(98 days)
Not Found
No
The device description and performance studies focus on a traditional clotting assay method and do not mention any AI or ML components.
No
The device is intended for the quantitative determination of functional Protein S activity in human plasma, which is a diagnostic purpose, not a therapeutic one.
Yes
The device "ThromboTek PSe" is intended for the "quantitative determination of functional Protein S activity in human plasma" and for "identifying inherited or acquired Protein S deficiency." This indicates its use in assessing a medical condition, which falls under the definition of a diagnostic device.
No
The device description clearly states that ThromboTek PSe is a "tissue factor pathway based clotting assay" and lists several lyophilized preparations and solutions as components. This indicates it is a reagent kit, not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use clearly states it's for the "quantitative determination of functional Protein S activity in human plasma." This indicates it's used to test a sample taken from the human body (plasma) to provide information about a medical condition (Protein S deficiency).
- Device Description: The description details the components of a "tissue factor pathway based clotting assay," which is a laboratory test performed on biological samples.
- Performance Studies: The document describes various performance studies (precision, linearity, sensitivity, interference, normal range, method comparison, stability) which are typical evaluations for IVD devices to demonstrate their analytical performance.
- Predicate Device: The mention of a "Predicate Device" (K913424; StaClot® Protein S) is a strong indicator that this device is being compared to an already cleared IVD device, a common practice in regulatory submissions for IVDs.
All these elements align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
ThromboTek PSe is intended for the quantitative determination of functional Protein S activity in human plasma.
ThromboTek PSe is intended for the quantitative determination of functional Protein S activity, such as when identifying inherited or acquired Protein S deficiency.
Product codes (comma separated list FDA assigned to the subject device)
GGP
Device Description
ThromboTek PSe is a tissue factor pathway based clotting assay. The assay activator is a lyophilized preparation incorporating rabbit thromboplastin, calcium, buffer, and stabilizers. The remaining components of the assay are lyophilized activated Protein C, lyophilized human plasma depleted of Protein S, Imidazole buffered saline for use as a plasma diluent, and deionized water containing a preservative for reconstitution of the lyophilized components.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Performance evaluation of the ThromboTek PSe kit included studies of precision, linearity, analytical sensitivity, common interferants, normal range, correlation with the StaClot® kit, and reconstituted and accelerated stability. The method, samples, reagents, and results of each study are described in detail in section 23, Performance Data. No bench (section 20), animal (section 21), or clinical (section 22) testing was required. Summaries of the studies are:
Precision:
Precision estimates of three lots of ThromboTek PSe were determined in a two run per day, twenty day exercise using a normal plasma and an abnormal plasma as described in the CLSI guideline EP5-A2 (7).
- Normal Plasma: Repeatability 4.9%, Total 5.7%
- Abnormal Plasma: Repeatability 7.8%, Total 9.2%
Linearity:
Linearity studies of three lots of ThromboTek PSe were determined on a Stago ST4 analyzer. The ThromboTek PSe assay was linear from 10% Protein S to the maximum tested concentration of 156% Protein S.
Analytical Sensitivity:
The lower limit of detection for three lots of ThromboTek PSe were determined by replicate measurement of IBS alone as the sample on an AMAX 200 analyzer in mechanical mode, and the % PS activity was calculated from the sum of the mean and 3 standard deviations. The lower limit of detection of the assay was 1% PS.
Interferences:
Interference studies of multiple lots of ThromboTek PSe were determined on an AMAX 200 analyzer in mechanical mode. Interferant was spiked into pooled normal plasma and a dilution series prepared. The maximum concentration tolerated in the assay was defined as the highest concentration of interferant wherein any consistent shift relative to the recovered value of the base PNP was less than 10%.
- Hemolysis (Hemoglobin): Maximum tolerated concentration 500 mg/dL
- Icterus (Unconjugated bilirubin): Maximum tolerated concentration 20 mg/dL
- Lipemia (IntraLipid®): Maximum tolerated concentration 2,000 mg triglyceride/dL
- Heparin: Maximum tolerated concentration 1.0 U/mL
Normal Reference Range:
In a representative study one hundred twenty healthy donors were analyzed for Protein S activity with each of three lots of ThromboTek PSe on an AMAX 200 analyzer in mechanical mode. Assay calibration was performed using the SSC/ISTH Secondary Coagulation Standard Lot #3 available from NIBSC.
