(104 days)
GTI-FVIII Inhibitor Assay is designed as a solid phase Enzyme-Linked Immunosorbent Assay (ELISA). The product is intended to be used as an in vitro diagnostic kit by hemostasis and other laboratories providing factor VIII inhibitor assay to assist in screening samples for the presence of alloantibodies to epitopes on FVIII molecule.
FVIII Inhibitor Assay is an ELISA platform which is designed to detect IgG antibodies to human recombinant FVIII in human plasma samples. Recombinant human FVIII molecules are passively immobilized in microtiter wells. Patient plasma is tested against wells containing immobilized recombinant FVIII and compared to the reaction obtained from the negative control sera included in the kit. The results are obtained in optical density (OD) values. The patient samples having OD values greater than the cutoff value are regarded as being positive.
1. A table of acceptance criteria and the reported device performance
| Acceptance Criteria (Implied) | Reported Device Performance (GTI-FVIII Inhibitor Assay) |
|---|---|
| Detects FVIII antibodies with high concordance to Bethesda assay | Concordance: 89.6% |
| Detects FVIII antibodies with high sensitivity compared to Bethesda assay | Sensitivity: 98.9% |
| Detects FVIII antibodies with high negative predictive value compared to Bethesda assay | Negative Predictive Value: 98.8% |
| Lot-to-lot consistency | Comparable between three different lots |
| Tech-to-tech consistency | Good correlation of results obtained by three different individuals |
| Stability over dating period | Stable over a 27-month period |
2. Sample size used for the test set and the data provenance
The sample size for the test set is not explicitly stated in the provided text.
The data provenance is retrospective, comparing the GTI-FVIII Inhibitor Assay to the Bethesda assay in previously collected samples. The country of origin is not specified, but the study was conducted in "two independent clinical laboratories."
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. The Bethesda assay is used as the reference standard (ground truth), but the number and qualifications of experts involved in performing or interpreting the Bethesda assay results are not detailed.
4. Adjudication method for the test set
Not explicitly stated. Given that the comparison is against the Bethesda assay, it's implied that the Bethesda assay results served as the reference without a separate adjudication process for the test set itself beyond what is inherent in the Bethesda assay's methodology.
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
No, an MRMC comparative effectiveness study was not done. The study compares the performance of a device (ELISA kit) to a predicate assay, not the performance of human readers with or without AI assistance.
6. If a standalone (i.e. algorithm only, without human-in-the-loop performance) was done
Yes, a standalone study was done. The reported performance (concordance, sensitivity, negative predictive value) is for the GTI-FVIII Inhibitor Assay device itself, without human interpretation as part of the primary outcome measure. The device provides "optical density (OD) values" which are then compared to a cutoff value to determine positive or negative results. While human technical staff operate the ELISA, the interpretation of the results as positive or negative is algorithm-driven based on the OD values.
7. The type of ground truth used
The type of ground truth used is a reference assay/methodology, specifically the Bethesda assay.
8. The sample size for the training set
The text does not mention a separate training set. The study describes the comparison of the GTI-FVIII Inhibitor Assay to the Bethesda assay, implying a validation or test set, but no distinct training set for developing the device is detailed in this summary.
9. How the ground truth for the training set was established
Not applicable, as a separate training set and its ground truth establishment are not discussed in the provided summary. The device's underlying principles (ELISA platform detecting IgG antibodies to FVIII) suggest it was developed based on established immunological assays, but the specifics of its internal development and training (if any, in a machine learning sense) are not provided.
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1 2000 FEB
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510(K) SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with requirements of SMDA 1990 and 21 CFR 807.92.
