MICT TSH

K110761 · Magnabiosciences, LLC · JLW · Mar 9, 2012 · Clinical Chemistry

Device Facts

• Record ID: K110761
• Device Name: MICT TSH
• Applicant: Magnabiosciences, LLC
• Product Code: JLW · Clinical Chemistry
• Decision Date: Mar 9, 2012
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1690
• Device Class: Class 2

Indications for Use

The MICT® TSH is a magnetic lateral flow immunoassay for the in-vitro quantitative determination of TSH in human serum. The measurements of thyroid stimulating hormone (TSH) produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders. The MICT System is intended for use in clinical laboratories.

Device Story

MICT TSH is a magnetic lateral flow immunoassay for quantitative TSH measurement in human serum. Input: 100 uL serum sample mixed with lyophilized conjugate (monoclonal anti-TSH antibody coupled to 300 nm super paramagnetic particles). Process: Sample/conjugate mixture migrates along a nitrocellulose membrane (sandwich assay format) for 30-45 minutes; test cassette inserted into MICT Instrument. Instrument detects magnetic moment at test/control lines. Output: Quantitative TSH results printed automatically. Used in clinical laboratories by trained personnel. Benefits: Provides diagnostic information for thyroid/pituitary disorders via magnetic detection technology.

Clinical Evidence

Bench testing only. Performance evaluated across three sites (n=204). Method comparison against predicate showed high correlation (r=0.99). Sensitivity: LOB 0.04 µIU/mL, LOD 0.077 µIU/mL, LOQ 0.077 µIU/mL. Precision (%CV) ranged from 7.5% to 14.4% across various TSH concentrations. Interference testing confirmed no significant interference for bilirubin (40 mg/dL), hemoglobin (1000 mg/dL), triglycerides (3200 mg/dL), and phospholipids (800 mg/dL). Specificity tested against LH and FSH (500 mIU/mL) with no cross-reactivity.

Technological Characteristics

Magnetic lateral flow immunoassay. Solid phase: nitrocellulose membrane with polyclonal goat anti-rabbit IgG (control) and monoclonal anti-TSH (test) antibodies. Label: 300 nm super paramagnetic particles. Detection: magnetic moment. Sample volume: 100 µL. Assay range: 0.13 to 100 µIU/mL. Semi-automated processing via MICT Instrument. Storage: 1-30°C. Calibration: factory-generated master curve.

Indications for Use

Indicated for the in-vitro quantitative determination of TSH in human serum to aid in the diagnosis of thyroid or pituitary disorders in clinical laboratory settings.

Regulatory Classification

Identification

A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known as thyrotrophin and thyrotrophic hormone, in serum and plasma. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.

Predicate Devices

• Qualigen FastPack® TSH (K052301)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE

A. 510(k) Number:
k110761

B. Purpose for Submission:
New device

C. Measurand:
Thyroid-stimulating hormone (TSH)

D. Type of Test:
Quantitative magnetic lateral flow immunoassay

E. Applicant:
MagnaBioSciences LLC

F. Proprietary and Established Names:
MICT® TSH, MICT® Instrument

G. Regulatory Information:

1. Regulation section:
21 CFR § 862.1690 Thyroid Stimulating Hormone Test System
21 CFR § 862.1315 Colorimeter, Photometer, Spectrophotometer for Clinical Use

2. Classification:
Class II (assay), Class I (instrument)

3. Product code:
JLW, JJQ

4. Panel:
Clinical Chemistry (75)

H. Intended Use:

1. Intended use(s):
See “Indication(s) for use” below

2. Indication(s) for use:
The MICT TSH is a magnetic lateral flow immunoassay for the in vitro quantitative determination of TSH in human serum. The measurements of thyroid stimulating hormone (TSH) produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders. The MICT System is intended for use in clinical laboratories.

The MICT Instrument is intended for use with the MICT (Magnetic Immuno-

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Chromatographic Test) lateral flow assays. The instrument measures the test signal, calculates, and reports results.

3. Special conditions for use statement(s):
For prescription use only

4. Special instrument requirements:
MICT instrument

I. Device Description:
The device consists of the MICT instrument and the MICT TSH in vitro diagnostic test cassettes. The cassettes contain:
1. Solid phase nitrocellulose membrane cassette with two detection zones
a. Control line region containing a polyclonal goat anti-rabbit IgG antibody, and
b. Test line region containing a murine monoclonal anti-TSH antibody
2. Lyophilized conjugate containing rabbit monoclonal anti-TSH antibody covalently coupled to 300 nm super paramagnetic particles.

