LUPOTEK KCT
Device Facts
| Record ID | K090105 |
|---|---|
| Device Name | LUPOTEK KCT |
| Applicant | R2 Diagnostics, Inc. |
| Product Code | GGW · Hematology |
| Decision Date | Dec 30, 2010 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 864.7925 |
| Device Class | Class 2 |
Intended Use
The LupoTek kaolin clotting time (KCT) assay is a kaolin activated partial thromboplastin reagent without phospholipid. The LupoTek KCT is a qualitative in vitro coagulation screening assay for use in professional laboratories as an aid in the detection of circulating lupus-like anticoagulants in citrated human plasma.
Device Story
LupoTek KCT is a qualitative in vitro coagulation screening assay; utilizes kaolin-activated partial thromboplastin reagent without added phospholipid. Input: citrated human plasma samples. Principle: in absence of phospholipid, assay poorly accelerates clotting cascade; sensitive to coagulopathies in contact and common pathways. Operation: performed in professional laboratories; reagent mixed with patient plasma and calcium chloride; clotting time measured via coagulation analyzer. Output: clotting time (seconds). Clinical use: aids detection of circulating lupus-like anticoagulants. Benefit: assists clinicians in identifying lupus anticoagulant presence in patient plasma.
Clinical Evidence
Bench testing only. Precision studies (CLSI EP5-A2) on three lots over 20 days showed repeatability CVs of 1.2% (normal) and 3.1% (abnormal). Method comparison study (n=180) evaluated KCT against clinical status for lupus anticoagulant (LA) using ISTH-compliant reference methods. KCT demonstrated 100% positive percent agreement (PPA) with clinical status for LA. Interference studies confirmed tolerance to hemoglobin (500 mg/dL), bilirubin (20 mg/dL), lipemia (2,000 mg/dL), and heparin (< 0.1 Units/mL). Reference range established using 131 healthy donors (49.2–90.7 seconds).
Technological Characteristics
Liquid, single-component reagent. Contains kaolin activator and 0.25M calcium chloride stabilized with 0.02% sodium azide. Contact pathway activation principle. No added phospholipids. Dimensions/form factor: 5x5 mL vials. Standalone use on professional coagulation analyzers. No software/algorithm component.
Indications for Use
Indicated for use in professional laboratories as an aid in the detection of circulating lupus-like anticoagulants in citrated human plasma.
Regulatory Classification
Identification
A partial thromboplastin time test is a device used for primary screening for coagulation abnormalities, for evaluation of the effect of therapy on procoagulant disorders, and as an assay for coagulation factor deficiencies of the intrinsic coagulation pathway.
Predicate Devices
- Phospholin ES (k033471)
Related Devices
- K052124 — ACTICLOT, MODEL 824 · American Diagnostica, Inc. · Oct 17, 2005
- K050221 — HEMOSIL SILICA CLOTTING TIME · Instrumentation Laboratory CO · Mar 30, 2005
Submission Summary (Full Text)
{0}
1
# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE
A. 510(k) Number:
k090105
B. Purpose for Submission:
Clearance of a new device.
C. Measurand:
Kaolin clotting time (for lupus-like anticoagulants)
D. Type of Test:
Partial thromboplastin time test
E. Applicant:
r² Diagnostics, Inc.
F. Proprietary and Established Names:
LupoTek KCT
G. Regulatory Information:
1. Regulation section:
21 CFR §864.7925; Partial thromboplastin time tests
2. Classification:
Class II
3. Product code:
GGW; Test, Time, Partial Thromboplastin
4. Panel:
81 Hematology
H. Intended Use:
1. Intended use(s):
The LupoTek kaolin clotting time (KCT) assay is a kaolin activated partial thromboplastin reagent without phospholipid. The LupoTek KCT is a qualitative in vitro coagulation screening assay for use in professional laboratories as an aid in the detection of circulating lupus-like anticoagulants in citrated human plasma.
