(147 days)
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.
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 antibody-bound and free antigen. DELFIA Inducer dissociates europium ions from the labeled antibody into solution where they form highly fluorescent chelates with components of DELFIA Inducer. The fluorescence in each well is then measured. The fluorescence of each sample is inversely proportional to the concentration of T4 in the sample.
The provided text describes a 510(k) premarket notification for an in vitro diagnostic device, the GSP Neonatal Thyroxine (T4) kit. This type of submission focuses on demonstrating substantial equivalence to a legally marketed predicate device rather than conducting a full clinical study with specific acceptance criteria and ground truth for disease diagnosis in the same way an AI/ML powered device might.
Therefore, the requested information regarding "acceptance criteria" for an AI device, "sample size for the test set," "number of experts," "adjudication method," "MRMC study," "standalone performance," and "ground truth for training/testing" in the context of an AI/ML study does not directly apply to this submission.
However, I can extract the closest analogous information available within this document, focusing on the performance characteristics presented to demonstrate equivalence.
Here's an attempt to answer the questions based on the provided document, interpreting "acceptance criteria" as performance metrics for this diagnostic kit.
1. Table of Acceptance Criteria and Reported Device Performance
For an in-vitro diagnostic kit like this, "acceptance criteria" are typically defined by demonstrating that the new device performs comparably to or within acceptable ranges relative to a predicate device and established analytical performance specifications. The document provides a comparison of various features and performance characteristics between the new GSP Neonatal T4 kit and its predicate device, AutoDELFIA Neonatal T4 Kit.
| Performance Characteristic | Predicate Device (AutoDELFIA T4) Performance (Analogous to "Acceptance Criteria" for comparison) | GSP Neonatal T4 Kit Reported Performance (Analogous to "Device Performance") |
|---|---|---|
| Precision (CVs) | Control 1; 3.95 µg/dL serum - Intra-assay variation 14.9 % - Inter-assay variation 10.0 % - Total variation 18.0 % Control 2; 8.08 µg/dL serum - Intra-assay variation 10.6 % - Inter-assay variation 7.1 % - Total variation 12.7 % Control 3; 18.2 µg/dL serum - Intra-assay variation 8.2% - Inter-assay variation 4.3% - Total variation 9.3 % | Sample 1; 2.0 µg/dL - Within run 1.0% - Within lot 15.5% - Total variation 15.8% Sample 2; 4.8 µg/dL - Within run 7.3% - Within lot 10.7% - Total variation 11.4% Sample 3; 7.5 µg/dL - Within run 6.5% - Within lot 8.4% - Total variation 8.6% Sample 4; 16.6 µg/dL - Within run 4.5% - Within lot 7.8% - Total variation 8.5% Sample 5; 19.8 µg/dL - Within run 7.2% - Within lot 9.9% - Total variation 10.3% Sample 6; 21.4 µg/dL - Within run 7.1% - Within lot 9.8% - Total variation 10.1% |
| Measuring Range | 1.5 µg/dL to the highest level calibrator | 1.6 to 30 µg/dL serum |
| Limit of Blank (LoB) | < 1.5 µg/dL | 0.457 µg/dL |
| Limit of Detection (LoD) | Not available | 0.99 µg/dL |
| Limit of Quantitation (LoQ) | Not available | 1.61 µg/dL |
| Interference | Bilirubin at 20 mg/dL has no significant effect. | 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), Lipemic (Intralipid¹ ≤ 15 mg/mL in serum), and Hemoglobin up to 15 g/L samples do not interfere. [¹Intralipid is a registered trademark of Fresenius Kabi AB.] |
| Cross-reactivity | LT3: 0.89% 3,3',5-Triiodoacetic acid: 0.45% 3,5-Diiodo-L-thyronine: < 0.1% 3,5-Diiodotyrosine (DIT): < 0.1% 5,5 Diphenylhydantoin: < 0.1% 3-iodo-L-tyrosine (MIT): < 0.1% Phenylbutazone: < 0.1% 6-n-Propyl-2-thiouracil: < 0.1% Methimazole: < 0.1% L-Tyrosine: < 0.1% Acetylsalicylic acid: < 0.1% | LT3: 1.67% 3,3',5-Triiodothyroacetic acid: 0.14% 3,5-Diiodo-L-thyronine: < 0.1% 3,5-Diiodotyrosine (DIT) dihydrate: < 0.1% 5,5-Diphenylhydantoin: < 0.1% 3-iodo-L-tyrosine (MIT): < 0.1% Phenylbutazone: < 0.1% 6-n-Propyl-2-thiouracil: < 0.1% Methimazole: < 0.1% L-Tyrosine: < 0.1% Acetylsalicylic acid: < 0.01% |
2. Sample size used for the test set and the data provenance
The document does not specify a separate "test set" sample size in the context of an AI/ML algorithm validation. Instead, it describes analytical performance studies.
