(130 days)
The AutoDELFIA Neonatal IRT kit is intended for the quantitative determination of human immunoreactive trypsin(ogen) (IRT) in blood specimens dried on filter paper as an aid in screening newborns for cystic fibrosis using the 1235 AutoDELFIA® automatic immunoassay system.
The AutoDELFIA Neonatal IRT assay is a solid phase, two-site fluoroimmunometric assay based on the direct sandwich technique in which two monoclonal antibodies (derived from mice) are directed against two separate antigenic determinants on the IRT molecule. Calibrators, controls and test specimens containing IRT are reacted simultaneously with immobilized monoclonal antibodies directed against a specific antigenic site on the IRT molecule and europium-labeled monoclonal antibodies (directed against a different antigenic site) in assay buffer. The assay buffer elutes IRT from the dried blood on filter paper disks. The complete assay requires only one incubation step. Enhancement Solution dissociates europium ions from the labeled antibody into solution where they form highly fluorescent chelates with components of the Enhancement Solution. The fluorescence in each well is then measured. The fluorescence of each sample is proportional to the concentration of IRT in the sample.
The provided text describes a 510(k) premarket notification for the AutoDELFIA Neonatal IRT kit. This submission focuses on demonstrating substantial equivalence to a predicate device, rather than providing a detailed study report with specific acceptance criteria and performance data in the format typically used for AI/ML device evaluations. As such, many of the requested fields for AI/ML device studies are not directly applicable or explicitly stated in this document.
However, I can extract information related to the device's analytical performance characteristics, which serve as a form of acceptance criteria for this type of in-vitro diagnostic device.
Here's an attempt to populate the table and answer the questions based on the provided text, indicating where information is not available.
1. Table of Acceptance Criteria and the Reported Device Performance
For this in-vitro diagnostic device, "acceptance criteria" are generally established by demonstrating performance characteristics that are comparable to or better than a legally marketed predicate device, and that meet the required analytical performance for its intended use.
| Characteristic (Feature) | Acceptance Criteria (from Predicate Device) | Reported Device Performance (New Device: B005-212/B005-204) |
|---|---|---|
| Measuring Range | 4 (as defined by LoB) to 500 (as defined by upper calibrator) ng/mL blood | 16 to 480 ng/mL blood |
| Linearity Range | No claims for linearity in labeling. | 16 to 480 ng/mL blood |
| Analytical Sensitivity / Limit of Blank (LoB) | < 4 ng/mL blood | 0.53 ng/mL blood |
| Limit of Detection (LoD) | Not explicitly stated, implied to be around 4 ng/mL blood (from LoB) | 2.9 ng/mL blood |
| Antibody Cross-Reactions | α2-macroglobulin < 4 ng/ml blood, α1-antitrypsin < 4 ng/ml blood, Phospholipase A2 < 4 ng/ml blood, Chymotrypsin < 4 ng/ml blood, Human IgG < 4 ng/ml blood, Uropepsinogen < 4 ng/ml blood | α2-macroglobulin < 4 ng/ml blood, α1-antitrypsin < 4 ng/ml blood, Phospholipase A2 < 4 ng/ml blood, Chymotrypsin < 4 ng/ml blood, Human IgG < 4 ng/ml blood, Uropepsinogen < 4 ng/ml blood (All "Same" as predicate, which explicitly lists these values) |
| Hook effect | No hook effect has been found with IRT concentrations up to 40,000 ng/mL | No hook effect has been found with IRT concentrations up to 40,000 ng/mL |
| Precision (Total Variation CV%) | 42.6 ng/mL blood CV% 9.3, 98.8 ng/mL blood CV% 10.0, 266 ng/mL blood CV% 9.6 | 16.7 ng/mL blood CV% 8.7, 22.5 ng/mL blood CV% 9.6, 48.0 ng/mL blood CV% 9.1, 104 ng/mL blood CV% 8.0, 247 ng/mL blood CV% 8.3, 401 ng/mL blood CV% 8.4, 449 ng/mL blood CV% 9.4 |
Note on "Acceptance Criteria": For this 510(k) submission, the "acceptance criteria" are implied to be achieving analytical performance characteristics that are comparable to or improved from the predicate device, thereby demonstrating substantial equivalence. The table shows that the new device generally performs comparably or better (e.g., lower LoB, explicit linearity claim, more detailed precision data, and a wider range of concentrations with good precision).
