(107 days)
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No
The device is a standard ELISA assay with a colorimetric endpoint, and the summary explicitly states "Not Applicable (ELISA assay, not a machine learning model)" for sections related to training and test sets. There is no mention of AI or ML in the device description or performance studies.
No
This device is an in vitro diagnostic (IVD) kit designed to detect antibodies in human serum and plasma, which is used for diagnostic purposes, not for treating or preventing disease.
Yes
Explanation: The "Intended Use / Indications for Use" section explicitly states, "This product is intended to be used as an in vitro diagnostic kit by hemostasis and other laboratories to screen patient samples for the presence of IgG antibodies reactive with human Factor VIII." This clearly indicates its purpose is to diagnose (screen for) the presence of certain antibodies in patient samples.
No
The device is an in vitro diagnostic kit that utilizes a solid phase enzyme-linked immunosorbent assay (ELISA) with a colorimetric endpoint, which involves physical reagents and laboratory procedures, not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The document explicitly states the device is "intended to be used as an in vitro diagnostic kit by hemostasis and other laboratories to screen patient samples for the presence of IgG antibodies reactive with human Factor VIII." This directly aligns with the definition of an in vitro diagnostic device, which is used to examine specimens taken from the human body to provide information for diagnosis, monitoring, or screening.
- Device Description: The description details how the assay works using human serum and plasma samples, which are specimens taken from the human body.
- Performance Studies: The performance studies involve testing human samples (normal, healthy, non-hemophiliacs, patients with antibodies, hemophiliac donors) to evaluate the device's accuracy, precision, and agreement with other diagnostic methods.
- Key Metrics: The document provides key metrics like sensitivity and specificity, which are standard performance indicators for diagnostic tests.
- Predicate Device(s): The mention of a predicate device (GTI Factor VIII Inhibitor Assay) with a K number indicates a regulatory submission process typical for IVD devices.
All of these points strongly support the classification of this device as an In Vitro Diagnostic.
N/A
Intended Use / Indications for Use
The Factor VIII Antibody Screen is a qualitative solid phase enzyme linked immunosorbent assay (ELISA) designed to detect IgG antibodies reactive with recombinant human factor VIII (FVII) in human serum and plasma.
The Factor VIII Antibody Screen is designed as a solid phase enzyme-linked immunosorbent assay (ELISA) with a colorimetric endpoint. This product is intended to be used as an in vitro diagnostic kit by hemostasis and other laboratories to screen patient samples for the presence of IgG antibodies reactive with human Factor VIII.
Product codes
GGP
Device Description
The Factor VIII Antibody Screen is an Enzyme Linked Immunosorbent Assay with a colorimetric endpoint. The Factor VIII Antibody Screen is designed to detect IgG antibodies reactive with recombinant human Factor VIII in human serum and plasma. The Factor VIII Antibody Screen kit contains all of the reagents necessary to perform the assay.
The Factor VIII Antibody Screen solid phase ELISA microwells provide immobilized recombinant human FVIII as target molecules for the detection of anti-Factor VIII IgG antibodies.
Diluted patient serum or plasma is added to microwells coated with recombinant FVIII molecules allowing antibody, if present, to bind. Unbound material is then washed away. An alkaline phosphatase labeled anti-human immunoglobulin reagent (Anti-IgG) is added to the wells and incubated. The unbound Anti-IgG is washed away and the substrate PNPP (p-nitrophenyl phosphate) is added. After a 30 minute incubation period, the reaction is stopped by a sodium hydroxide solution. The optical density of the color that develops is measured in a spectrophotometer at 405 nm with no reference filter.
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
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Anatomical Site
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Indicated Patient Age Range
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Intended User / Care Setting
hemostasis and other laboratories
Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies
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Factor VIII Antibody Screen Assay Cutoff:
- Description: Since there is no internationally accepted standard for measurement of anti-FVIII antibodies, GTI developed its own standardization system and material used for the assay cutoff. The cutoff value is set by a kit control. The appropriate value for the kit control was determined by analysis of samples from normal, healthy, non-hemophiliacs and samples from patients known to contain antibodies to FVIII. A cutoff which best distinguishes between the two populations was chosen.
