(414 days)
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No
The document explicitly states "Mentions AI, DNN, or ML: Not Found" and describes a standard immunoassay technology with calibration curves, not AI/ML algorithms.
No.
Explanation: This device is an in vitro diagnostic (IVD) assay used to measure free thyroxine levels for diagnostic purposes, not to provide therapy or treatment.
Yes
The "Intended Use / Indications for Use" section explicitly states, "Measurements obtained by this device are used in the diagnosis and treatment of thyroid disease."
No
The device is an in vitro diagnostic immunoassay kit intended for use on specific hardware analyzers (cobas e immunoassay analyzers). It involves reagents and a chemical reaction (electrochemiluminescence immunoassay) to determine the concentration of free thyroxine. This is a hardware-dependent assay, not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states: "Assay for the in vitro quantitative determination of free thyroxine in human serum and plasma." The term "in vitro" is a key indicator of an IVD. It also mentions that the measurements are used in the "diagnosis and treatment of thyroid disease," which is a diagnostic purpose.
- Device Description: The description reiterates that it is an "in vitro quantitative determination of free thyroxine in human serum and plasma."
- Technology: The use of "electrochemiluminescence immunoassay (ECLIA)" on an "immunoassay analyzer" is a common method for performing in vitro diagnostic tests on biological samples.
- Performance Studies: The detailed description of performance studies (precision, linearity, interference, method comparison, reference range) are typical evaluations performed for IVD devices to demonstrate their analytical and clinical performance.
All these elements strongly indicate that the device is designed to be used outside of the body (in vitro) to analyze biological samples for diagnostic purposes, which is the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
Assay for the in vitro quantitative determination of free thyroxine in human serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of thyroid disease.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on the cobas e immunoassay analyzers.
Product codes (comma separated list FDA assigned to the subject device)
CEC
Device Description
The Elecsys FT4 IV immunoassay a fourth generation FT4 assay by Roche Diagnostics for the for the in vitro quantitative determination of free thyroxine in human serum and plasma. It is intended for use on the cobas e immunoassay analyzers. The cobas e family of analyzers uses electrochemiluminescence immunoassay "ECLIA" technology. The assay is an 18 minute assay utilizing a competition principle using a monoclonal antibody which is specifically directed against free thyroxine. Results are determined via a calibration curve which is instrument specifically generated by 2-point calibration against the master curve for that reagent lot.
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
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Anatomical Site
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Indicated Patient Age Range
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Intended User / Care Setting
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Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Non-clinical performance evaluation for Elecsys FT4 IV executed with the study briefly summarized.
Precision: Precision measurements were conducted for both 21 days and 5 days with the Elecsys FT4 IV assay to evaluate repeatability (within-run precision) and intermediate precision (withinlaboratory precision) according the CLSI guideline EP05-A3. All predefined acceptance criteria was met for the precision experiments.
Lot-to-lot reproducibility: Lot-to-lot reproducibility was performed for the Elecsys FT4 IV assay using three reagent lots according the CLSI guideline EP05-A3. All predefined acceptance criteria was met for the lot-to-lot reproducibility experiment.
Analytical Sensitivity (LoB, LoD, LoQ):
LoB: Experimental Design included three reagent lots evaluated on one cobas e 411 analyzer, six runs over three or more days with one blank sample with ten replicates per run. The zero-level (blank) sample used was fT4 depleted human serum sample pool. In total, 60 determinations for analyte free samples have been obtained. The LoB was calculated according to CLSI EP17-A2. The LoB claim in the labeling will be set to 0.02 ng/dL (0.3 pmol/L).
LoD: Experimental Design included three reagent lots evaluated on one cobas e 411 analyzer, six runs over three or more days with five samples with two replicates/sample/run. The five samples were low-level human serum sample pools (diluted). A pooled estimate of the precision (SD total) for the 5 low-level samples was calculated. The LoD was calculated according to CLSI EP17-A2. The LoD claim in the labeling will be set to 0.04 ng/dL (0.5 pmol/L).
LoQ: Experimental Design included three reagent lots evaluated on one cobas e 411 analyzer, one run per day over five days. Five replicates per each sample per run with at least five low level samples of serum and 25 replicates/sample/reagent lot. The LoQ was calculated according to CLSI EP17-A2. The LoQ claim in the labeling will be set to 0.101 ng/dL (1.3 pmol/L).
Linearity/Assay Reportable Range: Linearity of the Elecsys FT4 IV assay was assessed using human serum samples on the cobas e 411 Immunoassay Analyzer according to CLSI EP6-Ed2. Linearity was confirmed in the range of 0.098-8.13 ng/dL (1.26-105 pmol/L), and a measuring range of 0.101-7.77 ng/dL (1.3-100 pmol/L) will be claimed in the labeling.
Human Anti-Mouse Antibodies (HAMA): Not Applicable (no mouse antibodies used)
Endogenous Interferences: Nine endogenous substances were evaluated for potential interference with the Elecsys FT4 IV assay on the cobas e 411 analyzer according the CLSI guideline EP07-A3. All predefined acceptance criteria was met.
