The Trinidad Immunoassay (IM) system is an automated, immunoassay analyzer designed to perform in vitro diagnostic tests on clinical specimens. The Trinidad IM system's assay applications utilize chemiluminescent technology for clinical use.

The Trinidad IM Thyroid Stimulating Hormone (TSH) assay is for in vitro diagnostic use in the quantitative determination of thyroid-stimulating hormone (TSH, thyrotropin) in human serum and plasma (EDTA and lithium heparin) using the Trinidad IM system. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.

The Trinidad IM TSH Calibrators are for in vitro diagnostic use in calibrating the Trinidad IM system TSH assay.

Device Description

The Siemens Healthcare Diagnostics Trinidad Immunoassay (IM) system is a floor model, fully automated, microprocessor-controlled, integrated instrument system that utilizes chemiluminescent technology and uses pre-packaged reagent packs to measure a variety of analytes in human body fluids. It is controlled through a combination of custom and off-the-shelf software.

The Trinidad IM TSH assay reagent kit comes in two configurations (100 or 500 test kit) and each kit contains the following:
500 Test Kit:

5 ReadyPack primary reagent packs containing Trinidad IM TSH Lite Reagent, Solid Phase, and Ancillary Reagent
2 vials of lyophilized Trinidad IM TSH low calibrator
2 vials of lyophilized Trinidad IM TSH high calibrator

100 Test Kit:

1 ReadyPack primary reagent packs containing Trinidad IM TSH Lite Reagent, Solid Phase, and Ancillary Reagent
1 vial of lyophilized Trinidad IM TSH low calibrator
1 vial of lyophilized Trinidad IM TSH high calibrator

The ReadyPack consists of the following:

Lite Reagent 6.0 mL/ reagent pack: The Lite Reagent contains bovine serum albumin (BSA) conjugated to murine monoclonal anti-TSH (~0.3 µg/mL) antibody labeled with acridinium ester, buffer, stabilizers (murine, bovine, caprine proteins), surfactant, and preservatives.
Solid Phase Reagent 21.0 mL/ reagent pack: The Solid Phase reagent contains anti-fluorescein murine monoclonal antibody covalently linked to paramagnetic particles (~85 µg/mL), buffer, stabilizers (bovine, caprine proteins), surfactant, and preservatives.
Ancillary Reagent 6.0 mL/ reagent pack: The Ancillary reagent contains FITC conjugated to murine monoclonal anti-TSH antibody (~3 µg/mL), buffer, stabilizers (murine, bovine, caprine proteins), surfactant, and preservatives.

The TSH Calibrator consists of the following:

After reconstitution, low and high levels of thyroid stimulating hormone (TSH) in HEPES buffered equine serum with sodium azide (< 0.1%) and preservatives. The low and high calibrators are targeted at ~ 0.032 and 97.5 µIU/mL, respectively.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the Trinidad IM Thyroid Stimulating Hormone (TSH) assay, Trinidad Immunoassay (IM) system, and Trinidad IM TSH Calibrators, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance:

Performance Characteristic	Acceptance Criteria (Implicit)	Reported Device Performance (Trinidad IM TSH Assay)
Detection Limits
Limit of Blank (LoB)	Per CLSI Document EP17-A2	0.001 µIU/mL
Limit of Detection (LoD)	Per CLSI Document EP17-A2	0.005 µIU/mL
Limit of Quantitation (LoQ)	Total imprecision ≤ 20%	0.008 µIU/mL
Linearity	Good correlation (R value)	Linear from 0.0001 to 150 µIU/mL (R = 1.000)
Precision	Per CLSI Document EP05-A2
Repeatability (CV%)	Low %CV	1.45% - 3.68% (across various specimens)
Within-Lab (CV%)	Low %CV	3.59% - 5.95% (across various specimens)
Interfering Substances	< 10% effect	< 5% change at tested interferent levels
Hemolyzed		500 mg/dL of hemoglobin
Lipemic		1000 mg/dL of triglycerides
Icteric (conjugated)		40 mg/dL of conjugated bilirubin
Icteric (unconjugated)		40 mg/dL of unconjugated bilirubin
Heterophile Interference	No interference observed	No interference observed
Cross-reactivity	Non-detectable	Non-detectable for hCG, FSH, LH at tested levels
High Dose Hook Effect	No hook effect	No high dose hook effect up to 3,000 µIU/mL
Method Comparison (vs. Predicate)	Good correlation (R value)	R = 0.994, Slope = 1.07, Intercept = -0.003
Serum Plasma Matrix Equivalency	Equivalent with good correlation	R = 1.00 (Lithium Heparin), R = 1.00 (EDTA Plasma)
Expected Values	Verified	Verified across infant, children, adolescent, adult populations
Stability	Verified shelf-life	12 months at 2 – 8°C