- Sample Size: Testing included assaying 78 different serum samples from normal, healthy, nonhemophilic donors and 3 known positive samples with low reactivity.
- Data Source: Normal samples were from healthy, nonhemophilic donors.
- Annotation Protocol: A target value for the kit control is then chosen to be three times (3x) the average OD value of the normal samples. A dilution of the FVIII antibody positive serum is chosen such that it matches the target OD within 0.020 (+/-). The dilution which best matches the target value is used to manufacture the kit control. The 3 known positive samples with low reactivity must be positive and >98% of the normal samples must be negative.
- Key Results: The kit control is a diluted serum known to contain antibodies to Factor VII. The dilution chosen to make the kit control is lot specific and is determined based on the specific reactivity of each kit lot.
-
Qualification of Sample Type:
- Description: This study aimed to support the use of various sample types (serum, plasma collected in ACD, plasma collected in 3.2% or 3.8% sodium citrate) in the Factor VIII Antibody Screen. The effect of different sample matrices was investigated by comparing results from serum and plasma drawn from the same individuals, and by testing spiked samples.
- Sample Size: 59 normal donors for serum vs. 3.2% sodium citrate plasma comparison. 14 healthy, non-hemophilia donors for three-way comparison (serum, 3.2% sodium citrate, and ACD plasma). Spiked samples using Factor VIII antibody positive plasma.
- Data Source: Samples collected from normal donors and spiked with antibody positive plasma. Normal plasma samples from healthy, non-hemophiliacs were purchased as whole blood collected in 3.2% sodium citrate (blue-top) or ACD (yellow top) or were collected from GTI employees. Normal sera samples were collected from the same individuals into non-anticoagulated serum tubes (red-top).
- Key Results: No difference was observed between the reportable results obtained from samples collected as 3.2% sodium citrate plasma, ACD plasma or as serum. All spiked samples yielded the same reportable result regardless of the sample matrix.
-
Factor VIII Antibody Screen Precision:
- Description: Assessed precision of OD values and reportable results.
- Sample Size: 8 samples tested in duplicate in 10 separate assays.
- Key Results: The assay demonstrated 0.600 and
§ 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).
0
( )
NOV 20 2008
| IN USA | 800 . 233 . 1843 |
|---|---|
| TEL | 262 . 754 . 1000 |
262 . 754 . 9831 FAX
gtidiagnostics.com אואוא
20925 Crossroads Circle, Suite 200 Waukesha, WI 53186 USA
510(k) Summary
GTI. DIAGNOSTICS
Good science starts with peopler
I. Submitter:
Owner's Name: Address:
Phone: Fax: Name of Contact Person: Date Summary Prepared: Genetic Testing Institute, Inc. (GTI) 20925 Crossroads Circle Suite 200, Waukesha, WI 53186 262.754.1000 262.754.9831 Michelle A. Stapleton, Ph.D. June 24, 2008
II. Name of Device:
| Device Name: | Factor VIII Antibody Screen |
|---|---|
| Common Name: | ELISA for Factor VIII Antibody Detection |
| Classification Name: | Test, Qualitative And Quantitative Factor Deficiency |
| Product Code: | GGP |
III. Name of predicate device for claiming equivalence
GTI Factor VIII Inhibitor Assay (K993553)
IV. Description of Device:
The Factor VIII Antibody Screen is an Enzyme Linked Immunosorbent Assay with a colorimetric endpoint. The Factor VIII Antibody Screen is designed to detect IgG antibodies reactive with recombinant human Factor VIII in human serum and plasma. The Factor VIII Antibody Screen kit contains all of the reagents necessary to perform the assay.
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Image /page/1/Picture/0 description: The image shows the logo for GTI Diagnostics. The logo consists of a stylized human figure above the text "GTI. DIAGNOSTICS". Below the company name is the tagline "Good science starts with people".
