HEMOSIL SILICA CLOTTING TIME

K050221 · Instrumentation Laboratory CO · GFO · Mar 30, 2005 · Hematology

Device Facts

• Record ID: K050221
• Device Name: HEMOSIL SILICA CLOTTING TIME
• Applicant: Instrumentation Laboratory CO
• Product Code: GFO · Hematology
• Decision Date: Mar 30, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7925
• Device Class: Class 2

Indications for Use

HemosIL Silica Clotting Time is intended for the detection of Lupus Anticoagulants in human citrated plasma on the IL Coagulation Systems by the use of screening (SCT Screen) and confirmatory (SCT Confirm) reagents sensitized to phospholipids dependent antibodies.

Device Story

In vitro diagnostic assay; detects Lupus Anticoagulants (LA) in human citrated plasma. Uses two liquid reagents: SCT Screen (low phospholipid concentration) and SCT Confirm (high phospholipid concentration); both contain colloidal silica. Includes calcium chloride activator with polybrene to neutralize heparin. Performed on IL Coagulation Systems (ACL Advance, ACL Futura). Principle: LA antibodies interfere with phospholipid-dependent coagulation; high phospholipid concentration in Confirm reagent neutralizes LA effect. Normalized SCT ratio calculated by dividing Screen ratio by Confirm ratio. Ratio >1.24 indicates LA presence. Used in clinical laboratories by technicians; results assist clinicians in diagnosing anti-phospholipid antibody syndrome or related coagulation disorders.

Clinical Evidence

Clinical study of 206 citrated plasma samples (121 normal, 85 abnormal) compared the device to predicate devices on an ACL Futura system. Results showed a relative sensitivity of 92.4% (95% CI: 82.1-97.0) and a relative specificity of 100% (95% CI: 97.6-100.0). All 48 known Lupus Anticoagulant samples tested positive (normalized ratio > 1.24). Precision studies (n=80) demonstrated total %CV ranging from 2.95% to 6.00% across three control levels.

Technological Characteristics

Liquid reagents containing colloidal silica, synthetic phospholipids, buffer, and Tektamer preservative. Activator contains 0.025Mol/L Calcium chloride and polybrene. Clotting-based assay principle. Designed for automated IL Coagulation Systems. Storage at 2-8°C. Complies with NCCLS C28-A2 and EP5-T2 standards.

Indications for Use

Indicated for the detection of Lupus Anticoagulants in human citrated plasma samples. For in vitro diagnostic use by prescription.

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

• HemosIL LAC Screen and HemosIL LAC Confirm (K990302)

Submission Summary (Full Text)

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY ONLY TEMPLATE

A. 510(k) Number:
K050221

B. Purpose for Submission:
To seek clearance of a new assay

C. Measurand:
Lupus Anticoagulant

D. Type of Test:
Clotting

E. Applicant:
Instrumentation Laboratory Co.

F. Proprietary and Established Names:
HemosIL Silica Clotting Time (SCT)

G. Regulatory Information:
1. Regulation section:
21 CFR 864.7925
2. Classification:
Class II
3. Product code:
GFO
4. Panel:
81

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H. Intended Use:

1. Intended use(s):

HemosIL Silica Clotting Time is intended for the detection of Lupus Anticoagulants in human citrated plasma on the IL Coagulation Systems by the use of screening (SCT Screen) and confirmatory (SCT Confirm) reagents sensitized to phospholipids dependent antibodies.

2. Indication(s) for use:

3. Special conditions for use statement(s):

4. Special instrument requirements:

I. Device Description:

HemosIL SCT Screen is a liquid preparation containing colloidal silica, buffer and Tektamer 0.4 g/L as a preservative. HemosIL SCT Confirm Reagent is a liquid preparation containing colloidal silica, synthetic phospholipids, buffer and Tektamer 0.4 g/L as a preservative. The assay also contains a HemosIL Calcium Chloride activator which consists of 0.025Mol/L Calcium chloride with polybrene, a heparin neutralizer.

