CRYOCHECK CLOT S

K043571 · Precision Biologic, Inc. · GGP · Mar 18, 2005 · Hematology

Device Facts

• Record ID: K043571
• Device Name: CRYOCHECK CLOT S
• Applicant: Precision Biologic, Inc.
• Product Code: GGP · Hematology
• Decision Date: Mar 18, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7290
• Device Class: Class 2

Intended Use

CryoCHECK™ Clot S™ is a clot based assay intended for the quantitative determination of protein S activity in citrated human plasma.

Device Story

CryoCHECK™ Clot S™ is a clinical laboratory assay for quantitative determination of functional protein S in citrated human plasma. The assay utilizes a clot-based method to measure coagulation time. The reagent kit includes protein S deficient plasma and a Clot S Activator containing activated protein C, Russell's viper venom, and heparin neutralizing agents. The activator initiates the common pathway of the coagulation cascade; the presence of functional protein S in the patient sample modulates the clotting time. The assay is performed in a clinical laboratory setting by trained technicians. Results are used by clinicians to identify protein S deficiency, aiding in the assessment of thromboembolic risk. The frozen format distinguishes it from the lyophilized predicate.

Clinical Evidence

Performance validated via a 3-site clinical study comparing the subject device to the predicate. Total sample size n=281 (115, 120, and 46 samples per site). Correlation coefficients (r) ranged from 0.857 to 0.880. Analytical precision: intra-assay %CV 3.9% (normal) to 8.2% (abnormal); inter-assay %CV 8.7% (normal) to 11.2% (abnormal). Linearity established between 10-140%. Interference testing showed no impact from UFH/LMWH up to 1.0 IU/mL, but potential interference from direct thrombin inhibitors (hirudin).

Technological Characteristics

Clot-based coagulation assay. Reagents: Protein S deficient plasma (immunoadsorbed), Clot S Activator (activated protein C, Russell's viper venom, heparin neutralizers, buffers). Format: Frozen. Measurement principle: Clotting time proportional to functional protein S concentration, quantified via calibration curve. Analyte: Functional Protein S.

Indications for Use

Indicated for the diagnosis of congenital or acquired protein S deficiency, which is associated with an increased risk of thromboembolism and recurrent thrombotic episodes.

Predicate Devices

• STA® - Staclot® Protein S (K913424)

Submission Summary (Full Text)

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

A. 510(k) Number:
K043571

B. Purpose for Submission:
Clearance of a new assay

C. Measurand:
Functional Protein S

D. Type of Test:
Clotting Assay

E. Applicant:
Precision BioLogic Inc.

F. Proprietary and Established Names:
CRYOcheck™ Clot S™

G. Regulatory Information:
1. Regulation section:
21 CFR 864.7290
2. Classification:
Class II
3. Product code:
GGP
4. Panel:
81

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H. Intended Use:

1. Intended use(s):

CryoCHECK™ Clot S™ is a clot based assay intended for the quantitative determination of protein S activity in citrated human plasma.

2. Indication(s) for use:

CryoCHECK™ Clot S™ is used to diagnose protein S deficiency (congenital or acquired) which is indicative of an increased risk of thromboembolism. A deficiency in protein S may produce recurrent thrombotic episodes.

3. Special conditions for use statement(s):

4. Special instrument requirements:

I. Device Description:

The CryoCHECK™ Clot S™ assay consists of Protein S Deficient Plasma which is derived from citrated pooled normal human plasma that has been depleted of protein S by immunoadsorption, and Clot S Activator, which contains activated protein C, Russell's viper venom, heparin neutralizing agents, buffers and stabilizers. The assay also requires Precision BioLogic Cot C & S Diluent which is available separately.

J. Substantial Equivalence Information:

1. Predicate device name(s):

Diagnostica Stago STA®-Staclot® Protein S

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

K913424

3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use | Quantitative measurement of | same |

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| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| | functional Protein S | |
| Method | Clot based | same |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Format | Frozen | Lyophilized |

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

## L. Test Principle:

The CryoCHECK™ Clot S™ assay initiates the common pathway of the coagulation cascade through the Clot S Activator reagent. The Russell’s viper venom (RVV-X) in the activator converts factor X to Xa in the presence of activated protein C (APC), bypassing all factors above the common pathway. When mixed with protein S deficient plasma, samples from patients with a protein S deficiency or dysfunction will have shortened CryoCHECK™ Clot S™ clotting times relative to samples with normal levels of functional protein S. The clotting time is proportional to the amount of functional protein S in the patient’s plasma which is quantified using a calibration curve.

## M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Intra-assay precision was determined by testing one normal sample, and one sample closes to the clinically critical decision point 20 times each, and calculating %CV. Results – Normal 3.9%, Abnormal 8.2%.

Inter-assay precision was determined by testing one normal sample and one abnormal sample over seven days. Seven different calibration curves and two different operators were used. On days 1-6 each sample was run 5X in sequence. On day 7 each sample was run 20X in sequence. Results –Normal 8.7%CV, Abnormal 11.2% CV.

b. Linearity/assay reportable range:

Aliquots of a normal plasma sample with a high protein S level was diluted in

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protein S deficient plasma to produce a series of samples with known protein S values. The samples were tested with the CryoCHECK™ Clot S™ assay in four replicates and the protein S values were determined. Results demonstrated linearity between 10-140%.

Samples greater than 140% are recommended to be diluted 1:20 and retested.

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

d. Detection limit:

e. Analytical specificity: A heparin interference study was performed using plasma with a known normal protein S activity. Baseline protein S was measured, and then aliquots of the plasma were then prepared to contain I creased levels of unfractionated heparin (UFH) or low molecular weight heparin (LMWH). Results indicated that CryoCHECK™ Clot S™ is unaffected by UFH and LMWH up to 1.0 IU/mL.

A hirudin interference study was performed following the same study design as the heparin interference study. Results indicated that CryoCHECK™ Clot S™ may be affected by hirudin and other direct thrombin inhibitors. A statement indicating this has been included under the Limitations of the Procedure section of the package insert.

f. Assay cut-off:

2. Comparison studies:

a. Method comparison with predicate device:

3 site clinical study in which samples from patients referred for protein S testing were compared to the predicate device. Separate operators and instruments were used at each site. Laboratory A- y = 0.818x - 6.8, n = 115, r=0.880, std error of slope = 13.9; Laboratory B- y = 0.816x - 5.7, n = 120, r =0.875, std error of slope = 14.4; Laboratory C- y = 0.943x + 3.0, n = 46, r =0.857, std error of slope = 18.7;

b. Matrix comparison:

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3. Clinical studies:

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

4. Clinical cut-off:

5. Expected values/Reference range: 104 normal (normal PT, normal APTT, normal fibrinogen, neg APC, neg lupus anticoagulant, non medicated) individual donor samples were tested. Ages range from 18-67. 64 males, 40 females, and females were not taking oral contraceptives.

| | Males | Females | Total Pop |
| --- | --- | --- | --- |
| n | 64 | 40 | 104 |
| Mean % Protein S | 100.1 | 97.9 | 99.3 |
| Standard Deviation | 27.9 | 29.5 | 28.2 |

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.