2. Indication(s) for use:
Same as intended use
3. Special conditions for use statement(s):
Not applicable
4. Special instrument requirements:
Not applicable
I. Device Description:
LupoTek KCT consists of 5x5 mL vials of KCT reagent and 5x5 mL vials of 0.25M calcium chloride reagent stabilized with 0.02% sodium azide. The KCT reagent a low turbidity, s;ow-setting kaolin formulated with enhanced colloidal stability.
J. Substantial Equivalence Information:
1. Predicate device name(s):
Phospholin ES
2. Predicate 510(k) number(s):
k033471
{1}
3. Comparison with predicate:
| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| | LupoTek KCT | Phospholin ES (k033471) |
| Intended Use | The LupoTek (KCT) assay is a kaolin activated partial thromboplastin reagent without phospholipid. The LupoTek KCT is a qualitative in vitro coagulation screening assay for use in professional laboratories as an aid in the detection of circulating lupus-like anticoagulants in citrated human plasma. | Phospholin ES Activated Partial Thromboplastin Time reagent is a liquid activated reagent with phospholipids derived from soybean lecithin for use in the determination of Activated Partial Thromboplastin Time (APTT) and related coagulation procedures. Phospholin ES is to be used as an APTT reagent (qualitative assay) on patient plasma for the routine screening in the general patient population for deficiencies involving the intrinsic pathway of coagulation. Phospholin ES is sensitive to lupus-like inhibitors. |
| Format | Liquid, single component reagent | Same |
| Analyte | Antibody inhibitors including lupus-anticoagulants | Antibody inhibitors including LA |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Measurement principle | Contact pathway activated partial thromboplastin time without added phospholipid | Contact pathway activated partial thromboplastin time |
| Activator | Kaolin | Ellagic acid |
| Reagent components | Phospholipid not necessary | Phospholipid necessary |
| Analyte | Lupus-like inhibitors | Factor deficiencies, heparin monitoring |
K. Standard/Guidance Document Referenced (if applicable):
CLSI EP5-A2 Evaluation of Precision of Quantitative Measurement Methods; Approved Guideline – 2nd Edition, 2004
CLSI EP15-A2 User Verification of Performance for Precision and Trueness; Approved Guideline, 2nd Edition, 2005
CLSI H21-A5 Collection, Transport, and Processing of Blood Samples for Testing Plasma-based Coagulation Assays and Molecular Hemostasis Assays, Approved Guideline, 5th Edition, 2008
CLSI EP12-A2 User Protocol for Evaluation of Qualitative Test Performance, Approved Guideline, 2nd Edition, 2008
Guidance for Industry and FDA Staff - Statistical Guidance on Reporting Results from Studies Evaluating Diagnostic Tests, March 2007
{2}
3
L. Test Principle:
The LupoTek KCT is an activated partial thromboplastin time reagent without any added phospholipids and with kaolin as the contact activator. In the absence of added phospholipid the assay only poorly accelerates the clotting cascade and is sensitive to coagulopathies in the contact and common pathways.
M. Performance Characteristics (if/when applicable):
1. Analytical performance:
a. Precision/Reproducibility:
Precision (repeatability) studies were conducted on three lots of LupoTek KCT reagent, two runs per day over 20 days using a normal and an abnormal (LA positive – k083878) quality control plasmas as described in CLSI guideline EP5-A2. Acceptance criterion of ≤ 10% CV was met. The clotting times for the first replicate obtained on a STA Compact and summary %CV and 95% CI of the precision results were as follows:
| Plasma | Mean Clot Times (rep #1 - secs) | Repeatability | Total |
| --- | --- | --- | --- |
| Normal | 61.5 | 1.2% CI (1.0 – 1.6%) | 2.2% CI (1.9 – 2.6%) |
| Abnormal (95% CI) | 256.9 | 3.1% CI (2.5 – 3.9%) | 6.6% CI (5.7 – 7.8%) |
b. Linearity/assay reportable range:
Not applicable
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
The open vial stability of the LupoTek KCT reagent was assessed by longitudinal studies of three lots on a Diagnostica Stago STart4 analyzer. The recoveries of two control plasmas (normal and abnormal) were assessed at the initial use 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. Acceptance criteria were an age-related trend and a maximum shift of ±10% of the zero point clotting time to determine open vial stability of 24 hours when stored at room temperature (23 – 25°C).
