K Number
K131244
Device Name
ELECSYS FT4 II ASSAY, ELECSYS FT4 II CALSET
Manufacturer
Date Cleared
2014-01-27

(271 days)

Product Code
Regulation Number
862.1695
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP Authorized
Intended 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. Elecsys FT4 II CalSet is used for calibrating the quantitative Elecsys FT4 II assay on the Elecsys and cobas e immunoassay analyzers.
Device Description
1) The Elecsys F4 II Assay is a quantitative test for determination of free thyroxine in human serum and plasma. The total duration of the assay is 18 minutes. Elecsys FT4 II is a two-step competitive immunoassay with streptavidin microparticles, T4-specific polyclonal anti-T4-antibody (sheep) labeled with a sulfonyl-ruthenium complex, and electrochemiluminescence detection. Results are determined via a calibration curve which is instrument-specifically generated by a two-point calibration and a master curve provided via the reagent barcode. (2) The Elecsys FT4 II CalSet is a ready-for-use buffer/protein (bovine serum albumin) matrix with added L-Thyroxine in two concentration ranges. FT4 II Cal1: 2 bottles, each containing 1.0 mL of calibrator 1 FT4 II Cal2: 2 bottles, each containing 1.0 mL of calibrator 2 Note: The reagent and calibrator are packaged separately.
More Information

Not Found

No
The description details a standard immunoassay and calibration process, with no mention of AI or ML algorithms for data analysis, interpretation, or decision-making. The results are determined via a calibration curve, which is a traditional method.

No.
This device is an in vitro diagnostic (IVD) device used for the quantitative determination of free Thyroxine, which aids in the diagnosis and treatment of thyroid diseases. It provides information for diagnosis and treatment but does not directly deliver therapy or treat a condition itself.

Yes

The "Intended Use / Indications for Use" section explicitly states that "Measurements obtained by this device are used in the diagnosis and treatment of thyroid diseases." This clearly indicates its diagnostic purpose.

No

The device is an in vitro diagnostic assay and calibrator intended for use on specific immunoassay analyzers, which are hardware devices. The description details the chemical reactions and physical components of the assay and calibrator.

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

  • Intended Use: The "Intended Use / Indications for Use" section explicitly states that the Elecsys FT4 II Assay is "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.
  • Purpose: The intended use also states that the measurements are "used in the diagnosis and treatment of thyroid diseases." This indicates a medical purpose for the test results, which is characteristic of IVDs.
  • Sample Type: The assay is performed on "human serum and plasma," which are biological samples. IVDs are designed to analyze biological samples.
  • Device Description: The description details a laboratory-based immunoassay ("electrochemiluminescence immunoassay 'ECLIA'") performed on specific analyzers ("Elecsys and cobas e immunoassay analyzers"). This is consistent with the nature of IVD tests.
  • Calibration: The mention of the "Elecsys FT4 II CalSet" for calibrating the assay further supports its use in a controlled laboratory setting for quantitative measurements, typical of IVDs.
  • Performance Studies: The extensive performance studies described (precision, limits, linearity, method comparison, interference, stability) are standard evaluations for IVD devices to demonstrate their analytical performance and suitability for clinical use.
  • Predicate Device: The identification of a "Predicate Device(s)" with a K number (K961489, Elecsys FT4 Assay; K961489, Elecsys FT4 CalSet) indicates that this device is being compared to a previously cleared or approved IVD.

All these factors collectively confirm that the Elecsys FT4 II Assay and its associated CalSet are intended for in vitro diagnostic use.

N/A

Intended Use / Indications for Use

Elecsys FT4 II Reagent:
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.

Elecsys FT4 II CalSet: Elecsys FT4 II CalSet is used for calibrating the quantitative Elecsys FT4 11 assay on the Elecsys and cobas e immunoassay analyzers.

Product codes (comma separated list FDA assigned to the subject device)

CEC, JIT

Device Description

  1. The Elecsys F4 II Assay is a quantitative test for determination of free thyroxine in human serum and plasma. The total duration of the assay is 18 minutes. Elecsys FT4 II is a two-step competitive immunoassay with streptavidin microparticles, T4-specific polyclonal anti-T4-antibody (sheep) labeled with a sulfonyl-ruthenium complex, and electrochemiluminescence detection. Results are determined via a calibration curve which is instrument-specifically generated by a two-point calibration and a master curve provided via the reagent barcode.

(2) The Elecsys FT4 II CalSet is a ready-for-use buffer/protein (bovine serum albumin) matrix with added L-Thyroxine in two concentration ranges. FT4 II Cal1: 2 bottles, each containing 1.0 mL of calibrator 1 FT4 II Cal2: 2 bottles, each containing 1.0 mL of calibrator 2 Note: The reagent and calibrator are packaged separately.

