AFIAS TSH-SP, for use in conjunction with the AFIAS-6/SP Analyzer, is an immunofluorometric test system intended for in vitro diagnostic use at clinical laboratories and Point-of-Care (POC) sites for the quantitative measurement of thyroid stimulating hormone (TSH) levels in serum, sodium-heparinized plasma samples. The test system is intended for use as an aid in the diagnosis of thyroid or pituitary disorders.

AFIAS-6/SP Analyzer is a fluorescence-scanning instrument for in vitro diagnostic use at clinical laboratories and Pointof-Care (POC) sites in conjunction with various in vitro diagnostic AFIAS immunoassays for measuring the concentration of designated analytes in serum or plasma samples.

AFIAS TSH-VB, for use in conjunction with the AFIAS-6/VB Analyzer, is an immunofluorometric test system intended for in vitro diagnostic use at clinical laboratories and Point-of-Care (POC) sites for the quantitative measurement of thyroid stimulating hormone (TSH) levels in sodium-heparinized or EDTA venous whole blood samples. The test system is intended for the monitoring of TSH levels in euthyroid and hypothyroid individuals.

AFIAS-6/VB Analyzer is a fluorescence-scanning instrument for in vitro diagnostic use at clinical laboratories and Pointof-Care (POC) sites in conjunction with various in vitro diagnostic AFIAS immunoassays for measuring the concentration of designated analytes in venous whole blood samples.

Device Description

AFIAS TSH-SP as well as AFIAS TSH-VB Test Cartridge is a plastic structure molded in the form of a disposable, self-contained, unitized device which houses the 'lyophilized detection buffer', the 'diluent i.e. reconstitution buffer' as well as the 'test strip'; all of which are integral components of the test. The test cartridge is an elongated structure having 140 mm length. 17 mm width and 17 mm height.

'AFIAS TSH-SP ID Chip' as well as 'AFIAS TSH-VB ID Chip' is a flat, rectangular device with its main body measuring 24 mm × 20 mm × 3 mm. Another rectangular portion measuring 12 mm × 10 mm × 2 mm protrudes out from the apical side of the main body. The ID Chip is an electronic memory device fitted into a plastic matrix. Lot-specific 'ID Chip' is an integral component of the test.

AFIAS-6/SP as well as AFIAS-6/VB analyzer is a compact, bench-top, automated, fluorometric analyzer measuring 42 cm (L) x 33.6 cm (W) x 29.3 cm (H). AFIAS-6 weighs 15.1 kg. Either analyzer is a flourometer instrument of closed-system analyzer type.

AI/ML Overview

Here's an analysis of the provided text, outlining the acceptance criteria and study details for the AFIAS TSH devices:

Acceptance Criteria and Device Performance for AFIAS TSH-SP and AFIAS TSH-VB

Note: The document presents acceptance criteria implicitly through performance study results and comparisons to a predicate device. Specific numerical acceptance criteria (e.g., "CV must be <= X%") are not explicitly stated for all metrics but are inferred from the reported "achieved performance" values. Where a direct "acceptance criterion" is not explicitly given, the achieved performance itself serves as the benchmark demonstrated by the study.

1. Table of Acceptance Criteria and Reported Device Performance

Feature/Metric	Acceptance Criterion (Inferred from Predicate/Good Practice)	AFIAS TSH-SP Reported Performance	AFIAS TSH-VB Reported Performance
Limit of Blank (LoB)	Not explicitly stated; expected to be low.	0.03 µIU/ml	0.13 µIU/ml
Limit of Detection (LoD)	Not explicitly stated; expected to be low.	0.05 µIU/ml	0.2 µIU/ml
Limit of Quantitation (LoQ) / Functional Sensitivity	Inter-assay CV ≤ 20% (explicitly stated for calculation)	0.07 µIU/ml with inter-assay CV ≤ 20%	0.3 µIU/ml with inter-assay CV ≤ 20%
Measuring/Reportable Range	Comparable to predicate device.	0.07 - 80.00 µIU/ml	0.3 - 80.0 µIU/ml
Linearity (R²)	High correlation (implied by good linearity).	0.9993 (Serum)	0.9997 (Na-heparinized whole blood)
Susceptibility to High-dose Hook Effect	No hook effect below a very high concentration.	No hook/prozone effect up to 3000 µIU/ml	No hook/prozone effect up to 3000 µIU/ml
Analytical Specificity (Interference/Cross-reactivity)	Analyte recovery within 90-110% in presence of specified interferants/cross-reactants.	Analyte recovery within 90-110%	Analyte recovery within 90-110%
Site-to-Site Precision/Reproducibility (Total Imprecision %CV)	Not explicitly stated; typical clinical assay precision targets vary (e.g., <10-15%).	Individual site total %CVs range from 3.7% to 6.7% (low to moderate TSH). Combined sites total %CVs range from 4.0% to 5.6%.	Individual site total %CVs range from 6.3% to 8.1% (low to moderate TSH). Combined sites total %CVs range from 6.5% to 7.2%.
Matrix Comparison (Correlation Coefficient)	High correlation (e.g., >0.95 or higher).	0.9998 (Serum vs. Sodium heparin plasma), 0.9997 (Serum vs. Di-Potassium EDTA plasma)	0.9998 (Sodium heparin venous whole blood vs. Di-Potassium EDTA venous whole blood)
Clinical Method Comparison (Correlation Coefficient)	High correlation (e.g., >0.95 or higher) with predicate device.	0.9994	0.9999
Clinical Method Comparison (Weighted Deming Regression Slope)	Close to 1 (e.g., 0.9-1.1) to indicate agreement with predicate.	0.976	0.909
Clinical Method Comparison (Weighted Deming Regression Y-intercept)	Close to 0 to indicate agreement with predicate.	-0.003	0.012