One of the most detrimental complications observed in the treatment of hemophilia A is the development of antibodies to FVII. These antibodies can be either inhibitory or non-inhibitory in regards to FVIII activity. The presence of inhibitory antibodies may lead to the direct neutralization of transfused or endogenous FVIII activity. The non-inhibitory antibodies may lead to increased clearance of FVII from circulation in an antibody mediated manner or by preventing the FVIII from binding to its carrier protein, von Willebrand Factor. Antibodies to Factor VIII are also present in patients with acquired hemophilia.
The Factor VIII Antibody Screen solid phase ELISA microwells provide immobilized recombinant human FVIII as target molecules for the detection of anti-Factor VIII IgG antibodies.
Diluted patient serum or plasma is added to microwells coated with recombinant FVIII molecules allowing antibody, if present, to bind. Unbound material is then washed away. An alkaline phosphatase labeled anti-human immunoglobulin reagent (Anti-IgG) is added to the wells and incubated. The unbound Anti-IgG is washed away and the substrate PNPP (p-nitrophenyl phosphate) is added. After a 30 minute incubation period, the reaction is stopped by a sodium hydroxide solution. The optical density of the color that develops is measured in a spectrophotometer at 405 nm with no reference filter.
V. Intended Use
The Factor VIII Antibody screen is a qualitative solid phase enzyme linked immunosorbent assay (ELISA) designed to detect IgG antibodies reactive with recombinant human factor VIII (FVII) in human serum and plasma.
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Image /page/2/Picture/0 description: The image contains a logo for GTI Diagnostics. The logo consists of a stylized black and white graphic above the text "GTI. DIAGNOSTICS". Below the company name is the tagline "Good science starts with people."
VI. Support of substantial equivalence based on comparison of features, characteristics and components to the predicate device:
A comparison of the features and characteristics of the two devices can be summarized as follows:
| | Factor VIII Inhibitor
Assay | Factor VIII Antibody
Screen |
|-----------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The Factor VIII Inhibitor
Assay is a solid phase
enzyme linked
immunosorbent assay
(ELISA) designed to detect
IgG antibodies reactive with
recombinant human factor
VIII. | The Factor VIII Antibody
Screen is a qualitative solid
phase enzyme linked
immunosorbent assay
(ELISA) designed to detect
IgG antibodies reactive with
recombinant human factor
VIII (FVIII) in human serum
and plasma. |
| Indications for Use | The 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 the FVIII
molecule. | The Factor VIII Antibody
Screen is designed as a solid
phase enzyme-linked
immunosorbent assay
(ELISA) with a colorimetric
endpoint. This product is
intended to be used as an in
vitro diagnostic kit by
hemostasis and other
laboratories to screen patient
samples for the presence of
lgG antibodies reactive with
human FVIII. |
| Technology | ELISA with a colorimetric
endpoint | ELISA with a colorimetric
endpoint |
| Reportable Results | Qualitative assay; results are
reported as positive or
negative | Qualitative assay; results are
reported as positive or
negative |
| Interpretation of Test
Results | Samples with average OD
values greater than or equal
to twice (2x) the average OD
value of the negative control
are positive. Samples with
average OD values less than
twice (2x) the average OD
value of the negative control
are negative. | Samples with average OD
values greater than the
average OD value of the kit
control are positive. Samples
with average OD values less
than or equal to the average
OD value of the kit control
are negative. |
| Packaging Configuration | 6 to 45 tests per kit | 6 to 44 tests per kit |
| Sample Matrix | plasma collected in ACD or
3.2% sodium citrate | plasma collected in ACD or
sodium citrate and serum |
| Reagents | | |
| Microwell Strips | Immobilized recombinant
FVIII in starwell microwells | Immobilized recombinant
FVIII in low-volume, flat
bottom microwells |
| Source of Antigen | Recombinante (recombinant
full-length human FVIII
stabilized with human serum
albumin) | Kogenate FS (recombinant
full-length human FVIII
stabilized with sucrose) |
| Concentrated Wash
Solution | 10X Tris Buffer, NaCl,
