VITROS Immunodiagnostic Products TSH Reagent Pack: For the in vitro quantitative measurement of thyroid stimulating hormone (TSH) in human serum and plasma (EDTA or Heparin) using the VITROS ECi/ECiQ Immunodiagnostic Systems and VITROS 5600 Integrated System to aid in the differential diagnosis of thyroid disease.
VITROS Immunodiagnostic Products TSH Calibrators: For in vitro use in the calibration of the VITROS ECI/ECIQ Immunodiagnostic Systems and VITROS 5600 Integrated System for the quantitative measurement of thyroid stimulating hormone (TSH) in human serum and plasma (EDTA or Heparin).
VITROS Chemistry Products PHYT Slides: For in vitro diagnostic use only. VITROS Chemistry Products PHYT Slides quantitatively measure phenytoin (PHYT) concentration in serum and plasma using VITROS 250/350/950 and 5,1 FS Chemistry Systems and the VITROS 5600 Integrated System.
VITROS Chemistry Products Calibrator Kit 9: For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 9 is used to calibrate VITROS 250/350/950 and 5.1 FS Chemistry Systems and the VITROS 5600 Integrated System for the quantitative measurement of ACET, CRBM, DGXN, PHBR, and PHYT.
VITROS 5600 Integrated System: For use in the in vitro quantitative, semi-quantitative measurement of a variety of analytes of clinical interest, using VITROS Chemistry Products Slides, VITROS Chemistry Products MicroTip Reagents and VITROS Immunodiagnostic Products Reagents.

Device Description

The VITROS Immunodiagnostic Products TSH assay and VITROS Chemistry Products PHYT assay are intended for use on the VITROS 5600 Integrated System. The VITROS 5600 Integrated System combines the existing VITROS 5,1 FS Chemistry System (K031924) and the VITROS ECi/ECiQ Immunodiagnostic System (K962919) into a single system. All technology, methodologies and analytical methods currently available on the existing two systems are available on the new integrated system.

AI/ML Overview

This is a 510(k) premarket notification for modifications to existing assays (VITROS Immunodiagnostic Products TSH and VITROS Chemistry Products PHYT) to be used with a new integrated system (VITROS 5600 Integrated System). The submission focuses on demonstrating substantial equivalence to previously cleared devices.

Therefore, the typical "acceptance criteria" and "study that proves the device meets the acceptance criteria" in the context of a new diagnostic algorithm's performance are not explicitly detailed in the provided text. This is because the submission is for a system modification rather than a new algorithmic diagnostic device with performance metrics like sensitivity, specificity, etc.

However, based on the context of a 510(k) for a laboratory diagnostic system, we can infer the types of performance criteria that would be relevant for demonstrating substantial equivalence for the modified use of the assays on the new system. These would typically include:

Method Comparison: Showing that results obtained on the new integrated system are comparable to those obtained on the predicate systems.
Precision: Demonstrating acceptable within-run and between-run variability on the new system.
Linearity/Analytical Measurement Range: Confirming the ability to accurately measure analytes across a defined range on the new system.
Interference: Ensuring common interfering substances do not significantly impact results on the new system.
Stability: Verifying the stability of reagents and calibrators when used with the new system.
Reference Range: Confirming the appropriate reference intervals for the assays on the new system.

Since the provided text does not contain detailed study results for these specific performance characteristics (as it's a summary document), I cannot fill out all sections. I will address what can be inferred or is explicitly stated:

1. Table of Acceptance Criteria and the Reported Device Performance:

The document doesn't explicitly state numerical acceptance criteria for performance metrics (e.g., "TSH bias must be within X%") or report detailed performance data. Instead, the submission relies on the concept of "substantial equivalence" of the modified device to the predicate devices. This implies that the performance on the new combined system is expected to be equivalent to the already cleared separate systems.