2. Sample Size and Data Provenance

Limit of Blank (LoB):
- Test Set Sample Size: 5 unique blank/TSH-depleted human serum samples (for TSH-SP) and 5 unique blank/TSH-depleted whole blood samples (for TSH-VB). Each tested in 5 replicates, with 3 lots on 3 analyzers for 3 days, leading to 75 replicates per lot/analyzer.
- Data Provenance: Not explicitly stated (e.g., country). Appears to be laboratory-controlled samples (TSH-depleted).
Limit of Detection (LoD):
- Test Set Sample Size: 5 unique low TSH-spiked human serum samples (for TSH-SP) and 5 unique low TSH-spiked whole blood samples (for TSH-VB). Each tested in 5 replicates, with 3 lots on 3 analyzers for 3 days, leading to 75 replicates per lot/analyzer.
- Data Provenance: Not explicitly stated (e.g., country). Appears to be laboratory-controlled samples (TSH-spiked).
Limit of Quantitation (LoQ):
- Test Set Sample Size:
  - TSH-SP: 5 low TSH-spiked serum samples, tested in 2 replicates daily in two runs, for 21 successive days (total 210 measurements per sample per lot/analyzer combination).
  - TSH-VB: 4 low TSH-spiked venous whole blood samples, tested in 5 replicates daily in two runs, for 5 successive days (total 200 measurements per sample per lot/analyzer combination).
- Data Provenance: Not explicitly stated (e.g., country). Appears to be laboratory-controlled samples (TSH-spiked).
Linearity and Reportable Range:
- Test Set Sample Size: 22 test samples each for TSH-SP (serum) and TSH-VB (whole blood), prepared by mixing high and TSH-depleted samples. Each tested in triplicate.
- Data Provenance: Not explicitly stated (e.g., country). Laboratory-prepared samples.
Susceptibility to High-dose Hook Effect:
- Test Set Sample Size: 12 spiked samples (TSH concentrations 25 to 3000 µIU/ml). Tested in triplicate.
- Data Provenance: Not explicitly stated (e.g., country). Laboratory-prepared samples.
Analytical Specificity:
- Test Set Sample Size: Samples spiked with various interferants/cross-reactants. Specific number of samples not detailed, but substances and concentrations are listed.
- Data Provenance: Not explicitly stated (e.g., country). Laboratory-prepared samples.
Site-to-Site Precision/Reproducibility:
- Test Set Sample Size:
  - TSH-SP: 4 serum samples (TSH levels ~0.5, ~5.0, ~15.0 & ~55.0 µIU/ml). Each tested in 5 replicates, with 3 lots on 3 analyzers (1 per site) by 9 operators (3 per site). Total 15 replicates per sample per site, 45 replicates per sample combined.
  - TSH-VB: 4 whole blood samples (TSH levels ~0.5, ~5.0, ~15.0 & ~55.0 µIU/ml). Each tested in 5 replicates, with 3 lots on 3 analyzers (1 per site) by 9 operators (3 per site). Total 15 replicates per sample per site, 45 replicates per sample combined.
- Data Provenance: External point-of-care sites. Not explicitly stated (e.g., country). Uses clinical samples (Clinical Serum Sample 1, 2, Clinical Venous Whole Blood Sample 1, 2) and spiked samples (Spiked Serum Sample 3, 4, Spiked Venous Whole Blood Sample 3, 4).
Matrix Comparison:
- Test Set Sample Size:
  - TSH-SP: 81 matched serum vs. sodium heparin plasma samples; 79 matched serum vs. Di-Potassium EDTA plasma samples.
  - TSH-VB: 63 matched sodium heparin venous whole blood vs. Di-Potassium EDTA venous whole blood samples.
- Data Provenance: Clinical samples from same study subjects. Not explicitly stated (e.g., country).
Adult Reference Interval:
- Test Set Sample Size:
  - TSH-SP: 128 apparently healthy adults (65 males, 63 females, age 21-70 years) for serum samples.
  - TSH-VB: 133 apparently healthy adults (69 males, 64 females, age 21-70 years) for sodium heparin venous whole blood samples.
- Data Provenance: Not explicitly stated (e.g., country). Appears to be prospective collection of healthy adult samples.
Clinical Method Comparison:
- Test Set Sample Size:
  - TSH-SP: 183 serum samples (including 22 spiked).
  - TSH-VB: 157 sodium heparinized venous whole blood samples (including 22 spiked).
- Data Provenance: Clinical sites (three point-of-care sites). Samples collected from across the three study sites. Not explicitly stated (e.g., country).

3. Number of Experts and Qualifications for Ground Truth

The document describes in vitro diagnostic devices for measuring TSH levels. The performance studies for these types of devices primarily rely on established analytical methods and reference standards rather than expert human interpretation of images or clinical cases.
No "experts" were used to establish ground truth in the typical sense of a diagnostic imaging study (e.g., radiologists interpreting images). Instead, ground truth is established by:
- Reference testing (e.g., predicate device, or other established laboratory methods) for method comparison studies.
- Known concentrations for spiked samples (LoD, LoQ, Linearity, Hook Effect, Analytical Specificity).
- Large cohorts of 'apparently healthy adults' for reference intervals.

4. Adjudication Method

None specified. For in vitro diagnostic assays, ground truth is typically analytical (known concentrations, reference method results) rather than requiring adjudication of human interpretations.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No. This is an in vitro diagnostic (IVD) test, not an imaging device that requires human interpretation. Therefore, an MRMC study comparing human readers with and without AI assistance is not applicable. The precision study did involve multiple operators at POC sites using the device, but this is different from an MRMC study for diagnostic interpretation.