J. Substantial Equivalence Information:

1. Predicate device name(s):

HemosIL LAC Screen and HemosIL LAC Confirm

2. Predicate 510(k) number(s):

K990302

3. Comparison with predicate:

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| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended use | for the detection of Lupus Anticoagulants in human citrated plasma on the IL Coagulation Systems | same |
| Storage | 2-8°C | same |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| composition | Russell’s viper venom, phospholipids, calcium, polybrene, buffers, stabilizers, and preservatives | Colloidal silica, synthetic phospholipids, buffer, and preservative |

# K. Standard/Guidance Document Referenced (if applicable):

NCCLS C28-A2, How to Define and Determine Reference Intervals in the Clinical Laboratory

NCCLS EP5-T2, User Evaluation of Precision Performance of Clinical Chemistry Devices

# L. Test Principle:

Lupus Anticoagulants (LA) has traditionally been classified as anti-phospholipid antibodies, but a more correct view is that they are antibodies directed against plasma proteins, which also bind to phospholipid surfaces. They are usually IgG, IgM, or mixtures of both, and frequently interfere with standard phospholipid-dependent coagulation tests.

SCT Screen is a low phospholipids concentration reagent to screen samples and SCT Confirm Reagent is a high phospholipids concentration reagent to confirm specificity. Both reagents use a calcium chloride activator solution that contains polybrene to inhibit heparin sensitivity.

A Screen ratio is determined by dividing the patient SCT Screen result by the mean of the SCT Screen normal range. A Confirm ratio is determined by dividing the patient SCT Confirm result by the mean of the SCT Confirm normal range. A normalized SCT ratio is determined by dividing the SCT Screen ratio by the SCT Confirm ratio. A normalized SCT ration $>1.24$ indicates the presence of LA.

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M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Precision was performed on an ACL Advance (K002400) and the ACL Futura Coagulation Analyzer (K951891) using 3 levels of controls: HemosIL Normal Control (K021023) and GradiPlasma LA Low and High Controls (K993332). On the ACL Advance, each control was run in duplicate twice a day for twenty days (n=80). On the ACL Futura, each control was run in duplicate twice a day for 10 days (n=40). Within run, between run and total %CV was calculated per NCCLS EP5-T2 for SCT Screen, SCT Confirm and Normalized SCT Ratio.

ACL Advance

| SCT Screen | | | | |
| --- | --- | --- | --- | --- |
| Material | N | Within run
%CV | Between Run
% CV | Total
%CV |
| Normal Control | 80 | 2.18 | 0.85 | 2.47 |
| GradiPlasma LA Low | 80 | 4.11 | 3.71 | 5.53 |
| GradiPlasma LA High | 80 | 4.14 | 0.00* | 4.94 |
| SCT Confirm | | | | |
| --- | --- | --- | --- | --- |
| Material | N | Within run
%CV | Between Run
% CV | Total
%CV |
| Normal Control | 80 | 1.50 | 0.95 | 1.86 |
| GradiPlasma LA Low | 80 | 1.20 | 1.38 | 1.83 |
| GradiPlasma LA High | 80 | 2.14 | 1.78 | 2.77 |
| Normalized SCT Ratio | | | | |
| --- | --- | --- | --- | --- |
| Material | N | Within run
%CV | Between Run
% CV | Total
%CV |
| Normal Control | 80 | 2.47 | 1.14 | 2.95 |
| GradiPlasma LA Low | 80 | 4.05 | 4.37 | 6.00 |
| GradiPlasma LA High | 80 | 5.24 | 0.00 | 5.60 |