J. Substantial Equivalence Information:
1. Predicate device name(s):
Qualigen FastPack TSH Immunoassay
2. Predicate 510(k) number(s):
k052301
3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | MICT® TSH | FastPack® TSH |
| Intended Use | immunoassay for the in vitro quantitative determination of TSH in human serum. The measurements of thyroid stimulating hormone (TSH) produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders. | same |
| Assay Methodology | Sandwich immunoassay | Same |
| Data analysis | Internal data reduction via microcomputer | Same |
| Test processing | Semi-automated | Same |
| Assay Range | 0.13 – 100 uIU/mL | Same |
| Sample volume | 100 μL | Same |

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| Similarities | | |
| --- | --- | --- |
| Item | MICT® TSH | FastPack® TSH |
| Detection Antibody | Monoclonal (mouse) | Same |
| Throughput | Single sample | Same |
| Differences | | |
| --- | --- | --- |
| Item | MICT TSH | FastPack TSH |
| Storage condition | 1-30 °C | 2 – 8 °C |
| Sample type | Serum | Plasma |
| Detector | Magnetic instrument | Photomultiplier tube |
| Label | Super Magnetic Particles | Alkaline Phosphatase – Lucegine |
| Instrument required | MICT Magnetic instrument | FastPact system |
| Solid phase | Nitrocellulose membrane | Magnetic particles |
| Control Antibody | Polyclonal (goat anti-rabbit) | Monoclonal |
| Detection | Magnetic moment | Chemiluminescence |
| Calibration | Factory generated master curve; stable until expiration date of assay lot | Factory generated calibration curve using 6 standards; requires monthly recalibration |
| Calibration frequency | Factory calibration | Every 14 days by user |
| Time to result | 30 minutes | 15 minutes |
| Reagents supplied | Box of 20 reagent cassettes with lyophilized conjugate tubes | Box of 50 individual tests |

# K. Standard/Guidance Document Referenced (if applicable):

a. EN61010-1 – Safety requirements for electrical equipment for measurement, control, and laboratory use (2nd edition)
b. EN 61326 – Electrical equipment for measurement, control and laboratory use, EMC requirements (Version 04: 1997+A1; Version 06: 1998+A2)
c. CLSI EP5-A2 – Evaluation of precision Performance of Quantitative Measurement Methods (2nd edition)
d. CLSI EP9-A2-IR – Method Comparison and Bias Estimation Using Patient Samples (2nd edition)
e. CLSI EP6-A – Evaluation of Linearity of Quantitative Measurement Procedures: A Statistical Approach (1st edition)
f. CLSI EP17-A – Protocols for the Determination of Limits of Detection and Limits of Quantitation (1st edition)

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# L. Test Principle:

MICT TSH is a magnetic immuno-chromatographic test (MICT) using Super Paramagnetic particles (SPMPs) as the labeling agent. The SPMP magnetic field is quantified by a MICT instrument.

MICT TSH is based on the principle of capillary flow and separation of immune complexes bound to SPMPs within a porous matrix. In the test device, TSH antibody (Ab) – antigen (Ag) immune reactions occur on a narrow strip of capillary membrane. The narrow strip is housed in a disposable plastic cassette to form a test device.

The specimen containing the TSH antigens is mixed with a lyophilized conjugate pellet and added into the sample well of the MICT cassette. As the TSH Ab-Ag, SPMP immune complexes migrate through the test device, they are captured by the second antibodies at the test line. A control line is formed by the control SPMP immune complexes. The MICT instrument is used to analyze the quantity of magnetic particles captured on both control and test lines. A visible line is not necessary for interpreting the MICT test result. The TSH concentration is directly proportional to the magnetic signal and is reported based on the predetermined test algorithms that are embedded in the cassette barcode labels.

# M. Performance Characteristics (if/when applicable):

# 1. Analytical performance:

# a. Precision/Reproducibility:

The precision was determined using the CLSI EP5-A2 protocol as a guide. The study was conducted at three external sites. Each site was supplied with three levels (low, medium, high) of human serum samples. The high TSH sample was prepared by spiking purified TSH antigen into pooled serum. The data was collected over 20 days in duplicate with 2 runs per day with a total of 80 samples analyzed per level at each site. The results are summarized below:

Low Concentration #1 with observed mean $= 0.19$ uIU/mL

| | Site 1 | Site 2 | Site 3 |
| --- | --- | --- | --- |
| Mean, μIU/mL | 0.19 | 0.19 | 0.18 |
| Repeatability, %CV | 12.1 | 13.3 | 14.4 |
| Between-run, %CV | 6.2 | 0 | 0 |
| Between-day, %CV | 3.8 | 7.0 | 3.7 |
| Within-laboratory, %CV | 14.1 | 15.0 | 14.4 |