Tween 20, 1% NaN3 | 10X Tris Buffer, NaCl,
Tween 20, 1% NaN3 |
| Specimen Diluent | Tris buffered solution
containing sodium chloride
and 0.05% NaN3 | Tris buffered solution
containing sodium chloride
and 0.05% NaN3 and 5%
bovine serum albumin |
| Substrate Buffer | Diethanolamine and
magnesium chloride, 0.02%
NaN3 | Diethanolamine and
magnesium chloride, 0.02%
NaN3 |
| Substrate | PNPP (crystalline powder) | PNPP (crystalline powder) |
| Stopping Solution | 3 M NaOH | 3 M NaOH |
| Positive Control | Human serum containing
antibodies to human FVIII in
bovine albumin and 0.1%
NaN3 | Human serum containing
antibodies to human FVIII in
bovine albumin and 0.1%
NaN3 |
| | | Human serum containing
antibodies to human FVIII in |
| | | bovine albumin and 0.1%
NaN3 |
| Kit Control | None | Human serum containing antibodies to human FVIII in bovine albumin and 0.1% NaN3 |
| Negative Control | Normal (from non-
hemophilia donors) human
serum containing 0.1% NaN3 | Normal (from non-
hemophilia donors) human
serum containing 0.1% NaN3 |
| Conjugate | Goat anti-human IgG
conjugated to alkaline
phosphatase enzyme | Goat anti-human IgG
conjugated to alkaline
phosphatase enzyme |
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Image /page/3/Picture/0 description: The image shows the logo for GTI Diagnostics. The logo consists of a stylized graphic above the company name. Below the company name is the tagline "Good science starts with people."
·
:
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Image /page/4/Picture/0 description: The image shows the logo for GTI Diagnostics. The logo features a stylized black and white graphic above the text. Below the company name is the tagline "Good science starts with people."
The similarities between these two devices can be summarized as follows:
- Both the Factor VIII Inhibitor Assay and the Factor VIII Antibody Screen have similar . intended uses and the similar indications for use.
- Both the Factor VIII Inhibitor Assay and the Factor VIII Antibody Screen use the same . technology (ELISA with a colorimetric endpoint) and the same general assay steps.
- Both the Factor VIII Inhibitor Assay and the Factor VIII Antibody Screen use identical . reagents with the exception of the microwell plates, specimen diluent, and kit control.
The difference between the two devices can be summarized as follows:
- The microwells for the Factor VIII Inhibitor Assay use starwells with immobilized . Recombinate as the source of Factor VIII. The microwells are blocked with bovine serum albumin and coated with a stabilizing agent. The microwell plates for the Factor VIII Antibody Screen use low-volume, flat bottom microwells with immobilized Kogenate FS as the source of Factor VIII. The microwells for the Factor VIII Antibody Screen are not blocked with bovine serum albumin and are coated with the same stabilizing agent as the Factor VIII Inhibitor Assay.
- The Factor VIII Inhibitor Assay uses a Tris buffered solution containing sodium chloride and . 0.05% sodium azide as the specimen diluent. The Factor VIII Antibody Screen uses a Tris buffered solution containing sodium chloride and 0.05% sodium azide with 5% bovine serum albumin as the specimen diluent.
- The Factor VIII Inhibitor Assay uses the negative control to determine the cutoff for positive . samples. Any sample with an average optical density (OD) value greater than or equal to
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Image /page/5/Picture/0 description: The image contains a logo for GTI Diagnostics. The logo features a stylized graphic above the text. Below the company name is the tagline "Good science starts with people."
twice (2x) the average OD value of the negative control is positive. Any sample with an average OD value less than twice (2x) the average OD value of the negative control is negative. The Factor VIII Antibody Screen uses the kit control to determine the cutoff for positive samples. Any sample with an average OD value greater than the average OD value of the kit control is positive. Any sample with an average OD value less than or equal to the average OD value of the kit control is negative.
VII. Support of substantial equivalence based on performance data:
The details of each of the following studies are coved in Section 7: Performance Data of this 510(k). Only a brief summary of these studies is provided in this section.