Acceptance Criteria (Inferred from Substantial Equivalence for IVD assays)	Reported Device Performance (Inferred/Not explicitly detailed in summary)
Method Comparison: Results from VITROS 5600 Integrated System are comparable to predicate systems (VITROS ECi/ECiQ and VITROS 5,1 FS Chemistry System).	The submission asserts "All technology, methodologies and analytical methods currently available on the existing two systems are available on the new integrated system" and that the "modified devices have the same intended use, fundamental scientific technology and operating principle as the predicate devices." This implies performance equivalence.
Precision: Acceptable within-run and between-run precision for TSH and PHYT assays on VITROS 5600.	Not explicitly detailed in the summary. Implied to be equivalent to predicate.
Accuracy/Bias: Acceptable accuracy for TSH and PHYT assays on VITROS 5600.	Not explicitly detailed in the summary. Implied to be equivalent to predicate.
Analytical Measurement Range: Proper quantification across the defined analytical range for TSH and PHYT on VITROS 5600.	Not explicitly detailed in the summary. Implied to be equivalent to predicate.
Interference: No significant interference from common substances when using TSH and PHYT assays on VITROS 5600.	Not explicitly detailed in the summary. Implied to be equivalent to predicate.
Reagent/Calibrator Stability: Demonstrated stability when used with VITROS 5600.	The new system uses "reagents, calibrators and controls identical to the VITROS ECi/ECiQ Immunodiagnostic System and VITROS 5,1 FS Chemistry System," implying their established stability carries over.

2. Sample size used for the test set and the data provenance:

Sample Size: Not explicitly stated in the summary document. For method comparison studies in IVDs, hundreds of clinical samples are typically used across the analytical range.
Data Provenance: Not explicitly stated. Assumed to be clinical samples relevant to the intended use.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience):

This is not applicable in the context of this 510(k) for an in vitro diagnostic (IVD) system. For IVDs, "ground truth" is typically established by reference methods, comparison to predicate devices, or spiking studies, not by expert interpretation of images or clinical data.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

Not applicable. Diagnostic assays like TSH and PHYT use quantitative measurements, and "adjudication" in the sense of resolving discrepancies between human readers is not relevant. The comparison would be between the numerical results of the new system and the predicate system.

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 an IVD system for quantitative measurement, not an AI-assisted diagnostic imaging device that involves human reader interpretation.

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

The device (VITROS 5600 Integrated System running the TSH and PHYT assays) is a standalone automated system for quantitative measurement. Its performance is evaluated intrinsically through analytical studies (precision, accuracy, method comparison, etc.) as described under point 1.

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

For this type of IVD device, ground truth would typically be established by:

Reference Methods: Comparison against established, highly accurate analytical methods.
Predicate Device Comparison: Demonstrating statistical equivalence of results when compared to the existing cleared devices (VITROS ECi/ECiQ and VITROS 5,1 FS Chemistry System) on the same samples.
Spiked Samples: Using samples with known concentrations of the analyte.

The submission heavily relies on the "substantial equivalence" to predicate devices, indicating that the predicate device's performance effectively serves as the "ground truth" for comparison.

8. The sample size for the training set:

Not applicable in the AI/machine learning sense. For IVD systems, "training" refers to calibration and quality control. The training of the system for measuring TSH and PHYT would involve:

Calibration: Using the specific calibrators (VITROS Immunodiagnostic Products TSH Calibrators and VITROS Chemistry Products Calibrator Kit 9). The sample sizes for calibration materials are determined by statistical design to ensure accurate curve fitting.
Quality Control: Regular testing of quality control materials to ensure the system is performing within specifications.

9. How the ground truth for the training set was established:

Calibrators: The ground truth (assigned value) for the calibrators is established through a rigorous process by the manufacturer, typically involving reference methods, traceability to international standards (if available for TSH), and extensive internal validation studies.
Quality Control Materials: Similar to calibrators, assigned values for quality control materials are established by the manufacturer through reference methods and internal validation.

Summary

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510(k) Summary

OCT 2 3 2008

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.

