The HISCL TSH assay Kit is a magnetic particle chemiluminescent enzyme immunoassay (CLEIA) for the quantitative determination of TSH levels in human serum using the Automated Immunoassay System HISCL-800. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.

The HISCL TSH Calibrator is used for calibrating the HISCL TSH Assay Kit on the Automated Immunoassy System HISCL-800.

The HISCL Immuno Multi Control is used for quality control of the Assay Kit on the Automated Immunoassay System HISCL-800.

Device Description

The HISCL-800 is a fully automated floor model random access immunoassay system that can quantitatively or qualitatively analyze samples for minute traces of a variety of chemistry analytes. The HISCL-800 has a maximum through-put of 100 tests / hour with an analysis time per analyte of 17 minutes and has capacity for 24 on board reagent sets in the cooled reagent storage. Reagent tracking utilizes RFID technology. Using six 5-sample racks, the HISCL-800 has a walk-away capacity for 30 specimens and one STAT sample loading position. An onboard mixer automatically mixes the magnetic particle reagent as needed. The analyzer has a dedicated sample arm which uses disposable tips and three reagent dispensing arms. The HISCL-800 employs chemiluminescent enzyme technology based on CDP-Star™ chemiluminescent substrate. The analyzer has the capacity to run both one-step and two-step sandwich immunoassays.

The HISCL TSH Assay Kit measures TSH based on the chemiluminescent enzyme immunoassay method with CDP-Star® chemiluminescent substrate. The assay utilizes a 1step sandwich immunoassay.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and the study that proves the device meets them, structured according to your requested information:

Device: Automated Immunoassay System HISCL -800, HISCL TSH Assay Kit, HISCL TSH Calibrator, HISCL Immuno Multi Control.
Indication for Use: Quantitative determination of TSH levels in human serum for the diagnosis of thyroid or pituitary disorders.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as a separate table with pass/fail metrics. However, the document describes the performance targets and the results obtained for various non-clinical and clinical studies. I will synthesize these into a table format based on the descriptions.

Performance Metric	Acceptance Criteria (Inferred/Target)	Reported Device Performance
Non-Clinical Performance
20-Day Precision (Within-Laboratory %CV)	(Inferred to be within acceptable clinical laboratory limits, generally <10% for TSH, and specific targets for each sample level would be internal.)	Sample 2 (0.138 µIU/mL): 2.9%Control 1 (1.984 µIU/mL): 2.7%Control 2 (5.991 µIU/mL): 2.8%Sample 1 (5.044 µIU/mL): 2.7%Sample 3 (23.260 µIU/mL): 2.9%
Limit of Blank (LoB)	Measuring range is 0.008 to 75 µIU/mL. LoB should be lower than the measuring range.	0.0007 µIU/mL (lower than the measuring range)
Limit of Detection (LoD)	Measuring range is 0.008 to 75 µIU/mL. LoD should be lower than the measuring range.	0.001 µIU/mL (lower than the measuring range)
Limit of Quantitation (LoQ) / Functional Sensitivity	Lowest TSH concentration with reasonable precision; target ≤ 0.002 µIU/mL (with 20% CV cutoff).	Range from 0.0010 to 0.0014 µIU/mL (all values lower than 0.002 µIU/mL with a 20% CV cutoff). Validated 0.002 µIU/mL functional sensitivity.
Interference	Differences for potential interferents within 10% of the neat control.	Not affected (all differences within 10% of neat control) by: Hemoglobin up to 500 mg/dL, Bilirubin up to 40 mg/dL, HAMA up to 138 ng/mL, Rheumatoid factor up to 500 mg/dL, Triglycerides up to 750 mg/dL, Biotin up to 10 ng/mL, Total protein up to 12 g/dL, Acetaminophen up to 20 mg/dL, Ibuprofen up to 50 mg/dL, Aspirin up to 65 mg/dL.
Cross-reactivity	(Inferred criterion: low percentage of cross-reactivity for hCG, FSH, and LH to ensure specificity.)	Reported very low percentage cross-reactivity: hCG (up to $1.12 \times 10^{-7}$), FSH (up to $2.06 \times 10^{-5}$), LH (up to $3.31 \times 10^{-5}$).
High Dose Hook Effect	No hook effect observed within the measuring range.	No hook effect observed. Samples ~2,000 µIU/mL and 400 µIU/mL reported >200 µIU/mL when undiluted or diluted appropriately.
Spike Recovery	Recoveries such that native samples reflect a 10x increase (100 µIU/mL spike) and 100x increase (1,000 µIU/mL spike) within 20% tolerance.	All data found to be acceptable (met the targeted recovery within 20% tolerance).
Sample Storage Stability	Stable at various conditions (refrigerated, freeze-thaw cycles, long-term frozen) for specified durations.	Samples stable for every sample, at each condition, and at each time point (refrigerated up to 8 days, multiple freeze-thaws up to 5x, long-term storage at -20°C up to 3 months).
Sample On-board Stability	Percent differences within 10% of the Time 0 time point.	Percent differences were all within 10% of the Time 0 time point (up to 8 hours on the instrument).
Reagent, Calibrator, and Control Stability	Specified shelf life for open/closed vials.	HISCL TSH Assay Kit: Expiration Date (closed 2-8°C), 30 days (open/on board 2-8°C).HISCL TSH Calibrators: Expiration Date (closed 2-8°C), 60 days (open 2-8°C).HISCL Immuno Multi Control: Expiration Date (closed 2-8°C), 60 days (reconstituted -20°C), 7 days (reconstituted 2-8°C), 8 hours (reconstituted 8-30°C).
Sample Carryover	No carryover observed.	No carryover was observed.
Linearity/Reportable Range	High correlation coefficient (R²) for expected vs. observed values over the reportable range of 0.008 µIU/mL to 75 µIU/mL.	Regression equation: y = 0.994x + 8.115 x 10^-3; Correlation coefficient: R² = 1.00 (evaluated from 0.001 to 257.887 µIU/mL, ensuring linearity within the reportable range).
Clinical Performance
Reference Range Study (Central 95% interval)	Establish a reference range consistent with expected physiological values for healthy individuals.	0.446 µIU/mL and 4.780 µIU/mL (for N=127, age 21-70).
Method Comparison Study (Agreement with Predicate)	High correlation (slope close to 1, y-intercept close to 0, R² close to 1).	Deming regression: slope 0.950 (95% CI: 0.936 to 0.964); y-intercept -0.0019 (95% CI: -0.0056 to 0.0018); Correlation coefficient 0.993 (95% CI: 0.991 to 0.995).