- All Donors (120): Mean 120% PS, Range 47% - 193% PS
- Males only (35): Mean 135% PS, Range 62% - 209% PS
- Females only (85): Mean 114% PS, Range 45% - 183% PS
Method Comparison:
A total of one hundred seventy-four patient samples were assayed for Protein S activity with multiple lots of ThromboTek PSe and two lots of another commercially available Protein S activity assay. The data was collected in two sites, one using an AMAX 200 analyzer and the other a STart4 analyzer. As determined by Kruskal-Wallis analysis the data was pooled and then further analyzed by linear regression. The correlation coefficient was 0.895 (95% CI, 0.875-0.912) and the coefficient of determination was 0.801, with a slope and intercept of 1.71 and -8.59 respectively.
Reconstituted Stability:
The reconstituted stability of the ThromboTek PSe kit was assessed by longitudinal studies of three lots. The recoveries of two control plasmas were assessed at the initial reconstitution of each kit, and thereafter at periodic time points. The kit components were stored capped when not in use and freshly reconstituted control plasmas were prepared at each time point. With criteria of an age-related trend and a maximum shift of twice the precision CV, the predicted reconstituted stability of the ThromboTek PSe kit is 24 hours when stored at 2-8°C and 8 hours when stored at room temperature (23-25°C).
Accelerated Stability:
Expiry dating was predicted by a heat stress accelerated stability study of one lot of ThromboTek PSe. The study used two different sets of the kit lyophilized components, with one set stressed at 37℃ for up to 25 days and the second set at 45℃ for up to 7 days. Thereafter three lots of control plasmas were assayed with the unstressed and stressed components, and assessed for any age-related shift in recoveries. With criteria of an age-related trend and a maximum shift of 10%, the predicted expiry dating of the ThromboTek PSe kit is 2 years when stored at 2-8°C.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Sensitivity: 1% PS (Lower limit of detection).
Correlation coefficient: 0.895 (Method Comparison).
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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
DEC 1 7 2008
Section 7: 510(k) Summary
510(k) Substantial Equivalence Determination Decision Summary Assay Only Template
This summary of 510(k) safety and effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.
A. 510(k) Number
-
B. Date and Purpose for Submission September 9, 2008
To obtain clearance for the ThromboTek PSe assay, a functional (clotting) assay for the determination of Protein S activity in human plasma. -
ن Measurand Protein S
-
D. Type of Test Quantitative factor determination, clotting assay.
-
Applicant E. r2 Diagnostics, Inc 1801 Commerce Drive South Bend, IN 46628
-
F. Proprietary and Established Name ThromboTek PSe
-
G. Regulatory Information 1. Regulation Section 864.7290, Factor Deficiency Test
- 2. Classification II
-
- Product Code GGP
-
- Panel Hematology
Page_1 Section
1
- H. Intended Use
-
- Intended Use
-
ThromboTek PSe is intended for the quantitative determination of functional Protein S activity in human plasma.
2. Indication(s) for Use
ThromboTek PSe is intended for the quantitative determination of functional Protein S activity, such as when identifying inherited or acquired Protein S deficiency.
-
- Special conditions for use statement(s) Not applicable
-
- Special instrument requirements Not applicable
I. Device Description
ThromboTek PSe is a tissue factor pathway based clotting assay. The assay activator is a lyophilized preparation incorporating rabbit thromboplastin, calcium, buffer, and stabilizers. The remaining components of the assay are lyophilized activated Protein C, lyophilized human plasma depleted of Protein S, Imidazole buffered saline for use as a plasma diluent, and deionized water containing a preservative for reconstitution of the lyophilized components.
