(238 days)
No
The summary describes a standard automated immunoassay system and assay kit. There is no mention of AI, ML, or any features that would typically involve such technologies for data analysis, interpretation, or system control beyond basic automation.
No
This device is an in vitro diagnostic (IVD) system used to measure analytes in human serum, specifically TSH levels, for diagnostic purposes, not for treating any condition.
Yes
The device, "Automated Immunoassay System HISCL-800", is described as a "chemiluminescent chemistry analyzer for the determination of analytes in human serum," and specifically mentions that "Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders." This clearly indicates its use in diagnosing health conditions.
No
The device description clearly details a physical, automated immunoassay system (HISCL-800) with hardware components like sample arms, reagent dispensing arms, mixers, and RFID technology. The software is integral to controlling this hardware and processing the data generated by the physical assay.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states the system is for the "determination of analytes in human serum" and the TSH assay kit is for the "quantitative determination of TSH levels in human serum." This indicates the device is used to test samples taken from the human body.
- Device Description: The description details a system designed to analyze samples using chemical reactions (chemiluminescent enzyme immunoassay).
- Performance Studies: The performance studies describe testing the device's ability to accurately measure TSH in human serum samples, including precision, linearity, interference, and method comparison with a predicate device.
- Intended User/Care Setting: While it's for professional use in a laboratory, this is a common setting for IVD devices.
The core function of the device is to analyze biological samples (human serum) to provide information about a person's health status (TSH levels for diagnosing thyroid or pituitary disorders). This aligns directly with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for 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.
The HISCL Immuno Multi Control is used for quality control of the Assay Kit on the Automated Immunoassay System HISCL-800.
Product codes (comma separated list FDA assigned to the subject device)
JLW, JJE, JIT, JJY
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, as follows:
-
- 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.
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
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Anatomical Site
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Indicated Patient Age Range
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Intended User / Care Setting
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Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
20-Day Precision:
- Study Type: Precision study (CLSI EP5-A3)
- Sample Size: 5 samples (2 controls, 3 serum samples), assayed in duplicate, two runs per day for 20 days (80 results per sample).
- Key Results:
- Sample 2 (Mean 0.138 µIU/mL): Within-Laboratory Precision %CV: 2.9%
- Control 1 (Mean 1.984 µIU/mL): Within-Laboratory Precision %CV: 2.7%
- Control 2 (Mean 5.991 µIU/mL): Within-Laboratory Precision %CV: 2.8%
- Sample 1 (Mean 5.044 µIU/mL): Within-Laboratory Precision %CV: 2.7%
- Sample 3 (Mean 23.260 µIU/mL): Within-Laboratory Precision %CV: 2.9%
Limit of Blank (LoB):
- Study Type: LoB determination (CLSI EP17-A2)
- Sample Size: Four zero TSH samples from four distinct lots of HISCL Diluent, assayed in replicates of five over four days (n = 80) with each of two lots of test kits on two different instruments.
- Key Results: LoB determined to be 0.0007 µIU/mL. Measuring range is 0.008 to 75 µIU/mL.
Limit of Detection (LoD):
- Study Type: LoD determination (CLSI EP17-A2)
- Sample Size: Five low samples, assayed 8x/day for five days (n = 40/sample with each lot/instrument combination) for two reagent lots and one instrument.
- Key Results: LoD determined to be 0.001 µIU/mL. Measuring range is 0.008 to 75 µIU/mL.
Limit of Quantitation (Functional Sensitivity):
- Study Type: Functional sensitivity study
- Sample Size: Seven low TSH samples (four human pools, three serial dilutions), tested twice a day for 20 days (n = 40 results per level) using two lots of reagents and two lots of calibrators.
- Key Results: Concentrations of TSH meeting a 20% CV criterion ranged from 0.0010 to 0.0014 µIU/mL, which were lower than the target of 0.002 µIU/mL. The 0.002 µIU/mL functional sensitivity has been validated.
Interference:
- Study Type: Interference study
- Sample Size: Two serum samples (low and high TSH levels), tested in triplicate with moderate and high levels of various biological and pharmaceutical substances.
