K Number
K062581
Date Cleared
2006-11-29

(90 days)

Product Code
Regulation Number
862.1690
Reference & Predicate Devices
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The Olympus thyroid stimulating hormone (TSH) assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of TSH levels in human serum and plasma using the Olympus AU3000i™ Immunoassay System.

Measurements of TSH produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.

The Olympus TSH Calibrator is used for calibrating the quantitative Olympus TSH Assay on the Olympus AU3000i Immunoassay System.

The Olympus TSH Control is used for quality control of the Olympus TSH test system on the Olympus AU3000i Immunoassay System.

The Olympus AU3000i Immunoassay System is a chemiluminescent discrete photometric chemistry analyzer for the quantitative determination of analytes in human serum and plasma.

Device Description

The Olympus TSH assay is a two-step paramagnetic particle enzyme immunoassay. It is based on the sandwich principle and used to quantitate TSH in serum/plasma.

The Olympus TSH assay reagent and sample are added to the assay cuvette in the following sequence:

  1. Samples are incubated first with a monoclonal anti-TSH antibody bound to paramagnetic particles.
  2. After a washing step, a second monoclonal anti-TSH antibody conjugated with alkaline phosphatase is added. The TSH reacts with the paramagnetic particles and the conjugated antibody to form a sandwich complex. Washing steps remove the unbound material.
  3. The chemiluminescent substrate is added to the assay cuvette and reacts with the bound alkaline phosphatase (ALP). Light generated by the reaction is measured by the luminometer. The light emission is proportional to the quantity of TSH in the sample.
  4. Results are calculated from a pre-defined calibration curve. The Olympus AU3000i system automatically calculates the TSH concentration of each sample in mIU/L or µIU/mL.
AI/ML Overview

The provided 510(k) summary focuses on demonstrating substantial equivalence of the Olympus TSH Test System to predicate devices rather than establishing novel acceptance criteria and proving the device meets them with a dedicated study. Instead, the performance characteristics of the Olympus TSH Test System are compared directly to those of the predicate Roche Elecsys® TSH Test System.

Therefore, the response below will present the performance characteristics as a comparison to the predicate device, rather than explicit "acceptance criteria" and "reported device performance."

Here's the breakdown of the information requested, based on the provided text:


1. Table of Acceptance Criteria and Reported Device Performance

As this is a 510(k) submission demonstrating substantial equivalence, explicit "acceptance criteria" are not stated in the typical sense of a performance goal. Instead, the performance of the Olympus TSH Test System is compared directly to the predicate device, the Roche Elecsys® TSH Test System. The implicit acceptance criterion is that the performance of the new device is comparable to the predicate.

Performance CharacteristicPredicate Device Performance (Roche Elecsys® TSH)Olympus TSH Test System Performance
Precision (Total CV%)
Low Concentration8.72.9
Medium Concentration3.36.0
High Concentration3.63.7
Functional Sensitivity0.014 µIU/mL0.0013 µIU/mL
Analytical Sensitivity0.005 µIU/mL0.0002 µIU/mL
Measurable Range0.005 – 100.0 µIU/mL0.001 – 130 µIU/mL
Method Comparison (Passing Bablok)
Intercept0.01-0.0046
Slope1.010.935
R0.9440.9931
Applicable Interfering Substances
Bilirubin≤ 10% @ 41 mg/dL≤ 10% @ 40 mg/dL
Hemolysis≤ 10% @ 1 g/dL≤ 5% @ 5 g/L
Lipemia≤ 10% @ 1500 mg/dL≤ 3% @ 10 g/L
Specificity (LH, FSH, hGH, hCG)No significant interference for LH & FSH. hGH Not Detected. hCG Not Detected.No significant interference for LH & FSH. hGH Not Tested. hCG Not Detected.

2. Sample Size for the Test Set and Data Provenance

The document does not explicitly state the sample sizes used for the performance characteristic studies (e.g., precision, method comparison, interference). The data provenance (e.g., country of origin, retrospective/prospective) is also not specified.