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

Not Found

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)

The Elecsys FT4 II Assay was evaluated for several performance characteristics, including precision, limit of blank, limit of detection, limit of quantitation, linearity, method comparison, interfering substances, and calibration and reagent stability. There were no modifications to the Elecsys FT4 II CalSet from the Elecsys FT4 CalSet other than the name and catalog number.

  1. Precision (CLSI EP5-A2): The precision of the Elecsys FT4 II assay was evaluated on one cobas e 411 Immunoassay Analyzer according to CLSI EP5-A2 guideline. Repeatability and Intermediate precision were calculated according to EP5-A2.
    The protocol consisted of testing 2 replicates of each human serum sample and control per run, two (2) runs per day (whereas the runs were divided by dummy samples) for 21 days.
    Sample | Mean (ng/dL) | Repeatability SD (ng/dL) | Repeatability CV (%) | 95% UCL* (% or ng/dL) | Intermediate Precision SD (ng/dL) | Intermediate Precision CV (%) | 95% UCL* (% or ng/dL) | n
    PCU 1 | 1.22 | 0.011 | 0.9 | 1.1 | 0.022 | 1.8 | 2.4 | 84
    PCU 2 | 3.11 | 0.032 | 1.0 | 1.3 | 0.089 | 2.9 | 3.9 | 84
    HS 1 | 0.138 | 0.006 | 4.0 | 0.007 ng/dL | 0.011 | 7.6 | 0.014 ng/dL | 84
    HS 2 | 1.03 | 0.013 | 1.3 | 1.6 | 0.023 | 2.3 | 2.9 | 84
    HS 3 | 1.90 | 0.024 | 1.3 | 1.6 | 0.040 | 2.1 | 2.8 | 84
    HS 4 | 4.93 | 0.082 | 1.7 | 2.1 | 0.163 | 3.3 | 4.4 | 84
    HS 5 | 7.09 | 0.127 | 1.8 | 2.3 | 0.319 | 4.5 | 6.2 | 84
    Based on these data, the precision meets the specifications.

  2. Limit of Blank (LoB) (CLSI EP17-A2): LoB of the Elecsys FT4 II assay on two cobas e 411 Immunoassay Analyzers has been determined according to CLSI EP17-A2 using three reagent lots. The distribution of values for one analyte-free human serum sample has been determined on two cobas e 411 Immunoassay Analyzers over four days, one or two runs per day with five-fold determination in each run: (total 60 determinations). The LoB claim in the package insert will be set to ≤ 0.03 ng/dL.

  3. Limit of Detection (LoD) (CLSI EP17-A2): LoD of the Elecsys FT4 II assay has been determined according to CLSI EP17-A2, 5.3.3.2. The distribution of values for five low-level human serum samples has been determined on two cobas e 411 immunoassay analyzers over four days, one or two runs per day with a single measurement per run. The LoD claim in the package insert will be set to ≤ 0.05 ng/dL.

  4. LoQ / Functional Sensitivity (CLSI EP17-A2): The LoQ of the Elecsys FT4 II assay was determined on the cobas e 411 immunoassay analyzer according to CLSI Guideline EP17-A2. A Low-Level Sample Set of 8 samples was prepared by diluting native human serum samples with an analyte-free human serum matrix and were tested in single replicates for four days, one or two runs per day on two cobas e 411 immunoassay analyzers.
    Lot MP02: Functional sensitivity = 0.059 ng/dL
    Lot P2: Functional sensitivity = 0.069 ng/dL
    Lot P3: Functional sensitivity = 0.080 ng/dL
    The Limit of Quantitation/Functional sensitivity claim in the package insert will be set to 0.1 ng/dL.

  5. Linearity (CLSI EP6-A): Linearity of the Elecsys FT4 II assay was assessed on the cobas e 411 Immunoassay Analyzer according to CLSI EP6-A. Three high analyte serum sample pools (spiked with L-Thyroxine) were diluted with fT4 depleted human serum. For each sample pool, 13 concentrations (11 dilutions) throughout the measuring range were prepared. Samples were assayed in 3-fold determination within a single run. Linearity was confirmed in the range from 0.096 to 8.20 ng/dL.