Regarding the study proving the device meets the acceptance criteria:
The document describes the submission as a 510(k) for an in-vitro diagnostic kit. The "study" here refers to the analytical performance evaluation conducted by the manufacturer to demonstrate substantial equivalence to the predicate device. The information provided is a summary of the device's analytical characteristics.
2. Sample size used for the test set and the data provenance:
- Sample Size: Not explicitly stated in terms of number of individual patient samples. The precision data lists several concentration levels (e.g., 16.7 ng/mL, 22.5 ng/mL, etc.), implying multiple measurements were taken at each level. The cross-reactivity and hook effect studies would have involved specific spiked samples.
- Data Provenance: Not explicitly stated (e.g., country of origin). It's an in-house analytical validation, likely conducted at the manufacturer's facility. It is a retrospective analysis of laboratory-prepared samples or collected blood spots rather than a prospective clinical study involving external patient recruitment.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This question is more applicable to AI/ML devices that rely on expert interpretation for ground truth. For this in-vitro diagnostic assay, the "ground truth" for reported values (e.g., IRT concentration) is established by the analytical method itself and calibration against known standards. There's no mention of external expert consensus for establishing ground truth for the analytical performance data.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not applicable for this type of analytical performance study of an in-vitro diagnostic kit. Adjudication methods like 2+1 or 3+1 are typically used in clinical studies where multiple human readers interpret medical images or clinical data, and a disagreement resolution process is needed to establish a definitive ground truth.
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 not an AI/ML device designed to assist human readers. It's an automated immunoassay system for quantitative measurement.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- No, this is not an AI/ML algorithm. It is an automated immunoassay kit where the "algorithm" is the biochemical reaction and the instrument's measurement and calculation of IRT concentration. The device operates in a standalone analytical capacity to measure IRT.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- The ground truth for the analytical performance characteristics (such as concentration, linearity, limit of blank, limit of detection, cross-reactivity, hook effect, and precision) would be established by:
- Reference materials/known standards: For calibration, linearity, and determining accurate concentrations.
- Spiked samples: For cross-reactivity and hook effect studies where known interferents or high concentrations are added.
- Repeated measurements: For precision studies.
8. The sample size for the training set:
- Not explicitly stated, and the concept of a "training set" as understood in AI/ML is not directly applicable. For this type of device, development involves optimizing the assay components and conditions, which is an iterative process using various samples (e.g., patient samples, spiked samples, controls) but not typically referred to as a discrete "training set" in the AI/ML context.
9. How the ground truth for the training set was established:
- As above, the concept of a "training set" with established ground truth in the AI/ML sense is not relevant here. Ground truth for internal development and optimization would be based on the known biochemical properties of the reagents, reference standards, and performance evaluation criteria.
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510(k) SUMMARY
JUN 1 0 2011
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: January 26, 2010
Submitted by:
Wallac Oy, subsidiary of PerkinElmer 940 Winter Street Waltham, MA 02451 USA
Contact Person: Primary:
Susan K. Hamann Tel: 781-663-5872 Fax: 781-663-5983
Kay A. Taylor
JNO
Tel: 317-418-1735 Fax: 317-536-3064
Secondary:
Trade Name:
Common Name: Regulation:
AutoDELFIA Neonatal IRT kit 21 CFR 862.1725
Trypsin Test System and Electrode
Classification Name:
Product Code:
Predicate Device:
Device Description:
AutoDELFIA® Neonatal IRT kit, B005-112
AutoDELFIA® Neonatal IRT kit B005-212, B005-204
510(k) Number (K0003668)
The AutoDELFIA Neonatal IRT assay is a solid phase, two-site fluoroimmunometric assay based on the direct sandwich technique in which two monoclonal antibodies (derived from mice) are directed against two separate antigenic determinants on the IRT molecule. Calibrators, controls and test specimens containing IRT are reacted simultaneously with immobilized monoclonal antibodies directed against a specific antigenic site on the IRT molecule and europium-labeled monoclonal antibodies (directed against a different antigenic site) in assay buffer. The assay buffer elutes IRT from the dried blood on filter paper disks. The complete assay requires only one incubation step.