2. Sample Sizes Used for the Test Set and Data Provenance:

Detection Limits:
- LoB: 10 times in each of at least 10 runs using 1 lot of reagent on 2 systems over a period of at least 5 days (n = 200).
- LoD: Low level TSH serum samples assayed in duplicate in each of at least 20 runs using 1 lot of reagents on 2 systems over a period of at least 10 days (n=80).
- LoQ: Multiple patient samples with low TSH values assayed in duplicate in each of 10 runs on 2 systems over a period of 10 days. (Specific n not given, but many samples implied).
Linearity: Nine (9) equally spaced pools, ranging in TSH levels from 0.0001 to 151 ulU/mL, prepared from a high TSH serum sample mixed with an equine serum pool.
Precision: Four commercial controls, six serum samples, and six plasma samples. Each sample was assayed in 2 replicates per run, 2 runs per day for 20 days. (Total of 80 replicates per sample tested).
Interfering Substances: Specific number of samples not provided, but tested with various levels of hemolyzed, lipemic, and icteric specimens.
Cross-reactivity: Human samples containing TSH, with added hCG, FSH, and LH. Specific number of samples not provided.
High Dose Hook Effect: Serial dilutions of a very high TSH sample. Specific number of samples not provided.
Method Comparison: Sample Range of 0.008 – 148.8 µIU/mL. (Exact number of samples not provided).
Serum Plasma Matrix Equivalency: Sample Range of 0.014 – 134.5 µIU/mL for both lithium heparin and EDTA plasma vs. serum. (Exact number of samples not provided).
Expected Values:
- Infants (01 - 23 months): N = 46
- Children (02 - 12 years): N = 136
- Adolescents (13 - 20 years): N = 160
- Adults (≥ 21 years): N = 155

Data Provenance: The document does not explicitly state the country of origin of the data or whether it was retrospective or prospective. It refers to "human serum and plasma" samples and "patient samples," suggesting clinical samples were used.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:

This type of immunoassay device measures a quantitative biomarker. The "ground truth" for each sample is typically the concentration of TSH in that sample, as measured by a highly accurate and precise reference method or an existing, validated device. Therefore, the concept of "experts" to establish ground truth in the way it's used for AI image analysis (e.g., radiologists interpreting images) is not directly applicable here. The ground truth for method comparison studies is the measurement from the predicate device (ADVIA Centaur TSH3 Ultra assay).

4. Adjudication Method for the Test Set:

Not applicable in the context of quantitative laboratory assays. The "ground truth" values are instrumental measurements, not subjective interpretations requiring adjudication.

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

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic imaging devices where human readers interpret cases, and the AI's effect on their performance is evaluated. For this TSH assay, the comparison is directly between the new device's readings and a predicate device's readings.

6. Standalone Performance:

Yes, a standalone performance was done. All the performance characteristics listed (detection limits, linearity, precision, interference, cross-reactivity, high dose hook effect, serum plasma matrix equivalency, expected values, stability) evaluate the algorithm's performance independent of human intervention once the sample is loaded into the automated system. The "method comparison" also compares the new device's standalone measurements directly against those of the predicate device.

7. Type of Ground Truth Used:

Quantitative measurements: For most performance characteristics, the ground truth is implicitly defined by highly accurate and precise laboratory methods or reference materials.
Predicate device measurements: For the method comparison study, the "ground truth" against which the new device's performance was compared was the measurements obtained from the legally marketed ADVIA Centaur TSH3 Ultra assay.