  6. Specificity/Cross Reactivity: The specificity of the Elecsys FT4 II assay was determined using native human serum samples or human serum samples spiked with L-Thyroxine (single donors) spiked with potential cross-reactant compounds tested in duplicate on cobas e 411 Immunoassay Analyzer.
    Cross Reactant | Cross Reactivity (%)
    L-T3 | ≤ 0.005
    D-T3 | ≤ 0.001
    rT3 | ≤ 0.003
    3-iodo-L-trosine | ≤ 0.000
    3,5-diiodo-L-tyrosine | ≤ 0.000
    3,3',5-triiodohyroacetic acid | ≤ 0.000
    3,3',5,5'-tetraiodothyroacetic acid | ≤ 0.001

  7. Exogenous Interferences - Drugs: 17 pharmaceutical compounds (concentration defined as x times the maximum daily dose) and 12 thyroid drugs and Furosemide were spiked into human serum samples and tested with the Elecsys FT4 II assay on the cobas e 411 Immunoassay Analyzer. Each compound, except Levothyroxine and Furosemide, was found to be non-interfering at the concentration listed. Levothyroxine and Furosemide will be listed as interfering substances in the "Limitations - Interference" section of the package insert.

  8. Exogenous Interferences - Anticoagulants: The effect on quantitation of analyte in the presence of anticoagulants with the Elecsys FT4 II Immunoassay was determined by comparing values obtained from native samples or samples spiked with L-Thyroxine (single donors) drawn into serum, Li-Heparin, K2-EDTA-, and K3-EDTA-plasma primary tubes, and Li-Heparin Plasma Separation Tubes. Between 53 and 63 serum/plasma pairs per sample material were tested in single determination with one reagent lot on one cobas e 411 Immunoassay Analyzer. The resulting data support the package insert claim that serum, Li-Heparin, K2-EDTA-, and K3-EDTA-plasma specimens are acceptable sample types for use with the Elecsys FT4 II Immunoassay.

  9. Endogenous Interferences: Effect on quantitation of analyte in the presence of endogenous interfering substances using the Elecsys FT4 II Immunoassay was determined on the cobas e 411 Immunoassay Analyzer using pooled human serum samples spiked with L-Thyroxine. For each interfering substance, 3 serum samples containing low, mid, and high concentrations of fT4 were tested. The assay is unaffected by icterus (bilirubin

§ 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

CONFIDENTIAL

JAN 2 7 2014

510(k) Summary

According to the requirements of 21 CFR 807.92, the following information Introduction provides sufficient detail to understand the basis for a determination of substantial equivalence.

Submitter Name, Address, Contact

Roche Diagnostics 9115 Hague Road Indianapolis, IN 46250

Contact Person: Edie Eads

Date Prepared: January 21, 2014

| Device Name | Proprietary name: | (1) Elecsys FT4 II Assay
(2) Elecsys FT4 II CalSet |
|-------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------|
| | Common name: | (1) FT4 II Assay
(2) FT4 II Calibrator |
| | Classification name: | (1) Radioimmunoassay, Free thyroxine test system
(2) Calibrator |
| | Product Codes: | (1) CEC, 21 CFR 862.1695
(2) JIT, 21 CFR 862.1150 |
| | Predicate Devices: | (1) Elecsys FT4 Assay (K961489)
CEC, 21 CFR 862.1695
(2) Elecsys FT4 CalSet (K961489)
JIS, 21 CFR 862.1150 |
| Establishment
Registration | For the Elecsys FT4 II Assay and the Elecsys FT4 II CalSet, the
establishment registration number for Roche Diagnostics GmbH in
Mannheim, Germany, is 9610126 and for Penzberg, Germany, is 9610529. | |

The establishment registration number for Roche Diagnostics United States is

, t

1

.

·

| Device
Description | 1) The Elecsys F4 II Assay is a quantitative test for determination of free
thyroxine in human serum and plasma. The total duration of the assay is 18
minutes. Elecsys FT4 II is a two-step competitive immunoassay with
streptavidin microparticles, T4-specific polyclonal anti-T4-antibody (sheep)
labeled with a sulfonyl-ruthenium complex, and electrochemiluminescence
detection. Results are determined via a calibration curve which is instrument-
specifically generated by a two-point calibration and a master curve provided
via the reagent barcode.

(2) The Elecsys FT4 II CalSet is a ready-for-use buffer/protein (bovine serum
albumin) matrix with added L-Thyroxine in two concentration ranges.
FT4 II Cal1: 2 bottles, each containing 1.0 mL of calibrator 1 FT4 II Cal2: 2 bottles, each containing 1.0 mL of calibrator 2 Note: The reagent and calibrator are packaged separately. |
|--------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended
Use/
Indications
for Use | Elecsys FT4 II Reagent:
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.

  • Elecsys FT4 II CalSet: Elecsys FT4 II CalSet is used for calibrating . the quantitative Elecsys FT4 11 assay on the Elecsys and cobas e immunoassay analyzers.

