GSP NEONATAL THYROXINE (T4)

K103484 · Wallac Oy, A Subsidiary of Perkinelmer, Inc. · KLI · Apr 22, 2011 · Clinical Chemistry

Device Facts

• Record ID: K103484
• Device Name: GSP NEONATAL THYROXINE (T4)
• Applicant: Wallac Oy, A Subsidiary of Perkinelmer, Inc.
• Product Code: KLI · Clinical Chemistry
• Decision Date: Apr 22, 2011
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1700
• Device Class: Class 2
• Attributes: Pediatric

Intended Use

The GSP Neonatal Thyroxine (T4) kit is intended for the quantitative determination of human thyroxine (T4) in blood specimens dried on filter paper as an aid in screening newborns for congenital (neonatal) hypothyroidism using the GSP® instrument.

Device Story

GSP Neonatal Thyroxine (T4) kit is a solid-phase time-resolved fluoroimmunoassay for quantitative T4 measurement in newborn dried blood spots. Input: 3.2 mm filter paper blood disk. Principle: Competitive reaction between europium-labeled T4 and sample T4 for monoclonal antibody binding sites; ANS and salicylate release T4 from binding proteins; secondary antibody on solid phase captures IgG-thyroxine complex. DELFIA Inducer dissociates europium ions to form fluorescent chelates. Output: Fluorescence intensity inversely proportional to T4 concentration. Used in clinical laboratories by trained personnel on GSP instrument. Results assist healthcare providers in screening for congenital hypothyroidism, facilitating early diagnosis and intervention.

Clinical Evidence

Clinical performance evaluated using 4,312 routine neonatal DBS specimens across two U.S. state laboratories, including 36 retrospective congenital hypothyroidism (CH) positive samples. All 36 CH-positive samples were correctly identified as screen-positive. Comparison with the predicate (AutoDELFIA) showed overall percent agreement of 95.2% (Study 1) and 94.1% (Study 2). Positive percent agreement was 77.5% and 73.8% respectively. Bench testing included precision (CVs 5.3-14.1%), linearity (1.6-30 μg/dL), and interference studies (bilirubin, hemoglobin, intralipids showed no interference).

Technological Characteristics

Solid-phase time-resolved fluoroimmunoassay. Materials: Anti-mouse IgG coated Nunc MaxiSorb microtitration strips. Energy: Fluorescence detection. Connectivity: GSP workstation. Software: GSP Workstation software. Reagents: Europium-labeled T4, monoclonal antibodies, ANS, salicylate, DELFIA Inducer.

Indications for Use

Indicated for quantitative determination of human thyroxine (T4) in dried blood spot specimens to aid in screening newborns for congenital (neonatal) hypothyroidism. For use by trained laboratory personnel.

Regulatory Classification

Identification

A total thyroxine test system is a device intended to measure total (free and protein bound) thyroxine (thyroid hormone) in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of thyroid diseases.

Special Controls

*Classification.* Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.

Predicate Devices

• AutoDELFIA® Neonatal Thyroxine T4 (K943416)

Submission Summary (Full Text)

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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:

Date: April 12, 2011

Submitted by:

Wallac Oy, subsidiary of PerkinElmer 940 Winter Street Waltham, MA 02451 USA

Contact Person: Susan K. Hamann Primary: Tel: [phone] Fax: [phone]

Secondary:

Kay A. Taylor Tel: [phone] Fax: [phone]

Trade Name:

Common Name: GSP Neonatal Thyroxine (T4) kit

Regulation: 21 CFR 862.1700

Classification Name: Total Thyroxine Test System

Product Code:

AutoDELFIA® Neonatal Thyroxine T4 Predicate Device: 510(k) Number (K943416)

KLI

Device Description: The GSP Neonatal T4 assay is a solid phase time-resolved fluoroimmunoassay based on the competitive reaction between europium-labeled T4 and sample T4 for a limited amount of binding sites on T4 specific monoclonal antibodies (derived from mice). The use of 8-anilino-1-naphthalenesulfonic acid (ANS) and salicylate in the T4 Assay Buffer facilitates the release of T4 from the binding proteins. Thus the assay measures the total amount of T4 in the test specimen. A second antibody, directed against mouse IgG, is coated to the solid phase, and binds the IgG-thyroxine complex, giving convenient separation of the antibodybound and free antigen.