6. Standalone Performance Study

Yes. All the analytical and clinical studies described (LoB, LoD, LoQ, Linearity, Hook Effect, Analytical Specificity, Site-to-Site Precision, Matrix Comparison, and Reference Interval determination) assess the algorithm/device performance in a standalone manner. The "human-in-the-loop" aspect is limited to the operator performing the test according to instructions, not interpreting results in a diagnostic imaging sense.
The Clinical Method Comparison study also implicitly evaluates standalone performance by comparing the device's results to a predicate device.

7. Type of Ground Truth Used

Known concentrations: For LoB, LoD, LoQ, Linearity, Hook Effect, and Analytical Specificity, ground truth is established by preparing samples with known or precisely characterized TSH concentrations (e.g., TSH-depleted, TSH-spiked samples).
Predicate device results: For Clinical Method Comparison, the results from the Access Fast hTSH (on the Access 2 system) are used as the reference/ground truth for comparison.
Statistically derived from healthy population: For Adult Reference Interval determination, ground truth is derived from the statistical distribution (2.5th and 97.5th percentiles) of TSH levels in a large cohort of apparently healthy adults.

8. Sample Size for the Training Set

The document does not explicitly describe a "training set" in the context of machine learning or AI models, as this is an IVD device and the performance studies focus on analytical validation.
However, the calibration process for the device (Lot-specific master calibration curve encoded in an ID chip) implies that a set of characterized samples would have been used by the manufacturer to establish these curves. The size of this internal calibration data set is not provided in this document.

9. How the Ground Truth for the Training Set Was Established

As above, due to this being an IVD device and not an AI/ML model with a distinct "training set" in the conventional sense, this information is not explicitly provided.
The calibration curves provided on the ID chips would have been established by the manufacturer using a reference method and a range of TSH standards/samples with known concentrations. This would involve a comprehensive analytical process to ensure accuracy and precision across the measuring range.

Summary

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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of a caduceus, a symbol often associated with medicine and healthcare.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002 October 13, 2017

BODITECH MED INC. HYUNG-JU OH GENERAL MANAGER (REGULATORY AFFAIRS) 43, GEODUDANJI 1-GIL, DONGNAE-MYEON CHUNCHEON-SI, GANG-WON-DO, SOUTH KOREA 200-883

Re: K170232

Trade/Device Name: AFIAS TSH-SP, AFIAS-6/SP Analyzer AFIAS TSH-VB, AFIAS-6/VB Analyzer Regulation Number: 21 CFR 862.1690 Regulation Name: Thyroid stimulating hormone test system Regulatory Class: II Product Code: JLW, KHO Dated: August 31, 2017 Received: September 5, 2017

Dear Hyung-Ju Oh:

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

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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/ResourcesforYou/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,

Kellie B. Kelm -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

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Indications for Use

510(k) Number (if known)

K170232

Device Name

AFIAS TSH-SP, AFIAS-6/SP Analyzer

Indications for Use (Describe)

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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Indications for Use

K170232

510(k) Number (if known)

Device Name

AFIAS TSH-VB, AFIAS-6/VB Analyzer

Indications for Use (Describe)

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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Section 5: 510(k) Summary

This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of 21 CFR 807.92.

510(k) number: K170232

Preparation date: October 6, 2017

Device Type/Common Name: Radioimmunoassay, Thyroid-Stimulating Hormone

Trade/Proprietary Name : AFIAS TSH-SP, AFIAS-6/SP Analyzer AFIAS TSH-VB, AFIAS-6/VB Analyzer

Type of Submission	: Traditional 510(k) Submission
Basis for Submission	: Traditional 510(k) Submission for a New Device
Submitter	: Boditech Med Inc.43, Geodudanji 1-gil, Dongnae-myeon,Chuncheon-si, Gang-won-do, 24398,Republic of Korea (South Korea)Phone No.: +82 33 243 1400Fax No.: +82 33 243 9373E-mail: ohj@boditech.co.krWebsite: www.boditech.co.kr
Contact Person	: Hyung-Ju Oh/General Manager (Regulatory Affairs)
Classification Regulation	: 21CFR § 862.1690 Thyroid stimulating hormone test system
Class	: II (for AFIAS TSH-SP Test Cartridge)II (for AFIAS TSH-VB Test Cartridge)I (for AFIAS-6/SP Analyzer)I (for AFIAS-6/VB Analyzer)
Panel	: Clinical Chemistry
Product Code	: JLW; Thyroid stimulating hormone test systemKHO; Fluorometer for Clinical Use
Predicate Device	: Access Fast hTSH with Access 2 System
Predicate Device 'K' Number	: K042281

Intended Use/Indication for Use of AFIAS TSH-SP Test:

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plasma samples. The test system is intended for use as an aid in the diagnosis of thyroid or pituitary disorders.

Intended Use/Indication for Use of AFIAS-6/SP Analyzer:

AFIAS-6/SP Analyzer is a fluorescence-scanning instrument for in vitro diagnostic use at clinical laboratories and Point-of-Care (POC) sites in conjunction with various in vitro diagnostic AFIAS immunoassays for measuring the concentration of designated analytes in serum or plasma samples.

Intended Use/Indication for Use of AFIAS TSH-VB Test:

Intended Use/Indication for Use of AFIAS-6/VB Analyzer:

AFIAS-6/VB Analyzer is a fluorescence-scanning instrument for in vitro diagnostic use at clinical laboratories and Point-of-Care (POC) sites in conjunction with various in vitro diagnostic AFIAS immunoassays for measuring the concentration of designated analytes in venous whole blood samples.

