(56 days)
For in vitro diagnostic use in the quantitative determination of free thyroxine (FTA) in serum or plasma (heparinized or EDTA), using the ADVIA Centaur and ADVIA Centaur XP systems. Measurements of free thyroxine are used in the diagnosis and treatment of thyroid disease.
For in vitro diagnostic use in the quantitative determination of thyroxine (T4) in serum using the ADVIA Centaur and ADVIA Centaur XP systems. Measurements of thyroxine are used in the diagnosis and treatment of thyroid disease.
Not Found
The provided 510(k) summary focuses on the addition of pediatric reference intervals to existing ADVIA Centaur FT4 and T4 assays, rather than the development of a new device or a comparative effectiveness study involving AI. Therefore, many of the requested elements for a study proving device meets acceptance criteria (such as MRMC, standalone performance, ground truth establishment for training, etc.) are not directly applicable or explicitly detailed in this document.
However, based on the information provided, here's a breakdown of the acceptance criteria and the study conducted for the pediatric reference intervals:
1. A table of acceptance criteria and the reported device performance
The "acceptance criteria" here are implicitly tied to the established pediatric reference intervals themselves, and the "reported device performance" is the statistical summary of the patient data used to derive these intervals. The document states that the previously established euthyroid adult reference intervals and analytical measuring ranges already apply. The acceptance criteria for the pediatric reference intervals specifically are:
- The established pediatric reference intervals must be either within or above the previously established euthyroid adult reference intervals.
- The established pediatric reference intervals must be within the analytical measuring ranges of the ADVIA Centaur FT4 and T4 assays.
| Age Group | Pediatric Reference Interval (FT4) | Pediatric Reference Interval (T4) | Analytical Measuring Range (FT4) | Analytical Measuring Range (T4) | Euthyroid Adult Reference Interval (FT4) | Euthyroid Adult Reference Interval (T4) |
|---|---|---|---|---|---|---|
| Infants (01 - 23M) | 0.94 – 1.44 ng/dL | 6.03 – 13.18 µg/dL | 0.10 - 12.0 ng/dL | 0.30 - 30.00 µg/dL | 0.89 – 1.76 ng/dL | 4.50 - 10.90 µg/dL |
| Children (02 - 12Y) | 0.86 – 1.40 ng/dL | 5.50 - 12.10 µg/dL | 0.10 - 12.0 ng/dL | 0.30 - 30.00 µg/dL | 0.89 – 1.76 ng/dL | 4.50 - 10.90 µg/dL |
| Adolescents (13 - 21Y) | 0.83 – 1.43 ng/dL | 5.50 - 11.10 µg/dL | 0.10 - 12.0 ng/dL | 0.30 - 30.00 µg/dL | 0.89 – 1.76 ng/dL | 4.50 - 10.90 µg/dL |
As stated in the conclusions: "The newly-established pediatric reference intervals are either within or are above the previously-established reference intervals for euthyroid (normal thyroid) adult populations and they are within the analytical measuring ranges of the ADVIA Centaur FT4 and T4 assays." This confirms the device (when interpreted with these new intervals) meets its implicitly defined acceptance criteria.
2. Sample size used for the test set and the data provenance
- Sample Size: A total of 454 patients were analyzed: 72 infants, 190 children, and 129 adolescents.
- Data Provenance: Not explicitly stated, but typically reference interval studies use samples collected from healthy individuals within the specified age groups, often from multiple geographic locations to ensure generalizability. It's not specified if this was retrospective or prospective, though the term "analyzed" suggests it could have been retrospective analysis of collected samples.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This information is not provided in the summary. For establishing reference intervals, the "ground truth" is typically defined by recruiting a statistically robust population of "healthy" or "euthyroid" individuals based on clinical criteria and medical examination, rather than expert consensus on individual cases. The document refers to CLSI C28-A3c, which is a guideline for establishing reference intervals. This guideline outlines methods for selecting reference individuals and statistical methods for calculating intervals, but not necessarily "experts" in the sense of adjudicating individual cases.
4. Adjudication method for the test set
This information is not provided and is generally not applicable to the establishment of reference intervals. The process involves clinical selection criteria for healthy individuals and statistical determination of intervals.