- Precision study: The precision data (Within run, Within lot, Total variation) is presented for six different samples at various concentration levels (2.0, 4.8, 7.5, 16.6, 19.8, 21.4 µg/dL). The number of replicates or runs for each sample is not explicitly stated.
- Interference study: Not explicitly stated, but the document mentions testing with specific concentrations of bilirubin, Intralipid, and hemoglobin.
- Cross-reactivity study: Not explicitly stated, but specific substances and their cross-reactivity percentages are listed.
- Data Provenance: The document does not specify the country of origin or whether the data was retrospective or prospective. Given the nature of a premarket submission for an IVD kit, these studies are typically conducted by the manufacturer as part of the validation process.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This question is not applicable. For an immunoassay kit like this, the "ground truth" is established by the direct measurement of T4 concentration using the device itself, calibrated against known standards. There are no human "experts" establishing ground truth through image review or clinical assessment in the way an AI/ML device for diagnosis would require. The "qualification" of personnel pertains to "adequately trained laboratory personnel" running the assay.
4. Adjudication method for the test set
This question is not applicable. Adjudication methods are relevant for studies where multiple independent human readers or algorithms are assessing the same data, and their results need to be reconciled (e.g., in medical image interpretation). This is an analytical performance study of an immunoassay.
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
This question is not applicable. This is an immunoassay kit, not an AI/ML-powered device intended for human-in-the-loop assistance in clinical decision-making or image interpretation. Therefore, no MRMC study was performed.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This question is not applicable. The device itself is a standalone diagnostic kit (reagents and instrument) that produces quantitative T4 measurements. It is not an AI/ML algorithm.
7. The type of ground truth used
For an immunoassay, the "ground truth" for evaluating the device's performance is typically established through:
- Known Calibrator Concentrations: The device's measurements are compared against a standard curve generated from calibrators with precisely known T4 concentrations.
- Reference Methods: If available, comparison to a gold standard reference method for T4 measurement would be part of validation (though not explicitly detailed as "ground truth" in this summary).
- Control Materials: Use of quality control materials with target T4 concentrations.
The document discusses "calibrators" and "controls" which are used to establish and verify the accuracy of the measurements.
8. The sample size for the training set
This question is not applicable. This is not an AI/ML device that requires a "training set" for model development. The performance data presented relates to the validation of the manufactured kit through analytical studies.
9. How the ground truth for the training set was established
This question is not applicable as there is no "training set" in the context of an AI/ML model for this type of medical device submission.
{0}------------------------------------------------
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: 781-663-5872 Fax: 781-663-5983
Secondary:
Kay A. Taylor Tel: 317-418-1735 Fax: 317-536-3064
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.