2

CONFIDENTIAL

510(k) Summary, continued

| Substantial
Equivalence | The Elecsys FT4 II Test System is substantially equivalent to other
devices legally marketed in the United States.

(1) Elecsys FT4 II Assay is equivalent to the Elecsys FT4 Assay
(K961489).

(2) Elecsys FT4 II CalSet is equivalent to the Elecsys FT4 CalSet
(K961489). |
|--------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Substantial
Equivalence -
Comparison | The following tables compare the Elecsys FT4 II Test System and the
Elecsys FT4 II CalSet with their predicates. |

Comparison of Assays-Similarities and Differences

FeatureElecsys FT4 II AssayPredicate Device: Elecsys FT4 Assay (K961489)
General Assay Features
Intended Use/ Indications for UseThe 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. | Immunoassay for the in vitro quantitative determination of free Thyroxine in human serum and plasma.

The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. |
| Assay Protocol | Quantitative electrochemiluminescence immunoassay | Same |
| Detection Protocol | Electrochemiluminescence | Same |
| Applications | 18-minute application | Same |
| Assay Comparison | | |
| Feature | Elecsys FT4 II Assay | Predicate Device: Elecsys FT4 Assay (K961489) |
| General Assay Features | | |
| Instrument Platform | cobas e 411, | cobas e 411, Elecsys 2010,
MODULAR ANALYTICS E170,
cobas e 411, cobas e 601 and cobas e 602 |
| Sample Volume | 15 µL | Same |
| Sample Type | Undiluted human serum and undiluted
plasma treated with Li-heparin, K2-EDTA, and K3-EDTA. | Undiluted human serum and undiluted
plasma treated with Li-, Na-, NH+4 -
heparin, K3-EDTA, sodium citrate,
and sodium fluoride/potassium oxalate. |
| Reagents | The Elecsys FT4 II assay is a
competitive immunoassay which
includes a specific polyclonal anti-T4-
antibody (sheep) labeled with a
sulfonyl-ruthenium complex,
thyroxine labeled with biotin and
streptavidin coated microparticles. | The Elecsys FT4 assay is a
competitive immunoassay which
includes a specific anti-T4 antibody
labeled with a ruthenium complex,
thyroxine labeled with biotin and
streptavidin coated microparticles. |
| Calibrator | Elecsys FT4 II CalSet, 2 levels | Elecsys FT4 CalSet, 2 levels |
| Calibration Interval | Calibration of an Elecsys FT4 II
reagent lot is recommended every 28
days. During that time period, fresh
reagent kits of the same lot can be
used without calibration by using the
calibration curve of the Day 0 reagent
kit. Renewed calibration is
recommended as follows:

• After 1 month (28 days) when
using the same reagent lot.
• After 7 days (when using the
same reagent kit on the
analyzer).
As required: e.g. quality control
findings outside the specified limits | Same |
| Controls | Elecsys PreciControl Universal or
other suitable control material | Same |
| Assay Comparison | | |
| Feature | Elecsys FT4 II Assay | Predicate Device: Elecsys FT4 Assay (K961489) |
| General Assay Features | | |
| Traceability /
Standardization | The Elecsys FT4 II Assay has been
standardized against the Elecsys FT4
method. The Elecsys FT4 assay is
traceable to the Enzymun-Test which
was standardized using equilibrium
dialysis. | The Elecsys FT4 Assay has been
standardized against the
Enzymun-Test FT4 method,
which was standardized using
equilibrium dialysis. |
| Reagent
Stability | Unopened at 2-8 °C—up to stated
expiration date | Same |
| | After opening at 2-8 °C—84 days (12
weeks) | Same |
| | On the Elecsys and cobas e
immunoassay analyzers – 28 days (4
weeks) onboard or 56 days when stored
alternatively in the refrigerator and on
the analyzer, with the total time
onboard the analyzer not exceeding 120
hours. | On the Elecsys and cobas e
immunoassay analyzers – 4
weeks onboard |