| The assigned 510(k) number is | K993553 |
|---|---|
| Name: | FVIII Inhibitor |
| Equivalence: | PF4 ELISA |
| Description: | FVIII Inhibitor Assay is an ELISA platform which is designed to detect IgG antibodies to human recombinant FVIII in human plasma samples. Recombinant human FVIII molecules are passively immobilized in microtiter wells. Patient plasma is tested against wells containing immobilized recombinant FVIII and compared to the reaction obtained from the negative control sera included in the kit. The results are obtained in optical density (OD) values. The patient samples having OD values greater than the cutoff value are regarded as being positive. |
| Intended Use: | FVIII Inhibitor Assay is a solid phase Enzyme-Linked Immunosorbent Assay (ELISA) which is used to detect IgG antibodies reactive with recombinant human FVIII. |
Comparison of FVIII Inhibitor Assay to the predicate device:
The following table demonstrates the comparison:
| Feature/Characteristic | GTI-PF4ELISA | GTI-FVIIIInhibitor Assay |
|---|---|---|
| INTENDED USE | Solid Phase ELISA for thedetection of heparin-associated antibodies reactivewith PF4/PVS complexes. | Solid Phase ELISA for thedetection of antibodiesdirected against epitopes onrecombinant human factorVIII molecule |
| IMMUNOASSAY FORMAT | SOLID PHASE ELISA | |
| TYPE OF TEST | QUALITATIVE |
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| ANTIGEN SOURCE | Affinity purifiedHuman PF4 | Recombinant human FVIII |
|---|---|---|
| TARGET ANTIGENIMMOBILIZATION | PF4/PVS complex passivelyadsorbed in microtiter wells | Recombinant human FVIIIPassively adsorbed inmicrotiter wells |
| INTERPRETATION OFTEST RESULTS | The OD for each microtiterWell is compared to a cut offvalue in order to determine thepositive & negative results | The OD for each microtiterwell is compared to a cutoffvalue in order to determine thepositive & negative results |
| TYPE OF ANTIBODIESDETECTED | Heparin-associated antibodiesReactive with PF4/PVScomplexes | FVIII inhibitor antibodiesreactive with recombinanthuman factor VIII |
Support of 510(k) with Clinical Data
GTI-FVIII Inhibitor Assay was compared to Bethesda assay in two independent clinical laboratories. Results indicated that GTI-FVIII Inhibitor Assay detects FVIII antibodies with a concordance of 89.6%, sensitivity of 98.9%, and negative predictive value of 98.8% as compared to Bethesda assay.
Support of 510(k) with Non-Clinical Data
Lot-to-lot testing of GTI-FVIII Inhibitor Assay was comparable between three different lots.
Tech-to-tech testing of GTI-FVIII Inhibitor Assay showed good correlation of the results obtained by three different individuals.
Stability data carried out over a 27 month period indicated that GTI- FVIII Inhibitor Assay remains stable during the dating period.
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Image /page/2/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 words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized symbol that resembles a caduceus, a traditional symbol of medicine, with three wavy lines representing snakes or streams.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
FEB 1 2000
Mr. Michael Moghaddam Director, Product Development Genetic Testing Institute 150 North Patrick Boulevard Brookfield, Wisconsin 53045-5837
Re: K993553 Trade Name: GTI-FVIII Inhibitor Assay Regulatory Class: II Product Code: GGP Dated: January 4, 2000 Received: January 5, 2000
Dear Mr. Moghaddam:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (OS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic OS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.
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This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".
Sincerely yours,
Steven Sutman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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510(k) Number (if known): K993553
Device Name: _________________________________________________________________________________________________________________________________________________________________
INDICATIONS FOR USE
GTI-FVIII Inhibitor Assay is designed as a solid phase Enzyme-Linked Immunosorbent Assay (ELISA). The product is intended to be used as an in vitro diagnostic kit by hemostasis and other laboratories providing factor VIII inhibitor assay to assist in screening samples for the presence of alloantibodies to epitopes on FVIII molecule.
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Suta E. Machi
(Division Sign-Off) Division of Clinical Laboratory Devices 510(k) Number
Prescription Use
(Per 21 CFR 801.109)
OR
Over-The-Counter Use_
(Optional Format 1-2-96)
§ 864.7290 Factor deficiency test.
(a)
Identification. A factor deficiency test is a device used to diagnose specific coagulation defects, to monitor certain types of therapy, to detect coagulation inhibitors, and to detect a carrier state (a person carrying both a recessive gene for a coagulation factor deficiency such as hemophilia and the corresponding normal gene).(b)
Classification. Class II (performance standards).