81543 The assigned 510(k) number is: Ortho-Clinical Diagnostics, Inc. Submitter: 100 Indigo Creek Drive MC00881 Rochester, New York 14626-5101 Leah Van De Water Contact Person: Phone: (585) 453-4131 FAX: (585) 453-4402 Email: Ivandewa@ocdus.jnj.com September 22, 2008 Preparation date: Registration Number: The establishment number for the VITROS Immunodiagnostic Products TSH Reagent Pack and Calibrators is 9680658. The establishment number for the VITROS Chemistry Products PHYT Slides is 1319809. The establishment number for the VITROS Chemistry Products Calibrator Kit 9 is 1319808. The establishment number for the VITROS 5600 Integrated System is 1319681. Purpose for Submission: Ortho-Clinical Diagnostics hereby submits this Special 510(k) to provide notification of modification to the VITROS Immunodiagnostic Products TSH assay and VITROS Chemistry Products PHYT assay. The TSH assay is cleared for use with the VITROS ECi/ECiQ Immunodiagnostic System. The PHYT assay is cleared for use with the VITROS 5,1 FS Chemistry System. The modifications include the use of the VITROS TSH and PHYT assays with the VITROS 5600 Integrated System. The VITROS 5600 Integrated System is a new member of the VITROS family of analyzers and uses reagents, calibrators and controls identical to the VITROS ECi/ECiQ Immunodiagnostic System and VITROS 5,1 FS Chemistry System. The VITROS 5600 Integrated System is an integration of the VITROS 5,1 FS Chemistry System, which performs MicroSlide and MicroTip assays and the VITROS ECi/ECiO Immunodiagnostic System, which performs MicroWell assays. The VITROS 5,1 FS Chemistry System was cleared as part of Premarket Notification number K031924. The VITROS ECi/ECiO Immunodiagnostic System was cleared as part of Premarket Notification number K962919.

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Trade or ProprietaryName:	VITROS® Immunodiagnostic Products TSH Reagent PackVITROS® Immunodiagnostic Products TSH CalibratorsVITROS® Chemistry Products PHYT SlidesVITROS® Chemistry Products Calibrator Kit 9VITROS® 5600 Integrated System
Common Name:	VITROS TSH Test System, VITROS PHYT Test System
Classification Name:	Thyroid Stimulating Hormone Test System (21 CFR 862.1690);Diphenylhydantoin test system (21 CFR 862.3350); Calibrators(21 CFR 862.1150); Discrete photometric chemistry analyzer forclinical use (21 CFR 862.2160); Fluorometer for clinical use (21CFR 862.2560)
Device Intended Use:	VITROS Immunodiagnostic Products TSH Reagent PackFor the in vitro quantitative measurement of thyroid stimulatinghormone (TSH) in human serum and plasma (EDTA or Heparin)using the VITROS ECi/ECiQ Immunodiagnostic Systems andVITROS 5600 Integrated System to aid in the differentialdiagnosis of thyroid disease.
	VITROS Immunodiagnostic Products TSH CalibratorsFor in vitro use in the calibration of the VITROS ECI/ECIQImmunodiagnostic Systems and VITROS 5600 IntegratedSystem for the quantitative measurement of thyroid stimulatinghormone (TSH) in human serum and plasma (EDTA orHeparin).
	VITROS Chemistry Products PHYT SlidesFor in vitro diagnostic use only.VITROS Chemistry Products PHYT Slides quantitativelymeasure phenytoin (PHYT) concentration in serum and plasmausing VITROS 250/350/950 and 5,1 FS Chemistry Systems andthe VITROS 5600 Integrated System.
	VITROS Chemistry Products Calibrator Kit 9For in vitro diagnostic use only.VITROS Chemistry Products Calibrator Kit 9 is used to calibrateVITROS 250/350/950 and 5,1 FS Chemistry Systems andthe VITROS 5600 Integrated System for the quantitativemeasurement of ACET, CRBM, DGXN, PHBR, and PHYT.
	VITROS 5600 Integrated SystemFor use in the in vitro quantitative, semi-quantitative, andqualitative measurement of a variety of analytes of clinicalinterest, using VITROS Chemistry Products Slides, VITROSChemistry Products MicroTip Reagents and VITROSImmunodiagnostic Products Reagents.

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Device description:	The VITROS Immunodiagnostic Products TSH assay andVITROS Chemistry Products PHYT assay are intended for useon the VITROS 5600 Integrated System.
	The VITROS 5600 Integrated System combines the existingVITROS 5,1 FS Chemistry System (K031924) and the VITROSECi/ECiQ Immunodiagnostic System (K962919) into a singlesystem. All technology, methodologies and analytical methodscurrently available on the existing two systems are available onthe new integrated system.
Substantial Equivalence:	The modified devices have the same intended use, fundamentalscientific technology and operating principle as the predicatedevices. The VITROS Immunodiagnostic Products TSH Assayis substantially equivalent to the product previously cleared withPremarket Notification number K964558. The VITROSChemistry Products PHYT Assay is substantially equivalent tothe product previously cleared with Premarket Notificationnumber K941142.