3

. 4

510(k) Summary, continued

Comparison of Assays-Similarities and Differences, continued

4

Comparison of Assays-Similarities and Differences, continued

5

Assay Comparison
FeatureElecsys FT4 II AssayPredicate Device: Elecsys FT4 Assay (K961489)
Labeled Performance Characteristics
Measuring Range0.1 ng/dL to 7.77 ng/dL
(1.3 - 100 pmol/L)0.300-100 pmol/L
Precisioncobas e 411:
Within-run (will be labeled Repeatability) n=84, human sera
HS 1: 4.0% CV @ 0.138 ng/dL (1.78 pmol/L)
HS 2: 1.3% CV @ 1.03 ng/dL (13.3 pmol/L)
HS 3: 1.3% CV @ 1.90 ng/dL (24.5 pmol/L)
HS 4: 1.7% CV @ 4.93 ng/dL (63.5 pmol/L)
HS 5: 1.8% CV @ 7.09 ng/dL (91.2 pmol/L)
Total (will be labeled Intermediate)
HS 1: 7.6% CV @ 0.138 ng/dL (1.78 pmol/L)
HS 2: 2.3% CV @ 1.03 ng/dL (13.3 pmol/L)
HS 3: 2.1% CV @ 1.90 ng/dL (24.5 pmol/L)
HS 4: 3.3% CV @ 4.93 ng/dL (63.5 pmol/L)
HS 5: 4.5% CV @ 7.09 ng/dL (91.2 pmol/L)Elecsys 2010 and cobas e 411:
Within-run (will be labeled Repeatability) n=60, human sera
HS 1: 1.6% CV @ 8.7 pmol/L
HS 2: 1.7% CV @ 21.1 pmol/L
HS 3: 2.9% CV @ 50.8 pmol/L
Total (will be labeled Intermediate)
HS 1: 3.5% CV @ 8.7 pmol/L
HS 2: 3.3% CV @ 21.1 pmol/L
HS 3: 6.6% CV @ 50.8 pmol/L

MODULAR ANALYTICS E170, cobas e 601 , and cobas e 602:
Within-run (will be labeled Repeatability) n=60, human sera
HS 1: 1.4% CV @ 9.15 pmol/L
HS 2: 1.8% CV @ 16.9 pmol/L
HS 3: 2.0% CV @ 34.2 pmol/L
Total (will be labeled Intermediate)
HS 1: 2.7% CV @ 14.9 pmol/L
HS 2: 2.6% CV @ 17.5 pmol/L
HS 3: 3.6% CV @ 42.7 pmol/L |
| Assay Comparison | | |
| Feature | Elecsys FT4 II Assay | Predicate Device: Elecsys FT4 Assay (K961489) |
| Analytical
Sensitivity | Limit of Blank (LoB): 0.03 ng/dL
(0.4 pmol/L)
Limit of Detection (LoD): 0.05 ng/dL
(0.6 pmol/L)
Limit of Quantitation (LoQ) (Functional
Sensitivity) 0.1 ng/dL
(1.3 pmol/L) with an intermediate
precision of ≤ 20% | Lower Detection Limit: 0.300 pmol/L |
| Analytical
Specificity | Cross Reactant
L-T3
D-T3
rT3
3-iodo-L-trosine
3,5-diiodo-L-tyrosine
3,3',5-
triiodohyoacetic acid
3,3',5,5'- tetraiodothyroacetic acid | Cross
Reactivity
(%)
L-T4 100
D-T4 100
L-T3 1.53
D-T3 1.38
3-iodo-L-tyrosine 0.002
3,5-diiodo-L-tyrosine 0.01
3,3',5,5;-
tetraiodothyroacetic acid 38.5 |
| | Cross
Reactivity
(%)
≤ 0.005
≤ 0.001
≤ 0.003
≤ 0.000
≤ 0.000
≤ 0.0002
0.4-7.77 ng/dL: CV ≤ 5% Specification for Intermediate/within-laboratory precision:
Concentrations of ≤ 0.4 ng/dL: SD ≤ 0.03 ng/dL Concentrations of > 0.4-7.77 ng/dL: CV ≤ 8% |

9

Performance Studies Summary, continued

The table below summarizes the results of the precision studies performed with the Elecsys FT4 II test system. Based on these data, the precision meets the specifications.

| Sample | Mean
(ng/dL) | Repeatability | | | Intermediate Precision | | | n |
|--------|-----------------|---------------|-----------|-----------------------------|------------------------|-----------|-----------------------------|----|
| | | SD
(ng/dL) | CV
(%) | 95% UCL*
(% or
ng/dL) | SD
(ng/dL) | CV
(%) | 95% UCL*
(% or
ng/dL) | |
| PCU 1 | 1.22 | 0.011 | 0.9 | 1.1 | 0.022 | 1.8 | 2.4 | 84 |
| PCU 2 | 3.11 | 0.032 | 1.0 | 1.3 | 0.089 | 2.9 | 3.9 | 84 |
| HS 1 | 0.138 | 0.006 | 4.0 | 0.007
ng/dL | 0.011 | 7.6 | 0.014
ng/dL | 84 |
| HS 2 | 1.03 | 0.013 | 1.3 | 1.6 | 0.023 | 2.3 | 2.9 | 84 |
| HS 3 | 1.90 | 0.024 | 1.3 | 1.6 | 0.040 | 2.1 | 2.8 | 84 |
| HS 4 | 4.93 | 0.082 | 1.7 | 2.1 | 0.163 | 3.3 | 4.4 | 84 |
| HS 5 | 7.09 | 0.127 | 1.8 | 2.3 | 0.319 | 4.5 | 6.2 | 84 |