8. Sample Size for the Training Set:

This document does not specify a separate "training set" in the context of machine learning. For traditional immunoassay development, methods are developed and validated using various samples to establish performance characteristics. The document describes several testing phases:

Detection Limits, Linearity, Precision, Interference, Cross-reactivity, High Dose Hook Effect: These involve testing across various samples and conditions to characterize the assay's fundamental performance.
Expected Values: Human populations are tested (Infants N=46, Children N=136, Adolescents N=160, Adults N=155) to establish reference ranges.
Method Comparison: Samples covering a range from 0.008 – 148.8 µIU/mL were used for comparison against the predicate.

While these tests inform the overall validation, they are not typically referred to as "training sets" in the AI sense. The assay principle is a fixed chemical reaction, not a machine learning model that "learns" from data.

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

As there isn't a traditional "training set" for a machine learning algorithm, this question isn't directly applicable. For the performance characteristics, the "ground truth" is established as follows:

Reference Methods/Materials: For limits and linearity, the "true" concentrations are often derived from highly controlled preparations or validated reference materials.
Predicate Device: For method comparison, the results from the previously cleared predicate device (ADVIA Centaur TSH3 Ultra assay) serve as the comparative "ground truth."
Standardization to WHO International Standard: The TSH assay and calibrators are stated to be traceable to the World Health Organization (WHO) 3rd International standard for human TSH (IRP 81/565), which acts as a primary ground truth for TSH measurement comparability.

Summary

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

November 20, 2015

SIEMENS HEALTHCARE DIAGNOSTICS.INC. PHILIP LIU SENIOR MANAGER, REGULATORY AFFAIRS AND COMPLIANCE 511 BENEDICT AVENUE TARRYTOWN NY 10591

Re: K151792

Trade/Device Name: Trinidad IM Thyroid Stimulating Hormone (TSH) assay, Trinidad Immunoassay (IM) system, Trinidad IM TSH Calibrators Regulation Number: 21 CFR 862.1690 Regulation Name: Thyroid stimulating hormone test system Regulatory Class: II Product Code: JLW, JJE, JIT Dated: October 15, 2015 Received: October 16, 2015

Dear Philip Liu:

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

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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,

Katherine Serrano -S

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

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration
Indications for Use	Form Approved: OMB No. 0910-0120Expiration Date: January 31, 2017See PRA Statement below.
510(k) Number (if known)	K151792
Device Name	Trinidad Immunoassay (IM) systemTrinidad IM Thyroid Stimulating Hormone (TSH) assayTrinidad IM TSH Calibrators
Indications for Use (Describe)	The Trinidad Immunoassay (IM) system is an automated, immunoassay analyzer designed to perform in vitro diagnostictests on clinical specimens. The Trinidad IM system's assay applications utilize chemiluminescent technology for clinicaluse.The Trinidad IM Thyroid Stimulating Hormone (TSH) assay is for in vitro diagnostic use in the quantitative determinationof thyroid-stimulating hormone (TSH, thyrotropin) in human serum and plasma (EDTA and lithium heparin) using theTrinidad IM system. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in thediagnosis of thyroid or pituitary disorders.The Trinidad IM TSH Calibrators are for in vitro diagnostic use in calibrating the Trinidad IM system TSH assay.
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)

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

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information unless it displays a currently valid OMB number."

FORM FDA 3881 (1/14) Page 1 of 1 PSC Publishing Services (301) 443-6740 EF

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510(k) Summary of Safety and Effectiveness for the

Trinidad Immunoassay (IM) System Trinidad IM Thyroid Stimulating Hormone Assay

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

A. 510(k) Number:

B. Date of Preparation: November 18, 2015

C. Proprietary and Established Names:

Trinidad IM Thyroid Stimulating Hormone (TSH) Assay Trinidad IM TSH Calibrators Trinidad Immunoassay (IM) System