GSP® Neonatal Thyroxine (T4) kit (3302-001U)

DELFIA Inducer dissociates europium ions from the labeled antibody into solution where they form highly fluorescent chelates with components of DELFIA Inducer.

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The fluorescence in each well is then measured. The fluorescence of each sample is inversely proportional to the concentration of T4 in the sample.

Intended Use:

The GSP Neonatal IRT kit is intended for the quantitative determination of human thyroxine (T4) in blood specimens dried on filter paper as an aid in screening newborns for congenital (neonatal) hypothyroidism using the GSP® instrument.

Substantial Equivalence:

The GSP® Neonatal Thyroxine (T4) kit is substantially equivalent to our currently marketed AutoDELFIA® Neonatal Thyroxine T4 (K943416). There are the following similarities and differences between the two kits:

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| Predicate<br>Device | FEATURE | Similarities (AutoDELFIA T4) | Differences (GSP T4) |
|-------------------------------|------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| AutoDELFIA<br>Neonatal T4 Kit | Intended User | Adequately trained laboratory personnel in<br>laboratories performing newborn screening. | Same |
| AutoDELFIA<br>Neonatal T4 Kit | Intended use | This kit is intended for the quantitative<br>determination of human thyroxine (T4) in<br>blood specimens dried on filter paper as an<br>aid in screening newborns for congential<br>(neonatal) hypothyroidism using the<br>AutoDELFIA automatic immunoassay<br>system. | The kit is intended for the quantitative<br>determination of human thyroxine (T4) in blood<br>specimens dried on filter paper as an aid in<br>screening newborns for congenital (neonatal)<br>hypothyroidism using the GSP instrument. |
| AutoDELFIA<br>Neonatal T4 Kit | Chemical<br>Principle | The Neonatal T4 assay is a solid phase<br>time-resolved fluoroimmunoassay based on<br>the competitive reaction between europium-<br>labeled T4 and sample T4 for a limited<br>amount of binding sites on T4 specific<br>monoclonal antibodies (derived from mice).<br>The use of 8-anilino-1-naphthalenesulfonic<br>acid (ANS) and salicylate in the T4 Assay<br>Buffer facilitates the release of T4 from the<br>binding proteins. Thus the assay measures<br>the total amount of T4 in the test specimen.<br>A second antibody, directed against mouse<br>IgG, is coated to the solid phase, and binds<br>the IgG-thyroxine complex, giving<br>convenient separation of the antibody-bound<br>and free antigen. | Same |
| AutoDELFIA<br>Neonatal T4 Kit | Chemical<br>Principle | Europium ions are dissociated from the<br>labeled antibody into solution where they<br>form highly fluorescent chelates with<br>components of the dissociation solution.<br><br>The fluorescence in each well is then<br>measured. The fluorescence of each sample<br>is inversely proportional to the concentration<br>of T4 in the sample | Same |
| AutoDELFIA<br>Neonatal T4 Kit | Dissociation<br>Solution | Enhancement Solution. | DELFIA Inducer |
| AutoDELFIA<br>Neonatal T4 Kit | Detection<br>Principle | Time-resolved fluorescence | Same |
| AutoDELFIA<br>Neonatal T4 Kit | Specimen | Dried blood on filter paper disks with a<br>diameter of approximately 3.2 mm (1/8 inch) | Same |
| AutoDELFIA<br>Neonatal T4 Kit | Antibodies | Primary mouse monoclonal antibody and | Same |
| | FEATURE | Similarities (AutoDELFIA T4) | Differences (GSP T4) |