d. Detection limit:
Not applicable
e. Analytical specificity:
Interference studies of LupoTek KCT were determined on an STA Compact. Interferent was spiked into pooled normal plasma (PNP) and a dilution series prepared. The maximum concentration tolerated in the assay was defined as the highest concentration of interferent wherein any consistent shift relative to the recovered value of the base PNP clotting time was less than 10%. The maximum concentrations were hemoglobin 500 mg/dL, unconjugated bilirubin 20 mg/dL, lipemia 2,000 mg/dL and heparin < 0.1 Units/mL.
f. Assay cut-off:
Not applicable
{3}
2. Comparison studies:
a. Method comparison with predicate device:
A total of 180 patients of known clinical status, including known lupus anticoagulant patients were analyzed in three laboratories with a test lot of KCT and with Phospholin ES, and an LA sensitive APTT reagent. Clinical status for lupus anticoagulant was determined using the Stago hexagonal phase phospholipid assay and several dilute Russell Viper Venom (dRVVT) assays.
Each sample was scored as abnormal for either KCT or the APTT according to their raw clotting times. Laboratory diagnosis was determined by testing according to International Society of Thrombosis and Hemostasis (ISTH) guidelines and included two or more assays of different principles, one of which demonstrates phospholipid dependence.
Each sample was classified in reference to the clinical status for LA provided by the referring lab and tested for the LupoTek KCT neat clot times and the predicate APTT clot times.
Each sample was also classified for agreement between KCT and the APTT. Percent positive, percent negative and overall percent agreement in relation to clinical status were calculated according to FDA guidance Statistical Guidance on Reporting Results from Studies Evaluating Diagnostic Tests. Agreement tables of summary data are reported by site and immediately followed by the corresponding raw data agreement tables.
| Pooled data (3 sites) | KCT vs. Clinical Status for LA | APTT vs. Clinical Status for LA | KCT vs. APTT |
| --- | --- | --- | --- |
| PPA (95% CI) | 100% (87/87)
(95.8% – 100%) | 87% (76/87)
(66.1% – 79.9%) | 74% (114/155)
(66.1% - 79.9%) |
| PNA (95% CI) | 59% (55/93)
(49.0% - 68.6%) | 15% (14/93)
(9.2% - 23.7%) | 56% (14/25)
(37.1% - 73.3%) |
| Overall % agreement | 79%
(142/180) | 50%
(90/180) | 71%
(128/180) |
| Pooled data (n=180) | Predicate | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | KCT vs. Clinical Status for LA | | APTT vs. Clinical Status for LA | | KCT vs. APTT | |
| Test | | Positive | Negative | Positive | Negative | Positive | Negative |
| | Positive | 87 | 38 | 76 | 79 | 114 | 11 |
| | Negative | 0 | 55 | 11 | 14 | 41 | 14 |
| Total | | 87 | 93 | 87 | 93 | 155 | 25 |
{4}
5
| r² site | | KCT vs. Clinical Status for LA | APTT vs. Clinical Status for LA | KCT vs. APTT |
| --- | --- | --- | --- | --- |
| PPA (95% CI) | 100% (30/30) | 77% (23/30) | 87% (40/46) | |
| | | (88.7% - 100%) | (59.1% - 88.2%) | (74.3% - 93.9%) |
| PNA (95% CI) | 39% (11/28) | 18% (5/28) | 42% (5/12) | |
| | | (23.6% - 57.6%) | (7.9% - 35.6%) | (19.3% - 68.0%) |
| Overall % agreement | 71% | 48% | 78% | |
| | | (41/58) | (28/58) | (45/58) |
| r² site (n=58) | Predicate | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | KCT vs. Clinical Status for LA | | APTT vs. Clinical Status for LA | | KCT vs. APTT | |