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

20-Day Precision: 5 samples (2 controls, 3 serum samples), each tested 80 times (20 days * 2 runs/day * 2 duplicates).
Limit of Blank: 4 zero TSH samples, tested 80 times each (not specified if these are human serum or contrived).
Limit of Detection: 5 low TSH samples (contrived by adding TSH to diluent), tested 40 times each (8x/day for 5 days).
Limit of Quantitation (Functional Sensitivity): 7 low TSH samples (4 human pools, 3 serial dilutions of TSH low control), tested 40 times each (twice a day for 20 days).
Interference & Cross-reactivity: 2 serum samples (low and high TSH), tested in triplicate for each interferent/cross-reactant level.
High Dose Hook Effect: 5 high concentration TSH samples (~2,000 µIU/mL), tested in triplicate for each dilution level (neat + 3 serial dilutions).
Spike Recovery: 4 native low TSH serum samples, tested in triplicate with two different spike levels and non-spiked.
Sample Storage Stability: 14 serum samples (10 neat, 4 spiked), tested in replicates of three at various time points/conditions. Provenance: "collected from donors."
Sample On-board Stability: 14 serum samples (10 neat, 4 spiked), tested in replicates of three at various time points. Provenance: "collected from donors."
Sample Carryover: 3 contrived TSH serum pools (low, middle, high), tested in a specific sequence (4 sets/day for 5 days).
Linearity/Reportable Range: 39 intermediate samples (contrived mixture of high and low serum samples). Range tested: 0.001 to 257.887 µIU/mL.
Reference Range Study: N = 127 (65 males, 62 females), Age range 21 and 70 years. Provenance: Clinical specimens from an external clinical laboratory. Presumed prospective collection given the nature of a reference range study.
Method Comparison Study: N = 165. TSH range = 0.009 µIU/mL to 74.604 µIU/mL. Provenance: Clinical specimens from an external clinical laboratory, likely prospective or a mix of prospective/retrospective samples with TSH values across the range.

Data Provenance (General):

Non-Clinical Studies: Primarily in-house studies (in-house stated for precision, prepared for some contrived samples). Samples for stability were collected from donors.
Clinical Studies: Performed by an "external clinical laboratory with clinical specimens." This indicates real-world patient samples. The studies are described as a "reference range study" and a "method comparison study," typically implying prospective or at least recently collected and processed samples within a clinical setting to assess performance against a predicate and establish norms.

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

The document does not specify the number or qualifications of experts used to establish ground truth for the device's performance characteristics. This is common for IVD devices for quantitative analytes.

For performance studies (precision, LoB, LoD, etc.): Ground truth is established by the analytical measurement principles, reference methods, or gravimetric/volumetric preparation of standards. Not typically expert consensus.
For clinical studies (reference range, method comparison): The ground truth for the method comparison is the measurement of the predicate device (Siemens ADVIA Centaur TSH3-Ultra Assay). For the reference range, it is derived statistically from a healthy population.