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 submission is for updating reference intervals for an existing IVD assay, not for an AI-based device or a comparative effectiveness study involving human readers or AI assistance.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
The device is an in vitro diagnostic (IVD) assay, not an algorithm or AI. Its performance is inherent in its analytical capabilities, which were previously established and cross-referenced to earlier 510(k) submissions (K905532, K080167, K971418). The current submission states, "The inclusion of pediatric reference intervals in the Instructions for Use (Package Inserts) does not necessitate the collection of additional analytical performance data." Therefore, no new standalone performance study was conducted for this submission as the analytical performance was deemed sufficient by previous submissions.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
For this type of study (establishing reference intervals), the "ground truth" is typically an "apparently healthy" or "euthyroid" state for the pediatric population, as defined by rigorous clinical selection criteria (e.g., absence of diseases, medications, or conditions known to affect thyroid function) as per CLSI guidelines. The specific criteria are not detailed but are implied by the reference to CLSI C28-A3c.
8. The sample size for the training set
This study is focused on establishing reference intervals, which typically involves a single dataset used for derivation. There isn't a "training set" in the context of machine learning. The 454 patients (72 infants, 190 children, 129 adolescents) constitute the dataset used to establish these reference intervals.
9. How the ground truth for the training set was established
As noted in point 7, the "ground truth" for the individuals included in the study (which acts as the "training set" for interval derivation) would be their status as "apparently healthy" or "euthyroid" pediatric individuals. This status would have been established through a process of screening, clinical assessment, and potentially other diagnostic tests, following the methodologies outlined in the CLSI C28-A3c guideline mentioned in the submission. The specific clinical criteria used for selection are not provided in this summary.
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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:
Date Prepared 1.
August 8, 2013
Applicant Information 2.
| Contact: | Matthew Gee, M.Sc.Senior Manager, Regulatory Affairs | |
|---|---|---|
| Address: | Siemens Healthcare Diagnostics Inc.511 Benedict AvenueTarrytown, NY 10591-5097 | |
| Phone:914-524-2099 | ||
| Fax: | 914-524-3579 | |
| Email: | matthew.gee@siemens.com |
SEP 1 3 2013
Regulatory Information 3.
Table 1. Regulatory Information for ADVIA Centaur FT4 and T4 Assays
| FT4 | T4 | |
|---|---|---|
| Trade Name | ADVIA Centaur® FT4 | ADVIA Centaur® T4 |
| Model Numbers | 06490106 (5-pack)06490092 (1-pack) | 09236439 (5-pack)08074354 (1-pack) |
| Common Name | Radioimmunoassay,free thyroxine | Enzyme immunoassay,non-radiolabeled, total thyroxine |
| Classification Name | Free thyroxine test system | Total thyroxine test system |
| FDA Classification | Class II | Class II |
| Review Panel | Clinical Chemistry | Clinical Chemistry |
| Product Code | CEC | KLI |
| Regulation Number | 862.1695 | 862.1700 |
4. Predicate Device Information
The inclusion of pediatric reference intervals to the labeling (Package Inserts) of the ADV/A Centaur FT4 and T4 assays does not require any other device modifications (i.e. no change to design or manufacturing process). Therefore, as shown in the table below, the predicate and subject devices are the same.
| Table 2. Summary of Predicate Devices for ADVIA Centaur FT4 and T4 Assays | |||||||
|---|---|---|---|---|---|---|---|
| FT4 | T4 | |
|---|---|---|
| Predicate Device | ADVIA Centaur® FT4 | ADVIA Centaur® T4 |
| Subject Device | Same (As above) | Same (As above) |
| Original 510(k) | K080167 | K905532 |
Siemens Healthcare Diagnostics Inc., Tarrytown, NY ADVIA Centaur Thyroid Assays Pediatric Reference Intervals
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Substantial Equivalence Information 5.