J. Substantial Equivalence Information
-
- Predicate device name(s) StaClot® Protein S
-
- Predicate device 510(k) number K913424
Section 7, Page 2
2
2. Comparison with predicate
| Table 7-1: Comparison of submitted device (ThromboTek PSe) to
| predicate device (StaClot Protein S) | ||
|---|---|---|
| Similarities | ||
| Item | Submitted Device | Predicate Device |
| Intended use | Quantitative determination of | |
| function Protein S activity. | Quantitative determination of | |
| function Protein S activity. | ||
| Patient sample | Citrated human plasma | Citrated human plasma |
| Measurement principle | Protein S is rate limiting in a | |
| clotting reaction. | Protein S is rate limiting in a | |
| clotting reaction. | ||
| Format of assay components | Lyophilized activator, | |
| lyophilized aPC, lyophilized | ||
| Protein S deficient plasma | Lyophilized activator, | |
| lyophilized aPC, lyophilized | ||
| Protein S deficient plasma | ||
| Analyte | Protein S activity | Protein S activity |
| Differences | ||
| Item | Submitted Device | Predicate Device |
| Assay linearity | 10%-156% (max tested) | 10%-105% (per Directional |
| Insert) | ||
| Reconstituted Stability | RT: 8 hrs | |
| 2-8C: 24 hrs | RT: 4 hrs | |
| 2-8C: 4 hrs | ||
| (per Directional Insert) | ||
| Analytical Sensitivity | 1% | 8% |
| (per Directional Insert) | ||
| Remaining components | ||
| necessary to run the assay | Imidazole buffered saline and | |
| reconstitution solution (water) | ||
| are provided in kit. | Owen-Koller buffer and calcium | |
| chloride are purchased | ||
| separately, and reconstitution | ||
| grade water is provided by user |
K. Standard/Guidance Documents Referenced (if applicable) Not applicable
L. Test Principle
Thromboplastin is a tissue-derived complex incorporating the protein Tissue Factor (TF) associated with lipid vesicles. When Thromboplastins are added to plasmas the endogenous Factor VII (FVII) or activated Factor VII (FVIIa) in the plasma complex with the Tissue Factor and lipid vesicle in the presence of calcium, which then activates the Tissue Factor pathway of blood coagulation. This TF/FVIIa complex activates Factor X (FX) to activated FX (FXa). Factor Xa complexes with activated Factor V (FVa) on a lipid surface in the presence of calcium to form the prothrombinase complex. The prothrombinase complex activates Prothrombin to Thrombin. Thrombin, without any cofactors or ion dependency, will cleave Fibrinogen to Fibrin, leading to formation of a solid clot.
Activated Protein C (aPC) in the presence of its cofactor Protein S (PS) degrades activated Factor Va (and VIIIa), reducing the catalytic efficiency of the prothrombinase complex. When the assay conditions are chosen such that an excess of aPC is present and the concentration of Protein S in the patient sample is rate limiting, the time to clot of the patient plasma becomes proportional to the
3
concentration of the patient PS and can be used to quantify the PS activity in the sample.
- M. Performance Characteristics (if/when applicable)
Performance evaluation of the ThromboTek PSe kit included studies of precision, linearity, analytical sensitivity, common interferants, normal range, correlation with the StaClot® kit, and reconstituted and accelerated stability. The method, samples, reagents, and results of each study are described in detail in section 23, Performance Data. No bench (section 20), animal (section 21), or clinical (section 22) testing was required. Summaries of the studies are:
Precision: Precision estimates of three lots of ThromboTek PSe were determined in a two run per day, twenty day exercise using a normal plasma and an abnormal plasma as described in the CLSI guideline EP5-A2 (7). The average precision results as %CV were:
| Plasma | Repeatability | Total |
|---|---|---|
| Normal | 4.9% | 5.7% |
| Abnormal | 7.8% | 9.2% |
Linearity: Linearity studies of three lots of ThromboTek PSe were determined on a Stago ST4 analyzer. The ThromboTek PSe assay was linear from 10% Protein S to the maximum tested concentration of 156% Protein S.
Analytical Sensitivity: The lower limit of detection for three lots of ThromboTek PSe were determined by replicate measurement of IBS alone as the sample on an AMAX 200 analyzer in mechanical mode, and the % PS activity was calculated from the sum of the mean and 3 standard deviations. The lower limit of detection of the assay was 1% PS.