D. Applicant:

Siemens Healthcare Diagnostics Inc., 511 Benedict Ave, Tarrytown, NY 10591 Philip Liu, Senior Manager, Requlatory Affairs and Compliance Office: (914) 524-2443 Fax: (914) 524-3579

E. Regulatory Information:

System

1. Requlation section: 21 CFR § 862.2160
1. Classification: Class I
1. Product Code: JJE, Photometric Analyzer for Clinical Use
1. Panel: Clinical Chemistry

Assay

1. Regulation section: 21 CFR § 862.1690
1. Classification: Class II
1. Product Code: JLW, Thyroid stimulating hormone test system
1. Panel: Clinical Chemistry

Calibrator

1. Regulation section: 21 CFR § 862.1150
1. Classification: Class II
1. Product Code: JIT Calibrator, Secondary
1. Panel: Clinical Chemistry

F. Predicate Devices:

ADVIA® Centaur XP system cleared under 510(k) K041133.

ADVIA® Centaur Thyroid Stimulating Hormone (TSH3 Ultra) Assay and Calibrators cleared under K150403.

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G. Device Description:

Trinidad Immunoassay (IM) System:

The Trinidad IM system performs the following functions:

. Aspirates and dispenses samples
. Performs dilutions
. Adds reagents
. Incubates reaction vessels
. Separates solid and liquid wastes
. Measures photon emissions
. Performs data reduction
. Collects and maintains patient demographics and results

Trinidad IM TSH assay:

The Trinidad IM TSH assay reagent kit comes in two configurations (100 or 500 test kit) and each kit contains the following:

500 Test Kit:

5 ReadyPack primary reagent packs containing Trinidad IM TSH Lite Reagent, . Solid Phase, and Ancillary Reagent
. 2 vials of lyophilized Trinidad IM TSH low calibrator
. 2 vials of lyophilized Trinidad IM TSH high calibrator

100 Test Kit:

1 ReadyPack primary reagent packs containing Trinidad IM TSH Lite Reagent, . Solid Phase, and Ancillary Reagent
. 1 vial of lyophilized Trinidad IM TSH low calibrator
. 1 vial of lyophilized Trinidad IM TSH high calibrator

The ReadyPack consists of the following:

Lite Reagent 6.0 mL/ reagent pack: ● The Lite Reagent contains bovine serum albumin (BSA) conjugated to murine monoclonal anti-TSH (~0.3 µg/mL) antibody labeled with acridinium ester, buffer, stabilizers (murine, bovine, caprine proteins), surfactant, and preservatives.
. Solid Phase Reagent 21.0 mL/ reagent pack: The Solid Phase reagent contains anti-fluorescein murine monoclonal antibody covalently linked to paramagnetic particles (~85 µg/mL), buffer, stabilizers (bovine, caprine proteins), surfactant, and preservatives.
. Ancillary Reagent 6.0 mL/ reagent pack: The Ancillary reagent contains FITC conjugated to murine monoclonal anti-TSH antibody (~3 µg/mL), buffer, stabilizers (murine, bovine, caprine proteins), surfactant, and preservatives.

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The TSH Calibrator consists of the following:

After reconstitution, low and high levels of thyroid stimulating hormone (TSH) in ● HEPES buffered equine serum with sodium azide (< 0.1%) and preservatives. The low and high calibrators are targeted at ~ 0.032 and 97.5 µIU/mL, respectively.

H. Intended Use / Indications for Use:

The Trinidad IM TSH Calibrators are for in vitro diagnostic use in calibrating the Trinidad IM system TSH assay.

