IMMULITE 2000 Third Generation TSH, IMMULITE 2000 Free T4

{0}------------------------------------------------ Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of three faces in profile, stacked on top of each other. The faces are simple and abstract, and they appear to be facing to the right. May 31, 2016 Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002 SIEMENS HEALTHCARE DIAGNOSTICS INC. MATTHEW GEE SENIOR MANAGER, REGULATORY AFFAIRS 511 BENEDICT AVENUE TARRYTOWN, NY 10591 Re: K160647 Trade/Device Name: IMMULITE 2000 Third Generation TSH IMMULITE 2000 Free T4 Regulation Number: 21 CFR 862.1690 Regulation Name: Thyroid stimulating hormone test system Regulatory Class: II Product Code: JLW. CEC Dated: March 4, 2016 Received: March 7, 2016 Dear Matthew Gee: We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading. If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the {1}------------------------------------------------ electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050. If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), 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/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 vours. # Katherine Serrano -S For : Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health Enclosure {2}------------------------------------------------ # Indications for Use Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below. 510(k) Number (if known) k160647 Device Name IMMULITE® 2000 Third Generation TSH IMMULITE® 2000 Free T4 ### Indications for Use (Describe) For in vitro diagnostic use with the IMMULITE® 2000 Systems Analyzers - for the quantitative measurement of thyrotropin (TSH) in serum. 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 with the IMMULITE® 2000 Systems Analyzers — for the quantitative measurement of nonprotein-bound thyroxine (free T4) in serum and heparinized plasma. Measurements of free thyroxine are used in the diagnosis and treatment of thyroid disease. | Type of Use (Select one or both, as applicable) | |-------------------------------------------------| |-------------------------------------------------| X Prescription Use (Part 21 CFR 801 Subpart D) Over-The-Counter Use (21 CFR 801 Subpart C) ## CONTINUE ON A SEPARATE PAGE IF NEEDED. This section applies only to requirements of the Paperwork Reduction Act of 1995. ## *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.* The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to: > Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov "An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number." {3}------------------------------------------------ # 510(k) Summary of Safety and Effectiveness This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of 21 CFR 807.92 and the Safe Medical Device Act of 1990. The assigned 510(k) Number is: k160647 #### Date Prepared 1. May 3, 2016 #### Applicant Information 2. | Contact: | Matthew Gee, M.Sc.<br>Senior Manager, Regulatory Affairs | |----------|----------------------------------------------------------------------------------------| | Address: | Siemens Healthcare Diagnostics Inc.<br>511 Benedict Avenue<br>Tarrytown, NY 10591-5097 | | Phone: | 914-524-2099 | | Fax: | 914-524-3579 | | Email: | matthew.gee@siemens.com | #### 3. Regulatory Information ## Table 1. Regulatory Information for IMMULITE 2000 Third Generation TSH and Free T4 | | Third Generation TSH | Free T4 | |---------------------|---------------------------------------------------|--------------------------------------------| | Trade Name | IMMULITE® 2000<br>Third Generation TSH | IMMULITE® 2000<br>Free T4 | | Model Numbers | L2KTS2 (200 tests)<br>L2KTS6 (600 tests) | L2KFT42 (200 tests)<br>L2KFT46 (600 tests) | | Common Name | Radioimmunoassay, thyroid-<br>stimulating hormone | Radioimmunoassay,<br>free thyroxine | | Classification Name | Thyroid stimulating hormone test<br>system | Free thyroxine test system | | Product Code | JLW | CEC | | Regulation Number | 862.1690 | 862.1695 | | FDA Classification | Class II | Class II | | Review Panel | Clinical Chemistry | Clinical Chemistry | {4}------------------------------------------------ #### Predicate Device Information 4. The Predicate Device for the modified IMMULITE 2000 Free T4 assay is the unmodified IMMULITE 2000 Free T4 assay (K083373). The Predicate Device for the modified IMMULITE 2000 Third Generation TSH assay is the unmodified IMMULITE 2000 Third Generation TSH assay (described in K970227). The modifications to the IMMULITE 2000 Free T4 and Third Generation TSH assays to add pediatric reference intervals to the Package Inserts are limited to changes in labeling. The update of reference