3. Number of Experts and Qualifications for Ground Truth

For in vitro diagnostic (IVD) devices like the Olympus TSH Test System, "ground truth" is typically established through reference methods, certified calibrators, or established analytical techniques, rather than expert human interpretation (like radiologists). The document indicates traceability to "WHO" (World Health Organization) for both the predicate and proposed device, implying the use of international reference standards. No human experts are mentioned for establishing ground truth.


4. Adjudication Method for the Test Set

Not applicable for an IVD device where ground truth is typically assessed through quantitative analytical methods and reference standards, not human adjudication of subjective interpretations.


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

Not applicable. This is an in vitro diagnostic device for quantitative determination of TSH levels, not an imaging or diagnostic aid for human readers.


6. Standalone Performance Study

Yes, the performance characteristics listed in the table above (Precision, Functional Sensitivity, Analytical Sensitivity, Measurable Range, Method Comparison, Interference, Specificity) represent the standalone (algorithm/device only) performance of the Olympus TSH Test System. These are intrinsic analytical performance metrics of the device itself.


7. Type of Ground Truth Used

The ground truth for this type of IVD device is based on reference materials, certified calibrators, and/or comparison to a well-established and accepted reference method. The document states "Traceability: WHO" for both the Olympus TSH Test System (WHO 3rd IS 81/565) and the predicate (WHO 2nd IRP 80/558), indicating that the results are standardized against internationally recognized standards for TSH measurement.


8. Sample Size for the Training Set

The document does not specify a separate "training set" sample size. For IVD devices, method development and optimization studies are conducted, but usually, a distinct "training set" and "test set" in the context of machine learning (where this terminology is common) are not explicitly detailed in 510(k) summaries for traditional immunoassay systems. The performance characteristics described are typically derived from verification and validation studies.


9. How Ground Truth for the Training Set Was Established

Not explicitly detailed as a "training set" in the machine learning sense. However, for the development and calibration of such an assay, ground truth would be established through a combination of:

  • Using calibrators with known TSH concentrations (e.g., Olympus TSH Calibrator, referenced to WHO standards).
  • Testing against reference samples or patient samples analyzed by established, validated reference methods, often traceable to international standards.
  • The "Olympus TSH Calibrator is used for calibrating the quantitative Olympus TSH Assay," and its matrix is "Bovine serum human pituitary TSH," implying that the calibrators themselves embody the "ground truth" for the device's measurement scale.

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K062581

510(k) Summary

NOV 2 9 2006

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


1.Submitter name,address, contactOlympus America3131 W Royal LaneIrving, TX 75063Telephone:Fax:Contact Person:Date Prepared:(972) 556-9697(972) 556-0365David DavisOctober 6, 2006
2.Device nameProprietary Name:Common Name:Classification Name:Olympus TSH ReagentOlympus TSH CalibratorOlympus TSH ControlOlympus AU3000i™ Immunoassay SystemTSH Reagent, Calibrator & ControlImmunoassay AnalyzerThyroid-Stimulating Hormone Test System,Calibrator, secondarySingle (specified) analyte control (assayed andunassayed)Analyzer, Chemistry (Photometric, Discrete),For Clinical Use
3.Predicate deviceReagent:Calibrator:Control:Analyzer:Roche Elecsys® TSH Assay (K961491)Roche Elecsys® TSH CalSet (K060754)Roche Elecsys® PreciControl TSH (K962573)Roche Elecsys® 2010 analyzer (K961481)