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Enhancement Solution dissociates europium ions from the labeled antibody into solution where they form highly fluorescent chelates with components of the Enhancement Solution. The fluorescence in each well is then measured. The fluorescence of each sample is proportional to the concentration of IRT in the sample.
The AutoDELFIA Neonatal IRT kit is intended for the quantitative determination of human immunoreactive trypsin(ogen) (IRT) in blood specimens dried on filter paper as an aid in screening newborns for cystic fibrosis using the 1235 AutoDELFIA® automatic immunoassay system.
Substantial Equivalence: The AutoDELFIA Neonatal IRT kit (B005-212/B005-204) is substantially equivalent to the currently marketed AutoDELFIA IRT kit (B005-112) (K0003668). There are the following similarities and differences between the two kits:
Intended Use:
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Table 1. Characteristics of the two kits.
・.
| Characteristic (Feature) | AutoDELFIA NeonatalIRT kitB005-212/B005-204(New Device) | AutoDELFIA NeonatalIRT kitB005-112(Predicate Device) |
|---|---|---|
| Similarities | ||
| Intended User | Adequately trained laboratorypersonnel in laboratoriesperforming newbornscreening | Same |
| Intended Use / Indications for Use | The AutoDELFIA NeonatalIRT kit (B005-212/B005-204)is intended for the quantitativedetermination of humanimmunoreactive trypsin(ogen)(IRT) in blood specimensdried on filter paper as an aidin screening newborns forcystic fibrosis using the 1235AutoDELFIA® automaticimmunoassay system. | The AutoDELFIA NeonatalIRT (B005-112) is intendedfor the quantitativedetermination of humanimmunoreactive trypsin (IRT)in blood specimens dried onfilter paper as an aid inscreening newborns for cysticfibrosis using the 1235AutoDELFIA® automaticimmunoassay system. |
| Chemical Principle | The AutoDELFIA NeonatalIRT assay is a solid phase,two-site fluorimmunometricassay based on the directsandwich technique in whichtwo monoclonal antibodies(derived from mice) aredirected against two separateantigenic determinants on theIRT molecule. Calibrators,controls, or test specimenscontaining IRT are reactedsimultaneously withimmobilized monoclonalantibodies directed against aspecific antigenic site on theIRT molecule and europium-labeled monoclonal antibodies(directed against a differentantigenic site) in assay buffer.The assay buffer elutes IRTfrom dried blood on filterpaper disks. The completeassay requires only oneincubation step. | Same |
| Characteristic (Feature) | AutoDELFIA NeonatalIRT kitB005-212/B005-204(New Device) | AutoDELFIA NeonatalIRT kitB005-112(Predicate Device) |
| from the labeled antibody into solution where they formhighly fluorescent chelates with components of theEnhancement Solution. The fluorescence in each well isthen measured. The fluorescence of each sample isproportional to theconcentration of IRT in the sample. | ||
| Detection principle | Time-resolved fluorescence | Same |
| Specimen | Dried blood on filter paperdisks with a diameter ofapproximately 3.2 mm (1/8inch) | Same |
| Antibodies | Two different mousemonoclonal antibodies | Same |
| Calibrator and Control Matrix | Human blood derivative witha hematocrit of 50-55% andspotted onto filter paper(Whatman, no. 903) | Same |
| (Washed blood cells in buffercontaining BSA and proteaseinhibitors)(Filter paper on a supportiveframe called "cassette") | (Washed blood cells in salinecontaining saccharose)(Filter paper as sheets) | |
| Kit Calibrators | 6 levels.(approx. values 0, 25, 50, 100,250, 500 ng/mL blood. | Same |
| Kit Controls | 3 levels (approx. values 30, 70and. 110 ng/mL blood) | 3 levels (approx. values 40,70 and 120 ng/mL blood) |
| Calibration | Calibrated using gravimetricmethods | Same |
| (In-house calibrators containprotease inhibitors and BSAitem 1.) | (In-house calibrators withoutprotease inhibitors, containBSA item 2.) | |
| Assay buffer | IRT Assay Buffer, ready foruseTris-HCl buffered (pH 7.8)salt solution with bovineserum albumin, and additives. | Same |