| Test | | Positive | Negative | Positive | Negative | Positive | Negative |
| | Positive | 30 | 17 | 23 | 23 | 40 | 7 |
| | Negative | 0 | 11 | 7 | 5 | 6 | 5 |
| Total | | 30 | 28 | 30 | 28 | 46 | 12 |
| HRL site | KCT vs. Clinical Status for LA | APTT vs. Clinical Status for LA | KCT vs. APTT |
| --- | --- | --- | --- |
| PPA (95% CI) | 100% (31/31) (89.0% - 100%) | 94% (29/31) (79.3% - 98.2%) | 56% (34/61) (43.3% - 67.5%) |
| PNA (95% CI) | 86% (31/36) (71.3% - 93.9%) | 11% (4/36) (4.4% - 25.3%) | 67% (4/6) (30.0 - 90.3%) |
| Overall % agreement | 93% (62/37) | 49% (33/67) | 57% (38/67) |
| HRL site (n=67) | Predicate | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | KCT vs. Clinical Status for LA | | APTT vs. Clinical Status for LA | | KCT vs. APTT | |
| Test | | Positive | Negative | Positive | Negative | Positive | Negative |
| | Positive | 31 | 5 | 29 | 32 | 34 | 2 |
| | Negative | 0 | 31 | 2 | 4 | 27 | 4 |
| Total | | 31 | 36 | 31 | 36 | 61 | 6 |
| Clinisys site | KCT vs. Clinical Status for LA | APTT vs. Clinical Status for LA | KCT vs. APTT |
| --- | --- | --- | --- |
| PPA (95% CI) | 100% (26/26) (87.1% - 100%) | 92% (24/26) (75.9% - 97.9%) | 83% (48/48) (70.4% - 91.3%) |
| PNA (95% CI) | 45% (13/29) (28.4% - 62.5%) | 17% (5/29) (7.5% - 34.5%) | 71% (5/7) (35.9% - 91.8%) |
| Overall % agreement | 71% (39/55) | 53% (29/55) | 82% (45/55) |
{5}
| Clinisys site (n=55) | Predicate | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | KCT vs. Clinical Status for LA | | APTT vs. Clinical Status for LA | | KCT vs. APTT | |
| Test | | Positive | Negative | Positive | Negative | Positive | Negative |
| | Positive | 26 | 16 | 24 | 24 | 40 | 2 |
| | Negative | 0 | 13 | 2 | 5 | 8 | 5 |
| Total | | 26 | 29 | 26 | 29 | 48 | 7 |
b. Matrix comparison:
Samples were obtained from 10 known LA positive patients and from 12 random patients sent to the coagulation laboratory. Each sample was tested before and after freezing at -70°C. The difference between the fresh and frozen samples was calculated and expressed in seconds and in percent of the fresh value. The clot times were compared to the upper limit of the normal range and evaluated for any change that would result in changing the diagnosis between LA positive or LA negative. Data from two random samples reported abnormal results for the freshly collected samples; however frozen results were reported as normal. Sponsor noted that results were borderline results, i.e., minimally outside the established normal and abnormal ranges. Remaining study results indicate that change in clot times were not significant enough to change the result status of the sample.
3. Clinical studies:
a. Clinical Sensitivity:
Not applicable
b. Clinical specificity:
Not applicable
c. Other clinical supportive data (when a. and b. are not applicable):
Not applicable
4. Clinical cut-off:
Not applicable
5. Expected values/Reference range:
To determine the normal reference range 131 healthy donors were tested with LupoTek KCT on an STA Compact analyzer. The geometric mean and standard deviations of the clotting times were calculated and the range was calculated as the mean ± 2 SD. The mean was 70.0 seconds, with a 2SD range of 49.2 – 90.7 seconds. Each laboratory should establish its own reference range.
N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