The following table demonstrates substantial equivalence between the predicate ADVIA Centaur thyroid assays (with unmodified labeling) and ADVIA Centaur thyroid assays which have modified Instructions for Use (Package Inserts) including pediatric reference intervals.
| Item | Predicate Device(Unmodified Labeling) | Subject Device(With Pediatric Reference Intervals) |
|---|---|---|
| Analytes | free thyroxine (FT₄)total thyroxine (T₄) | Same |
| Reagents | ADVIA Centaur FT4ADVIA Centaur T4 | Same |
| Instruments | ADVIA CentaurADVIA Centaur XP | Same |
| Intended UseStatements | ADVIA Centaur FT4For in vitro diagnostic use in thequantitative determination of freethyroxine (FT₄) in serum or plasma(heparinized or EDTA), using theADVIA Centaur and ADVIA CentaurXP systems. Measurements of freethyroxine are used in the diagnosis andtreatment of thyroid disease. | ADVIA Centaur FT4Same |
| ADVIA Centaur T4For in vitro diagnostic use in thequantitative determination of thyroxine(T₄) in serum using the ADVIA Centaurand ADVIA Centaur XP systems. | ADVIA Centaur T4For in vitro diagnostic use in thequantitative determination of thyroxine(T₄) in serum using the ADVIA Centaurand ADVIA Centaur XP systems.Measurements of thyroxine are used inthe diagnosis and treatment of thyroiddisease. | |
| AnalyticalMeasuring Range(Assay Range) | ADVIA Centaur FT40.1 – 12 ng/dL (1.3 – 155 pmol/L) | ADVIA Centaur FT4Same |
| ADVIA Centaur T40.3 – 30 µg/dL (3.9 – 387 nmol/L) | ADVIA Centaur T4Same | |
| AdultReference Intervals | ADVIA Centaur FT4Euthyroid, Hypothyroid, Hyperthyroid | ADVIA Centaur FT4Same |
| ADVIA Centaur T4Apparently Healthy Individuals,Hypothyroid, Hyperthyroid,Pregnant Euthyroid, Sick Euthyroid | ADVIA Centaur T4Same | |
| PediatricReference Intervals | None | Infants (01 – 23 months)Children (02 – 12 years)Adolescents (13 – 21 years) |
| Table 3. Summary of Substantial Equivalence for ADVIA Centaur Thyroid Assays | ||||
|---|---|---|---|---|
| -- | ------------------------------------------------------------------------------ | -- | -- | -- |
Standard/Guidance Document Reference 6.
Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline -- Third Edition (CLSI C28-A3c).
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Pediatric Reference Intervals 7.
Data from a total of 454 patients (72 infants, 190 children, 129 adolescents) were analyzed to establish the ADVIA Centaur thyroid assay reference intervals for the studied pediatric population. These pediatric reference intervals, as well as the previously-established euthyroid adult reference intervals and analytical measuring ranges, are presented below.
| FT4 | T4 | |
|---|---|---|
| Infants (01 - 23M) | 0.94 – 1.44 ng/dL | 6.03 – 13.18 µg/dL |
| Children (02 - 12Y) | 0.86 – 1.40 ng/dL | 5.50 - 12.10 µg/dL |
| Adolescents (13 - 21Y) | 0.83 – 1.43 ng/dL | 5.50 - 11.10 µg/dL |
| Euthyroid Adults* | 0.89 – 1.76 ng/dL | 4.50 - 10.90 µg/dL |
| Assay Range* | 0.10 - 12.0 ng/dL | 0.30 - 30.00 µg/dL |
Table 4. Comparison of Pediatric and Adult 95% Reference Intervals
- Information taken from existing Instructions for Use (Package Inserts)
Performance Characteristics 8.
The inclusion of pediatric reference intervals in the Instructions for Use (Package Inserts) does not necessitate the collection of additional analytical performance data. Therefore, all analytical performance data previously reviewed for the ADVIA Centaur FT4 and T4 assays continues to apply to these assays. All performance data is cross-referenced to the original 510(k) submissions for the FT4 and T4 assays (K905532 and K080167) and subsequent submissions demonstrating performance of the assays on the ADVIA Centaur system (K971418).
Specifically, the following studies are not needed for the purpose of this submission:
- Precision/Reproducibility 트
- . Linearitv
- l Calibrator/Assay Traceability
- 요 Calibrator/Assay Stability
- 1 Assay Cut-off
- . Method Comparison
- . Matrix Comparison
- Sensitivity (Detection Limits, LoB, LoD, LoQ)
- 장 Analytical Specificity
Shelf-Life 9.