Interferences: Interference studies of multiple lots of ThromboTek PSe were determined on an AMAX 200 analyzer in mechanical mode. Interferant was spiked into pooled normal plasma and a dilution series prepared. The maximum concentration tolerated in the assay was defined as the highest concentration of interferant wherein any consistent shift relative to the recovered value of the base PNP was less than 10%. The maximum concentrations were:
4
| Interferant
class | Added
interferant | Maximum
concentration tested | Maximum
tolerated
concentration |
|----------------------|---------------------------|---------------------------------|---------------------------------------|
| Hemolysis | Hemoglobin | 500 mg/dL | 500 mg/dL |
| Icterus | Unconjugated
bilirubin | 20 mg/dL | 20 mg/dL |
| Lipemia | IntraLipid® | 2,000 mg
triglyceride/dL | 2,000 mg
triglyceride/dL |
| Heparin | Heparin | 2.0 Unit/mL | 1.0 U/mL |
Normal Reference Range:
In a representative study one hundred twenty healthy donors were analyzed for Protein S activity with each of three lots of ThromboTek PSe on an AMAX 200 analyzer in mechanical mode. Assay calibration was performed using the SSC/ISTH Secondary Coagulation Standard Lot #3 available from NIBSC. The geometric means and standard deviations were calculated, and the ranges were calculated as the mean +/- 2 standard deviations. The results were:
| Donors | Number | Mean % PS | Range %PS |
|---|---|---|---|
| All | 120 | 120% | 47% - 193% |
| Males only | 35 | 135% | 62% - 209% |
| Females only | 85 | 114% | 45% - 183% |
Method Comparison:
A total of one hundred seventy-four patient samples were assayed for Protein S activity with multiple lots of ThromboTek PSe and two lots of another commercially available Protein S activity assay. The data was collected in two sites, one using an AMAX 200 analyzer and the other a STart4 analyzer. As determined by Kruskal-Wallis analysis the data was pooled and then further analyzed by linear regression. The correlation coefficient was 0.895 (95% CI, 0.875-0.912) and the coefficient of determination was 0.801, with a slope and intercept of 1.71 and -8.59 respectively.
Reconstituted Stability
The reconstituted stability of the ThromboTek PSe kit was assessed by longitudinal studies of three lots. The recoveries of two control plasmas were assessed at the initial reconstitution of each kit, and thereafter at periodic time points. The kit components were stored capped when not in use and freshly reconstituted control plasmas were prepared at each time point. With criteria of an age-related trend and a maximum shift of twice the precision CV, the predicted reconstituted stability of the ThromboTek PSe kit is 24 hours when stored at 2-8°C and 8 hours when stored at room temperature (23-25°C).
Accelerated Stability:
Expiry dating was predicted by a heat stress accelerated stability study of one lot of ThromboTek PSe. The study used two different sets of the kit lyophilized components, with one set stressed at 37℃ for up to 25 days and the second set at
5
45℃ for up to 7 days. Thereafter three lots of control plasmas were assayed with the unstressed and stressed components, and assessed for any age-related shift in recoveries. With criteria of an age-related trend and a maximum shift of 10%, the predicted expiry dating of the ThromboTek PSe kit is 2 years when stored at 2-8°C.
Proposed labeling N.
The labeling is sufficient and satisfies the requirements of 21 CFR Part 809.10.
The label text for the directional insert and for the vial and box labels is included in section 15.
O. Conclusion
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
Other Supportive Information P.
Q. Administrative Information
- Applicant contact information Marc Goldford, Director of Research and Development r2 Diagnostics, Inc. 1801 Commerce Drive South Bend, IN 46628 Voice: 574-288-4377 Fax: 574-288-2272 Email: marc@r2diagnostics.com
Section 7, Page 6
6
DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. Inside the circle is an abstract image of an eagle.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
R2 Diagnostics, Inc. C/o Marc D. Goldford 1801 Commerce Drive South Bend, Indiana 46628
Re: K082631
Trade/Device Name: Thrombo Tek PSe Regulation Number: 21 CFR 864.7290 Regulation Name: Factor Deficiency Test Regulatory Class: Class II Product Code: GGP Dated: November 19, 2008 Received: November 20, 2008
DEC 1 7 2008
Dear Mr. Goldford:
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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed
7
Page 2 – Mr. Goldford
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), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at 240-276-0450. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. 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 (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours.
Josephine Bautista
Marian Chan, PhD
Acting Division Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
8
Section 6: Indication for Use Statement
Indication for Use
510(k) Number (if known):
Device Name: ThromboTek PSe
Indication For Use: r2 Diagnostics' ThromboTek PSe Protein S assay is used for the quantitative determination of functional Protein S activity in human plasma.
Prescription Use _ X (21 CFR Part 801 Subpart D)
And/Or
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety
Josephine Bautista
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K082163|
Section