Description of AFIAS TSH-SP and AFIAS TSH-VB Test Cartridges:

The test cartridge is an elongated structure having 140 mm length. 17 mm width and 17 mm height.

Description of AFIAS TSH-SP and AFIAS TSH-VB ID Chips:

The ID Chip is an electronic memory device fitted into a plastic matrix. Lot-specific 'ID Chip' is an integral component of the test.

Before initiating the test run for testing a clinical sample or a calibrator/control using AFIAS TSH-SP or AFIAS TSH-VB test cartridge belonging to a new lot, the operator needs to mandatorily insert the lot-specific AFIAS TSH-SP or AFIAS TSH-VB ID Chip into one of the 'ID Chip Ports' of the AFIAS-6/SP or AFIAS-6/VB analyzer respectively.

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Description of AFIAS-6/SP and AFIAS-6/VB Analyzer:

For performing AFIAS TSH-SP test on a clinical serum/plasma sample or a calibrator/control, AFIAS TSH-SP test cartridge needs to be used in conjunction with the AFIAS-6/SP analyzer.

Similarly, for performing AFIAS TSH-VB test on a clinical venous whole blood sample or a calibrator/control, AFIAS TSH-VB test cartridge needs to be used in conjunction with the AFIAS-6/VB analyzer.

AFIAS-6/SP as well as AFIAS-6/VB analyzer is a compact, bench-top, automated, fluorometric analyzer measuring 42 cm (L) x 33.6 cm (W) x 29.3 cm (H). AFIAS-6 weighs 15.1 kg.

Either analyzer is a flourometer instrument of closed-system analyzer type. The operator does not have access to those configuration parameters that could affect the assay process, test analysis or result calculation or any other parameter that could affect test result outcome. These and other operational parameters can only be configured by the 'System Administrator' through software and/or firmware upgrade and modification of operational settings in consultation with the manufacturer or an authorized service provider.

With a simple computerized touchscreen user interface, the analyzer enables the operator to initiate the test run which is completed automatically and terminates with display of test result or an error message alert (in case of any procedural error and/or system malfunction).

Similarities between AFIAS TSH-SP (with AFIAS-6/SP Analyzer) and the predicate device Access Fast hTSH (with Access 2 System):

Following table shows the similarities between AFIAS TSH-SP (with AFIAS-6/SP Analyzer) and the predicate device Access Fast hTSH with Access 2 System

Similarities between AFIAS TSH-SP (with AFIAS-6/SP Analyzer)
and the predicate device Access Fast hTSH (with Access 2 System)
No.	ComparisonParameter	Candidate Device/TestAFIAS TSH-SP(with AFIAS-6/SP Analyzer)	Predicate Device/Test(Access hTSH Assay withAccess 2 Immunoassay System)
1	Nature of thetest	Quantitative in vitro diagnostic testsystem for human TSH	Quantitative in vitro diagnostictest system for human TSH
2	Intended use	Quantitative measurement of ThyroidStimulating Hormone (TSH) in humanserum and plasma samples	Quantitative determination ofthyroid stimulating hormone(thyrotropin, hTSH) levels inhuman serum and plasma
3	Indications foruse(s)	Indicated for use as an aid in thediagnosis of thyroid or pituitarydisorders.	Indicated for use with patientswhere an assessment of theirthyroid status is desired
4	Intended usesites	Clinical laboratories andPOC sites (e.g. near-the-patientlaboratories of hospitals, out-patientclinics, physician offices etc.)	Clinical laboratories andhospitals

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5 Assaymethodology	Sandwich immunoassay	Sandwich immunoassay
6 Result unit	μIU/ml (= mIU/l)	μIU/ml (= mIU/l)

Differences between AFIAS TSH-SP (with AFIAS-6/SP Analyzer) and the predicate device Access Fast hTSH (with Access 2 System):

Following table shows the differences between AFIAS TSH-SP (with AFIAS-6/SP Analyzer) and the predicate device Access Fast hTSH with Access 2 System.

Differences between AFIAS TSH-SP (with AFIAS-6/SP Analyzer)
and the predicate device Access Fast hTSH (with Access 2 System)
	Comparison	Candidate Device/Test	Predicate Device/Test
No.	Parameter	AFIAS TSH-SP	(Access hTSH Assay with
		(with AFIAS-6/SP Analyzer)	Access 2 Immunoassay System)
		- Clinical laboratories
		- Central laboratories of hospitals	- Clinical laboratories
1	Intended use	- Near-the-patient/POC laboratories of	- Central laboratories of
	sites	hospitals	hospitals
		- Out-patient clinics
		- Physician offices
			Paramagnetic particle
2		Assay principle Immunofluorometric assay	chemiluminiscent
			immunoassay
3	Test device	Self-contained, unitized, ready-to-use,	Ready to use reaction vessel
		disposable test cartridge	containing reagents
4	Associated	AFIAS-6/SP Analyzer	Access 2 Immunoassay
	instrument		System
5		Test throughput 1-6 samples at a time	Batch testing with random
			access
		Reaction/incubation time =15 minutes
	Turnaroundtime	Time for first result in a batch of 6	20 min for Fast hTSH
6		samples = ~ 16 minutes	45 min for HYPERsensitive
		Time to last result in batch of 6 samples	hTSH
		= ~18 minutes
		For serum and plasma samples:
	Sample volume	200 µ1 (minimum 150 µ1)
7		required per test For Calibrators/Controls	Minimum 300 µL
		200 µ1 (minimum 150 µ1)
	Sample volume	For serum and plasma samples:	55 µL for Fast hTSH
8		100 µ1	110 uL for HYPERsensitive
	utilized per test	For Calibrators/Controls: 100 ul	hTSH
	Limit of		0.03 µIU/ml for Fast hTSH
9	Quantitation	0.07 µIU/ml with inter-assay CV ≤ 20%	assay
	/Functional		0.01 µIU/ml for
	Sensitivity		HYPERsensitive hTSH assay