Substantial Equivalence Information: -

Both the Trinidad IM TSH assay (New Device) on the Trinidad IM system and the ADVIA Centaur TSH3 Ultra assay on the ADVIA Centaur (Predicate Device cleared under K150403) employ the same prepackaged reagents for use on automated test systems. The Intended Use / Indications for Use. Assay Principle and reagent formulations are the same. The major differences between the New and Predicate Devices are the reagent packaging and the instrument. A comparison of the important similarities and differences of these assays, calibrators, and systems are shown in the following tables:

System:

Similarities and Differences:

Feature	Predicate Device:ADVIA Centaur XP	New Device:Trinidad IM
Intended Use	Automated, immunoassay analyzerdesigned to perform in vitrodiagnostic tests on clinicalspecimens.	Same
Principles of AssayOperation	Chemiluminescence using magnetic-particle solid phase andchemiluminescent label	Same
Type of System	Random Access and Batch	Same
Throughput Rate	120 to 240 tests/hr.	250 to 450 tests/hr.
Time to First Result	18 min., 30 min., 60 min. dependingupon assay protocol	10 min., 14 min., 28 min., 55 mindepending upon assay protocol
Feature	Predicate Device:ADVIA Centaur XP	New Device:Trinidad IM
Optical System	PMT used in photon counting mode	Same
Temp control	Ambient temp 18-30C	Same
Test Processing	Sample scheduling optimized forthroughput; continuous operation7.5 minute incubation, single step20 minute incubation, single step7.5 minute - 20 minute incubation,two step20 minute - 20 minute incubation,two StepReactions are controlled at 37°C	Same"Fast 1-pass" assays: 8 minuteincubation"Routine 1-pass" assays: 12 minuteincubationNA"2-pass" assay: 12 minute - 12 minuteincubationsor12 minute - 20 minute incubationsSame
Sample Handling
Sample Container	Sample cups or primary tubes maybe used	Same
Sample Type	Serum, plasma, urine, whole bloodhemolysate, amniotic	Same
Dispense System	Disposable Sample Pipette TipsAutomated pipetting of samplesusing precision syringe	Same
Sample Probe	Air pressure fluid sensing anddisposable tip sensing; clog detectionmechanism to alert operator toclogged sample probe	Same
Sample Volume	10 to 200 μl	10 to 100 μl
Sample Rack	5 tube racks hold sample tubes. TheSample Input, In-Process and OutputQueue holds up to 180 samples;tube size selected on sample tuberack using an encoded barcode withthe additional capability of multiplesize tubes on the same rack.	Samples identified delivered byTrinidad Direct load
Dilutions	Allowed on a per-assay basis;capability of dilution of samplesrequiring pretreatment	Same
Reagent Handling
Assay Reagent Tray	Refrigerated with 30 positions;Reagent Pack contains both SolidPhase and Tracer Reagent inseparate wells	Rotating refrigerated tray with 42positions; Reagent Pack contains bothSolid Phase and Tracer Reagent inseparate wells
Ancillary Reagent Tray	Refrigerated compartment with 25positions for ancillary packs	Rotating refrigerated compartmentwith 42 positions
Reagent Storage	4°C to 8°C	4°C to 8°C
Feature	Predicate Device:ADVIA Centaur XP	New Device:Trinidad IM
Reagents	Primary Reagent Pack contains bothSolid Phase and Tracer Reagent inseparate wells; solid phase isChemiluminescent labeled(Acridinium Ester)Ancillary Reagent Pack - containscomponents of the primary reagentand/or sample diluents	Same (identical reagent formulation)Modifications in container shape
System Bulk Fluids	Wash 1, Acid and Base	Modifications in container size andshape
Dispense system	Automated pipetting using precisionsyringe	Same
Mixing	Reagents mixed via rocking platform	Reagent mixing is via rotation and notrocking
Reagent Probes	Reagent preheating; no level sense;probe sent to bottom of container;fluid monitoring during aspiration	No reagent preheating; fluidmonitoring on aspiration and dispenseusing liquid pressure sensing
Calibration	6 to 10 point stored calibration foreach reagent2 point user run calibrationCalibrators checked with barcodeCalibrator lot numbers stored anddisplayedCapability to dilute controls	Same
Controls	Capability to dilute controls	Same
GeneralSpecifications
Power Requirements	<2000 watts	~3000 watts
Dimensions	42 in D x 58 in L x 60 in H	880 mm D x 1350mm L x1500 mm H
Weight	~550 kg	< 750 kg
Computers/OS
CPU	Primary PC - Sun Sparc Station	Intel processor with Windows 7operating system
Display/Monitor	19" display (optional Touch screen)	24" touch screen
Software
GUI Application	User interface is unique to ADVIACentaur systems	Universal Instrument Workstationcommon to new Siemens IVD systems
On-Line Help	Separate for System application andADVIA QC	Not available at this time
QC	ADVIA QC V3.2x applicationprovides stored control results,Levy-Jennings plotting, and statistics	Similar
LIS Interfaces	LIS ASTM standards 1394/1381, andLIS HL7 standards	Not available at this time
LAS Interfaces	Siemens URAP LAS Interface	Utilize pick and place sampling ratherthan point in space
Feature	Predicate Device:ADVIA Centaur XP	New Device:Trinidad IM
Real-Time Solutions(RTS) support	Interface to RTS via LabCom protocol and RTS via i2i protocol	Not available at this time
External printers	Parallel port and USB interfaced printers	Not available at this time