| Characteristic (Feature) | AutoDELFIA NeonatalIRT kitB005-212/B005-204(New Device)(BSA item 1 used) | AutoDELFIA NeonatalIRT kitB005-112(Predicate Device)(BSA item 2 used) |
| Coated Plates | Anti-IRT MicrotitrationStrips, 8 X 12 wells coatedwith antibodies directedagainst a specific site on theIRT molecule (mousemonoclonal) | Same |
| Tracer | Anti-IRT-Eu tracer stocksolution (~50 µg/mL), mousemonoclonal, ready for use. . | Same |
| Instrument | 1235 AutoDELFIA Instrument | Same |
| Dissociation solution | Enhancement Solution | Same |
| Expected Values | The measurement of IRTfrom dried blood spots is usedas a means of identifying apopulation of newborns whoare at increased risk of havingCF and should be selected for2nd tier testing. Theidentification is based on theuse of a fixed cut-off value orpopulation percentile. TheIRT cut-off levels must bedetermined by each newbornscreening laboratory to meetthe desired sensitivity andspecificity of the screen andshould be evaluatedperiodically. | Same |
| Measuring Range | 16 to 480 ng/mL bloodLinearity Range: 16 to 480ng/mL blood | 4(as defined by LoB) to 500 (asdefined by upper calibrator)ng/mL bloodLinearity Range: No claims forlinearity in labeling. |
| Analytical Sensitivity / Limit ofBlank, | Limit of Blank0.53 ng/mL blood | Limit of Blank< 4 ng/mL blood |
| Limit of Detection | Limit of Detection2.9 ng/mL blood | |
| AntibodyCross-Reactionsin the Assay | α2-macroglobulin < 4 ng/mlbloodal-antitrypsin < 4 ng/ml bloodPhospholipase A2 < 4 ng/mlbloodChymotrypsin < 4 ng/ml blood | Same |
| Characteristic (Feature) | AutoDELFIA NeonatalIRT kitB005-212/B005-204 | AutoDELFIA NeonatalIRT kitB005-112 |
| (New Device) | (Predicate Device) | |
| Human IgG < 4 ng/ml bloodUropepsinogen < 4 ng/ml blood | ||
| Hook effect | No hook effect has beenfound with IRTconcentrations up to 40,000ng/mL | Same |
| Precision (Total Variation usinga full calibration curve on eachplate) | 16.7 ng/mL blood CV% 8.722.5 ng/mL blood CV% 9.648.0 ng/mL blood CV% 9.1104 ng/mL blood CV% 8.0247 ng/mL blood CV% 8.3401 ng/mL blood CV% 8.4449 ng/mL blood CV% 9.4 | 42.6 ng/mL blood CV% 9.398.8 ng/mL blood CV% 10.0266 ng/mL blood CV% 9.6 |
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Image /page/6/Picture/12 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 image of an eagle or bird-like figure.
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993
Wallac Oy A Subsidiary of PerkinElmer, Inc. c/o Ms. Susan K. Hamann Regulatory Affairs Manager 940 Winter Street Waltham, MA 02451
10 2011
Re: K110274 Trade Name: AutoDELFIA® Neonatal IRT Kit Regulation Number: 21 CFR 862.1725 Regulation Name: Trysin test system. Regulatory Class: I exempt, exceeds the limitation to exemption in 862.9(c) (2) Product Codes: JNO Dated: May 05, 2011 Received: May 06, 2011
Dear Ms. Susan K. 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 (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 no mber (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
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Indications for Use Form
510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________
Device Name: AutoDELFIA Neonatal IRT kit (B005-212)
Indications for Use:
The AutoDELFIA Neonatal IRT kit is intended for the quantitative determination of human immunoreactive trypsin(ogen) (IRT) in blood specimens dried on filter paper as an aid in screening newborns for cystic fibrosis using the 1235 AutoDELFIA® automatic immunoassay system.
Prescription Use X (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)
Rus
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K110274
§ 862.1725 Trypsin test system.
(a)
Identification. A trypsin test system is a device intended to measure the activity of trypsin (a pancreatic enzyme important in digestion for the breakdown of proteins) in blood and other body fluids and in feces. Measurements obtained by this device are used in the diagnosis and treatment of pancreatic disease.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.