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10	Measuring/reportable range	0.07-80.00 µIU/ml	0.03-100 µIU/ml for FasthTSH assay0.01-100 µIU/ml forHYPERsensitive hTSH assay
11	Calibration	Lot-specific master calibrationcurve/equation is encoded in the 'Lot-specific AFIAS TSH-SP ID Chip' whichneeds to be inserted in one of the 'IDChip Ports' of AFIAS-6/SP analyzerprior to using that AFIAS TSH-SP testcartridge lot for the first time.AFIAS-6/SP can store the informationof up to 100 ID Chips most recentlyinserted in it for performing AFIASTSH-SP or other AFIAS tests.This AFIAS TSH-SP test cartridge lot-specific master calibration curve isfurther automatically adjusted byperiodic duplicate testing of two levelsof AFIAS TSH Calibrators by the user atits discretion.	Manual calibration by testingAccess HYPERsensitivehTSH Calibrators is requiredevery 28 days
12	Operationalenvironment	Ambient temperature 15~35°CInternal/system temperature 33-37°C	15~30℃

Similarities between AFIAS TSH-VB (with AFIAS-6/VB Analyzer) and the predicate device Access Fast hTSH (with Access 2 System):

Following table shows the similarities between AFIAS TSH-VB (with AFIAS-6/VB Analyzer) and the predicate device Access Fast hTSH with Access 2 System

No.	ComparisonParameter	Candidate Device/TestAFIAS TSH-VB(with AFIAS-6/VB Analyzer)	Predicate Device/Test(Access hTSH Assay withAccess 2 Immunoassay System
1	Nature of thetest	Quantitative in vitro diagnostic testsystem for human TSH	Quantitative in vitro diagnostictest system for human TSH
2	Intended use	Quantitative measurement of ThyroidStimulating Hormone (TSH) in Sodiumheparinized or EDTA venous wholeblood samples	Quantitative determination ofthyroid stimulating hormone(thyrotropin, hTSH) levels inhuman serum and plasma
3	Indications foruse(s)	Indicated for monitoring TSH levels ineuthyroid and hypothyroid individuals.	Indicated for use with patientswhere an assessment of theirthyroid status is desired

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	Intended use	Clinical laboratories and POC sites (e.g.near-the-patient laboratories of	Clinical laboratories and
	sites	hospitals, out-patient clinics, physicianoffices etc.)	hospitals
1	Assaymethodology	Sandwich immunoassay	Sandwich immunoassay
	6 Result unit	uIU/ml (= mIU/l)	uIU/ml (= mIU/l)

Differences between AFIAS TSH-VB (with AFIAS-6/VBAnalyzer) and the predicate device Access Fast hTSH (with Access 2 System):

Following table shows the differences between AFIAS TSH-VB (with AFIAS-6/VB Analyzer) and the predicate device Access Fast hTSH with Access 2 System.

Differences between AFIAS TSH-VB (with AFIAS-6/VB Analyzer)and the predicate device Access Fast hTSH (with Access 2 System)
No.	Comparison Parameter	Candidate Device/TestAFIAS TSH-VB(with AFIAS-6/VB Analyzer)	Predicate Device/Test(Access hTSH Assay withAccess 2 Immunoassay System)
1	Intended use sites	- Clinical laboratories- Central laboratories of hospitals- Near-the-patient/POC laboratories of hospitals- Out-patient clinics- Physician offices	- Clinical laboratories- Central laboratories of hospitals
2	Assay principle	Immunofluorometric assay	Paramagnetic particle chemiluminiscent immunoassay
3	Test device	Self-contained, unitized, ready-to-use, disposable test cartridge	Ready to use reaction vessel containing reagents
4	Associated instrument	AFIAS-6/VB Analyzer	Access 2 Immunoassay System
5	Test throughput	1-6 samples at a time	Batch testing with random access
6	Turnaround time	Reaction/incubation time =15 minutesTime for first result in a batch of 6 samples = ~16 minutesTime to last result in batch of 6 samples = ~18 minutes	20 min for Fast hTSH45 min for HYPERsensitive hTSH
7	Sample volume required per test	For venous whole blood samples: 150 $\mu$ l (minimum 100 $\mu$ l)For Calibrators/Controls 200 $\mu$ l (minimum 150 $\mu$ l)	Minimum 300 $\mu$ L
8	Sample volume utilized per test	For venous whole blood samples: 50 $\mu$ lFor Calibrators/Controls: 100 $\mu$ l	55 $\mu$ L for Fast hTSH110 $\mu$ L for HYPERsensitive hTSH

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9	Limit ofQuantitation/FunctionalSensitivity	0.3 µIU/ml with inter-assay CV ≤ 20%	0.03 µIU/ml for Fast hTSHassay0.01 µIU/ml forHYPERsensitive hTSH assay
10	Measuring/reportable range	0.3-80 µIU/ml	0.03-100 µIU/ml for FasthTSH assay0.01-100 µIU/ml forHYPERsensitive hTSH assay
11	Calibration	Lot-specific master calibrationcurve/equation is encoded in the 'Lot-specific AFIAS TSH-VB ID Chip'which needs to be inserted in one of the'ID Chip Ports' of AFIAS-6/VBanalyzer prior to using that AFIAS TSH-VB test cartridge lot for the first time.AFIAS-6/VB can store the informationof up to 100 ID Chips most recentlyinserted in it for performing AFIASTSH-VB or other AFIAS tests.Each AFIAS TSH-VB test cartridge lot-specific master calibration curve isfurther automatically adjusted byperiodic duplicate testing of two levelsof AFIAS TSH Calibrators by the user atits discretion.	Manual calibration by testingAccess HYPERsensitivehTSH Calibrators is requiredevery 28 days
12	Operationalenvironment	Ambient temperature 15~35°CInternal/system temperature 33-37°C	15~30°C