{1}------------------------------------------------
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:
{2}------------------------------------------------
| PredicateDevice | FEATURE | Similarities (AutoDELFIA T4) | Differences (GSP T4) |
|---|---|---|---|
| AutoDELFIANeonatal T4 Kit | Intended User | Adequately trained laboratory personnel inlaboratories performing newborn screening. | Same |
| AutoDELFIANeonatal T4 Kit | Intended use | This kit is intended for the quantitativedetermination of human thyroxine (T4) inblood specimens dried on filter paper as anaid in screening newborns for congential(neonatal) hypothyroidism using theAutoDELFIA automatic immunoassaysystem. | The kit is intended for the quantitativedetermination of human thyroxine (T4) in bloodspecimens dried on filter paper as an aid inscreening newborns for congenital (neonatal)hypothyroidism using the GSP instrument. |
| AutoDELFIANeonatal T4 Kit | ChemicalPrinciple | The Neonatal T4 assay is a solid phasetime-resolved fluoroimmunoassay based onthe competitive reaction between europium-labeled T4 and sample T4 for a limitedamount of binding sites on T4 specificmonoclonal antibodies (derived from mice).The use of 8-anilino-1-naphthalenesulfonicacid (ANS) and salicylate in the T4 AssayBuffer facilitates the release of T4 from thebinding proteins. Thus the assay measuresthe total amount of T4 in the test specimen.A second antibody, directed against mouseIgG, is coated to the solid phase, and bindsthe IgG-thyroxine complex, givingconvenient separation of the antibody-boundand free antigen. | Same |
| AutoDELFIANeonatal T4 Kit | ChemicalPrinciple | Europium ions are dissociated from thelabeled antibody into solution where theyform highly fluorescent chelates withcomponents of the dissociation solution.The fluorescence in each well is thenmeasured. The fluorescence of each sampleis inversely proportional to the concentrationof T4 in the sample | Same |
| AutoDELFIANeonatal T4 Kit | DissociationSolution | Enhancement Solution. | DELFIA Inducer |
| AutoDELFIANeonatal T4 Kit | DetectionPrinciple | Time-resolved fluorescence | Same |
| AutoDELFIANeonatal T4 Kit | Specimen | Dried blood on filter paper disks with adiameter of approximately 3.2 mm (1/8 inch) | Same |
| AutoDELFIANeonatal T4 Kit | Antibodies | Primary mouse monoclonal antibody and | Same |
| FEATURE | Similarities (AutoDELFIA T4) | Differences (GSP T4) | |
| DELFIANeonatal T4 Kit | Calibrators | Six levels of T4 calibrators | Same |
| DELFIANeonatal T4 Kit | Source | Human blood with a hematocrit value of 50-55% | Same |
| DELFIANeonatal T4 Kit | Matrix | Filter paper sheets(Whatman no. 903) | Filter paper cassettes (Whatman no.903) |
| DELFIANeonatal T4 Kit | CalibratorConcentrations | A 0 µg/dL serumB 2 µg/dL serumC 4 µg/dL serumD 8 µg/dL serumE 16 µg/dL serumF 30 µg/dL serum | Same |
| DELFIANeonatal T4 Kit | Controls | Three levels of T4 controls | Same |
| DELFIANeonatal T4 Kit | ControlConcentrations | Approx. values:C1 3 µg/dL serumC2 7 µg/dL serumC3 12 µg/dL serum | Same |
| DELFIANeonatal T4 Kit | Tracer | T4-Eu (~25 nmol/L);6 vials, lyophilized | T4-Eu (~10 nmol/L);3 vials, 2.8 mL |
| DELFIANeonatal T4 Kit | Antibody | T4 antibody stock solution (~40 nmol/L);6 vials, 1.5 mL | T4 antibody (~12 nmol/L);3 vials, 2.8 mL |
| DELFIANeonatal T4 Kit | Assay Buffer | T4 Assay Buffer3 bottles, 110 mL | Same |
| DELFIANeonatal T4 Kit | Plates | Anti-Mouse IgG Microtitration strips (NuncPolySorb); 12 plates | Anti-Mouse IgG Microtitration strips (NuncMaxiSorb); 12 plates |