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4.Device descriptionThe Olympus TSH assay is a two-step paramagnetic particle enzymeimmunoassay. It is based on the sandwich principle and used to quantitateTSH in serum/plasma.
The Olympus TSH assay reagent and sample are added to the assaycuvette in the following sequence:
1. Samples are incubated first with a monoclonal anti-TSH antibodybound to paramagnetic particles.2. After a washing step, a second monoclonal anti-TSH antibodyconjugated with alkaline phosphatase is added. The TSH reacts withthe paramagnetic particles and the conjugated antibody to form asandwich complex. Washing steps remove the unbound material.
3. The chemiluminescent substrate is added to the assay cuvette andreacts with the bound alkaline phosphatase (ALP). Light generatedby the reaction is measured by the luminometer. The light emission isproportional to the quantity of TSH in the sample.4. Results are calculated from a pre-defined calibration curve. The
Olympus AU3000i system automatically calculates the TSHconcentration of each sample in mIU/L or µIU/mL.
5.Intended useThe Olympus thyroid stimulating hormone (TSH) assay is a paramagneticparticle, chemiluminescent immunoassay for the quantitativedetermination of TSH levels in human serum and plasma using theOlympus AU3000i™ Immunoassay System.
Measurements of TSH produced by the anterior pituitary are used in thediagnosis of thyroid or pituitary disorders.
The Olympus TSH Calibrator is used for calibrating the quantitativeOlympus TSH Assay on the Olympus AU3000i Immunoassay System.
The Olympus TSH Control is used for quality control of the Olympus TSHtest system on the Olympus AU3000i Immunoassay System.
The Olympus AU3000i Immunoassay System is a chemiluminescentdiscrete photometric chemistry analyzer for the quantitative determinationof analytes in human serum and plasma.

:

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    1. Comparison to
      predicate device
      The following tables compare the Olympus TSH Test System with the
      Roche Elecsys® TSH Test System.
ItemAU3000i with TSHRoche Elecsys® TSH
Intended UseQuantitative determination of thyroid stimulating hormone (TSH) levels in human serum/plasmaImmunoassay for the in vitro quantitative determination of thyrotropin in human serum and plasma.
TraceabilityWHOWHO
Detection/Operating PrincipleChemiluminescenceChemiluminescence
Assay MethodologySandwich immunoassaySandwich immunoassay
Solid PhaseMicro-particleMicro-particle
Sample TypeSerum and plasmaSerum and plasma
AntibodyMonoclonal anti-TSH mouse antibodyMonoclonal anti-TSH mouse antibody
Analyzer ReagentsOn-board StorageBar-coded (I-D & 2-D) reagent, calibrator & controlCap/septum for increased reagent stability and evaporation controlOn-board StorageBar-coded (1-D & 2-D) reagent, calibrator & controlCap/septum for increased reagent stability and evaporation control
Reagent, Calibrator and Control storage formLiquidLiquid
Calibration and Control StabilityUnopened• At 2-8°C up to the stated expiration dateOpened• 28 days / 4 weeks at 2-8°CUnopened• At 2-8°C up to the stated expiration dateOpened• 28 days / 4 weeks at 2-8°C
Control levels and target concentration rangeOne Euthyroid/Hyperthyroid thresholdOne Euthyroid/Hyperthyroid threshold
Control constituentsSingleSingle
Control MatrixHuman serum with added antigenHuman serum with added antigen
Analyzer SystemFully automatedRandom accessComputer controlledStat capabilityFully automatedRandom accessComputer controlledStat capability
Analyzer/User InterfaceKeyboard/touch screen controlColored touch screen monitorStationary barcode scannersGraphical user interfaceOn line helpKeyboard/touch screen controlColored touch screen monitorStationary barcode scannersGraphical user interfaceOn line help
Analyzer ConsumablesDisposable reaction vesselsDisposable sample tipsDisposable reaction vesselsDisposable sample tips
Analyzer Sample DetectionLiquid Level DetectionClot DetectionLiquid Level DetectionClot Detection
Analyzer Host InterfaceRS232C bidirectionalRS232C bidirectional
Differences
ItemAU3000i with TSHRoche Elecsys® TSH
Instrument RequiredOlympus AU3000i™Immunoassay SystemRoche Elecsys and Modularanalytics immunoassay analyzers.
TraceabilityWHO 3rd IS 81/565WHO 2nd IRP 80/558
Calibrator levels and targetConcentrationOneCal: 13 µIU/mLTwoCal 1: 0 µIU/mLCal 2: 1.5 µIU/Ml
Solid phase binding principleDirect coatingBiotin and streptavidin
Assay Range0.001 – 130 µIU/mL0.005 – 100 µIU/mL
Calibrator MatrixBovine serum human pituitaryTSHHorse serum with addedrecombinant TSH
Analyzer Sample Volume10 – 100 µl10 – 50 µl
Analyzer Reagent Positions24 reagent positions2 diluent/pretreatment positions15 reagent positions2 diluent/pretreatment positions
Analyzer Throughput240 results/hour88 results/hour