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Assay:

Similarities and Differences:

ltem	Predicate Device:ADVIA Centaur TSH3 Ultra Assay	New Device:Trinidad IM TSH Assay
Intended Use	For in vitro diagnostic use in thequantitative determination of thyroid-stimulating hormone (TSH,thyrotropin) in serum, heparinizedplasma, and EDTA plasma	Same
Indications for Use	Measurements of thyroid stimulatinghormone produced by the anteriorpituitary are used in the diagnosis ofthyroid or pituitary disorders.	Same
Sample type	Serum and Plasma	Same
Measurement	Quantitative	Same
Assay Principle	Sandwich immunoassay	Same
Technology	Chemiluminescence	Same
Detection Antibody	Monoclonal murine anti-TSHantibody BSA conjugate labeled withacridinium ester (AE)	Same
Capture Antibody	Anti-fluorescein labeled (FITC)monoclonal murine anti-TSHantibody covalently bound toparamagnetic particles (PMP)	Same
Assay Range	0.008 - 150 ulU/mL	Same
Calibration	2 Point	Same
Calibrators	ADVIA Centaur TSH Calibrators	Trinidad TSH Calibrators(identical formulation)
Number ofcalibrators	Two (2) levels	Same
Use of Controls	Yes (recommended)	Same
Standardization /Traceability	Standardized to internal standardsand is traceable to the World HealthOrganization (WHO) 3rdInternational standard for humanTSH (IRP 81/565)	Same
Calibratorspackaging	Provided with reagent kit	Same
Expected Values	Infants: 0.87 - 6.15 µIU/mLChildren:0.67 - 4.16 µIU/mLAdolescent: 0.48- 4.17 µIU/mLAdult: 0.55 - 4.78 µIU/mL	Same
Item	Predicate Device:	New Device:
	ADVIA Centaur TSH3 Ultra Assay	Trinidad IM TSH Assay
IntendedUse/Indication foruse	For in vitro diagnostic use incalibrating TSH assay	Same
Antigen used incalibrators	Thyroid stimulating hormone	Same
Number of levels	2	Same
Matrix	Lyophilized buffered equine serum	Same
Storagetemperature	2-8°C	Same
Standardization /Traceability	Standardized to internal standards andis traceable to the World HealthOrganization (WHO) 3rd Internationalstandard for human TSH (IRP 81/565)	Same
Packaging	Provided with reagent kit	Same

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Calibrators:

Similarities and Differences:

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

CLSI Guideline EP05-A3: Evaluation of Precision Performance of Qualitative о Measurement Methods
CLSI Guideline EP17-A2: Evaluation of Detection Capability for Clinical O Laboratory Measurement Procedures
CLSI Guideline EP28-A3: Defining, Establishing, And Verifying Reference O Intervals In The Clinical Laboratory; Approved Guideline- Third Edition
CLSI Guideline EP7-A2: Interference Testing in Clinical Chemistry; Approved O Guideline

L. Test Principle

The Trinidad IM TSH assay is a third-generation assay that employs anti-FITC monoclonal antibody covalently bound to paramagnetic particles, an FITC-labeled anti-TSH capture monoclonal antibody, and a tracer consisting of a proprietary acridinium ester and an anti-TSH monoclonal antibody conjugated to bovine serum albumin (BSA) for chemiluminescent detection. A direct relationship exists between the amount of TSH present in the patient sample and the amount of relative light units (RLUs) detected by the system.

