (95% CI: -0.055 to 0.0451) |
|---|---|
| Number of Samples: 48 | Range Tested: 0.44 ~ 5.63 ng/dL |
-
- Clinical studies:
- a. Clinical Sensitivity Not applicable
- b. Clinical Specificity Not applicable
- c. Other clinical supportive data (when a. and b. are not applicable) Not applicable
-
- Clinical cut-off: Not applicable
5. Expected values/Reference range:
Serum samples from a total of 196 normal, apparently healthy adult individuals were assayed on 3 lots of the FREND™ Free T4 assay using a single FREND™ System. The reference interval for the FREND™ Free T4 Test System, determined according to CLSI C28-A3 guidelines, was found to be 0.83-1.60 ng/dL.
L. Proposed Labeling
The labeling is sufficient and it satisfies the requirements of 21 CFR §809.10.
M. Conclusion
The submitted information in this premarket notification is complete and supports a substantial equivalence determination.