Summary of Performance Evaluation Studies:

1) Limit of Blank:

-Limit of Blank (LoB) of AFIAS TSH-SP and AFIAS TSH-VB tests have been evaluated as per CLSI EP 17-A2.
5 replicates each of 5 blank/TSH-depleted human serum as well as 5 blank/TSH-depleted whole blood samples were tested with 3 lots of test cartridges on 3 respective analyzers for 3 days; thus testing 75 replicates per lot/analyzer.
Limit of Blank (LoB) was calculated by non-parametric analysis of the data. -
Limit of Blank of AFIAS TSH-SP test is 0.03 µIU/ml and that of AFIAS TSH-VB test is 0.13 µIU/ml.

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2) Limit of Detection:

Limit of Detection (LoD) of AFIAS TSH-SP and AFIAS TSH-VB tests have been evaluated as per CLSI EP 17-A2.
5 replicates each of 5 low TSH-spiked human serum as well as 5 low TSH-spiked whole blood samples were tested with 3 lots of test cartridges on 3 respective analyzers for 3 days; thus testing 75 replicates per lot/analyzer.
-Limit of Detection (LoD) was calculated by parametric analysis of the data.
Limit of Detection of AFIAS TSH-SP test is 0.05 µIU/ml and that of AFIAS TSH--VB test is 0.2 µIU/ml.

3) Limit of Quantitation:

Limit of Quantitation (LoO) of AFIAS TSH-SP and AFIAS TSH-VB tests have been evaluated as per CLSI EP 17-A2.
-For evaluating the LoQ of AFIAS TSH-SP test, 2 replicates of each of the 5 low TSH-spiked serum samples were tested daily in two different runs with two test cartridge lot/analyzer/operator combinations for 21 successive days.
-For evaluating the LoQ of AFIAS TSH-VB test. 5 replicates of each of the 4 low TSH-spiked venous whole blood samples were tested daily in two different runs with two test cartridge lot/analyzer/operator combinations for 5 successive days.
-Limit of Quantitation (LoQ) was calculated by considering accuracy goal of interassay CV ≤ 20%.
Limit of Quantitation of AFIAS TSH-SP test is 0.07 µIU/ml and that of AFIAS TSH--VB test is 0.3 µIU/ml.

4) Linearity and Reportable Range:

For evaluating linearity and measuring/reportable range of AFIAS TSH-SP test, a series of 22 test samples prepared by mixing a high TSH-spiked serum sample (TSH~100 µIU/mL) and a TSH-depleted serum sample (TSH ~ 0 µIU/mL) in various proportions, was tested in triplicate with the one lot of AFIAS TSH-SP test cartridges on one AFIAS-6/SP analyzer on the same day.
-Similarly, for evaluating linearity and measuring/reportable range of AFIAS TSH-VB test, a series of 22 test samples prepared by mixing a high TSH-spiked venous whole blood sample (TSH~100 µIU/mL) and a TSH-depleted venous whole blood sample (TSH ~ 0 uIU/mL) in various proportions, was tested in triplicate with the one lot of AFIAS TSH-VB test cartridges on one AFIAS-6/VB analyzer on the same day.
-Mean of the triplicate test results of each sample was plotted against its expected TSH concentration calculated mathematically.
The following linear regression equations were obtained: -

Serum: y = 1.0081x - 0.0785, R2=0.9993

Na-heparinized whole blood: y = 0.9824x + 0.216, R2=0.9997

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-Both tests showed linearity over the entire TSH concentration range (0~100 µIU/ml) tested for the study.
Measuring/reportable range of AFIAS TSH-SP test system has been programed as -0.07-80 uIU/ml while that of AFIAS TSH-VB test system has been programed as 0.3 -80.0 µIU/ml.

5) Susceptibility to High-dose Hook Effect:

For evaluating susceptibility to high dose hook (prozone) effect, a series of spiked samples having TSH concentrations 25, 50, 75, 100, 150, 200, 500, 1000, 1500, 2000, 2500 and 3000 uIU/ml was tested in triplicate with one lot of test cartridges using one analyzer on the same day by the same operator.
-No hook/prozone effect was observed up to TSH concentration of 3000 µIU/ml.

6) Analytical specificity:

Susceptibility of AFIAS TSH-SP and AFIAS TSH-VB test systems to interference from various endogenous substances, heterophiles and drugs as well as cross-reactivity with endogenous TSH structural analogs (hFSH, hLH, and hCG) has been evaluated at specified concentrations of the interferants/cross-reactants as follows:
- . Albumin/Protein (6 g/dL= 6000 mg/dL)
- . Conjugated Bilirubin (20 mg/dL)
- . Unconjugated Bilirubin (20 mg/dL)
- 트 Human hemoglobin (100 mg/dL and 500 mg/dL)
- " Triglycerides (3 g/dL= 3000 mg/dL)
- 트 HAMA (138 ng/mL)
- . Rheumatoid Factor (1500 IU/mL)
- . Biotin (56 ng/mL)
- . Levothyroxine (75 µg/L)
- 트 Methimazole (36 mg/L)
- 트 Metoprolol (4.99 mg/L)
- . Human Follicle-stimulating Hormone/hFSH (1,200 mIU/ml)
- . Human Luteinizing Hormone/hLH (1,200 mIU/ml)
- . Human Chorionic Gonadotropin/hCG (1,200 mIU/ml)
AFIAS TSH-SP as well as AFIAS TSH-VB tests showed analyte recovery within the acceptable range of 90-110% in presence of specified concentrations of above substances thereby indicating insignificant interference/cross-reactivity.