- Key Results: TSH system was not affected (all differences within 10% of neat control) for 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:
- Study Type: Cross-reactivity study
- Sample Size: Two serum samples (low and high TSH levels), tested in triplicate with high levels of hCG, FSH, and LH.
- Key Results:
- hCG (300,000 mIU/mL): -3.33 x 10^-10 to 1.12 x 10^-7 % cross-reactivity.
- FSH (1,000 mIU/mL): 2.00 x 10^-7 to 2.06 x 10^-5 % cross-reactivity.
- LH (1,000 mIU/mL): 6.00 x 10^-7 to 3.31 x 10^-5 % cross-reactivity.
High Dose Hook Effect:
- Study Type: High dose hook effect study
- Sample Size: Five high concentration TSH samples (~2,000 µIU/mL) and their serial dilutions.
- Key Results: No hook effect was observed. Diluted samples quantitated at their respective levels, and undiluted (~2,000 µIU/mL) and 400 µIU/mL samples reported >200 µIU/mL.
Spike Recovery:
- Study Type: Spike recovery study
- Sample Size: Four native low TSH serum samples, spiked with high TSH solutions (100 and 1,000 µIU/mL) and tested in triplicate.
- Key Results: All data found to be acceptable; recoveries within 20% tolerance of expected increase.
Sample Storage Stability:
- Study Type: Sample storage stability
- Sample Size: Fourteen serum samples (10 neat, 4 spiked), processed and aliquoted within 8 hours.
- Key Results: Samples stable at refrigerated (2-8℃) for 8 days, multiple freeze-thaw cycles (1x, 3x, 5x at -20℃), and long-term storage (-20℃) for 3 months.
Sample On-board Stability:
- Study Type: Sample on-board stability
- Sample Size: Fourteen serum samples (10 neat, 4 spiked).
- Key Results: Percent differences within 10% of Time 0 for time intervals of 1, 2, 4, 6, and 8 hours.
Reagent, Calibrator, and Control Stability:
- Study Type: Real-time stability for open and closed vials.
- Key Results:
- HISCL TSH Assay Kit: Expiration date before opening (2-8°C), 30 days after opening (2-8°C/on board).
- HISCL TSH Calibrators: Expiration date before opening (2-8°C), 60 days after opening (2-8°C).
- HISCL Immuno Multi Control: Expiration date before reconstitution (2-8°C), 60 days after reconstitution (-20°C or lower), 7 days after reconstitution (2-8°C), 8 hours after reconstitution (8-30°C).
Sample Carryover:
- Study Type: Sample carryover (CLSI EP-10-A3)
- Sample Size: Three levels of contrived TSH serum pools (low, middle, high), measured in a specific order for four sets of sequences per day for five days.
- Key Results: No carryover observed.
Linearity/Reportable Range:
- Study Type: Linearity study
- Sample Size: 39 intermediate samples prepared from a high and low contrived serum sample. Samples ranged from 0.001 to 257.887 µIU/mL.
- Key Results: Regression equation y = 0.994x + 8.115 x 10^-3, correlation coefficient R^2 = 1.00.
Reference Range Study:
- Study Type: Reference range study (CLSI EP28-A3c)
- Sample Size: N = 127 (65 males, 62 females).
- Key Results: Central 95% interval 0.446 µIU/mL and 4.780 µIU/mL.
Method Comparison Study:
- Study Type: Method comparison study
- Sample Size: N = 165
- Key Results: TSH range = 0.009 µIU/mL to 74.604 µIU/mL. Deming regression analysis: slope 0.950 (0.936 to 0.964), y-intercept -0.0019 (-0.0056 to 0.0018), correlation coefficient 0.993 (0.991 to 0.995).
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Limit of Blank (LoB): 0.0007 µIU/mL
- Limit of Detection (LoD): 0.001 µIU/mL
- Functional Sensitivity (LoQ): 0.002 µIU/mL (validated)
- Correlation coefficient (R^2) for Linearity: 1.00
- Correlation coefficient for Method Comparison: 0.993 (0.991 to 0.995)
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
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Image /page/0/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized graphic of three human profiles facing to the right. The profiles are connected and form a single, flowing shape. The graphic is surrounded by a circular border of text that reads "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA".
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.
1
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
2
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 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.