  • Upper confidence limit
    1. Limit of Blank (LoB) (CLSI EP17-A2): LoB of the Elecsys FT4 II assay on two cobas e 411 Immunoassay Analyzers has been determined according to CLSI EP17-A2 using three reagent lots.
      The distribution of values for one analyte-free human serum sample has been determined on two cobas e 411 Immunoassay Analyzers over four days, one or two runs per day with five-fold determination in each run: (total 60 determinations).

Since there are no natural human samples without FT4 analyte, the analyte-free sample was created by depleting T4. As the analyzers do not report negative sample concentrations, the data set is truncated and the data were evaluated according to EP17-A2. 5.3.3.1 as the linear interpolation of the 57th and 58th ranked observation.

The LoB claim in the package insert will be set to ≤ 0.03 ng/dL.

    1. Limit of Detection (LoD) (CLSI EP17-A2): LoD of the Elecsys FT4 II assay has been determined according to CLSI EP17-A2, 5.3.3.2.
      The distribution of values for five low-level human serum samples has been determined on two cobas e 411 immunoassay analyzers over four days, one or two runs per day with a single measurement per run.

A pooled estimate of the precision (SDota) for the 5 low level samples was calculated: LoD = LoB + 1.653 x SD total (of low analyte samples)

The LoD claim in the package insert will be set to ≤ 0.05 ng/dL.

10

  1. LoQ / Functional Sensitivity (CLSI EP17-A2): The LoQ of the Elecsys FT4 II assay was determined on the cobas e 411 immunoassay analyzer according to CLSI Guideline EP17-A2.

A Low-Level Sample Set of 8 samples was prepared by diluting native human serum samples with an analyte-free human serum matrix and were tested in single replicates for four days, one or two runs per day on two cobas e 411 immunoassay analyzers. Each run was calibrated separately using a two-point calibration in combination with the master curve stored on the reagent barcode. The Elecsys PreciControl Universal was tested and evaluated for each run to determine assay validity.

The mean, standard deviation and coefficient of variation for each sample were calculated. Functional sensitivity as the concentration corresponding to a coefficient of variation of 20% was obtained from plotting the %CV (y-axis) vs. measured FT4 values (x-axis).

Acceptance criterion:

  • Interassay coefficient of variation ≤ 20% .
    The Limit of Quantitation/Functional sensitivity claim in the package insert will be set to 0.1 ng/dL.

The following results were obtained:

Lot MP02:Functional sensitivity = 0.059 ng/dL
Lot P2:Functional sensitivity = 0.069 ng/dL
Lot P3:Functional sensitivity = 0.080 ng/dL

11

510(k) Summary, continued

  1. Linearity (CLSI EP6-A): Linearity of the Elecsys FT4 II assay was Performance assessed on the cobas e 411 Immunoassay Analyzer according to CLSI Studies Summary, EP6-A. continued Three high analyte serum sample pools (spiked with L-Thyroxine) were diluted with fT4 depleted human serum. For each sample pool, 13 concentrations (11 dilutions) throughout the measuring range were prepared. Samples were assayed in 3-fold determination within a single run. The linearity data were analyzed with regards to linear, quadratic and cubic polynomials according to CLSI EP6-A. In the first step, a linearity check was performed with a first order (linear) regression and then with higher order models (quadratic and cubic). Acceptance criteria: Significance level for deviation to higher order polynomial: 5% Limits for deviation of higher order polynomial regression: 0.1 - 0.388 ng/dL: -±0.078 ng/dL . > 0.388 -- 7.77 ng/dL: ± 10% Repeatability for linearity: ±0.039 ng/dL 0.1 - 0.388 ng/dL: . ± 5 % > 0.388 - 7.77 ng/dL: . Linearity was confirmed in the range from 0.096 to 8.20 ng/dL 6. Specificity/Cross Reactivity: The specificity of the Elecsys FT4 II assay was determined using native human serum samples or human serum samples spiked with L-Thyroxine (single donors) spiked with potential cross-reactant compounds tested in duplicate on cobas e 411 Immunoassay Analyzer. In the labeling. Roche will report the maximum cross-reactivity found and the highest concentration tested. See table below.
Cross ReactantCross Reactivity (%)
L-T3≤ 0.005
D-T3≤ 0.001
rT3≤ 0.003
3-iodo-L-trosine≤ 0.000
3,5-diiodo-L-tyrosine≤ 0.000
3,3',5-triiodohyroacetic acid≤ 0.000
3,3',5,5'-tetraiodothyroacetic acid≤ 0.001