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7) Site-to-Site Precision/Reproducibility:

Reproducibility of AFIAS TSH-SP test system was evaluated by testing 5 replicates of । each of the 4 serum samples (TSH levels ~0.5, ~5.0, ~15.0 & ~55.0 µIU/ml) with 3 lots of AFIAS TSH-SP test cartridges on 3 AFIAS-6/SP analyzers (1 analyzer per site) at 3 external point-of-care sites at the hands of 9 intended POC operators (3 operators per site).
The results are summarized in the following tables:

Site-wise Statistical Analysis of External POC Sites Precision Study Data of
AFIAS TSH-SP Test
SerumSampleTested	PrecisionStudySite	Number ofReplicates(n)	MeanTSH(µIU/mL)	Lot-to-LotImprecision		Day-to-DayImprecision		TotalImprecision
				SD	% CV	SD	% CV	SD	% CV
ClinicalSerumSample 1	Site 1	15	0.49	0.003	0.7	0.006	1.3	0.020	4.2
ClinicalSerumSample 1	Site 2	15	0.49	0.003	0.7	0.009	1.8	0.018	3.7
ClinicalSerumSample 1	Site 3	15	0.50	0.009	1.8	0.011	2.2	0.021	4.2
ClinicalSerumSample 2	Site 1	15	4.91	0.034	0.7	0.187	3.8	0.288	5.9
ClinicalSerumSample 2	Site 2	15	4.96	0.057	1.1	0.154	3.1	0.318	6.4
ClinicalSerumSample 2	Site 3	15	5.03	0.029	0.6	0.145	2.9	0.233	4.6
SpikedSerumSample 3	Site 1	15	14.96	0.423	2.8	0.658	4.4	1.008	6.7
SpikedSerumSample 3	Site 2	15	14.93	0.240	1.6	0.280	1.9	0.749	5.0
SpikedSerumSample 3	Site 3	15	15.26	0.423	2.8	0.277	1.8	0.604	4.0
SpikedSerumSample 4	Site 1	15	54.26	0.496	0.9	1.385	2.6	3.003	5.5
SpikedSerumSample 4	Site 2	15	54.35	2.136	3.9	1.381	2.5	3.141	5.8
SpikedSerumSample 4	Site 3	15	53.53	0.596	1.1	2.306	4.3	2.883	5.4

Combined-sites Statistical Analysis of External POC Sites Precision Study Data ofAFIAS TSH-SP Test
SerumSample Tested	Number ofReplicates(n)	MeanTSH(µIU/mL)	Lot-to-LotImprecision		Day-to-DayImprecision		TotalImprecision
			SD	% CV	SD	% CV	SD	% CV
Clinical SerumSample 1	45	0.49	0.005	1.0	0.007	1.5	0.020	4.0
Clinical SerumSample 2	45	4.97	0.028	0.6	0.072	1.5	0.280	5.6
Spiked SerumSample 3	45	15.05	0.297	2.0	0.244	1.6	0.801	5.3
Spiked SerumSample 4	45	54.05	0.468	0.9	0.531	1.0	2.965	5.5

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Similarly, reproducibility of AFIAS TSH-VB test system was evaluated by testing 5 i replicates of each of the 4 whole blood samples (TSH levels ~0.5, ~5.0, ~15.0 & ~55.0 µIU/ml) with 3 lots of AFIAS TSH-VB test cartridges on 3 AFIAS-6/VB analyzers (1 analyzer per site) at 3 external point-of-care sites at the hands of 9 intended POC operators (3 operators per site).

Site-wise Statistical Analysis of External POC Sites Precision Study Data of
AFIAS TSH-VB Test
Venous WholeBloodSample	PrecisionStudy Site	NumberofReplicates(n)	MeanTSH(µIU/mL)	Lot-to-LotImprecision		Day-to-DayImprecision		TotalImprecision
				SD	% CV	SD	% CV	SD	% CV
Clinical VenousWhole BloodSample 1	Site 1	15	0.45	0.008	1.7	0.015	3.4	0.029	6.3
Clinical VenousWhole BloodSample 1	Site 2	15	0.44	0.005	1.2	0.013	2.8	0.031	7.0
Clinical VenousWhole BloodSample 1	Site 3	15	0.46	0.004	0.9	0.024	5.3	0.029	6.4
Clinical VenousWhole BloodSample 2	Site 1	15	4.88	0.116	2.4	0.273	5.6	0.321	6.6
Clinical VenousWhole BloodSample 2	Site 2	15	5.00	0.105	2.1	0.183	3.7	0.350	7.0
Clinical VenousWhole BloodSample 2	Site 3	15	5.01	0.186	3.7	0.200	4.0	0.403	8.1
Spiked VenousWhole BloodSample 3	Site 1	15	15.97	0.532	3.3	0.581	3.6	1.161	7.3
Spiked VenousWhole BloodSample 3	Site 2	15	15.31	0.425	2.8	0.563	3.7	1.156	7.5
Spiked VenousWhole BloodSample 3	Site 3	15	16.10	0.344	2.1	0.712	4.4	0.995	6.2
Spiked VenousWhole BloodSample 4	Site 1	15	55.77	0.906	1.6	0.944	1.7	2.853	5.1
Spiked VenousWhole BloodSample 4	Site 2	15	56.57	0.450	0.8	1.326	2.3	2.977	5.3
Spiked VenousWhole BloodSample 4	Site 3	15	55.71	1.791	3.2	2.349	4.2	3.300	5.9