Low Concentration #1 with observed mean $= 0.29$ uIU/mL

| | Site 1 | Site 2 | Site 3 |
| --- | --- | --- | --- |
| Mean, uIU/mL | 0.29 | 0.29 | 0.29 |

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| Repeatability, %CV | 8.5 | 8.9 | 8.8 |
| --- | --- | --- | --- |
| Between-run, %CV | 0 | 0 | 0 |
| Between-day, %CV | 4.1 | 4.8 | 3.7 |
| Within-laboratory, %CV | 9.4 | 10.1 | 9.5 |

Low Concentration #2 with observed mean = 0.86 μIU/mL

| | Site 1 | Site 2 | Site 3 |
| --- | --- | --- | --- |
| Mean, uIU/mL | 0.83 | 0.87 | 0.87 |
| Repeatability, %CV | 8.3 | 6.0 | 5.8 |
| Between-run, %CV | 4.2 | 3.3 | 5.0 |
| Between-day, %CV | 0.0 | 3.8 | 0.0 |
| Within-laboratory, %CV | 9.4 | 7.8 | 7.6 |

Mid Concentration with observed mean = 3.92 μIU/mL

| | Site 1 | Site 2 | Site 3 |
| --- | --- | --- | --- |
| Mean, uIU/mL | 3.7 | 4.1 | 3.95 |
| Repeatability, %CV | 7.3 | 7.7 | 8.2 |
| Between-run, %CV | 4.2 | 3.8 | 1.9 |
| Between-day, %CV | 2.9 | 3.0 | 3.5 |
| Within-laboratory, %CV | 8.9 | 9.1 | 9.1 |

High Concentration with observed mean = 47.24 μIU/mL

| | Site 1 | Site 2 | Site 3 |
| --- | --- | --- | --- |
| Mean, uIU/mL | 46.71 | 46.63 | 48.39 |
| Repeatability, %CV | 6.6 | 5.8 | 6.6 |
| Between-run, %CV | 2.9 | 7.5 | 2.1 |
| Between-day, %CV | 5.1 | 0.0 | 2.9 |
| Within-laboratory, %CV | 8.8 | 9.5 | 7.5 |

b. Linearity/assay reportable range:

The linearity of the MICT TSH method was determined following the CLSI EP6-A procedure. Two samples were identified having TSH concentrations covering the reportable range. A series of intermediate serum samples were prepared by diluting the high level sample (126 μIU/mL) with the low level sample (0 μIU/mL). Sample 7 was mixed with the low level sample to generate samples with TSH < 8 μIU/mL (samples 2 to 6).

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The samples were then analyzed using the MICT TSH system. The MICT TSH assay is linear within the reportable range, $0.13 - 100\mu \mathrm{IU / mL}$

[TSH] $\mu \mathrm{IU} / \mathrm{mL}$

| Sample Number | Replicate 1 | Replicate 2 | Observed Average | Expected |
| --- | --- | --- | --- | --- |
| 1 | 0 | 0 | 0.00 | 0.00 |
| 2 | 0.12 | 0.14 | 0.13 | 0.11 |
| 3 | 0.33 | 0.35 | 0.34 | 0.35 |
| 4 | 0.87 | 0.94 | 0.91 | 0.89 |
| 5 | 3.73 | 3.55 | 3.64 | 3.54 |
| 6 | 6.21 | 7.78 | 7.00 | 7.09 |
| 7 | 10.88 | 10.63 | 10.76 | 10.62 |
| 8 | 20.5 | 21.4 | 20.95 | 21.00 |
| 9 | 40.09 | 41.6 | 40.85 | 42.00 |
| 10 | 68.7 | 70.2 | 69.45 | 63.00 |
| 11 | 85.28 | 82.13 | 83.71 | 84.00 |
| 12 | 107.4 | 107.8 | 107.6 | 105.00 |
| 13 | 124.3 | 129.3 | 126.8 | 126.00 |

The analysis yields the following relationship:

Observed $= 1.017$ (Expected) $+ .0494$ , $\mathrm{R}^2 = 0.9985$

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

A master file of the standard curve is generated for each lot of MICT TSH using master calibrators referenced to the WHO $2^{\text{nd}}$ IRP 80/558 standard. The master file information is transferred to the MICT Instrument through the barcode label on the test cassette. Each lot of MICT TSH device with dry reagent is calibrated at the manufacturing site. The reagent is stable throughout the stated product shelf life.