Continued on next page

CONFIDENTIAL

12

  1. Exogenous Interferences - Drugs: 17 pharmaceutical compounds Performance (concentration defined as x times the maximum daily dose according Studies to the SOP) and 12 thyroid drugs and Furosemide were spiked into Summary, human serum samples (human serum pools spiked with L-Thyroxine) continued and tested with the Elecsys FT4 II assay on the cobas e 411 Immunoassay Analyzer. Two samples with approximately1.1 ng/dL and 2.6 ng/dL of fT4 were divided into aliquots and spiked with potential interferents. The reference sample, without interferents, was spiked with the respective amount of solvent only. The fT4 concentration of the spiked aliquots was determined in triplicate and compared to the fT4 concentration determined for the reference aliquot (6-fold determination) on one cobas e 411 Immunoassay Analyzer. Acceptance criterion: 100 ± 10% of the reference value (unspiked sample) Each compound, except Levothyroxine and Furosemide, was found to be non-interfering at the concentration listed below. Levothyroxine and Furosemide will be listed as interfering substances in the "Limitations - Interference" section of the package insert. 8. Exogenous Interferences - Anticoagulants: The effect on quantitation of analyte in the presence of anticoagulants with the Elecsys FT4 II Immunoassay was determined by comparing values obtained from native samples or samples spiked with L-Thyroxine (single donors) drawn into serum, Li-Heparin, K2-EDTA-, and K3-EDTA-plasma primary tubes, and Li-Heparin Plasma Separation Tubes. Between 53 and 63 serum/plasma pairs per sample material were tested in single determination with one reagent lot on one cobas e 411 Immunoassay Analyzer. Potential effects are assessed by Passing/Bablok regression and linear regression analysis. Acceptance criteria: . Slope 0.9 - 1.1 Intercept 0.3 – 7.77 ng/dL:
    100 ± 10 % | |
    | | Renewed calibration is recommended as follows:
    After 1 month (28 days) when using the same reagent lot.

    After 7 days (when using the same reagent kit on the analyzer).
    As required: e.g. quality control findings outside the specified

    limits | |
    | | 12. Reagent On-Board Stability: Elecsys FT4 II reagent kits can be
    stored on board of the analyzers for up to 28 days and for 56 days when
    stored alternatively in the refrigerator and on the analyzer, with the
    total time on the analyzer not exceeding 120 hours. A new calibration
    of the kit kept on-board is recommended every 7 days. | |
    | | Acceptance criteria for recovery of samples compared to day 1:
    Concentrations from LoD to 0.3 ng/dL: ± 0.05 ng/dL
    Concentration of >0.3 to 7.77 ng/dL:
    100±10% | |
    | | 13. Reagent Accelerated Stability: Elecsys FT4 II reagent kits have a
    shelf life of ≥ 12 months when stored at 2-8°C. | |
    | | Accelerated reagent stability to estimate real time stability for the
    Elecsys FT4 II assay was tested on one cobas e 411 Immunoassay
    Analyzer. | |
    | | A kit was stored at 35℃ for 3 weeks and recovery of human samples
    and controls were tested compared to a fresh kit stored at 2-8 ℃. | |
    | Performance
    Studies
    Summary,
    continued | Samples tested included five human serum (HS) samples spiked with
    L-Thyroxine, and two controls. Each sample was tested in two-fold
    determination. | |
    | | Acceptance criteria for recovery of samples compared to day 0: | |
    | | • Concentrations from LoD to 0.3 ng/dL: | $\pm$ 0.05 ng/dL |
    | | • Concentration of >0.3 to 7.77 ng/dL: | 100 $\pm$ 10% |
    | | 14. Reagent Real-Time Stability: In the ongoing real-time stability
    study, the Elecsys FT4 II assay material is stored at 2-8°C. The stored
    assay reagents are tested at time point T=0 and at specified intervals
    over the shelf life of the device up to the planned shelf life plus one | |

14

CONFIDENTIAL

.

·

510(k) Summary, continued

.

Continued on next page

. .

15

CONFIDENTIAL

510(k) Summary, continued

1 and PreciControl Universal 2 (Stored at -20°C).