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:
| Product
| Code | Regulation Name | Classification | Regulation Section | Panel |
|---|---|---|---|---|
| JLW | Thyroid stimulating | |||
| hormone test system | Class II | 21 CFR § 862.1690 | Chemistry | |
| (75) | ||||
| JJE | Discrete photometric | |||
| chemistry analyzer for | ||||
| clinical 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-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, as follows:
-
- 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.
-
- R1 reagent: contains ALP-labeled anti-TSH monoclonal antibodies (mouse) 0.4 U/mL
-
- 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)
-
- HISCL TSH C1 (2 µIU/mL)
- HISCL TSH C2 (10 µIU/mL) 3)
-
- 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 Immunoassay
System HISCL-800 | Siemens ADVIA Centaur XP
Immunoassay System
K083844 |
|---------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Overview | | |
| Intended Use | The Automated Immunoassay
System HISCL-800 is a
chemiluminescent chemistry
analyzer for the determination of
analytes in human serum. | This system is intended for professional
use in a laboratory environment only.
Tests performed using this system are
intended for in vitro diagnostic use. As
with all diagnostic tests, a definitive
clinical diagnosis should not be based on
the results of a single test, but should
only be made by the physician after all
clinical and laboratory findings have
been evaluated. |
| System Description | Random access immunoassay
system | Random access immunoassay system |
| Throughput | 100 tests per hour | Up to 240 tests per hour |
| Assay Technology | Alkaline phosphatase for the
enzyme and CDP-Star®,
which shows a strong emission
intensity with chemiluminescent
substrates to achieve high
sensitivity | Direct chemiluninescence using
acridinium ester technology |
| Sample Handling | | |
| Sampler | Universal 5-position rack holds
multiple tube types. 6 position
rack adapter for sample cups. | Universal 5-position rack holds multiple
tube types. |
| | No pause load and unloading | No pause loading and unloading |
| STAT Handling | An urgent sample is given
priority over regular samples. A
sample can be placed in the
urgent sample holder. | Dedicated STAT port accepts samples
any time |
| Automatic Dilutions | Not Available | Available |
| Sample Barcodes | EAN/UPC/JAN,ITF, Codabar
/NW7,Code39,Code 128 | Code 128, Code 39, Codabar, Interleaved
2 of 5 |
| Reagent Handling | | |
| Reagent Cooling | 24 position on the reagent disk
cooled 2°C to 15°C | 30-position reagent tray cooled 4°C to
8°C |
| Reagent Integrity Control | Tracked using the RFID label
- Reagent item
- Reagent type
- test counts flag
- expired date flag
(Lot/onboard) | Barcode reagent identification, automatic
inventory tracking and flagging,
calibration validity tracked and flagged,
reagent on board stability tracked and
flagged, reagent expired/reagent low
flagging |
| Reagent Mixing | Automatically mixes the
magnetic particle reagent (R2) on
board. | ReadyPacks automatically rocked
onboard |
| User Interface | | |
| Monitor | 21.5 inch LCD screen | 19-inch diagonal high-resolution LCD
touch 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 | Approximately | |
| 51.0 (h) X 40.1 (w) X 42.9 (d) in | Approximately | |
| 51.5 (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 TSH
Assay Kit- K083844 |
|------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | 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. | For in vitro diagnostic use in the
quantitative determination of thyroid
stimulating hormone (TSH, thyrotropin)
in serum, heparinized plasma, and EDTA
plasma using the ADVIA Centaur and
the ADVIA Centaur XP systems. |
| Sample Type | Serum | Serum, Heparinized Plasma, EDTA
Plasma |
| 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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| Table 3: Calibrator Comparisons | ||
|---|---|---|
| Similarities | ||
| Item | HISCL TSH Calibrator | |
| (New Device) | ADVIA Centaur® | |
| Calibrator B | ||
| (K920372) | ||