| DELFIA<br>Neonatal T4 Kit | Calibrators | Six levels of T4 calibrators | Same |
| DELFIA<br>Neonatal T4 Kit | Source | Human blood with a hematocrit value of 50-55% | Same |
| DELFIA<br>Neonatal T4 Kit | Matrix | Filter paper sheets<br>(Whatman no. 903) | Filter paper cassettes (Whatman no.903) |
| DELFIA<br>Neonatal T4 Kit | Calibrator<br>Concentrations | A 0 µg/dL serum<br>B 2 µg/dL serum<br>C 4 µg/dL serum<br>D 8 µg/dL serum<br>E 16 µg/dL serum<br>F 30 µg/dL serum | Same |
| DELFIA<br>Neonatal T4 Kit | Controls | Three levels of T4 controls | Same |
| DELFIA<br>Neonatal T4 Kit | Control<br>Concentrations | Approx. values:<br>C1 3 µg/dL serum<br>C2 7 µg/dL serum<br>C3 12 µg/dL serum | Same |
| DELFIA<br>Neonatal T4 Kit | Tracer | T4-Eu (~25 nmol/L);<br>6 vials, lyophilized | T4-Eu (~10 nmol/L);<br>3 vials, 2.8 mL |
| DELFIA<br>Neonatal T4 Kit | Antibody | T4 antibody stock solution (~40 nmol/L);<br>6 vials, 1.5 mL | T4 antibody (~12 nmol/L);<br>3 vials, 2.8 mL |
| DELFIA<br>Neonatal T4 Kit | Assay Buffer | T4 Assay Buffer<br>3 bottles, 110 mL | Same |
| DELFIA<br>Neonatal T4 Kit | Plates | Anti-Mouse IgG Microtitration strips (Nunc<br>PolySorb); 12 plates | Anti-Mouse IgG Microtitration strips (Nunc<br>MaxiSorb); 12 plates |
| DELFIA<br>Neonatal T4 Kit | Detection | Defined by analyte specific protocol | Same |
| DELFIA<br>Neonatal T4 Kit | Calculation | Multicalc, X- axis LOG, Y-axis B/BMax;<br>fitting algorithm spline smoothed | GSP Workstation software,<br>X-axis Hyberbolic,<br>Y-axis Bound2Max; fitting algorithm spline<br>smoothed |
| DELFIA<br>Neonatal T4 Kit | Incubation Detail | 11min + 2 hours, 25°C | 10 min + 2 hours, 25°C |
| DELFIA<br>Neonatal T4 Kit | Precision<br>(levels/CVs) | Full standard curve on each plate:<br>Control 1; 3.95 µg/dL serum<br>Intra-assay variation 14.9 %<br>Inter-assay variation 10.0 %<br>Total variation 18.0 % | Full calibration curve on each plate:<br>Sample 1; 2.0 µg/dL<br>Within run 1.0%<br>Within lot 15.5%<br>Total variation 15.8% |
| Predicate Device | FEATURE | Similarities (AutoDELFIA T4) | Differences (GSP T4) |
| | | Control 2; 8.08 µg/dL serum<br>Intra-assay variation 10.6 %<br>Inter-assay variation 7.1 %<br>Total variation 12.7 % | Sample 2; 4.8 µg/dL<br>Within run 7.3%<br>Within lot 10.7%<br>Total variation 11.4% |
| | | Control 3; 18.2 µg/dL serum<br>Intra-assay variation 8.2%<br>Inter-assay variation 4.3%<br>Total variation 9.3 % | Sample 3; 7.5 µg/dL<br>Within run 6.5%<br>Within lot 8.4%<br>Total variation 8.6% |
| | | | Sample 4; 16.6 µg/dL<br>Within run 4.5%<br>Within lot 7.8%<br>Total variation 8.5% |
| | | | Sample 5; 19.8 µg/dL<br>Within run 7.2%<br>Within lot 9.9%<br>Total variation 10.3% |
| | | | Sample 6; 21.4 µg/dL<br>Within run 7.1%<br>Within lot 9.8%<br>Total variation 10.1% |
| AutoDELFIA<br>Neonatal T4 Kit | Measuring Range | 1.5 µg/dL to the highest level calibrator | 1.6 to 30 µg/dL serum |
| AutoDELFIA<br>Neonatal T4 Kit | Limit of Blank | < 1.5 µg/dL | 0.457 µg/dL |
| AutoDELFIA<br>Neonatal T4 Kit | Limit of Detection | Not available | 0.99 µg/dL |
| AutoDELFIA<br>Neonatal T4 Kit | Limit of Quantitation | Not available | 1.61 µg/dL |
| AutoDELFIA<br>Neonatal T4 Kit | Interference | Bilirubin at 20 mg/dL in has no significant effect on the assay. | Icteric (unconjugated bilirubin ≤ 342 µmol/L, equivalent to 20 mg/dL in serum, and conjugated bilirubin ≤ 237 µmol/L, equivalent to 20 mg/dL in serum) samples do not interfere with the assay.<br>Lipemic samples (Intralipid¹ ≤ 15 mg/mL in serum) do not interfere with the assay. Added |