4. Adjudication Method for the Test Set

Not applicable. For quantitative immunoassay devices like TSH, results are numerical. Ground truth is either the value from a reference method, an assigned value of a certified reference material, or a statistically derived value (e.g., in linearity or reference range studies). This does not involve expert adjudication as one would see in image-based diagnostic AI.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. This is a standalone quantitative immunoassay system, not an AI-assisted diagnostic device that involves human "readers" interpreting output for a diagnostic decision in the same way clinical imaging often does.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, the studies described are all standalone performance evaluations of the HISCL-800 Automated Immunoassay System and HISCL TSH Assay Kit. The system quantifies TSH levels automatically, and the performance metrics (precision, accuracy, linearity, interferences, etc.) are inherent to the device's analytical capabilities without human interpretative input into the final TSH value provided by the machine.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The ground truth used for various studies includes:

Reference Method Comparability: For the method comparison study, the Siemens ADVIA Centaur TSH3-Ultra Assay (the predicate device) served as the reference method or comparative standard.
Assigned Values: For calibrators and controls with known concentrations (e.g., based on WHO Standard 80/558 for calibrators).
Predefined Concentrations: For contrived samples in linearity, LoD, LoQ, interference, cross-reactivity, and hook effect studies where known amounts of TSH or interferents were added.
Statistical Derivation: For the reference range, values were statistically derived from a healthy population.
Analytical Measurement: For precision, stability, and carryover studies, the ground truth is the inherent analytical performance and measurement of the device itself.

8. The Sample Size for the Training Set

The provided document describes a 510(k) submission for an in vitro diagnostic (IVD) quantitative immunoassay system. It does not mention any "training set" in the context of machine learning or AI. The development of such systems typically involves extensive internal validation and optimization studies during the R&D phase, but these are not usually structured as "training sets" in the AI sense for regulatory submissions.

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

As no "training set" (in the AI/ML context) is explicitly described, the method for establishing its ground truth is not detailed. For traditional IVD development, reagent formulations are optimized and instrument parameters refined based on various scientific principles and experimental data to achieve target performance specifications.

Summary

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

SYSMEX AMERICA, INC. MICHELLE PARKER PROJECT MANAGER, REGULATORY AFFAIRS 577 APTAKISIC ROAD LINCOLNSHIRE IL 60069

October 21, 2016

Re: K160541

Trade/Device Name: Automated Immunoassay System HISCL -800. HISCL TSH Assav Kit, HISCL TSH Calibrator, HISCL Immuno Multi Control Regulation Number: 21 CFR 862.1690 Regulation Name: Thyroid stimulating hormone test system Regulatory Class: II Product Code: JLW, JIT, JJY, JJE Dated: September 8, 2016 Received: September 12, 2016

Dear Ms. Parker:

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 (OS) 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 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) K160541

Device Name

HISCL TSH Assay Kit, Automated Immunoassay System HISCL-800, HISCL TSH Calibrator, and HISCL Immuno Multi Control

Indications for Use (Describe)

The Automated Immunoassay System HISCL-800 is a chemiluminescent chemistry analyzer for the determination of analytes in human serum.

The HISCL TSH Calibrator is used for calibrating the HISCL TSH Assay Kit on the Automated Immunoassy System HISCL-800.

The HISCL Immuno Multi Control is used for quality control of the Assay Kit on the Automated Immunoassay System HISCL-800.

Type of Use (Select one or both, as applicable)

☑ Prescription Use (Part 21 CFR 801 Subpart D)
☐ Over-The-Counter Use (21 CFR 801 Subpart C)

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Image /page/3/Picture/0 description: The image shows the Sysmex logo. The logo consists of a stylized graphic element in the upper left and the word "sysmex" in blue to the right. The graphic element is composed of two overlapping shapes, one in blue and the other in green, creating a sense of movement or flow. The word "sysmex" is written in a bold, sans-serif font.

510(k) SUMMARY

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. The assigned 510(k) number is K160541.

807.92 (a)(1):

Name: Sysmex America, Inc.

577 AptakisicRoad Address: Lincolnshire, IL 60069

Phone:	224-543-9639
FAX:	224-543-9699
Contact:	Michelle Parker

807.92 (a)(2): Device name- trade name and common name, and classification

Trade name:

HISCL TSH AssayKit Automated Immunoassay System HISCL-800 HISCL TSH Calibrator HISCL Immuno Multi Control

Common Name:

TSH Assay Kit Automated Immunoassay System TSH Calibrator TSH Control

Classification:

ProductCode	Regulation Name	Classification	Regulation Section	Panel
JLW	Thyroid stimulatinghormone test system	Class II	21 CFR § 862.1690	Chemistry(75)
JJE	Discrete photometricchemistry analyzer forclinical use	Class I	21 CFR § 862.2160	Chemistry(75)
JIT	Calibrator, secondary	Class II	21 CFR§ 862.1150	Chemistry(75)
JJY	Quality control material(assayed and unassayed)	Class I,reserved	21 CFR §862.1660	Chemistry(75)

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Image /page/4/Picture/0 description: The image shows the Sysmex logo. The logo consists of a stylized graphic element in the upper left and the word "sysmex" in blue to the right. The graphic element is composed of two curved shapes, one in blue and the other in green, that appear to be intertwined. The word "sysmex" is written in a bold, sans-serif font.

807.92 (a)(3): Identification of the legally marketed predicate devices

The Sysmex TSH assay kit is substantially equivalent to the ADVIA Centaur TSH3-Ultra (TSH3-UL, Siemens Medical Solutions, Inc., Malvern, PA) cleared under K083844 on Mav 8, 2009.