Data for the time-points at 0, 7, 10, 13, 16, 19 and 25 months tested in duplicate will be available. The average on-test recovery value will be calculated as percent recovery compared to the reference value (Assigned value for PreciControl Universal 1 and PreciControl Universal 2).

month. Testing was/will be performed using PreciControl Universal

The acceptance criterion is recovery of 90-110% of the reference value.

Currently. the shelf life claim is 12 months based on the accelerated stability results and real-time stability data. The testing will continue with this stability protocol until data to support a claim of 24 months is achieved.

15. Reagent Stability after first opening (2-8°C): Elecsys FT4 II reagent kits can be used after first opening for up to 84 days (12 weeks) when stored at 2-8ºC.

Reagent stability after first opening for the Elecsys FT4 II assay was tested on one cobas e 411 Immunoassay Analyzer with one reagent lot.

A fresh kit was placed on the analyzer and calibrated. Reference values for the samples tested were determined. After measurement, the kit was removed from the analyzer and kept at 2-8 °C for up to 85 days. After 29, 57 and 85 days, the kit was placed on the analyzer again, calibrated, and the test samples were determined.

Samples tested included five human serum (HS) samples spiked with L-Thyroxine, and two controls. Each sample was tested in two-fold determination.

16

Performance

Studies

Summary, continued

510(k) Summary, continued

| Acceptance criteria for recovery of samples compared to Day 0:
Concentrations of: ≤ 0.3 ng/dL: ± 0.05 ng/dL

0.3 - 7.77 ng/dL: 100 ± 10 % |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Reagent stability after first opening for the Elecsys FT4 II assay was
tested on one cobas e 411 Immunoassay Analyzer with one reagent lot.
A fresh kit was placed on the analyzer and calibrated. Reference values
for the samples tested were determined. After measurement, the kit was
removed from the analyzer and kept at 2-8 °C for up to 85 days. After
29, 57 and 85 days, the kit was placed on the analyzer again, calibrated,
and the test samples were determined. |
| Samples tested included five human serum (HS) samples spiked with L-
Thyroxine, and two controls. Each sample was tested in two-fold
determination. |
| Acceptance criteria for recovery of samples compared to Day 0:
Concentrations of: ≤ 0.3 ng/dL: ± 0.05 ng/dL
0.3 - 7.77 ng/dL: 100 ± 10 % |

16. Reference Range Validation Study (CLSI C28-A3c): The Reference Range Validation Study was performed with 60 subjects (30 males and 30 females) with normal TSH values (0.270 - 4.20μIU/mL) as measured with the Elecsys TSH assay.

Results have been checked for outliers applying the method of Dixon/Reed as described in C28-A3c 9.2. (R = 11.1, D = 1/3 R = 3.7). All 60 determinations are valid and no outliers needed to be excluded.

Acceptance criterion: No more than 6 (10%) of the 60 tested subjects should fall outside of the established reference range of 0.93-1.7 ng/dL.

The FT4 values of 2 of the 60 subjects investigated fall outside of the reference range established for the Elecsys FT4 assay. The acceptance criterion is met. The reference range of 0.93-1.7 ng/dL can be transferred to the Elecsys FT4 II assay.

Conclusion

The data demonstrate that the performance of the Elecsys FT4 II Assay is substantially equivalent to that of the predicate device, Elecsys FT4 Assay (K961489).

17

Image /page/17/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three overlapping wing shapes, representing health, human services, and the public. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

January 27, 2014

ROCHE DIAGNOSTICS EDIE EADS REGULATORY AFFAIRS CONSULTANT 9115 HAGUE ROAD INDIANAPOLIS IN 46250-0416

Re: K131244

Trade/Device Name: Elecsys FT4 II Assay, Elecsys FT4 II CalSet Regulation Number: 21 CFR 862.1695 Regulation Name: Free thyroxine test system Regulatory Class: II Product Code: CEC, JIT Dated: December 13, 2013 Received: December 16, 2013

Dear Ms. Eads:

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. Ilisting 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 electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

18

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance 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. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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/ReportalProblem/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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industrv/default.htm.

Sincerely yours.

Courtney H. Lias -S

Courtney H. Lias, Ph.D. Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

19

Indications for Use Form

510(k) Number (if known):

Device Name: Elecsys FT4 II Assay, Elecsys FT4 II CalSet

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.

Elecsys FT4 II CalSet is used for calibrating the quantitative Elecsys FT4 II assay on the Elecsys and cobas e immunoassay analyzers.

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED) .

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)

Yung Dogan -S

Division Sign-Off Office of In Vitro Diagnostics and Radiological Health

K131244 210(k)

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