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1 Intralipid is a registered trademark of Fresenius Kabi AB.

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| Predicate<br>Device | FEATURE | Similarities (AutoDELFIA T4) | | Differences (GSP T4)<br>hemoglobin up to 15 g/L does not interfere with<br>the assay. | |
|-------------------------------|------------------|--------------------------------------|-----------------------|---------------------------------------------------------------------------------------|-------------------------|
| | | Substance | Cross reactivity<br>% | Substance | Cross reactivity<br>(%) |
| | | L-Thyroxine | 100 | L-thyroxine | 100 |
| | | 3,3',5-Triiodo-L-<br>thyronine (LT3) | 0.89 | 3,3',5-Triiodo-L-<br>thyronine (LT3) | 1.67 |
| | | 3,3',5-Triiodoacetic<br>acid | 0.45 | 3,3',5-Triiodothyroacetic<br>acid | 0.14 |
| | | 3,5-Diiodo-L-thyronine | < 0.1 | 3,5-Diiodo-L-thyronine | < 0.1 |
| AutoDELFIA<br>Neonatal T4 Kit | Cross reactivity | 3,5-Diiodotyrosine<br>(DIT) | < 0.1 | 3,5-Diiodotyrosine (DIT)<br>dihydrate | < 0.1 |
| | | 5,5 Diphenylhydantoin | < 0.1 | 5,5-Diphenylhydantoin | < 0.1 |
| | | 3-iodo-L-tyrosine (MIT) | < 0.1 | 3-iodo-L-tyrosine (MIT) | < 0.1 |
| | | Phenylbutazone | < 0.1 | Phenylbutazone | < 0.1 |
| | | 6-n-Propyl-2-thiouracil | < 0.1 | 6-n-Propyl-2-thiouracil | < 0.1 |
| | | Methimazole | < 0.1 | Methimazole | < 0.1 |
| | | L-Tyrosine | < 0.1 | L-Tyrosine | < 0.1 |
| | | Acetylsalicylic acid | < 0.1 | Acetylsalicylic acid | < 0.01 |

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Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES-USA" around the perimeter. Inside the circle is a stylized symbol that resembles a human figure.

Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993

APR 2 2 2011

Wallac Ov c/o Susan K. Hamann Regulatory Affairs Manager 940 Winter Street Waltham, MA, 02451

Re: k103484

> Trade Name: GSP Neonatal Thyroxine (T4) kit Regulation Number: 21 CFR §862.1700 Regulation Name: Total thyroxine test system. Regulatory Class: Class II Product Code: KLI Dated: November 24, 2010 Received: February 24, 2011

Dear Ms. Hamann:

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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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## Page 2 -

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. 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 Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours.

C.C.

Courtney Harper, 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 Form

510(k) Number (if known): __K103484

Device Name: The GSP Neonatal Thyroxine (T4) kit (3302-001U)

Indications for Use:

The GSP Neonatal Thyroxine (T4) kit is intended for the quantitative determination of human thyroxine (T4) in blood specimens dried on filter paper as an aid in screening newborns for congenital (neonatal) hypothyroidism using the GSP instrument.

Prescription Use ਮ (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 OF NEEDED)

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

Carol C. Benson

Division Sign Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K103484

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