807.92 (a)(4): Device Description

The HISCL TSH Assay Kit measures TSH based on the chemiluminescent enzyme immunoassay method with CDP-Star® chemiluminescent substrate. The assay utilizes a 1step sandwich immunoassay, as follows:

1. ALP (alkaline phosphatase)-labeled anti-TSH monoclonal antibodies (mouse) in R1 reagent specifically react with TSH in the sample. Biotinylated anti-TSH monoclonal antibodies (mouse) in R3 reagent specifically bind to TSH, and bind to streptavidin-coated MP (magnetic particles) in R2 reagent.

After bound/free (B/F) separation, ALP on MP decomposes CDP-Star® substrate in R5 to an excited intermediate, which produces a luminescent signal.

Because the light production increases in proportion to TSH concentration, sample TSH concentration can be obtained with a calibration curve prepared with calibrators.

Description of Reagents

HISCL TSH Assay Kit - All assay reagents contain sodium azide as a preservative.

1. R1 reagent: contains ALP-labeled anti-TSH monoclonal antibodies (mouse) 0.4 U/mL
1. R2 reagent: contains streptavidin coated with magnetic particles
R3 reagent: contains biotinylated anti-TSH monoclonal antibodies (mouse) 9ug/mL 3)

HISCL Substrate Reagent Set

R4 Reagent (contains sodium azide as a preservative): used for dispersing the magnetic particles before starting the chemiluminescence reaction. The reproducibility of chemiluminescence is improved by dispersing the magnetic particles. Futhermore, the R4 reagent contains inhibitors of endogenous alkaline phosphatase, which helps reduce the background.

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Image /page/5/Picture/0 description: The image shows the Sysmex logo. The logo consists of a stylized wave-like graphic in shades of blue and green, positioned to the left of the company name, "sysmex," which is written in a bold, blue sans-serif font. The wave graphic appears to be composed of two overlapping shapes, with the blue portion on the bottom left and the green portion on the top right.

R5 Reagent (alkaline solution with pH 9.6): contains the chemiluminescent substrate (6 Star®): Disodium 2-e-chloro-5-(4-methoxyspiro { 1,2-dioxetane-3,2 -(5'-chloro)-tricyclo [3.3.1.13,7] decan}-4-yl)-1-phenyl phosphate 0.48mM

HISCL TSH Calibrators- All calibrators contain sodium azide as a preservative.

HISCL TSH C0 (0 uIU/mL) 1)
1. HISCL TSH C1 (2 µIU/mL)
HISCL TSH C2 (10 µIU/mL) 3)
1. HISCL TSH C3 (50 uIU/mL)
HISCL TSH C4 (120 µIU/mL) 5)
HISCL TSH C5 (200 µIU/mL) 6)

HISCL TSH C1-C5 have been adjusted by in-house standard materials based on WHO Standard 80/558. The calibrators contain recombinant TSH, and no components contain human-derived materials.

HISCL Immuno Multi Control

HISCL Immuno Multi Control Level 1 (targeted at 2.006 µIU/mL) 1)
HISCL Immuno Multi Control Level 2 (targeted at 6.340 uIU/mL) 2)

HISCL Immuno Multi Control Level 1 and Level 2 contain human-derived materials.

HISCL Immuno Multi Controls are lyophilized and are reconstituted using distilled water.

HISCL Diluent

HISCL Diluent: contains Bovine Serum Albumin Diluent contain sodium azide as a preservative.

HISCL Probe Washing Solution

HISCL Probe Washing Solution: contains sodium hypochlorite

HISCL Line Washing Solution

HISCL Line Washing Solution: contains Tris(hydroxymethyl)aminomethane 1)

HISCL Washing Solution

HISCL Washing Solution: contains Tris-(hyroxymethyl)aminomethane 1)

807.92 (a)(5): Intended Use

The Automated Immunoassay System HISCL-800 is a chemiluminescent chemistry analyzer for the determination of analytes in human serum.

The HISCL TSH Assay Kit is a magnetic particle chemiluminescent enzyme immunoassay (CLEIA) for the quantitative determination of TSH levels in human serum using the Automated Immunoassay System HISCL-800. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.

The HISCL TSH Calibrator is used for calibrating the HISCL TSH Assay Kit on the Automated Immunoassay System HISCL- 800.

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Image /page/6/Picture/0 description: The image shows the Sysmex logo. The logo consists of a stylized graphic element in the upper left and the word "sysmex" in blue to the right. The graphic element is composed of two overlapping shapes, one in blue and the other in green, creating a sense of movement or flow.

The HISCL Immuno Multi Control is used for quality control of the HISCL TSH Assay Kit on the Automated Immunoassay System HISCL-800.

807.92 (a)(6): Technological Similarities and Differences to the Predicate

The HISCL TSH Assay Kit is substantially equivalent to the ADVIA Centaur TSH3-Ultra (TSH3-UL, Siemens Medical Solutions, Inc., Malvern, PA) cleared under K083844. The following summary (Table 1) describes similarities and differences between the ADVIA Centaur XP Immunoassay System and the Automated Immunoassay System HISCL-800. Table 2 describes the similarities and differences between the ADVIA Centaur TSH3-Ultra Assay Kit and the Sysmex HISCL TSH Assay Kit.