Device description:

The VITROS Immunodiagnostic Products TSH assay andVITROS Chemistry Products PHYT assay are intended for useon the VITROS 5600 Integrated System.

The VITROS 5600 Integrated System combines the existingVITROS 5,1 FS Chemistry System (K031924) and the VITROSECi/ECiQ Immunodiagnostic System (K962919) into a singlesystem. All technology, methodologies and analytical methodscurrently available on the existing two systems are available onthe new integrated system.

Substantial Equivalence:

The modified devices have the same intended use, fundamentalscientific technology and operating principle as the predicatedevices. The VITROS Immunodiagnostic Products TSH Assayis substantially equivalent to the product previously cleared withPremarket Notification number K964558. The VITROSChemistry Products PHYT Assay is substantially equivalent tothe product previously cleared with Premarket Notificationnumber K941142.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS). The seal features a stylized eagle with its wings spread, symbolizing protection and care. The eagle is surrounded by a circular border containing the text "DEPARTMENT OF HEALTH & HUMAN SERVICES. USA".

Public Health Service

Food and Druq Administration 2098 Gaither Road Rockville MD 20850

Ms. Leah Van De Water, M.S., RAC Regulatory Affairs Associate Ortho-Clinical Diagnostics 100 Indigo Creek Drive MC881 Rochester, NY 14626-5101

OCT 2 8 2008

Re: K081543

Trade/Device Name: VITROS Immunodiagnostic Products TSH Reagent Pack VITROS Immunodiagnostic Products TSH Calibrators VITROS Chemistry Products PHYT Slides VITROS Chemistry Products Calibrator Kit 9 VITROS 5600 Integrated System

Regulation Number: 21 CFR 862.1690 Regulation Name: Thyroid Stimulating Hormone test system Regulatory Class: Class II Product Code: JLW, DIP, JJE, JIT Dated: September 24, 2008 Received: September 25, 2008

Dear Ms. Van De Water:

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 either class II (Special 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 10gally 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) 276-0490. 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 no (800) 638-2041 or (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Jean M. Cooper, M.S., D.V.M.

Sean M. Cooper, M.S., D.V.M. 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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510(k) Number (if known):

Device Name: VITROS Immunodiagnostic Products TSH Reagent Pack VITROS Immunodiagnostic Products TSH Calibrators VITROS Chemistry Products PHYT Slides VITROS Chemistry Products Calibrator Kit 9 VITROS 5600 Integrated System

Indications for Use:

VITROS Immunodiagnostic Products TSH Reagent Pack

For the in vitro quantitative measurement of thyroid stimulating hormone (TSH) in human serum and plasma (EDTA or Heparin) using the VITROS ECi/ECiQ Immunodiagnostic Systems and VITROS 5600 Integrated System to aid in the differential diagnosis of thyroid disease.

VITROS Immunodiagnostic Products TSH Calibrators

For in vitro use in the calibration of the VITROS ECVECiQ Immunodiagnostic Systems and VITROS 5600 Integrated System for the quantitative measurement of thyroid stimulating hormone (TSH) in human serum and plasma (EDTA or Heparin).

VITROS Chemistry Products PHYT Slides

For in vitro diagnostic use only. VITROS Chemistry Products PHYT Slides quantitatively measure phenytoin (PHYT) concentration in serum and plasma using VITROS 250/350/950 and 5,1 FS Chemistry Systems and the VITROS 5600 Integrated System.

VITROS Chemistry Products Calibrator Kit 9

For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 9 is used to calibrate VITROS 250/350/950 and 5.1 FS Chemistry Systems and the VITROS 5600 Integrated System for the quantitative measurement of ACET, CRBM, DGXN, PHBR, and PHYT.

VITROS 5600 Integrated System

For use in the in vitro quantitative, semi-quantitative measurement of a variety of analytes of clinical interest, using VITROS Chemistry Products Slides, VITROS Chemistry Products MicroTip Reagents and VITROS Immunodiagnostic Products Reagents.

AND/OR Over-The-Counter Use Prescription Use X (Part 21 CFR 801 Subpart D) (21 CFR 807 Subpart C) (PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Carol C. Bensen

on Sign-Off

്റ്ice of In Vitro Diagnostic Device

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.