For accelerated stability testing, two lots of the MICT TSH reagent devices were heat-stressed at $40^{\circ}\mathrm{C}$ for varying time periods. For real-time testing, one lot was tested over a 14-month period. Based on accelerated and real-time stability testing, the shelf-life for the MICT TSH test is 14 months when stored at room temperature $(22^{\circ}\mathrm{C})$ .

d. Detection limit:

Five low TSH level human serum samples from different individuals were tested using two MICT instruments and one reagent lot over a period of three days, two runs per day following CLSI EP17-A guidelines. The TSH concentrations of the LoD samples were verified by ADVIA Centaur CP TSH3-Ultra assay, which is traceable to the WHO $3^{\mathrm{rd}}$ International Standard for human TSH (IRP 81/565). The LoD was

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estimated to be 0.077 µIU/mL.

The bias of each of the five low concentration samples was estimated as the mean MICT measured concentration of each sample minus its value as determined by the ADVIA Centaur CP TSH3-Ultra. The bias of the lowest concentration sample was used as an estimate of the bias of the LoQ since this concentration was closest to LoQ. The total error was calculated to be smaller than the allowable error. The LoQ therefore = LoD = 0.077 µIU/mL. The sponsor chose the reportable range to be 0.13 to 100 µIU/mL.

Hook effect: TSH was spiked into a human serum depleted of TSH standard that had been completely depleted of TSH at 25, 50, 100, 150, 200, 250, 500, 1000, and 20000 µIU/mL. No hook effect was observed at TSH concentrations up to 2000 µIU/mL.

e. Analytical specificity:

Interference

The study was conducted using bilirubin, hemoglobin, phospholipids, and triglycerides. Human serum samples with various TSH concentrations were spiked with potential interfering substances and tested using the MICT TSH System. Controls were prepared by spiking the samples with equal volumes of the solvents that were used to dissolve the interfering substances. The concentrations of spiked and control samples were recorded, and recovery rates were calculated. Bilirubin was dissolved in DMSO plus 40 mM NaOH. Lyophilized hemoglobin and phospholipids stabilized in triglycerides were weighed out and mixed with serum samples directly. No significant interference as defined by the sponsor as ±10% was found for bilirubin, hemoglobin, phospholipids, and triglycerides at the concentrations presented in the table below.

| Interfering Substance | Sample ID | Control (µIU/mL) | AVE( control) | with interfering substance (µIU/mL) | AVE (interfering) | Recovery Rate % |
| --- | --- | --- | --- | --- | --- | --- |
| Bilirubin (40 mg/dL) | 4 | 0.3 | 0.27 | 0.31 | 0.295 | 109 |
| | | 0.24 | | 0.28 | | |
| | 1 | 0.30 | 0.35 | 0.35 | 0.33 | 94 |
| | | 0.40 | | 0.31 | | |
| | 2 | 4.07 | 4.97 | 4.92 | 5.02 | 101 |
| | | 5.86 | | 5.11 | | |
| | 3 | 6.71 | 7.38 | 7.53 | 7.31 | 99 |
| | | 8.04 | | 7.08 | | |
| | 4 | 0.16 | 0.135 | 0.13 | 0.145 | 107 |
| | | 0.11 | | 0.16 | | |

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The effects of rheumatoid factor (Rf) and human anti-mouse antibodies (HAMA) on the MICT TSH assay were evaluated. Individual patient serum samples were mixed with equal volume of HAMA or Rf positive samples. The final concentrations of Rf and HAMA in these samples were 1,000 IU/mL and 400 ng/mL, respectively. The mixed samples were analyzed in duplicate using the MICT system. The MICT TSH assay shows no detectable interference within the sponsor's acceptable limits (±10%) with rheumatoid factor and HAMA.

The results are presented in the table below:

Rf Samples (1000 uIU/mL)

| Patient Sample (TSH, μIU/mL) | Rf Sample (TSH, μIU/mL) | Mixed RF Positive Sample (TSH, μIU/mL) | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | | Expected Value | Replicate 1 | Replicate 2 | Average | % Recovery |
| 0.41 | 0.25 | 0.33 | 0.36 | 0.29 | 0.325 | 98 |
| 1.7 | 1.3 | 1.5 | 1.47 | 1.46 | 1.46 | 97 |
| 17.0 | 1.3 | 9.13 | 8.56 | 8.48 | 8.52 | 93 |
| 10.9 | 1.3 | 6.14 | 5.74 | 5.93 | 5.84 | 95 |