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Image /page/7/Picture/0 description: The image shows the Sysmex logo. The logo consists of a stylized graphic element in shades of blue and green, resembling a wave or a stylized mountain range. To the right of the graphic is the word "sysmex" in a bold, sans-serif font, colored in a matching shade of blue.

	Table 1- Instrument Comparisons
--	---------------------------------	--	--

Feature	Automated ImmunoassaySystem HISCL-800	Siemens ADVIA Centaur XPImmunoassay SystemK083844
Overview
Intended Use	The Automated ImmunoassaySystem HISCL-800 is achemiluminescent chemistryanalyzer for the determination ofanalytes in human serum.	This system is intended for professionaluse in a laboratory environment only.Tests performed using this system areintended for in vitro diagnostic use. Aswith all diagnostic tests, a definitiveclinical diagnosis should not be based onthe results of a single test, but shouldonly be made by the physician after allclinical and laboratory findings havebeen evaluated.
System Description	Random access immunoassaysystem	Random access immunoassay system
Throughput	100 tests per hour	Up to 240 tests per hour
Assay Technology	Alkaline phosphatase for theenzyme and CDP-Star®,which shows a strong emissionintensity with chemiluminescentsubstrates to achieve highsensitivity	Direct chemiluninescence usingacridinium ester technology
Sample Handling
Sampler	Universal 5-position rack holdsmultiple tube types. 6 positionrack adapter for sample cups.	Universal 5-position rack holds multipletube types.
	No pause load and unloading	No pause loading and unloading
STAT Handling	An urgent sample is givenpriority over regular samples. Asample can be placed in theurgent sample holder.	Dedicated STAT port accepts samplesany time
Automatic Dilutions	Not Available	Available
Sample Barcodes	EAN/UPC/JAN,ITF, Codabar/NW7,Code39,Code 128	Code 128, Code 39, Codabar, Interleaved2 of 5
Reagent Handling
Reagent Cooling	24 position on the reagent diskcooled 2°C to 15°C	30-position reagent tray cooled 4°C to8°C
Reagent Integrity Control	Tracked using the RFID label- Reagent item- Reagent type- test counts flag- expired date flag(Lot/onboard)	Barcode reagent identification, automaticinventory tracking and flagging,calibration validity tracked and flagged,reagent on board stability tracked andflagged, reagent expired/reagent lowflagging
Reagent Mixing	Automatically mixes themagnetic particle reagent (R2) onboard.	ReadyPacks automatically rockedonboard
User Interface
Monitor	21.5 inch LCD screen	19-inch diagonal high-resolution LCDtouch screen with adjustable height

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Image /page/8/Picture/0 description: The image shows the Sysmex logo. The logo consists of a stylized wave-like graphic in blue and green, followed by the word "sysmex" in blue, lowercase letters. The wave graphic is positioned to the left of the text.

Table 1- Instrument Comparisons (continued)

General Specifications
Dimensions	Approximately51.0 (h) X 40.1 (w) X 42.9 (d) in	Approximately51.5 (h) X 72.4 (w) X 41.0 (d) in
Weight	Approximately 320 kg (704 lbs)	Approximately 545 kg (1200 lbs)

Table 2: Assay Comparisons

Feature	Sysmex HISCL TSH Assay Kit	Siemens ADVIA Centaur XP TSHAssay Kit- K083844
Intended Use	The HISCL TSH assay Kit is a magneticparticle chemiluminescent enzymeimmunoassay (CLEIA) for thequantitative determination of TSH levelsin human serum using the AutomatedImmunoassay System HISCL-800.Measurements of thyroid stimulatinghormone produced by the anteriorpituitary are used in the diagnosis ofthyroid or pituitary disorders.	For in vitro diagnostic use in thequantitative determination of thyroidstimulating hormone (TSH, thyrotropin)in serum, heparinized plasma, and EDTAplasma using the ADVIA Centaur andthe ADVIA Centaur XP systems.
Sample Type	Serum	Serum, Heparinized Plasma, EDTAPlasma
Sample Volume	200 μL	200 μL
Reportable Range	0.008 μIU/mL to 75 μIU/mL	0.008 μIU/mL to 150 μIU/mL

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Image /page/9/Picture/0 description: The image shows the Sysmex logo. The logo features a stylized graphic element in the upper left, composed of blue and green shapes that resemble a wave or a stylized mountain range. To the right of the graphic is the word "sysmex" in a bold, sans-serif font, colored in a matching blue to the graphic element.