intervals does not require modifications to the design or manufacturing processes of the devices. Therefore, the predicate devices and subject devices are the same. #### 5. Substantial Equivalence Information The following table demonstrates substantial equivalence between the predicate IMMULITE 2000 Free T4 (K083373) and the IMMULITE 2000 Free T4 which has modified Instructions for Use (Package Inserts) with added pediatric reference intervals. | Item | Predicate Device (K083373)<br>with Unmodified Labeling | Subject Device<br>with Updated Reference Intervals | |------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Analytes | free thyroxine (T4) | Same | | Instruments | IMMULITE 2000 systems | Same | | Intended Use<br>Statements | For in vitro diagnostic use with the<br>IMMULITE® 2000 Systems<br>Analyzers — for the quantitative<br>measurement of non-protein-bound<br>thyroxine (free T4) in serum and<br>heparinized plasma, as an aid in the<br>clinical assessment of thyroid<br>status. | For in vitro diagnostic use with the<br>IMMULITE® 2000 Systems<br>Analyzers — for the quantitative<br>measurement of non-protein-bound<br>thyroxine (free T4) in serum and<br>heparinized plasma. Measurements<br>of free thyroxine are used in the<br>diagnosis and treatment of thyroid<br>disease. | | Analytical<br>Measuring Range<br>(Assay Range) | 0.30 - 6.00 ng/dL<br>(3.9 - 77.2 pmol/L) | Same | | Adult<br>Reference Ranges | Euthyroid<br>Hypothyroid<br>Hyperthyroid | Same | | Pediatric<br>Reference Intervals | None | Infants: 01 – 23 months<br>Children: 02 – 12 years<br>Adolescents: 13 – 20 years | Table 2. Summary of Substantial Equivalence for IMMULITE 2000 Free T4 The following table demonstrates substantial equivalence between the predicate IMMULITE 2000 Third Generation TSH (described in K970227) and the IMMULITE 2000 Third Generation TSH which has modified Instructions for Use (Package Inserts) with updated pediatric reference intervals. {5}------------------------------------------------ | Item | Predicate Device (K970227)<br>with Unmodified Labeling | Subject Device<br>with Updated Reference Intervals | |------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Analytes | thyroid stimulating hormone (TSH) | Same | | Instruments | IMMULITE 2000 systems | Same | | Intended Use<br>Statements | For in vitro diagnostic use with the<br>IMMULITE® 2000 Systems<br>Analyzers — for the quantitative<br>measurement of thyrotropin (TSH)<br>in serum, as an aid in the clinical<br>assessment of thyroid status. | For in vitro diagnostic use with the<br>IMMULITE® 2000 Systems<br>Analyzers — for the quantitative<br>measurement of thyrotropin (TSH)<br>in serum. Measurements of thyroid<br>stimulating hormone produced by<br>the anterior pituitary are used in the<br>diagnosis of thyroid or pituitary<br>disorders. | | Analytical<br>Measuring Range<br>(Assay Range) | 0.004 – 75 μIU/mL (mIU/L) | Same | | Adult<br>Reference Ranges | Euthyroid<br>Hyperthyroid | Same | | Pediatric<br>Reference Intervals | Groupings by age (in years) from<br>1 year to 12 years | Infants: 01 – 23 months<br>Children: 02 – 12 years<br>Adolescents: 13 – 20 years | ## Table 3. Summary of Substantial Equivalence for IMMULITE 2000 Third Generation TSH #### Standard/Guidance Document Reference 6. Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline -- Third Edition (CLSI EP28-A3c); FDA Recognition Number 7-224. #### 7. Pediatric Reference Intervals ## Free T4 Data from a total of 426 patients (81 infants, 197 children, 148 adolescents) tested with the IMMULITE 2000 Free T4 assay were analyzed to establish the reference intervals for the studied pediatric population. Results are described in the following table. | Group | N | 95% Reference<br>Interval | Reference<br>Interval<br>Methodology | 90% Confidence<br>Interval for Lower<br>Limit of Reference<br>Interval | 90% Confidence<br>Interval for Upper<br>Limit of Reference<br>Interval | |--------------------------------|-----|-------------------------------------------|--------------------------------------|------------------------------------------------------------------------|------------------------------------------------------------------------| | Infants<br>(01 – 23 months) | 81 | 0.80 – 1.27 ng/dL<br>(10.3 – 16.3 pmol/L) | Robust<br>Symmetric | 0.76 – 0.84 ng/dL<br>(9.8 – 10.8 pmol/L) | 1.23 – 1.32 ng/dL<br>(15.8 – 17.0 pmol/L) | | Children<br>(02 – 12 years) | 197 | 0.74 – 1.28 ng/dL<br>(9.5 – 16.5 pmol/L) | Non-Parametric | --- | --- | | Adolescents<br>(13 – 20 years) | 148 | 0.75 – 1.27 ng/dL<br>(9.7 – 16.3 pmol/L) | Non-Parametric | --- | --- | ## Table 4. Pediatric 95% Reference Intervals (Free T4) As taken