The inclusion of pediatric reference intervals in the Instructions for Use (Package Inserts) does not necessitate the collection of additional stability data. Therefore, all stability methods, acceptance criteria and data previously reviewed for the ADVIA Centaur FT4 and T4 assays continues to apply to these assays. All stability information is cross-referenced to the original 510(k) submissions for the FT4 and T4 assays (K905532 and K080167) and subsequent submissions demonstrating performance of the assays on the ADVIA Centaur system (K971418).
Specifically, the following stability studies are not needed for the purpose of this submission:
- Shelf Life Stabilitv ■
- Onboard Stability
- 8 Open Vial Stability
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Conclusions 10.
The ADVIA Centaur FT4 and T4 assays with pediatric reference intervals are substantially equivalent to the currently marketed ADVIA Centaur FT4 and T4 assays.
The inclusion of pediatric reference intervals in the Instructions for Use (Package Inserts) does not require a change in the device design or a change in the manufacturing process.
All performance data is cross-referenced to the original 510(k) submissions for these assays (K905532 and K080167) and subsequent submissions demonstrating performance of the assays on the ADVIA Centaur system (K971418).
The addition of pediatric reference intervals for the ADVIA Centaur thyroid assays is further supported by the following rationale:
-
- Testing of pediatric patients is within the established indications for use in the diagnosis and treatment of thyroid disease), as described in 21 CFR §862.1695 and 21 CFR §862.1700.
-
- The newly-established pediatric reference intervals are either within or are above the previously-established reference intervals for euthyroid (normal thyroid) adult populations and they are within the analytical measuring ranges of the ADVIA Centaur FT4 and T4 assays. Therefore, the ADVIA Centaur FT4 and T4 assays have appropriate analytical performance to test pediatric patients.
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Image /page/4/Picture/0 description: The image shows the seal of the Department of Health & Human Services USA. The seal is circular, with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the perimeter. In the center of the seal is a stylized image of an eagle with its wings spread, with three wavy lines below it. The image is in black and white.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-Glob Silver Spring, MD 20993-0002
September 13, 2013
Siemens Healthcare Diagnostics, Inc. c/o Matthew Gee 511 Benedict Ave. TARRYTOWN NY 10591-5097
Re: K132249
Trade/Device Name: ADVIA Centaur® Ft4 ADVIA Centaur® T4 Regulation Number: 21 CFR 862.1695 Regulation Name: Free thyroxine test system Regulatory Class: II Product Code: CEC, KLI, Dated: August 9, 2013 Received: August 12, 2013
Dear Mr. 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 cither 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 electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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Page 2-Mr. Gee
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809). please contact the Division of Small Manufacturers, International and Consumer Assistance 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 Small Manufacturers. International and Consumer Assistance 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,
Carol C. Benson -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
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Indications for Use
510(k) Number (if known):
Device Name:
ADVIA Centaur® FT4 ADVIA Centaur® T4
Indications for Use:
For in vitro diagnostic use in the quantitative determination of free thyroxine (FTA) in serum or plasma (heparinized or EDTA), using the ADVIA Centaur and ADVIA Centaur XP systems. Measurements of free thyroxine are used in the diagnosis and treatment of thyroid disease.
For in vitro diagnostic use in the quantitative determination of thyroxine (T4) in serum using the ADVIA Centaur and ADVIA Centaur XP systems. Measurements of thyroxine are used in the diagnosis and treatment of thyroid disease.
Prescription Use × (Part 21 CFR 801 Subpart D) AND/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 and Radiological Health (OIR)
Yung W. Chan -S
Division Sign-Off Office of In Vitro Diagnostics and Radiological Health
K132249 510(k)
Page 1 of 1
§ 862.1695 Free thyroxine test system.
(a)
Identification. A free thyroxine test system is a device intended to measure free (not protein bound) thyroxine (thyroid hormone) in serum or plasma. Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may therefore determine the clinical metabolic status of thyroxine. Measurements obtained by this device are used in the diagnosis and treatment of thyroid diseases.(b)
Classification. Class II.