Table 3: Calibrator Comparisons
Similarities
Item	HISCL TSH Calibrator(New Device)	ADVIA Centaur®Calibrator B(K920372)
Intended Use	The HISCL TSH Calibrator is used forcalibrating the HISCL TSH Assay Kit onthe Automated Immunoassay SystemHISCL-800.	For in vitro diagnostic use incalibrating the following assaysusing ADVIA Centaur® orACIS:180® Systems: Digoxin;FSH; Total IgE; LH, LH2,Prolactin; Total hCG; TSH.
Number of Levels	6	10 standard calibrators2 adjusters
Form	Liquid	Lyophilized
Matrix	Triethanolamine hydrochloridebuffer	Equine serum
Calibrator Concentrations	Target Concentrations1. HISCL TSH C0 = 0 μIU/mL2. HISCL TSH C1 = 2 μIU/mL3. HISCL TSH C2 = 10 μIU/mL4. HISCL TSH C3 = 50 μIU/mL5. HISCL TSH C4 = 120 μIU/mL6. HISCL TSH C5 = 200 μIU/mL	Lot SpecificStandard CalibratorsLot Number: 1142907. 0 μIU/mL8. 0.125 μIU/mL9. 0.742 μIU/mL10. 1.99 μIU/mL11. 4.51 μIU/mL12. 9.26 μIU/mL13. 20.2 μIU/mL14. 51 μIU/mL15. 114 μIU/mL16. 191 μIU/mLAdjusterLot Number: CH901. 0.033 μIU/mL2. 102 μIU/mL
Storage Temperature	2 - 8°C	Same
Special instruments	HISCL-800 instrument	ADVIA Centaur® orACIS:180® Systems
Differences
Item	HISCL TSH Calibrator(New Device)	ADVIA Centaur®Calibrator B(Predicate Device)
Analytes	TSH	Multi Analyte:Digoxin, FSH, Total IgE, LHLH2, Prolactin, Total hCG,TSH

Table 3: Calibrator Comparisons

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Image /page/10/Picture/0 description: The image shows the Sysmex logo. The logo consists of a geometric shape in blue and green, resembling two overlapping waves or sails. To the right of the geometric shape is the word "sysmex" in blue, lowercase letters. The logo is clean and modern, with a focus on the company name.

	Similarities
Item	HISCL TSH Control(New Device)	BioRad LiquichekImmunoassay PlusControls (K122838)
Intended Use	The HISCL Immuno Multi Controlis used for quality control of theHISCL TSH Assay Kit on theAutomated Immunoassay SystemHISCL-800.	For in vitro diagnostic use tomonitor the precision and theaccuracy of laboratory tests asspecified in the package insert
Matrix	Human-derived material	Human serum
Control Concentrations	Level 1: Targeted at 2.006 µIU/mLLevel 2: Targeted at 6.340 µIU/mL	Lot SpecificStandard ControlsLot Number: 40900Level 1:Mean = 0.689 µIU/mLRange = 0.555 to 0.824µIU/mLLevel 2:Mean = 4.77 µIU/mLRange = 3.79 to 5.75 IU/mLLevel 3:Mean = 24.6 µIU/mLRange = 19.7 to 29.5µIU/mL
Storage Temperature	2 - 8°C before reconstitution	2 - 8°C
Special instruments	HISCL-800 instrument	Various, including theADVIA Centaur®
	Differences
Item	HISCL Immuno Multi Control (NewDevice)	BioRad LiquichekImmunoassay PlusControls (K122838)
Analytes	TSH	Multi-analytes, includingTSH
Number of Levels	2	3
Form	Lyophilized	Liquid

Table 4: Control Comparisons

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Image /page/11/Picture/0 description: The image shows the Sysmex logo. The logo consists of a blue and green abstract shape on the left, resembling two waves or ribbons intertwined. To the right of the shape is the word "sysmex" in a bold, blue sans-serif font. The logo appears to be for a company or organization named Sysmex.

807.92 (b)(1): Brief Description of Nonclinical Data

A series of studies were performed that evaluated traditional laboratory performance characteristics; a summary of each study follows.

20-Day Precision

Five samples (2 controls and 3 serum samples) were each assayed in- house according to CLSI EP5-A3, meaning testing was performed over 20 days, in duplicate, two runs per day, for a total of 80 results per sample. The study included four reagent lots and three instruments.

SampleID	Mean(µIU/mL)	Repeatability(Within-run)		Between-RunPrecision		Between-DayPrecision		Within- LaboratoryPrecision
		SD	%CV	SD	%CV	SD	%CV	SD	%CV
Sample 2	0.138	0.003	2.2%	0.000	0.0%	0.002	1.4%	0.004	2.9%
Control 1	1.984	0.045	2.3%	0.020	1.0%	0.021	1.1%	0.054	2.7%
Control 2	5.991	0.122	2.0%	0.088	1.5%	0.069	1.2%	0.165	2.8%
Sample 1	5.044	0.122	2.4%	0.040	0.8%	0.046	0.9%	0.137	2.7%
Sample 3	23.260	0.461	2.0%	0.193	0.8%	0.447	1.9%	0.670	2.9%

Limit of Blank, Limit of Detection

Limit of Blank

Four zero TSH samples were obtained from four distinct lots of HISCL Diluent; these were the blank samples. The samples were assayed in replicates of five over four days (n = 80) with each of two lots of test kits on two different instruments (total of four combinations). LoBs (for each lot/instrument combination) were calculated according to CLSI EP17-A2. The LoB with the highest concentration of the four combinations was selected to describe the LoB for the test system. The LoB was determined to be 0.0007uIU/mL, but the measuring range is 0.008 to 75 µIU/mL.