M. Performance Characteristics

Substantial equivalence of the Trinidad IM TSH assay on the Trinidad IM system was demonstrated by testing several performance characteristics including detection limits (LoB, LoD, and LoQ), imprecision, linearity, interfering substances and method comparison.

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a. Detection Limits

The limit of blank (LoB), limit of detection (LoD), and the limit of quantitation (LoQ) of the Trinidad IM TSH assay were determined as described in CLSI Document EP17-A2. The Trinidad IM TSH assay had a LoB of 0.001 µIU/mL, a LoD of 0.005 µIU/mL, and a LoQ of 0.008 µIU/mL.

The LoB is defined as the concentration of TSH that corresponds to the 95th percentile of the distribution of the TSH zero standard; the TSH zero standard was assayed 10 times in each of at least 10 runs using 1 lot of reagent on 2 systems over a period of at least 5 days (n = 200).

The LoD is defined as the lowest concentration of TSH that can be detected with 95% probability. The LoD was determined by using low level TSH serum samples that were assayed in duplicate in each of at least 20 runs using 1 lot of reagents on 2 systems over a period of at least 10 days (n=80).

The LoQ, or functional sensitivity, is the lowest concentration of TSH at which the total imprecision for the assay does not exceed 20%, and was determined by assaying multiple patient samples with low TSH values in duplicate in each of 10 runs on 2 systems over a period of 10 days.

b. Linearity

The Trinidad IM TSH analytical linearity was evaluated by testing a linearity pool that was prepared using a high TSH serum sample mixed with an equine serum pool to prepare nine (9) equally spaced pools, ranging in TSH levels from 0.0001 to 151 ulU/mL. The weighted linear regression of the Observed (y) vs. Expected (x) values for this pool is:

y = 0.957x + 0.0000, R = 1.000

The Trinidad IM TSH assay is linear from 0.0001 to 150 µIU/mL.

c. Precision

Precision estimates were computed according to CLSI Document EP05-A2, Evaluation of Precision Performance of Quantitative Measurement Methods: Approved Guideline. Repeatability and within lab imprecision were evaluated by testing four commercial control, six serum samples and six plasma samples. Each sample was assayed in 2 replicates per run, 2 runs per day for 20 days for a total of 80 replicates. Testing was done using two reagent lots on two systems.

A representative lot is summarized below:

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			Repeatability		Within-Lab
Specimen Type	N	Mean(µIU/mL)	SD(µIU/mL)	CV(%)	SD(µIU/mL)	CV(%)
Control 1	80	0.034	0.00	2.36	0.00	4.45
Control 2	80	0.40	0.01	1.96	0.02	4.20
Control 3	80	5.26	0.09	1.74	0.23	4.44
Control 4	80	32.8	0.60	1.82	1.62	4.95
Plasma Pool 1	80	3.38	0.08	2.34	0.15	4.51
Plasma Pool 2	80	37.9	1.26	3.32	2.25	5.95
Plasma Pool 3	80	144	3.68	2.56	7.67	5.34
Plasma Pool 4	80	0.72	0.01	1.45	0.03	4.00
Plasma Pool 5	80	4.99	0.11	2.12	0.21	4.19
Plasma Pool 6	80	79.9	1.79	2.24	3.86	4.82
Serum Pool 1	80	1.11	0.02	1.46	0.04	3.67
Serum Pool 2	80	5.83	0.09	1.47	0.24	4.15
Serum Pool 3	80	11.4	0.21	1.86	0.42	3.71
Serum Pool 4	80	34.7	0.63	1.80	1.25	3.59
Serum Pool 5	80	59.9	1.06	1.76	2.27	3.78
Serum Pool 6	80	132	2.66	2.01	6.23	4.72

d. Interfering Substances

Interfering substances were tested as described in CLSI Document EP7-A2 using the Trinidad IM TSH assay. There was no indication of interference (< 10% effect) up to the interferent levels claimed. Results showed less than 5% change at the interferent levels tested.