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ACL Futura

| SCT Screen | | | | |
| --- | --- | --- | --- | --- |
| Material | N | Within run %CV | Between Run % CV | Total %CV |
| Normal Control | 40 | 1.66 | 1.61 | 2.76 |
| GradiPlasma LA Low | 40 | 3.44 | 0.00 | 5.42 |
| GradiPlasma LA High | 40 | 6.43 | 2.29 | 8.67 |
| SCT Confirm | | | | |
| --- | --- | --- | --- | --- |
| Material | N | Within run %CV | Between Run % CV | Total %CV |
| Normal Control | 40 | 1.40 | 2.62 | 2.98 |
| GradiPlasma LA Low | 40 | 2.40 | 0.82 | 3.28 |
| GradiPlasma LA High | 40 | 2.92 | 1.73 | 3.39 |
| Normalized SCT Ratio | | | | |
| --- | --- | --- | --- | --- |
| Material | N | Within run %CV | Between Run % CV | Total %CV |
| Normal Control | 40 | 1.74 | 3.81 | 4.43 |
| GradiPlasma LA Low | 40 | 3.15 | 0.00 | 5.82 |
| GradiPlasma LA High | 40 | 6.78 | 4.53 | 8.88 |

b. Linearity/assay reportable range:

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

d. Detection limit:

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e. Analytical specificity: Specificity testing was performed on ACL Advance by spiking multiple levels of each interferent (bilirubin, triglycerides, UF and LMW Heparin) into pooled normal and low abnormal plasmas and comparing the results against the unspiked sample results. All samples were tested in duplicate with a single lot of HemosIL Silica Clotting Time (SCT Screen and SCT Confirm) reagents. Results demonstrated no significant interference by bilirubin up to 30 mg/dL, triglycerides up to 500 mg/dL, and Heparin (UF and LMW) up to 0.4 u/mL.

f. Assay cut-off:

A cut-off value of >1.24 for the SCT normalized ratio was established from the normal range data based on a 90% CI around the 95% range in accordance with NCCLS C28-A2.

2. Comparison studies:

a. Method comparison with predicate device:

An in-house study was conducted using 210 patient citrated plasma samples with the HemosIL Silica Clotting time versus the predicate HemosIL LAC Screen/LAC Confirm on an ACL Advance. y = 1.10X-0.0860, r=0.8738

A field study was conducted using 206 patient citrated plasma samples with the HemosIL Silica Clotting time versus the predicate HemosIL LAC Screen/LAC Confirm on an ACL Futura. y = 1.17x - 0.2467, r=0.9211

b. Matrix comparison:

3. Clinical studies:

a. Clinical Sensitivity:

b. Clinical specificity:

c. Other clinical supportive data (when a. and b. are not applicable):

Relative sensitivity and specificity of HemosIL Silica Clotting Time as compared

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directly to the predicate was calculated for the in-house and field study. Discrepant results were resolved using the Diagnostica Stago Staclot LA (K923731)

In-house:

LAC Screen/Confirm

SCT Screen/Confirm

| | + | - |
| --- | --- | --- |
| + | 31 | 3 |
| - | 2 | 174 |

- Relative Sensitivity (31/33) = 93.9% (95% C.I. = 77.0 - 96.9)
- Relative Specificity (174/177) = 98.3% (95% C.I. = 95.9-98.7)
- Overall Agreement (205/210) = 97.6%

Final Interpretation

SCT Screen/Confirm

| | + | - |
| --- | --- | --- |
| + | 31 | 3 |
| - | 0 | 176 |

- Relative Sensitivity (31/31) = 100% (95% C.I. = 89.0 - 100.0)
- Relative Specificity (176/179) = 98.3% (95% C.I. = 95.9-98.7)
- Overall Agreement (207/210) = 98.6%

Field Study:

LAC Screen/Confirm

SCT Screen/Confirm

| | + | - |
| --- | --- | --- |
| + | 49 | 0 |
| - | 4 | 153 |

- Relative Sensitivity (49/53) = 92.4% (95% C.I. = 82.1 - 97.0)
- Relative Specificity (153/153) = 100% (95% C.I. = 97.6-100.0)
- Overall Agreement (202/206) = 98.0%

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4. Clinical cut-off:

5. Expected values/Reference range:

120 citrated plasma samples (60 females and 60 male) were obtained from healthy donors and tested on an ACL Advance using a single lot of HemosIL Silica Clotting Time reagents. 95% reference interval with 90% confidence interval (2SD) was calculated. The data supports a normal range of 0.70-1.24 Normalized SCT Ratio.

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.

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