Limit of Detection

Five low samples were prepared by adding varying amounts of TSH to the diluent so that the values ranged from the LoB, to five-times (5x) the LoB. Each sample was assayed by each of two reagent lots and one instrument (two combinations) 8x/day for five days (n = 40/sample with each lot/instrument combination). From this testing, the LoDs were calculated per the CLSI EP17-A2, and the LoD with the highest concentration of the two combinations was selected to describe the LoD for the test system. The LoD was determined to be 0.001µIU/mL, but the measuring range is 0.008 to 75 uIU/mL.

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Image /page/12/Picture/0 description: The image contains the Sysmex logo. The logo features a stylized graphic element in the upper left, composed of blue and green shapes that resemble interconnected waves or a stylized infinity symbol. To the right of the graphic is the word "sysmex" in a bold, sans-serif font, colored in a matching blue to the graphic element.

Limit of Ouantitation (Functional Sensitivity)

The limit of quantitation was described by a functional sensitivity study. Functional sensitivity was defined as the lowest TSH concentration that may be measured with reasonable precision. The target for the LoQ was at, or lower than, 0.002 µIU/mL. The study included seven (7) low TSH samples. Four of the samples were human pools where 10 discrete, native serum samples were combined and TSH was stripped; the three remaining samples were serial dilutions of the TSH low control.

The samples were tested twice a day for 20 days (n = 40 results per level), and means, standard deviations, and %CVs were calculated. The study employed two lots of reagents and two lots of calibrators (4 combinations). For each combination, the TSH values (x-axis) were plotted against %CVs (y-axis). A cutoff of 20% was chosen to represent the highest allowable %CV, and the concentrations of TSH meeting this criterion ranged from 0.0010 to 0.0014uIU/mL. All values were lower than the target of 0.002µIU/mL, and therefore the 0.002µIU/mL functional sensitivity has been validated. The measuring range is 0.008 to 75 uIU/mL.

Interference

Two serum samples with low and high TSH levels targeted at 0.3uIU/mL and 8uIU/mL, respectively, were used. Moderate and high levels of various biological and pharmaceutical substances were added to the neat samples, and all samples were tested in triplicate. The impact of HAMA-positive samples was also evaluated. The differences and percent differences of the means between samples with the potential interferents and without the potential interferents (neat) were calculated.

The data demonstrated that the TSH system was not affected (all differences within 10% of the neat control) for the following substances at the following levels:

Hemoglobin up to 500 mg/dL
Conjugated and unconjugated bilirubin up to 40 mg/dL ●
HAMA up to 138 ng/mL
Rheumatoid factor up to 500 mg/dL ●
Triglycerides up to 750 mg/dL ●
Biotin up to 10 ng/mL ●
Total protein up to 12 g/dL
Acetaminophen up to 20 mg/dL
. Ibuprofen up to 50 mg/dL
Aspirin up to 65 mg/dL ●

Cross-reactivity

Two serum samples with low and high TSH levels targeted at 0.3uIU/mL and 8uIU/mL, respectively, were used. High levels of hCG, FSH, and LH were added to the neat samples, and all samples were tested in triplicate.

Representative data is shown in the following table:

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Sample TSHConcentration(Containing cross-reactant)(\u03bcIU/mL)	Reference TSHConcentration(No cross-reactant)(\u03bcIU/mL)	Interferent	Material added(mIU/mL)	% CrossReactivity
0.298	0.299	hCG	300,000	$-3.33 \times 10^{-10}$
0.301	0.299	FSH	1,000	$2.00 \times 10^{-7}$
0.305	0.299	LH	1,000	$6.00 \times 10^{-7}$
7.427	7.091	hCG	300,000	$1.12 \times 10^{-7}$
7.297	7.091	FSH	1,000	$2.06 \times 10^{-5}$
7.422	7.091	LH	1,000	$3.31 \times 10^{-5}$

High Dose Hook Effect

Five high concentration TSH samples (~2.000 uIU/mL) were prepared. From each sample, three. five-fold serial dilutions were created with the HISCL Diluent to achieve the following TSH levels: 400 uIU/mL, 80 uIU/mL, and 16 uIU/mL. Each serial dilution, plus the neat, high sample, was assayed in triplicate.

The data demonstrated that the diluted samples quantitated at their respective levels, and the undiluted sample (~2,000 µIU/mL) and the 400 µIU/mL samples reported >200 µIU/mL. Therefore, no hook effect was observed.

Spike Recovery

Four native low TSH serum level samples, with TSH concentrations between 0.002 to 4.22 µIU/mL, were identified and measured. Two solutions of high TSH, with levels of 100 and 1,000 ulU/mL, were prepared from WHO standards, and these prepared samples were spiked into the four native samples in the ratio of 1:9 and were tested in triplicate, along with non- spiked samples, in the same run. Performance was targeted to demonstrate that recoveries were such that the native samples would reflect a 10x increase with the 100 µIU/mL spike, and a 100x increase with the 1.000 uIU/mL spike, within a 20% tolerance.