The results are summarized in the following tables:

Combined-sites Statistical Analysis of External POC Sites Precision Study Data ofAFIAS TSH-VB Test
Venous Whole BloodSample	Number ofReplicates(n)	MeanTSH(µIU/mL)	Lot-to-LotImprecision		Day-to-DayImprecision		TotalImprecision
			SD	% CV	SD	% CV	SD	% CV
Clinical Venous WholeBlood Sample 1	45	0.45	0.005	1.0	0.012	2.6	0.029	6.5
Clinical Venous WholeBlood Sample 2	45	4.96	0.125	2.5	0.103	2.1	0.356	7.2
Spiked Venous WholeBlood Sample 3	45	15.79	0.206	1.3	0.362	2.3	1.136	7.2
Spiked Venous WholeBlood Sample 4	45	56.02	0.199	0.4	0.750	1.3	3.005	5.4

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8) Matrix Comparison:

Matching clinical serum, sodium heparin plasma and di-potassium EDTA plasma samples obtained from same study subjects were tested with one lot of AFIAS TSH-SP test cartridges on one AFIAS-6/SP analyzer for evaluating the effect of these anticoagulants on AFIAS TSH-SP test results.
Similarly, matching clinical sodium heparin venous whole blood and di-potassium -EDTA venous whole blood samples obtained from same study subjects were tested with one lot of AFIAS TSH-VB test cartridges on one AFIAS-6/VB analyzer for evaluating the effect of these anti-coagulants on AFIAS TSH-VB test results.

Sr.No.	Sample matrices compared& TSH Range of Compared Results	Number ofSamples	Linear RegressionEquation	CorrelationCoefficient
Measuring/reportable range of AFIAS TSH-SP Test = 0.07-80.0 µIU/ml
1	Serum vs. Sodium heparin plasma(0.09 – 77.52 µIU/mL)	81	y = 0.9565x + 0.0424	0.9998
2	Serum vs. Di-Potassium EDTAplasma(0.09 – 77.52 µIU/mL)	79	y = 0.9654x + 0.0131	0.9997

Measuring/reportable range of AFIAS TSH-VB Test = 0.3-80.0 µIU/ml
3	Sodium heparin venous whole bloodvs. Di-Potassium EDTA venouswhole blood(0.40 – 71.74 µIU/mL)	63	y = 0.993x + 0.0325	0.9998

The data and regression analysis are summarized below:

9) Adult Reference Interval:

Adult reference interval of AFIAS TSH-SP test was evaluated by testing serum samples collected from total 128 apparently healthy adults (65 males and 63 females) in the age group of 21-70 years.
Adult reference interval of AFIAS TSH-VB test was evaluated by testing sodium heparin venous whole blood samples collected from total 133 apparently healthy adults (69 males and 64 females) in the age group of 21-70 years.
Non-parametric reference interval encompassing the central 95% frequency distribution of test results was determined as per CLSI C28-A3c Standard.
2.5th percentile and 97.5th percentile of distribution of test results was taken as the । lower limit and upper limit respectively of the reference interval.
Adult reference intervals of AFIAS TSH-SP and AFIAS TSH-VB tests have been found to be 0.45-4.49 µIU/mL and 0.41-4.06 µIU/mL respectively.

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The manufacturer claims 0.45-4.50 uIU/mL as adult reference interval of AFIAS । TSH-SP test and 0.40-4.0 uIU/mL as the adult reference interval of AFIAS TSH-VB test.
। However, the user laboratories should establish their own reference intervals for specific population and/or specific group(s) of population they may cater to.

10) Clinical Method Comparison:

Method comparison studies of AFIAS TSH-SP and AFIAS TSH-VB tests were carried । out at three point-of-care clinical sites at the hands of typical POC operators.
183 serum samples (including 22 spiked serum samples) were tested in singlet with one lot AFIAS TSH-SP test cartridges on one AFIAS-6/SP analyzer per site.

Aliquot of each serum sample from across the three study sites was tested with the predicate device Access Fast hTSH (on the Access 2 system) at a centralized laboratory.

। Similarly, 157 sodium heparinized venous whole blood samples (including 22 spiked venous whole blood samples) were tested in singlet with one lot AFIAS TSH-VB test cartridges on one AFIAS-6/VB analyzer per site.
Matching serum samples from across the three study sites were tested with the predicate device Access Fast hTSH (on the Access 2 system) at the centralized laboratory.
Correlation/comparability between the candidate test results of the tested samples and predicate test results of matching serum samples was evaluated by performing weighted deming regression analysis of the data as summarized in the following table:

TSH Range of Candidate TestResults included in theRegression Analysis ofMethod Comparison Data	Number ofSamples	Weighted DemingRegression Equation(with 95% Confidence Intervalsfor Slope and Y-intercept)	CorrelationCoefficient
AFIAS TSH-SP0.07 – 79.91 µIU/mL	Compared = 183	$y = 0.976x - 0.003$(0.969-0.981) (-0.0055 – -0.0007)	0.9994
AFIAS TSH-VB0.31 – 76.26 µIU/mL	Compared = 157	$y = 0.909x + 0.012$(0.904-0.913) (0.006-0.017)	0.9999

Conclusion:

Based on the intended use, principle and non-clinical as well as clinical performance characteristics described above, AFIAS TSH-SP (with AFIAS-6/SP analyzer) and AFIAS TSH-VB (with AFIAS-6/VB analyzer) test systems are substantially equivalent to the predicate device Acces Fast hTSH (with Access 2 System).

Regulation Number and Section

§ 862.1690 Thyroid stimulating hormone test system.

(a)
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.(b)
Classification. Class II.