Factor VIII Antibody Screen Assay Cutoff
Description of Study
Since there is no internationally accepted standard for measurement of anti-FVIII antibodies, GTI developed its own standardization system and material used for the assay cutoff. In the Factor VIII Antibody Screen, the cutoff value used to assign a reportable result (positive or negative) to a patient sample is set by the kit control. Any sample with an average OD value > than the average OD value of the kit control is positive. Any sample with an average OD value 98% of the normal samples must be negative.
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Image /page/6/Picture/0 description: The image shows the logo for GTI Diagnostics. The logo consists of a stylized human figure inside of a square. Below the logo, the text "GTI. DIAGNOSTICS" is printed in a bold, sans-serif font. The tagline "Good science starts with people:" is printed below the company name in a smaller font.
Qualification of Sample Type
Description of Study
In the method comparison study, described in this submission, samples collected as serum, plasma samples collected in ACD, plasma samples collected in 3.2% or 3.8% sodium citrate, and samples collected as plasma and converted to serum were included. For some sample types only small numbers of samples were available. The purpose of this study was to collect data further supporting the use of various sample types in the Factor VIII Antibody Screen. The unmodified Factor VIII Inhibitor Assay only allowed for plasma collected in ACD (acid citrate dextrose) or 3.2% sodium citrate to be used in the assay.
The effect of the different sample matrices were investigated in a series of experiments. First the FVIII Antibody Screen reportable results obtained from 3.2% sodium citrate plasma and serum drawn from the same 59 normal healthy, non-hemophiliacs were compared. Secondly, a three-way comparison testing samples collected from 14 healthy, non-hemophilia donors collected in serum, 3.2% sodium citrate, and ACD was conducted. Normal plasma samples from healthy, non-hemophiliacs were purchased as whole blood collected in 3.2% sodium citrate (blue-top) or ACD (yellow top) or were collected from GTI employees. Normal sera samples were collected from the same individuals into non-anticoagulated serum tubes (red-top).
In addition to normal samples, a study using spiked samples was conducted. Since we did not have access to the 3 sample types of interest collected from FVIII antibody positive patients, small amounts of Factor VIII antibody positive plasma were spiked into either 3.2% sodium citrate plasma and serum pairs drawn from normal, healthy, non-hemophiliacs or spiked into 3.2% sodium citrate plasma and ACD plasma pairs drawn from normal, healthy, non-hemophiliacs. The spiking was conducted such that the matrix was >90% serum or plasma (i.e. the lowest dilution was 1:10). The reportable results for each spiked sample pair were compared to determine if there was any significant difference in how the two sample matrices responded to the spike.
Results and Analysis
Samples from 59 normal donors drawn as serum or as plasma in 3.2% sodium citrate gave negative reportable results regardless of the sample matrix. In a three way comparison of serum, 3.2% sodium citrate plasma, and ACD plasma, samples from 14 normal donors gave negative reportable results regardless of the sample matrix. When antibody positive plasma was spiked into serum and 3.2% sodium citrate plasma pairs, all spiked samples vielded the same reportable result, regardless of the sample matrix. A total of 12 plasma and serum pairs became positive in this experiment. When antibody positive plasma was spiked into 3.2% sodium citrate plasma and ACD plasma pairs, all spiked samples yielded the same reportable result, regardless of the sample matrix. A total of 24 plasma pairs became positive in this experiment.
Conclusions:
In this set of experiments, no difference was observed between the reportable results obtained from samples collected as 3.2% sodium citrate plasma, ACD plasma or as serum. Differences between average OD values were noticed however there was no correlation to a specific sample matrix. From this study it
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can be concluded that for the Factor VIII Antibody Screen, either plasma collected in 3.2% sodium citrate or ACD or serum can be used as the sample source. The method comparison study additionally supports the use of these sample types in the FVIII Antibody Screen.
Factor VIII Antibody Screen Precision
Description of Study
In this study a total of 8 samples were tested in duplicate in the Factor VIII Antibody Screen in 10 separate assays according the Factor VIII Antibody Screen direction insert.
Results and Analysis
To obtain imprecision of the OD values, the data were analyzed by ANOVA. In addition, the reportable result (positive or negative) was analyzed for agreement within and between runs.
The calculations of imprecision for the OD values showed that the assay demonstrated