HAMA Samples (400 ng/mL)

| Patient Sample (TSH, μIU/mL) | HAMA Sample (TSH, μIU/mL) | Mixed HAMA Positive Sample (TSH, μIU/mL) | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | | Expected Value | Replicate 1 | Replicate 2 | Average | % Recovery |
| 0.16 | 0.42 | 0.29 | 0.26 | 0.28 | 0.27 | 92 |
| 1.94 | 1.3 | 1.62 | 1.59 | 1.76 | 1.68 | 104 |

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| 8.13 | 1.3 | 4.72 | 4.59 | 4.23 | 4.41 | 93 |
| --- | --- | --- | --- | --- | --- | --- |
| 1.74 | 1.3 | 1.52 | 1.43 | 1.38 | 1.41 | 93 |

## Cross reactivity

Human serum samples with various TSH concentrations were spiked with potential cross reactants FSH, LH, and hCG dissolved in PBS with 1% BSA and tested in MICT TSH system. Controls were prepared by spiking samples with equal volumes of the PBS-BSA solution used in dissolving the FSH, LH, and hCG. The concentrations of spiked and control samples were recorded, and recovery rates were calculated. None of the analytes tested significantly cross-reacted with stated cross-reactants as recovery rates were within ±10%.

| Cross Reactant | Sample ID | Control (μIU/mL) | AVE (control) | with cross reactant (μIU/mL) | AVE (interfering) | Recovery Rate |
| --- | --- | --- | --- | --- | --- | --- |
| LH (500 mIU/mL) | 1 | 1.66 | 1.57 | 1.69 | 1.69 | 108% |
| | | 1.48 | | 1.69 | | |
| | 2 | 7.27 | 7.29 | 7.38 | 7.46 | 102% |
| | | 7.31 | | 7.54 | | |
| FSH (500 mIU/mL) | 1 | 2.57 | 2.62 | 2.45 | 2.49 | 95% |
| | | 2.68 | | 2.53 | | |
| | 2 | 16.39 | 16.44 | 17.95 | 17.99 | 109% |
| | | 16.50 | | 18.02 | | |
| hCG (200 IU/mL) | 1 | 2.50 | 2.37 | 2.27 | 2.16 | 91% |
| | | 2.23 | | 2.05 | | |
| | 2 | 14.90 | 14.60 | 14.63 | 15.76 | 108% |
| | | 14.30 | | 16.89 | | |

f. Assay cut-off:

N/A

2. Comparison studies:

a. Method comparison with predicate device:

Patient serum samples (n=204) with TSH values ranging from 0.13 – 93.6 μIU/mL were collected and evaluated. Linear regression was used to correlate the MICT TSH assay to the Qualigen FastPack TSH assay. The results yielded the following linear regression equation: Y = 0.96X - 0.1, R = 0.99

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b. Matrix comparison:

Not applicable. Serum is the only sample type indicated.

3. Clinical studies:

a. Clinical Sensitivity:

N/A

b. Clinical specificity:

N/A

c. Other clinical supportive data (when a. and b. are not applicable):

N/A

4. Clinical cut-off:

N/A

5. Expected values/Reference range:

Serum samples from 147 normal, apparently healthy individuals, consisting of 97 females and 50 males were assayed on three lots of MICT TSH devices using two MICT Readers. The reference range was determined using the procedure in CLSI C28-A3. The expected normal range for the MICT TSH is 0.49 – 3.71 µIU/mL based on the central 95% of the frequency distribution.

N. Instrument Name:

MICT TSH Instrument

O. System Descriptions:

1. Modes of Operation:

Automatic

2. Software:

FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types:

Yes ☐ x ☐ or No ☐

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3. Specimen Identification:

Barcode

4. Specimen Sampling and Handling:

Patient samples are pipetted into the conjugate tube, mixed then manually transferred into the sample well of the assay cassette.

5. Calibration:

Calibration of the assay is performed at the manufacturer's site. The test kits are stable up to the expiration date. All instruments are calibrated against a known magnetic standard by the manufacturer. Each system is standardized to read the magnetic material within 2%.

6. Quality Control:

The sponsor recommends the use of commercially available external control materials for use with the MICT System. In the labeling the sponsor recommends that the quality control material be run each day the system is used to report patient results. Also the sponsor recommends that each day the MICT system is used to test patient samples the user tests the verification cassette to assess the operational status of the MICT instrument.

P. Other Supportive Instrument Performance Characteristics Data Not Covered In The "Performance Characteristics" Section above:

N/A

Q. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

R. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.