from information in the existing Instructions for Use (Package Insert), the claim for the euthyroid adult reference range is 0.89 - 1.76 ng/dL (11.5 - 22.7 pmol/L), and the {6}------------------------------------------------ current claim for the assay range is 0.30 – 6.00 ng/dL (3.9 – 77.2 pmol/L). This demonstrates that the new pediatric reference intervals are within the analytical measuring capability of the assay. # Third Generation TSH Data from a total of 433 patients (90 infants, 195 children, 148 adolescents) tested with the IMMULITE 2000 Third Generation TSH assay were analyzed to establish the reference intervals for the studied pediatic population. These pediatric reference intervals, as well as the previously-established euthyroid adult reference intervals and analytical measuring ranges, are presented below. | Group | N | 95% Reference Interval | Reference Interval Methodology | 90% Confidence Interval for Lower Limit of Reference Interval | 90% Confidence Interval for Upper Limit of Reference Interval | |--------------------------------|-----|------------------------------|--------------------------------------------|---------------------------------------------------------------|---------------------------------------------------------------| | Infants<br>(01 – 23 months) | 90 | 0.83 – 6.5 µIU/mL<br>(mIU/L) | Robust<br>Symmetric after<br>Log Transform | 0.70 – 0.99 µIU/mL<br>(mIU/L) | 5.58 – 7.65 µIU/mL<br>(mIU/L) | | Children<br>(02 – 12 years) | 195 | 0.58 – 4.1 µIU/mL<br>(mIU/L) | Non-Parametric | --- | --- | | Adolescents<br>(13 – 20 years) | 148 | 0.39 – 4.0 µIU/mL<br>(mIU/L) | Non-Parametric | --- | --- | Table 5. Pediatric 95% Reference Intervals (Third Generation TSH) As taken from information in the existing Instructions for Use (Package Insert), the claim for the euthyroid adult reference range is 0.40 - 4.0 µIU/mL (mIU/L), and the current claim for the assay range is 0.004 – 75 µIU/mL (mIU/L). This demonstrates that the new pediatric reference intervals are within the analytical measuring capability of the assay. #### Performance Characteristics 8. The inclusion of pediatric reference intervals in the Instructions for Use (Package Insert) does not necessitate the collection of additional analytical performance data. Therefore, all analytical performance data currently claimed for the IMMULITE Free T4 and Third Generation TSH assays continue to apply to these devices. Specifically, the following studies are not needed for the purpose of this submission: - l Precision/Reproducibility - I Linearity - l Calibrator/Assay Traceability - Calibrator/Assay Stability - l Assay Cut-off - I Method Comparison - I Matrix Comparison - l Sensitivity (Detection Limits, LoB, LoD, LoQ) - Analytical Specificity {7}------------------------------------------------ #### 9. Shelf-Life The inclusion of pediatric reference intervals in the Instructions for Use (Package Insert) does not necessitate the collection of additional stability data. Therefore, all stability methods, acceptance criteria and data currently claimed for the IMMULITE Free T4 and Third Generation TSH assays continue to apply to these devices. Specifically, the following stability studies are not needed for the purpose of this submission: - . Shelf Life Stability - Onboard Stability - Open Vial Stability #### 10. Conclusions The IMMULITE Free T4 and Third Generation TSH assays with updated pediatric reference intervals are substantially equivalent to the currently marketed IMMULITE Free T4 and Third Generation TSH assays. The modification of the Instructions for Use (Package Insert) to add/update pediatric reference intervals does not require a change in the device design or a change in the manufacturing process. All analytical data currently claimed for the IMMULITE Free T4 and Third Generation TSH assays continue to apply to these devices. The modification of pediatric reference intervals for the IMMULITE Free T4 and Third Generation TSH assays is further supported by the following rationale: - 1. Testing of pediatric patients is within the established indications for use (i.e. for use in the diagnosis of thyroid or pituitary disorders), as described in 21 CFR §862.1695 and 21 CFR §862.1690. - 2. The newly-established pediatric reference intervals are at comparable levels or above the existing reference ranges for euthyroid (normal thyroid) adult populations. In addition, the pediatric reference intervals are well within the analytical measuring ranges of the IMMULITE Free T4 and Third Generation TSH assays. Therefore, the IMMULITE Free T4 and Third Generation TSH assays have appropriate analytical performance to test pediatric patients.