| DELFIANeonatal T4 Kit | Detection | Defined by analyte specific protocol | Same |
| DELFIANeonatal T4 Kit | Calculation | Multicalc, X- axis LOG, Y-axis B/BMax;fitting algorithm spline smoothed | GSP Workstation software,X-axis Hyberbolic,Y-axis Bound2Max; fitting algorithm splinesmoothed |
| DELFIANeonatal T4 Kit | Incubation Detail | 11min + 2 hours, 25°C | 10 min + 2 hours, 25°C |
| DELFIANeonatal T4 Kit | Precision(levels/CVs) | Full standard curve on each plate:Control 1; 3.95 µg/dL serumIntra-assay variation 14.9 %Inter-assay variation 10.0 %Total variation 18.0 % | Full calibration curve on each plate:Sample 1; 2.0 µg/dLWithin run 1.0%Within lot 15.5%Total variation 15.8% |
| Predicate Device | FEATURE | Similarities (AutoDELFIA T4) | Differences (GSP T4) |
| Control 2; 8.08 µg/dL serumIntra-assay variation 10.6 %Inter-assay variation 7.1 %Total variation 12.7 % | Sample 2; 4.8 µg/dLWithin run 7.3%Within lot 10.7%Total variation 11.4% | ||
| Control 3; 18.2 µg/dL serumIntra-assay variation 8.2%Inter-assay variation 4.3%Total variation 9.3 % | Sample 3; 7.5 µg/dLWithin run 6.5%Within lot 8.4%Total variation 8.6% | ||
| Sample 4; 16.6 µg/dLWithin run 4.5%Within lot 7.8%Total variation 8.5% | |||
| Sample 5; 19.8 µg/dLWithin run 7.2%Within lot 9.9%Total variation 10.3% | |||
| Sample 6; 21.4 µg/dLWithin run 7.1%Within lot 9.8%Total variation 10.1% | |||
| AutoDELFIANeonatal T4 Kit | Measuring Range | 1.5 µg/dL to the highest level calibrator | 1.6 to 30 µg/dL serum |
| AutoDELFIANeonatal T4 Kit | Limit of Blank | < 1.5 µg/dL | 0.457 µg/dL |
| AutoDELFIANeonatal T4 Kit | Limit of Detection | Not available | 0.99 µg/dL |
| AutoDELFIANeonatal T4 Kit | Limit of Quantitation | Not available | 1.61 µg/dL |
| AutoDELFIANeonatal 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.Lipemic samples (Intralipid¹ ≤ 15 mg/mL in serum) do not interfere with the assay. Added |
.
{3}------------------------------------------------
:
r
י
{4}------------------------------------------------
1 Intralipid is a registered trademark of Fresenius Kabi AB.
.
{5}------------------------------------------------
| PredicateDevice | FEATURE | Similarities (AutoDELFIA T4) | Differences (GSP T4)hemoglobin up to 15 g/L does not interfere withthe assay. | ||
|---|---|---|---|---|---|
| Substance | Cross reactivity% | Substance | Cross reactivity(%) | ||
| L-Thyroxine | 100 | L-thyroxine | 100 | ||
| 3,3',5-Triiodo-L-thyronine (LT3) | 0.89 | 3,3',5-Triiodo-L-thyronine (LT3) | 1.67 | ||
| 3,3',5-Triiodoaceticacid | 0.45 | 3,3',5-Triiodothyroaceticacid | 0.14 | ||
| 3,5-Diiodo-L-thyronine | < 0.1 | 3,5-Diiodo-L-thyronine | < 0.1 | ||
| AutoDELFIANeonatal T4 Kit | Cross reactivity | 3,5-Diiodotyrosine(DIT) | < 0.1 | 3,5-Diiodotyrosine (DIT)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 |
.
.
and the comments of the comments of the comments of
. .
{6}------------------------------------------------
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).
{7}------------------------------------------------
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 (301) 796-5450. 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 (800) 638-2041 or (301) 796-7100 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
{8}------------------------------------------------
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
Page 1 of 1
§ 862.1700 Total thyroxine test system.
(a)
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.(b)
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.