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Performance Characteristics
ItemAU3000i with TSHRoche Elecsys® TSH
PrecisionSample Total CV%Sample Total CV%
Low 2.9Low 8.7
Med 6.0Med 3.3
High 3.7High 3.6
Functional Sensitivity0.0013 µIU/mL0.014 µIU/mL
Analytical Sensitivity0.0002 µIU/mL0.005 µIU/mL
Measurable Range0.001 – 130 µIU/mL0.005 – 100.0 µIU/mL
Method Comparison (PassingBablok)Intercept-0.0046Slope 0.935R 0.9931Intercept0.01Slope 1.01R 0.944
Applicable Interfering SubstancesBilirubin ≤ 10% @ 40 mg/dLHemolysis ≤ 5% @ 5 g/LLipemia ≤ 3% @ 10 g/LBilirubin ≤ 10% @ 41 mg/dLHemolysis ≤ 10% @ 1 g/dLLipemia ≤ 10% @ 1500 mg/dL
SpecificityLH No significantinterferenceFSH No significantinterferencehGH Not TestedhCG Not DetectedLH No significantinterferenceFSH No significantinterferencehGH Not DetectedhCG Not Detected

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Image /page/4/Picture/1 description: The image shows a circular logo with text around the perimeter and a stylized symbol in the center. The text reads "DEPARTMENT OF HEALTH & HUMAN SERVICES USA". The symbol in the center appears to be an abstract representation of an eagle or bird, with three curved lines forming its body and wings.

Public Health Service

Food and Druq Administration 2098 Gaither Road Rockville MD 20850

Mr. David Davis Manager, RA/QA Olympus America, Inc. 3131 West Royal Lane Irving, TX 75063

NOV 2 9 2006

K062581 Re: Trade/Device Name: Olympus TSH (thyroid stimulating hormone) Test System and Olympus AU3000i™ Immunoassay System Regulation Number: 21 CFR 862.1690 Regulation Name: Thyroid stimulating hormone test system ﻣﻌﺪﺩﺳﻤﺴ Regulatory Class: Class II Product Code: JLW, JIS, JJX, JJE Dated: August 28, 2006 Received: August 31, 2006

Dear Mr. Davis: ·

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.

If your device is classified (see above) into cither class II (Spccial Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Albert Gutz

Alberto Gutierrez, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

009581

510(k) Number (if known):

Device Name:

Olympus TSH (thyroid stimulating hormone) Test System and Olympus AU3000i™ Immunoassay System

Indications for Use:

The Olympus thyroid stimulating hormone (TSH) assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of TSH levels in human serum and plasma using the Olympus AU3000i™ Immunoassay System.

Measurements of TSH produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.

The Olympus TSH Calibrator is used for calibrating the quantitative Olympus TSH Assay on the Olympus AU3000i Immunoassay System.

The Olympus TSH Control is used for quality control of the Olympus TSH test system on the Olympus AU3000i Immunoassay System.

The Olympus AU3000i Immunoassay System is a chemiluminescent discrete photometric chemistry analyzer for the quantitative determination of analytes in human serum and plasma.

Prescription Use (Part 21 CFR 801 Subpart D) OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

                            • -Concurrence of CDRH, Office of In Vitro Diagnostics Devices (OIVD)

Division Sign-Off

Office of In Vitro Diagnostic Device luation and Sa

§ 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.