Analytical Specificity/Cross-Reactivity: A cross-reactivity study was conducted with Elecsys FT4 IV on the cobas e 411 analyzer to evaluate the potential cross-reacting compounds using human serum samples (native human single donor sera).
Exogenous Interferences – Drugs: An exogenous interference study was conducted to evaluate 17 commonly and 15 specially used pharmaceutical compounds for potential interference with the Elecsys FT4 IV assay on the cobas e 411 analyzer. No significant interference was found with the highest concentration tested listed in the table. The drugs Furosemide, Carbamazepine, Phenytoin and Levothyroxine Sodium (L-T4, synthetic levothyroxine) caused elevated FT4 findings at the daily therapeutic dosage level.
Sample Matrix Comparison: The effect on quantitation of analyte in the presence of anticoagulants with the Elecsys FT4 IV immunoassay was determined by comparing values obtained from samples (native single donors and pools as well as spiked or diluted samples) drawn into Serum, Li-Heparin, K2-and K3-EDTA plasma primary tubes. All predefined acceptance criteria was met, supporting the labeling claim that serum, Li-Heparin, K2-EDTA and K3-EDTA plasma are acceptable sample types.
Method Comparison to Predicate: A method comparison was performed with the Elecsys FT4 II assay (predicate device) and the Elecsys FT4 IV assay, using a total of 121serum samples on the cobas e 411 analyzer using one lot of the Elecsys FT4 II assay and one lot of the FT4 IV assay covering the entire measuring range. The sample concentrations were between 0.13 and 7.68 ng/dL (1.65 and 98.8 pmol/L) for the reference method.
Reagent Stability:
Study 1: Reagent stability after first opening at 2-8°C (84 days) .
Study 2: On board reagent stability (28 days) .
Calibration Stability:
Study 1. Lot calibration stability
Study 2. On-board calibration stability .
Reference Range Study: A Reference Range study was performed in order to determine the specific reference intervals for Elecsys FT4 IV on the cobas e 411 immunoassay analyzer from health donors in the United States under routine laboratory conditions according to CLSI EP28-A3c. Serum samples from apparently healthy donors in the United States were obtained from a commercial vendor according to the inclusion and exclusion criteria. One clinical laboratory was contracted to measure samples with Elecsys FT4 IV assay on the cobas e 411 analyzer. The calculated 95% reference range corresponds to the 2.5th and 97.5th percentiles of results obtained from 150 apparently healthy subjects is 0.92 – 1.68 ng/dL (11.9 – 21.6 pmol/L).
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Analytical Sensitivity:
Limit of Blank = 0.02 ng/dL (0.3 pmol/L)
Limit of Detection = 0.04 ng/dL (0.5 pmol/L)
Limit of Quantitation = 0.101 ng/dL (1.3 pmol/L)
Precision:
Human serum 1: Repeatability CV 2.5%, Intermediate precision CV 5.6%
Human serum 2: Repeatability CV 1.1%, Intermediate precision CV 2.3%
Human serum 3: Repeatability CV 1.1%, Intermediate precision CV 2.0%
Human serum 4: Repeatability CV 1.0%, Intermediate precision CV 1.7%
Human serum 5: Repeatability CV 1.2%, Intermediate precision CV 2.1%
Human serum 6: Repeatability CV 1.7%, Intermediate precision CV 2.6%
PC Universal 1: Repeatability CV 0.9%, Intermediate precision CV 1.7%
PC Universal 2: Repeatability CV 1.2%, Intermediate precision CV 2.1%
Method Comparison to Predicate:
Passing Bablok: y = 1.03x - 0.025, τ = 0.967
Linear regression: y = 1.04x - 0.034, r = 0.999
Reference Range (95% CI):
2.5th percentile: 0.92 ng/dL (11.9 pmol/L) (95% Cl 0.81-0.96 ng/dL, 10.4-12.3 pmol/L)
97.5th percentile: 1.68 ng/dL (21.6 pmol/L) (95% Cl 1.51-2.00 ng/dL, 19.4-25.8 pmol/L)
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.
Elecsys FT4 II (K131244)
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.
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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).
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§ 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.
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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. Underneath the square are the words "U.S. FOOD & DRUG ADMINISTRATION" in blue.
April 7, 2023
Roche Diagnostics Bin Sun Regulatory Affairs Program Manager 9115 Hague Road Indianapolis, IN 46250
Re: K220456
Trade/Device Name: Elecsys FT4 IV Regulation Number: 21 CFR 862.1695 Regulation Name: Free Thyroxine Test System Regulatory Class: Class II Product Code: CEC Dated: December 8, 2022 Received: December 9, 2022
Dear Bin Sun:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
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
1
801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4. Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about 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,
Digitally signed by Paula V. Paula V. Caposino -S Caposino -S Date: 2023.04.07
Paula Caposino, Ph.D. Acting 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) K220456
Device Name Elecsys FT4 IV
Indications for Use (Describe)
Assay for the in vitro quantitative determination of free thyroxine in human serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of thyroid disease.