| Intended Use | The HISCL TSH Calibrator is used for | |
| calibrating the HISCL TSH Assay Kit on | ||
| the Automated Immunoassay System | ||
| HISCL-800. | For in vitro diagnostic use in | |
| calibrating the following assays | ||
| using ADVIA Centaur® or | ||
| ACIS:180® Systems: Digoxin; | ||
| FSH; Total IgE; LH, LH2, | ||
| Prolactin; Total hCG; TSH. | ||
| Number of Levels | 6 | 10 standard calibrators |
| 2 adjusters | ||
| Form | Liquid | Lyophilized |
| Matrix | Triethanolamine hydrochloride | |
| buffer | Equine serum | |
| Calibrator Concentrations | Target Concentrations |
- HISCL TSH C0 = 0 μIU/mL
- HISCL TSH C1 = 2 μIU/mL
- HISCL TSH C2 = 10 μIU/mL
- HISCL TSH C3 = 50 μIU/mL
- HISCL TSH C4 = 120 μIU/mL
- HISCL TSH C5 = 200 μIU/mL | Lot Specific
Standard Calibrators
Lot Number: 114290 - 0 μIU/mL
- 0.125 μIU/mL
- 0.742 μIU/mL
- 1.99 μIU/mL
- 4.51 μIU/mL
- 9.26 μIU/mL
- 20.2 μIU/mL
- 51 μIU/mL
- 114 μIU/mL
- 191 μIU/mL
Adjuster
Lot Number: CH90 - 0.033 μIU/mL
- 102 μIU/mL |
| Storage Temperature | 2 - 8°C | Same |
| Special instruments | HISCL-800 instrument | ADVIA Centaur® or
ACIS:180® Systems |
| Differences | | |
| Item | HISCL TSH Calibrator
(New Device) | ADVIA Centaur®
Calibrator B
(Predicate Device) |
| Analytes | TSH | Multi Analyte:
Digoxin, FSH, Total IgE, LH
LH2, Prolactin, Total hCG,
TSH |
Table 3: Calibrator Comparisons
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| Similarities | |||
|---|---|---|---|
| Item | HISCL TSH Control | ||
| (New Device) | BioRad Liquichek | ||
| Immunoassay Plus | |||
| Controls (K122838) | |||
| Intended Use | The HISCL Immuno Multi Control | ||
| is used for quality control of the | |||
| HISCL TSH Assay Kit on the | |||
| Automated Immunoassay System | |||
| HISCL-800. | For in vitro diagnostic use to | ||
| monitor the precision and the | |||
| accuracy of laboratory tests as | |||
| specified in the package insert | |||
| Matrix | Human-derived material | Human serum | |
| Control Concentrations | Level 1: Targeted at 2.006 µIU/mL | ||
| Level 2: Targeted at 6.340 µIU/mL | Lot Specific | ||
| Standard Controls | |||
| Lot Number: 40900 | |||
| Level 1: | |||
| Mean = 0.689 µIU/mL | |||
| Range = 0.555 to 0.824 | |||
| µIU/mL | |||
| Level 2: | |||
| Mean = 4.77 µIU/mL | |||
| Range = 3.79 to 5.75 IU/mL | |||
| Level 3: | |||
| Mean = 24.6 µIU/mL | |||
| Range = 19.7 to 29.5 | |||
| µIU/mL | |||
| Storage Temperature | 2 - 8°C before reconstitution | 2 - 8°C | |
| Special instruments | HISCL-800 instrument | Various, including the | |
| ADVIA Centaur® | |||
| Differences | |||
| Item | HISCL Immuno Multi Control (New | ||
| Device) | BioRad Liquichek | ||
| Immunoassay Plus | |||
| Controls (K122838) | |||
| Analytes | TSH | Multi-analytes, including | |
| TSH | |||
| Number of Levels | 2 | 3 | |
| Form | Lyophilized | Liquid |
Table 4: Control Comparisons
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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.
| Sample
ID | Mean
(µIU/mL) | Repeatability
(Within-run) | | Between-Run
Precision | | Between-Day
Precision | | Within- Laboratory
Precision | |
|--------------|------------------|-------------------------------|------|--------------------------|------|--------------------------|------|---------------------------------|------|
| | | 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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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 TSH
Concentration
(Containing cross-
reactant)
(\u03bcIU/mL) | Reference TSH
Concentration
(No cross-reactant)
(\u03bcIU/mL) | Interferent | Material added
(mIU/mL) | % Cross
Reactivity |
|---------------------------------------------------------------------------------|------------------------------------------------------------------------|-------------|----------------------------|-------------------------|
| 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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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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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.