The means were calculated for each sample at each concentration. Also, the expected TSH levels, based on the mathematical calculations from the spikes, were calculated, and then the difference and percent difference between the mean observed concentration and expected concentration were compared. All data was found to be acceptable.

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Image /page/14/Picture/0 description: The image shows the Sysmex logo. The logo consists of a blue and green abstract shape on the left, resembling two intersecting curves. To the right of the shape is the word "sysmex" in blue, lowercase letters. The logo is clean and modern, with a focus on the company name.

Sample Storage Stability

Fourteen (14) serum samples were collected from donors. Ten (10) serum samples were neat and the other four (4) serum samples were spiked with TSH values ranging from approximately 5 µIU/mL to 120 µIU/mL TSH and processed and aliquoted within 8 hours of collection. This was considered the Time 0 timepoint. Samples were retained at the following conditions and time points, and were tested in replicates of three at each timepoint/condition, and then compared back to the Time 0 quantitations.

refrigerated (2-8℃) Days 3, 5, 7, and 8 ●
. multiple freeze thaws (-20 ℃) 1x, 3x, 5x
. long-term storage at -20 ℃ 1month, 2 months, 3 months.

The data was found to be acceptable. The samples were stable for every sample, at each condition, and at each time point.

Sample On-board Stability

Fourteen (14) serum samples were collected from donors. Ten (10) serum samples were neat and the other four (4) serum samples were spiked with TSH values ranging from approximately 5 µIU/mL to 120 µIU/mL TSH and processed and aliquoted within 8 hours of collection. Samples were tested upon aliquoting and this was considered the Time 0 timepoint. The samples were placed on the instrument and tested in replicates of three at the time intervals of 1, 2, 4, 6, and 8 hours past Time 0. The data demonstrated that percent differences were all within 10% of the Time 0 time point.

Reagent, Calibrator, and Control Stability

The results of real time stability for open and closed vials for the HISCL TSH Assay Kit reagents, HISCL TSH Calibrators, and HISCL Immuno Multi Controls are shown below:

HISCL TSH Assay Kit

Storage Temperature	Shelf Life
Storage at 2-8°C before opening	Expiration Date
Storage at 2-8°C/on board after opening	30 days

HISCL TSH Calibrators

Storage Temperature	Shelf Life
Storage at 2-8°C before opening	Expiration Date
Storage at 2-8°C after opening	60 days

HISCL Immuno Multi Control

Storage Temperature	Shelf Life
Storage at 2-8°C before reconstitution	Expiration date
After reconstitution at -20°C or lower	60 days
After reconstitution at 2-8°C	7days
After reconstitution at 8-30°C	8 hours

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Image /page/15/Picture/0 description: The image shows the Sysmex logo. The logo consists of a stylized graphic element in blue and green, resembling interconnected shapes, placed to the left of the company name "sysmex" in blue, lowercase letters. The overall design is clean and modern.

Sample Carryover

Three levels of contrived TSH serum pools (low [L], middle [M] and high [H]) were prepared and measured in the following order: of M, H, L, M, M, L, L, H, H, and M in accordance with CLSI EP-10-A3. Four sets of carryover sequences were assayed per day for five days. The data were found to be acceptable and no carryover was observed.

Linearity/Reportable Range:

A contrived high serum sample was mixed with a low contrived sample to create 39 intermediate samples with concentrations that are known relative to one another. The samples tested in this study ranged from 0.001 to 257.887 uIU/mL. The expected values were plotted against the observed values and the following regression equation was obtained:

y = 0.994x + 8.115 x 10-3
correlation coefficient: R2 = 1.00 ।

807.92 (b)(2): Brief Description of Clinical Data

Clinical performance of the Automated Immunoassay System HISCL 800 and HISCL TSH Assay was assessed via two studies where testing was performed by an external clinical laboratory with clinical specimens. The first study was a reference range study to identify the HISCL reference range according to CLSI EP28-A3c, and the second study was a method comparison study where TSH quantitations obtained with the Automated Immunoassay System HISCL 800 and HISCL TSH Assay were directly compared to the clinical site's reference method, the Siemens ADVIA Centaur TSH3-Ultra Assay (and Centaur instrument), using paired samples.

For the reference range study, the data demonstrated the following:

N = 127 (65 males, 62 females)
Age range 21 and 70 years ●
Central 95% interval 0.446 µIU/mL and 4.780 µIU/mL .

For the method comparison study, the data demonstrated the following:

N = 165
TSH range = 0.009 µIU/mL to 74.604 µIU/mL
Deming regression analysis (95% confidence interval) ●
- slope 0.950 (0.936 to 0.964) - y-intercept -0.0019 (-0.0056 to 0.0018)
- 0.993 (0.991 to 0.995) - correlation coefficient

807.92 (b)(3): Conclusions from Nonclinical and Clinical Testing

The data from the nonclinical and clinical testing indicate that the test system is safe and effective for its intended use.

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.