Serum specimens that are	Demonstrate ≤ 5% change in results up to
hemolyzed	500 mg/dL of hemoglobin
lipemic	1000 mg/dL of triglycerides
icteric	40 mg/dL of conjugated bilirubin
icteric	40 mg/dL of unconjugated bilirubin

e. Heterophile Interference

HAMA Type 1 and Type 2 interference studies were provided with the ADVIA Centaur TSH3 Ultra assay cleared in 510(k) K150403; no interference was observed. The Trinidad IM TSH reagents are the same reagents as the Predicate ADVIA Centaur TSH3 Ultra reagents. The packaging is identical and the only difference is the labeling. Therefore, the performance of the Trinidad IM TSH reagents are the same as the ADVIA Centaur TSH3 Ultra reagents in regards to Heterophile interference.

f. Cross-reactivity

Cross reactivity was evaluated in the Trinidad IM TSH with hCG, FSH, and LH by adding these hormones to human samples containing TSH. Cross reactivity was nondetectable at the levels tested for hCG (200,000 µIU/mL), FSH (1500 µIU/mL) and LH (600 µIU/mL).

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g. High Dose Hook Effect

The potential for the high dose hook effect in the Trinidad IM TSH assay was evaluated by testing serial dilutions of a very high TSH sample. No high dose hook effect was observed in samples with TSH levels as high as 3,000 µIU/mL.

h. Method Comparison

A method comparison study with the Trinidad IM TSH assay was done versus the Predicate ADVIA Centaur TSH3 Ultra assay. The Trinidad IM assay shows good correlation (R value) in sample results compared to and the Predicate. Based on the weighted Deming regression results, the Trinidad IM TSH assay is equivalent to the Predicate.

X-axis	Y-axis	Slope	Intercept	R*	Sample Range
ADVIA CentaurTSH3 Ultra	Trinidad IMTSH	1.07	-0.003	0.994	0.008 – 148.8 µIU/mL

*From Least squares linear regression

i. Serum Plasma Matrix Equivalency

Lithium heparin and EDTA plasma samples were compared to serum in the Trinidad IM TSH assay. The weighted Deming analyses of the lithium heparin and EDTA plasma samples versus serum demonstrate that these matrices are equivalent using the Trinidad IM TSH assay.

X-axis	Y-axis	Slope	Intercept	R	Sample Range
Serum	Lithium Heparin Plasma	1.01	-0.001	1.00	0.014 – 134.5 µIU/mL
Serum	EDTA Plasma	1.00	-0.000	1.00	0.014 – 134.5 µIU/mL

j. Expected Values

The Expected Values for the ADVIA Centaur TSH3 Ultra assay (cleared under 510(k) K150403) were verified on the Trinidad IM TSH assay by testing infant (1 - 23 months), children (2 - 12 years), adolescent (13 - 20 years) and adult (> 21 years) populations. The number of individuals tested and used in the analysis and the Expected Values are as follows:

Age Range	N	Expected Values
Infants (01 - 23 months)	46	0.87 - 6.15 µIU/mL
Children (02 - 12 years)	136	0.67 - 4.16 µIU/mL
Adolescents (13 - 20 years)	160	0.48-4.17 µIU/mL
Adults (≥ 21 years)	155	0.55 - 4.78 µIU/mL

k. Stability

The Trinidad IM TSH reagents are the same reagents as the Predicate ADVIA Centaur TSH3 Ultra reagents cleared in 510(k) K150403. The packaging is identical and the only difference is the labeling. Therefore, the shelf-life stability of the Trinidad IM TSH

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reagents is identical to those of the ADVIA Centaur TSH3 Ultra reagents. The shelf-life stability of the reagents was provided in 510(k) K150403 as 12 months at 2 – 8°C.

N. Conclusions

Comparative testing of the Trinidad IM TSH assay on the Trinidad IM system is substantially equivalent in principle and performance to the Predicate Device ADVIA Centaur TSH3 Ultra assay on the ADVIA Centaur system cleared under 510(k) K150403.

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.