The electrochemiluminescence immunoasay "ECLIA" is intended for use on the cobas e immunoassay analyzers.
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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K220456 Elecsys FT4 IV 510(k) Summary
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
| Submitter Name | Roche Diagnostics |
|---|---|
| Address | 9115 Hague Road |
| P.O. Box 50416 | |
| Indianapolis, IN 46250-0457 | |
| Contact | Bin Sun |
| Phone: (317) 292-3781 | |
| Email: bin.sun.bs2@roche.com | |
| Date Prepared | April 6, 2023 |
| Proprietary Name | Elecsys FT4 IV |
| Common Name | Free thyroxine |
| Classification Name | Radioimmunoassay, Free thyroxine test system |
| Product Codes, | |
| Regulation Numbers | CEC, 21CFR862.1695 |
| Predicate Devices | Elecsys FT4 II (K131244) |
| Establishment Registration | Roche Diagnostics GmbH Mannheim, Germany: 9610126 |
| Roche Diagnostics GmbH Penzberg, Germany: 9610529 | |
| Roche Diagnostics Indianapolis, IN United States: 1823260 |
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1. DEVICE DESCRIPTION
The Elecsys FT4 IV immunoassay a fourth generation FT4 assay by Roche Diagnostics for the for the in vitro quantitative determination of free thyroxine in human serum and plasma. It is intended for use on the cobas e immunoassay analyzers. The cobas e family of analyzers uses electrochemiluminescence immunoassay "ECLIA" technology. The assay is an 18 minute assay utilizing a competition principle using a monoclonal antibody which is specifically directed against free thyroxine. Results are determined via a calibration curve which is instrument specifically generated by 2-point calibration against the master curve for that reagent lot.
1.1. Reagents
The reagent working solutions include:
Rackpack (kit placed on analyzer)
- M: Streptavidin-coated microparticles .
- . R1: Anti-T4-Ab~Ru(bpy)
- . R2: T4~biotin
INDICATIONS FOR USE 2.
Assay for the in vitro quantitative determination of free thyroxine in human serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of thyroid disease.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on the cobas e immunoassay analyzers.
TECHNOLOGICAL CHARACTERISTICS 3.
The following tables compare the Elecsys FT4 IV with its predicate device, Elecsys FT4 II assay (K131244).
| Item | Predicate
(Elecsys FT4 II, K131244) | Candidate Device
(Elecsys FT4 IV ) |
|---------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Proprietary name | Elecsys FT4 II | Elecsys FT4 IV |
| Item | Predicate
(Elecsys FT4 II, K131244) | Candidate Device
(Elecsys FT4 IV ) |
| Indications for Use | The Elecsys FT4 II assay is for the in
vitro quantitative determination of free
Thyroxine in human serum and
plasma. Measurements obtained by
this device are used in the diagnosis
and treatment of thyroid diseases.
The electrochemiluminescence
immunoassay "ECLIA" is intended
for use on Elecsys and cobas e
immunoassay analyzers | The Elecsys FT4 IV assay is for the in
vitro quantitative determination of free
Thyroxine in human serum and
plasma. Measurements obtained by
this device are used in the diagnosis
and treatment of thyroid disease.
The electrochemiluminescence
immunoassay “ECLIA" is intended
for use on cobas e immunoassay
analyzers. |
| Test Principle | The Elecsys FT4 II assay is a two-step
competitive immunoassay with
streptavidin microparticles and
electrochemiluminescence detection
system. | No change |
| Technology | ECLIA | No change |
| Test format | Competitive | No change |
| Test type | Quantitative | No change |
| Application time | 18 min | No change |
| Assay protocol | 1st Incubation:
R1+sample
2nd incubation:
Addition of R2 + streptavidin-coated
microparticles (beads) | No change |
| Sample type | Undiluted human serum and undiluted
plasma treated with Li-heparin, K2-
EDTA and K3-EDTA | No change |
| Pipetting volume
sample | 15 μL | No change |
| Pipetting volume beads | 35 μL | No change |
| Pipetting volume R1 | 75 μL | No change |
| Pipetting volume R2 | 75 μL | No change |
| Handling of R1 and R2 | Liquid, ready to use | No change |
| Buffer composition R1 | phosphate buffer 100 mmol/L | No Change |
| | - | Anti-Biotin Antibody; specific for
free, unconjugated biotin ("scavenger
antibody"). MAKrK-21E12-
IgG |
| Antibodies used in R1 | Ruthenylated polyclonal T4-specific
sheep antibody PABS-Fab-sRu | Ruthenylatedmonoclonal T4-specific
rabbit antibody. MABrK-38F8-
Fab-sRu |
| Buffer composition R2 | phosphate buffer 100 mmol/L | No Change |
| | D-Biotin | N-Biotinylsarcosine (Biotin-derivate) |
| Item | Predicate
(Elecsys FT4 II, K131244) | Candidate Device
(Elecsys FT4 IV ) |
| Biotinylated component
in R2 | T4(OSu)-bis-DADOO-Bi | No change |
| Biotin Tolerance |